The life experience and status of Chinese rural women from observation of three age groups.
Interview data gathered during 2 surveys in Anhui and Shejiang Provinces in 1986 and 1987 are used to depict changes in the social status and life situation of rural women in China in 3 age groups, 18-36, 37-55, and 56 and over. For the younger women, marriage increasingly is a result of discussion with parents, not arrangement, but 3rd-party introductions are increasing. They are active in household and township enterprises and aspire to more education and economic independence. The middle-aged group experienced war and revolution and now work nonstop under the responsibility system of household production, aspiring to university education for sons and enterprise work for daughters. The older women, while supported by their sons, live a frugal existence. In general, preference for sons is still prevalent and deep-seated. At the same time, the bride price and costs of marriage are increasing and of widespread concern. Rural socioeconomic growth is required before Confucian traditions are overcome.


Obligatory role for phosphatidylinositol 4,5-bisphosphate in activation of native TRPC1 store-operated channels in vascular myocytes.
In the present study the effect of phosphatidylinositol 4,5-bisphosphate (PIP(2)) was studied on a native TRPC1 store-operated channel (SOC) in freshly dispersed rabbit portal vein myocytes. Application of diC8-PIP(2), a water soluble form of PIP(2), to quiescent inside-out patches evoked single channel currents with a unitary conductance of 1.9 pS. DiC8-PIP(2)-evoked channel currents were inhibited by anti-TRPC1 antibodies and these characteristics are identical to SOCs evoked by cyclopiazonic acid (CPA) and BAPTA-AM. SOCs stimulated by CPA, BAPTA-AM and the phorbol ester phorbol 12,13-dibutyrate (PDBu) were reduced by anti-PIP(2) antibodies and by depletion of tissue PIP(2) levels by pre-treatment of preparations with wortmannin and LY294002. However, these reagents did not alter the ability of PIP(2) to activate SOCs in inside-out patches. Co-immunoprecipitation techniques demonstrated association between TRPC1 and PIP(2) at rest, which was greatly decreased by wortmannin and LY294002. Pre-treatment of cells with PDBu, which activates protein kinase C (PKC), augmented SOC activation by PIP(2) whereas the PKC inhibitor chelerythrine decreased SOC stimulation by PIP(2). Co-immunoprecipitation experiments provide evidence that PKC-dependent phosphorylation of TRPC1 occurs constitutively and was increased by CPA and PDBu but decreased by chelerythrine. These novel results show that PIP(2) can activate TRPC1 SOCs in native vascular myocytes and plays an important role in SOC activation by CPA, BAPTA-AM and PDBu. Moreover, the permissive role of PIP(2) in SOC activation requires PKC-dependent phosphorylation of TRPC1.


Bacterial Outer Membrane Vesicles Loaded with Perhexiline Suppress Tumor Development by Regulating Tumor-Associated Macrophages Repolarization in a Synergistic Way.
Tumor-associated macrophages (TAMs) promote tumor development and metastasis and are categorized into M1-like macrophages, suppressing tumor cells, and M2-like macrophages. M2-like macrophages, occupying a major role in TAMs, can be repolarized into anti-tumoral phenotypes. In this study, outer membrane vesicles (OMVs) secreted by Escherichia coli Nissle 1917 carry perhexiline (OMV@Perhx) to explore the influence of OMVs and perhexiline on TAM repolarization. OMV@Perhx was internalized by macrophages and regulated the phenotype of TAMs from M2-like to M1-like efficiently to increase the level of tumor suppressor accordingly. Re-polarized macrophages promoted apoptosis and inhibited the mobility of tumor, cells including invasion and migration. The results indicate that OMVs improve the efficacy of perhexiline and also represent a promising natural immunomodulator. Combining OMVs with perhexiline treatments shows powerfully synergistic anti-tumor effects through co-culturing with re-polarized macrophages. This work is promising to exploit the extensive applications of OMVs and chemical drugs, therefore developing a meaningful drug carrier and immunomodulator as well as expanding the purposes of traditional chemical drugs.


Upregulation of microRNA-876 Induces Endothelial Cell Apoptosis by Suppressing Bcl-Xl in Development of Atherosclerosis.
The injury and apoptotic cell death of endothelial cells hallmark the development of atherosclerosis (AS), characterized by dysregulation of lipid homeostasis, immune responses, and formation of coronary plaques. However, the mechanisms underlying the initiation of endothelial cell apoptosis remain ill-defined. Recent evidence suggests a role of microRNAs in the processes of AS-associated endothelial cell apoptosis. Thus, we studied this question in the current study. AS was developed in ApoE (-/-) mice suppled with high-fat diet (HFD), compared to ApoE (-/-) mice suppled with normal diet (ND). Mouse endothelial cells were isolated from the aortic arch using flow cytometry based on their expression of Pecam-1. Oxidized low-density lipoprotein (ox-LDL) were used to treat human aortic endothelial cells (HAECs) as an in vitro model for AS. Gene expression was quantified by RT-qPCR and protein levels were analyzed by Western blotting. Apoptosis was evaluated by FITC Annexin V Apoptosis essay and by TUNEL staining. Prediction of the binding between miRNAs and 3'-UTR of mRNA from the target gene was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. HFD mice, but not ND mice, developed AS in 12 weeks. Significantly reduced endothelial cell marks and significantly increased mesenchymal cell marks were detected in the aortic arch of the HFD mice, compared to the ND mice. The endothelial cell apoptosis was significantly higher in HFD mice, seemingly due to functional suppression of protein translation of anti-apoptotic Bcl-Xl protein through upregulation of miR-876. Similar results were obtained from in vitro study. Inhibition of miR-876 abolished the effects of ox-LDL-induced apoptotic cell death of HAECs. AS-associated endothelial cell apoptosis may partially result from downregulation of Bcl-Xl, through upregulation of miR-876 that binds and suppresses translation of Bcl-Xl mRNA.


Increased expression of gallbladder cholecystokinin: a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin.
A series of our studies have shown that formation of cholesterol-supersaturated bile in patients with cholesterol gallstone disease is causatively related to decreased gallbladder contractility and mucin hypersecretion by the gallbladder. Supersaturated bile may modify the composition of gallbladder membranes so that the transduction of smooth muscle regulatory signals is impaired, and it may enhance the inflammation-induced mucin secretion by the gallbladder. To achieve a better understanding of the mechanism by which supersaturated bile impairs the contractility, we studied changes in the expression levels of gallbladder cholecystokinin (CCK-A) receptor messenger ribonucleic acid (mRNA) in prairie dogs fed a high-cholesterol diet. Levels of pathobiological determinants in arachidonate metabolism which are important for mucin secretion were also measured in their bile. Adult male prairie dogs were randomly assigned to receive either a semisynthetic diet (SSD) or an SSD plus 1.2% cholesterol (a high-cholesterol diet) for 2-, 4-, and 6-week periods. The contractile force in response to CCK-octapeptide (CCK-8) was measured by using gallbladder muscle strips. The mRNA levels of the CCK-A receptor were determined by reverse-transcription polymerase chain reaction (RT-PCR). Parallel to the increase in the cholesterol saturation index, the contractile responses to CCK-8 decreased in the animals fed a high-cholesterol diet for 4 weeks and markedly decreased in the animals with gallstone formation. However, in contrast to the decreased contractility, the steady-state mRNA levels of the gallbladder CCK-A receptor were significantly increased in the animals fed a high-cholesterol diet in comparison with the corresponding control animals. In the bile, a high-cholesterol diet caused an increase in the proportion of arachidonyl-phosphatidylcholine species, where phospholipase A(2) activity, prostaglandin E(2), and mucin concentrations were increased parallel to the feeding period. Up-regulation of the CCK-A receptor mRNA in the gallbladder of animals fed a high-cholesterol diet associated with decreased contractility may be due to an impairment of CCK signaling related to increased membrane cholesterol contents and its related reaction of biological compensation in order to increase the receptor concentration. The results of the present study suggest that in prairie dogs fed a high-cholesterol diet both a decrease in gallbladder contractility related to impairment of CCK signaling and phospholipase A(2) (PLA(2))-induced mucosal inflammation in the gallbladder with associated biliary alterations favoring cholesterol crystal formation pathogenetically contribute to the formation of cholesterol gallstones.


Brain buffering is restored in hyponatremic rats by correcting their plasma sodium concentration.
Previous studies from this laboratory showed that both acute and chronic hyponatremia impaired active brain buffering. These studies were performed to determine whether correcting the plasma sodium restored normal buffering in hyponatremic rats. Acute (1- and 2-day) and chronic (7- and 14-day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration combined with a liquid diet. Plasma sodium was corrected by stopping desmopressin for 6 h, substituting solid chow, and allowing free access to water. Studies were performed 24 h later. Uncorrected hyponatremic rats who continued to receive desmopressin and liquid diet served as controls. Brain pH was determined by [31P]NMR in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was determined by the response to CO2 loading. Resting brain pH was the same in corrected and uncorrected rats, but the two groups responded differently to CO2 loading. Thus, 55 min after ventilation with 20% CO2, corrected rat brain pH was 0.13 pH units higher than in uncorrected rats despite statistically similar changes in CO2 tension and arterial pH in both groups. Moreover, 15 min into recovery from CO2 exposure, brain pH in corrected rats overshot resting pH by 0.07, whereas no overshoot occurred in uncorrected rats. Buffering in corrected rats was identical to that shown previously in normonatremic rats. The complete restoration of late-phase buffering achieved by normalizing the plasma sodium of hyponatremic rats indicates that at least some portion of active hydrogen ion transport is sodium dependent in the brain.


Crossover comparison of drug information online database vendors: Dialog and MEDLARS.
To compare Dialog EMBASE with the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE, and TOXLIT to evaluate differences among the databases and vendors in a method consistent with routine drug information practice. Crossover comparison. NLM MEDLARS databases MEDLINE, TOXLINE, and TOXLIT were searched directly. EMBASE was searched via Dialog Information Services. MEDLINE was searched back to 1980; TOXLINE and TOXLIT were searched back to 1981, reflecting the different database structures. EMBASE was searched back to 1980. To control bias, searches were randomized; identical strategies were used during the same session and were performed by the same trained searcher. Twenty-six drug information requests were compared. The MEDLARS and Dialog databases were generally similar, with no significant differences in the number of potentially relevant references, English references, clinically relevant references, available abstracts, unique citations, time online, and number of questions answered. EMBASE searches were more costly (p = 0.0005). TOXLIT was costlier than TOXLINE and MEDLINE (p = 0.0018). NLM MEDLARS databases were comparable to Dialog EMBASE. Although MEDLARS provided more total and English-language citations, the differences were small and did not influence the proportion of questions answered. The greatest difference between the vendors was the significantly lower cost of searching on MEDLARS. Although this difference may be partially offset by the significantly shorter search times on EMBASE, the mean 1.9 minutes saved would not recoup the mean $7.89 difference in cost. MEDLARS databases are less expensive for routine drug information requests.


Contact allergy to air-exposed geraniol: clinical observations and report of 14 cases.
The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways. To investigate whether testing with oxidized geraniol detects more cases of contact allergy than testing with pure geraniol. The pattern of reactions to pure and oxidized geraniol, and metabolites/autoxidation products, was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Pure and oxidized geraniol were tested at 2.0% petrolatum in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626 and 1055 consecutive patients, respectively. Pure and oxidized geraniol gave positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to oxidized geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients' dermatitis was found in 11 of 14 cases. Testing with oxidized geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol.


Misalignment analysis of combination-cylinder discharge CO(2) laser.
The axes of a laser resonator will deviate away from the initial places when the combination-cylinder discharge CO2 laser (CCDCL) is misaligned. The new cavity axes are established through using the misaligned augmented matrixes. The influences of the misalignments on the properties of the laser beams are studied in detail, such as the line deviations and angle deviations of oscillation beams in CCDCL, the near- and far-field distribution of output beams, the diffraction loss and output power, and the beam quality factor. It is shown that the influences of the misalignments on the above properties of the laser beams are obvious when the misaligned angle of the laser resonator exceeds 30 s. The studied results can afford references for the design of a CCDCL.


Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: An observational study.
During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. Observational study. Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. ACTRN12616001479493.


Foliar graphene oxide treatment increases photosynthetic capacity and reduces oxidative stress in cadmium-stressed lettuce.
The application of graphene oxide (GO) in the environment can have a positive or negative effect on the toxicity of pollutants, but the effect of GO on cadmium (Cd2+)-stressed lettuce has not yet been thoroughly studied. Therefore, we assessed the potential effects of foliar GO sprays on photosynthesis and antioxidant systems in Cd-stressed lettuce. We found that the foliar application of 30 mg L-1 of GO could significantly reduce signs of Cd2+ toxicity in lettuce. We observed increased net photosynthetic rates, stomatal conductance, transpiration rates, chlorophyll content, primary maximum photochemical efficiency of photosystem II, actual quantum yield, photosynthetic electron transport rates, ribulose-1,5-bisphosphate carboxylase and oxygenase concentrations, and biomass in Cd2+-stressed lettuce treated with GO. In addition, the foliar application of 30 mg L-1 of GO reduced the accumulation of the reactive oxygen species O·̄2 and H2O2, malondialdehyde content, and the activity of antioxidant enzymes. The decreased antioxidant enzyme activity could have been due to the decrease in reactive oxygen species. Cd2+ pollution is highly destructive to agricultural products, and the foliar application of GO provides a new potential tactic to improve the tolerance of plants to heavy metals.


Understanding the impacts of childhood adversity on sleep problems in children with fetal alcohol spectrum disorder: A comparison of cumulative and dimensional approaches.
The developmental impacts of prenatal alcohol exposure (PAE) and postnatal exposure to adversity are typically considered in isolation. However, both contribute independently to sleep problems. Children with fetal alcohol spectrum disorder (FASD) have PAE and significant sleep disturbances. What is not clear is the relative contribution to these disturbances of exposure to early life adversity. This study examined how exposure to such adversity impacts frequent insomnia symptoms and nightmares in children with FASD and "At Risk" designations. We compared two approaches to modeling adversity in children who had undergone a diagnostic assessment for FASD: a cumulative risk approach that sums adversities to create a total score and an approach that treats exposure to threat and deprivation as independent dimensions. Data on caregiver-reported exposure to adversity and sleep problems for 63 children (aged 3 years 4 months to 7 years 8 months) were extracted from clinical archives. Cumulative risk, threat exposure, and deprivation exposure scores were computed and were tested as predictors of insomnia symptoms and nightmares. All analyses controlled for age and gender. There were high rates of caregiver-reported sleep problems with 60.3% (n = 38) of children having nightmares and 44.4% (n = 28) having a frequent insomnia symptom. The cumulative risk analysis showed that for every additional exposure to adversity, the odds of having a caregiver-reported insomnia symptom increased by 38%. The dimensional analysis showed no relationship between deprivation and sleep problems. However, every additional exposure to threat increased the odds of nightmares by 93%. Exposure to postnatal adversity contributes to sleep disturbances in children with FASD, with unique roles for cumulative risk and the threat dimension of adversity. The implications of these findings for the etiology and treatment of sleep disturbances in children with FASD are discussed.


Homogeneous nucleation of droplets from supersaturated vapor in a closed system.
Kinetic equations describing homogeneous nucleation kinetics within standard model are solved numerically under the condition of a constant number of molecules in the considered system. It has consequences to decrease the supersaturation of the supersaturated vapor during the process of the formation of small droplets of a new phase. The decrease of supersaturation occurs in a short time and reaches some value which remains unchanged for a relatively long time (quasistationary regime), especially at lower initial supersaturations. This time interval decreases with increasing value of the initial supersaturation. In the quasistationary regime the nucleation rate reaches its stationary value. At higher initial supersaturation, the rate of formation of nuclei goes to some maximum value corresponding to the stationary nucleation rate and then decreases with time due to the decrease of supersaturation.


Collection of Wound Exudate From Human Digit Tip Amputations Does Not Impair Regenerative Healing: A Randomized Trial.
The regrowth of amputated digit tips represents a unique regenerative healing in mammals with subcutaneous volume regrowth, restoration of dactylogram, and suppression of scar formation. Although factor analysis in amphibians and even in mice is easy to obtain, safety of harvesting biomaterial from human digit tip amputations for analysis has not yet been described.The aim of this study was to evaluate if recovering wound exudate does hamper clinical outcome or influence microbiologic or inflammation status.A predefined cohort of 18 patients with fresh digit tip amputations was randomly assigned to receive standard therapy (debridement, occlusive dressing) with (n = 9) or without (n = 9) collection of the whole wound exudate in every dressing change. Primary endpoint (lengthening) and secondary endpoints (regeneration of dactylogram, nail bed and bone healing, time to complete wound closure, scar formation, 2-point discrimination, microbiologic analysis, inflammatory factors interleukin (IL)-1α, tumor necrosis factor-α, IL-4, and IL-6) were determined by an independent, blinded observer.Patients' characteristics showed no significant differences between the groups. All patients completed the study to the end of 3 months follow-up. Exudate collection did not influence primary and secondary endpoints. Furthermore, positive microbiologic findings as well as pus- and necrosis-like appearance neither impaired tissue restoration nor influenced inflammatory factor release.Here, the authors developed an easy and safe protocol for harvesting wound exudate from human digit tip amputations. For the first time, it was shown that harvesting does not impair regenerative healing. Using this method, further studies can be conducted to analyze regeneration associated factors in the human digit tip.DRKS.de Identifier: DRKS00006882 (UTN: U1111-1166-5723).


Polymorphic di-2-pyridyl ketone 4-nitrophenylhydrazone (dpknph): the structure of beta-dpknph.
A new polymorph of di-2-pyridyl ketone 4-nitrophenylhydrazone [alternative name: N-(dipyridin-2-ylmethylene)-N'-(4-nitrophenyl)hydrazine], C17H13N5O2, isolated from the filtrate of a sonicated acetonitrile solution of dpknph and CdCl2, was found to crystallize in the monoclinic space group P21/c, in contrast to the known form which crystallizes in P21/n. The non-coplanar molecules pack in parallel stacks without any intermolecular hydrogen-bonding interactions. This packing pattern contrasts with the interlocked interdigitated packing seen in the previously known polymorph.


Influence of Vitamin D Deficiency on the Expression of Genes and Proteins in Patients With Medium Rotator Cuff Tears.
Whether vitamin D deficiency is related to rotator cuff muscle and tendon physiology is controversial. To assess the relationship between vitamin D deficiency and various gene expression patterns in patients with rotator cuff tears. Controlled laboratory study. During arthroscopic surgery, samples from the supraspinatus muscle, deltoid muscle, and supraspinatus tendon were acquired from 12 patients with vitamin D deficiency (serum 25-hydroxyvitamin D concentration <20 ng/dL) and 12 patients with sufficient vitamin D levels (control group, serum 25-hydroxyvitamin D concentration ≥30 ng/dL) who were matched for age, sex, and tear size. Alterations in the expression of genes and proteins associated with myogenesis, muscle atrophy, adipogenesis, inflammation, and apoptosis, as well as in vitamin D receptor expression, were assessed using quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry and were compared between the 2 groups. Vitamin D receptor gene expression in the deltoid muscle was significantly lower in the vitamin D deficiency group than in the control group (P = .043). Additionally, in the deltoid muscle, myoDgene expression levels were lower and atrogin levels were higher in the vitamin D deficiency group than in the control group (P = .034 and P = .011, respectively). However, in the supraspinatus muscle, no differences were observed between groups in the expression of myogenesis- or atrophy-related genes (all P > .05). The expression of inflammation-related genes (interleukin (IL)-1β and IL-6) was significantly higher in the vitamin D deficiency group, in both the deltoid and supraspinatus muscles (all P < .05). The supraspinatus tendon tissue did not show any significant differences in any gene expression evaluated (all P > .05). A correlation between gene and protein expression was observed for atrogin and IL-1β in the deltoid muscle (P = .019 and P = .037, respectively) and for IL-6 in the supraspinatus muscle (P = .044). Vitamin D deficiency was not associated with the expression of myogenesis-related or muscle atrophy-related genes in the supraspinatus muscle of patients with rotator cuff tears, unlike in the deltoid muscle; rather, vitamin D deficiency was associated with increased proinflammatory cytokine expression. In patients with rotator cuff tears, vitamin D deficiency was observed to be associated with increased levels of proinflammatory cytokines in the rotator cuff muscles, without significant changes in gene expression related to myogenesis or muscle atrophy.


The suitability of dogs as guide dogs for the blind: criteria and testing procedures.
Criteria and testing procedures with regard to the suitability of dogs as guide dogs for the blind were developed on the basis of a literature study and own observations. A profile of the guide dog comprising physical characteristics, skillfulness, behaviour, and obedience was drawn up. As a rule, the testing procedures concern health and skills of the dogs. In the skill test some elements of the behavioural and obedience test were included. The final evaluation is based on the results of physical examination and the skill test, unless testing of behaviour and/or obedience appears necessary as well. A method for evaluating the performance of the dogs as objectively as possible is described. Some implications of using and testing guide dogs are discussed.


Ensemble distribution for immiscible two-phase flow in porous media.
We construct an ensemble distribution to describe steady immiscible two-phase flow of two incompressible fluids in a porous medium. The system is found to be ergodic. The distribution is used to compute macroscopic flow parameters. In particular, we find an expression for the overall mobility of the system from the ensemble distribution. The entropy production at the scale of the porous medium is shown to give the expected product of the average flow and its driving force, obtained from a black-box description. We test numerically some of the central theoretical results.


[The dynamics of ischemic heart disease and the risk factors among the male population of Moscow in the 1985 to 1995 period].
The trends in prevalence of ischemic heart disease (IHD) and risk factors for 1985-1995 have been studied on random representative samples of male population from Moscow. For the decade studied IHD incidence increased, especially in younger males. Changes in IHD risk factors were the following: systolic and diastolic pressures were on the increase. HDLP cholesterol and total cholesterol in the blood lowered, total triglycerides were unchanged, incidence of smoking remained high.


Epigenetic control in the immune response.
Helper T cells engaged in an immune response confront a prevalent challenge for developmentally regulated gene expression: How does a cell give rise to daughter cells with different fates? Additionally, lymphocyte function is intimately associated with the processes of cell division and migration. This imposes an additional burden for daughter cells, to remember inductive events from which they are temporally and spatially removed. An emerging view is that helper T cells use epigenetic mechanisms tied to the structure of chromatin and its covalent modifications to achieve at least two important features of their programmed gene expression. Epigenetic effects organize the ability of signal transduction pathways to generate a restricted set of progeny from a multi-potent progenitor. In addition, epigenetic effects seem to allow dividing cells to memorize, or imprint, signaling events that occurred earlier in their development. Beyond helper T cells, the use of epigenetic effects is emerging as a common strategy in development and function of the mammalian immune system, suggesting that epigenetic effects may play a more prominent role in metazoan cell differentiation than previously appreciated. Lymphocytes are, thus, becoming a tractable system for genetic and biochemical dissection of the ways in which the genome is embedded with regulatory information to achieve developmental complexity.


Histological differentiation between palmoplantar pustulosis and pompholyx.
Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. Pompholyx is characterized by recurrent crops of vesicles on the lateral aspects of the fingers and the palms and soles. Because both PPP and pompholyx share similar clinical and histological features, it is difficult to differentiate between these two diseases even for dermatologists. To compare the histological features of PPP and pompholyx and to analyse their clinical characteristics. The clinical history from 45 patients with PPP and 42 with pompholyx was evaluated. Among these patients, the punch biopsies from acute lesions of 40 PPP patients and 35 pompholyx ones were analysed, blind to the clinical diagnosis. There was no sexual predilection in either group, and 65.5% of PPP patients had smoking history. About half of the patients had concomitant palmoplantar lesions in PPP and pompholyx respectively. In histological evaluation, loss of granular layer, suprapapillary plates thinning, eosinophils in the pustules or vesicles, tortuous capillaries, capillaries touching the undersurface of epidermis and extravasated erythrocytes were statistically significant features of PPP. Confluent parakeratosis, psoriasiform epidermal hyperplasia, clubbing and anastomosing of the rete ridges favoured PPP. Meanwhile, multiple foci of parakeratosis, irregular epidermal hyperplasia and thinning of rete ridges were more often observed in pompholyx. However, dyskeratotic cells, papillary dermal oedema, dilated capillaries and acrosyringium were not significantly different between the two diseases. Several histological features could serve as useful 'clues' to differentiate between PPP and pompholyx.


Studies using a monoclonal antibody against soman.
The production of antibodies against the organophosphorus hapten soman has been undertaken in vivo in rabbits and in vitro by employing monoclonal techniques. The polyclonal rabbit antibodies did not cross-react with soman but were inhibited by soman analogs in a competitive inhibition enzyme immunoassay ( CIEIA ). In contrast the monoclonal antisoman antibodies were inhibited specifically by soman in the CIEIA but not by sarin nor the hydrolysis products of soman. The monoclonal antibodies were able to compete with acetylcholinesterase (AChE) for soman when the antibody was present in a molar concentration equal to the antibody-soman dissociation constant, resulting in a retardation of the rate of inhibition of AChE by soman. When monoclonal antibodies were administered to mice in a passive immunization regimen, the times-to-death increased twofold at an LD70 or LD90 dose level. These results suggest that the monoclonal antibodies have proper characteristics for use as an immunocytochemical reagent of high specificity. The ability of the antisoman monoclonal antibodies to compete with AChE for soman in vitro and the preliminary in vivo data indicate that selected monoclonal antibodies may prove useful in a therapeutic or prophylactic mode for organophosphorus poisoning.


Prune-belly syndrome: ongoing controversies regarding pathogenesis and management.
Classical prune-belly syndrome (also known as Triad syndrome, Eagle-Barrett syndrome, abdominal muscular deficiency syndrome) consists of a triad of anomalies: deficient abdominal wall musculature, urinary tract dilatation, and cryptorchidism. Although most investigators consider prune-belly syndrome a distinct entity, there is no consensus as to its pathogenesis despite extensive study of clinical cases and pathological material. Prognosis may vary from death in utero to a near-normal life expectancy. The lack of understanding of pathogenesis and wide range of severity result in dilemmas in treatment planning, and surgeons vary widely in their approach. This article discusses prune-belly syndrome, presents the currently favored hypotheses regarding its pathogenesis, and gives an overview of accepted management strategies.


Amino-Functionalized Layered Crystalline Zirconium Phosphonates: Synthesis, Crystal Structure, and Spectroscopic Characterization.
Two new layered zirconium phosphonates functionalized with amino groups were synthesized starting from aminomethylphosphonic acid in the presence of different mineralizers, and their structures were solved from powder X-ray diffraction data. Their topologies are unprecedented in zirconium phosphonate chemistry: the first, of formula ZrH[F3(O3PCH2NH2)], prepared in the presence of hydrofluoric acid, features uncommon ZrO2F4 units and a remarkable thermal stability; the second, of formula Zr2H2[(C2O4)3(O3PCH2NH2)2]·2H2O, prepared in the presence of oxalic acid, is based on ZrO7 units with oxalate anions coordinated to the metal atom, which were never observed before in any zirconium phosphonate. In addition, the structure of another compound based on (2-aminoethyl)phosphonic acid is reported, which was the object of a previously published study. This compound has layered α-type structure with -NH3(+) groups located in the interlayer space. All of the reported compounds were further characterized by means of vibrational spectroscopy, which provided important information on fine structural details that cannot be deduced from the powder X-ray diffraction data.


Medical staff extremity dosimetry in CT fluoroscopy: an anthropomorphic hand voxel phantom study.
This work aims to contribute to the study of the radiation dose distribution delivered to the hands of medical staff members during a general computed tomographic (CT) fluoroscopic guided procedure. In this study, both Monte Carlo simulations and measurements were performed. For free-in-air and computed tomography dose index (CTDI) body phantom measurements, a standard pencil ionization chamber (IC) 100 mm long was used. The CT scanner model was implemented using MCNPX (Monte Carlo N-Particle eXtended) and was successfully validated by comparing the simulated results with measurements. Subsequently, CT images of a hand, together with an anthropomorphic phantom, were voxelized and used with the MCNPX code for dose calculations. The hand dose distribution study was performed both by using thermo-luminescent detector measurements and Monte Carlo simulations. The validated simulation tool provides a new perspective for detailed investigations of CT-irradiation scenarios. Simulations show that there is a strong dose gradient, namely the even zones of the hand that are in precise vicinity to the x-ray beam only receive about 4% of the maximum dose delivered to adjacent areas which are directly exposed to the primary x-ray beam. Finally, the scatter contribution of the patient was also studied through MC simulations. The results show that for directly exposed parts of the hand surface, the dose is reduced by the body of the patient (due to the shielding), whereas the dose is increased by scattered radiation from the patient for parts of the skin that receive scattered radiation only.


Lipid coating of paramagnetic microspheres reduces non-specific binding to Kelly neuroblastoma cells.
In an effort to reduce non-specific binding interactions (binding in the absence of antibody), sheep anti-mouse IgG1 (Fc) antibody linked to magnetic microspheres (also referred to as microbeads or beads) were treated with phosphatidylcholine (PC), phosphatidylglycerol (PG), or a mixture of PC and PG. The lipid-treated microspheres were mixed with Kelly neuroblastoma cells, which had been pre-labelled with Hoechst fluorochrome. After 30 minutes of incubation, the microsphere adherent cells were separated from the non-adherent cells and counted. PC or mixed lipid treatment of beads reduced nonspecific binding to 8.3%, compared to 25.8% in the untreated samples. PG, on the other hand, increased non-specific binding. Lipid treatment of beads did not adversely affect specific antibody mediated binding. When a non-specific antibody was added to the incubation mixture, non-specific binding of untreated control beads to cells was increased, but binding of PC-treated beads was unaffected.


Expression of death receptor-3 in human breast cancer and its functional effects on breast cancer cells in vitro.
Death receptor-3 (DR3) plays controversial roles in cancer. Currently, DR3 is known to be a functional receptor of vascular endothelial growth inhibitor (VEGI). The role of DR3 in breast cancer remains unclear. The present study investigated DR3 expression in a clinical cohort of breast cancer patients and its role in breast cancer cells in vitro. The expression of DR3 was examined in a breast cancer cohort using quantitative PCR (Q-PCR) and immunohistochemistry (IHC) in comparison to the patients' data. In vitro function of DR3 was examined through the targeting of this molecule in MCF7 and MDA-MB-231 breast cancer cells using ribozyme transgene technology. Decreased DR3 expression was noted in breast cancer tissues compared to normal tissues and decreased expression of DR3 was generally associated with a poorer prognosis as well as a significantly shorter long-term survival (p=0.038). Targeting of DR3 in vitro in breast cancer cell lines resulted in impaired migratory rates compared to respective control cells. Collectively, these data suggest a complex role for DR3 in breast cancer development and progression.


A consensus layer V pyramidal neuron can sustain interpulse-interval coding.
In terms of a single neuron's long-distance communication, interpulse intervals (IPIs) are an attractive alternative to rate and binary codes. As a proxy for an IPI, a neuron's time-to-spike can be found in the biophysical and experimental intracellular literature. Using the current, consensus layer V pyramidal neuron, the present study examines the feasibility of IPI-coding and examines the noise sources that limit the information rate of such an encoding. In descending order of importance, the noise sources are (i) synaptic variability, (ii) sodium channel shot-noise, followed by (iii) thermal noise. The biophysical simulations allow the calculation of mutual information, which is about 3.0 bits/spike. More importantly, while, by any conventional definition, the biophysical model is highly nonlinear, the underlying function that relates input intensity to the defined output variable is linear. When one assumes the perspective of a neuron coding via first hitting-time, this result justifies a pervasive and simplifying assumption of computational modelers-that a class of cortical neurons can be treated as linearly additive, computational devices.


Overview of EBV-Associated T/NK-Cell Lymphoproliferative Diseases.
Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative diseases (EBV-T/NK-LPDs) are a group of rare diseases resulting from ectopic infection of T or natural killer (NK) lymphocytes with Epstein-Barr virus (EBV). EBV-T/NK-LPDs include chronic active EBV infection, EBV-associated hemophagocytic lymphohistiocytosis, hydroa vacciniforme-like lymphoproliferative disease, and severe mosquito bite allergy. Extra-nodal NK/T-cell lymphoma-nasal type and aggressive NK-cell leukemia can also be included in this broad spectrum. Currently, the etiology of EBV-T/NK-LPDs is unknown and no curative therapy has been established, except for hematopoietic stem cell transplantation. While most cases of EBV-T/NK-LPDs have been documented in specific areas of the world, they have also been documented more broadly across East Asia and Latin America. Consequently, active research and discussion of EBV-T/NK-LPDs are both necessary and important within the extensive international community of scientists and clinicians, to elucidate their etiology and develop a standard therapy.


Retrospective Analysis of Pediatric Dermatologic Hospital Admissions.
Statistical data on the frequency of skin conditions in the Pomeranian region of Poland are limited in the field of pediatric dermatology, requiring a multidisciplinary approach to each patient. Dermatitis and skin allergies are the 10 most common pediatric conditions, with a prevalence of 20% among such chronic illnesses in developed countries. This analysis is limited to the recurrence of dermatologic diseases in the hospitalized pediatric population within the Pomeranian region for the purpose of future targeted education. Retrospective analysis included 282 participants over a 3-year period between 2013 and 2015, with admissions to the Department of Dermatology, Venereology, and Allergology at the Medical University of Gdansk. Diagnoses were obtained from the ward admission book and CliniNet database.


Multiorgan eosinophilic infiltration after initiation of clozapine therapy: a case report.
The eosinophilic response to clozapine is well described in the literature, causing a variety of responses, from serositis to colitis. However, there are not case reports describing a clozapine-induced marked eosinophilia resulting in multiorgan dysfunction. In this case report, we describe a 24 year old Caucasian male who presented with severe systemic eosinophilia resulting in eosinophilic GI tract infiltration, myocarditis, pericardial and pleural effusions with dramatic improvement following drug withdrawal. Clozapine associated eosinophilia should be suspected in the setting of eosinophilic infiltration of multiple organs.


Status Quo or Drop-Off: Do Older Adults Maintain Benefits From Choose to Move-A Scaled-Up Physical Activity Program-12 Months After Withdrawing the Intervention?
Choose to Move is one of few scaled-up health-promoting interventions for older adults. The authors evaluated whether Choose to Move participants maintained their intervention-related gains in physical activity (PA), mobility, and social connectedness 12 months after the intervention ended. The authors assessed PA, mobility, loneliness, social isolation, and muscle strength via questionnaire and objective measures in 235 older adults at 0 months (baseline), 6 months (end of intervention), and 18 months (12-months postintervention). The authors fitted linear mixed models to examine the change in each outcome from 6 to 18 months (primary objective) and 0 to 18 months (secondary objective) and reported by age group (60-74 and ≥75 y). In younger participants, PA decreased between 6 and 18 months, but remained significantly higher than at baseline. Intervention-related benefits in loneliness, social isolation, mobility, and muscle strength were maintained between 6 and 18 months in the younger participants. Older participants maintained their intervention benefits in loneliness, mobility, and muscle strength. When compared with baseline values, PA levels in older participants were unchanged, whereas social isolation increased. Older adults maintained some, but not all, health benefits of Choose to Move 12 months after the intervention ended. Long-term commitments are needed to deliver effective health-promoting interventions for older adults if benefits are to be maintained.


Ceftriaxone versus ampicillin/cloxacillin as antibiotic prophylaxis in elective caesarean section.
We carried out a prospective, randomized, controlled clinical trial to evaluate the clinical efficacy of ceftriaxone and ampicillin/cloxacillin prophylaxis in decreasing the frequency of post-caesarean section infection-related morbidity. Two hundred patients randomly received either ceftriaxone (single dose) or ampicillin/cloxacillin (3 doses) intravenously at induction of anaesthesia. There was no statistical difference in incidence of endometritis (P = 0.34), wound infection (P = 0.44), or other febrile morbidity (P = 0.5). Eleven babies had a low Apgar score (< 8) in the ceftriaxone group and 13 in the ampicillin/cloxacillin group (P = 0.82). There were 2 perinatal deaths in each group. One dose of ceftriaxone was as effective as ampicillin/ cloxacillin in preventing post-caesarean section complications and is easier to administer.


'Instead of popping pills, perhaps you should add frog breathing': experiences of glossopharyngeal insufflation/breathing for people with cervical spinal cord injury.
People with cervical spinal cord injury have impaired function of the respiratory muscles, which results in reduced ventilation. Glossopharyngeal insufflation/breathing increases total lung capacity and improves cough function, however, knowledge of the experiences regarding learning and practicing glossopharyngeal insufflation in everyday life is missing. To describe and explore the experiences of learning and practicing glossopharyngeal insufflation among people with cervical spinal cord injury. Twenty six individuals with cervical spinal cord injury, who had participated in a previous intervention study on glossopharyngeal insufflation, were interviewed. Semi-structured telephone interviews were analyzed with qualitative content analysis. An overall theme and seven categories emerged. Glossopharyngeal insufflation was perceived as a possibility to make a difference in one's life by improving respiratory function, both immediately and for time ahead and thereby ease everyday activities, and by increasing participation, independence, and overall health. The participants with cervical spinal cord injury described that they could learn glossopharyngeal insufflation, but it could be perceived as difficult. However, the use of glossopharyngeal insufflation could be experienced by the individual as being different, and there were sometimes doubts about its effectiveness. Use of glossopharyngeal insufflation can enable people with cervical spinal cord injury to increasingly participate in everyday activities. Increased autonomy might lead to improved self-esteem and provide well-being. However, ambivalence about the usefulness of glossopharyngeal insufflation may arise and the technique can be difficult to learn. Therefore, individualized information and instructions from health professionals are required. Implications for Rehabilitation Practicing glossopharyngeal insufflation leads to increased participation in everyday activities for people with cervical spinal cord injuries and provides the individual hope to influence future life situation. People with cervical spinal cord injuries therefore need support from health care professionals in order to be motivated to learn and then use the glossopharyngeal insufflation technique also as health promotion Glossopharyngeal insufflation can improve respiratory function and also increase awareness of breathing; health professionals should therefore be able to assess which patients who can benefit from glossopharyngeal insufflation in order to make the technique become an important part of the rehabilitation. The technique can be difficult to perform perfectly and is sometimes perceived as uncomfortable. It may also cause unpleasant side effects and therefore individualized information and instructions regarding glossopharyngeal insufflation are required.


Influence of feed type and its effect on repressing wool-biting behavior in housed sheep.
Sheep sometimes develop an abnormal behavior termed as wool-biting when kept in an indoor system; however, little is known about this behavior. As the provided feed type may affect the foraging behavior and repress abnormal behavior in animals, we tested the effect of feed type on repressing wool-biting behavior in this study. We used hay prepared in three forms, that is hay bales, rolls and cubes. The wool-biting frequency associated with hay bales was significantly higher than that associated with rolls (P < 0.05) and cubes (P < 0.05); however, there was no significant difference between rolls and cubes. For hay rolls, wool-biting significantly decreased after feeding (P < 0.05), suggesting that rolls may provide sheep with appropriate oral stimulation; thus, decreasing the post-feeding oral abnormal behavior. An individual difference of wool-biting behavior between sheep was also detected, and an unexpected bed-eating behavior was found in the hay cube treatment. We suggest that sheep performing movements that are similar to their natural foraging behavior while grazing would repress wool-biting behavior, which happened in hay roll and hay cube treatments. Considering sanitation and animal welfare, providing sheep with hay rolls may provide an easier method to control wool-biting behavior in housed sheep.


Dimensions of the supportive role of the nurse in palliative care.
The purpose of this study was to describe the clinical component of the nurse's role in supportive or palliative care. Data were derived from in-depth retrospective descriptions of the care given by a supportive care nurse to 10 patients and their families. Constant comparative analysis revealed that the nurse's role was a supportive one with multiple dimensions. A model of the supportive role in palliative care was developed, comprised of six interwoven but discrete dimensions: Valuing, Connecting, Empowering, Doing For, Finding Meaning, and Preserving Own Integrity. Valuing and Preserving Own Integrity were key concepts related to the nurse as person and were central to the other dimensions. The findings imply that the nurse as a professional cannot be separated from the nurse as a person.


Role of salicylic acid in systemic resistance induced by Pseudomonas fluorescens against Fusarium oxysporum f. sp. ciceri in chickpea.
Selected isolates of Pseudomonas fluorescens (Pf1-94, Pf4-92, Pf12-94, Pf151-94 and Pf179-94) and chemical resistance inducers (salicylic acid, acetylsalicylic acid, DL-norvaline, indole-3-carbinol and lichenan) were examined for growth promotion and induced systemic resistance against Fusarium wilt of chickpea. A marked increase in shoot and root length was observed in P. fluorescens treated plants. The isolates of P. fluorescens systemically induced resistance against Fusarium wilt of chickpea caused by Fusarium. oxysporum f.sp. ciceri (FocRs1), and significantly (P = 0.05) reduced the wilt disease by 26-50% as compared to control. Varied degree of protection against Fusarium wilt was recorded with chemical inducers. The reduction in disease was more pronounced when chemical inducers were applied with P. fluorescens. Among chemical inducers, SA showed the highest protection of chickpea seedlings against wilting. Fifty two- to 64% reduction of wilting was observed in soil treated with isolate Pf4-92 along with chemical inducers. A significant (P = 0.05; r = -0.946) negative correlation was observed in concentration of salicylic acid and mycelial growth of FocRs1 and at a concentration of 2000 microg ml(-1) mycelial growth was completely arrested. Exogenously supplied SA also stimulated systemic resistance against wilt and reduced the disease severity by 23% and 43% in the plants treated with 40 and 80 microg ml(-1) of SA through root application. All the isolates of P. fluorescens produced SA in synthetic medium and in root tissues. HPLC analysis indicated that Pf4-92 produced comparatively more SA than the other isolates. 1700 to 2000 nanog SA g(-1) fresh root was detected from the application site of root after one day of bacterization whereas, the amount of SA at distant site ranged between 400-500 nanog. After three days of bacterization the SA level decreased and was found more or less equal at both the detection sites.


Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation.
Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation.


Regeneration of rat tracheal epithelium after mechanical injury. II. Restoration of surface integrity during the early hours after injury.
Mechanical injury to ciliated and goblet cells of the rat tracheal epithelium results in sloughing of these cells. The basal cells of the pseudostratified epithelium remain. These cells, studied by scanning electron microscopy, transmission electron microscopy, and en face light microscopy after silver staining, are rounded and separated from one another for the first 2 hours after injury. They become flat and are apposed to each other by 4 hours after injury, but inter-cellular junctions are not uniformly present until 6 hours after injury. By that time, early evidence of stratification of cells is observed, and lanthanum hydroxide, as a colloidal tracer placed in the tracheal lumen, is excluded from the spaces between cells. The changes are indicative of rapid restoration of barrier function after mild injury to the respiratory tract lining as a first step in the reparatve process.


Sperm competition, immunity, selfish genes and cancer.
Sperm competition is widespread and has played an important role in shaping male reproductive characters such as testis size and numbers of sperm produced, and this is reflected in the rapid evolution of many reproductive genes. Additionally, sperm competition has been implicated in the rapid evolution of seminal fluids. However, our understanding of the molecular basis of many traits thought to be important in sperm competition is rudimentary. Furthermore, links between sperm competition and a range of issues not directly related to reproduction are only just beginning to be explored. These include associations between sperm competition and selfish genes, immunity and diseases such as cancer.We briefly review these topics and suggest areas we consider worthy of additional research.


Active Control of Inertial Focusing Positions and Particle Separations Enabled by Velocity Profile Tuning with Coflow Systems.
Inertial microfluidics has drawn much attention not only for its diverse applications but also for counterintuitive new fluid dynamic behaviors. Inertial focusing positions are determined by two lift forces, that is, shear gradient and wall-induced lift forces, that are generally known to be opposite in direction in the flow through a channel. However, the direction of shear gradient lift force can be reversed if velocity profiles are shaped properly. We used coflows of two liquids with different viscosities to produce complex velocity profiles that lead to inflection point focusing and alteration of inertial focusing positions; the number and the locations of focusing positions could be actively controlled by tuning flow rates and viscosities of the liquids. Interestingly, 3-inlet coflow systems showed focusing mode switching between inflection point focusing and channel face focusing depending on Reynolds number and particle size. The focusing mode switching occurred at a specific size threshold, which was easily adjustable with the viscosity ratio of the coflows. This property led to different-sized particles focusing at completely different focusing positions and resulted in highly efficient particle separation of which the separation threshold was tunable. Passive separation techniques, including inertial microfluidics, generally have a limitation in the control of separation parameters. Coflow systems can provide a simple and versatile platform for active tuning of velocity profiles and subsequent inertial focusing characteristics, which was demonstrated by active control of the focusing mode using viscosity ratio tuning and temperature changes of the coflows.


A seven-transmembrane methyltransferase catalysing N-terminal histidine methylation of lytic polysaccharide monooxygenases.
Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes that help break down lignocellulose, making them highly attractive for improving biomass utilization in industrial biotechnology. The catalytically essential N-terminal histidine (His1) of LPMOs is post-translationally modified by methylation in filamentous fungi to protect them from auto-oxidative inactivation, however, the responsible methyltransferase enzyme is unknown. Using mass-spectrometry-based quantitative proteomics in combination with systematic CRISPR/Cas9 knockout screening in Aspergillus nidulans, we identify the N-terminal histidine methyltransferase (NHMT) encoded by the gene AN4663. Targeted proteomics confirm that NHMT was solely responsible for His1 methylation of LPMOs. NHMT is predicted to encode a unique seven-transmembrane segment anchoring a soluble methyltransferase domain. Co-localization studies show endoplasmic reticulum residence of NHMT and co-expression in the industrial production yeast Komagataella phaffii with LPMOs results in His1 methylation of the LPMOs. This demonstrates the biotechnological potential of recombinant production of proteins and peptides harbouring this specific post-translational modification.


Interpatient and intrapatient variability in phenytoin protein binding.
The authors retrospectively assessed the relation between total and free serum concentrations and serum albumin in a sample of hospitalized patients to evaluate how well free serum concentrations can be estimated from total phenytoin serum concentrations. The authors also assessed the interpatient and intrapatient variability of the phenytoin free fraction. Paired serum samples of total and free phenytoin serum concentrations and serum albumin were obtained from 48 hospitalized patients (28 males, 20 females; mean age, 51 y; range, 13-90 y). Concomitant medications were recorded. Phenytoin free fraction and adjusted total phenytoin serum concentrations (adjusted for serum albumin) were calculated. One hundred sixty-three samples were obtained (mean, 3.4 samples per patient; range, 1-16 samples); 28 patients had more than one pair of samples obtained. Mean phenytoin free fraction was 15% +/- 7% (range, 4%-61%) for the 163 samples. The variability for the total, free, and free fractions were 65%, 75.9%, and 45.8%, respectively. There was significant variability in the phenytoin free fraction within individual patients who had more than one pair of serum concentrations obtained. The intraindividual coefficient of variation in phenytoin free fraction was 85% +/- 21.3% (range, 2%-94%). Despite strong overall correlation between the total phenytoin serum and free serum concentrations, there is excessive variability in phenytoin protein binding. Correction for serum albumin was not useful in this patient group. Because of significant interpatient and intrapatient variability in phenytoin serum concentrations, monitoring of total serum concentrations is unreliable and free phenytoin serum concentrations should be considered for monitoring in hospitalized patients.


Dialysate sodium and intradialytic hypotension.
Intradialytic hypotension (IDH) is a common complication in hemodialysis, particularly with the time and frequency constraints of standard session delivery in contemporary practice. High intradialytic weight gain (IDWG), high ultrafiltration rates (UFR), and frequent IDH are highly interlinked, and separately or together contribute to the high cardiovascular morbidity and mortality observed in the hemodialysis population. Using a lower concentration of sodium in the dialysate (D-Na) reduces sodium delivery to the patient during dialysis, and several studies reported the beneficial effect in controlling IDWG, UFR, and hypertension. On the other hand, high dialysate sodium is associated with more hemodynamic benefits in an unstable patient. The resulting sodium loading may, however, induce a vicious cycle of higher IDWG, requiring more rapid ultrafiltration, eventually contributing to intradialytic symptoms and hypotension. In this article, we review the available literature on fixed and profiled dialysate sodium prescriptions, and we recommend a tailored approach that considers the patient's status to optimize dialysis delivery.


Conflict in community pharmacy practice: The experience of pharmacists, technicians and assistants.
Intraprofessional conflict among pharmacists, regulated technicians and assistants may undermine attempts to advance patient care in community pharmacy. There is no available research examining this issue in light of the evolution of the profession and roles within the profession. A combination of interviews and focus groups involving pharmacists, technicians and assistants was undertaken. Each participant completed the Conflict Management Scale as a way of identifying conflict management style. Data were analyzed and coded using a constant-comparative, iterative method. A total of 41 pharmacy team members participated in this research (14 pharmacists, 14 technicians and 13 assistants). Four key themes were identified that related to conflict within community pharmacy: role misunderstanding, threats to self-identity, differences in conflict management style and workplace demotivation. As exploratory research, this study highlighted the need for greater role clarity and additional conflict management skills training as supports for the pharmacy team. The impact of conflict in the workplace was described by participants as significant, adverse and multifactorial. To support practice change, there has been major evolution of roles and responsibilities of pharmacists, technicians and assistants. Conflict among pharmacy team members has the potential to adversely affect the quality of care provided to patients and is an issue for managers, owners, regulators and educators.


[Strips versus gel: a clinical comparison of two over-the-counter bleaching systems].
The objective of this clinical, randomized, examiner-blinded split-mouth study was to compare the efficacy, the side effects and patients acceptance of two over-the-counter bleaching systems (strips versus gel) with respect to the bleaching times required to achieve six grades of whitening in human teeth. Tooth shades were documented by matching with the VITA shade guide, or dered according to value and assigned a numeric ranking from 1 to 16, lightest to darkest. Twenty-six adults participated in the study. Both treatments were applied twice daily according to the manufacturer's instructions. Efficacy and the PBI were measured by a dental examiner. Tooth hypersensitivity, gingival irritations as well as patients acceptance were recorded by a visual analog scale ranging from 0 to 10. In order to detect changes in the enamel surface due to treatment epoxy casts of the study teeth were analysed by SEM. A total of 20 volunteers completed the study. The subjects teeth treated with the strips-system exhibited a 6.0 +/- 0.0 mean shade scores improvement compared to baseline (53.7 cycles; 1610.3 min), and the subjects teeth treated with the gel-system exhibited a 3.3 +/- 1.4 mean shade scores improvement (64.6 cycles; 969.0 min). However, both treatments were able to whiten teeth statistically significantly compared to baseline. Side effects caused by the two systems were minimal and reversible. None of the teeth studied showed detectible enamel surface changes in the subsequent SEM analysis. Both methods were well accepted.


Utilization of capecitabine plus oxaliplatin and 5-fluorouracil/folinic acid plus oxaliplatin in the adjuvant treatment of stage IIB and stage III colon cancer: A multi-centre, retrospective, chart review study.
Purpose First, to assess drug utilization rates of capecitabine plus oxaliplatin (CAPOX) versus 5-fluorouracil plus oxaliplatin (mFOLFOX6) regimens in the treatment of stage IIB and stage III colon cancer. Second, to assess patient characteristics used to select CAPOX versus FOLFOX therapy, dose-limiting toxicities, dose intensities and treatment completion rates. Methods Patients with resected stage IIB or stage III colon cancer from five British Columbia Cancer Agency centres treated with CAPOX or mFOLFOX6 were selected for the analysis. Protocol utilization rates, patient characteristics and toxicities of the two regimens were collected and compared by descriptive statistics. Results A total of 306 patients were included over study period. mFOLFOX6 is the most commonly used regimen with 69% utilization rate. CAPOX patients were younger (57 years old vs. 62 years old, p < 0.01), but no other significant differences were found. CAPOX was associated with more dose-limiting toxicities compared to mFOLFOX6 (95% vs. 82%, p < 0.01). Fewer patients completed the intended 24-week course of CAPOX compared to mFOLFOX6 (67% vs. 82%, p < 0.01). Conclusion FOLFOX is the most commonly utilized adjuvant treatment option for stage IIB and stage III colon cancer in British Columbia, and is associated with better tolerability and higher treatment completion rates.


Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.
Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age.


The formation of phosphatidylglycerol and other phospholipids by the transferase activity of phospholipase D.
1. Purified phospholipase D can catalyse the transfer of a ;phosphatidyl' unit from lecithin to various aliphatic alcohols such as glycerol, ethanolamine, methanol and ethylene glycol with the formation of the equivalent phospholipid. 2. The transferase reaction occurs simultaneously with hydrolase activity but at high alcohol concentrations the former predominates. 3. The acceptor molecule must contain a primary alcoholic grouping. 4. The chromatographic and ionophoretic mobilities of the deacylation products of many enzymically synthesized phospholipids are reported. 5. Enzymically prepared phosphatidylglycerol has been isolated in good yield. Chemical degradation showed that the ;phosphatidyl unit' of lecithin had been transferred predominantly to the alpha-hydroxyl groups of glycerol. 6. Water-soluble alcohols can markedly stimulate the liberation of choline from ultrasonically treated lecithin by phospholipase D. The stimulation is usually due to an increase in hydrolase activity although often the associated transferase activity contributes.


Predictors of health-related quality of life in patients with obstructive sleep apnoea.
This paper is a report of a study to identify the common symptoms and demographic and physiological factors of obstructive sleep apnoea that are predictive of health-related quality of life in a Chinese population. Health-related quality of life impairment in obstructive sleep apnoea is an increasingly important consideration, but little is known about the factors that influence quality of life in this population. A total of 108 Chinese patients with newly diagnosed obstructive sleep apnoea were recruited in 2003 and assessed for health-related quality of life, daytime sleepiness, depression and anxiety. Associations between symptoms, demographic and physiological factors and quality of life were examined by Pearson linear correlation. Hierarchical multiple regression were used to determine predictors of overall quality of life and its dimensions. Forty-six patients (42.6%) had depressed mood and 21 (19.4%) were anxious. Fifty-nine (54.6%) were hypersomnolent. The severity of symptoms of sleepiness, depression, and anxiety was statistically significantly inversely correlated with each domain and the total score for health-related quality of life. No statistically significant correlation was observed between disease severity and quality of life. Controlling for age and gender, anxiety and sleepiness predicted 45.2% of the variance of overall quality of life (R(2) = 0.452, P < 0.001). Anxiety was the strongest predictor of overall and each domain of health-related quality of life. Assessment of mood in patients with obstructive sleep apnoea should be an essential part of nursing practice. Comprehensive evaluation of symptoms, especially mood disturbance, is important for improving quality of life for these patients.


Indigenous Cases of Leprosy (Hansen's Disease) in Southern Mississippi.
Hansen's disease or leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. In the U.S., leprosy is mainly reported in immigrants, but indigenous leprosy cases have been also reported in this country, especially in semitropical southern states (i.e., Texas, Louisiana). The objective of this series of cases is to describe indigenous leprosy cases reported in southern Mississippi (MS) during the period 2012-2014. Information was collected from medical records at Hattiesburg Clinic and the MS Department of Health. Four cases were reported during the period of study (3 Caucasian males, 1 African-American woman). Non of visited endemic leprosy country. The age ranged from 60 to 83 years (median: 75.5 years). Of the four cases, three presented with a slowly progressive erythematous rash disseminated mainly on the thorax and abdomen, with a lesser degree on the extremities. The time between onset of rash until the diagnosis ranged from 5 to 16 months (median: 7 months). Only one case had direct contact with armadillos (blood exposure). Non of these patients had a history of immunosuppression. The most common symptoms were neuropathic pain (n=2), generalized pruritus (n=2) and loss of sensation in extremities (n=2). One case had severe peripheral neuropathy with muscle weakness, atrophy in left arm, and wasting on left hand. Skin biopsies showed diffuse granulomatous infiltrate with foamy histiocytes along with acid fast bacilli by Fite stain. By Ridley-Jopling classification system, three cases were diagnosis as lepromatous leprosy, and one, borderline lepromatous. Treatment included clofazimine, dapsone and rifampin that was offered free of charge by the National Hansen's Diseases Program, Baton Rouge, L.A. One patient did not tolerate therapy. In conclusion, a slowly progressive disseminated erythematous skin rash on the trunk should raise suspicion for leprosy in the elderly population in south MS.


Emotion regulation: exploring the impact of stress and sex.
Emotion regulation is a major prerequisite for adaptive behavior. The capacity to regulate emotions is particularly important during and after the encounter of a stressor. However, the impact of acute stress and its associated neuroendocrine alterations on emotion regulation have received little attention so far. This study aimed to explore how stress-induced cortisol increases affect three different emotion regulation strategies. Seventy two healthy men and women were either exposed to a stressor or a control condition. Subsequently participants viewed positive and negative images and were asked to up- or down-regulate their emotional responses or simultaneously required to solve an arithmetic task (distraction). The factors stress, sex, and strategy were operationalized as between group factors (n = 6 per cell). Stress caused an increase in blood pressure and higher subjective stress ratings. An increase in cortisol was observed in male participants only. In contrast to controls, stressed participants were less effective in distracting themselves from the emotional pictures. The results further suggest that in women stress enhances the ability to decrease negative emotions. These findings characterize the impact of stress and sex on emotion regulation and provide initial evidence that these factors may interact.


The effect of IL-12 treatment on vaccine-enhanced illness during infection with respiratory syncytial virus.
In humans and mice, sensitisation to respiratory syncytial virus (RSV) antigens can result in severe inflammatory lung disease during subsequent infection with the virus. Although specific antiviral T cells are thought to be responsible for this augmentation of disease, the precise role of different functional subsets is unknown. BALB/c mice sensitised to the major surface glycoprotein (G) of RSV expressed by recombinant vaccinia virus develop Th2-driven lung eosinophilia after intranasal challenge with the virus. Mice treated with IL-12 at various times during vaccination and challenge, had reduced vaccine-induced lung eosinophilia but increased total pulmonary lymphoid cell infiltration. Intracellular cytokine analysis showed that interferon-gamma production during challenge was increased and IL-4 and IL-5 reduced by IL-12 treatment. Though IL-12 treatment reduced lung eosinophilia, illness (as assessed by weight loss) was not eliminated and sometimes increased. Reversing Th2-associated pathology with IL-12 does not necessarily benefit the host.


Impact of commercial precooking of common bean (Phaseolus vulgaris) on the generation of peptides, after pepsin-pancreatin hydrolysis, capable to inhibit dipeptidyl peptidase-IV.
The objective of this research was to determine the bioactive properties of the released peptides from commercially available precook common beans (Phaseolus vulgaris). Bioactive properties and peptide profiles were evaluated in protein hydrolysates of raw and commercially precooked common beans. Five varieties (Black, Pinto, Red, Navy, and Great Northern) were selected for protein extraction, protein and peptide molecular mass profiles, and peptide sequences. Potential bioactivities of hydrolysates, including antioxidant capacity and inhibition of α-amylase, α-glucosidase, dipeptidyl peptidase-IV (DPP-IV), and angiotensin converting enzyme I (ACE) were analyzed after digestion with pepsin/pancreatin. Hydrolysates from Navy beans were the most potent inhibitors of DPP-IV with no statistical differences between precooked and raw (IC50 = 0.093 and 0.095 mg protein/mL, respectively). α-Amylase inhibition was higher for raw Red, Navy and Great Northern beans (36%, 31%, 27% relative to acarbose (rel ac)/mg protein, respectively). α-Glucosidase inhibition among all bean hydrolysates did not show significant differences; however, inhibition values were above 40% rel ac/mg protein. IC50 values for ACE were not significantly different among all bean hydrolysates (range 0.20 to 0.34 mg protein/mL), except for Red bean that presented higher IC50 values. Peptide molecular mass profile ranged from 500 to 3000 Da. A total of 11 and 17 biologically active peptide sequences were identified in raw and precooked beans, respectively. Peptide sequences YAGGS and YAAGS from raw Great Northern and precooked Pinto showed similar amino acid sequences and same potential ACE inhibition activity. Processing did not affect the bioactive properties of released peptides from precooked beans. Commercially precooked beans could contribute to the intake of bioactive peptides and promote health.


Interaction of Interleukin-17A with a Th2 Response in a Mouse Model of Allergic Airway Inflammation.
A total of 262 million people worldwide suffer from asthma and 461000 people died from it in 2019. Asthma is a disease with different endotypes defined by the granulocytes found in the asthmatic lung. In allergic asthma, the eosinophilic endotype is present, driven by a TH2 response. A TH17 immune response leads to the neutrophil endotype. This often causes uncontrolled asthma and is triggered by pollutants, microbes, and oxidative stress. It has been described that a significant number of patients with eosinophilic asthma develop mixed granulocytic asthma over time. The severity of asthma in the mixed endotype is related to the proportion of neutrophils in the lungs. In this report, we address the question of how a TH2 response interacts with IL-17A in allergic asthma. To this end, we used a mouse model to induce allergic asthma followed by an aerosol challenge with ovalbumin. To investigate the role of IL-17A, we administered IL-17A intranasally during the challenge phase. IL-17A alone did not elicit an immune response, whereas in combination with allergic asthma, it resulted in a shift of the asthmatic endotype from eosinophilic to neutrophilic. TGFβ1 was increased in these lungs compared to asthmatic lungs without IL-17A, as was the expression of the IL-17A receptor subunits IL-17RA and IL-17RC. In cultures with human cells, we also found that IL-17A increased the expression of its receptors only in combination with IL-13. We also found this effect for IL-8, which attracts neutrophils in humans. The TH2 response increased the sensitivity to IL-17A in a mouse asthma model as well as in human cell lines.


Human ocular thelaziasis caused by gravid Thelazia callipaeda - A unique and rare case report.
An 80-year-old male reported to the clinic with complaints of diminished vision, foreign body sensation, and occasionally some black object moving in front of the right eye. Detailed ocular examination revealed three slender creamy white live worms in the conjunctival sac of the right eye. Total three worms were retrieved and sent to the pathology department for detailed examination. The worm was identified as gravid Thelazia callipaeda. As per the search results in PubMed and Cochrane search engine, this is the first report of human case of gravid Thelazia infestation with simultaneous existence of embryonated or ensheathed eggs and primary-stage larvae in the same worm.


DICOM Standard Conformance in Veterinary Medicine in Germany: a Survey of Imaging Studies in Referral Cases.
In 2016, the recommendations of the DICOM Standards Committee for the use of veterinary identification DICOM tags had its 10th anniversary. The goal of our study was to survey veterinary DICOM standard conformance in Germany regarding the specific identification tags veterinarians should use in veterinary diagnostic imaging. We hypothesized that most veterinarians in Germany do not follow the guidelines of the DICOM Standards Committee. We analyzed the metadata of 488 imaging studies of referral cases from 115 different veterinary institutions in Germany by computer-aided DICOM header readout. We found that 25 (5.1%) of the imaging studies fully complied with the "veterinary DICOM standard" in this survey. The results confirmed our hypothesis that the recommendations of the DICOM Standards Committee for the consistent and advantageous use of veterinary identification tags have found minimal acceptance amongst German veterinarians. DICOM does not only enable connectivity between machines, DICOM also improves communication between veterinarians by sharing correct and valuable metadata for better patient care. Therefore, we recommend that lecturers, universities, societies, authorities, vendors, and other stakeholders should increase their effort to improve the spread of the veterinary DICOM standard in the veterinary world.


Acute effects of methadone on EEG power spectrum and event-related potentials among heroin dependents.
Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain's electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts. EEG spectral analysis and single-trial event-related potential (ERP) measurements were used to investigate possible alterations in the brain's electrical activities, as well as the cognitive attributes associated with MMN and P3. The results confirmed abnormal brain activities predominantly in the beta band and diminished information processing ability including lower amplitude and prolonged latency of cognitive responses among heroin addicts compared to healthy controls. In addition, the alteration of EEG activities in the frontal and central regions was found to be associated with the withdrawal symptoms of drug users. Certain brain regions were found to be influenced significantly by methadone intake; acute effects of methadone induction appeared to be associative to its dosage. The findings suggest that methadone administration affects cognitive performance and activates the cortical neuronal networks, resulting in cognitive responses enhancement which may be influential in reorganizing cognitive dysfunctions among heroin addicts. This study also supports the notion that the brain's oscillation powers and ERPs can be utilized as neurophysiological indices for assessing the addiction treatment traits.


Characterization and regulation of the gbuA gene, encoding guanidinobutyrase in the arginine dehydrogenase pathway of Pseudomonas aeruginosa PAO1.
The arginine dehydrogenase (or oxidase) pathway catabolically converts arginine to succinate via 2-ketoglutarate and 4-guanidinobutyrate (4-GB) with the concomitant formation of CO(2) and urea. Guanidinobutyrase (GBase; EC 18.104.22.168) catalyzes the conversion of 4-guanidinobutyrate to 4-aminobutyrate and urea in this pathway. We investigated the structure and regulation of the gene for GBase (designated gbuA) of Pseudomonas aeruginosa PAO1 and characterized the gbuA product. The gbuA and the adjacent gbuR genes were cloned by functional complementation of a gbuA9005 mutant of strain PAO1 defective in 4-GB utilization. The deduced amino acid sequence of GbuA (319 amino acids; M(r) 34,695) assigned GBase to the arginase/agmatinase family of C-N hydrolases. Purified GbuA was a homotetramer of 140 kDa that catalyzed the specific hydrolysis of 4-GB with K(m) and K(cat) values of 49 mM and 1,012 s(-1,) respectively. The divergent gbuR gene, which shared the intergenic promoter region of 206 bp with gbuA, encoded a putative regulatory protein (297 amino acids; M(r) 33,385) homologous to the LysR family of proteins. Insertional inactivation of gbuR by a gentamicin resistance cassette caused a defect in 4-GB utilization. GBase and gbuA'::'lacZ fusion assays demonstrated that this gbuR mutation abolishes the inducible expression of gbuA by exogenous 4-GB, indicating that GbuR participates in the regulation of this gene. Northern blotting located an inducible promoter for gbuA in the intergenic region, and primer extension localized the transcription start site of this promoter at 40 bp upstream from the initiation codon of gbuA. The gbuRA genes at the genomic map position of 1547000 are unlinked to the 2-ketoarginine utilization gene kauB at 5983000, indicative of at least two separate genetic units involved in the arginine dehydrogenase pathway.


Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.
Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival. Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated. Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years. Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.


Low-grade fibromyxoid sarcoma of the vulva.
Patients with a low-grade fibromyxoid sarcoma of the vulva should undergo wide local excision as the primary treatment, but only after the histologic diagnosis is confirmed.


Soybean isoflavone extract improves glucose tolerance and raises the survival rate in streptozotocin-induced diabetic rats.
The present study evaluated the effect of various dosages of soybean isoflavone extract on body weight changes, glucose tolerance and liver function in streptozotocin-induced diabetic rats. One group of normal rats (normal control) was fed an AIN-76-based experimental diet and four groups of diabetic rats were fed the same diet supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The daily consumption of isoflavone at the level of 3.0mg per kilogram of body weight resulted in the suppression of body weight loss and increased the survival rate of diabetic animals one and half times compared to that of the diabetic control group. Blood glucose levels in a fasting state and after the oral administration of glucose were significantly lower in the ISO-II group during the oral glucose tolerance test. The ISO-II group showed a tendency to elongate the gastrointestinal transit time. The activity of serum aminotransferases, indicator of liver function, was not negatively affected by any intake level of isoflavone. The present study demonstrated that the soybean isoflavone extract may be beneficial to diabetic animals by improving their glucose tolerance and suppressing weight loss without incurring hepatotoxicity at the daily dosage of 3.0 mg per kg of body weight.


Scyphocephalione A isolated from the stem bark of Scyphocephalium ochocoa (Myristicaceae) attenuate acute and chronic pain through the antiinflammatory activity.
In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound isolated from Scyphocephalium ochocoa (Myristicaceae), a medicinal plant traditionally used in African countries. Recently, an in vitro study has shown its anti-inflammatory and cytotoxic activities on MCF-7 cell line of mammary carcinoma. The purpose of the present study was to assess the in vitro anti-inflammatory and in vivo anti-nociceptive activities of Scyphocephalione A. In vitro tests were carried out on cyclooxygenase and 5-lipoxygenase activities, and on protein denaturation; while in vivo tests were performed on acute and chronic pain models. It was noticed that Scyphocephalione A (1000 µg/ml), inhibits proteins denaturation, cyclooxygenase and 5-lipoxygenase activities respectively by 74.21%, 75.80% and 64.43%. The dose 50 mg/kg of Scyphocephalione A, inhibits acetic acid (63.43%, p < 0.001) and formalin (42.12%, p < 0.001) within first phase and 67.53% (p < 0.001) within second phase)-induced pains. At the same dose, Scyphocephalione A significantly inhibited mechanical and heat hyperalgesia, as well as cold allodynia induced by vincristine. In addition, the compound restored haematological, biochemical and oxidative stress parameters which were altered following Vincristine administration. These results suggest that Scyphocephalione A is endowed with anti-inflammatory potential and antinociceptive properties. Therefore, Scyphocephalione A can be classified as a promising molecule for the management of peripheral neuropathic pain triggered by anti-cancer drug.


[Carbon nanotubes - Characteristic of the substance, biological effects and occupational exposure levels].
Carbon nanotubes (CNTs) are a diverse group of nano-objects in terms of structure, size (length, diameter), shape and characteristics. The growing interest in these structures is due to the increasing number of people working in exposure to CNTs. Occupational exposure to carbon nanotubes may occur in research laboratories, as well as in plants producing CNTs and their nanocomposites. Carbon nanotubes concentration at the emission source may reach 107 particles/cm3. These values, however, are considerably reduced after the application of adequate ventilation. Animal studies suggest that the main route of exposure is inhalation. Carbon nanotubes administered orally are largely excreted in the feces. In animals exposed by inhalation, CNTs caused mainly inflammation, as a result of oxidative stress, leading above all to changes in the lungs. The main effect of animal dermal exposure is oxidative stress causing local inflammation. In animals exposed by ingestion the mild or no toxicity was observed. Carbon nanotubes did not induce mutations in the bacterial tests, but they were genotoxic in a series of tests on cells in vitro, as well as in exposed mice in vivo. Embryotoxicity of nanotubes depends mainly on their modifications and carcinogenicity - primarily on the CNT size and its rigidity. Occupational exposure limits for CNTs proposed by world experts fall within the range of 1-80 μg/m3. The different effects of various kinds of CNT, leads to the conclusion that each type of nanotube should be treated as a separate substance with individual estimation of hygienic normative. Med Pr 2017;68(2):259-276.


The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients.
Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.


3-Hydroxy-3-methylglutaric aciduria with bilateral basal ganglia lesion: A case report.
3-Hydroxy-3-methylglutaric aciduria (3-HMG, OMIN 246450) is a rare autosomal recessive metabolic disorder caused by a deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase, a key enzyme in leucine metabolism and ketone body synthesis. Acute episodes of 3-HMG may be triggered by fasting or infection, and symptoms include vomiting, diarrhea, lethargy and hypotonia. If left untreated, prolonged hypoglycemia and metabolic acidosis may cause breathing problems, seizures, and coma. In addition, 3-HMG is associated with damage to the central nervous system, and there are several reports of white matter abnormality or cerebral atrophy. The presence of bilateral basal ganglia damage in 3-HMG has been rarely reported. Here, we present a case report of a 20-month old male with severe 3-HMG and prominent bilateral lesions in the basal ganglia.


Clinical practice of endoscopic submucosal dissection for early colorectal neoplasms by a colonoscopist with limited gastric experience.
Objectives. Endoscopic submucosal dissection (ESD) for early colorectal neoplasms is regarded as a difficult technique and should commence after receiving the experiences of ESD in the stomach. The implementation of colorectal ESD in countries where early gastric cancer is uncommon might therefore be difficult. The aim is to delineate the feasibility and the learning curve of colorectal ESD performed by a colonoscopist with limited experience of gastric ESD. Methods. The first fifty cases of colorectal ESD, which were performed by a single colonoscopist between July 2010 and April 2013, were enrolled. Results. The mean of age was 64 (±9.204) years with mean size of neoplasm at 33 (±12.63) mm. The mean of procedure time was 70.5 (±48.9) min. The rates of en bloc resection, R0 resection, and curative resection were 86%, 86%, and 82%, respectively. Three patients had immediate perforation, but no patient developed delayed perforation or delayed bleeding. Conclusion. Our result disclosed that it is feasible for colorectal ESD to be performed by a colonoscopist with little experience of gastric ESD through satisfactory training and adequate case selection.