Seonamhaeicola marinus sp. nov., isolated from marine algae.
A Gram-stain-negative, facultatively anaerobic, rod-shaped, non-flagellated and non-gliding bacterium, designated strain B011T, was isolated from marine algae Gracilaria blodgettii collected from the coast of Lingshui county, Hainan, China. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain B011T, Seonamhaeicola algicola (96.8 % 16S rRNA gene sequence similarity) and Seonamhaeicola aphaedonensis (95.0 %) belonged to the same clade. Optimal growth occurred in the presence of 3.0 % (w/v) NaCl, at pH 6.5-7.5 and at 28 °C. Menaquinone-6 (MK-6) was the predominant respiratory quinone. The major fatty acids (>10 %) were iso-C15 : 1 G (23.4 %) and iso-C15 : 0 (22.8 %). The major polar lipids were phosphatidylethanolamine, one aminolipid and three unknown lipids. The DNA G+C content of strain B011T was 33.9 mol%. On the basis of polyphasic analysis, strain B011T is considered to represent a novel species in the genus Seonamhaeicola, for which the name Seonamhaeicolamarinus sp. nov. is proposed. The type strain is B011T (=MCCC 1H00146T=NBRC 112333T).


Lessons learned from the statewide implementation of the Music & Memory program in nursing homes in Wisconsin in the USA.
The movement of evidence-based interventions into institutional settings such as nursing homes is challenging. Among ecopsychosocial interventions to address behavioral problems of nursing home residents with dementia, Music and Memory, a popular intervention that provides individualized music listening, has shown potential to improve residents' quality of life. In Wisconsin in the USA, the Music and Memory program has been implemented in nursing home facilities statewide. In the present study, to examine facilitators and barriers related to implementation and sustainability of the Music and Memory program, all nursing homes in Wisconsin were invited to participate in a survey (online or mail). A total of 161 facilities participated, representing a response rate of 41%. Descriptive statistics and content analysis were conducted. Over 80% of responding facilities were providing the Music and Memory program, and 86% of those facilities planned to continue its use. The majority of respondents found Music and Memory to be beneficial to residents, but they also reported that the program was not equally effective for everyone and that it was time and labor intensive. Barriers to sustainability included lack of buy-in by direct care staff, use of technology, costs of equipment, inconsistency of volunteers, and families not supportive or helpful. Facilitators included support of facility personnel, family, and volunteers; observing positive effects of program; Music and Memory training provision and support; and accessibility of equipment. For the program to be successful, facilities must identify the residents most likely to benefit from it, realistically estimate its costs and required labor, and ensure staff buy-in.


Prevalence of Clostridioides difficile Infection in Critically Ill Patients with Extreme Leukocytosis and Diarrhea.
While early empiric antibiotic therapy is beneficial for patients presenting with sepsis, the presentation of sepsis from Clostridioides difficile (formerly Clostridium difficile) infection (CDI) has not been well studied in large cohorts. We sought to determine whether the combination of extreme leukocytosis and diarrhea was strongly predictive of CDI in a cohort of 8659 patients admitted to the intensive care unit. We found that CDI was present in 15.0% (95% CI, 12.1-18.3%) of patients with extreme leukocytosis and diarrhea and that mortality for those with CDI, diarrhea, and extreme leukocytosis was 33.8% (95% CI, 23.2-44.3%). These data support consideration of empiric treatment for CDI in unstable critically ill patients with extreme leukocytosis and diarrhea, along with treatment of other possible sources of sepsis as appropriate. Empiric treatment for CDI can usually be discontinued promptly, along with narrowing of other broad-spectrum antimicrobial coverage, if a sensitive C. difficile test is negative.


Treatment of Boiler Condensate by Ultrafiltration for Reuse.
The generation of water vapor is crucial for the petrochemical industry. In order to protect the boiler from damage, the re-injected water must not contain any suspended matter, especially hydrocarbons. Moreover, it is condensed steam with a temperature close to 100 °C and the unintentional creation or chronic generation of pollution, respectively, that can more or less produce the concentrated pollution. In this context, membrane processes appear promising in order to achieve this reuse and more especially crossflow ceramic membranes. The novelty of this paper is to study the retention of hydrocarbons and suspended solids contained in the condensate hot water of a high-capacity boiler using ceramic ultrafiltration membranes. In total, two ultrafiltration molecular weight cut-offs were used: 50-150 kDa. Several operating parameters were studied such as effluent type (accidental or chronic pollution), temperature, transmembrane pressure, initial volume, and pilot plant size. In all cases, retention of suspended matter was above 90% and residual hydrocarbon concentrations were under 0.1 ppm even for high-volume concentrations. Control of the transmembrane pressure and the molecular weight cut-off of the membrane are key to optimizing the process. Despite the high-volume concentration obtained, the membranes were perfectly regenerated with conventional cleaning procedures.


A new technique for intraoperative reduction of occipitocervical instability.
Occipitocervical instability with vertical migration of the odontoid is a rare but potentially debilitating anomaly of the craniocervical junction. Anterior decompression by means of a transoral or transcervical approach followed by posterior instrumentation commonly is used to treat this pathology. To develop an innovative operative technique to correct reducible occipitocervical instability using a purely posterior approach. Two patients presented to our institution with occipitocervical instability. One patient developed vertical migration of the odontoid secondary to a retropharyngeal abscess after radiation treatment. The second patient developed occipitocervical instability as a result of pathological destruction of C2 from a breast metastasis. Both patients were myelopathic with severe neck pain. Both patients were brought to the operating room for intraoperative reduction and fixation using a purely posterior approach. This new technique obviated the need for an anterior decompression procedure or preoperative halo reduction. Postoperatively, both patients had excellent restoration of spinal alignment as well as improvement in both pain and myelopathy. We achieved intraoperative reduction of occipitocervical instability through a purely posterior approach. This technique adds a tool to the armamentarium of techniques used for the treatment of occipitocervical instability.


The Influence of Altered-Gravity on Bimanual Coordination: Retention and Transfer.
Many of the activities associated with spaceflight require individuals to coordinate actions between the limbs (e.g., controlling a rover, landing a spacecraft). However, research investigating the influence of gravity on bimanual coordination has been limited. The current experiment was designed to determine an individual's ability to adapt to altered-gravity when performing a complex bimanual force coordination task, and to identify constraints that influence coordination dynamics in altered-gravity. A tilt table was used to simulate gravity on Earth [90° head-up tilt (HUT)] and microgravity [6° head-down tilt (HDT)]. Right limb dominant participants (N = 12) were required to produce 1:1 in-phase and 1:2 multi-frequency force patterns. Lissajous information was provided to guide performance. Participants performed 14, 20 s trials at 90° HUT (Earth). Following a 30-min rest period, participants performed, for each coordination pattern, two retention trials (Earth) followed by two transfer trials in simulated microgravity (6° HDT). Results indicated that participants were able to transfer their training performance during the Earth condition to the microgravity condition with no additional training. No differences between gravity conditions for measures associated with timing (interpeak interval ratio, phase angle slope ratio) were observed. However, despite the effective timing of the force pulses, there were differences in measures associated with force production (peak force, STD of peak force mean force). The results of this study suggest that Lissajous displays may help counteract manual control decrements observed during microgravity. Future work should continue to explore constraints that can facilitate or interfere with bimanual control performance in altered-gravity environments.


Physician advice to adolescents about drinking and other health behaviors.
This report assessed the proportion of US 10th graders (average age, 16) who saw a physician in the past year and were asked and given advice about their drinking. We hypothesized that advice would vary by whether students were asked about drinking and their drinking, bingeing, and drunkenness frequency. A nationally representative sample of 10th graders in 2010 (N = 2519) were asked their past 30-day frequency of drinking, bingeing, and intoxication and whether, during their last medical examination, their drinking was explored and they received advice about alcohol's risks and reducing or stopping. In the past month, 36% reported drinking, 28% reported bingeing, and 23% reported drunkenness (11%, 5%, and 7%, respectively, 6 or more times). In the past year, 82% saw a doctor. Of that group, 54% were asked about drinking, 40% were advised about related harms, and 17% were advised to reduce or stop. Proportions seeing a doctor and asked about drinking were similar across drinking patterns. Respondents asked about drinking were more often advised to reduce or stop. Frequent drinkers, bingers, and those drunk were more often advised to reduce or stop. Nonetheless, only 25% of them received that advice from physicians. In comparison, 36% of frequent smokers, 27% of frequent marijuana users, and 42% of frequent other drug users were advised to reduce or quit those behaviors. Efforts are warranted to increase the proportion of physicians who follow professional guidelines to screen and counsel adolescents about unhealthy alcohol use and other behaviors that pose health risks.


Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults.
Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements. We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L. Serum samples from the cross-sectional NHANES 2007-2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC-tandem mass spectrometry. In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L. UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.


Stimulation artifact source separation (SASS) for assessing electric brain oscillations during transcranial alternating current stimulation (tACS).
Brain oscillations, e.g. measured by electro- or magnetoencephalography (EEG/MEG), are causally linked to brain functions that are fundamental for perception, cognition and learning. Recent advances in neurotechnology provide means to non-invasively target these oscillations using frequency-tuned amplitude-modulated transcranial alternating current stimulation (AM-tACS). However, online adaptation of stimulation parameters to ongoing brain oscillations remains an unsolved problem due to stimulation artifacts that impede such adaptation, particularly at the target frequency. Here, we introduce a real-time compatible artifact rejection algorithm (Stimulation Artifact Source Separation, SASS) that overcomes this limitation. SASS is a spatial filter (linear projection) removing EEG signal components that are maximally different in the presence versus absence of stimulation. This enables the reliable removal of stimulation-specific signal components, while leaving physiological signal components unaffected. For validation of SASS, we evoked brain activity with known phase and amplitude using 10 Hz visual flickers across 7 healthy human volunteers. 64-channel EEG was recorded during and in absence of 10 Hz AM-tACS targeting the visual cortex. Phase differences between AM-tACS and the visual stimuli were randomized, so that steady-state visually evoked potentials (SSVEPs) were phase-locked to the visual stimuli but not to the AM-tACS signal. For validation, distributions of single-trial amplitude and phase of EEG signals recorded during and in absence of AM-tACS were compared for each participant. When no artifact rejection method was applied, AM-tACS stimulation artifacts impeded assessment of single-trial SSVEP amplitude and phase. Using SASS, amplitude and phase of single trials recorded during and in absence of AM-tACS were comparable. These results indicate that SASS can be used to establish adaptive (closed-loop) AM-tACS, a potentially powerful tool to target various brain functions, and to investigate how AM-tACS interacts with electric brain oscillations.


The effect of rhBMP-2 and PRP delivery by biodegradable β-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model.
This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.


Fatness and Fitness With Cardiometabolic Risk Factors in Adolescents.
The relative importance of fitness and fatness with cardiometabolic risk factors is uncertain during the crucial developmental stage of late adolescence. We aimed to compare the concurrent influences of cardiorespiratory fitness and fatness in relationship to cardiometabolic risk factors in adolescents from the Western Australian Pregnancy Cohort Study. Cross-sectional analysis was performed on 1128 participants with complete blood pressure (BP) data and 963 participants with complete blood biochemistry at 17 years of age. Fatness (waist circumference) and cardiorespiratory fitness (physical work capacity 170) were assessed as continuous measures to avoid the use of arbitrary cut points. Analyses used linear regression models adjusted for sex and potential lifestyle confounders. Cardiometabolic risk factors. Fatness was positively associated with systolic BP (coefficient, 0.19; P < 0.001; β coefficient, 0.20), triglycerides (log coefficient, 0.009; P < 0.001; β coefficient, 0.24), low-density lipoprotein cholesterol (coefficient, 0.005; P = 0.007; β coefficient, 0.10), and high-sensitivity C-reactive protein (log coefficient, 0.05; P < 0.001; β coefficient, 0.35). There were no significant effects of fitness on any of these measures. A positive association between homeostasis model of assessment for insulin resistance and fatness (log coefficient, 0.02; P < 0.001; β coefficient, 0.33) was attenuated by fitness (log coefficient, -0.0.18; P < 0.001; β coefficient, -0.18). Fatness was inversely associated with high-density lipoprotein cholesterol (HDL-C) in both sexes (coefficient, -0.006; P < 0.001; β coefficient, -0.23), whereas fitness was positively associated with HDL-C only in females (coefficient, 0.08; P = 0.03; β coefficient, 0.15). The adverse effects of central adiposity seen across a broad range of cardiometabolic risk factors were only partially ameliorated by fitness in this adolescent population.


Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases.
During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabeled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of kinin-B1 receptors did not appear to be enhanced in the other biopsies. Within the multiple steps of the inflammatory cascade in wound healing, our results suggest an important regulatory role for kinin-B1 receptors during the first phase of inflammation following injury.


Evidence that serpin architecture intrinsically supports papain-like cysteine protease inhibition: engineering alpha(1)-antitrypsin to inhibit cathepsin proteases.
The closely related serpins squamous cell carcinoma antigen-1 and -2 (SCCA-1 and -2, respectively) are capable of inhibiting cysteine proteases of the papain superfamily. To ascertain whether the ability to inhibit cysteine proteases is an intrinsic property of serpins in general, the reactive center loop (RCL) of the archetypal serine protease inhibitor alpha(1)-antitrypsin was replaced with that of SCCA-1. It was found that this simple substitution could convert alpha(1)-antitrypsin into a cysteine protease inhibitor, albeit an inefficient one. The RCL of SCCA-1 is three residues longer than that of alpha(1)-antitrypsin, and therefore, the effect of loop length on the cysteine protease inhibitory activity was investigated. Mutants in which the RCL was shortened by one, two, or three residues were effective inhibitors with second-order rate constants of 10(5)-10(7) M(-)(1) s(-)(1). In addition to loop length, the identity of the cysteine protease was of considerable importance, since the chimeric molecules inhibited cathepsins L, V, and K efficiently, but not papain or cathepsin B. By testing complexes between an RCL-mimicking peptide and the mutants, it was found that the formation of a stable serpin-cysteine protease complex and the inhibition of a cysteine protease were both critically dependent on RCL insertion. The results strongly indicate that the serpin body is intrinsically capable of supporting cysteine protease inhibition, and that the complex with a papain-like cysteine protease would be expected to be analogous to that seen with serine proteases.


A new automated stem CO2 efflux chamber based on industrial ultra-low-cost sensors.
Tree autotrophic respiratory processes, especially stem respiration or stem CO2 efflux (Estem), are important components of the forest carbon budget. Despite efforts to investigate the controlling processes of Estem in recent years, a considerable lack in our knowledge remains on the abiotic and biotic drivers affecting Estem dynamics. It has been strongly advocated that long-term measurements would shed light onto those processes. The expensive scientific instruments needed to measure gas exchange have prevented Estem measurements from being applied on a larger temporal and spatial scale. Here, we present an automated closed dynamic chamber system based on inexpensive and industrially broadly applied CO2 sensors, reducing the costs for the sensing system to a minimum. The CO2 sensor was cross-calibrated with a commonly used gas exchange system in the laboratory and in the field, and we found very good accordance of these sensors. We tested the system under harsh tropical climatic conditions, characterized by heavy tropical rainfall events, extreme humidity and temperatures, in a moist lowland forest in Malaysia. We recorded Estem of three Dyera costulata (Miq.) trees with our prototype over various days. The variation of Estem was large among the three tree individuals and varied by 7.5-fold. However, clear diurnal changes in Estem were present in all three tree individuals. One tree showed high diurnal variation in Estem, and the relationship between Estem and temperature was characterized by a strong hysteresis. The large variations found within one single tree species highlight the importance of continuous measurement to quantify ecosystem carbon fluxes.


Histopathological and cognitive defects induced by Nef in the brain.
Complex mechanisms of human immunodeficiency virus type-1 (HIV-1) brain pathogenesis suggest the contribution of individual HIV-1 gene products. Among them, the Nef protein has been reported to harbor a major determinant of pathogenicity in AIDS-like disease. The goal of the present study was to determine whether Nef protein expressed in vivo by primary macrophages could induce a brain toxicity also affecting the behavior of the rat. To achieve this goal we grafted Nef-transduced macrophages into the rat hippocampus. Two months post-transplantation, we observed that Nef induces monocyte/macrophage recruitment, expression of TNF-alpha, and astrogliosis. No apoptotic event was detected. We further demonstrated that Nef neurotoxicity is associated with cognitive deficits.


Excision patterns of Activator (Ac) and Dissociation (Ds) elements in Zea mays L.: implications for the regulation of transposition.
The pattern of aleurone variegation of maize kernels carrying Ac and bz-m2(DI) as reporter allele for Ac activity depends on the dosage of both Ac and Ds. Alterations of Ac dosage can abolish Ds excision at certain times and allow it to occur at other times. wx-m7 and wx-m9 are different Ac insertions in the Waxy gene which have different dosage effects on Ds excision. Kernels, heterozygous for the two Ac alleles and being either wx-m7/wx-m7/wx-m9 or wx-m9/wx-m9/wx-m7 exhibit characteristic patterns of predominantly late excisions; this is in strong contrast to the pattern of early excisions present on wx-m7/wx-m7/wx-m7 homozygotes. This observation supports the hypothesis that the Ac alleles express different amounts of transposase (TPase) during development and that above a certain level of TPase transposition is inhibited. Furthermore, experimental results suggest that the frequency of Ac-induced events is influenced by the dosage and composition of the transactivated Ds or Ac allele. Thus, transposition frequency seems not to be exclusively determined in trans by the amount of active TPase, but also by specific cis-acting properties of the TPase substrate.


High-frequency ventilation: is there a clinical role?
Mechanical ventilation of the lungs is an integral component of modern medical practice, being utilized predominantly in the operating room and intensive care unit. The first mechanical ventilators were of the negative-pressure type. Currently, positive-pressure mechanical ventilation with frequency rates of up to 60 breaths per minute is referred to as conventional mechanical ventilation. In the 1960s, Sjöstrand developed the concept of high-frequency positive-pressure ventilation. This development was a logical continuation of physiology studies that built on earlier observations, which were then directly applied to clinical use. This paper is a synopsis of the current rationale for the clinical use of high-frequency ventilation.


[Changes in the vessels of the kidneys in rats on a choline- and protein-deficient diet].
Prolonged (from 4 to 10 months) keeping of rats on a cholinoprotein- and protein-deficient diets produces an associated moderate damage to the wall on renal blood vessels and glomerulopathy. There take place dystrophic alterations in the elastic skeleton of the interlobular arteries in the form of elasticity loss and impairment of the tinctorial properties on the internal elastic membrane combined with vacuolization of the smooth muscle cells of the media.


'In vitro' capacitation and further 'in vitro' progesterone-induced acrosome exocytosis are linked to specific changes in the expression and acrosome location of protein phosphorylation in serine residues of boar spermatozoa.
The aim of this study is to determine changes in the expression and location of protein serine phosphorylation (pSer) during 'in vitro' capacitation (IVC) and 'in vitro' acrosome exocytosis (IVAE) in boar spermatozoa. This was performed in both mono- and bi-dimensional analyses of protein expression through Western blot, as well as through immunocytochemistry. Furthermore, IVC was induced through incubation in an IVC medium, and afterwards, progesterone-induced IVAE was performed. The mono-dimensional Western blot analysis showed the presence of a predominant pSer band of approximately 70-75 kDa, which was accompanied by fainter bands, especially three with molecular weights of approximately 50, 35 and 32 kDa. Neither IVC nor IVAE significantly modified this pattern. Bi-dimensional analyses showed a more complex pattern, with at least five protein clusters. The attainment of IVC caused the disappearance of the proteins with the highest molecular weight concomitantly with the appearance of pSer proteins of 75-kDa/pI 9.5 and 80-kDa/pI 10. The induction of IVAE caused the appearance of new pSer proteins of a 75-kDa/pI 6.5-7.5 and 75-kDa/pI 10. Immunocytochemistry showed that the main pSer expression in boar expression before the attainment of IVC was located at the midpiece. The IVC induced the appearance of acrosomal pSer, which was greatly increased during IVAE. Our results indicate that the changes in serine protein phosphorylation associated with IVC and IVAE comprise not only the appearance of specific phosphorylated proteins, such as the pSer-75 kDa, but also changes in pI and displacements in the sperm location of phosphorylated proteins, like the specific acrosomal pSer signal induced during IVC.


Reactive Astrocytes in Neurodegenerative Diseases.
Astrocytes, the largest and most numerous glial cells in the central nervous system (CNS), play a variety of important roles in regulating homeostasis, increasing synaptic plasticity and providing neuroprotection, thus helping to maintain normal brain function. At the same time, astrocytes can participate in the inflammatory response and play a key role in the progression of neurodegenerative diseases. Reactive astrocytes are strongly induced by numerous pathological conditions in the CNS. Astrocyte reactivity is initially characterized by hypertrophy of soma and processes, triggered by different molecules. Recent studies have demonstrated that neuroinflammation and ischemia can elicit two different types of reactive astrocytes, termed A1s and A2s. However, in the case of astrocyte reactivity in different neurodegenerative diseases, the recently published research issues remain a high level of conflict and controversy. So far, we still know very little about whether and how the function or reactivity of astrocytes changes in the progression of different neurodegenerative diseases. In this review, we aimed to briefly discuss recent studies highlighting the complex contribution of astrocytes in the process of various neurodegenerative diseases, which may provide us with new prospects for the development of an excellent therapeutic target for neurodegenerative diseases.


Quality of anesthesia for the maxillary primary anterior segment in pediatric patients: comparison of the P-ASA nerve block using CompuMed delivery system vs traditional supraperiosteal injections.
The purpose of this study was to compare the quality of 2 injection techniques to anesthetize the maxillary primary anterior segment by applying either the palatal approach anterior superior alveolar nerve block (P-ASA) utilizing a computer-controlled injection device (CompuMed with the Wand handpiece) or traditional multiple supraperiosteal (TMS) injections with a hand-operated syringe. Depth and duration of anesthesia was assessed by the number of disruptive behaviors 20 minutes following injection. Twenty-one preschoolers aged 3 to 5 years, who required pulp tissue removal with subsequent crown placement and/or extraction of at least 2 teeth in the maxillary incisor segment on opposite sides of the midline, participated in this study. They were randomly assigned to either the P-ASA or the TMS injection group. The procedure was separated into 3 segments: (1) the injection; (2) overall procedure; and (3) painful event. Each segment was scored for disruptive behaviors (body movements, crying, restraint, or dentist interference) using an established scale. Scores were analyzed via analysis of variance for significance. During injection, disruptive behaviors occurred significantly less in the P-ASA group than in the TMS group. No significant differences were found between the 2 groups for the overall procedure and the painful event segments. Whereas anesthetic solution delivery with CompuMed system caused significantly less disruptive behavior during the injection phase, both methods seem to provide a comparable quality of anesthesia for the maxillary primary incisor segment 20 minutes after deposition of the anesthetic solution.


Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats.
The most important etiological factors of resistance to medical treatments for secondary hyperparathyroidism are the decreased contents of the vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct maxacalcitol (OCT) injection into PTG in terms of these factors were investigated in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH), Ca(2+), and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca(2+)-PTH curves were examined. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level, and a significant difference in this level between DI-OCT and DI-vehicle was observed. However, serum Ca(2+) and phosphorus levels did not changed markedly in both groups. The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca(2+)-PTH curve, and the induction of apoptosis after DI-OCT were observed. These findings were not observed in the DI-vehicle-treated rats. Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism.


Nanoinformatics, and the big challenges for the science of small things.
The combination of computational chemistry and computational materials science with machine learning and artificial intelligence provides a powerful way of relating structural features of nanomaterials with functional properties. However, combining these fundamentally different scientific approaches is not as straightforward as it seems. Machine learning methods were developed for large data sets with small numbers of consistent features. Typically nanomaterials data sets are small, with high dimensionality and high variance in the feature space, and suffer from numerous destructive biases. None of the established data science or machine learning methods in widespread use today were devised with (nano)materials data sets in mind, but there are ways to overcome these challenges and use them reliably. In this review we will discuss domain-specific constraints on data-driven nanomaterials design, and explore the differences between nanomaterials simulation and nanoinformatics that can be leveraged for greater impact.


Modular microstructure design to build neuronal networks of defined functional connectivity.
Theoretical and in vivo neuroscience research suggests that functional information transfer within neuronal networks is influenced by circuit architecture. Due to the dynamic complexities of the brain, it remains a challenge to test the correlation between structure and function of a defined network. Engineering controlled neuronal networks in vitro offers a way to test structural motifs; however, no method has achieved small, multi-node networks with stable, unidirectional connections. Here, we screened ten different microchannel architectures within polydimethylsiloxane (PDMS) devices to test their potential for axonal guidance. The most successful design had a 92% probability of achieving strictly unidirectional connections between nodes. Networks built from this design were cultured on multielectrode arrays and recorded on days in vitro 9, 12, 15 and 18 to investigate spontaneous and evoked bursting activity. Transfer entropy between subsequent nodes showed up to 100 times more directional flow of information compared to the control. Additionally, directed networks produced a greater amount of information flow, reinforcing the importance of directional connections in the brain being critical for reliable communication. By controlling the parameters of network formation, we minimized response variability and achieved functional, directional networks. The technique provides us with a tool to probe the spatio-temporal effects of different network motifs.


Stoichiometric molecularly imprinted polymers for the recognition of anti-cancer pro-drug tegafur.
Molecularly imprinted polymers (MIPs) targeting tegafur, an anti-cancer 5-fluorouracil pro-drug, have been prepared by stoichiometric imprinting using 2,6-bis(acrylamido)pyridine (BAAPy) as the functional monomer. Solution association between tegafur and BAAPy was studied by (1)H NMR titration, which confirmed the formation of 1:1 complexes with an affinity constant of 574±15M(-1) in CDCl3. Evaluation of the synthesised materials by HPLC and equilibrium rebinding experiments revealed high selectivity of the imprinted polymer for the pro-drug vs. 5-fluorouracil and other competing analytes, with maximum imprinting factors of 25.3 and a binding capacity of 45.1μmolg(-1). The synthesised imprinted polymer was employed in solid-phase extraction of the pro-drug using an optimised protocol that included a simple wash with the porogen used in the preparation of the material. Tegafur recoveries of up to 96% were achieved from aqueous samples and 92% from urine samples spiked with the template and three competing analytes. The results demonstrate the potential of the prepared polymers in the pre-concentration of tegafur from biological samples, which could be an invaluable tool in the monitoring of patient compliance and drug uptake and excretion.


Influence of spinal posture on abnormalities demonstrated by lumbar myelography.
During spinal movements the dural end sac undergoes displacement and deformation, chiefly because of bulging of intervertebral disks and flaval ligaments in lumbar extension. Under normal circumstances these dural changes of form do not lead to clinical symptoms. However, in patients with spinal stenosis radiologic signs may be accentuated in lumbar extension. These tend to disappear in flexion. This implies that examination techniques performed in extension (prone lumbar myelography) tend to enhance abnormalities, while techniques in which the spine is more or less flexed (epidural phlebography, computed tomography) tend to mask them. In addition, there may be discrepancy between the picture during surgery (usually in lumbar flexion) and the situation in which a patient experiences symptoms (usually in lumbar extension in spinal stenosis).


[Diagnosis and treatment of liver abscess after orthotopic liver transplantation].
To investigate etiology, diagnosis, treatment and prophylaxis of liver abscess after orthotopic liver transplantation (OLT). Of 274 recipients of OLT from January 1993 to June 2003 in our transplant center, liver abscess were identified in 6 recipients (2.2%). The clinical presentation included fever, shiver, abdominal pain, jaundice, hepatic dysfunction, hypoalbuminemia, anemia, leukocytosis and neutrophilia. They were diagnosed mainly according to the clinical presentation and Ultrasonography or CT scan. The treatments included aspiration and drainage of abscess, removing bile sludge, antibiotics and supportive therapy. Of 6 patients, 2 were cured, 3 refused liver retransplantation and 2 died of serious systemic infection. The cure rate was 33.3%. the etiology of liver abscess after OLT is complicated. The predisposing factors might be included hepatic artery thrombosis or stenosis, MP pulse therapy, cholangitis and biliary interventional therapy. Its prognosis seemed disappointing. Strong prophylactic measures should be recommended to reduce the liver abscess after OLT.


Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging.
Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3 alpha (DNMT3A) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G > A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS), their mosaic father, and 15 TBRS patients with distinct pathogenic de novo DNMT3A variants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated as genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. These findings were most marked in a carrier of the AML-associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype-related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders: NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamental new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance, and determinants of biological aging in these growth disorders.


Accelerated wound healing by S-methylmethionine sulfonium: evidence of dermal fibroblast activation via the ERK1/2 pathway.
S-Methylmethionine sulfonium (SMMS) is a derivative of the amino acid methionine, and is synthesized in a variety of plants. SMMS is widely referred to as vitamin U because of its potent therapeutic effect on gastrointestinal ulceration. Skin wounds are accompanied by mucosal erosion and share similar histopathological aspects with gastric ulcers, so it is plausible that SMMS may promote skin wound healing. In animal models, topical administration of SMMS for a given period of time, to both physical and chemical wounds, facilitated wound closure and promoted re-epithelialization compared with a control. In addition, single SMMS treatment was sufficient to promote the growth of human dermal fibroblasts (hDFs) as well as the migration of hDFs, which are indispensable steps for skin wound healing. The promotion of hDF proliferation and migration resulted from considerable activation of ERK1/2 by SMMS, and inhibition of ERK activity by a chemical inhibitor significantly abrogated both the promoted proliferation and migration of hDFs. Therefore, we concluded that SMMS facilitated the repair process of skin damage by activation of dermal fibroblasts, which suggests that SMMS has potential as a skin wound-healing agent.


On the Emergence of Intersexual Selection: Arbitrary Trait Preference Improves Female-Male Coevolution.
Sexual selection is a fundamental aspect of evolution for all eukaryotic organisms with mating types. This article suggests intersexual selection is best viewed as a mechanism with which to compensate for the unavoidable dynamics of coevolution between sexes that emerge with isogamy. Using the NKCS model it is shown by varying fitness landscape size, ruggedness, and connectedness, how a purely arbitrary trait preference sexual selection mechanism proves beneficial with high dependence between the sexes. This is found to be the case whether one or both sexes exploit such intersexual selection.


Metabolomics method to comprehensively analyze amino acids in different domains.
Amino acids play essential roles in both metabolism and the proteome. Many studies have profiled free amino acids (FAAs) or proteins; however, few have connected the measurement of FAA with individual amino acids in the proteome. In this study, we developed a metabolomics method to comprehensively analyze amino acids in different domains, using two examples of different sample types and disease models. We first examined the responses of FAAs and insoluble-proteome amino acids (IPAAs) to the Myc oncogene in Tet21N human neuroblastoma cells. The metabolic and proteomic amino acid profiles were quite different, even under the same Myc condition, and their combination provided a better understanding of the biological status. In addition, amino acids were measured in 3 domains (FAAs, free and soluble-proteome amino acids (FSPAAs), and IPAAs) to study changes in serum amino acid profiles related to colon cancer. A penalized logistic regression model based on the amino acids from the three domains had better sensitivity and specificity than that from each individual domain. To the best of our knowledge, this is the first study to perform a combined analysis of amino acids in different domains, and indicates the useful biological information available from a metabolomics analysis of the protein pellet. This study lays the foundation for further quantitative tracking of the distribution of amino acids in different domains, with opportunities for better diagnosis and mechanistic studies of various diseases.


Exploring psychosocial experiences of behavior therapists dealing with children having autism spectrum disorder.
Behavior therapists play an important role in the life of children with an autism spectrum disorder (ASD). Literature reported that child's improvement depends on the quality of therapy they receive. Therefore, the current study aims to explore the psychosocial experiences of behavior therapist working with children having ASD, and suggest the coping strategies which they use to deal with those stressors. The study utilizes a qualitative research design with a phenomenological research approach to explore the psychosocial experiences. For this purpose, the researchers conduct semi-structured interviews of 6 behavior therapists, ages ranging from 25 to 35 years. They note the verbatim of the therapists and convert into codes to create themes and categories. Furthermore, the study utilizes Interpretative Phenomenological Analysis for the interpretation of the results. The results of this phenomenological research indicate six superordinate themes emerged from the transcripts. The results demonstrate professional and psychological experiences of behavior therapists along with the social and the health issues faced by the children with ASD, and the coping strategies used by the therapists that is emotion focused coping, problem focused coping and maladaptive copings. Gaining insight into therapists' psychosocial experiences can pave the way for developing approaches aimed at enhancing their overall welfare. These approaches may encompass initiatives to alleviate stress, mitigate burnout, and boost job satisfaction.


Arl13b and the non-muscle myosin heavy chain IIA are required for circular dorsal ruffle formation and cell migration.
The Arf-like protein Arl13b has been implicated in ciliogenesis and Sonic hedgehog signaling. Furthermore, we have previously shown that it regulates endocytic recycling traffic and interacts with actin. Herein, we report that the non-muscle myosin heavy chain IIA, also known as Myh9, is an Arl13b effector. Moreover, we found that both proteins localized to circular dorsal ruffles (CDRs) induced by platelet-derived growth factor stimulation and are required for their formation. CDRs are ring-shaped actin-dependent structures formed on the dorsal cell surface and are involved in diverse processes, such as macropinocytosis, integrin recycling, internalization of receptor tyrosine kinases and cell migration. We found that Arl13b or Myh9 silencing impaired cell migration, suggesting that Arl13b is required for this function through the interaction with Myh9. Moreover, Arl13b silencing impaired neural crest cell migration in zebrafish embryos. Furthermore, we showed that Arl13b is required for the formation of CDRs in migrating cells. Thus, our results indicate a new role for Arl13b in actin cytoskeleton remodeling through the interaction with Myh9, by driving the formation of CDRs necessary for cell migration.


Consumption of Ultra-Processed Foods and Mortality: A National Prospective Cohort in Spain.
To assess the prospective association between ultra-processed food consumption and all-cause mortality and to examine the effect of theoretical iso-caloric non-processed foods substitution. A population-based cohort of 11,898 individuals (mean age 46.9 years, and 50.5% women) were selected from the ENRICA study, a representative sample of the noninstitutionalized Spanish population. Dietary information was collected by a validated computer-based dietary history and categorized according to their degree of processing using NOVA classification. Total mortality was obtained from the National Death Index. Follow-up lasted from baseline (2008-2010) to mortality date or December 31th, 2016, whichever was first. The association between quartiles of consumption of ultra-processed food and mortality was analyzed by Cox models adjusted for the main confounders. Restricted cubic-splines were used to assess dose-response relationships when using iso-caloric substitutions. Average consumption of ultra-processed food was 385 g/d (24.4% of the total energy intake). After a mean follow-up of 7.7 years (93,599 person-years), 440 deaths occurred. The hazard ratio (and 95% CI) for mortality in the highest versus the lowest quartile of ultra-processed food consumption was 1.44 (95% CI, 1.01-2.07; P trend=.03) in percent of energy and 1.46 (95% CI, 1.04-2.05; P trend=.03) in grams per day per kilogram. Isocaloric substitution of ultra-processed food with unprocessed or minimally processed foods was associated with a significant nonlinear decrease in mortality. A higher consumption of ultra-processed food was associated with higher mortality in the general population. Furthermore, the theoretical iso-caloric substitution ultra-processed food by unprocessed or minimally processed foods would suppose a reduction of the mortality risk. If confirmed, these findings support the necessity of the development of new nutritional policies and guides at the national and international level. clinicaltrials.gov Identifier: NCT01133093.


Dioxin exposure and benign prostatic hyperplasia.
Dioxins decrease prostate weight, reduce androgen responsiveness, and inhibit prostate morphogenesis in rats. We assessed the association of dioxins and benign prostatic hyperplasia (BPH) in participants in the National Health and Nutritional Examination Survey 1999-2000. Forty-two participants were classified as having BPH and 99 were classified as controls. Dioxin exposure was expressed as dioxin toxic equivalents (TEQ). Age, body mass index, waist circumference, race/ethnicity, smoking, physical activity, and education were assessed as potential confounders. After age adjustment, men without BPH had 20.9% higher TEQs (95% confidence interval [CI] = 5.4-38.7%) as compared with men with BPH. On weighted, multivariate, logistic regression analyses, men with higher dioxin levels had lower odds of having BPH (odds ratio = 0.22, 95% CI = 0.08-0.62). Dioxin exposure in the general population may be associated with decreased odds of BPH. Our study findings need to be confirmed.


Spontaneous spinal epidural hematoma leading to acute paraplegia: a case report.
Spontaneous spinal epidural hematoma is an infrequent yet potentially debilitating condition characterized by blood accumulation in the epidural space, with only 300 documented cases globally. Although the exact etiology of spontaneous spinal epidural hematoma remains poorly understood, theories suggest arteriovenous malformations, rupture of epidural vessels, or epidural veins as possible causes. This study presents a 58-year-old Malay woman patient from Singapore with well-controlled hypertension, hyperlipidemia, type II diabetes mellitus, and microscopic hematuria. Despite a prior cystoscopy revealing no abnormalities, she presented to the emergency department with sudden-onset back pain, weakness, and numbness in both lower limbs. Rapidly progressing symptoms prompted imaging, leading to the diagnosis of a spinal epidural hematoma from thoracic (T) 9 to lumbar (L) 1. Prompt decompressive surgery was performed, and the patient is currently undergoing postoperative rehabilitation for paralysis. This case emphasizes the severity and life-altering consequences of spontaneous spinal epidural hematomas. Despite various proposed causative factors, a definitive consensus remains elusive in current literature. Consequently, maintaining a low threshold of suspicion for patients with similar presentations is crucial. The findings underscore the urgent need for swift evaluation and surgical intervention in cases of acute paraplegia.


Adult human colonic subepithelial myofibroblasts express extracellular matrix proteins and cyclooxygenase-1 and -2.
Interactions between epithelial cells and subepithelial myofibroblasts are increasingly recognized as important in the regulation of epithelial cell function. We have established primary cultures of subepithelial myofibroblasts from adult human colonic mucosal samples denuded of epithelial cells and maintained in culture. During culture of mucosal tissue, subepithelial myofibroblasts migrated out via basement membrane pores before establishment in culture. Despite prolonged culture and passage, the myofibroblasts maintained their phenotype, as demonstrated by expression of alpha-smooth muscle actin and vimentin. The cells expressed transcripts and protein for cyclooxygenase (COX)-1 and -2 enzymes, and their release of prostaglandin E2 (PGE2) was inhibited by selective COX-1 and -2 inhibitors. The myofibroblasts also expressed the extracellular matrix (ECM) proteins collagen type IV, laminin-beta 1 and -gamma 1, and fibronectin. Adult human colonic subepithelial myofibroblasts may influence epithelial cell function via products of COX-1 and -2 enzymes, such as PGE2 and secreted ECM proteins.


Altered calcium regulation by thermosensitive transient receptor potential channels in etoposide-resistant WERI-Rb1 retinoblastoma cells.
Differences in transient receptor potential (TRP) and cannabinoid receptor type 1 (CB1) expression levels can serve as prognostic factors for retinoblastoma (RB) tumor progression. We hypothesized in RB tissue that such differences are also indicators of whether or not they are sensitive to etoposide. Accordingly, we compared in malignant etoposide-sensitive and etoposide-resistant WERI-Rb1 cells TRPV1, TRPM8 and TRPA1 subtype and CB1 gene expression pattern levels and accompanying functional activity using quantitative real-time RT-PCR, immunohistochemistry, immunofluorescence microscopy, calcium imaging as well as patch-clamp technology. Gene expression patterns were evaluated in enucleated human RB tissues (n = 4). Both etoposide-resistant and etoposide-sensitive WERI-Rb1 cells expressed all of the aforementioned channels based on responses to known activators and thermal challenges. However, TRPA1 was absent in the etoposide-resistant counterpart. Even though both types of RB cells express TRPV1 as well as TRPM8 and CB1, the capsaicin (50 μM) (CAP)-induced Ca(2+) rise caused by TRPV1 activation was prompt and transient only in etoposide-resistant RB cells (n = 8). In this cell type, the inability of CB1 activation (10 μM WIN) to suppress Ca(2+) responses to CAP (50 μM; n = 4) may be attributable to the absence of TRPA1 gene expression. Therefore, using genetic approaches to upregulate TRPA1 expression could provide a means to induce etoposide sensitivity and suppress RB cell tumorigenesis.


[Shock as an adverse reaction to rituximab: Case report].
Rituximab is a plausible alternative first-line treatment of ANCA-associated vasculitis. Adverse effects related to its infusion are common and usually have a benign course. However, there have been reports of refractory cardiogenic shock simulating septic shock. We report an 81-year-old male with the diagnosis of ANCA associated vasculitis. Rituximab 500 mg was administered intravenously for a relapse. The infusion proceeded without incident. However, 24 hours after its administration the patient began with fever, chills, coughing and strong malaise. The patient was transferred to the critical patient unit where a septic shock was suspected and resuscitative measures were started. However, the fast response to moderate doses of vasoactive drugs and complementary tests did not support an infectious etiology for the shock. Antimicrobials were discontinued and systemic corticosteroids were maintained, achieving remission of the symptoms. Shock as an unusual adverse reaction to Rituximab was suspected.


[Adsorption of different cell cultures on colonies of M. hominis].
A study was made of sorption of 6 continuous lines of cells on the colonies of 55 M. hominis strains isolated from patients with inflammatory diseases of the urogenital tract. M. hominis proved to be capable of sorbing various cell cultures on the colonies. The sorption depended on the type of the culture. The greatest sorption capacity was possessed by the cells of human origin --FL and HeLa. M. hominis strains under study differed by their capacity to cell sorbtion. The method of cell sorption on the colonies can be suggested for the determination of heterogeneity of the population and of the intrastrain differences in M. hominis.


Sporadic unilateral retinoblastoma or first sign of bilateral disease?
A small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma). We analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma to identify risk factors for the development of metachronous bilateral disease. Fifteen (3.1%) of 480 children with unilateral retinoblastoma later developed metachronous bilateral retinoblastoma (latency period >30 days). The maximum latency period was 2.3 years after initial diagnosis. Nine (22.5%) of 40 children with a RB1 mutation detectable in blood developed metachronous bilateral disease while all 155 children proved to be without a germline RB1 mutation remained unilaterally affected. Clinically, the risk of developing metachronous bilateral retinoblastoma was higher for age at diagnosis ≤0.5 years compared with >0.5 years (19.6% vs 1.2%), and for multifocal compared with unifocal unilateral retinoblastoma (17.1% vs 2.2%). This study shows that an oncogenic RB1 mutation in the blood is a risk factor for metachronous bilateral retinoblastoma. Additional clinical risk factors for metachronous bilateral disease are diagnosis at young age (≤0.5 years) and multifocal unilateral retinoblastoma. Early genetic analysis may identify children at high risk of developing metachronous bilateral disease and may help to preserve vision using risk-adapted follow-up and early treatment.


Wakame seaweed suppresses the proliferation of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats.
We examined the anti-tumor proliferation effects of wakame seaweed on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumor. DMBA was administered to 8-week-old female Sprague-Dawley rats, and rats which developed mammary tumors were assigned randomly to three groups. Commercial rat feed was used in a control group (group I-A), and two feed mixtures were prepared, which contained commercial rat feed blended with wakame at 1.0% (group I-B) and 5.0% (group I-C) by weight. The respective feeds were given to each group for 8 weeks, and changes in mammary tumor size were compared. At the end of the experiment, mammary tumors and thyroid glands were resected to compare their weights. Serum total iodine and thyroxin (T4) levels were measured. Immunohistochemical studies for bromodeoxyuridine (BrdU) labeling, transforming growth factor (TGF)-beta, and apoptosis were carried out in the resected tumor. Significant suppression of tumor growth was observed in groups I-B and I-C compared with I-A. In groups I-B and I-C, the weights of resected mammary tumors were significantly lower and serum total iodine concentration was significantly higher than in I-A. BrdU indices were significantly lower in groups I-B and I-C, compared with I-A. TGF-beta and apoptotic index were inversely related to BrdU. These results suggest that iodine is transported from the serum into mammary tissues and induces apoptosis through the expression of TGF-beta. In conclusion, wakame suppressed the proliferation of DMBA-induced mammary tumors.


Orbital histiocytosis and fibrohistiocytosis: the clinicopathological characteristics of 117 patients, over a decade of experience.
To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH) and non-LCH disorders, and correlate patients' clinical characteristics with their pathological diagnosis. In this retrospective study, medical records of patients presenting to Farabi Eye Hospital, a tertiary eye care center in Tehran, Iran, from 2010 until 2022, were reviewed. Patients' demographics, chief complaint, location and laterality of the tumor, best-corrected visual acuity, presence of bone erosion on imaging, and their pathological diagnosis were retrieved. Excisional biopsy was performed and evaluated through light microscopy and immunohistochemistry study for their respective markers, including CD1a, CD68, CD207, and S100. A total of 117 patients with 11 pathological subtypes of histiocytoses and fibrohistiocyosis were identified, with 56.4% male and 43.6% female patients. The mean age at presentation was 23.4 years (range 1.5 months-73 years). Swelling and palpable mass were the most common chief complaints. LCH was the most common pathology (32.5%), followed by juvenile xanthogranuloma (26.5%) and adult xanthogranuloma (21.4%). Age, lesion location, and bone erosion had a statistically significant difference among the various diagnosed subtypes. Histiocytoses and fibrohistiocytosis are diverse and rare disorders potentially involving multiple organ systems. Ophthalmic manifestations of these diseases are even more uncommon. We reviewed their orbital presentation along with their respective histopathological findings. Our results also suggested that an orbital CT scan can be of diagnostic value to discriminate LCH from other histiocytic pathologies.


Sulfate availability affects ABA levels and germination response to ABA and salt stress in Arabidopsis thaliana.
Sulfur-containing compounds play a critical role in the response of plants to abiotic stress factors including drought. The phytohormone abscisic acid (ABA) is the key regulator of responses to drought and high-salt stress. However, our knowledge about interaction of S-metabolism and ABA biosynthesis is scarce. Here we report that sulfate supply affects synthesis and steady-state levels of ABA in Arabidopsis wild-type seedlings. By using different mutants of the sulfate uptake and reduction pathway, we confirmed the impact of sulfate supply on steady-state ABA content in Arabidopsis and demonstrated that this impact was due to cysteine availability. Loss of the chloroplast sulfate transporter3;1 function (sultr3;1) resulted in significantly decreased aldehyde oxidase (AO) activity and ABA levels in seedlings and seeds. These mutant phenotypes could be reverted by exogenous application of cysteine or ectopic expression of SULTR3;1. In addition the sultr3;1 mutant showed a decrease of xanthine dehydrogenase activity, but not of nitrate reductase, strongly indicating that in seedlings cysteine availability limits activity of the molybdenum co-factor sulfurase, ABA3, which requires cysteine as the S-donor for sulfuration. Transcription of ABA3 and NCED3, encoding another key enzyme of the ABA biosynthesis pathway, was regulated by S-supply in wild-type seedlings. In contrast, ABA up-regulated the transcript level of SULTR3;1 and other S-metabolism-related genes. Our results provide evidence for a significant co-regulation of S-metabolism and ABA biosynthesis that operates to ensure sufficient cysteine for AO maturation and highlights the importance of sulfur for stress tolerance of plants.


The ethics and politics of patient-physician mistrust in contemporary China.
Focusing on the shared sense of victimization and disadvantage-ness by both patients and doctors/medical workers in cases of medical conflicts, this paper aims to examine the current patient-doctor tensions in the larger context of moral transformation in Chinese society since the 1980s. Although the decline of public trust in certain aspects is closely associated with the impact of commodification and commercialization of medical sector during the past two decades, other factors play important role as well. In the case of patient-doctor tension, mutual disrespect and mistrust also result from the ongoing process of individualization and the remaking of moral self, in which the individual demand for respect, dignity, and trust seem to have unexpectedly and ironically contributed to the rise of tensions and conflicts between patients and doctors as well as other medical workers.


JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data.
Janus kinase (JAK) Inhibitors are the latest drug class of disease-modifying medication to emerge for the treatment of rheumatoid arthritis (RA). They are a small molecule-targeted treatment and are the first oral option to compare favourably to existing biologic disease-modifying anti-rheumatic drugs (DMARDs). Tofacitinib, baricitinib and upadacitinib are the first 3 JAK inhibitors to become commercially available in the field and are the core focus of this review. To date, they have demonstrated comparable efficacy to tumour necrosis factor (TNF) inhibitors in terms of American College of Rheumatology (ACR) response rates and disease activity (DAS28) scores with similar cost to the benchmark adalimumab. This narrative review article aims to synthesise and distil the key available trial data on JAK inhibitor efficacy and safety, along with their place in the ACR and European League Against Rheumatism (EULAR) guidelines for RA. The novel mechanism of action of the JAK/STAT pathway is highlighted along with the potential effects of modulating each pathway. The rapid onset of action, role in attenuation of central pain processing and effect on structural damage and radiographic progression are also all examined in detail. We also explore the latest meta-analyses and comparative performance of each of the 3 available JAKs in an effort to determine which is most efficacious and which has the most favourable safety profile. Post marketing concerns regarding thromboembolism risk and herpes zoster infection are also discussed. Additionally, we review the cost-benefit analyses of the available JAK inhibitors and address some of the pharmacoeconomic considerations for real-world practice in the UK and US by detailing the raw acquisition cost and the value they provide in comparison to the benchmark biologic adalimumab and the anchor DMARD methotrexate.


The influence of cytotoxicity of macromolecules and of VEGF gene modulated vascular permeability on the enhanced permeability and retention effect in resistant solid tumors.
To study the influence of cytotoxicity of macromolecules, VEGF gene expression, and vascular permeability on the enhanced permeability and retention (EPR) effect. Mice bearing xenografts of A2780 multidrug resistant human ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound DOX (P(GFLG)-DOX), Texas Red (P-TR), and FITC (P-FITC). Antitumor activity, drug distribution in tumor, vascular permeability, VEGF gene expression, and DNA fragmentation were studied. The accumulation of free DOX led to the VEGF gene overexpression and increased the vascular permeability, which in turn enhanced the drug accumulation in the same location. This positive feedback loop led to a highly inhomogeneous distribution of the drug within the tumor. In contrast, P(GFLG)-DOX down-regulated the VEGF gene and decreased vascular permeability. This negative feedback seemed to prevent additional drug accumulation in dead necrotic tissue, resulting in a more uniform drug distribution and enhanced the antitumor activity P(GFLG)-DOX. The EPR effect significantly differed for macromolecules containing DOX when compared to macromolecules without drug. The cytotoxicity of P(GFLG)-DOX amplified the EPR effect, led to a more homogenous distribution of the drug, increased the average drug concentration in tumor and augmented its efficacy.


Individual change amid stable smoking patterns in polydrug users over 3 years.
The pattern of stability/change in smoking status was examined annually in 254 community-dwelling polydrug users over 3 years. Respondents' smoking status was classified as nonsmoker, intermittent smoker, or "everyday" smoker. Results showed that the typical probability of retaining the same smoking status across any two consecutive assessments was: 0.77 for nonsmokers (never smokers and former smokers combined), 0.82 for everyday smokers, and 0.16 for intermittent smokers. The transition matrix proved stable across three observations; the predicted equilibrium distribution matched well with observed distributions. Fifty-five percent of intermittent smokers converted to everyday smoking within a year, but 29% converted to former-smoker status in the same period. No other transition exceeded 12%. Considerable flux in individual smoking status, particularly among intermittent smokers, was observed despite stable prevalence of smoking status in this population. Intermittent smoking status appeared to be a temporary "way station" between the two more stable everyday smoker and nonsmoker classifications. Results challenge current assumptions about "occasional" or "chipper" smokers.


Quantitative biomechanical comparison of ankle fracture casting methods.
The incidence of ankle fractures is increasing rapidly due to the ageing demographic. In older patients with compromised distal circulation, conservative treatment of fractures may be indicated. High rates of malunion and complications due to skin fragility motivate the design of novel casting systems, but biomechanical stability requirements are poorly defined. This article presents the first quantitative study of ankle cast stability and hypothesises that a newly proposed close contact cast (CCC) system provides similar biomechanical stability to standard casts (SC). Two adult mannequin legs transected at the malleoli, one incorporating an inflatable model of tissue swelling, were stabilised with casts applied by an experienced surgeon. They were cyclically loaded in torsion, measuring applied rotation angle and resulting torque. CCC stiffness was equal to or greater than that of SC in two measures of ankle cast resistance to torsion. The effect of swelling reduction at the ankle site was significantly greater on CCC than on SC. The data support the hypothesis that CCC provides similar biomechanical stability to SC and therefore also the clinical use of CCC. They suggest that more frequent re-application of CCC is likely required to maintain stability following resolution of swelling at the injury site.


Expression patterns of proliferating cell nuclear antigen in the small intestine of mice infected with Metagonimus yokogawai and Metagonimus Miyata type.
Genus Metagonimus has been a subject of taxonomic debates for several years. In morphological aspects, M. yokogawai has been thought to have three subtypes, namely Yokogawa type (M. yokogawai in strict sense), Miyata type and Koga type, But differences in the intestinal pathology induced by these subtypes have not been studied yet. In this study we compared the pathological reactions induced by M. yokogawai and Metagonimus Miyata type using proliferating cell nuclear antigen (PCNA) index. Metacercariae (Mc) of M. yokogawai were collected by artificial digestion of Plecoglossus altivelis and Mc of Metagonimus Miyata type were collected from Zacco platypus. Three hundreds Mc of each species were infected orally to ICR mice. The mice were sacrificed at 3, 6, 10, 16 and 23 days after infection and the small intestines were resected into three portions (proximal, middle, and distal). Immunohistochemical staining for PCNA was done using PC-10 (DAKO-PCNA, CA, USA). The PCNA indices in M. yokogawai infected group on the 6th and 23rd day after infection were lower than in the control and Miyata type infected groups (p < 0.05) from all of the three intestinal regions. On the other hand, the control group and Metagonimus Miyata type infected group did not make any differences in PCNA indices. The villus/crypt (V/C) ratio was also decreased significantly in M. yokogawai infected mice but not in Metagonimus Miyata type infected ones. It is suggested that M. yokogawai induce villous atrophy through a decrease in the cell proliferation at the crypt. The results of this study suggested that M. yokogawai induce more serious intestinal pathology than Metagonimus Miyata type.


Measuring the quality of well-being in cystic fibrosis and lung transplantation. The importance of the area under the curve.
The quality of well-being scale (QWB) has been used to measure overall life quality in a number of different clinical conditions, including cystic fibrosis and chronic obstructive pulmonary disease. Evidence supports its validity and reliability in both cross-sectional and longitudinal studies. One of the strengths of the QWB is that it is not organ-specific, so that it can take into account the broad impact of a disease and/or intervention, including unanticipated effects. The well-year of life is a concept that includes both morbidity and mortality: if a disease reduces quality of life by one-half, over a period of two years, that person can be said to have lost one full well-year. As we examine the impact of diseases such as cystic fibrosis, and of interventions such as lung transplantation, it is important to consider changes in overall well-being over time to help individual patients and families make difficult therapeutic choices and to help formulate health policy.


The management of inoperable gastrointestinal obstruction in terminal cancer patients.
The aim of the study was to assess vomit and pain control in terminal cancer patients with inoperable gastrointestinal obstruction, using a pharmacologic symptomatic treatment which prevents recourse to nasogastric tube placement and intravenous hydration, in hospital and home care settings. Twenty-two symptomatic patients, who were judged as inoperable, were treated with a pharmacologic association of morphine hydrochloride and scopolamine butylbromide as analgesics and haloperidol as an antiemetic. The drugs were administered by continuous subcutaneous infusion via a syringe driver or intravenously only when a central venous catheter had been inserted previously. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (T0), 2 days after (T2) and 2 days before death (T-2). They showed that there was a significant decrease in the pain score (p less than 0.001) on T2 and a further decrease on T-2 (p less than 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastric tube placement. Dry mouth showed an upward trend throughout the observation period (p less than 0.05) but was successfully treated by administering liquids by mouth or ice-cubes to suck. Drowsiness too presented an upward trend from T0 to T-2 (p less than 0.001). Only one patient out of 16 who reported to be thirsty required intravenous hydration. We believe that in terminal cancer patients, vomit and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administration of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasogastric tube placement or intravenous hydration.


Morphology, pathology, and surgery of idiopathic vitreoretinal macular disorders. A review.
Macular pucker, the vitreomacular traction syndrome, and impending macular hole are three idiopathic macular disorders sometimes treated by vitreous surgery. Each condition has distinctive clinical features, pathogenic mechanisms, vitreoretinal anatomy, surgical findings, results, and complications. The clinical and pathologic features of these three conditions are compared based on a series of: (1) 101 idiopathic macular pucker cases for which clinicopathologic correlation with transmission electron microscopy (CPC-EM) was available, (2) 24 cases of the vitreomacular traction syndrome (7 patients with CPC-EM), and (3) 43 cases of impending macular hole (7 patients with CPC-EM). All cases of macular pucker, 16 cases of vitreomacular traction syndrome, and 15 cases of impending macular hole have been reported. The median visual acuity for patients with epiretinal membrane and vitreomacular traction syndrome improved from 20/200 preoperatively to 20/70 and 20/50 postoperatively. Macular holes occurred postoperatively in 11 of 43 patients with impending macular hole. The three conditions must be differentiated clinically so that proper recommendations regarding prognosis and possible surgical management can be made.


Radiation-induced apoptosis in a murine T-cell hybridoma.
Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X-radiation, 43 degrees C heat shock, A254 light, and hydrogen peroxide. In 5-Gy-exposed cells, a radiation-induced G2 phase cell cycle progression block was maximum by 8 h. The cells began to escape this progression block by 10 h. Nuclear DNA fragmentation and uptake of the vital dye trypan blue began at 12 and 14 h, respectively, and were complete by 28 h. X-radiation-induced cell death was diminished when cells were irradiated in the presence of dimethyl sulfoxide, indicating that cell death was induced by oxidative cell damage. Substitution of nuclear DNA with bromodeoxyuridine enhanced death in cells exposed to either X-radiation or A310 light, indicating that apoptosis could be induced by DNA damage. The results are consistent with radiation-induced apoptosis being stimulated by oxidative DNA damage. DNA damage stimulates a long-lived signal which controls the expression of apoptosis. Apoptosis is expressed in the G1 phase of the cell cycle subsequent to the cell irradiation.


Extended wear hydrogel lenses. Long-term effectiveness and costs.
During the period 1976-79, 1,201 of 1,552 aphakic patients were successfully fitted with third generation extended wear hydrogen lenses of thin-membrane design (CSI¿ lens) and highly hydrated polymer design (Permalens,¿Sauflon¿) without significant or permanent visula loss. Between 79% and 82% of the patients who failed did so in the first 90 days, and thereafter failure rates declined with time. Replacement rates for lenses approximated one lens per eye per year. Rates of required removal for cleaning varied. Ten to 13% of patients required cleaning at less than three-month intervals, and 5-6% at less than one month. For average patients with unilateral devices and no complication, extended wear lenses in Georgia are estimated to cost approximately three times as much as an intraocular lens over a 20-year follow-up period. General advantages ofextended wear third generation lenses include: (1) an acceptably savce and visually effective way to correct aphakia when patients are carefully selected, fitted, educated, and followed; (2) can be easily removeed, refitted or updated as technology advances; and (3) will not replace intraocular lenses, but can be used when implantation is contraindicated and should prevent the need for secondary or bilateral implantation or keratophakia in most cases.


Total Knee Arthroplasty in Unrecognized Septic Arthritis-A Descriptive Case Series Study.
Synovitis, like that associated with chronic bacterial arthritis, is a very rare finding during the implantation of knee endoprostheses. In such cases, we fix the knee prostheses with cement containing two antibiotics and carry out a course of systemic antibiotic administration. The aim was to analyze these cases for incidence, detection of bacteria, risk factors, and outcome. Out of 7534 knee replacements between January 2013 and December 2020, 25 cases were suspected during the surgical procedure to have suffered from bacterial arthritis and were treated accordingly. Total synovectomy was carried out, whereby five intraoperative synovial samples were examined bacteriologically, and the complete synovitis was analyzed histologically. The mean follow-up was 65.3 ± 27.1 (24-85) months. In nine cases (0.12%), the diagnosis of bacterial arthritis was made histologically and by clinical chemistry (elevated CRP), and in two of these cases, pathogen verification was performed. Eight of these nine patients had previously had injections or surgery associated with the corresponding knee joint or had an underlying immunomodulatory disease. None of the patients developed a periprosthetic infection at a later stage. With an incidence of 0.12%, it is rare to unexpectedly detect bacterial synovitis during surgery. Total synovectomy, use of bone cement with two antibiotics, and immediate systemic antibiotic therapy seem to keep the risk of periprosthetic infection low.


The size and continuity of DNA segments integrated in Bacillus transformation.
We investigated the size and continuity of DNA segments integrated in Bacillus subtilis transformation. We transformed B. subtilis strain 1A2 toward rifampicin resistance (coded by rpoB) with genomic DNA and with a PCR-amplified 3.4-kb segment of the rpoB gene from several donors. Restriction analysis showed that smaller lengths of donor DNA integrated into the chromosome with transformation by PCR-amplified DNA than by genomic DNA. Nevertheless, integration of very short segments (< 2 kb) from large, genomic donor molecules was not a rare event. With PCR-amplified segments as donor DNA, smaller fragments were integrated when there was greater sequence divergence between donor and recipient. There was a large stochastic component to the pattern of recombination. We detected discontinuity in the integration of donor segments within the rpoB gene, probably due to multiple integration events involving a single donor molecule. The transfer of adaptations across Bacillus species may be facilitated by the small sizes of DNA segments integrated in transformation.


Molecular gene profiling of Clostridium botulinum group III and its detection in naturally contaminated samples originating from various European countries.
We report the development of real-time PCR assays for genotyping Clostridium botulinum group III targeting the newly defined C. novyi sensu lato group; the nontoxic nonhemagglutinin (NTNH)-encoding gene ntnh; the botulinum neurotoxin (BoNT)-encoding genes bont/C, bont/C/D, bont/D, and bont/D/C; and the flagellin (fliC) gene. The genetic diversity of fliC among C. botulinum group III strains resulted in the definition of five major subgroups named fliC-I to fliC-V. Investigation of fliC subtypes in 560 samples, with various European origins, showed that fliC-I was predominant and found exclusively in samples contaminated by C. botulinum type C/D, fliC-II was rarely detected, no sample was recorded as fliC-III or fliC-V, and only C. botulinum type D/C samples tested positive for fliC-IV. The lack of genetic diversity of the flagellin gene of C. botulinum type C/D would support a clonal spread of type C/D strains in different geographical areas. fliC-I to fliC-III are genetically related (87% to 92% sequence identity), whereas fliC-IV from C. botulinum type D/C is more genetically distant from the other fliC types (with only 50% sequence identity). These findings suggest fliC-I to fliC-III have evolved in a common environment and support a different genetic evolution for fliC-IV. A combination of the C. novyi sensu lato, ntnh, bont, and fliC PCR assays developed in this study allowed better characterization of C. botulinum group III and showed the group to be less genetically diverse than C. botulinum groups I and II, supporting a slow genetic evolution of the strains belonging to C. botulinum group III.


Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections.
We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013-2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (<5 single-nucleotide polymorphisms), and >21,000 single-nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures.


Daily prickly pear consumption improves platelet function.
Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.


Chronic spinal disorders and psychopathology. research findings and theoretical considerations.
Numerous studies have documented a strong association between chronic spinal disorders and psychopathology. However, there have been methodological shortcomings associated with much of this. This article reviews the relevant research literature, including methodological refinements that have resulted in improved measurement of psychopathology, in order to provide the most updated conclusions concerning the links between spinal disorders and psychopathology. A systematic review of all Medline referenced articles on this subject during the past three decades. Previous research has shown that chronic spinal disorders are most often associated with depressive disorders, somatoform disorders, anxiety disorders, substance use disorders, and personality disorders. In addition to reviewing this research, the relationship between chronic spinal disorders and depressive disorders is examined in more detail. Although the relationship between spinal disorders and psychopathology is complex, a diathesis-stress model is emerging as the dominant overarching theoretical model. In this model, diatheses are conceptualized as pre-existing semidormant characteristics of the individual before the onset of chronic spinal disorders, which are then activated by the stress of this chronic condition, eventually resulting in a diagnosable depressive disorder. In the present review, a diathesis-stress model was applied specifically to the relationship between chronic spinal disorders and depressive disorders. Such a model may also be applicable to the relationship between chronic spinal disorders and other types of psychopathology, such as anxiety and substance use disorders. However, conclusive empirical support will require a prospective research design, given that these diatheses could be validly assessed only before the onset of the chronic pain condition.


Screening of natural phenazine producers for electroactivity in bioelectrochemical systems.
Mediated extracellular electron transfer (EET) might be a great vehicle to connect microbial bioprocesses with electrochemical control in stirred-tank bioreactors. However, mediated electron transfer to date is not only much less efficient but also much less studied than microbial direct electron transfer to an anode. For example, despite the widespread capacity of pseudomonads to produce phenazine natural products, only Pseudomonas aeruginosa has been studied for its use of phenazines in bioelectrochemical applications. To provide a deeper understanding of the ecological potential for the bioelectrochemical exploitation of phenazines, we here investigated the potential electroactivity of over 100 putative diverse native phenazine producers and the performance within bioelectrochemical systems. Five species from the genera Pseudomonas, Streptomyces, Nocardiopsis, Brevibacterium and Burkholderia were identified as new electroactive bacteria. Electron discharge to the anode and electric current production correlated with the phenazine synthesis of Pseudomonas chlororaphis subsp. aurantiaca. Phenazine-1-carboxylic acid was the dominant molecule with a concentration of 86.1 μg/ml mediating an anodic current of 15.1 μA/cm2 . On the other hand, Nocardiopsis chromatogenes used a wider range of phenazines at low concentrations and likely yet-unknown redox compounds to mediate EET, achieving an anodic current of 9.5 μA/cm2 . Elucidating the energetic and metabolic usage of phenazines in these and other species might contribute to improving electron discharge and respiration. In the long run, this may enhance oxygen-limited bioproduction of value-added compounds based on mediated EET mechanisms.


The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients.
It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.


Do different means of recording sexual orientation affect its relationship with health and wellbeing?
Analyses of an individual's sexual orientation over time are desirable for policy evaluations and in estimating causal effects. We explore whether accounting for those who change sexual orientation over two time points, to create a measure of fluidity, produces substantially different results compared to sexual orientation measured at one time point and extrapolated to subsequent survey waves. We use seven waves of the UK Household Longitudinal Study which asked sexual orientation identity questions at two time points: waves three (2011-2013) and nine (2017-2019). Using the relationship with sexual orientation and various health outcomes as an empirical example, via a correlated random effects estimation approach, we find that the infrequent reporting of sexual orientation could over-estimate the negative impact for lesbian, gay and "other" individuals and under-estimate the negative impact for bisexuals. We further test the feasibility of the fluidity measure by examining attrition by sexual orientation identity and find small but statistically significant probabilities of attrition. Correction for attrition bias through inverse probability weighting makes little difference to the results. These results highlight the importance of accounting for changes in sexual orientation in empirical analysis and that doing so is feasible.


Sequence-tagged microsatellite profiling (STMP): a rapid technique for developing SSR markers.
We describe a technique, sequence-tagged microsatellite profiling (STMP), to rapidly generate large numbers of simple sequence repeat (SSR) markers from genomic or cDNA. This technique eliminates the need for library screening to identify SSR-containing clones and provides an approximately 25-fold increase in sequencing throughput compared to traditional methods. STMP generates short but characteristic nucleotide sequence tags for fragments that are present within a pool of SSR amplicons. These tags are then ligated together to form concatemers for cloning and sequencing. The analysis of thousands of tags gives rise to a representational profile of the abundance and frequency of SSRs within the DNA pool, from which low copy sequences can be identified. As each tag contains sufficient nucleotide sequence for primer design, their conversion into PCR primers allows the amplification of corresponding full-length fragments from the pool of SSR amplicons. These fragments permit the full characterisation of a SSR locus and provide flanking sequence for the development of a microsatellite marker. Alternatively, sequence tag primers can be used to directly amplify corresponding SSR loci from genomic DNA, thereby reducing the cost of developing a microsatellite marker to the synthesis of just one sequence-specific primer. We demonstrate the utility of STMP by the development of SSR markers in bread wheat.


Reversal of 2-bromoethanesulfonate inhibition of methanogenesis in Methanosarcina sp.
2-Bromoethanesulfonate (BES) inhibition of methanogenesis from methanol by resting-cell suspensions or cell extracts of Methanosarcina was reversed by coenzyme M. BES inhibition of methylcoenzyme M methylreductase activity in cell-free extracts was reversed by methylcoenzyme M but not by coenzyme M. Methanol/coenzyme M methyltransferase activity was not inhibited by 10 microM BES. Inhibition of methylreductase by BES and 3-bromopropionate was competitive with methylcoenzyme M, but inhibition by 2-bromoethanol exhibited mixed kinetics. The Ki values for the inhibitors in cell-free extracts were similar to the concentrations which inhibited intact cells. BES-resistant mutants of strain 227 were apparently permeability mutants because in vitro assays showed that mutant and parent strain methylreductases were equally sensitive to BES.


Educational inequalities in the prevalence and outcomes of diabetes in the Emilian Longitudinal Study.
Studies carried out in Italy in the last decades reported an effect modification in the association between socioeconomic position and diabetes outcomes, and the disease integrated care approach has been suggested as an explanatory factor. Whether this is true in Emilia-Romagna region in recent years is unknown and the aim of this study is to describe the role of educational level both on diabetes prevalence and health outcomes among the adult population with and without diabetes enrolled in the Emilian Longitudinal Study. Inequalities in diabetes prevalence were evaluated through standardised estimates and prevalence ratios by educational level and inequalities in outcomes through standardised hospitalisation and mortality ratios and rate ratios by educational level. The lower the education the greater the diabetes prevalence; such differences were larger among women and younger age groups. Diabetes conferred a higher risk of hospitalisation and mortality; those outcomes also presented a social gradient with the less educated bearing the higher risk. However, educational differences were slightly stronger among the disease-free subjects, especially in the case of mortality. In both genders, inequalities tended to disappear with age. This study confirms that diabetes increases the risk of unfavourable outcomes, but does not increase social inequalities in outcomes as might be expected. Similarly to what has been previously shown, it is likely that the protective effect of diabetes on the negative health effects of the low social position is attributable to the disease integrated care approach.


An inverted double seismic zone in chile: evidence of phase transformation in the subducted slab.
Data from two microseismic field experiments in northern Chile revealed an elongated cluster of earthquakes in the subducted Nazca plate at a depth of about 100 kilometers in which down-dip tensional events were consistently shallower than a family of compressional earthquakes. This double seismic zone shows a distribution of stresses of opposite polarity relative to that observed in other double seismic zones in the world. The distribution of stresses in northern Chile supports the notion that at depths of between 90 to 150 kilometers, the basalt to eclogite transformation of the subducting oceanic crust induces tensional deformation in the upper part of the subducted slab and compressional deformation in the underlying mantle.