A pharmacy carer support service: obtaining new insight into carers in the community.
Unpaid carers have many and varied responsibilities in society, which can include medication management for the person they support. However, the potential for Australian community pharmacies to better assist carers is relatively unexplored. This mixed-methods study investigated the acceptability of a local carer support service by trained community pharmacy staff, including issues regarding the implementation and impact of this service. Staff from 11 community pharmacies in South East Queensland, Australia, were trained to deliver a six-step carer support service between September 2016 and March 2017. Pharmacies were supported by a carer and pharmacist mentor pair and asked to recruit up to six carers each. Evaluations of staff training were descriptively analysed. Semi-structured interviews were undertaken with pharmacy staff, and interview transcripts were analysed thematically. Staff training evaluations were positive; participants acquired new information about carers and rated the service highly in terms of its importance within the pharmacy setting. Feedback was obtained on how to improve the training, such as further opportunities for role-play. Seven staff members were interviewed, and data analysis revealed two main themes: (1) implementation of the carer support service and (2) perceived impact on pharmacy staff. Positive attitudes towards recognising and supporting carers, and training and mentoring were identified with community pharmacies viewed as a suitable place for delivering this new service. New insights into the impact of caring were widely reported, which staff had not appreciated from previous carer interactions. Structural issues, including space and time pressures, and a lack of awareness about the types of support currently available to carers were emphasised. Pharmacy staff are well positioned to support carers. Engaging carers in conversation to better understand their needs is a small step with potential for big gains, including a more empathetic understanding of their individual circumstances and overall well-being.


Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation.
This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D(2)-receptors are not involved in the hypoxia-induced decrease in the maximal heart rate. These data suggest that receptor uncoupling, and not down-regulation, of cardiac adrenoreceptors, is responsible for the early decrease in heart rate at maximal hypoxic exercise.


The Salmonella LysR Family Regulator RipR Activates the SPI-13-Encoded Itaconate Degradation Cluster.
Itaconate is a dicarboxylic acid that inhibits the isocitrate lyase enzyme of the bacterial glyoxylate shunt. Activated macrophages have been shown to produce itaconate, suggesting that these immune cells may employ this metabolite as a weapon against invading bacteria. Here, we demonstrate that in vitro, itaconate can exhibit bactericidal effects under acidic conditions similar to the pH of a macrophage phagosome. In parallel, successful pathogens, including Salmonella, have acquired a genetic operon encoding itaconate degradation proteins, which are induced heavily in macrophages. We characterized the regulation of this operon by the neighboring gene ripR in specific response to itaconate. Moreover, we developed an itaconate biosensor based on the operon promoter that can detect itaconate in a semiquantitative manner and, when combined with the ripR gene, is sufficient for itaconate-regulated expression in Escherichia coli Using this biosensor with fluorescence microscopy, we observed bacteria responding to itaconate in the phagosomes of macrophages and provide additional evidence that gamma interferon stimulates macrophage itaconate synthesis and that J774 mouse macrophages produce substantially more itaconate than the human THP-1 monocyte cell line. In summary, we examined the role of itaconate as an antibacterial metabolite in mouse and human macrophages, characterized the regulation of Salmonella's defense against it, and developed it as a convenient itaconate biosensor and inducible promoter system.


Postoperative pain management in the postanesthesia care unit: an update.
Acute postoperative pain remains a major problem, resulting in multiple undesirable outcomes if inadequately controlled. Most surgical patients spend their immediate postoperative period in the postanesthesia care unit (PACU), where pain management, being unsatisfactory and requiring improvements, affects further recovery. Recent studies on postoperative pain management in the PACU were reviewed for the advances in assessments and treatments. More objective assessments of pain being independent of patients' participation may be potentially appropriate in the PACU, including photoplethysmography-derived parameters, analgesia nociception index, skin conductance, and pupillometry, although further studies are needed to confirm their utilities. Multimodal analgesia with different analgesics and techniques has been widely used. With theoretical basis of preventing central sensitization, preventive analgesia is increasingly common. New opioids are being developed with minimization of adverse effects of traditional opioids. More intravenous nonopioid analgesics and adjuncts (such as dexmedetomidine and dexamethasone) are introduced for their opioid-sparing effects. Current evidence suggests that regional analgesic techniques are effective in the reduction of pain and stay in the PACU. Being available alternatives to epidural analgesia, perineural techniques and infiltrative techniques including wound infiltration, transversus abdominis plane block, local infiltration analgesia, and intraperitoneal administration have played a more important role for their effectiveness and safety.


Deep Learning Classification of Lake Zooplankton.
Plankton are effective indicators of environmental change and ecosystem health in freshwater habitats, but collection of plankton data using manual microscopic methods is extremely labor-intensive and expensive. Automated plankton imaging offers a promising way forward to monitor plankton communities with high frequency and accuracy in real-time. Yet, manual annotation of millions of images proposes a serious challenge to taxonomists. Deep learning classifiers have been successfully applied in various fields and provided encouraging results when used to categorize marine plankton images. Here, we present a set of deep learning models developed for the identification of lake plankton, and study several strategies to obtain optimal performances, which lead to operational prescriptions for users. To this aim, we annotated into 35 classes over 17900 images of zooplankton and large phytoplankton colonies, detected in Lake Greifensee (Switzerland) with the Dual Scripps Plankton Camera. Our best models were based on transfer learning and ensembling, which classified plankton images with 98% accuracy and 93% F1 score. When tested on freely available plankton datasets produced by other automated imaging tools (ZooScan, Imaging FlowCytobot, and ISIIS), our models performed better than previously used models. Our annotated data, code and classification models are freely available online.


Sequence and structural features of carbohydrate binding in proteins and assessment of predictability using a neural network.
Protein-Carbohydrate interactions are crucial in many biological processes with implications to drug targeting and gene expression. Nature of protein-carbohydrate interactions may be studied at individual residue level by analyzing local sequence and structure environments in binding regions in comparison to non-binding regions, which provide an inherent control for such analyses. With an ultimate aim of predicting binding sites from sequence and structure, overall statistics of binding regions needs to be compiled. Sequence-based predictions of binding sites have been successfully applied to DNA-binding proteins in our earlier works. We aim to apply similar analysis to carbohydrate binding proteins. However, due to a relatively much smaller region of proteins taking part in such interactions, the methodology and results are significantly different. A comparison of protein-carbohydrate complexes has also been made with other protein-ligand complexes. We have compiled statistics of amino acid compositions in binding versus non-binding regions- general as well as in each different secondary structure conformation. Binding propensities of each of the 20 residue types and their structure features such as solvent accessibility, packing density and secondary structure have been calculated to assess their predisposition to carbohydrate interactions. Finally, evolutionary profiles of amino acid sequences have been used to predict binding sites using a neural network. Another set of neural networks was trained using information from single sequences and the prediction performance from the evolutionary profiles and single sequences were compared. Best of the neural network based prediction could achieve an 87% sensitivity of prediction at 23% specificity for all carbohydrate-binding sites, using evolutionary information. Single sequences gave 68% sensitivity and 55% specificity for the same data set. Sensitivity and specificity for a limited galactose binding data set were obtained as 63% and 79% respectively for evolutionary information and 62% and 68% sensitivity and specificity for single sequences. Propensity and other sequence and structural features of carbohydrate binding sites have also been compared with our similar extensive studies on DNA-binding proteins and also with protein-ligand complexes. Carbohydrates typically show a preference to bind aromatic residues and most prominently tryptophan. Higher exposed surface area of binding sites indicates a role of hydrophobic interactions. Neural networks give a moderate success of prediction, which is expected to improve when structures of more protein-carbohydrate complexes become available in future.


Nicotiana tabacum protoplasts secretome can evidence relations among regulatory elements of exocytosis mechanisms.
An alternative study involving proteome analysis of the 24 hour Nicotiana tabacum protoplast culture medium was performed with the aim to confirm relations among regulatory elements of exocytotic processes. Protoplasts present many convenient features to study cellular processes during transient over-expression or suppression of specific gene's products. We performed a proteomic analysis of the culture medium fraction of protoplasts transiently expressing transgenes for 24 hours to characterize the effect of various regulatory proteins dominant negative mutants. A total number of 49 spots were found reproducible in the medium. 24 of these spots were identified with nano RP-HPLC-ESI-MS/MS. Only three and six spots were respectively identified as canonical and non-canonical secreted cell wall proteins. The low number of spots present in the culture medium fraction allowed us the ambitious experiment to analyze the influence of various SNAREs (SYP121, SYP122, SNAP33) and Rab (Rab11) dominant negative mutants. Missing a reasonable number of identified proteins the analyses gave rise to a similarity matrix statistically analyzed considering variation within the presence of 24 spots reproducible in presence of transient over-expression of SNAREs (SYP121 and SYP122) and Rab11 native cDNAs. The similarity confirmed the closer relation between the function of SYP122 and Rab11 as evidenced by the secRGUS based analysis. This analysis included the effect of SNAP33 DN mutant and showed that this Qb-c-SNARE influence both SYP121 and SYP122 SNARE complexes.


Detection and Molecular Analysis of Bovine Enteric Norovirus and Nebovirus in Turkey.
Bovine Norovirus (BoNeV) which has been confirmed in Asia, America, and Europe, seems to be distributed worldwide, even though only reported from a number of countries. Bovine noroviruses are predominantly detected in diarrhoeic animals rather than neboviruses. The study reveals the importance of noro- and neboviruses in early age diarrhoea of calves. A total of 127 stool samples were collected from three provinces located in the central region of Turkey. Samples were subjected to nucleic acid isolation and reverse transcription and polymerase chain reaction (PCR). Positive samples were sequenced and analysed. According to PCR, five samples (3.93%) were found to be positive for bovine norovirus while 32 (25.19%) samples were found to be positive for bovine nebovirus. Phylogenetic analysis indicated that the novel Turkish norovirus strains were found to be of genotype III.2 and all novel neboviruses were substituted under Nebraska-like strains. Although predominantly bovine noroviruses are detected worldwide, the study indicated that bovine neboviruses were more prevalent in the studied area. We suggest that bovine neboviruses are more frequently responsible for calf diarrhoea than supposed by virologists. This is also the first report of neboviruses other than Kirklareli virus which is distantly related to neboviruses detected in Turkey.


The way you say it, the way I feel it: emotional word processing in accented speech.
The present study examined whether processing words with affective connotations in a listener's native language may be modulated by accented speech. To address this question, we used the Event Related Potential (ERP) technique and recorded the cerebral activity of Spanish native listeners, who performed a semantic categorization task, while listening to positive, negative and neutral words produced in standard Spanish or in four foreign accents. The behavioral results yielded longer latencies for emotional than for neutral words in both native and foreign-accented speech, with no difference between positive and negative words. The electrophysiological results replicated previous findings from the emotional language literature, with the amplitude of the Late Positive Complex (LPC), associated with emotional language processing, being larger (more positive) for emotional than for neutral words at posterior scalp sites. Interestingly, foreign-accented speech was found to interfere with the processing of positive valence and go along with a negativity bias, possibly suggesting heightened attention to negative words. The manipulation employed in the present study provides an interesting perspective on the effects of accented speech on processing affective-laden information. It shows that higher order semantic processes that involve emotion-related aspects are sensitive to a speaker's accent.


Adventitial Sca1+ Cells Transduced With ETV2 Are Committed to the Endothelial Fate and Improve Vascular Remodeling After Injury.
Vascular adventitial Sca1+ (stem cell antigen-1) progenitor cells preferentially differentiate into smooth muscle cells, which contribute to vascular remodeling and neointima formation in vessel grafts. Therefore, directing the differentiation of Sca1+ cells toward the endothelial lineage could represent a new therapeutic strategy against vascular disease. We thus developed a fast, reproducible protocol based on the single-gene transfer of ETV2 (ETS variant 2) to differentiate Sca1+ cells toward the endothelial fate and studied the effect of cell conversion on vascular hyperplasia in a model of endothelial injury. After ETV2 transduction, Sca1+ adventitial cells presented a significant increase in the expression of early endothelial cell genes, including VE-cadherin, Flk-1, and Tie2 at the mRNA and protein levels. ETV2 overexpression also induced the downregulation of a panel of smooth muscle cell and mesenchymal genes through epigenetic regulations, by decreasing the expression of DNA-modifying enzymes ten-eleven translocation dioxygenases. Adventitial Sca1+ cells grafted on the adventitial side of wire-injured femoral arteries increased vascular wall hyperplasia compared with control arteries with no grafted cells. Arteries seeded with ETV2-transduced cells, on the contrary, showed reduced hyperplasia compared with control. These data give evidence that the genetic manipulation of vascular progenitors is a promising approach to improve vascular function after endothelial injury.


Preliminary results of a randomized, equivalence trial of fluoroscopic caudal epidural injections in managing chronic low back pain: Part 2--Disc herniation and radiculitis.
The pathophysiology of lumbar radicular pain is a subject of ongoing research. The prevalence of sciatica or radiculitis ranges from 1.2% to 43%. Epidural injections are one of the most commonly performed interventions in the United States in managing chronic low back and lower extremity pain secondary to disc herniation and radiculitis. There is a paucity of evidence with contemporary methodology used in performing epidural injections under fluoroscopy and based on pain relief and functional status improvement. A randomized, double-blind, equivalence trial. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of caudal epidural injections with or without steroids in managing chronic low back and lower extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief and evaluate the differences between local anesthetic with or without steroids. Patients were assigned to one of 2 groups; Group I patients received caudal epidural injections with an injection of local anesthetic (lidocaine 0.5%), whereas, Group II patients received caudal epidural injections with 0.5% lidocaine 9 mL mixed with 1 mL of steroid. Randomization was performed by computer-generated random allocations sequence by simple randomization. Multiple outcome measures were utilized which included the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3 months, 6 months, and 12 months post-treatment. Significant pain relief was defined as 50% or more, whereas significant improvement in disability score was defined as a reduction of 40% or more. The percentage of patients with significant pain relief of 50% or greater at 12 months was 79% in Group I and 81% in Group II. Reduction of Oswestry scores of at least 40% was seen in 83% of the patients in Group I and 91% in Group II. The overall average procedures per year were 3.9 +/- 1.26 in Group I and 3.6 +/- 1.08 in Group II with an average total relief per year of 35.2 +/- 17.18 weeks in Group I and 35.9 +/- 15.34 weeks in Group II over a period of 52 weeks. The results of this study are limited by lack of a placebo group and a preliminary report of 42 patients in each group. Caudal epidural injections with or without steroids may be effective in patients with disc herniation or radiculitis with between 79% to 91% of patients showing significant pain relief and improvement in functional status.


The influence of diet and environment on the gut microbial community of field crickets.
The extent to which diet and environment influence gut community membership (presence or absence of taxa) and structure (individual taxon abundance) is the subject of growing interest in microbiome research. Here, we examined the gut bacterial communities of three cricket groups: (1) wild caught field crickets, (2) laboratory-reared crickets fed cat chow, and (3) laboratory-reared crickets fed chemically defined diets. We found that both environment and diet greatly altered the structure of the gut bacterial community. Wild crickets had greater gut microbial diversity and higher Firmicutes to Bacteroidetes ratios, in contrast to laboratory-reared crickets. Predictive metagenomes revealed that laboratory-reared crickets were significantly enriched in amino acid degradation pathways, while wild crickets had a higher relative abundance of peptidases that would aid in amino acid release. Although wild and laboratory animals differ greatly in their bacterial communities, we show that the community proportional membership remains stable from Phylum to Family taxonomic levels regardless of differences in environment and diet, suggesting that endogenous factors, such as host genetics, have greater control in shaping gut community membership.


Comparison of SWAN and WISE menopausal status classification algorithms.
Classification of menopausal status is important for epidemiological and clinical studies as well as for clinicians treating midlife women. Most epidemiological studies, including the Study of Women's Health Across the Nation (SWAN), classify women based on self-reported bleeding history. The Women's Ischemia Syndrome Evaluation (WISE) study developed an algorithm using menstrual and reproductive history and serum hormone levels to reproduce the menopausal status classifications assigned by the WISE hormone committee. We applied that algorithm to women participating in SWAN and examined characteristics of women with concordant and discordant SWAN and WISE classifications. Of the 3215 SWAN women with complete information at baseline (1995-1997), 2466 (76.7%) received concordant classifications (kappa = 0.52); at the fifth annual follow-up visit, of the 1623 women with complete information, 1154 (72.7%) received concordant classifications (kappa = 0.57). At each time point, we identified subgroups of women with discordant SWAN and WISE classifications. These subgroups, ordered by chronological age, showed increasing trends for menopausal symptoms and follicle-stimulating hormone (FSH) and a decreasing trend for estrogen (p < 0.001). The WISE algorithm is a useful tool for studies that have access to blood samples for hormone data unrelated to menstrual cycle phase, with or without an intact uterus, and no resources for adjudication. Future studies may want to combine aspects of the SWAN and WISE algorithms by adding hormonal measures to the series of bleeding questions in order to determine more precisely where women are in the perimenopausal continuum.


Categorical data analysis of the effect on bull fertility of butylated hydroxytoluene addition to semen extenders prior to freezing.
Butylated hydroxytoluene is an antioxidant that has antiviral properties and sustains sperm viability during freezing and thawing. A field trial involving 11 bulls and 19,000 AI was conducted to determine whether addition of .5 mM butylated hydroxytoluene to whole milk extender during seminal processing affected bull fertility as estimated by nonreturn rates generated by cows bred to the bulls. Effects of bull, batch of semen nested within bull, treatment, and month of AI were studied. Nonreturn rates were recorded for each month for every bull, batch of semen (ejaculates pooled on a given day), and treatment combination. Because some bulls had < 6 batches of semen, the original experimental design was reduced to two smaller designs. Categorical data analysis with maximum likelihood estimation was used for analysis of nonreturn rates. The results from three models were used to interpret the data. The nonreturn rates were approximately 73.9% for the butylated hydroxytoluene treatment and 74.1% for the control. In all models, bull effect was significant, but batch, month of AI, and treatment had no effect on bull fertility. Addition of .5 mM butylated hydroxytoluene to whole milk extender during semen processing did not affect bull nonreturn rates.


Determination of beta2-agonists in bovine urine: comparison of two extraction/clean-up procedures for high-resolution gas chromatography-mass spectrometry analysis.
Two extraction/clean-up analytical procedures were investigated and compared regarding their recovery and matrix-purification efficiency for screening beta2-agonist residues in fortified bovine urine by high-resolution gas chromatography-mass spectrometry (GC-MS). The first procedure, based on an analytical method originally developed for detecting anabolic steroids, consists of the employment of the nonionic resin, Amberlite XAD-2, a styrene-divinylbenzene copolymer for solid-phase extraction (SPE), followed by liquid-liquid extraction with diethyl ether. The second focuses on the use of a mixed SPE cartridge (reversed-phase and ion-exchange sorbent, Bond Elut Certify). In both cases, the trimethylsilylated derivatives were analyzed by GC-MS with an ion-trap detector. Clenbuterol, salbutamol, and terbutaline were used to spike urine samples during the comparison experimental phase. Afterwards, tulobuterol, mabuterol, mapenterol, cimbuterol, and brombuterol were included in the evaluation of the second procedure (the Bond Elut Certify procedure). At this stage, the detection was accomplished by GC-MS (quadrupole mass analyzer) with selective ion monitoring acquisition. The isotopic dilution method with the hexadeuterated analogues of clenbuterol and salbutamol was applied to prepare calibration curves and calculate recovery percentages. With XAD-2 resin, terbutaline and salbutamol (resorcinol and phenol-type beta2-agonists, respectively) could not be detected at 20 ng/mL or at 40 ng/mL. In spite of clenbuterol having been detected at 20 ng/mL, the results obtained were not reproducible. The use of the reversed-phase and ion-exchange sorbent Bond Elut Certify allowed multiresidue detection and showed several advantages for the screening of clenbuterol such as higher recoveries, cleaner final extracts, reduced sample preparation time, less labor intensive, and easier solvent consumption and disposal. Recoveries over 88% (concentrations ranging from 0.5 to 10 ppb) and limits of detection equal to 0.5 ppb were met for all the beta2-agonists studied with the last method.


Spinal monoaminergic receptors mediate the antinociception produced by glutamate in the medullary lateral reticular nucleus.
Focal electrical stimulation and microinjection of the excitatory amino acid glutamate in the lateral reticular nucleus (LRN) both inhibit the heat-evoked tail flick (TF) reflex in rats. The stimulation-produced inhibition from the LRN has previously been demonstrated to be mediated by spinal monoaminergic receptors. In the present study, inhibition of responses to noxious thermal stimuli by glutamate microinjected into the LRN was examined and characterized; this study is the first to examine the spinal receptors mediating inhibition produced by selective activation of cell bodies in the LRN. Microinjection of glutamate (100 mM) into the LRN in rats lightly anesthetized with pentobarbital produced a transient (less than 5 min) inhibition of the heat-evoked TF reflex, the magnitude of which increased with the volume of glutamate injected (100, 200, or 400 nl). This glutamate-produced inhibition of the TF reflex was antagonized by the intrathecal administration of phentolamine (30 micrograms), yohimbine (15 and 30 micrograms), or methysergide (15 and 30 micrograms) to the level of the lumbar spinal cord, but was not antagonized by prazosin (30 micrograms) or naloxone (20 micrograms). Yohimbine (15 and 30 micrograms) administered to the level of the cervical spinal enlargement did not significantly alter inhibition of the TF reflex produced by glutamate microinjected into the LRN. Microinjection of glutamate (100 mM, 400 nl) into the LRN elevated TF latencies and hindpaw lick latencies in the hot plate test performed on conscious rats. This inhibition of responses to noxious thermal stimuli in conscious rats was short-lasting (less than 5 min), and was also attenuated by intrathecal administration of yohimbine (30 micrograms) or methysergide (30 micrograms), but not by prazosin (30 micrograms) or naloxone (20 micrograms). While it has previously been established that cell bodies in the LRN mediate descending inhibition of spinal nociceptive reflexes, the present results establish that spinal alpha 2-adrenoceptors and serotonin receptors mediate LRN-produced antinociception and extend our understanding of LRN-mediated modulation of nociceptive responses integrated spinally and supraspinally.


Superfast vocal muscles control song production in songbirds.
Birdsong is a widely used model for vocal learning and human speech, which exhibits high temporal and acoustic diversity. Rapid acoustic modulations are thought to arise from the vocal organ, the syrinx, by passive interactions between the two independent sound generators or intrinsic nonlinear dynamics of sound generating structures. Additionally, direct neuromuscular control could produce such rapid and precisely timed acoustic features if syringeal muscles exhibit rare superfast muscle contractile kinetics. However, no direct evidence exists that avian vocal muscles can produce modulations at such high rates. Here, we show that 1) syringeal muscles are active in phase with sound modulations during song over 200 Hz, 2) direct stimulation of the muscles in situ produces sound modulations at the frequency observed during singing, and that 3) syringeal muscles produce mechanical work at the required frequencies and up to 250 Hz in vitro. The twitch kinematics of these so-called superfast muscles are the fastest measured in any vertebrate muscle. Superfast vocal muscles enable birds to directly control the generation of many observed rapid acoustic changes and to actuate the millisecond precision of neural activity into precise temporal vocal control. Furthermore, birds now join the list of vertebrate classes in which superfast muscle kinetics evolved independently for acoustic communication.


Efficacy of VeinViewer in pediatric peripheral intravenous access: a randomized controlled trial.
Peripheral venous access in infants and children is technically challenging, because their veins are small and located deep in subcutaneous tissue, which makes them difficult to palpate or visualize. The VeinViewer® (Luminetx Corporation, Memphis, TN, USA) is a near-infrared light device that delineates the running course of subcutaneous veins. In this study, we investigated whether the use of the VeinViewer® in infants and children facilitated peripheral venous access, especially in difficult cases. This study was a randomized, controlled trial of a convenience sample of pediatric patients between the ages of 1 month and 16 years who required peripheral venous access in the pediatric ward. Prior to randomization, difficult intravenous access (DIVA) score, a four-variable clinical prediction rule for first-attempt success, was estimated. We compared the first-attempt success rates and procedural times between the VeinViewer® group and a control group. We evaluated 111 patients: 54 in the VeinViewer® group and 57 in the control group. Patient demographics and factors related to the success of vein access were similar for both groups. The overall first-attempt success rate was 69.4%: i.e., 77/111 in the VeinViewer® group and 38/57 in the control group, a difference that was not statistically significant. However, the first-attempt success rate increased from 5/20 in the control group to 14/24 in the VeinViewer® group for difficult veins with a DIVA score greater than 4 (p=0.026). There were no significant differences in procedural time between the two groups. The VeinViewer® facilitated peripheral venous access for pediatric patients with difficult veins, which enhanced first-attempt success rates.


Family-focused interventions and resources for veterans and their families.
Accelerated by the decreasing military presence in Iraq and Afghanistan, many military members are currently transitioning out of active duty into civilian life. Many of these new veterans have recently experienced combat deployment(s), and some are struggling with the aftermath of combat exposure, separation from family, and reintegration stressors. These challenges often follow these military families as they enter the civilian world, a time with its own major life changes vocationally, socially, and interpersonally. Although numerous resources have been developed to assist service members during their transition to the civilian world, relatively fewer exist for partners, children, and broader family systems. Family psychoeducation is a nonpathologizing, strengths-focused model of care that has documented benefits in the arena of mental illness. This article describes some manualized family psychoeducational programs and online and phone-based resources that may be useful to veteran families during this time of change. The programs and resources described herein are all available for free, primarily online. Because of a wide variety of barriers and limitations for family based care in the Veterans Affairs health care system, veteran families are and will continue to seek mental health care in public sector settings. Community providers can enhance their military culture competence by familiarizing themselves with these resources and drawing upon them in working with transitioning military families. (PsycINFO Database Record


Screening for in-vivo regional contractile defaults to predict the delayed Doxorubicin Cardiotoxicity in Juvenile Rat.
Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute and irreversible cardiotoxicity. Currently, there is no method to predict the future development of the HF in these patients. In order to identify early biomarkers to predict anthracycline cardiotoxicity in long-term survivors of childhood cancer, this longitudinal study aimed to analyze early and late in-vivo regional myocardial anthracycline-induced cardiotoxicity, related to in-vitro cardiac myocytes dysfunction, in a juvenile rat model. Methods: Young male Wistar rats (4 weeks-old) were treated with different cumulative doses of doxorubicin (7.5, 10 or 12.5 mg/kg) or NaCl (0.9%) once a week for 6 weeks by intravenous injection. Cardiac function was evaluated in-vivo by conventional (left ventricular ejection fraction, LVEF) and regional two-dimensional (2D) speckle tracking echocardiography over the 4 months after the last injection. The animals were assigned to preserved (pEF) or reduced EF (rEF) groups at the end of the protocol and were compared to controls. Results: We observed a preferential contractile dysfunction of the base of the heart, further altered in the posterior segment, even in pEF group. The first regional alterations appeared 1 month after chemotherapy. Functional investigation of cardiomyocytes isolated from the LV base 1 month after doxorubicin treatment showed that early in-vivo contractile alterations were associated with both decreased myofilament Ca2+ sensitivity and length-dependent activation. Changes in post-translational modifications (phosphorylation; S-glutathionylation) and protein degradation of the cardiac myosin binding protein-C may contribute to these alterations. Conclusion: Our data suggest that screening of the contractile defaults of the base of the heart by regional 2D strain echocardiography is useful to detect subclinical myocardial dysfunction prior to the development of delayed anthracycline-induced cardiomyopathy in pediatric onco-cardiology.


Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions.
The majority of states have fully legalized the use of medical cannabis (MC), and nearly all other states allow limited access to cannabidiol (CBD), a non-intoxicating constituent of cannabis often touted for a range of therapeutic indications. Further, the Agricultural Improvement Act of 2018 legalized hemp-derived products in all 50 states; typically high in CBD, these products are derived from cannabis varieties containing ≤0.3% delta-9-tetrahydrocannabinol (THC) by weight. The recent "green rush" has resulted in a striking increase in cannabis use among patients and consumers who often use a wide variety of novel product types, each with a unique blend of cannabinoid constituents. Importantly, however, several cannabinoids have the potential to cause drug-drug interactions (DDI) with other medications, primarily due to their involvement with the hepatic cytochrome P450 (CYP450) system. This article examines the potential for individual cannabinoids, particularly CBD, to interact with the hepatic metabolic system, which is concerning given its involvement in the metabolism of commonly-prescribed medications. CBD and other cannabinoids are metabolized extensively by the CYP450 system, and also inhibit many of these enzymes, potentially leading to variable serum levels of other medications, as well as variable levels of cannabinoids when other medications modify the system. As access and interest in cannabinoid-based products continues to increase, critical questions remain unanswered regarding their safety. The complex relationship between cannabinoids and the hepatic metabolic system, including common potential DDI resulting from cannabinoid exposure, are explored along with the clinical significance of these potential interactions and monitoring or mitigation strategies.


Momordica charantia for type 2 diabetes mellitus.
Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. To assess the effects of mormodica charantia for type 2 diabetes mellitus. Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used. We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions. Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice). Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs. There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.


[Reaction of various components of the erythrocyte system to periodic action of submaximal loads].
During repeated exposures of rats to hypergravity two stages of catabolic and adaptive developments in red blood were distinguished. The first stage that lasted about a week was characterized by decrease of resistance and hemolysis of red blood cells, hemosiderosis in the spleen, circulation hypoxia in the liver. The second stage was characterized by the predominance of adaptive processes, viz. increased activity of red blood cells, enhanced erythropoiesis in the spleen pulp, and appearance of highly active hepatocytes.


Longitudinal Analysis of Circulating Markers of Bone Turnover Across Multiple Decades in Osteoporotic Women.
The objective of this study was to analyze changes in serum markers of bone turnover across multiple decades in osteoporotic women compared with nonosteoporotic controls, to determine their utility as potential predictors for osteoporosis. Early prediction of those at risk for osteoporosis can enable early intervention before the irreversible loss of critical bone mass. Serum samples were obtained from 20 women given the diagnosis of osteoporosis after age 46 years and 20 age-matched women with normal bone mineral density from 4 time points in their life (ages 25-31, 32-38, 39-45, and 46-60 years). Serum levels of bone turnover markers (propeptide of type I collagen, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, C-terminal telopeptide of type I collagen, sclerostin, osteoprotegerin, osteopontin, and 25-OH vitamin D) were measured using commercially available arrays and kits. We used logistic regression to assess these individual serum markers as potential predictors of osteoporosis, and mixed-effects modeling to assess the change in bone turnover markers between osteoporotic and control groups over time, then performed fivefold cross-validation to assess the classification ability of the models. Markers of bone turnover, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, sclerostin, and osteocalcin were all independent predictors at multiple time points; osteopontin was an independent predictor in the 39- to 45-year age group. Receiver operating characteristic analyses demonstrated moderately strong classification ability at all time points. Sclerostin levels among groups diverged over time and were higher in the control group than the osteoporotic group, with significant differences observed at time points 3 and 4. Serum markers of bone turnover may be used to estimate the likelihood of osteoporosis development in individuals over time. Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place. Diagnostic II.


Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with two-stage hepatectomy for multiple and bilobar desmoplastic small round cell tumor liver metastases.
Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor usually affecting young patients. Local dissemination is common, and liver is the most common site for extraperitoneal metastases. Multimodal management has been shown to be the most effective treatment. Some authors consider liver metastases especially bi-lobar disease as a contraindication for surgical resection. We present a case of a DSRCT with bi-lobar metastases in an adult patient who underwent multi-modal management along with hepatectomy. A 51-year-old man was found to have a large intraperitoneal mass with bi-lobar liver metastases during work up for new onset reflux and abdominal pain. Biopsy confirmed it as DSRCT. The patient was treated with multi-modal therapy including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), two-stage hepatectomy (TSHP) combined with (90Y) Yittrium-90 radioembolization of the right hepatic lobe and systemic chemotherapy. The patient had a right-sided pleural empyema one month after the surgery for which he required right-sided video-assisted thoracoscopy and decortication. He remains disease free at 2 years follow-up. DSRCT with bi-lobar liver metastases are best managed with multimodal therapy. TSHP seems to be a feasible and safe option in selected cases, with a potentially good outcome.


Posterior chain and core training improves pelvic posture, hamstrings-to-quadriceps ratio, and vertical jump performance.
Poor pelvic posture demonstrated through anterior pelvic tilt (APT) have been known to produce musculoskeletal imbalances involving weakness of the abdominal and pelvic musculature. While stretching and massage techniques have been reported to be effective in alleviating APT, it remains unclear if similar improvements can be elicited by posterior chain and core strength training. Therefore, the aim of this study was to examine the effect of an 8-week posterior and core strengthening program on APT, hamstrings-to-quadriceps (H:Q) strength ratio, and vertical jump performance in healthy individuals. Ten healthy males (age = 26±12 years; mass = 87±14 kg; height = 1.8±0.1 m) and nine healthy females (age = 22±4 years; mass = 70±14 kg; heigh t = 1.7±0.1 m) performed resistance training (2×/week; 40-45 mins) involving a combination of hip extensors and abdominal strengthening exercises for 8 weeks. APT (°), vertical jump power (W), vertical jump height (m), and H:Q ratio at 60, 180, and 300°/s were assessed prior to and following the resistance training program. APT, vertical jump power, vertical jump height, and H:Q ratio at 60 and 180°/s, were significantly improved following 8 weeks of resistance training (all Ps<0.05). Our main finding was that 8 weeks of resistance training emphasizing posterior chain and core strengthening was effective in reducing APT, improving vertical jump performance and H:Q ratio in healthy individuals. Our findings have potential implications for clinicians prescribing resistance training exercises to improve pelvic posture in healthy asymptomatic individuals at risk of developing chronic low back pain and lumbar-spinal pathologies due to excessive anterior pelvic tilt.


Forest phenoclusters for Argentina based on vegetation phenology and climate.
Forest biodiversity conservation and species distribution modeling greatly benefit from broad-scale forest maps depicting tree species or forest types rather than just presence and absence of forest, or coarse classifications. Ideally, such maps would stem from satellite image classification based on abundant field data for both model training and accuracy assessments, but such field data do not exist in many parts of the globe. However, different forest types and tree species differ in their vegetation phenology, offering an opportunity to map and characterize forests based on the seasonal dynamic of vegetation indices and auxiliary data. Our goal was to map and characterize forests based on both land surface phenology and climate patterns, defined here as forest phenoclusters. We applied our methodology in Argentina (2.8 million km2 ), which has a wide variety of forests, from rainforests to cold-temperate forests. We calculated phenology measures after fitting a harmonic curve of the enhanced vegetation index (EVI) time series derived from 30-m Sentinel 2 and Landsat 8 data from 2018-2019. For climate, we calculated land surface temperature (LST) from Band 10 of the thermal infrared sensor (TIRS) of Landsat 8, and precipitation from Worldclim (BIO12). We performed stratified X-means cluster classifications followed by hierarchical clustering. The resulting clusters separated well into 54 forest phenoclusters with unique combinations of vegetation phenology and climate characteristics. The EVI 90th percentile was more important than our climate and other phenology measures in providing separability among different forest phenoclusters. Our results highlight the potential of combining remotely sensed phenology measures and climate data to improve broad-scale forest mapping for different management and conservation goals, capturing functional rather than structural or compositional characteristics between and within tree species. Our approach results in classifications that go beyond simple forest-nonforest in areas where the lack of detailed ecological field data precludes tree species-level classifications, yet conservation needs are high. Our map of forest phenoclusters is a valuable tool for the assessment of natural resources, and the management of the environment at scales relevant for conservation actions.


Structural analysis of Brucella abortus RicA substitutions that do not impair interaction with human Rab2 GTPase.
Protein-protein interactions are at the basis of many cellular processes, and they are also involved in the interaction between pathogens and their host(s). Many intracellular pathogenic bacteria translocate proteins called effectors into the cytoplasm of the infected host cell, and these effectors can interact with one or several host protein(s). An effector named RicA was recently reported in Brucella abortus to specifically interact with human Rab2 and to affect intracellular trafficking of this pathogen. In order to identify regions of the RicA protein involved in the interaction with Rab2, RicA was subjected to extensive random mutagenesis using error prone polymerase chain reaction. The resulting allele library was selected by the yeast two-hybrid assay for Rab2-interacting clones that were isolated and sequenced, following the "absence of interference" approach. A tridimensional model of RicA structure was used to position the substitutions that did not affect RicA-Rab2 interaction, giving a "negative image" of the putative interaction region. Since RicA is a bacterial conserved protein, RicA homologs were also tested against Rab2 in a yeast two-hybrid assay, and the C. crescentus homolog of RicA was found to interact with human Rab2. Analysis of the RicA structural model suggested that regions involved in the folding of the "beta helix" or an exposed loop with the IGFP sequence could also be involved in the interaction with Rab2. Extensive mutagenesis of the IGFP loop suggested that loss of interaction with Rab2 was correlated with insolubility of the mutated RicA, showing that "absence of interference" approach also generates surfaces that could be necessary for folding. Extensive analysis of substitutions in RicA unveiled two structural elements on the surface of RicA, the most exposed β-sheet and the IGFP loop, which could be involved in the interaction with Rab2 and protein folding. Our analysis of mutants in the IGFP loop suggests that, at least for some mono-domain proteins such as RicA, protein interaction analysis using allele libraries could be complicated by the dual effect of many substitutions affecting both folding and protein-protein interaction.


The use of digital technologies by people with mild-to-moderate dementia during the COVID-19 pandemic: A positive technology perspective.
A growing body of research has shown that people with dementia are using digital technologies to enhance lived experience. The COVID-19 pandemic has brought new digital opportunities and challenges and so provides a unique opportunity to understand how people with dementia have adapted to this new digital landscape. Semi-structured interviews were conducted with 19 people with dementia and analysed thematically. We generated five themes, showing how participants used digital means to combat the stresses of the pandemic by facilitating social connection, self-actualisation, enhanced well-being and by assisting with activities of daily life. These technologies helped to reduce isolation, provide access to support groups, create opportunities for cognitive stimulation and self-development, and engendered a sense of identity at a time of perceived loss. Despite these benefits, participants also reported challenges regarding cognitive fatigue and usability issues. We recommend that training on how to use digital technologies is co-produced with people with dementia and designers engage with the voices of people with dementia throughout the design process. In turn, this could promote the social connectedness, well-being and self-worth of people with dementia.


Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller.
The cytosolic Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β-propeller domains. Here, we determined structures of CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gβ5, a component of Regulator of G protein Signaling (RGS) complexes. Cryo-EM and image processing revealed an ensemble of distinct snapshots that represent the folding trajectory of Gβ5 from an unfolded molten globule to a fully folded β-propeller. These structures reveal the mechanism by which CCT directs Gβ5 folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual β-sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT directs folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.


Transfer of insulin-binding antibodies from nanny goats to kids.
In 30 female goats hyperimmunized with bovine insulin, antibody concentrations in serum were determined by radioimmunoassay. Blood samples were taken from the newborn lambs immediately after birth and during the 12 weeks thereafter. Twin lambs were separated and reared in either a colostrum-fed or a colostrum-deprived group. Bovine insulin was added to the milk rations of colostrum-deprived lambs. At the age of 10 weeks, these kids were given a single dose of 1 IU of insulin in combination with complete Freund's adjuvant. Colostrum from nanny goats was also secured for further investigations. Most of the hyperimmunized adult goats responded with the development of insulin antibodies. Their kids were born without these specific immunoglobulins, but several hours after they were allowed to suckle colostrum, the antibody concentration reached values comparable with the values measured in the nanny's blood. Colostrum-deprived kids did not show an increase in binding capacity. The addition of insulin to the milk rations of bottle-fed kids did not act as a primer in antibody production. Immunoglobulins in blood serum of nanny goats and kids and in colostral whey belong mainly to the IgG class. These results indicate that in goats, maternal insulin antibodies are transferred from nanny to offspring only by colostrum.


Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.
To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes. Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3). HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide. For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.


Ribosomes, membranes and organelles during meiosis in angiosperms.
Evidence is presented from both observational and analytical techniques indicating profound changes to take place in the ribosome population during male and female meiosis in some flowering plants. During microsporogenesis these appear to involve the elimination of the major part of the ribosome complement early in the meiotic prophase, and its subsequent restoration by the disintegration in the tetrad cytoplasm of 'nucleoloids', themselves synthesized in the nucleus during late prophase. In female tissue the process is essentially similar except for differences in the restoration of the ribosome population. Immediately before the eradication of the ribosomes in both sexes, a sizeable proportion of the meiocyte cytoplasm is encapsulated by double, or multiple unit membrane profiles. Significantly this cytoplasm remains unaffected by the agents responsible for the degredation of the ribosome population. These events are also reflected in the organelle populations where cycles of dedifferentiation and redifferentiation take place. In view of evidence from other organisms, it is considered unlikely that these cycles are in any way a prerequisite of meiosis, but more a characteristic of cells undergoing major changes of phase, where a cytoplasmic 'clean-up' is required before the next stage of growth may begin.


Bacterial lysis liberates the neutrophil migration suppressor YbcL from the periplasm of uropathogenic Escherichia coli.
Uropathogenic Escherichia coli (UPEC) modulates aspects of the innate immune response during urinary tract infection to facilitate bacterial invasion of the bladder epithelium, a requirement for the propagation of infection. For example, UPEC-encoded YbcL suppresses the traversal of bladder epithelia by neutrophils in both an in vitro model and an in vivo murine cystitis model. The suppressive activity of YbcL requires liberation from the bacterial periplasm, though the mechanism of release is undefined. Here we present findings on the site of action of YbcL and demonstrate a novel mode of secretion for a UPEC exoprotein. Suppression of neutrophil migration by purified YbcL(UTI), encoded by cystitis isolate UTI89, required the presence of a uroepithelial layer; YbcL(UTI) did not inhibit neutrophil chemotaxis directly. YbcL(UTI) was released to a greater extent during UPEC infection of uroepithelial cells than during that of neutrophils. Release of YbcL(UTI) was maximal when UPEC and bladder epithelial cells were in close proximity. Established modes of secretion, including outer membrane vesicles, the type II secretion system, and the type IV pilus, were dispensable for YbcL(UTI) release from UPEC. Instead, YbcL(UTI) was liberated during bacterial death, which was augmented upon exposure to bladder epithelial cells, as confirmed by detection of bacterial cytoplasmic proteins and DNA in the supernatant and enumeration of bacteria with compromised membranes. As YbcL(UTI) acts on the uroepithelium to attenuate neutrophil migration, this mode of release may represent a type of altruistic cooperation within a UPEC population during colonization of the urinary tract.


Ideology and policy termination: restructuring California's mental health system.
The recent profound transformation of the California mental health system is viewed from the perspective of policy termination--that phase in the overall policy process involving the cessation or redirection of policy. State mental hospitals have been phased out, and the responsibility for patients has been shifted to local mental health programs. This article explores the processes of policy and organizational change that occurred with mental health reform and uncovers a number of significant policy outcomes associated with that change. The consequences of the new mental health policy are found to be intimately related to the manner in which previous policy was terminated. In conceptualizing the role of termination, an experimental approach to the development of public policy is contrasted with policy innovation justified on the basis of ideology. It is argued that the numerous resistances to the termination of current policy weaken the prospect of policy innovation. Ideological commitment is the powerful force that overcomes these resistances. But this in turn produces a policy context in which important termination considerations are systematically ignored. The ideology of community mental health, emerging concurrently with changes in certain characteristics of the larger social structure, served to augment and legitimize the redirection in medical health policy. Mental health reform in California, although leading to the provision of services to an expanded population, resulted in the neglect of the more severely disabled.


MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibit-ing TGF-β1 expression.
MicroRNAs are endogenous, non-coding small RNAs that are capable of regulating biological and pathological processes. Previous studies have shown that microRNA-1269a serves as an oncogene. However, the role of microRNA-1269a in the pathogenesis of osteosarcoma (OS) has not been reported. The aim of this work was to investigate the expression characteristics of microRNA-1269a in OS and to further study its regulatory effects on the malignant progression of OS. The expression of microRNA-1269a in 61 pairs of OS tissues and para-cancerous tissues was detected by quantitative Real Time-polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-1269a expression and the characteristics of OS patients, including age, sex, clinical stage and distant metastasis. Subsequently, microRNA-1269a expression in OS cell lines was detected as well. After knockdown of microRNA-1269a by constructing relevant small interference RNA, biological performances of MG63 and U2OS cells were accessed by cell counting kit-8 (CCK-8), colony formation and transwell assay. Meanwhile, the protein expressions of key genes in the EMT/Smad pathway were detected by Western blot. Finally, si-TGF-β1 (transforming growth factor-β1) was transfected into OS cells, and cell migration and invasion were detected by transwell assay. MicroRNA-1269a was highly expressed in OS tissues compared with para-cancerous tissues. High expression of microRNA-1269a was positively correlated with young OS patients and high rate of distant metastasis, whereas was not correlated with age, sex and Enneking stage. Kaplan-Meier survival curves showed that high expression of microRNA-1269a was significantly associated with poor prognosis of OS. The knockdown of microRNA-1269a in MG63 and U2OS cells significantly inhibited cell proliferation, migration and invasion. Meanwhile, microRNA-1269a knockdown in OS cells markedly downregulated the expressions of TGF-β1, p-Smad2, p-Smad3, N-cad, Vimentin and MMP9. Furthermore, TGF-β1 knockdown remarkably decreased migratory and invasive abilities of OS cells. MicroRNA-1269a is highly expressed in OS, which is remarkably correlated with tumor stage, distant metastasis and poor prognosis of OS. In addition, microRNA-1269a promotes the malignant progression of OS by regulating TGF-β1 expression.


[Functional neuroimaging in patients with rapid cycling bipolar depression].
Bipolar patients with a rapid cycling clinical course constitute an interesting sub-group for studies focused on the pathophysiology of the disorder, since several switches can be studied by the investigators in a short period of time. At present, functional neuroimaging techniques, as SPECT and PET, may be used for the neurobiological study of affective disorders. Few longitudinal functional neuroimaging studies assessing the different phases of bipolar disorder have been carried out. However, the published data suggest an asymmetrical temporal lobe dysfunction in depressive and manic phases of bipolar depression. Further studies with larger samples of patients are needed in order to improve our knowledge of the pathophysiology of bipolar disorder.


Sedimentation field flow fractionation of DNA's.
Sedimentation field flow fractionation (SFFF) is a method for purifying and providing mass or size distribution information on samples containing particulates or soluble macromolecules. Since SFFF separations are based on simple physical phenomena related to first principles, molecular weight (or particle sizes) can be determined without calibration standards. SFFF is a gentle technique suited for fractionating biomolecules. Studies with the fragile lambda DNA (molecular weight, 33 X 10(6] and smaller supercoiled plasmids have shown that these materials are not altered during SFFF separation; molecular weights and conformation remain unchanged, and biological activity is not reduced. Recoveries of nucleic acids approach 100 percent. Typically, components with about 20 percent difference in mass can be separated essentially to baseline if required. Fractionation time is usually independent of molecular weight, and separations often can be carried out within an hour.


Analysis of Successful Behaviors Leading to Groundwork Scoring Skills in Elite Judo Athletes.
The present study aimed (1) to propose an approach of observational analysis of the preceding standing judo (tachi-waza (TW)) context to a groundwork (ne-waza (NW)) grappling score (NWGS), and (2) to analyze the outcomes of applying such a model in high-level judoists. We conducted an observational analysis of 176 NW scoring actions of 794 combats observed in Baku's World Judo Championships of 2018. Women scored more NWGS, performing more corporal controls but less segmental controls compared with the men. Moreover, NWGS were scored predominately during the second and third minutes of combat, independently of the sex or the weight category. Most NWGS occurred after an asymmetrical lateral structure, without showing associations with a particular type of NWGS. The movement structure of the attacking action during TW leading to an NWGS was predominantly techniques without turn, followed closely by techniques with turn, and barely performed after supine position techniques. Data showed that NWGS occurred more frequently after a failed TW attack (68.6%) than after a scored TW attack (31.4%). The TW attacker achieved NWGS with a higher frequency (62%) than the TW defender (38%), who mainly took advantage of a failed TW attack (98.5% vs. 1.5%, after failed vs. scored TW, respectively). The grip configurations most frequently employed during TW were dorsal-sleeve and flap-sleeve; overall, frontal grips were predominant over dorsal grips. However, no specific TW grip was related to success or grip progression before an NWGS. Our results will help judo coaches understand the influence of these factors on judo performance and optimize the planning and execution of technical-tactical content.


No. 249-Asymptomatic Endometrial Thickening.
To formulate clinical recommendations for the assessment of endometrial thickening when it is found on ultrasound in a postmenopausal patient without bleeding. Ensure that women with asymptomatic thickening and endometrial polyps found on ultrasound are managed appropriately. Published literature was retrieved through searches of English language articles from the EMBASE, Cochrane, and PubMed databases for relevant peer-reviewed articles dating from 1970 to 2009, using appropriate controlled vocabulary (e.g., "asymptomatic endometrial thickness," "endometrial cancer," "postmenopausal bleeding," "transvaginal ultrasonography," "endometrial biopsy" and "endometrial polyp"). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to April 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The level of evidence was determined according to the criteria established by the Canadian Task Force on Preventive Health Care (Table 1). Recommendations are ranked according to this method. It is anticipated that the adoption of these recommendations would save postmenopausal women unnecessary anxiety, pain, and risk of procedural complication. It is also expected to decrease the cost to the health system by eliminating unnecessary interventions.


Preoperative androgen deprivation therapy: artificial lowering of serum prostate specific antigen without downstaging the tumor.
We studied 22 patients with clinical stage B2 (T2c) or C (T3) prostate cancer who underwent androgen deprivation therapy before radical prostatectomy as part of a downstaging protocol (group 1). The concentration of serum prostate specific antigen (PSA) was determined before and at the conclusion of androgen deprivation therapy, just before the operation. For each group 1 patient a match patient who had not received preoperative endocrine therapy (group 2) was chosen. The age of the group 2 patients was similar to that of the group 1 patients. The clinical stage of disease and pretreatment tumor grade in group 2 were identical to the stage and grade in group 1, and the serum PSA value in group 2 was similar to that of group 1 before initiation of androgen deprivation therapy. In group 1 the median serum PSA concentration was 14.8 ng./ml. (range 3.1 to 99) before endocrine therapy and 0.2 ng./ml. (range 0.1 to 3.4) after hormonal treatment. Group 2 had a median level of 13.3 ng./ml. (range 3.4 to 100). The median decrease in the serum PSA concentration for group 1 as a result of androgen deprivation therapy was 98.5%. The radical prostatectomy specimens from these 2 groups of similar patients had no difference with regard to maximal tumor dimension, pathological stage and deoxyribonucleic acid ploidy status. These findings indicate that serum PSA becomes an unreliable indicator of disease status after initiating preoperative androgen deprivation therapy and that preoperative androgen deprivation therapy has little or no benefit for decreasing the extent of tumor or pathological stage. The concept of downstaging is misleading and must be examined in a randomized clinical trial.


Low-dose intrapleural alteplase (without deoxyribonuclease) in complicated parapneumonic effusion: case series and literature reviews.
This case series reviews two cases of elderly patients who presented with fever, cough and shortness of breath. Clinical examinations and initial chest radiographs confirmed unilateral pleural effusion. Thoracenteses were consistent with exudative pleural effusion. We commenced intravenous antibiotics treating for parapneumonic effusions. The first case showed persistent effusion despite drainage, and the second case had a little aspirate from pleural tapping. Subsequent ultrasound of the thorax showed multiloculated effusions. We made the decisions for intrapleural fibrinolytic therapy using low-dose alteplase 2.5 mg each time, in view of the elderly patient as sacrosanct for risk of bleeding. Furthermore, DNase was not used, as it is not yet available in our setting. Both of our patients had good clinical and radiological outcomes, without the need for surgical interventions.


Tubular spinae are long-distance connectors between bacteria.
The marine pseudomonad D71 (NCMB 2018) ['Spinomonas maritima'] can be induced to produce long tubular surface appendages (spinae) in a growth medium of low osmolarity. In general, spina-carrying cells show these appendages with open distal ends. We examined cultured cells by scanning and transmission electron microscopy, using both critical-point drying and thin sectioning after embedding with agarose protection. By scanning electron microscopy, spinae were observed that connected cells over distances of several micrometers. Ultrathin sections often revealed an additional layer outside the outer membrane, resembling an S-layer. The inner and outer cell membranes were often joined at spina-insertion areas. Furthermore, evidence was found in ultrathin sections for uninterrupted tubes connecting two cells over a distance of up to 7 microns. We propose, therefore, that spinae form the framework for wide open cell clusters; we hypothesize that these spinae might also permit an exchange of cell-to-cell signals.


PET: Is myocardial flow quantification a clinical reality?
Positron emission tomography (PET) enables quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recent developments and improved availability of PET technology have resulted in growing interest in translation of quantitative flow analysis from mainly a research tool to routine clinical practice. Quantitative PET measurements of absolute MBF and MFR have potential to improve accuracy of myocardial perfusion imaging in diagnosis of multivessel coronary artery disease as well as definition of the extent and functional importance of stenoses. This article reviews recent advances and experience in the quantitative myocardial perfusion imaging together with issues that need to be resolved for quantitative analysis to become clinical reality.


Comparative host-pathogen associations of Snake Fungal Disease in sympatric species of water snakes (Nerodia).
The ascomycete fungus Ophidiomyces ophiodiicola (Oo) is the causative agent of ophidiomycosis (Snake Fungal Disease), which has been detected globally. However, surveillance efforts in the central U.S., specifically Texas, have been minimal. The threatened and rare Brazos water snake (Nerodia harteri harteri) is one of the most range restricted snakes in the U.S. and is sympatric with two wide-ranging congeners, Nerodia erythrogaster transversa and Nerodia rhombifer, in north central Texas; thus, providing an opportunity to test comparative host-pathogen associations in this system. To accomplish this, we surveyed a portion of the Brazos river drainage (~ 400 river km) over 29 months and tested 150 Nerodia individuals for the presence of Oo via quantitative PCR and recorded any potential signs of Oo infection. We found Oo was distributed across the entire range of N. h. harteri, Oo prevalence was 46% overall, and there was a significant association between Oo occurrence and signs of infection in our sample. Models indicated adults had a higher probability of Oo infection than juveniles and subadults, and adult N. h. harteri had a higher probability of infection than adult N. rhombifer but not higher than adult N. e. transversa. High Oo prevalence estimates (94.4%) in adult N. h. harteri has implications for their conservation and management owing to their patchy distribution, comparatively low genetic diversity, and threats from anthropogenic habitat modification.


Risks of organic UV filters: a review of environmental and human health concern studies.
Organic UV filters are compounds that absorb UV irradiation by their highly conjugated structure. With the developing consciousness over the last century of the skin damage UV radiation can cause, the demand for organic UV filters has risen, for use not only in sunscreens, but also in other personal care products. The massive production and usage of these organic UV filters has resulted in extensive release into the aquatic environment, and thereby making an important group of emerging contaminants. Considering the widespread occurrence of organic UV filters in not only ambient water, but also sediment, soil and even indoor dust, their threats towards the health of living organisms have been a subject of active investigation. In this review article, we present an overall review of existing knowledge on the risks of organic UV filters from the aspects of both environmental and human health impacts. As for the environment, some organic UV filters are proven to bioaccumulate in various kinds of aquatic organisms, and further to have adverse effects on different kinds of animal models. Toxicological studies including in vivo and in vitro studies are important and effective means to ascertain the effects and mechanisms of organic UV filters on both the ecosystem and humans. Subsequent concerns arise that these compounds will affect human health in the long term. This review concludes by suggesting future lines of research based on the remaining knowledge gaps.


Review: Molecular structure and functions of zinc binding metallothionein-1 protein in mammalian body system.
Zinc a major trace element; perform diverse roles in genetics and physiology in almost every vital body system of the mammalian body. Zinc regulates the expression of almost all essential genes responsible for performing pivotal functions in mammal cells through provision of structural integrity to the major transcriptional factors Zn finger Proteins (ZnF) and gene regulation for production of metallothionein protein. Zinc performed at least eight vital functions in living organisms including gene regulation e.g., as a promoter through metal response elements, structural i.e. zinc-finger motifs, catalytic e.g., metalloenzymes, DNA and RNA polymerase, DNA replication, Growth promotion, antioxidant, regulate functions of central nervous system and also act as hepato-protectant and detoxifying agent. Almost all of these vital functions are regulated through metallothionein protein, a cysteine rich Zn binding protein. These functions are basic mechanism for sustaining life. Therefore, this review paper was planned with the objective to highlight the important functions of Zn inside the mammal's body with particular reference to the metallothionein protein. Bioinformatics study performed for estimation of conservation and evolution of this important protein shows its greater conservancies in six important mammalian species.


Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern.
Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology.


Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants.
The lipid phosphatase synaptojanin 1 (synj1) is required for the disassembly of clathrin coats on endocytic compartments. In neurons such activity is necessary for the recycling of endocytosed membrane into synaptic vesicles. Mutations in zebrafish synj1 have been shown to disrupt the activity of ribbon synapses in sensory hair cells. After prolonged mechanical stimulation of hair cells, both phase locking of afferent nerve activity and the recovery of spontaneous release of synaptic vesicles are diminished in synj1 mutants. Presumably as a behavioral consequence of these synaptic deficits, synj1 mutants are unable to maintain an upright posture. To probe vestibular function with respect to postural control in synj1 mutants, we developed a method for assessing the vestibulospinal reflex (VSR) in larvae. We elicited the VSR by rotating the head and recorded tail movements. As expected, the VSR is completely absent in pcdh15a and lhfpl5a mutants that lack inner ear function. Conversely, lhfpl5b mutants, which have a selective loss of function of the lateral line organ, have normal VSRs, suggesting that the hair cells of this organ do not contribute to this reflex. In contrast to mechanotransduction mutants, the synj1 mutant produces normal tail movements during the initial cycles of rotation of the head. Both the amplitude and temporal aspects of the response are unchanged. However, after several rotations, the VSR in synj1 mutants was strongly diminished or absent. Mutant synj1 larvae are able to recover, but the time required for the reappearance of the VSR after prolonged stimulation is dramatically increased in synj1 mutants. Collectively, the data demonstrate a behavioral correlate of the synaptic defects caused by the loss of synj1 function. Our results suggest that defects in synaptic vesicle recycling give rise to fatigue of ribbons synapses and possibly other synapses of the VS circuit, leading to the loss of postural control.


The role of oxidative stress in Friedreich's ataxia.
Oxidative stress and an increase in the levels of free radicals are important markers associated with several pathologies, including Alzheimer's disease, cancer and diabetes. Friedreich's ataxia (FRDA) is an excellent paradigmatic example of a disease in which oxidative stress plays an important, albeit incompletely understood, role. FRDA is a rare genetic neurodegenerative disease that involves the partial silencing of frataxin, a small mitochondrial protein that was completely overlooked before being linked to FRDA. More than 20 years later, we now know how important this protein is in terms of being an essential and vital part of the machinery that produces iron-sulfur clusters in the cell. In this review, we revisit the most important steps that have brought us to our current understanding of the function of frataxin and its role in disease. We discuss the current hypotheses on the role of oxidative stress in FRDA and review some of the existing animal and cellular models. We also evaluate new techniques that can assist in the study of the disease mechanisms, as well as in our understanding of the interplay between primary and secondary phenotypes.


Inappropriate expression of HLA class II molecules in endocrine epithelial cells: the phenomenon, the new experimental data and comparison with animal models.
Physiologically, HLA Class II molecules are primarily expressed on immunoregulatory cells. In recent years, it has been shown that tissues affected by autoimmunity, including beta cells of 'diabetic' pancreases, 'inappropriately' express these glycoproteins. Cytokines are potent Class II inducers on a variety of cells but they exert a heterogenous effect when incubated with different human endocrine cells, i.e. thyroid cells are readily inducible, beta cells are much more resistant. The fine modulation of Class II expression by cytokines has been extensively studied and recent information on their action on endocrine cells is reported here. The possibility that distinct environmental factors from those postulated until now may be responsible for triggering the inappropriate expression of MHC molecules in epithelial cells in vivo is also emphasized. Despite several similarities between human Type I diabetes and spontaneous animal models of the disease, major differences still exist. Transgenic models have now been produced. However, even if they offer interesting new insights, they have not so far provided the decisive answer to explain the pathogenesis of human autoimmune diseases.


Excision repair of cis-diamminedichloroplatinum(II)-induced damage to DNA of Chinese hamster cells.
Platinum was lost from the DNA of cis-diamminedichloroplatinum(II) [cis-Pt(II)]-treated exponentially growing Chinese hamster V79-379A cells with a half-life of 28 hr. By contrast, platinum was lost from the DNA of cells treated in stationary-phase culture with a half-life of 4 days. Cells treated in and allowed to remain as a stationary-phase culture maintained an intact and apparently viable appearance. When the stationary-phase culture was diluted with fresh medium, cell division occurred, and cell survival, as measured by colony-forming ability, could be determined. Dilution of cells immediately after treatment with 40 micron cis-Pt(II) resulted in 0.19% control survival. There was an increase in the ability of the stationary-phase cells to survive cis-Pt(II) damage with time after treatment. Thus, after 3 days, the survival had increased from 0.19 to 15.9%. We demonstrate that this increased ability of stationary-phase cells to survive with time after treatment is due to DNA excision repair and hence that survival is inversely related to the extent of reaction of cis-Pt(II) with the DNA.


Role of β-catenin in post-meiotic male germ cell differentiation.
Though roles of β-catenin signaling during testis development have been well established, relatively little is known about its role in postnatal testicular physiology. Even less is known about its role in post-meiotic germ cell development and differentiation. Here, we report that β-catenin is highly expressed in post-meiotic germ cells and plays an important role during spermiogenesis in mice. Spermatid-specific deletion of β-catenin resulted in significantly reduced sperm count, increased germ cell apoptosis and impaired fertility. In addition, ultrastructural studies show that the loss of β-catenin in post-meiotic germ cells led to acrosomal defects, anomalous release of immature spermatids and disruption of adherens junctions between Sertoli cells and elongating spermatids (apical ectoplasmic specialization; ES). These defects are likely due to altered expression of several genes reportedly involved in Sertoli cell-germ cell adhesion and germ cell differentiation, as revealed by gene expression analysis. Taken together, our results suggest that β-catenin is an important molecular link that integrates Sertoli cell-germ cell adhesion with the signaling events essential for post-meiotic germ cell development and maturation. Since β-catenin is also highly expressed in the Sertoli cells, we propose that binding of germ cell β-catenin complex to β-catenin complex on Sertoli cell at the apical ES surface triggers a signaling cascade that regulates post-meiotic germ cell differentiation.


Mechanism of neurotransmitter release coming into focus.
Research for three decades and major recent advances have provided crucial insights into how neurotransmitters are released by Ca2+ -triggered synaptic vesicle exocytosis, leading to reconstitution of basic steps that underlie Ca2+ -dependent membrane fusion and yielding a model that assigns defined functions for central components of the release machinery. The soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs) syntaxin-1, SNAP-25, and synaptobrevin-2 form a tight SNARE complex that brings the vesicle and plasma membranes together and is key for membrane fusion. N-ethyl maleimide sensitive factor (NSF) and soluble NSF attachment proteins (SNAPs) disassemble the SNARE complex to recycle the SNAREs for another round of fusion. Munc18-1 and Munc13-1 orchestrate SNARE complex formation in an NSF-SNAP-resistant manner by a mechanism whereby Munc18-1 binds to synaptobrevin and to a self-inhibited "closed" conformation of syntaxin-1, thus forming a template to assemble the SNARE complex, and Munc13-1 facilitates assembly by bridging the vesicle and plasma membranes and catalyzing opening of syntaxin-1. Synaptotagmin-1 functions as the major Ca2+ sensor that triggers release by binding to membrane phospholipids and to the SNAREs, in a tight interplay with complexins that accelerates membrane fusion. Many of these proteins act as both inhibitors and activators of exocytosis, which is critical for the exquisite regulation of neurotransmitter release. It is still unclear how the actions of these various proteins and multiple other components that control release are integrated and, in particular, how they induce membrane fusion, but it can be expected that these fundamental questions can be answered in the near future, building on the extensive knowledge already available.


End-of-life care in the neonatal intensive care unit: experiences of staff and parents.
The aim of the study is to determine the perceptions of end-of-life care practices and experience with infants who have died in the NICU among neonatologists, advanced practitioners, nurses, and parents, and also to determine perceived areas for improvement and the perceived value of a palliative care team. This descriptive, exploratory cross-sectional study using surveys consisting of 7-point Likert scales and free response comments was sent to all neonatologists (n = 14), advanced practitioners (n = 40), and nurses (n = 184) at Connecticut Children's Medical Center's neonatal intensive care units (NICUs) in April 2013 and to all parents whose infants died in these NICUs from July 1, 2011, to December 31, 2012 (n = 28). The response rates were 64.3% for physicians; 50.0% for practitioners; 40.8% for nurses; and 30.4% for parents. Most providers reported they feel comfortable delivering end-of-life care. Bereavement support, debriefing/closure conferences, and education did not occur routinely. Families stressed the importance of memory making and bereavement/follow-up. Consistent themes of free responses include modalities for improving end-of-life care, inconsistency of care delivery among providers, and the importance of memory making and follow-up. End-of-life experiences in the NICU were perceived as variable and end-of-life practices were, at times, perceived as inconsistent among providers. There are areas for improvement, and participants reported that a formalized palliative care team could help. Families desire memory making, follow-up, and bereavement support.


Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster).
Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of social behavior(s) and anxiety. Due to its notable pro-social effects, it has been proposed as a treatment in the management of neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, and social anxiety; however, effects of long-term daily treatment are still being explored. Previously, we have shown that in male prairie voles (Microtus ochrogaster) exposure to Oxt during the peri-adolescent period impaired adult pair bonding in a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared to facilitate pair bonding, and the low and medium doses were associated with fewer lines crossed in the open field. In this study, we examined central receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a closely related peptide. Voles were treated with saline vehicle, or one of three doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42, and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor binding and immunohistochemistry to examine Oxt and Avp - IR cells in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females that received the medium dose of Oxt had higher Oxt receptor binding in the nucleus accumbens shell (NAS), while males that received the medium dose had lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long-term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted dose currently being used in clinical trials in humans.


On the nature of selenium toxicity and carcinostatic activity.
Selenium toxicity was first confirmed in 1933 to occur in livestock that consumed plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya in the western regions of the United States. In 1957 selenium was identified as an essential nutrient for laboratory rats and soon thereafter for chickens and sheep. Essentiality for mammalian species was established in 1973 with the discovery that the enzyme glutathione peroxidase contained selenium. During this same period of time, human epidemiological evidence suggested that selenium possessed anticarcinogenic effects. Since the 1970s, many animal studies have confirmed the human epidemiologic evidence that selenium compounds possess carcinostatic activity. Less progress has been made in explaining why many of these compounds of selenium are toxic and why these same compounds are carcinostatic. In 1988 the observation was made that oxidation of glutathione by selenite produced superoxide, opening a new area for selenium research. This present paper, drawing information from the literature on selenium metabolism in plants and animals, selenium toxicology, selenium cytotoxicity, and selenium carcinostatic activity in animals over the last sixty years, sets forth a probable biochemical catalytic mechanism that encompasses both selenium toxicity and selenium carcinostatic activity. The thesis presented here for scrutiny is that compounds of selenium are toxic owing to their prooxidant catalytic activity to produce superoxide (O2.-), hydrogen peroxide, and very likely other cascading oxyradicals. The toxicity of selenium compounds is countered by plant and animal methylation reactions and antioxidant defenses. As carcinostasis is mostly known to occur at supranutritional levels of selenium in animals, carcinostasis appears to be directly correlated to selenium toxicity. The catalytic toxic selenium specie appears to be the metabolic selenide (RSe-) anion.


Building a quality future.
How can healthcare leaders stay ahead of the curve? What can they do to see what the future holds and to secure a place for their employees and their organizations? They must begin doing today what they need to do to survive tomorrow. Furthermore, they must take wise action today or there will be no tomorrow. This article looks into the future and connects it with what we must see and do today. The article begins with a glimpse of the future and with an exploration of what people really want from health and healthcare. Next, it examines what appear to be inexorable megatrends and healthcare trends that are sweeping through society. This leads us to consider the quality and value imperatives that must be faced to secure a stake in the healthcare delivery. We will discuss a model for managing care for individual patients and small populations by focusing on where patients, populations, and caregivers meet--at the front lines of patients care. We conclude with some advice on how to build sustainable organizations by exploiting the inevitable.