Socialization, and its modulation by sex, on the development and recovery of activity-based anorexia in rats.
The activity-based anorexia (ABA) animal model has been used in the laboratory to study the role of excessive physical activity in the manifestation of anorexia nervosa (AN) in humans. Factors of social context are crucial in human health and the emergence of many psychological disorders, which have also been observed in studies using different mammal species that, like human beings, set their lives in groups. In the present study, the animals' social condition was manipulated to observe the effect of socialization in ABA development, and the possible different influence of the variable sex on the phenomenon. Eighty Wistar Han rats were distributed into four male and four female groups with 10 subjects each, manipulating social conditions (group housing or social isolation) and physical activity (access or not to a running wheel). Throughout the procedure, all groups had food restricted to 1 h/day during the light period. Furthermore, ABA experimental groups with access to the running wheel had two periods of access to the wheel of 2 h each, one before and the other after the food period. In this experiment, socialized rats were less vulnerable to weight loss during the procedure, although there were no differences between the ABA groups. Moreover, social enrichment was shown to be an enabling variable of the animals' recovery after their withdrawal from the procedure, with this effect being more pronounced in females. The results in this study suggest the need to further in the analysis of the role of socialization in the development of ABA.


Evidence of vancomycin resistance gene transfer between enterococci of human origin in the gut of mice harbouring human microbiota.
Potential intra- and inter-species transfers of vancomycin resistance genes (vanA gene cluster) between Enterococcus strains were evaluated in the gut of heteroxenic mice harbouring a human microbiota. Mice colonized with a stable population of E. faecium 64/3 or E. faecalis JH2-2 recipient strain and harbouring an enterococci-free human microbiota were obtained. Donor strain E. faecium HC-VI2 of clinical origin was administered orogastrically to these mice and transfers were evaluated over time in faecal samples. Only intraspecies transfers were detected in the digestive tract (DT) of mice harbouring a human microbiota. E. faecium 64/3 transconjugants were detected at several sampling times over the 60 day experiment to levels up to 10(3) cfu/g of faeces, but they did not steadily colonize the DT. Here, we show for the first time that transfer of the vanA gene cluster can occur between Enterococcus strains in the DT colonized with a human microbiota and in the absence of selective pressure. The colonization properties of other enterococci transconjugants and the influence of vancomycin intake should be further investigated since transfers in the DT of animals and humans might contribute to emergence and dissemination of new vancomycin-resistant bacteria.


Decontamination of collards (Brassica oleracea var. acephala L.) using electrolyzed water and corona discharge plasma jet.
Acidic electrolyzed water (AEW) was used for collards sanitization. In the AEW (pH of 3.6; 230 mg/L chlorine) generator, the rates of brine inflow and catholyte outflow were 2.73 and 442 mL/min, respectively. Following treatment of the collards with the AEW alone (5 min), the counts of aerobic bacterial contaminants were reduced by 1.91 log CFU/g, whereas 2.22 log CFU/g reduction was noted by the AEW soaking (5 min) followed by a corona discharge plasma jet treatment (1 min). In a similar manner, the counts of yeasts and mold contaminants were reduced (1.48 and 1.75 log CFU/g, respectively). The combination treatment exhibited an additive effect on the microbial inactivation. The combined treatment did not affect significantly the DPPH-radical scavenging activity and sensory properties (appearance, color and flavor) of the collards compared to negative controls. However, significant alterations in the levels of total phenolics and ascorbic acid were observed post-treatment.


Effects of nephron reduction and dietary protein content on renal ammoniagenesis in the rat.
Urinary ammonium excretion, in vitro ammoniagenesis and the activities of renal cortical phosphate-dependent glutaminase (PDG) and glutamic dehydrogenase (GLDH) were measured in rats with a reduced renal mass. Following contralateral nephrectomy, ammonium excretion per nephron, ammonia production and the activities of PDG and GLDH were all increased significantly in remnant kidneys of rats fed high protein diets. In rats fed low protein diets, although PDG activity increased, GLDH activity and ammonia production and excretion did not increase in remnant kidneys following contralateral nephrectomy. Ammonia production and excretion were greater in rats fed high than low protein diets, a difference that was corrected by the addition of mineral acid to the diets of low protein-fed rats. Acid supplementation to the low protein group did not result in enhanced ammonia production or GLDH activity following a reduction in renal mass. The data indicate that the increased rate of ammoniagenesis which occurs following nephron reduction is markedly influenced by dietary protein content. A lack of enhanced GLDH activity may underlie the lack of increased ammonia production of low protein-fed rats following nephron reduction.


Successful stereotaxic evacuation of an acute pontomedullary hematoma. Case report.
A healthy young woman developed a rapidly progressive pontomedullary lesion 24 hours after delivery of her first child. The lesion was shown on computerized tomography (CT) to be a primary hematoma. Stereotaxic aspiration was carried out, and the patient recovered. Angiography and CT scanning demonstrated a vascular lesion compatible with an arteriovenous malformation.


High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana.
We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis. This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and <20%. Overall, 66.7% (16/24) of participants had at least one HIV-1 drug resistance mutation in the CSF and/or plasma. A total of 15/22 (68.2%) participants had HIV-1 drug resistance mutations at ≥20% threshold in the plasma and of those, 11 (73.3%) had been on ART longer than 6 months. HIV-1 drug resistance mutations were highly concordant between the CSF and plasma at ≥20% threshold despite a substantial number of individuals experiencing CSF viral escape and with only 54.5% with CSF WBC count ≥20 cells/mm3. Minority HIV-1 drug resistance mutations were detected in 20.8% (5/24) of participants. There were no mutations in the CSF that were not detected in the plasma. There was high concordance in HIV-1 drug resistance mutations in the CSF and plasma, suggesting intercompartmental mixing and possibly a lack of compartmentalization. Some individuals harboured minority HIV-1 drug resistance mutations, demonstrating the need to employ more sensitive genotyping methods such as next-generation sequencing for the detection of low-abundance mutations.


Erotomanic delusions in mentally handicapped patients: two case reports.
Two cases of mentally handicapped patients, who developed delusions of passion, are described. The relationship of these cases to de Clerambault's Syndrome, and their pathogenetic features, are discussed.


Detection of urine C2C and trace element level in patients with knee osteoarthritis.
The objective is to determine the relation between severity of knee osteoarthritis (KOA) and levels of Collagen type II metabolite (C2C) and trace elements in the urine. The urine sample and knee joint films (anteroposterior and lateral) from the KOA patients and control subjects were collected. The KOA patients were divided into five groups (controls and grades I-IV) according to the Kellgren-Lawrence radiographic grading standards. Urine levels of C2C and trace elements were detected by enzyme-linked immunosorbent assay and inductively coupled plasma atomic emission spectrometry, respectively. Urine C2C levels in the KOA subjects (261.235 ± 39.944 pg/ml) were higher than those of the control group (218.341 ± 22.270 pg/ml). The Fe content in KOA groups was significantly lower than that of control group (group IV > group III > group II > group I or controls). The contents of Cu and Zn were also significantly higher in the KOA patients than in the control group (p < 0.05). However, Cr, Al, Cd, Ni, and Se levels of KOA patients were not significantly different from those of the controls (p > 0.05). Determination of the urine levels of C2C and trace elements may prove to be informative for an early diagnosis of KOA. It can also assist in the prognosis judgment of the disease and selecting an appropriate therapeutic regimen.


Randomized clinical trials of COVID-19 vaccines: Do adenovirus-vector vaccines have beneficial non-specific effects?
We examined the possible non-specific effects of novel mRNA- and adenovirus-vector COVID-19 vaccines by reviewing the randomized control trials (RCTs) of mRNA and adenovirus-vector COVID-19 vaccines. We calculated mortality risk ratios (RRs) for mRNA COVID-19 vaccines vs. placebo recipients and compared them with the RR for adenovirus-vector COVID-19 vaccine recipients vs. controls. The RR for overall mortality of mRNA vaccines vs. placebo was 1.03 (95% confidence interval [CI]: 0.63-1.71). In the adenovirus-vector vaccine RCTs, the RR for overall mortality was 0.37 (0.19-0.70). The two vaccine types differed significantly with respect to impact on overall mortality (p = 0.015). The RCTs of COVID-19 vaccines were unblinded rapidly, and controls were vaccinated. The results may therefore not be representative of the long-term effects. However, the data argue for performing RCTs of mRNA and adenovirus-vector vaccines head-to-head comparing long-term effects on overall mortality.


The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer-promoter communication.
How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle-one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer-promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.


Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis.
BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer.METHODS: One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system.


Subdiffusion supports joining of correct ends during repair of DNA double-strand breaks.
The mobility of damaged chromatin regions in the nucleus may affect the probability of mis-repair. In this work, live-cell observation and distance tracking of GFP-tagged DNA damage response protein MDC1 was used to study the random-walk behaviour of chromatin domains containing radiation-induced DNA double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair. It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.


Rhodospirillum centenum, sp. nov., a thermotolerant cyst-forming anoxygenic photosynthetic bacterium.
A novel non-sulfur purple photosynthetic bacterium, designated Rhodospirillum centenum, was isolated from an enrichment culture designed to favor growth of anoxygenic photosynthetic N2-fixing bacteria. R. centenum grows optimally at 40-42 degrees C and has the capacity to produce cytoplasmic 'R bodies', refractile structures not observed hitherto in photosynthetic prokaryotes. The bacterium is also unusual among photosynthetic bacteria in that it forms desiccation-resistant cysts when grown aerobically in darkness with butyrate as the sole carbon source.


TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial.
A number of recent studies have not replicated the association of the translocase of the outer mitochondrial membrane pore subunit (TOMM40) rs10524523 polymorphism, which is in linkage disequilibrium with apolipoprotein E (APOE), with age of onset of Alzheimer's disease (AD). This perspective describes the differences between these later studies and the original experiments. We highlight the necessity for using standardized and informative assessment tools and processes when determining the age of development of AD or AD symptoms, and also stress that this clinical phenotype is best measured reliably in prospective studies during which subjects are monitored over time. This is true when assessing potential biomarkers for age of onset and when assessing the therapeutic potential of medicines that may delay the onset or progression of this disease.


[Changes in imipramine induced noradrenaline potentiation by varying activity of gastric juice under oral medication].
From the serial studies on imipramine dependent noradrenaline (NA) rise at different values of gastric acid with 336 registrations of blood pressure, it follows that a lawful relation exists between imipramine absorption and gastric juice acidity. At pH values of 3.5--6.0 a distinct decreased absorption of orally supplied imipramine was stated. After changing the pH value by acid substitution, a full absorption is reached. This state seems to be of special practical importance in the treatment of depression with thymoleptics.


The effect of ophthalmic preservatives on the shape of corneal endothelial cells.
The mean area (293.6 +/- 53.6 micrometers 2) and perimeter (65.5 +/- 5.8 micrometers) of individual cells were determined from the photographed endothelium of a total of 54 guinea pig corneas, after staining with silver nitrate and removal of the epithelium and stroma. In addition a quantitative assessment of cell shape S (= P2/A) was calculated. The mean cell density (3406 +/- 619 cells per mm2) was similar to that for young humans, and the S value (14.76 +/- 0.73) was as expected for slightly irregular hexagonal and pentagonal shapes. Incubation of the corneas in glutathione-bicarbonate-Ringer solution for periods up to 4 h resulted in only slight changes in the endothelial cell shape (S = 15.21 +/- 0.89). However, incubation with thimerosal (0.01%) for 2 h (S = 16.78 +/- 1.79) or with disodium ethylenediaminetetraacetate (Na2EDTA) (0.2%) for 1 h (S = 17.20 +/- 2.36) gave a marked increase in the tortuosity of the cell 'outlines'. Longer periods of contact with Na2EDTA resulted in a rounding up and separation of endothelial cells.


Knowledge and use of and opportunities for emergency contraception in Northern Haiti.
To evaluate the knowledge and experience of, and desire for, emergency contraception (EC) in postpartum women in Haiti, and to determine the knowledge and practices of EC providers. As part of a larger postpartum family planning study, 6 focus groups were conducted with postpartum women (n=33), 3 were conducted with providers (n=22), and a questionnaire was given to postpartum women (n=250). Of the 249 women who completed the survey, 145 (58.2%) were aware of the concept of EC as an emergency measure in the postcoital period. Of these, 130 (89.7%) had knowledge of traditional methods only. Twenty-eight (11.2%) women had used some form of EC in the past, but only 2 (0.8%) reported ever using a modern form of EC. Providers reported that EC was offered to women only in cases of sexual assault. Their impression was that there was no demand for EC. Awareness and use of EC is low in the context of high unmet need. The results demonstrate a need for improved education and provision of modern effective EC as part of the constellation of family planning choices.


[Cyclothymia and the brain stem. The question of symptomatic cyclothymia on the basis of observations in insufficiency of the basilar arterial system].
Seven patients with an insufficiency in the basilar arterial system showed a typical endogenous depression. We assumed that the temporal coincidence of neurological and psychial syndromes was not accidental but both were caused by a circulation disturbance in the cerebral stem structures.


Immunomodulatory activity of polysaccharides isolated from Salicornia herbacea.
Several types of immunomodulatory polysaccharides originated from plants or mushrooms have been used as immunotherapeutic agents in the treatment of cancers. Here, we describe an immunomodulatory polysaccharide that cannot only activate monocytic cells strongly, but also induce differentiation of monocytic cells into macrophages. High molecular weight substances, SHE, were isolated from Salicornia herbacea, which has been used to treat a variety of diseases including cancers in traditional oriental remedy. The immunomodulatory activities of SHE were examined on a mouse monocytic cell line, RAW 264.7 cells. We found that SHE activated RAW cells to produce cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, and nitric oxide (NO) dose dependently. SHE also induced the expression of co-stimulatory molecules such as B7-1 and CD40, and increased phagocytic activity on opsonized sheep red blood cells. While increasing these parameters of macrophage activation, SHE inhibited the growth of RAW cells dose dependently inducing morphological changes from slightly adherent monocytic cells to strongly adherent macrophages. The active components of SHE appeared to be polysaccharides, and not an endotoxin. These results show that polysaccharides originated from S. herbacea possess potent immunomodulatory activity on monocyte/macrophage lineage cells.


A new training package (3Cs: Connect, Communicate and Collaborate) for improving family responsive service delivery in early intervention for children with hearing loss: A proof of concept study.
An objective of early intervention for children with hearing loss is to enhance family engagement in therapy to maximise a child's speech and language potential. However, requiring a service provider to work collaboratively with a child's family can create problems in developing and underdeveloped countries, where skilled service providers and services for children with hearing loss are lacking and where an expert model of intervention prevails. To determine the preliminary effectiveness of a new training package Connect, Communicate and Collaborate (3Cs), in improving the knowledge and confidence of service providers in the delivery of family responsive services in an early intervention program for children with hearing loss. Five learning modules were developed based on service provider experience working with children with hearing loss, and parents of children with hearing loss. Six participants completed the training package comprising five training modules and an introductory session over a 6-week period. Participants' confidence and knowledge in providing family responsive practice was measured pre and post training using visual analogue scales, and participants were also invited to provide their reflections on the program. Pre- and post-training confidence ratings revealed significant improvements in the perceptions of participants in the implementation of responsive family practice across four of five of programme learning modules (p < 0.002). Participant reflection statements indicate they became more considerated in their family responsive practice. Despite positive experiences working with parents, participants stated they had ongoing difficulties guiding families through the decision-making processes of habilitation. The reflection process assisted learning and improved practice by supporting participants to build on their strengths. The 3Cs package improved the confidence in and knowledge of delivery of responsive family services for six participants in Kuwait. It also improved the participant's self-evaluation skills. The 3Cs provides professional development that meets the needs of service providers working with children with hearing loss to improve inclusion of families in the therapy process.


Genome-wide investigation of toll-like receptor genes (TLRs) in Procambarus clarkia and their expression pattern in response to black may disease.
As a crucial component of pattern-recognition receptors (PRRs) that recognizing pathogen-associated molecular patterns (PAMPs) and defending against invading pathogens, the Toll-like receptors (TLRs) have been paid extensive attention. While the identification and functional roles of TLRs in innate immunity have been reported in a plenty of organisms, the systematic knowledge of TLRs is still lacking in the red swamp crayfish (Procambarus clarkia). In current study, a total of 7 tlr genes were identified in P. clarkia based on the published transcriptome and genome data. The PcTLRs length varied from 939 to 1517aa and contain typical domains of TLR protein, including transmembrane region, varied LRR and TIR domains. 7 Pctlr genes were distributed in 5 chromosomes and 2 scaffolds. The expression pattern of different Pctlr genes in different tissues (hepatopancreas, gill and muscle) and in response to black may disease (BMD) showed significant difference. In addition, 5 proteins that might interact with PcTLR-2 were predicted, among them the expression pattern of dorsal and relish was consistent with Pctlr-2 in three tissues, while the other genes were not. The PcTLR-2-Dorsal/Relish pathway might play crucial roles in response to BMD infection. The results provided a theoretical foundation for further studies on the molecular mechanisms of TLRs in BMD infection in the red swamp crayfish and provided reference for the research of other crustacean species.


Correlation of initial food reactions to observed reactions on challenges.
Food allergies occur in 2% to 3% of the pediatric population. These reactions can vary from mild cutaneous manifestations to severe life-threatening reactions. Limited information is available on which specific factors may predict the severity of subsequent reactions. To determine whether the organ system or the specific food involved in the initial allergic reaction predicts the outcome of subsequent food challenge. Retrospective review of all food sensitive children who underwent food challenges at The Children's Hospital of Philadelphia, Philadelphia, PA, in a 5-year period (n = 998 challenges). The specific food, initial symptom on presentation, and reaction on open challenges were recorded. A total of 413 of 998 food challenges produced positive results. Milk, egg, and peanut were the most common foods to be associated with a positive challenge result. The most common presentation of food allergy was cutaneous followed by multiorgan reactions. Peanut, milk, and egg sensitivities were more likely to cause a multiple-organ system reaction on challenge than wheat or other foods. Patients with egg allergy were more likely to have a different reaction on rechallenge than other foods. Milk, egg, and peanut are the most common foods associated with food challenges. Patients will typically experience similar reaction on re-exposure to the initial reaction. However, multiple-organ system reactions can occur after any initial clinical presentation, with milk, egg, and peanut having more multiple-organ reactions than other foods.


Airflow obstruction, lung function, and risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) study.
We examined the relationship between forced expiratory volume in 1 s (FEV(1)), airflow obstruction, and incident heart failure (HF) in black and white, middle-aged men and women in four US communities. Lung volumes by standardized spirometry and information on covariates were collected on 15 792 Atherosclerosis Risk in Communities (ARIC) cohort participants in 1987-89. Incident HF was ascertained from hospital records and death certificates up to 2005 in 13 660 eligible participants. Over an average follow-up of 14.9 years, 1369 (10%) participants developed new-onset HF. The age- and height-adjusted hazard ratios (HRs) for HF increased monotonically over descending quartiles of FEV(1) for both genders, race groups, and smoking status. After multivariable adjustment for traditional cardiovascular risk factors and height, the HRs [95% confidence intervals (CIs)] of HF comparing the lowest with the highest quartile of FEV(1) were 3.91 (2.40-6.35) for white women, 3.03 (2.12-4.33) for white men, 2.11 (1.33-3.34) for black women, and 2.23 (1.37-3.59) for black men. The association weakened but remained statistically significant after additional adjustment for systemic markers of inflammation. The multivariable adjusted incidence of HF was higher in those with FEV(1)/forced vital capacity <70% vs. ≥70%: HR 1.44 (95% CI 1.20-1.74) among men and 1.40 (1.13-1.72) among women. A consistent and positive association with HF was seen for self-reported diagnosis of emphysema and chronic obstructive pulmonary disease, but not for asthma. In this large population-based cohort with long-term follow-up, low FEV(1) and an obstructive respiratory disease were strongly and independently associated with the risk of incident HF.


OXIDATIVE SIGNAL-INDUCIBLE1 induces immunity by coordinating N-hydroxypipecolic acid, salicylic acid, and camalexin synthesis.
Expression of OXIDATIVE SIGNAL-INDUCIBLE1 (OXI1) is induced by a number of stress conditions and regulates the interaction of plants with pathogenic and beneficial microbes. In this work, we generated Arabidopsis OXI1 knockout and genomic OXI1 overexpression lines and show by transcriptome, proteome, and metabolome analysis that OXI1 triggers ALD1, SARD4, and FMO1 expressions to promote the biosynthesis of pipecolic acid (Pip) and N-hydroxypipecolic acid (NHP). OXI1 contributes to enhanced immunity by induced SA biosynthesis via CBP60g-induced expression of SID2 and camalexin accumulation via WRKY33-targeted transcription of PAD3. OXI1 regulates genes involved in reactive oxygen species (ROS) generation such as RbohD and RbohF. OXI1 knock out plants show enhanced expression of nuclear and chloroplast genes of photosynthesis and enhanced growth under ambient conditions, while OXI1 overexpressing plants accumulate NHP, SA, camalexin, and ROS and show a gain-of-function (GOF) cell death phenotype and enhanced pathogen resistance. The OXI1 GOF phenotypes are completely suppressed when compromising N-hydroxypipecolic acid (NHP) synthesis in the fmo1 or ald1 background, showing that OXI1 regulation of immunity is mediated via the NHP pathway. Overall, these results show that OXI1 plays a key role in basal and effector-triggered plant immunity by regulating defense and programmed cell death via biosynthesis of salicylic acid, N-hydroxypipecolic acid, and camalexin.


Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study.
Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. Cardiac arrest was induced in 18 female pigs (50 ± 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (≤20 µm) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05-100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's ρ 0.02-0.51) and after adjustment for multiple correlations it was non-significant. Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR.


Selection of reference genes for gene expression studies in virus-infected monocots using quantitative real-time PCR.
Both genome-wide transcriptomic surveys of the mRNA expression profiles and virus-induced gene silencing-based molecular studies of target gene during virus-plant interaction involve the precise estimation of the transcript abundance. Quantitative real-time PCR (qPCR) is the most widely adopted technique for mRNA quantification. In order to obtain reliable quantification of transcripts, identification of the best reference genes forms the basis of the preliminary work. Nevertheless, the stability of internal controls in virus-infected monocots needs to be fully explored. In this work, the suitability of ten housekeeping genes (ACT, EF1α, FBOX, GAPDH, GTPB, PP2A, SAND, TUBβ, UBC18 and UK) for potential use as reference genes in qPCR were investigated in five different monocot plants (Brachypodium, barley, sorghum, wheat and maize) under infection with different viruses including Barley stripe mosaic virus (BSMV), Brome mosaic virus (BMV), Rice black-streaked dwarf virus (RBSDV) and Sugarcane mosaic virus (SCMV). By using three different algorithms, the most appropriate reference genes or their combinations were identified for different experimental sets and their effectiveness for the normalisation of expression studies were further validated by quantitative analysis of a well-studied PR-1 gene. These results facilitate the selection of desirable reference genes for more accurate gene expression studies in virus-infected monocots.


Clinical utility of urinary mulberry bodies/cells testing in the diagnosis of Fabry disease.
Variants in the galactosidase alpha (GLA) gene cause Fabry disease (FD), an X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL) deficiency. Recently, disease-modifying therapies have been developed, and simple diagnostic biomarkers for FD are required to initiate these therapies in the early stages of the disease. Detection of urinary mulberry bodies and cells (MBs/MCs) is beneficial for diagnosing FD. However, few studies have evaluated the diagnostic accuracy of urinary MBs/MCs in FD. Herein, we retrospectively evaluated the diagnostic ability of urinary MBs/MCs for FD. We analyzed the medical records of 189 consecutive patients (125 males and 64 females) who underwent MBs/MCs testing. Out of these, two female patients had already been diagnosed with FD at the time of testing, and the remaining 187 patients were suspected of having FD and underwent both GLA gene sequencing and/or α-GalA enzymatic testing. Genetic testing did not confirm the diagnosis in 50 females (26.5%); hence, they were excluded from the evaluation. Two patients were previously diagnosed with FD, and sixteen were newly diagnosed. Among these 18 patients, 15, including two who had already developed HCM at diagnosis, remained undiagnosed until targeted genetic screening of at-risk family members of patients with FD was performed. The accuracy of urinary MBs/MCs testing exhibited a sensitivity of 0.944, specificity of 1, positive predictive value of 1, and negative predictive value of 0.992. MBs/MCs testing is highly accurate in diagnosing FD and should be considered during the initial evaluation prior to genetic testing, particularly in female patients.


Amino acid sequences of ferredoxins from Atropa belladonna and Hyoscyamus niger: their similarities to those in other tropane-alkaloid-containing plants.
The complete amino acid sequences of [2Fe-2S] ferredoxin from Atropa belladonna and Hyoscyamus niger have been determined by automated Edman degradation of the entire S-carboxymethylcysteinyl proteins and of the peptides obtained by enzymatic digestion. These two ferredoxins exhibited 1-8 differences in their amino acid sequences compared to those of other tropane-alkaloid-containing plants (Scopolia japonica, Datura stramonium, D. metel, and D. arborea), and only 1 or 4 differences compared to S. japonica and D. arborea. In contrast, 9-23 differences were observed among the other solanaceous ferredoxins. This suggests that tropane-alkaloid-containing plants are closely related taxonomically.


Inducibility of atrial fibrillation before and after radiofrequency catheter ablation of accessory atrioventricular connections.
The purpose of this study was to evaluate the inducibility of atrial fibrillation in patients with an accessory atrioventricular connection (AAVC) and to determine if the inducibility of atrial fibrillation is altered after successful radiofrequency catheter ablation of the AAVC. Thirty-seven patients with an AAVC and 36 control patients were prospectively evaluated using a standardized atrial pacing protocol. The high right atrium was paced using a 25-beat drive train, 1.5-second intertrain pause, 10-mA pulse amplitude, and 2-msec pulse duration at cycle lengths of 250 to 100 msec, in 10-msec decrements. Pacing was performed twice at each cycle length. Thirty patients with an AAVC underwent repeat atrial overdrive pacing after successful radiofrequency ablation of the AAVC. Atrial fibrillation was induced in 26 (70%) patients with an AAVC and 22 (61%) controls (P = NS). Atrial flutter was induced in 11 (30%) patients with an AAVC and 13 (36%) controls (P = NS). The cumulative percentage of patients with atrial fibrillation/flutter induced at each pacing cycle length was the same in each group. There was no difference in the duration of atrial fibrillation/flutter between control patients and patients with an AAVC. Among the 30 patients who underwent repeat atrial overdrive pacing after radiofrequency ablation of an AAVC, there was no difference in the inducibility or duration of atrial fibrillation/atrial flutter after ablation compared to baseline. These findings indicate that the vulnerability of the atrium to fibrillate in response to atrial pacing is independent of the presence of an AAVC.


12-Ethyl-6a,10a-di-hydro-5H-6-oxachrysene.
In the title compound, C19H16O, the pyran ring is in a half-chair conformation. The essentially planar naphthalene ring system (r.m.s. deviation = 0.020 Å) forms a dihedral angle of 14.37 (5)° with the fused benzene ring. In the crystal, pairs of mol-ecules are connected into inversion dimers by weak C-H⋯O hydrogen bonds to generate R 2 2(6) loops.


Myocardial histopathology in late-repaired and unrepaired adults with tetralogy of Fallot.
Survival of patients after repair of tetralogy of Fallot (TOF) is worse than for the general population. We aimed to assess the time-related effects of surgical repair on right (RV) and left ventricle (LV) myocardium by quantifying hypertrophy and fibrosis. Cardiomyocyte transverse diameter and percent of fibrosis were measured in 8 adult heart specimens with late-repaired TOF, 6 with unrepaired TOF, and 11 normal hearts (controls). The RV and LV mean and median cardiomyocyte diameter and percent of fibrosis were significantly greater than controls in both repaired and unrepaired hearts. The mean RV inferior wall myocyte diameter in unrepaired hearts was significantly greater at average age at death than in repaired hearts (24.9±2.5 vs. 16.4±1.3μm, P=.015), but not the mean RV anterior wall myocyte diameter (21.5±2.2 vs. 17±1.2μm, P=.09) or the mean LV myocyte diameter (19.7±1.5 vs. 16.7±0.8μm, P=.10). Of the RV myocyte diameter measurements, only the RV anterior wall myocyte diameter for repaired hearts correlated with age at death, while LV myocyte diameter for both repaired and unrepaired hearts correlated with age at death. None of the measures of myocyte diameter correlated with age at repair. The mean RV anterior wall, inferior wall, and LV percent fibrosis were all significantly greater in unrepaired hearts at average age at death compared with repaired hearts (16.3±1.3 vs. 13.0±0.7%, P=.04; 18.1±1.9 vs. 12.7±1.0%, P=.03; 15.7±0.8 vs. 11.6±0.4%, P=.004, respectively). There was a significant correlation between RV percent fibrosis (both locations) and age at death for repaired hearts but not for unrepaired hearts, while LV wall percent fibrosis correlated significantly with age at death for both groups. RV percent fibrosis was not significantly correlated with age at repair, while LV percent fibrosis was negatively correlated with age at repair. Hypertrophy and fibrosis in RV and LV of late-repaired TOF hearts progress during follow-up despite a good repair. These could be the substrate of ventricular dysfunction and arrhythmia seen clinically late after correction.


Minimizing acylation of peptides in PLGA microspheres.
The main objective of this study was to characterize and find mechanisms to prevent acylation of therapeutic peptides encapsulated in glucose-star poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. The effect of addition of divalent cation salts CaCl(2), MnCl(2) as well as carboxymethyl chitosan (CMCS) on inhibition of acylation of octreotide (Oct), salmon calcitonin (sCT), and human parathyroid hormone (hPTH) was evaluated. Peptide content and integrity inside the degrading microspheres was monitored by reversed-phase high performance liquid chromatography (HPLC) and mass spectrometry during release incubation under physiological conditions. The extent of peptide acylation was strongly inhibited in the formulations containing divalent cations and/or CMCS as excipients, although specific effects were dependent on the specific peptide and excipient combinations. Both inorganic cations improved stability of Oct and hPTH but not sCT. Addition of CMCS alone was ineffective. Combining inorganic cations with CMCS improved stability of Oct and sCT but it had no effect on hPTH stability. The operative stabilization mechanisms are consistent with blocking peptide-PLGA interactions by a) directly competing for PLGA interactions with dications and/or b) increasing peptide affinity in the stabilizer phase within PLGA pores. Hence, inorganic multivalent cations are general stabilizers against peptide acylation, the effect of which may be augmented in certain instances with addition of CMCS.


Comparison of interleukin 1 production by adherent cells and tissue pieces from human placenta.
Monocytes/macrophages from placenta have been reported to produce the immunological factor interleukin 1. In the present study both isolated adherent cells and tissue pieces produced interleukin 1, but the tissue piece culture supernatants also had colony stimulating activity. None of the following active factors were found in either culture supernatants: interleukin 2, interferon, erythropoietin and platelet-derived growth factor. Lysates of isolated placental cells contained interleukin 1, indicating that the factor was being produced in utero. Placentas from caesarean deliveries were likewise found to produce more interleukin 1 than placentas from normal term deliveries. The role(s) of placental-produced interleukin 1 is yet to be defined.


Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.
Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.


The Atomic, Molecular and Optical Science instrument at the Linac Coherent Light Source.
The Atomic, Molecular and Optical Science (AMO) instrument at the Linac Coherent Light Source (LCLS) provides a tight soft X-ray focus into one of three experimental endstations. The flexible instrument design is optimized for studying a wide variety of phenomena requiring peak intensity. There is a suite of spectrometers and two photon area detectors available. An optional mirror-based split-and-delay unit can be used for X-ray pump-probe experiments. Recent scientific highlights illustrate the imaging, time-resolved spectroscopy and high-power density capabilities of the AMO instrument.


Construction of a series of congenic mice with recombinant chromosome 1 regions surrounding the genetic loci for resistance to intracellular parasites (Ity, Lsh, and Bcg), DNA repair responses (Rep-1), and the cytoskeletal protein villin (Vil).
The interval of mouse chromosome 1 extending from Idh-1 to Pep-3 harbors the natural resistance gene Ity/Lsh/Bcg; it controls the outcome of infection with Salmonella typhimurium, Leishmania donovani, and several Mycobacterium species. This region also contains a DNA repair gene, Rep-1, which determines the rapidity with which double-strand breaks in chromatin are repaired. BALB/cAnPt and DBA/2N mice differ in their phenotypic expression of these genes. To generate appropriate strains of mice for the study of these genes, a series of 10 C.D2 congenic strains recombinant across a 28-centimorgan interval of mouse chromosome 1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3 congenic strain back to BALB/cAn. Analyses of these recombinant strains will allow the correlation of biological-immunological phenotypes with defined genetic regions.


One-stop hybrid coronary revascularization versus coronary artery bypass grafting and percutaneous coronary intervention for the treatment of multivessel coronary artery disease: 3-year follow-up results from a single institution.
This study sought to compare midterm clinical outcomes of 1-stop hybrid coronary revascularization (HCR) with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for the treatment of multivessel coronary artery disease. One-stop HCR has emerged to be a feasible and attractive alternative to CABG and PCI in selected patients with multivessel coronary artery disease. From June 2007 to December 2010, 141 consecutive patients underwent 1-stop HCR at Fuwai Hospital. Using propensity score methodology, these patients were matched with 2 separate groups of 141 patients who underwent isolated CABG or PCI during the same period. All patients were stratified by the EuroSCORE (European System for Cardiac Operative Risk Evaluation Score) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score. Cutoffs for EuroSCORE (low, ≤2; medium, >2 and <6; high, ≥6) and SYNTAX score (low, ≤24; medium, >24 and <30; high, ≥30) were identified by tertiles. Three groups' cumulative major adverse cardiac or cerebrovascular events (MACCE) rates in each risk tertile were compared. One-stop HCR incurred MACCE rate lower than that with PCI (p < 0.001), but similar to that with CABG (p = 0.140). After stratification by EuroSCORE or SYNTAX score, the cumulative MACCE rates were similar among the 3 groups in low and medium tertiles. But in the high EuroSCORE tertile, patients who underwent 1-stop HCR had a lower MACCE rate than did the groups that underwent CABG (p = 0.030) and PCI (p = 0.006). Meanwhile, patients with a high SYNTAX score who underwent 1-stop HCR had a MACCE rate lower than did those who underwent PCI (p = 0.002), but similar to that of those who underwent CABG (p = 0.362). One-stop HCR provides favorable midterm outcomes for selected patients with multivessel coronary artery disease in each risk tertile. For patients with high EuroSCORE or SYNTAX score, it might provide a promising alternative to CABG and PCI.


An atypical case of sporadic Creutzfeldt-Jakob disease with Parkinson's disease.
We report here an autopsy case of a 64-year-old female with slowly progressive dementia and parkinsonism in a 4-year-long clinical course. Post-mortem examination revealed a severely atrophic brain with spongiform degeneration, neuronal loss and gliosis in the gray matter. Many prion protein plaque deposits were present in the occipital lobe, amygdala and cerebellum. Additionally, Lewy bodies were observed in the brainstem. Prion protein gene analysis of the patient revealed polymorphism at the codon-129 valine heterozygote. This genotype is known to sometimes accompany a missense mutation of the gene in uncommon hereditary prion diseases, but no mutation was found in the open reading frame. Thus, it might be suggested that this case showed simultaneously the features of both sporadic Creutzfeldt-Jakob disease (CJD) with codon-129 valine and Parkinson's disease. However, the predisposing factors for contracting both diseases simultaneously remain to be determined, because the incidence of Parkinson's disease accompanied by CJD is very low.


An adaptive strategy for single- and multi-cluster gene assignment.
Strict assignment of genes to one class, dimensionality reduction, a priori specification of the number of classes, the need for a training set, nonunique solution, and complex learning mechanisms are some of the inadequacies of current clustering algorithms. Existing algorithms cluster genes on the basis of high positive correlations between their expression patterns. However, genes with strong negative correlations can also have similar functions and are most likely to have a role in the same pathways. To address some of these issues, we propose the adaptive centroid algorithm (ACA), which employs an analysis of variance (ANOVA)-based performance criterion. The ACA also uses Euclidian distances, the center-of-mass principle for heterogeneously distributed mass elements, and the given data set to give unique solutions. The proposed approach involves three stages. In the first stage a two-way ANOVA of the gene expression matrix is performed. The two factors in the ANOVA are gene expression and experimental condition. The residual mean squared error (MSE) from the ANOVA is used as a performance criterion in the ACA. Finally, correlated clusters are found based on the Pearson correlation coefficients. To validate the proposed approach, a two-way ANOVA is again performed on the discovered clusters. The results from this last step indicate that MSEs of the clusters are significantly lower compared to that of the fibroblast-serum gene expression matrix. The ACA is employed in this study for single- as well as multi-cluster gene assignments.


Prevalence of abnormal liver function tests and comorbid psychiatric disorders among patients with anorexia nervosa and eating disorders not otherwise specified in the anorexia nervosa DSM-IV criteria.
Anorexia nervosa (AN) and eating disorders not otherwise specified (EDNOS) are on the rise in Singapore. Abnormal liver function tests have been reported for up to 12.2% of patients with AN. These patients are also known to present with comorbid psychiatric disorders. This study aims to investigate the correlation between body mass index (BMI) and the severity of abnormal liver function tests, and between BMI and the presence of comorbid psychiatric disorders. A retrospective cohort analysis of 373 patients diagnosed with AN or EDNOS at a tertiary hospital was performed. The clinical course of transaminitis and comorbid psychiatric disorders was correlated with the patient's BMI. Patients with a BMI of ≥ 16.6 kg/m(2) at their first consult had a significantly lower risk of having comorbid psychiatric disorders (χ(2) = 32.08, p < 0.001). These patients were five times less likely to have comorbid psychiatric disorders as compared to patients from the other BMI groups (odds ratio [OR] 0.21). On the other hand, patients with a BMI of < 14.6 kg/m(2) had a significantly higher risk of having transaminitis (χ(2) = 72.5, p < 0.001). They were 11.1 times more likely to develop transaminitis as compared to patients with a BMI of ≥ 14.6 kg/m(2) (OR 11.05). Severity of BMI can be used by clinicians as an indicator to assess for secondary psychiatric comorbidities and/or transaminitis during the first consultation. This could help reduce the morbidity and mortality rates in patients with AN or EDNOS.


Antidepressant Use and Subclinical Measures of Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.
Antidepressants are commonly prescribed medications used in primary care. The cardiovascular safety profile of antidepressant medications, in terms of subclinical atherosclerosis, is underexamined. A total of 6814 participants in the Multi-Ethnic Study of Atherosclerosis were examined. At baseline, the mean age was 62 years with 4 race/ethnic groups represented: European Americans (38%), Hispanic Americans (23%), African Americans (28%), and Chinese Americans (11%). Antidepressants were subgrouped as serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and "other" (bupropion, nefazodone, trazodone, mirtazapine). After adjusting for potential confounders, we estimated the association between antidepressant use and the following measures of subclinical atherosclerosis: coronary artery calcium (CAC), the ankle-brachial index, and carotid intima-media thickness, both cross-sectionally and prospectively. A total of 324 participants were exposed to SSRIs, 88 to TCAs, 41 to SNRIs, and 123 to other antidepressants. For CAC incidence, the fully adjusted longitudinal analyses revealed no consistent associations with SSRIs (relative risk [RR], 0.99; 95% confidence interval [CI], 0.71-1.37), SNRIs (RR, 0.49; 95% CI, 0.13-1.86), TCAs (RR, 0.94; 95% CI, 0.50-1.77), other antidepressant (RR, 0.87; 95% CI, 0.73-1.03) exposure, and subclinical disease. Similar null results were obtained in the cross-sectional and longitudinal exposure to antidepressants with changes in baseline CAC greater than 0, ankle-brachial index, and carotid intima-media thickness. The results of the current study do not support an association between antidepressants and subclinical atherosclerosis.


Corrigendum: The changes of umami substances and influencing factors in preserved egg yolk: pH, endogenous protease, and proteinaceous substance.
[This corrects the article DOI: 10.3389/fnut.2022.998448.].


Identification of a new gibberellin receptor agonist, diphegaractin, by a cell-free chemical screening system.
Gibberellin (GA) is a phytohormone that regulates various developmental processes during the plant life cycle. In this study, we identify a new GA agonist, diphegaractin, using a wheat cell-free based drug screening system with grape GA receptor. A GA-dependent interaction assay system using GA receptors and DELLA proteins from Vitis vinifera was constructed using AlphaScreen technology and cell-free produced proteins. From the chemical compound library, diphegaractin was found to enhance the interactions between GA receptors and DELLA proteins from grape in vitro. In grapes, we found that diphegaractin induces elongation of the bunch and increases the sugar concentration of grape berries. Furthermore, diphegaractin shows GA-like activity, including promotion of root elongation in lettuce and Arabidopsis, as well as reducing peel pigmentation and suppressing peel puffing in citrus fruit. To the best of our knowledge, this study is the first to successfully identify a GA receptor agonist showing GA-like activity in agricultural plants using an in vitro molecular-targeted drug screening system.


Coupling of spectrometric, chromatographic, and chemometric analysis in the investigation of the photodegradation of sulfamethoxazole.
A workflow is proposed for the study of the photodegradation process of the sulfamethoxazole (SMX) based on the combination of different experimental techniques, including liquid chromatography, mass spectrometry, UV-Visible spectrophotometry, and the treatment of all the analytical data with advanced chemometric methods. SMX, which is one of the most widely used antibiotics worldwide and has been found at remarkable concentrations in various rivers and effluents over all Europe, was degraded in the laboratory under a controlled source of UV radiation, which simulates the environmental solar radiation (Suntest). Kinetic monitoring of the photodegradation process was performed using UV-Visible spectrophotometric measurements and by further Liquid Chromatography with Diode Array Detector and Mass Spectrometry analysis (LC-DAD-MS). Additionally, the acid-base properties were also investigated to see how the pH can affect the speciation of this substance during the photodegradation process. Based on the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) application, the proposed chemometric method coped with the large amounts of data generated by the different analytical techniques used to monitor the evolution of the photodegradation process. Their simultaneous analysis involved applying a data fusion strategy and an advanced MCR-ALS constrained analysis, which allowed and improved the description of the complete degradation process, detecting the different species of the reaction, and identifying the possible transformation products formed. A total number of six species were resolved in the degradation process of SMX. In addition to the initial SMX, a second species corresponded to a conformational isomer, and the other four species represented different photoproducts, which have also been identified. Furthermore, three different acid-base species of SMX were obtained, and their pKa values were estimated.


Mechanisms of human inherited epilepsies.
It is just over a decade since the discovery of the first human epilepsy associated ion channel gene mutation. Since then mutations in at least 25 different genes have been described, although the strength of the evidence for these genes having a pathogenic role in epilepsy varies. These discoveries are allowing us to gradually begin to unravel the molecular basis of this complex disease. In the epilepsies, virtually all the established genes code for ion channel subunits. This has led to the concept that the idiopathic epilepsies are a family of channelopathies. This review first introduces the epilepsy syndromes linked to mutations in the various genes. Next it collates the genetic and functional analysis of these genes. This part of the review is divided into voltage-gated channels (Na+, K+, Ca2+, Cl(-) and HCN), ligand-gated channels (nicotinic acetylcholine and GABA(A) receptors) and miscellaneous proteins. In some cases significant advances have been made in our understanding of the molecular and cellular deficits caused by mutations. However, the link between molecular deficit and clinical phenotype is still unknown. Piecing together this puzzle should allow us to understand the underlying pathology of epilepsy ultimately providing novel therapeutic strategies to complete the clinic-bench-clinic cycle.


Formate, acetate, and propionate as substrates for sulfate reduction in sub-arctic sediments of Southwest Greenland.
Volatile fatty acids (VFAs) are key intermediates in the anaerobic mineralization of organic matter in marine sediments. We studied the role of VFAs in the carbon and energy turnover in the sulfate reduction zone of sediments from the sub-arctic Godthåbsfjord (SW Greenland) and the adjacent continental shelf in the NE Labrador Sea. VFA porewater concentrations were measured by a new two-dimensional ion chromatography-mass spectrometry method that enabled the direct analysis of VFAs without sample pretreatment. VFA concentrations were low and surprisingly constant (4-6 μmol L(-1) for formate and acetate, and 0.5 μmol L(-1) for propionate) throughout the sulfate reduction zone. Hence, VFAs are turned over while maintaining a stable concentration that is suggested to be under a strong microbial control. Estimated mean diffusion times of acetate between neighboring cells were <1 s, whereas VFA turnover times increased from several hours at the sediment surface to several years at the bottom of the sulfate reduction zone. Thus, diffusion was not limiting the VFA turnover. Despite constant VFA concentrations, the Gibbs energies (ΔGr) of VFA-dependent sulfate reduction decreased downcore, from -28 to -16 kJ (mol formate)(-1), -68 to -31 kJ (mol acetate)(-1), and -124 to -65 kJ (mol propionate)(-1). Thus, ΔGr is apparently not determining the in-situ VFA concentrations directly. However, at the bottom of the sulfate zone of the shelf station, acetoclastic sulfate reduction might operate at its energetic limit at ~ -30 kJ (mol acetate)(-1). It is not clear what controls VFA concentrations in the porewater but cell physiological constraints such as energetic costs of VFA activation or uptake could be important. We suggest that such constraints control the substrate turnover and result in a minimum ΔGr that depends on cell physiology and is different for individual substrates.


Phosphate removal by a La(OH)3 loaded magnetic MAPTAC-based cationic hydrogel: Enhanced surface charge density and Donnan membrane effect.
Cationic hydrogels have received great attention to control eutrophication and recycle phosphate. In this study, a type of La(OH)3 loaded magnetic MAPTAC-based cationic hydrogel (La(OH)3@MMCH) was developed as a potential adsorbent for enhanced phosphate removal from aqueous environment. La(OH)3@MMCH exhibited high adsorption capacity of 105.72±5.99 mg P/g, and reached equilibrium within 2 hr. La(OH)3@MMCH could perform effectively in a wide pH range from 3.0 to 9.0 and in the presence of coexisting ions (including SO42-, Cl-, NO3-, HCO3-, SiO44- and HA). The adsorption-desorption experiment indicated that La(OH)3@MMCH could be easily regenerated by using NaOH-NaCl as the desorption agent, and 73.3% adsorption capacity remained after five cycles. Moreover, La(OH)3@MMCH was employed to treat surface water with phosphate concentration of 1.90 mg/L and showed great removal efficiency of 95.21%. Actually, MMCH showed high surface charge density of 34.38-59.38 meq/kg in the pH range from 3.0 to 11.0 and great swelling ratio of 3014.57% within 24 h, indicating that MMCH could produce the enhanced Donnan membrane effect to pre-permeate phosphate. Furthermore, the bifunctional structure of La(OH)3@MMCH enabled it to capture phosphate through electrostatic attraction and ligand exchange. All the results prove that La(OH)3@MMCH is a promising adsorbent for eutrophication control and phosphate recovery.


The Effects of the Levels of Hypoxia in the Olfactory Nervous System in Mouse Model.
Intermittent hypoxia (IH) results in low-grade inflammation, sympathetic overactivity, and oxidative stress. However, the specific effects of IH on olfaction have not yet been directly assessed and remain unclear. Therefore, the purpose of this study was to investigate the cytotoxic effects of IH exposure on the mouse olfactory epithelium and the relationship between the concentration of hypoxia and the degree of destruction of the olfactory system. Thirty mice were randomly divided into six groups: control (room air for 4 weeks), recovery control (room air for 5 weeks), IH 5% oxygen concentration, IH 7% oxygen concentration, recovery 5% hypoxia, and recovery 7% hypoxia groups. Mice in the two hypoxia groups were exposed to 5% and 7% oxygen for 4 weeks. Mice in the two recovery groups were exposed to room air for 1 week after 4 weeks of hypoxia period. Based on, the olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL were lower, whereas S100b and NGFRAP1 messenger RNA (mRNA) levels were higher in the 5% hypoxia group than those in the control group in the olfactory neuroepithelium. In the brain tissue, the changes in RNA analysis for Olfr 1507, OMP, ADCY, and GNAL mRNA were not typical. However, NeuN and GFAP levels were decreased under 5% hypoxia in the brain tissue. In the recovery state, CNPase, S100b and NeuN levels were increased significantly in both the olfactory neuroepithelium and brain tissue in the 5% hypoxia group. The change in RNA activity in PCR was much higher in the 5% hypoxia group than in the 7% hypoxia group. Our findings suggest that IH damages the olfactory neuroepithelium and brain tissue in mouse model. The activity of olfactory marker genes and neurogenesis in the olfactory neuroepithelium were decreased. The levels of oxygen may be affect changes in the olfactory neuroepithelium. The olfactory ensheathing cell may be a major factor in the recovery of the olfactory neuroepithelium.


Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in patients with advanced breast cancer (ABC).
A phase I dose-escalation study of a new formulation of oral vinorelbine was conducted to determine the maximum tolerated dose (MTD) of a once weekly regimen and preliminary pharmacokinetic profile in patients with advanced breast cancer (ABC). Twenty-six patients were treated at dose levels ranging from 60 to 100 mg/m2/week. Pharmacokinetics was assessed during the first administration. All patients had histologically confirmed locally advanced or metastatic breast cancer and had received no more than two prior chemotherapy regimens for ABC. The MTD was 100 mg/m2/week due to the occurrence of dose-limiting neutropenia, nausea/vomiting and constipation in five of six patients. Toxicities at 80 mg/m2/week were manageable, neutropenia being the main toxicity (grade 3-4 seen in 10 of 13 patients). Nausea, vomiting and diarrhoea were common but rarely severe. Vinorelbine was rapidly absorbed with maximum blood concentration (Cmax) of 103.8 +/- 41.6 ng x ml(-1) observed 1.2 +/- 0.8 hours (Tmax) after administration of 80 mg/m2. Pharmacokinetic exposure increased linearly with dose. Area under the concentration-time curve (AUC) and concentration measured 24 hours after drug intake (C24h) were significantly correlated with depletion of neutrophils. Objective tumour responses were reported in 6 of the 14 evaluable patients treated at doses > or = 80 mg/m2/week. The safety profile of oral vinorelbine appears comparable to that of intravenous dosing. The recommended phase II dose is 80 mg/m2/week and requires regular monitoring of neutrophil counts.


Normal Tissue Toxicity Prediction: Clinical Translation on the Horizon.
Improvements in radiotherapy delivery have enabled higher therapeutic doses and improved efficacy, contributing to the growing number of long-term cancer survivors. These survivors are at risk of developing late toxicity from radiotherapy, and the inability to predict who is most susceptible results in substantial impact on quality of life and limits further curative dose escalation. A predictive assay or algorithm for normal tissue radiosensitivity would allow more personalized treatment planning, reducing the burden of late toxicity, and improving the therapeutic index. Progress over the last 10 years has shown that the etiology of late clinical radiotoxicity is multifactorial and informs development of predictive models that combine information on treatment (eg, dose, adjuvant treatment), demographic and health behaviors (eg, smoking, age), co-morbidities (eg, diabetes, collagen vascular disease), and biology (eg, genetics, ex vivo functional assays). AI has emerged as a useful tool and is facilitating extraction of signal from large datasets and development of high-level multivariable models. Some models are progressing to evaluation in clinical trials, and we anticipate adoption of these into the clinical workflow in the coming years. Information on predicted risk of toxicity could prompt modification of radiotherapy delivery (eg, use of protons, altered dose and/or fractionation, reduced volume) or, in rare instances of very high predicted risk, avoidance of radiotherapy. Risk information can also be used to assist treatment decision-making for cancers where efficacy of radiotherapy is equivalent to other treatments (eg, low-risk prostate cancer) and can be used to guide follow-up screening in instances where radiotherapy is still the best choice to maximize tumor control probability. Here, we review promising predictive assays for clinical radiotoxicity and highlight studies that are progressing to develop an evidence base for clinical utility.


[The application of BTA stat in the diagnosis of bladder tumor and hematuria].
To analyze the value of the Bard BTA Stat for the diagnosis of bladder tumor and hematuria in order to find a new, noninvasive examination method. BTA Stat, an one step monoclonal antibody immunofluorescence analysis that qualitatively detects the presence of bladder tumor associated antigen (hCFHrp), was used. 65 patients with hematuria, 71 patients with bladder transitional cell carcinoma, and 10 normal people underwent voided urine BTA Stat analysis. The specificity of the technique for patients with bladder transitional cell carcinoma and hematuria was 84.6% and 31.1% respectively, with a sensitivity of 73.7% and 90.0% respectively. BTA Stat was considered a convenient, rapid and noninvasive method in the diagnosis of bladder tumor. However, the results were interfered by the presence of erythrocyte in urine, infection, urinary lithiasis. This method is proved to be useful in the surveillance of bladder tumor.


A Multicenter Phase 2 Study of Ultrahypofractionated Stereotactic Boost After External Beam Radiotherapy in Intermediate-risk Prostate Carcinoma: A Very Long-term Analysis of the CKNO-PRO Trial.
Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. The median follow-up period was 88 mo (range, 81-99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1-6.6%) and 11.0% (95% CI: 5.1-19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77-95%) and 76.9% (95% CI: 63.1-86.1), respectively. A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.


Rapid and slow benzbromarone elimination phenotypes in man: benzbromarone and metabolite profiles.
Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation. 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes. 10 subjects who eliminated the drug rapidly (S1-10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0-96) of the parent drug in S11 was 145 micrograms.ml-1 h. and in the other individuals it averaged 18.3 (11.4-24.5) micrograms.ml-1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77-5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1-10 amounted to 20.1 (11.9-41.2) h for M1, and 17.2 (12.9-30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.


Slow molecular recognition by RNA.
Molecular recognition is central to biological processes, function, and specificity. Proteins associate with ligands with a wide range of association rate constants, with maximal values matching the theoretical limit set by the rate of diffusional collision. As less is known about RNA association, we compiled association rate constants for all RNA/ligand complexes that we could find in the literature. Like proteins, RNAs exhibit a wide range of association rate constants. However, the fastest RNA association rates are considerably slower than those of the fastest protein associations and fall well below the diffusional limit. The apparently general observation of slow association with RNAs has implications for evolution and for modern-day biology. Our compilation highlights a quantitative molecular property that can contribute to biological understanding and underscores our need to develop a deeper physical understanding of molecular recognition events.


Caustic esophageal lesions in childhood: prevention of stricture formation.
Accidental caustic ingestion, a problem of childhood, can lead to esophageal stricture formation. We studied 132 children less than 19 years of age who were admitted to our hospital for suspected caustic ingestion. Forty-nine had burns in the esophagus, 11 of whom had deep and circular burns and were therefore prone to developing esophageal strictures. Only these 11 children were treated for prevention of stricture formation with a special nasogastric tube, functioning as intraluminal stent; this was their sole treatment. No corticosteroids were used. Only one of the 11 developed mild stenosis. In none of the other untreated children was stricture formation observed. Therefore, we believe that this approach spares many children unnecessary treatment and hospitalization, that our nasogastric tube effectively prevents stricture formation, and that there is no need for the use of corticosteroids in the treatment of caustic esophageal lesions in childhood.


Simulating the relative influence of tire, vehicle and driver factors on forward collision accident rates.
There is currently a strong focus within the automotive industry centered on traffic safety, with topics such as distracted driving, accident avoidance technologies, and autonomous vehicles. These papers tend to focus on the possible improvements from a single factor. However, there are many factors that are present in each accident, and it is important to understand the influence of each factor on the relative accident risk in order to identify the most effective approaches for improving driver safety. Rear-end accidents tend to be the most common accident type with approximately 1.8 M cases, or 31% of all accidents, in 2012, according to NHTSA. Of the rear-end accident scenarios, approximately 18-23% occur on wet surfaces. A Monte Carlo Forward Collision Simulation models the conditions of a wet rear-end accident and estimates the relative impact of various vehicle collision parameters. The model takes distributions of these parameters as inputs, and outputs a risk of collision relative to a known reference case. The parameters that can be studied include: tire grip level, road grip level, vehicle velocity, following distances, and the presence of vehicle technologies (ABS, FCW & AEB). Distributions of some of these parameters have been improved thanks to Naturalistic Driving Study data from SHRP2. This study shows that these vehicle systems have a large impact on safety and can change the amount of influence attributed to other parameters such as tire grip levels. As the use of automated vehicle systems expands, so will the influence of tire grip performance levels on collision risks. Practical Applications: It is more important than ever for consumers and auto manufacturers to consider tire performance levels. Therefore, the tire industry should continue to focus on wet grip as a key performance related to safety and should strive to continue to improve tire performance.


The interaction of defoliation and nutrient uptake in Sporobolus kentrophyllus, a short-grass species from the serengeti plains.
Sporobolus kentrophyllus, a grazing-tolerant C4 grass from the southeastern Serengeti Plains, was grown in solution culture to examine the effects of clipping on the uptake, preference and subsequent transport of varying nitrogen forms. Clipping reduced offtake mass, crown mass ane root mass, resulting in a 58% decline in plant mass. Proportional biomass allocation to roots decreased with clipping, while tillering rates increased. Clipping also increased the nitrogen concentrations of all tissues, and plant nitrogen uptake (nitrogen accumulated throughout the experiment per gram root). The 15N concentrations (% atom excess) of all tissues were higher in clipped compared with unclipped plants, and the average 15N uptake rate of clipped plants was twice that of unclipped plants. The relative 15N allocation to aboveground mass, a measure of canopy sink strength, was higher in clipped plants. Plants fed 15N-ammonium or 15N-nitrate during the 15N pulse experiment had greater 15N tissue concentrations compared with urea-fed plants, and 15N uptake rates were higher in ammonium-fed and nitrate-fed plants, compared with urea-fed plants. The relative magnitudes of these differences were higher when plants were clipped. Clipped plants had higher uptake rates for potassium, phosphorus and sodium, while differences between clipping treatments for calcium, iron, and magnesium were indistinguishable. Rapid uptake rates for species on the southeastern Serengeti plains, particularly during grazing periods, have important implications for nutrient cycling in this system.


On the findings of stroke-prone SHR.
The fundus of 82 SHRSP were observed and all of them showed the narrowing caliber irregularity of retinal arterioles and optic disc edema. Moreover, tortuosity of retinal arterioles was characteristic.


Evaluation of maintenance of the common androgen deprivation therapy with the new antiandrogen therapy in patients with castration-resistant prostate cancer: a systematic review.
Advanced prostate cancer does not respond to traditional androgen deprivation therapy (ADT) at some point in the treatment. The development of new hormonal agents demonstrated clear efficacy and changed the treatment scenario. To evaluate the use of new antiandrogens alone versus their use in combination with maintenance ADT in patients with advanced castration-resistant prostate cancer. A literature systematic review of randomized clinical trials, cohorts, and real-life studies including patients who received the new antiandrogens with or without ADT due to histologic confirmed advanced castration-resistant prostate adenocarcinoma was carried out. 2181 articles were identified and three studies were included with a total of 246 patients. Two studies were randomized clinical trials, and the third was a retrospective study, which showed similar results for both arms, in relation to PSA response, radiological progression-free survival, and testosterone levels, in addition to cost analysis with savings avoided in the ADT maintenance-free arm. Despite the positive data, it is still not possible to categorically state whether there is a statistical benefit in suspending the ADT during the use of new antiandrogens, due to the heterogeneity of the studies. The literature is limited on the issue. Available data are still immature with no clear benefit of the use of newer antiandrogens alone in the setting of advanced castration-resistant prostate cancer.


Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight.
Craniometric and stereotaxic data from rats of different sex, strain and weight were compared. It was found that stereotaxic atlases can be used with rats of different sex and strain provided that the weights of the rats conform to those used in the reference atlas. If rats of different weights are used, greater accuracy can be achieved if bregma is used as the reference point for work with rostral structures and the interaural line for work with caudal structures.


Preparation of 3-spirocyclic indolin-2-ones as ligands for the ORL-1 receptor.
A novel series of indolin-2-ones having a spirocyclic piperidine ring at the 3-position was synthesized and found to bind with high affinity to the ORL-1 receptor. Structure-activity relationships at the piperidine nitrogen were investigated. Substitution on the phenyl ring and nitrogen atom of the indolin-2-one core generated several selective high-affinity ligands that were antagonists of the ORL-1 receptor.


Increases in Cardiac Output and Oxygen Consumption During Enhanced External Counterpulsation.
Regular enhanced external counterpulsation (EECP) improves exercise capacity possibly through a training effect, but the roles of oxygen consumption (VO2) vs. direct EECP effects (diastolic augmentation, DA-ratio), and their relation to cardiac index (CI) during EECP are unknown. We studied eight patients with angina pectoris (median [range] age 72 [53-85], 25% women), who underwent EECP for 35 daily sessions. Before, during and after the first and last sessions, we assessed VO2, DA-ratio and CI. At first EECP, CI increased from 2.2 (1.7-2.9) L/min/m2 prior to EECP to 3.0 (2.2-3.8) during EECP (p=0.011), and returned to 2.4 (0.8-3.0). Similarly, VO2 increased during EECP and returned to baseline after EECP. These patterns were reproduced at the last EECP session. Absolute values of CI and VO2 correlated with each other during but not prior to or after EECP. The increase in CI correlated with the increase in VO2 by trend: (first session, r 0.52, p=0.19; second session r 0.69, p=0.09), but not with DA-ratio. Acutely during EECP, there is an increase in cardiac output that is unrelated to direct EECP effects but related to, and may be secondary to, an increase in peripheral O2 demand. This may represent a training effect.


Extraction of pinocembrin from leaves of different species of Eucalyptus and its quantitative analysis by qNMR and HPTLC.
Pinocembrin, a flavanone with a variety of biological activities was isolated from Eucalyptus sieberi leaves and quantified in several other Eucalyptus species using qNMR and HPTLC densitometry. The effect of different extraction procedures on the extraction of the compound from Eucalyptus sieberi was also studied. The methods were validated in terms ofselectivity, specificity, linearity, recovery, precision and repeatability.


Sublethal effects of four insecticides on folding and spinning behavior in the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae).
The rice leaffolder, Cnaphalocrocis medinalis, is an important rice pest. The sublethal effects of chlorpyrifos, chlorantraniliprole, emamectin benzoate and spinosad were investigated on the folding and spinning behaviors of third- to fifth-instar C. medinalis larvae (L3 - L5) after insecticidal exposure of the second instar. A 25% lethal concentration (LC25 ) of chlorpyrifos prolonged the leaf selection time of L5, and reduced the number of binds per primary fold for L4 and L5. An LC10 of chlorantraniliprole reduced the number of binds per primary fold for L4 and increased the number of head swings per bind for L5. An LC10 of emamectin benzoate shortened the primary fold length for L5 and decreased the number of head swings per primary fold for L3 and L4 and the number of head swings per bind for L3, while an LC25 of emamectin benzoate shortened the fold length per 24 h for L5 and folding time for L3. An LC10 of spinosad lowered the fold length per 24 h and the number of head swings for L5. An LC25 of spinosad prolonged leaf selection time, and decreased primary fold length, binds per primary fold, binds per fold and fold length per 24 h in L5. Emamectin benzoate and spinosad exerted stronger sublethal effects on the folding and spinning behavior of C. medinalis than chlorpyrifos and chlorantraniliprole. These results provide better understanding of the sublethal effects of interactions of insecticides on C. medinalis. © 2017 Society of Chemical Industry.


Recovery study of cholinesterases and neurotoxic signs in the non-target freshwater invertebrate Chilina gibbosa after an acute exposure to an environmental concentration of azinphos-methyl.
Azinphos-methyl belongs to the class of organophosphate insecticides which are recognized for their anticholinesterase action. It is one of the most frequently used insecticides in the Upper Valley of Río Negro and Río Neuquén in Argentina, where agriculture represents the second most important economic activity. It has been detected in water from this North Patagonian region throughout the year and the maximum concentration found was 22.48 μg L(-1) during the application period. Chilina gibbosa is a freshwater gastropod widely distributed in South America, particularly in Patagonia, Argentina and in Southern Chile. Toxicological studies performed with C. gibbosa in our laboratory have reported neurotoxicity signs and cholinesterase inhibition after exposure to azinphos-methyl for 48 h. Recovery studies together with characterization of the enzyme and sensitivity of the enzyme to pesticides can improve the toxicological evaluation. However, little is known about recovery patterns in organisms exposed to organophosphates. The aim of the present work was to evaluate the recovery capacity (during 21 days in pesticide-free water) of cholinesterase activity and neurotoxicity in C. gibbosa after 48 h of exposure to azinphos-methyl. Also, lethality and carboxylesterase activity were registered during the recovery period. Regarding enzyme activities, after a 48-h exposure to 20 μg L(-1) of azinphos-methyl, cholinesterases showed an inhibition of 85% with respect to control, while carboxylesterases were not affected. After 21 days in pesticide-free water, cholinesterases continued to be inhibited (70%). Severe neurotoxicity signs were observed after exposure: 82% of the snails presented lack of adherence to vessels, 11% showed weak adherence, and 96% exhibited an abnormal protrusion of the head-foot region from shell. After 21 days in pesticide-free water, only 15% of the snails presented severe signs of neurotoxicity. However, during the recovery period significant lethality (30%) was registered in treated snails. C. gibbosa is a very sensitive organism to azinphos-methyl. These snails play an important role in the structure and function of aquatic food webs in this region. Thus, a decline of this species' population would probably have an impact on aquatic and non-aquatic communities. Our results show that C. gibbosa is a relevant sentinel species for studying exposure and effects of azinphos-methyl using behavioral and biochemical biomarkers. Neurotoxic behavioral signs are very sensitive, non-destructive biomarkers, which can be easily detected for about one week after acute exposure. Cholinesterse activity is a very useful biomarker showing a high sensitivity and a slow recovery capacity increasing the possibility to indirectly detect organophosphates for long periods after a contaminant event.


Microbial diversity in Mediterranean sponges as revealed by metataxonomic analysis.
Although the Mediterranean Sea covers approximately a 0.7% of the world's ocean area, it represents a major reservoir of marine and coastal biodiversity. Among marine organisms, sponges (Porifera) are a key component of the deep-sea benthos, widely recognized as the dominant taxon in terms of species richness, spatial coverage, and biomass. Sponges are evolutionarily ancient, sessile filter-feeders that harbor a largely diverse microbial community within their internal mesohyl matrix. In the present work, we firstly aimed at exploring the biodiversity of marine sponges from four different areas of the Mediterranean: Faro Lake in Sicily and "Porto Paone", "Secca delle fumose", "Punta San Pancrazio" in the Gulf of Naples. Eight sponge species were collected from these sites and identified by morphological analysis and amplification of several conserved molecular markers (18S and 28S RNA ribosomal genes, mitochondrial cytochrome oxidase subunit 1 and internal transcribed spacer). In order to analyze the bacterial diversity of symbiotic communities among these different sampling sites, we also performed a metataxonomic analysis through an Illumina MiSeq platform, identifying more than 1500 bacterial taxa. Amplicon Sequence Variants (ASVs) analysis revealed a great variability of the host-specific microbial communities. Our data highlight the occurrence of dominant and locally enriched microbes in the Mediterranean, together with the biotechnological potential of these sponges and their associated bacteria as sources of bioactive natural compounds.


Impacts of smoking on endocrine treatment response in a prospective breast cancer cohort.
The association between smoking and breast cancer prognosis remains unclear. The purpose of this study was to investigate whether preoperative smoking was associated with prognosis in different treatment groups. This population-based cohort consisted of 1065 breast cancer patients without preoperative treatment included between 2002 and 2012 in Lund, Sweden. Smoking status was examined in relation to patient and tumour characteristics, and prognosis in different treatment groups. At the preoperative visit, 21.0% smoked. Median follow-up time was 5.1 years. Overall, in the 1016 patients included in the survival analyses, there was no significant association between smoking and risk of breast cancer events (adjusted hazard ratio (adjHR): 1.45; 95% confidence interval (CI): 0.95-2.20). For the 309 aromatase inhibitor (AI)-treated patients ⩾50 years with oestrogen receptor-positive (ER+) tumours, smoking was associated with risk of breast cancer events (adjHR: 2.97; 95% CI: 1.44-6.13), distant metastasis (adjHR: 4.19; 95% CI: 1.81-9.72), and death (adjHR: 3.52; 95% CI: 1.59-7.81). Smoking was not associated with breast cancer events or distant metastasis in other treatment groups. Preoperative smoking was only associated with an increased risk for breast cancer events and distant metastasis in AI-treated patients. If confirmed, smoking status should be taken into consideration when selecting an endocrine therapy.


Apical sorting of lysoGPI-anchored proteins occurs independent of association with detergent-resistant membranes but dependent on their N-glycosylation.
Most glycosylphosphatidylinositol-anchored proteins (GPI-APs) are located at the apical surface of epithelial cells. The apical delivery of GPI-APs is believed to result from their association with lipid rafts. We find that overexpression of C-terminally tagged PGAP3 caused predominant production of lysoGPI-APs, an intermediate precursor in the GPI lipid remodeling process in Madin-Darby canine kidney cells. In these cells, produced lysoGPI-APs are not incorporated into detergent-resistant membranes (DRMs) but still are delivered apically, suggesting that GPI-AP association with DRMs is not necessary for apical targeting. In contrast, apical transport of both fully remodeled and lyso forms of GPI-APs is dependent on N-glycosylation, confirming a general role of N-glycans in apical protein transport. We also find that depletion of cholesterol causes apical-to-basolateral retargeting not only of fully remodeled GPI-APs, but also of lysoGPI-APs, as well as endogenous soluble and transmembrane proteins that would normally be targeted to the apical membrane. These findings confirm the essential role for cholesterol in the apical protein targeting and further demonstrate that the mechanism of cholesterol-dependent apical sorting is not related to DRM association of GPI-APs.


The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline.
Rats were decerebrated and treated with a beta-adrenoceptor blocker (toliprolol, Kö 592, 5 mg/kg). Increases of blood pressure were repeatedly elicited by i.v. injection of angiotensin (0.03-0. 125 mug/kg) ant eh accompanying reflex bradycardia was measured. The vagally mediated reflex bradycardia was significantly increased by clonidine, 3o mug/kg i.v., in non-pretreated animals as well as after pretreatment with reserpine (7.5 mg/kg s.c., 20 hr) and alpha-methyl-p-tyrosine-methylester (250 mg/kg i.p., 5 hr), separately or in combination. The facilitatory effect of clonidine was antagonized in all groups by i.v. injection of the alpha-adrenoceptor blocking drugs, phentolamine (5 mg/kg) and piperoxan (1 mg/kg). In the control periods before clonidine, reflex bradycardia was similar in pretreated animals to that in animals without pretreatment. It was concluded therefore that catecholamines have no essential transmitter functions in the cardiodepressor reflex loop. Therefore, the action of clonidine on cardiovascular centers in the medulla is independent of endogenous noradrenaline storage and synthesis. A direct effect is assumed on central alpha-adrenoceptors, which have a modulatory 'effector' function on the cardiodepressor reflex.


Preparation of AAEK-functionalized cellulose film with antibacterial and anti-adhesion activities.
Bacterial adhesion infection caused by medical materials in clinical application has become a serious threat, and it urgently needs new strategies to deal with these clinical challenges. The purpose of this study is to explore the effectiveness of surface-decorated aryl (β-amino) ethyl ketones (AAEK), a promising sorting enzyme A (SrtA) inhibitor of Staphylococcus aureus, to improve the anti-adhesion ability of biomaterials. AAEK was covalently grafted onto cellulose films (CF) via copper-catalyzed azide-alkyne 1, 3-dipolar cycloaddition click reaction. The data of contact angle measurements, ATR-FTIR and XPS proved the successful covalent attachment of AAEK-CF, and the antimicrobial efficacy of AAEK coating was assessed by CFUs, crystal violet staining, scanning electron microscopy and Living/Dead bacteria staining assay. The results illustrated that AAEK-CF exhibited excellent anti-adhesion ability to Staphylococcus aureus, and significantly reduced the number of bacteria adhering to the film. More importantly, AAEK-CF could hinder the formation of bacterial biofilm. Furthermore, AAEK-CF indicated no cytotoxicity to mammalian cells, and the cells could grow normally on the modified surface. Hence, our present work demonstrated that the grafting of the SrtA inhibitor-AAEK onto cellulose films enabled to combat bacterial biofilm formation in biomedical applications.


Substance use among young indigenous Sami--a summary of findings from the North Norwegian Youth Study.
To summarise knowledge about substance use among young indigenous Sami living in Norway. Data from the North Norwegian Youth Study (NNYS)--a longitudinal questionnaire study conducted in 1994-1995 and 1997-1998 that represents the main source of information in the 1990s. The 1994-1995 sample included 3,000 ethnically diverse high school students (response rate [RR]: 85%), while the 1997-1998 follow-up sample included 1500 respondents (RR: 55%). Young Sami did not show higher rates than their non-Sami peers for any of the investigated substances. In contrast, young Sami reported lower drinking rates at both assessments when compared with regional and national non-indigenous peers. Nonetheless, Sami with weaker cultural ties reported the highest intraethnic smoking and drinking rates. Young Sami are not at higher risk for substance use than their regional and national non-indigenous peers. These findings contrast some findings among other indigenous groups indicating "high" indigenous and "low" majority substance use rates.


Chemiluminescence-linked immunoassay.
Covalent complexes of a chemiluminescent compound (a luminol derivative), protein and a steroidal hapten have been used as a labelled antigen in a way analogous to the radioactive label in radioimmunoassay. The antibody-bound complex emits light when treated with hydrogen peroxide and copper acetate at high pH. The chemiluminescent complex bound to antibody can be displaced by free steroid to produce a standard curve in a way analogous to radioimmunoassay.