Surgical management of Parkinson's disease.
There has been a renaissance in the surgical treatment of Parkinson's disease (PD) over the last 15-20 years as a result of the long-term complications of L-DOPA use. The current cornerstone of surgical treatment for PD is high-frequency deep-brain stimulation (DBS) of the subthalamic nucleus (STN) using implantable electrodes and an implantable pulse generator/battery. Among well-selected patients, that is, patients with idiopathic PD, L-DOPA-responsive symptoms and no significant psychiatric comorbidities or cognitive decline, STN DBS can provide improvements in motor symptoms and quality of life, with low risks of adverse effects. In this article, we briefly describe the evolution of surgical treatments for PD, and the rationale for current DBS procedures. We also provide details of our practice, including patient selection, surgical technique and postoperative stimulation programming and medication adjustment. Current and possible future alternatives to DBS of the STN are also discussed.


Transcriptional regulation of the human CAD gene during myeloid differentiation.
CAD codes for a trifunctional protein involved in the catalysis of the first three enzymatic activities in the de novo pyrimidine biosynthetic pathway, namely, carbamoyl-phosphate synthetase II (EC 22.214.171.124), aspartate transcarbamylase (EC 22.214.171.124), and dihydroorotase (EC 22.214.171.124). CAD regulation was studied in the human promyelocyte leukemic line HL-60 as it differentiated into monocytic or granulocytic lineages after induction by 12-O-tetradecanoylphorbol-13-acetate or trans-retinoic acid and dibutyryl cyclic AMP, respectively. Within 12 h of induction of HL-60 cells with either inducer, total cellular levels of CAD RNA essentially disappeared. On the other hand, no apparent decreases in beta-actin RNA levels were seen even 48 h after HL-60 cells were induced, as compared with untreated cells. With nuclear runoff assays, it was clearly shown that the inactivation of CAD gene expression during the induction of HL-60 cells with either inducer was at the transcriptional level. The nuclear runoff experiments also demonstrated that the CAD gene expression was shut down in less than 4 h after induction, well before morphological changes were observed in these cells. At the enzymatic level, the activity of aspartate transcarbamylase, one of the three enzymes encoded by the CAD gene, decreased by about half within 24 h of induction, suggesting a CAD protein half-life of 24 h in differentiating HL-60 cells. Nevertheless, this means that significant levels of aspartate transcarbamylase activity remained even after the cells have stopped proliferating. From the RNA data, it is clear that CAD gene expression is rapidly turned off as promyelocytes begin to terminally differentiate into macrophages and granulocytes. We suspect that the inactivation of the CAD gene in induced HL-60 cells is a consequence of the differentiating cells leaving the cell cycle and becoming nonproliferating.


Cerebral oxygen saturation does not normalize until after stage 2 single ventricle palliation.
In an effort to optimize neurologic outcome, cerebral oxygen saturation (SCO2) is often measured intraoperatively and postoperatively. We hypothesized that SCO2 would be related to stage of palliation in children with single ventricle congenital heart disease. Cerebral oxygen saturation was continuously recorded intraoperatively in 34 infants and children undergoing palliative surgery on cardiopulmonary bypass for single ventricle congenital heart defects and in a control group of 12 neonates with ductus-dependent circulation undergoing complete repair. Saturations were correlated with the patient's stage and outcome. Baseline SCO2 was 61% in single ventricle neonates (group P1, n = 10), 55% in neonates undergoing repair (group R), 42% in infants undergoing stage 2 palliation (group P2, n = 6), and 70% in children undergoing Fontan (group P3, n = 14). Baseline was lowest (41%) in infants undergoing interstage operations (group I, n = 4). After bypass, there was a significant improvement in SCO2 to 53% in group P2 infants (p = 0.04); there were no significant changes in the other groups. By the end of the operation, there was a significant decrease in SCO2 to 48% in group P1 (p = 0.001), with other groups unchanged from baseline. There were five perioperative deaths. Cerebral oxygen saturation at the conclusion of surgery was lower in children who died (38% versus 61%, p = 0.01). In children with single ventricle physiology, SCO2 decreases after initial palliation, remains low before second-stage palliation, but is normal before and after the Fontan. This has implications for perioperative mortality, neurologic injury, and potentially for interim mortality. Low postoperative SCO2 predicts perioperative mortality.


Comparative computational analysis of active and inactive cofactors of nitric oxide synthase.
Nitric oxide synthases (NOSs) are heme proteins that catalyze the formation of nitric oxide from L-Arg in the presence of oxygen. Of the two electrons required for the first step of the reaction, the second is primarily donated by the tetrahydrobiopterin (H4B) cofactor bound adjacent to the heme, which is eventually reduced back to resting state by the ultimate electron source of the reaction, the flavins of the NOS reductase domain. Density functional theory calculations were carried out to identify those protonation states of different cofactor molecules that best support radicalization of the cofactor and the coupled increase in the electron density of the heme-bound oxygen molecule. Three cofactor molecules were studied, native H4B, an active analogue, 5-methyl-H4B, and the inactive 4-amino-H4B. Findings support the emerging model where H4B and 5-methyl-H4B are coupled proton/electron sources of NOS catalysis, while 4-amino-H4B is an inhibitor due to its inability to donate the catalytically required proton.


Recent advances in understanding the microbiology of the female reproductive tract and the causes of premature birth.
Data derived from molecular microbiological investigations of the human vagina have led to the discovery of resident bacterial communities that exhibit marked differences in terms of species composition. All undergo dynamic changes that are likely due to intrinsic host and behavioral factors. Similar types of bacteria have been found in both amniotic fluid and the vagina, suggesting a potential route of colonization. Given that not all of the species involved in intrauterine infections are readily cultivated, it is important that culture-independent methods of analysis must be used to understand the etiology of these infections. Further research is needed to establish whether an ascending pathway from the vagina to the amniotic cavity enables the development of intrauterine infections.


Boron-Dependent Translational Suppression of the Borate Exporter BOR1 Contributes to the Avoidance of Boron Toxicity.
Boron (B) is an essential element for plants; however, as high B concentrations are toxic, B transport must be tightly regulated. BOR1 is a borate exporter in Arabidopsis (Arabidopsis thaliana) that facilitates B translocation into shoots under B deficiency conditions. When the B supply is sufficient, BOR1 expression is down-regulated by selective degradation of BOR1 protein, while additional BOR1 regulatory mechanisms are proposed to exist. In this study, we identified a novel B-dependent BOR1 translational suppression mechanism. In vivo and in vitro reporter assays demonstrated that BOR1 translation was reduced in a B-dependent manner and that the 5'-untranslated region was both necessary and sufficient for this process. Mutational analysis revealed that multiple upstream open reading frames in the 5'-untranslated region were required for BOR1 translational suppression, and this process depended on the efficiency of translational reinitiation at the BOR1 open reading frame after translation of the upstream open reading frames. To understand the physiological significance of BOR1 regulation, we characterized transgenic plants defective in either one or both of the BOR1 regulation mechanisms. BOR1 translational suppression was induced at higher B concentrations than those triggering BOR1 degradation. Plants lacking both regulation mechanisms exhibited more severe shoot growth reduction under high-B conditions than did plants lacking BOR1 degradation alone, thus demonstrating the importance of BOR1 translational suppression. This study demonstrates that two mechanisms of posttranscriptional BOR1 regulation, each induced under different B concentrations, contribute to the avoidance of B toxicity in plants.


Modulatory role of 5-HT3 receptors in gastric function and ethanol-induced mucosal damage in rat stomachs.
The involvement of 5-hydroxytryptamine (5-HT) in gastric function and mucosal damage has been defined. 5-HT also potentiates lesion formation in animals. The current study investigated further whether these actions are mediated through 5-HT3 receptors in rats. Ondansetron, a 5-HT3 receptor antagonist, was given subcutaneously, 2 or 4 mg/kg, 30 min before the gastric parameters were measured. The higher dose of ondansetron, 4 mg/kg, significantly increased gastric mucosal blood flow (GMBF) and also basal acid and Na+ secretion. However, it did not affect pepsin output. 5-HT time dependently reduced GMBF and pepsin secretion, but not that of acid and Na+. These actions were not altered by ondansetron pretreatment. The drug, however, dose dependently reduced ethanol-induced gastric mucosal lesions in the 5-HT-treated animals. These findings indicate that 5-HT3 receptors regulate not only basal GMBF, but also acid and Na+ secretion in stomachs. However, the depressive action of 5-HT on GMBF and pepsin secretion is most likely not mediated through 5-HT3 receptors. Ondansetron also modulates the toxicities of ethanol in the stomach and this action is likely to be mediated through the preservation of GMBF.


Good Spirit, Good Life: A Quality of Life Tool and Framework for Older Aboriginal Peoples.
The lack of appropriate quality of life (QoL) measures is a major barrier to planning and delivering health and aged care services for older Indigenous peoples worldwide. QoL is dependent on cultural values and priorities may vary between age groups. This project aims to develop a QoL tool for older Aboriginal Australians. The study was completed with Aboriginal Australians aged over 45 years living in Perth and Melbourne, Australia. Participatory Action Research methods were applied with an Indigenous research paradigm. Semistructured interviews were undertaken to identify the factors important to having a good life. Factors were further explored in yarning groups with older Aboriginal peoples to develop the draft QoL tool questions. Face validity of the tool was completed in two regions. The participants preferred the term "a good life" to QoL. Having a good spirit is at the core of having a good life. The protective factors for a good life were family and friends, health, culture, Elder role, respect, Country, spirituality, services and supports, community, future plans, safety and security, and basic needs. Twelve factors were identified and developed into key questions for the Good Spirit, Good Life tool. The draft tool will undergo quantitative validity testing, prior to embedding in service provision to inform care for older Aboriginal peoples. With local adaptation, the tool, accompanying framework, and participatory methods for development may have wider applicability to other Indigenous populations worldwide.


Ischemia induced peroxynitrite dependent modifications of cardiomyocyte MLC1 increases its degradation by MMP-2 leading to contractile dysfunction.
Damage to cardiac contractile proteins during ischemia followed by reperfusion is mediated by reactive oxygen species such as peroxynitrite (ONOO(-)), resulting in impairment of cardiac systolic function. However, the pathophysiology of systolic dysfunction during ischemia only, before reperfusion, remains unclear. We suggest that increased ONOO(-) generation during ischemia leads to nitration/nitrosylation of myosin light chain 1 (MLC1) and its increased degradation by matrix metalloproteinase-2 (MMP-2), which leads to impairment of cardiomyocyte contractility. We also postulate that inhibition of ONOO(-) action by use of a ONOO(-) scavenger results in improved recovery from ischemic injury. Isolated rat cardiomyocytes were subjected to 15 and 60 min. of simulated ischemia. Intact MLC1 levels, measured by 2D gel electrophoresis and immunoblot, were shown to decrease with increasing duration of ischemia, which correlated with increasing levels of nitrotyrosine and nitrite/nitrate. In vitro degradation of human recombinant MLC1 by MMP-2 increased after ONOO(-) exposure of MLC1 in a concentration-dependent manner. Mass spectrometry analysis of ischemic rat cardiomyocyte MLC1 showed nitration of tyrosines 78 and 190, as well as of corresponding tyrosines 73 and 185 within recombinant human cardiac MLC1 treated with ONOO(-). Recombinant human cardiac MLC1 was additionally nitrosylated at cysteine 67 and 76 corresponding to cysteine 81 of rat MLC1. Here we show that increased ONOO(-) production during ischemia induces MLC1 nitration/nitrosylation leading to its increased degradation by MMP-2. Inhibition of MLC1 nitration/nitrosylation during ischemia by the ONOO(-) scavenger FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), or inhibition of MMP-2 activity with phenanthroline, provides an effective protection of cardiomyocyte contractility.


Arthroscopy update #8. Auxiliary portal for assessing patellofemoral alignment.
An auxiliary arthroscopic portal may be used to improve visualization and evaluation of the patellofemoral joint. A reusable transquadriceps tendon portal, which assesses patellar alignment within a 0 degree to 90 degrees range of motion, is described.


Motor control of velopharyngeal structures during vowel production.
This investigation was designed to measure the ability of normal adult speakers to exert voluntary control over velopharyngeal positioning. Speakers were asked to phonate the vowels [a] and [i] at 50 percent and 75 percent of complete velopharyngeal closure, using visual feedback of velopharyngeal opening and closing gestures from a phototransducer. The musculature of the velopharyngeal mechanism was hypothesized to act as a coordinated system that may demonstrate both motor flexibility and plasticity (Folkins, 1985) when forced to function in a novel way. Evidence of both motor system responses to a novel speaking condition was observed. Speakers were able either to phonate at intermediate closure levels without having to learn new motor rules, or to learn new rules for velopharyngeal muscle activation that resulted in the ability over time to position the velopharyngeal mechanism appropriately. As such, support is derived for the notion (Folkins, 1985) that speakers develop motor rules or coordinative structures involving the velopharyngeal mechanism that govern velopharyngeal movement. The characteristics of this coordinative structure framework has not yet been described, however, and are the subject of ongoing research efforts.


The immunological effect of photopheresis in children with newly diagnosed type 1 diabetes.
Photopheresis has been claimed to have immune-modulating effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1- and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation.


[LASIK interface fluid accumulation caused by glaucoma associated with herpetic keratouveitis: case report].
Herpes simplex virus infection is a frequent cause of intraocular inflammation or anterior uveitis. Ocular hypertension is a common feature in herpetic keratouveitis. We describe a fluid accumulation and flap displacement in late postoperative period (28 months) of LASIK associated with ocular hypertension caused by herpetic keratouveitis. This finding supports the theory that flap attachment after LASIK is only partial and the virtual space remains indefinitely. The presence of ocular hypertension may lead to corneal edema and fluid accumulation in the interface.


Population-based volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy.
In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer's lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer's lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer's lactate solution. A two-volume model best described the pharmacokinetics of Ringer's lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance (kr) and central volume of distribution at baseline (Vc0), respectively. The parameter estimates were as follows: kr (mL/min) = 124 + (MAP/70)14.2, Vc0 (mL) = 0.95 + 3440 × (WT/63), Vt0 (mL) = 2730, and kt (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.


The role of computerized ECG interpretation in clinical trials.
The Lipid Research Clinics project consisted of the Prevalence Study and the Coronary Primary Prevention Study. The first study characterized the levels of blood lipids in the population studied, and related these to the presence of coronary artery disease as detected by medical history, symptom analysis, resting ECG and treadmill exercise ECG tests. The prevention trial tested whether a reduction of elevated serum cholesterol would reduce the incidence of coronary events (Table I). Both projects collected resting 12-lead ECGs and treadmill exercise test data on the participants. Instrumentation and methodology were standardized. Rest and exercise electrocardiographic data were recorded on analog magnetic tape. Tapes were sent to the ECG Center where they were digitized, analyzed and also reproduced for visual analysis according to the Minnesota Code of Blackburn. There were two reasons for using both visual coding and computer analyses in these projects. It was thought that computer methodology would enhance the accuracy of the electrocardiographic data, but on the other hand its accuracy had not been adequately documented and its output statements were not in the language of the Minnesota Code, which is traditionally accepted by epidemiologists. The other and more pressing reason for using the Minnesota Code is that the computer programming had not been completed at the start of the project, and visual coding was required in order to provide the ECG data necessary for the randomization of the Prevention Trial participants.


Area-based socioeconomic characteristics of industries at high risk for violence in the workplace.
This study examined socioeconomic factors associated with the presence of workplaces belonging to industries reported to be at high risk for worker homicide. The proportion of 2004 North Carolina workplaces in high-risk industries was computed following spatial linkage of individual workplaces to 2000 United States Census Block Groups (n = 3,925). Thirty census-derived socioeconomic variables (selected a priori as potentially predictive of violence) were summarized using exploratory factor analysis into poverty/deprivation, human/economic capital, and transience/instability. Multinomial logistic regression models indicate associations between higher proportion of workplaces belonging to high-risk industries and Block Groups with more poverty/deprivation or transience/instability and less human/economic capital. The relationship between human/economic capital and Block Groups proportion of high-risk industry workplaces was modified by levels of transience/instability. Community characteristics therefore contribute to the potential for workplace violence, and future research should continue to understand the relationship between social context and workplace violence risk.


Varied and principled understandings of autonomy in English law: justifiable inconsistency or blinkered moralism?
Autonomy is a concept that holds much appeal to social and legal philosophers. Within a medical context, it is often argued that it should be afforded supremacy over other concepts and interests. When respect for autonomy merely requires non-intervention, an adult's right to refuse treatment is held at law to be absolute. This apparently simple statement of principle does not hold true in practice. This is in part because an individual must be found to be competent to make a valid refusal of consent to medical treatment, and capacity to decide is not an absolute concept. But further to this, I argue that there are three relevant understandings of autonomy within our society, and each can demand in differing cases that different courses of action be followed. Judges, perhaps inadvertently, have been able to take advantage of the equivocal nature of the concept to come tacitly to decisions that reflect their own moral judgments of patients or decisions made in particular cases. The result is the inconsistent application of principle. I ask whether this is an unforeseen outcome or if it reflects a wilful disregard for equal treatment in favour of silent moral judgments in legal cases. Whatever the cause, I suggest that once this practice is seen to occur, acceptable justification of it in some cases is difficult to find.


CT angiography of the intracranial circulation.
Rapidly acquired, anatomically accurate depictions of intracranial vascular anatomy can be obtained with helical CT. This article discusses data acquisition, reconstruction techniques, normal anatomy, pitfalls, aneurysms, and a number of other vascular pathologies that have been successfully imaged with CT angiography.


[Comparative analysis of approaches to surgical cochlear implantation in adults and children].
The aim of a surgical stage of cochlear implantation (CI) is to place the implanted part of the device in the temporal space. Criteria of the decision on the side of the intervention and components of it in CI are outlined. To help selection of an optimal variant of surgical intervention in CI at the initial stage, the techniques of the implanted parts insertion are reviewed. Types of skin cuts, approaches to the cochlea, location of cochleostoma, methods of fixing the stimulator are described. The importance of intraoperative registration of the musculus stapedius reflex and action potential of the acoustic nerve in response to cochlear electrostimulation is emphasized. Basing on the experience of treating 38 deaf patients, the author states that for effective performance of the operation it is desirable to conduct reverse U-cut of the skin, make posterior tympanostoma, cochleostoma in the basic cochlear margin, suturing of the cut with intracutaneous suture.


Evidence for the regulation of the activity of protein kinase C through changes in membrane properties.
We measured the effects of two branched-chain analogs of distearoyl-phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein. We also compared the effects of hexachlorophene on lipid polymorphism and protein kinase C activity at high and at low calcium concentrations. We also found that the effect of hexachlorophene forming a complex with Ca2+ is to increase both the hexagonal phase forming propensity of the membrane as well as to increase the activity of protein kinase C, again demonstrating the correlation between lipid phase propensity and effects on protein kinase C activity.


Growth hormone deficiency presenting under age 2 years.
Twenty nine (1.8%) of a national cohort of 1600 patients with growth hormone deficiency presented before the age of 2 years. Sixteen of the 29 presented before 6 months of age--11 with symptomatic hypoglycaemia, four with failure to thrive, and one with obesity. Hypoglycaemia was persistent and difficult to control until growth hormone treatment was started. Ten of the 11 hypoglycaemic patients had multiple pituitary hormone deficiencies compared with two of the remaining five. Thirteen children presented between 6 months and 2 years of age; 12 had failure to thrive and one had spontaneous hypoglycaemia. Twelve of the 29 were boys and all but one of these had microgenitalia . Growth hormone deficiency should be considered in the differential diagnosis of infants presenting with refractory hypoglycaemia and in boys with failure to thrive and microgenitalia .


Accessibility, reliability, and usability of neurosurgical resources.
OBJECTIVE Closing the knowledge gap that exists between patients and health care providers is essential and is facilitated by easy access to patient education materials. Although such information has the potential to be an effective resource, it must be written in a user-friendly and understandable manner, especially when such material pertains to specialized and highly technical fields such as neurological surgery. The authors evaluated the accessibility, usability, and reliability of current educational resources provided by the American Association of Neurological Surgeons (AANS), Healthwise, and the National Institute for Neurological Disorders and Stroke (NINDS). METHODS Online neurosurgical patient education information provided by AANS, Healthwise, and NINDS was evaluated using the LIDA scale, a website quality assessment tool, by medical professionals and nonmedical professionals. A high achieving score is regarded as 90% or greater using the LIDA scale. RESULTS Accessibility scores were 76.7% (AANS), 83.3% (Healthwise), and 75.0% (NINDS). Average usability scores for the AANS, Healthwise, and NINDS were 73.3%, 82.6%, and 82.9%, respectively, when evaluated by medical professionals and 78.5%, 80.7%, and 75.9%, respectively, for nonmedical professionals, respectively. Average reliability scores were 58.5%, 53.3%, 72.6%, respectively, for medical professionals and 70.4%, 66.7%, and 78.5%, respectively, for nonmedical professionals when evaluating the AANS, Healthwise, and NINDS websites. CONCLUSIONS Although organizations like AANS, Healthwise, and NINDS should be commended for their ongoing commitment to provide health care-oriented materials, modification of this material is suggested to improve the patient education value.


Development of an Influenza Rapid Diagnostic Kit Specific for the H7 Subtype.
Since the spring of 2013, human infections with H7N9 viruses have been detected in China. Some of these viruses have become highly pathogenic. Highly and low pathogenic avian influenza H7N9 viruses are currently co-circulating with the seasonal influenza A viruses H3N2 and H1N1pdm09. Prompt identification and isolation of H7N9 patients is one measure to prevent the spread of H7N9 virus and help prevent a pandemic. The majority of commercially available point-of-care rapid influenza diagnostic kits can differentiate between influenza A and B viruses, but cannot distinguish between H7N9 viruses and seasonal influenza A viruses. Accordingly, we have developed a rapid diagnostic kit specific for the H7 subtype that is accessible, easy to use. Although the detection limit of this H7 kit is one-tenth lower than that of a commercially available rapid influenza A and B diagnostic kit of similar design, except for the specificity of the monoclonal antibodies used, this kit is highly specific, detecting only H7-subtype influenza viruses, including the recent highly pathogenic H7N9 viruses from humans, and does not show any non-specific reactions with other HA subtypes. This H7 kit will be of value for the early detection of H7N9-infected patients.


Characterization of novel recombinant mycobacteriophages derived from homologous recombination between two temperate phages.
Comparative analyses of mycobacteriophage genomes reveals extensive genetic diversity in genome organization and gene content, contributing to widespread mosaicism. We previously reported that the prophage of mycobacteriophage Butters (cluster N) provides defense against infection by Island3 (subcluster I1). To explore the anti-Island3 defense mechanism, we attempted to isolate Island3 defense escape mutants on a Butters lysogen, but only uncovered phages with recombinant genomes comprised of regions of Butters and Island3 arranged from left arm to right arm as Butters-Island3-Butters (BIBs). Recombination occurs within two distinct homologous regions that encompass lysin A, lysin B, and holin genes in one segment, and RecE and RecT genes in the other. Structural genes of mosaic BIB genomes are contributed by Butters while the immunity cassette is derived from Island3. Consequently, BIBs are morphologically identical to Butters (as shown by transmission electron microscopy) but are homoimmune with Island3. Recombinant phages overcome antiphage defense and silencing of the lytic cycle. We leverage this observation to propose a stratagem to generate novel phages for potential therapeutic use.


Soccer (Football Association) and chronic traumatic encephalopathy: A short review and recommendation.
Chronic traumatic encephalopathy (CTE) was initially described in boxers, but in recent years it has been reported in other settings, particularly in contact sports and military personnel. Soccer (football association) had previously been (and still is) considered relatively safe when compared to other sports, such as American football. However, a few cases of professional soccer players with CTE have been reported in the last few years. It is still unknown how frequent this condition is in soccer players, and the role played by heading the ball remains elusive. Other traumas to the head, face and neck caused by contact with another player's head, arm or other body parts are among the most frequent in soccer. In spite of the lack of more in-depth knowledge, there is reasonable evidence for recommending severe punishment (red card and suspension for several matches) for players causing avoidable trauma to another player's head.


Stimulation of ethylene production in apple tissue slices by methionine.
Methionine can induce more than a 100% increase in ethylene production by apple tissue slices. The increased amount of ethylene derives from carbons 3 and 4 of methionine. Only post-climacteric fruit tissues are stimulated by methionine, and stimulation is optimum after 8 months' storage. Copper chelators such as sodium diethyl dithiocarbamate and cuprizone very markedly inhibit ethylene production by tissue slices. Carbon monoxide does not effect ethylene production by the slices. These data suggest that the mechanism for the conversion of methionine to ethylene, in apple tissues, is similar to the previously described model system for producing ethylene from methionine and reduced copper. Therefore, it is suggested that one of the ethylene-forming systems in tissues derives from methionine and proceeds to ethylene via a copper enzyme system which may be a peroxidase.


Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ.
Regulation of ENaC occurs at several levels. The principal hormonal regulator of ENaC, aldosterone, acts through the mineralocorticoid receptor to modulate ENaC-mediated sodium transport, and considerable attention has focused on defining the components of the early phase of this response. Two genes, SGK1 and GILZ, have now been implicated in this regulation. While the functional significance of SGK1 in mediating aldosterone effects is well established, new evidence has enhanced our understanding of the mechanisms of SGK1 action. In addition, recent work demonstrates a novel role for GILZ in the stimulation of ENaC-mediated sodium transport. Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia.


Nutrition-related care needs of older patients in hospital: A qualitative multimethod study.
To investigate the nutrition-related care needs of older patients in hospitals. A qualitative multimethod study was performed. By purposive sampling, older patients were included for observations of the nutrition process and interviews from a perioperative unit, an internal Medicine unit, and one acute geriatric care ward of an acute care hospital. Preliminary findings were discussed, validated, and further explored in two focus group discussions with interprofessional nutritional healthcare experts. Seventeen women and five men with a mean age of 86 years participated in patient observations and interviews. Eight experts with at least 10 years of professional experience who were employed in this setting for 3 years or more participated in interviews. Three themes of nutrition-related care needs were elaborated: The need to assess and address older patients' attitudes toward life, the need for nutrition-related education, and the need for food intake support. These care needs added to the development and validation of a new nursing diagnosis "risk for inadequate protein energy nutrition" and in consequence to develop a complex nursing intervention to optimize the nutrition of older patients. It is crucial to assess and understand the patients' attitudes toward life, which affect purposes of treatment, diet, and menu choices. Implementation of assessing nutrition-related care needs of older inpatients is needed. Addressing these care needs within the Advanced Nursing Process can lead to appropriate nursing diagnoses, nursing outcomes, and interventions, which enhance person-centered care, patients' self-care abilities, and consequently patients' nutritional status.


Evaluation of a novel periodontal risk assessment model in patients presenting for dental care.
The present study was designed to develop a new periodontal risk assessment model based on the periodontal risk assessment (PRA) model by Lang and Tonetti, and to evaluate the risk assessment capability of the proposed model. Twenty-six patients diagnosed with chronic periodontitis were selected randomly and a thorough examination and charting of the periodontal status was performed. An intra-oral periapical radiograph of the area with the deepest probing depth was also taken. The following parameters were recorded: percentage of sites with BOP, number of sites with pocket depths > or = 5mm, number of teeth lost, bone loss/age ratio, attachment loss/age ratio, diabetic and smoking status, dental status, other systemic factors and risk determinants. Using Microsoft Excel, the parameters were plotted on the radar chart as per the original and the proposed model. Of the cases identified by the original model, 42.3% were high-risk cases and 30.8% of the cases were low-risk cases. In the proposed model, 46.2% of high-risk cases and 46.2% of low-risk cases were identified. Only 7.7% of the cases identified with the new model were moderate-risk cases. Statistical analysis demonstrated that there was no significant difference between the risk scores of the two models. The results suggest that risk assessment by this model does not vary significantly as compared to the original model, and both are equally adept at detecting potential risk groups.


Designing virtual communities of practice for informal caregivers of Alzheimer's patients: An integrative review.
The main aim of this study is to review the literature to show how ideas around virtual communities of practice (VCoP) offer a model for supporting informal caregivers of Alzheimer's patients (caregivers) to learn how to deal with caregiving demands. Caregivers are individuals who have a significant personal relationship with and provide a broad range of unpaid assistance to an older person or an adult with a chronic or disabling condition outside of a professional or formal framework. This review will examine the current evidence on the needs of caregivers, identify dimensions to be considered in VCoP design and suggest further directions of research. The investigation is an integrative review that builds a bridge between different areas of work. The outcome is eleven dimensions for the design of successful VCoPs for caregivers: Network Structure, Technology, Moderator, Scale, Alignment, Community Design, Sense of Trust, Knowledge Sharing, Sustainability, Ethics and Evaluation. In addition, we propose a Tree Metaphor to present our research results. Well-designed interventions based on VCoP principles have the potential of addressing caregivers' needs.


Association of Diet Quality with Low Muscle Mass-Function in Korean Elderly.
There is a growing body of evidence that links nutrition to muscle mass and function in the elderly, suggesting that it has an important role to play both in the prevention and management of age-related sarcopenia. Some nutrients have been studied, but less is known about the influence of overall diet quality on the loss of skeletal muscle mass and function. This study investigated the interrelationship between the recommended food score (RFS), as an indicator of overall diet quality, and muscle mass function among the Korean elderly. The sample consisted of 521 participants (263 men and 258 women), aged >65 years, who participated in the 2014-2015 National Fitness Award project. Appendicular skeletal muscle mass (ASM) was assessed by bioelectrical impedance analysis. Low muscle mass was defined as having an ASM corrected for height lower than the cutoff value established by the European Working Group on Sarcopenia in Older People. Muscle function, assessed by handgrip strength (HGS), was defined as low if it was below the 20th percentile of elderly men and women. Low muscle mass-function, defined as low muscle mass with low muscle strength (HGS), was found in 29 men (11.0%) and 22 women (8.5%). In elderly men, the low muscle mass-function group had significantly lower RFS values than the normal group after adjustments for age, body fat percentage, drinking, smoking, education, and physical activity (p = 0.019). However, there was no association between RFS and muscle mass-function in elderly women. Our findings suggest that better diet quality may be associated with higher muscle mass in elderly Korean men.


Research priorities to support the development of integrated national strategies to control skin-neglected tropical diseases.
Skin-presenting neglected tropical diseases (skin-NTDs) impose large burdens on affected people, families and communities. The NTD Roadmap 2021-2030 presents a strategic plan to guide collaborative, multisectoral action to overcome these burdens, defining targets to control, eliminate and/or eradicate skin-NTDs by 2030. One of its targets is for 40 countries to adopt integrated skin-NTD strategies. Despite this high-level support for integration, only four countries were implementing integrated skin-NTD strategies in 2020. We hosted workshops at the 2021 annual meeting of the Coalition for Operational Research on NTDs, to discuss the operationalisation of Roadmap goals into national strategies and interventions for skin-NTD control. Speakers included NTD Programme Managers from NTD-endemic countries, technical experts and researchers of different aspects of skin-NTDs. Challenges include community perceptions of interventions, demonstrating the cost-effectiveness of integrated care, availability and accessibility of community-based and primary healthcare services, the quality of data on skin-NTD morbidity and changes to operational structures required for integration. Research priorities included the identification of optimal case detection platforms, evaluation of integrated care, understanding the impacts of integration on community members and community health staff and development of point-of-care diagnostics. The operational research priorities are intended to support the scale-up of integrated skin-NTDs programmes.


Homeostasis: apoptosis and cell cycle in normal and pathological prostate.
Prostatic diseases such as hyperplasia and cancer are a consequence of glandular aging due to the loss of homeostasis. Glandular homeostasis is guaranteed by the delicate balance between production and cell death. Both cell renewal and apoptosis are part of this delicate balance. We will explore the predictive capacity for biochemical progression, following prostatectomy, of some members of the Bcl-2 family and of proteins involved in cell cycle inhibition in conjunction with established classical markers. The expression of Bcl-2, Bcl-xL, Mcl-1, Bax, Bim, Bad, PUMA, Noxa, p21, p27, Rb and p53 were analyzed by immunochemistry in 86 samples of radical prostatectomy and correlated with each of the markers established clinicopathological tests using statistical tests such as Sperman, Kaplan-Meier curves, unifactorial Cox, and multifactorial. The most relevant results are: (1) Positive correlation between: p27 with clinical T stage; and PUMA with pathological T stage; (2) Negative correlation between: Bcl-2 with clinical T stage, Bcl-xL with survival, Noxa and pRb with Gleason score.Our results suggest that the expression of Bcl-2, Bcl-xL, PUMA, Noxa, p27, and Rb were related to some of the classic markers established to predict biochemical progression after prostatectomy.


Pain relief in terminally ill patients.
A systematic approach to identifying the cause of pain and rational use of drug therapy are keys to providing pain relief to cancer patients. Aspirin, acetaminophen and nonsteroidal anti-inflammatory drugs are effective for mild to moderate pain, and they enhance the effectiveness of weak oral narcotics, such as codeine. For severe pain, morphine is the drug of choice. A variety of adjuvant drugs can be used to enhance the effect of narcotics and to treat specific side effects of the disease or of therapy. For the terminally ill patient, a peaceful death with dignity should always be possible.


Bipartite structure of the inactive mouse X chromosome.
In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. In mouse, the boundary region also contains a minisatellite, Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation compared with the active alleles and with genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.


Digit ratio predicts sense of direction in women.
The relative length of the second-to-fourth digits (2D:4D) has been linked with prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values in males than females, and appears to correlate with diverse measures of behavior. However, the relationship between digit ratio and cognition, and spatial cognition in particular, has produced mixed results. In the present study, we hypothesized that spatial tasks separating cue conditions that either favored female or male strategies would examine this structure-function correlation with greater precision. Previous work suggests that males are better in the use of directional cues than females. In the present study, participants learned a target location in a virtual landscape environment, in conditions that contained either all directional (i.e., distant or compass bearing) cues, or all positional (i.e., local, small objects) cues. After a short delay, participants navigated back to the target location from a novel starting location. Males had higher accuracy in initial search direction than females in environments with all directional cues. Lower digit ratio was correlated with higher accuracy of initial search direction in females in environments with all directional cues. Mental rotation scores did not correlate with digit ratio in either males or females. These results demonstrate for the first time that a sex difference in the use of directional cues, i.e., the sense of direction, is associated with more male-like digit ratio.


Queen sex pheromone of the slave-making ant, Polyergus breviceps.
Workers of the slave-making ant, Polyergus breviceps, raid nests of Formica ants and return with Formica pupae that mature into worker ants in the slave-makers' colony. These Formica workers then tend the Polyergus brood, workers, and reproductives. During raids in the mating season, winged virgin Polyergus queens accompany the workers in the raiding columns. During the raid, the virgin queens release a pheromone that attracts males that quickly mate with the queens. We report the identification, synthesis, and bioassay of the sex attractant pheromone of the queens as an approximately 1:6 ratio of (R)-3-ethyl-4-methylpentan-1-ol and methyl 6-methylsalicylate. The ants produce exclusively the (R)-enantiomer of the alcohol, and the (S)-enantiomer has no biological activity, neither inhibiting nor increasing attraction to blends of methyl 6-methylsalicylate with the (R)-enantiomer.


Acute-on-chronic liver failure: update on pathogenesis, therapeutic targets, predictive models, and liver transplantation.
Acute-on-chronic liver failure (ACLF) is a clinical syndrome in patients with chronic liver disease that is associated with multiple organ failures and a high short-term mortality. Systemic inflammation is suggested to play a key role in its pathogenesis, although the precise causative mechanism is unknown. The purpose of this review is to present and discuss new findings related to: mechanisms underlying ACLF, therapeutic targets, risk prediction models for developing ACLF, and liver transplantation for ACLF. Recent studies of ACLF pathophysiology classified the immunosuppressive phenotype in monocytes. Investigation of therapeutic strategies identified inhibition of toll-like receptor-4 (TLR-4) and glutamine synthetase (GLUL) as potential targets. Recent studies identified novel risk prediction models for developing ACLF and enhanced our understanding of liver transplantation for ACLF to guide clinicians in determining that patients will benefit from transplantation. Improved knowledge on the pathogenesis of ACLF and identification of TLR-4 and GLUL may lead to clinical trials to study the efficacy of these novel therapeutic targets for patients with ACLF. Liver transplantation is the only current treatment for ACLF. Given the limited availability of donor organs, recent studies have identified ACLF patients who may merit the highest waitlist priority.


Unidirectional Magneto-Resistance in Modulation-Doped Magnetic Topological Insulators.
Nonlinear unidirectional spin Hall magnetoresistance (USMR) has been reported in heavy metal/ferromagnet bilayers, which could be employed as an effective method in detecting the magnetization orientation in spintronic devices with two-terminal geometry. Recently, another unidirectional magnetoresistance (UMR) was reported in magnetic topological insulator (TI)-based heterostructures at cryogenic temperature, whose amplitude is orders of magnitude larger than the USMR measured in heavy metal-based magnetic heterostructures at room temperature. Here, we report the UMR effect in the modulation-doped magnetic TI structures. This UMR arises due to the interplay between the magnetic dopant's magnetization and the current-induced surface spin polarization, when they are parallel or antiparallel to each other in the TI material. By varying the dopant's position in the structure, we reveal that the UMR is mainly originating from the interaction between the magnetization and the surface spin-polarized carriers (not bulk carriers). Furthermore, from the magnetic field-, the angular rotation-, and the temperature-dependence, we highlight the correlation between the UMR effect and the magnetism in the structures. The large UMR versus current ratio in TI-based magnetic bilayers promises the easy readout in TI-based spintronic devices with two-terminal geometry.


Effects of clinical Pilates exercises in individuals with fibromyalgia: A randomized controlled trial.
This study aimed to investigate the effects of clinical Pilates exercises in patients with fibromyalgia (FM) and to compare the effects of one-to-one and group-based exercise methods. A total of 42 women (mean age, 50.90±7.78 years) with FM were included. The participants were randomly divided into 2 groups (one-to-one exercise, n=16; group-based exercise, n=26). Disease impact was evaluated with the FM Impact Questionnaire, functional status with the Health Assessment Questionnaire, anxiety with the Beck Anxiety Inventory, quality of life with short form-36, and biopsychosocial status with the Bilişsel Egzersiz Terapi Yaklaşımı-biopsychosocial questionnaire. All the evaluations were performed pre- and post-treatment. Clinical Pilates exercises were carried out 2 days a week for 6 weeks. When the pre- and post-treatment data were compared, significant improvement was seen in all parameters in the group-based exercise group; in the one-to-one exercise group, improvement was noted in disease impact, quality of life, and biopsychosocial status. When post-treatment data were compared, only disease impact was significant for the one-to-one exercise group. Effect size results were found to be moderate and high for both methods. For clinical Pilates exercise in FM, one-to-one method was suggested to have high disease impact and low quality of life, whereas group-based exercise method showed high anxiety.


The dark side of the sublime: Distinguishing a threat-based variant of awe.
Theoretical conceptualizations of awe suggest this emotion can be more positive or negative depending on specific appraisal processes. However, the emergent scientific study of awe rarely emphasizes its negative side, classifying it instead as a positive emotion. In the present research we tested whether there is a more negative variant of awe that arises in response to vast, complex stimuli that are threatening (e.g., tornadoes, terrorist attack, wrathful god). We discovered people do experience this type of awe with regularity (Studies 1 & 4) and that it differs from other variants of awe in terms of its underlying appraisals, subjective experience, physiological correlates, and consequences for well-being. Specifically, threat-based awe experiences were appraised as lower in self-control and certainty and higher in situational control than other awe experiences, and were characterized by greater feelings of fear (Studies 2a & 2b). Threat-based awe was associated with physiological indicators of increased sympathetic autonomic arousal, whereas positive awe was associated with indicators of increased parasympathetic arousal (Study 3). Positive awe experiences in daily life (Study 4) and in the lab (Study 5) led to greater momentary well-being (compared with no awe experience), whereas threat-based awe experiences did not. This effect was partially mediated by increased feelings of powerlessness during threat-based awe experiences. Together, these findings highlight a darker side of awe. (PsycINFO Database Record


Feature instructions improve face-matching accuracy.
Identity comparisons of photographs of unfamiliar faces are prone to error but important for applied settings, such as person identification at passport control. Finding techniques to improve face-matching accuracy is therefore an important contemporary research topic. This study investigated whether matching accuracy can be improved by instruction to attend to specific facial features. Experiment 1 showed that instruction to attend to the eyebrows enhanced matching accuracy for optimized same-day same-race face pairs but not for other-race faces. By contrast, accuracy was unaffected by instruction to attend to the eyes, and declined with instruction to attend to ears. Experiment 2 replicated the eyebrow-instruction improvement with a different set of same-race faces, comprising both optimized same-day and more challenging different-day face pairs. These findings suggest that instruction to attend to specific features can enhance face-matching accuracy, but feature selection is crucial and generalization across face sets may be limited.


Ultrasound-guided interstitial Nd: YAG laser treatment of voluminous hemangiomas and vascular malformations in 92 patients.
In many cases voluminous vascular anomalies of the head and neck region are still treated with conventional surgery, although neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy offers a valuable treatment alternative. Ninety-two patients with voluminous hemangiomas and vascular malformations were treated with interstitial Nd:YAG laser therapy (power density, 1300 to 3300 W/cm2), partly complemented by a noncontact-mode Nd:YAG laser light application (energy density, 1000 to 2500 J/cm2). The vascular tumors had a diameter of more than 3 cm in at least two dimensions. Treatment was carried out under ultrasound and manual control. Nearly 60% of the patients (n = 55) showed a complete clinical regression. Thirty-three patients (35.8%) had a partial regression and were satisfied with the treatment outcome. Four patients were treated unsuccessfully with the laser, and three of them subsequently underwent conventional surgery. Only nine of the 92 patients (9.8%) showed cosmetic or functional impairments. The results of this first consecutive series study with a retrospective clinical evaluation of the interstitial Nd:YAG laser therapy of voluminous hemangiomas and vascular malformations in a large patient group demonstrate a high effectiveness of this novel therapy modality.


Effects of transportation, transport medium and re-housing on Xenopus laevis (Daudin).
Understanding the immediate and longer-term effects of transportation and re-housing in a laboratory species is crucial in order to refine the transfer process, enable the optimal introduction of new animals to a novel environment and to provide a sufficient acclimatisation period before usage. Whilst consideration of animal welfare in most model vertebrate species has received attention, little quantitative evidence exists for the optimal care of the common laboratory amphibian Xenopus laevis. Techniques for the non-invasive welfare assessment of amphibians are also limited and here a non-invasive physiological assay was developed to investigate the impacts of transportation, transport medium and re-housing on X. laevis. First the impacts of transportation and transport medium (water, damp sponge or damp sphagnum moss) were investigated. Transportation caused an increase in water-borne corticosterone regardless of transport medium. Frogs transported in damp sphagnum moss also had a greater decrease in body mass in comparison to frogs not transported, suggesting that this is the least suitable transport medium for X. laevis. Next the prolonged impacts of transportation and re-housing were investigated. Frogs were transported between research facilities with different housing protocols. Samples were collected prior to and immediately following transportation, as well as 1 day, 7 days and 35 days after re-housing. Water-borne corticosterone increased following transportation and remained high for at least 7 days, decreasing to baseline levels by 35 days. Body mass decreased following transportation and remained lower than baseline levels across the entire 35 day observation period. These findings suggest the process of transportation and re-housing is stressful in this species. Together these findings have important relevance for both improving animal welfare and ensuring optimal and efficient scientific research.


AWSEM-IDP: A Coarse-Grained Force Field for Intrinsically Disordered Proteins.
The associative memory, water-mediated, structure and energy model (AWSEM) has been successfully used to study protein folding, binding, and aggregation problems. In this work, we introduce AWSEM-IDP, a new AWSEM branch for simulating intrinsically disordered proteins (IDPs), where the weights of the potentials determining secondary structure formation have been finely tuned, and a novel potential is introduced that helps to precisely control both the average extent of protein chain collapse and the chain's fluctuations in size. AWSEM-IDP can efficiently sample large conformational spaces, while retaining sufficient molecular accuracy to realistically model proteins. We applied this new model to two IDPs, demonstrating that AWSEM-IDP can reasonably well reproduce higher-resolution reference data, thus providing the foundation for a transferable IDP force field. Finally, we used thermodynamic perturbation theory to show that, in general, the conformational ensembles of IDPs are highly sensitive to fine-tuning of force field parameters.


Circumcision anesthesia: a study of nursing implications for dorsal penile nerve block.
To compare responses to circumcision between a group of unanesthetized newborn males and a group having dorsal penile nerve block (DPNB). Thirty newborn males who met the selection criteria were randomly assigned to the treatment (n = 20) or control group (n = 10). Oxygen perfusion, blood pressure, respiratory rate, heart rate, and cardiac rhythm were measured before, during, and after circumcision. In addition, observations were recorded during the procedure on crying duration and type, vomiting, gagging, breath holding, and jitteriness. Data were analyzed by t-test, Mann-Whitney analysis, and frequencies. There were no significant differences between groups except on physiologic and subjective stress reactions during circumcision. The unanesthetized subjects displayed stress reactions that have implications for nursing care.


Differential expression and hormonal regulation of alternatively spliced IGF-I mRNA transcripts in salmon.
Salmon have been shown to express alternatively spliced IGF-I mRNA transcripts coding for four different IGF-I prohormones. These transcripts, now designated Ea-1, Ea-2, Ea-3 and Ea-4, differ in size due to the inclusion of additional sequences in the E domain-coding region of the molecule. In this study, the tissue distribution and hormonal regulation of expression of alternatively spliced IGF-I mRNA transcripts were investigated in coho salmon. IGF-I mRNAs were detected by solution hybridization/RNase protection assay in all tissues examined. GH treatment significantly increased hepatic IGF-I mRNA content. Hepatic IGF-I mRNA levels were not influenced by prolactin or somatolactin. Heart, fat, brain, kidney, spleen and ovary IGF-I mRNA levels were not affected by GH, prolactin or somatolactin. Ea-1, Ea-3 and Ea-4 mRNA transcripts were detectable in the liver, and Ea-1 and Ea-3 levels increased dramatically in response to GH treatment, whereas the amount of Ea-4 mRNA was unchanged. Most non-hepatic tissues expressed only the Ea-4 transcript, and expression was not influenced by GH, prolactin or somatolactin. Ea-1 and Ea-3 transcripts were visible in gill samples from fish treated with GH. The ovaries of juvenile fish expressed Ea-1, Ea-2 and Ea-4. The amounts of these transcripts were not changed by gonadotrophin treatment. During smoltification of juvenile coho salmon, liver and gill IGF-I mRNA levels increased with increasing plasma GH and thyroxine concentrations. Muscle, brain and ovary IGF-I mRNA levels were unchanged during this period. These data suggest that the liver is a major site of IGF-I production in response to GH. Heart, fat, brain, kidney, spleen and ovary did not show increased IGF-I mRNA levels in response to GH treatment. GH and prolactin had inconsistent effects on muscle IGF-I mRNA levels. Somatolactin and a gonadotrophin preparation did not stimulate IGF-I expression in tissues of juvenile fish. Differences in tissue GH responsiveness can be partially explained by the expression of alternatively spliced IGF-I mRNAs. Of the four hepatic IGF-I mRNA transcripts, Ea-1 and Ea-3 are GH-responsive, while Ea-2 and Ea-4 are not. Most non-hepatic tissues express only the Ea-4 transcript, and IGF-I mRNA levels do not increase after GH treatment. The increased IGF-I mRNA levels observed in gill tissue during smoltification suggest that other factors, in addition to GH, may regulate IGF-I expression.(ABSTRACT TRUNCATED AT 400 WORDS)


Sexual dysfunction is correlated with tenderness in female fibromyalgia patients.
The purpose of the current study was to evaluate sexual dysfunction among female fibromyalgia syndrome (FMS) patients. Fifty female subjects were recruited and were asked to complete a questionnaire regarding sexual functioning. The control group included fifty-five healthy age-matched volunteers. The participants underwent a physical examination and tender point assessment was performed using manual palpation. All participants filled out the Arizona Sexual Experience Scale, which evaluates five areas of sexual functioning: sexual drive, sexual arousal, vaginal wetting, orgasm and sexual satisfaction. FMS patients had significantly lower scores on all five aspects of sexual function assessed. A positive correlation was observed between the sexual drive score, signifying a decrease in sexual drive, and the number of tender points documented on examination. Similarly, a positive correlation was observed between the sexual satisfaction scale (indicating decreasing levels of sexual satisfaction) and the number of tender points documented. A positive correlation was demonstrated between the sexual arousal and orgasmatic scales and between the tender point counts, indicating a decrease in sexual arousal and in orgasmatic function in correlation with an increasing number of tender points. The results of the current study indicate a multi-factorial sexual dysfunction among female FMS patients. All stages of sexual functioning, evaluated were significantly disturbed in comparison with the healthy controls. Physicians treating FMS patients should be aware of, and actively inquire about, sexual dysfunction as part of a multi-disciplinary evaluation of such patients.


Mapping Local Conformational Landscapes of Proteins in Solution.
The ability of proteins to adopt multiple conformational states is essential to their function, and elucidating the details of such diversity under physiological conditions has been a major challenge. Here we present a generalized method for mapping protein population landscapes by NMR spectroscopy. Experimental NOESY spectra are directly compared with a set of expectation spectra back-calculated across an arbitrary conformational space. Signal decomposition of the experimental spectrum then directly yields the relative populations of local conformational microstates. In this way, averaged descriptions of conformation can be eliminated. As the method quantitatively compares experimental and expectation spectra, it inherently delivers an R factor expressing how well structural models explain the input data. We demonstrate that our method extracts sufficient information from a single 3D NOESY experiment to perform initial model building, refinement, and validation, thus offering a complete de novo structure determination protocol.


Amyotrophic lateral sclerosis in a patient with systemic lupus erythematosus.
We report the case of a 48-year-old woman diagnosed as having systemic lupus erythematosus who developed a neurological disorder that finally resulted in amyotrophic lateral sclerosis. Although neurological disturbances caused by systemic lupus erythematosus are protean, there are no reported cases of amyotrophic lateral sclerosis associating with lupus disease. This association and the suspected autoimmune mechanism of pathogenesis in amyotrophic lateral sclerosis suggest that this might not be a simple coincidence but perhaps a causal relationship.


Vitamin D and the occurrence of depression: causal association or circumstantial evidence?
While recent laboratory-based studies have substantially advanced our understanding of the action of vitamin D in the brain, much is still unknown concerning how vitamin D relates to mood. The few epidemiological studies of vitamin D and depression have produced inconsistent results and generally have had substantial methodological limitations. Recent findings from a randomized trial suggest that high doses of supplemental vitamin D may improve mild depressive symptoms, but important questions persist concerning how vitamin D may affect monoamine function and hypothalamic-pituitary-adrenal axis response to stress, whether vitamin D supplementation can improve mood in individuals with moderate-to-severe depression, and whether vitamin D sufficiency is protective against incident depression and recurrence. At this time, it is premature to conclude that vitamin D status is related to the occurrence of depression. Additional prospective studies of this relationship are essential.


Transoral incisionless fundoplication: initial experience in patients referred to an integrated academic institution.
Transoral incisionless fundoplication is a new treatment for patients with gastroesophageal reflux disease. We present our initial experience with 10 patients undergoing this procedure with varying past surgical histories. All procedures were performed under general nasotracheal anesthesia. RAND-36 and Visual Analog Scale symptom scores were collected at pre and postoperative appointments for a mean of 9.2 months. The mean procedure time was 68 minutes. There were no intraoperative or postoperative complications. Patients with prior pancreaticoduodenectomy had observed reduced working space due to prior distal gastrectomy and required additional insufflation due to no pyloric resistance to insufflation of the small bowel. The patient with prior fundoplication required additional time and force for fastener penetration of the resultant scar from the partially disrupted fundoplication. All patients were discharged within 23 hours of the procedure. Throughout the follow-up period, patients reported gradual changes in medication requirements and symptom scores. There were no late complications. Transoral incisionless fundoplication is technically safe in well-selected patients including those with prior esophageal and gastric surgery.


Parathyroid hormone action on phosphate transport is inhibited by high osmolality.
Parathyroid hormone (PTH) produces rapid inhibition of Na(+)-phosphate cotransport, characterized by a decreased maximal rate of transport, and the inhibition is independent of de novo protein synthesis. The present study determined whether the action of PTH on Na(+)-phosphate cotransport is mediated, at least in part, by rapid endocytic internalization of Na(+)-phosphate cotransporters present in the plasma membrane. Horseradish peroxidase, a fluid-phase marker, was used to demonstrate the presence of endocytosis in opossum kidney (OK) epithelial cells in monolayer culture. An increase in medium osmolality to 500 mosmol/kgH2O, by addition of sucrose, produced 80% inhibition of endocytosis within 1 h. The inhibition was reversed on returning the cells to normal medium. Incubation of OK cell monolayers with PTH (10(-8) M) for 3 h at normal osmolality (281 mosmol/kgH2O) inhibited Na(+)-phosphate cotransport (4 min uptakes) by 56-67%. In hyperosmolar medium (513 mosmol/kgH2O), when endocytosis was inhibited, PTH inhibited Na(+)-phosphate cotransport by only 25-39%, a change that was significantly different from the inhibition in normal medium. Hyperosomolality had no effect on PTH inhibition of Na(+)-H+ exchange or on PTH stimulation of intracellular adenosine 3',5'-cyclic monophosphate. We conclude that the full inhibitory action of PTH on Na(+)-phosphate cotransport may require an intact endocytic mechanism.


Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.
Transferrin receptor 2 (TFR2) is a transmembrane protein expressed mainly in hepatocytes and in developing erythroid cells and is an important focal point in systemic iron regulation. Loss of TFR2 function results in a rare form of the iron-overload disease hereditary hemochromatosis. Although TFR2 in the liver has been shown to be important for regulating iron homeostasis in the body, TFR2's function in erythroid progenitors remains controversial. In this report, we analyzed TFR2-deficient mice in the presence or absence of iron overload to distinguish between the effects caused by a high iron load and those caused by loss of TFR2 function. Analysis of bone marrow from TFR2-deficient mice revealed a reduction in the early burst-forming unit-erythroid and an expansion of late-stage erythroblasts that was independent of iron overload. Spleens of TFR2-deficient mice displayed an increase in colony-forming unit-erythroid progenitors and in all erythroblast populations regardless of iron overload. This expansion of the erythroid compartment coincided with increased erythroferrone (ERFE) expression and serum erythropoietin (EPO) levels. Rescue of hepatic TFR2 expression normalized hepcidin expression and the total cell count of the bone marrow and spleen, but it had no effect on erythroid progenitor frequency. On the basis of these results, we propose a model of TFR2's function in murine erythropoiesis, indicating that deficiency in this receptor is associated with increased erythroid development and expression of EPO and ERFE in extrahepatic tissues independent of TFR's role in the liver.


IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.
Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM) recovered from the lungs of mice undergoing cecal ligation and puncture (CLP) display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3) and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/-) mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.


Indian and African plate motions driven by the push force of the Réunion plume head.
Mantle plumes are thought to play an important part in the Earth's tectonics, yet it has been difficult to isolate the effect that plumes have on plate motions. Here we analyse the plate motions involved in two apparently disparate events--the unusually rapid motion of India between 67 and 52 million years ago and a contemporaneous, transitory slowing of Africa's motion--and show that the events are coupled, with the common element being the position of the Indian and African plates relative to the location of the Réunion plume head. The synchroneity of these events suggests that they were both driven by the force of the Réunion plume head. The recognition of this plume force has substantial tectonic implications: the speed-up and slowdown of India, the possible cessation of convergence between Africa and Eurasia in the Palaeocene epoch and the enigmatic bends of the fracture zones on the Southwest Indian Ridge can all be attributed to the Réunion plume.


Formulating diets based on digestible calcium instead of total calcium does not affect growth performance or carcass characteristics, but microbial phytase ameliorates bone resorption caused by low calcium in diets fed to pigs from 11 to 130 kg.
An experiment was conducted to test the hypothesis that the requirement for Ca expressed as a ratio between standardized total tract digestible (STTD) Ca and STTD P obtained in short-term experiments may be applied to pigs fed diets without or with microbial phytase from 11 to 130 kg. In a 5-phase program, 160 pigs (body weight: 11.2 ± 1.8 kg) were randomly allotted to 32 pens and 4 corn-soybean meal-based diets in a 2 × 2 factorial design with 2 diet formulation principles (total Ca or STTD Ca), and 2 phytase inclusion levels (0 or 500 units/kg of feed) assuming phytase released 0.11% STTD P and 0.16% total Ca. The STTD Ca:STTD P ratios were 1.40:1, 1.35:1, 1.25:1, 1.18:1, and 1.10:1 for phases 1 to 5, and STTD P was at the requirement. Weights of pigs and feed left in feeders were recorded at the end of each phase. At the conclusion of phase 1 (day 24), 1 pig per pen was euthanized and a blood sample and the right femur were collected. At the end of phases 2 to 5, a blood sample was collected from the same pig in each pen. At the conclusion of the experiment (day 126), the right femur of 1 pig per pen was collected and carcass characteristics from this pig were measured. No interactions were observed between diet formulation principle and phytase inclusion for growth performance in any phase and no differences among treatments were observed for overall growth performance. Plasma Ca and P and bone ash at the end of phase 1 were also not influenced by dietary treatments. However, on day 126, pigs fed nonphytase diets formulated based on total Ca had greater bone ash than pigs fed STTD Ca-based diets, but if phytase was used, no differences were observed between the 2 formulation principles (interaction P < 0.05). At the end of phases 2 and 3, pigs fed diets without phytase had greater (P < 0.05) plasma P than pigs fed diets with phytase, but no differences were observed at the end of phases 4 and 5. A negative quadratic effect (P < 0.05) of phase (2 to 5) on the concentration of plasma Ca was observed, whereas plasma P increased (quadratic; P < 0.05) from phases 2 to 5. However, there was no interaction or effect of diet formulation principle or phytase inclusion on any carcass characteristics measured. In conclusion, STTD Ca to STTD P ratios can be used in diet formulation for growing-finishing pigs without affecting growth performance or carcass characteristics and phytase inclusion ameliorates bone resorption caused by low dietary Ca and P.


Shallow Groundwater Conveyance of Geologically Derived Contaminants to Urban Creeks in Southern California.
In California alone, there are currently over 200 instances on the EPA's list of impaired water bodies with unknown sources of excessive salinity or trace contaminants. This investigation focuses on Orange County, CA, a region that has undergone extensive hydrological modification, relies heavily on imported water for municipal supply, and has come under regulatory scrutiny for elevated TDS, sulfate, Cd, Ni, and Se. A survey of shallow groundwater weeps and springs, discharging directly to urban creeks, reveals high concentrations of TDS, sulfate, Cd, Ni, Zn, Cu, and Se that are often far in excess of water quality standards. Isotopic (δ(34)S and δ(18)O) and geochemical evidence indicate that the source of sulfate and TDS is weathering of sulfide minerals in the Capistrano Formation marine mudstone and dissolution of secondary minerals formed during past periods of sulfide oxidation, rather than anthropogenic inputs. The relative availability of carbonate minerals along the flow path appears to control pH, which then influences trace metal mobility to surface waters. Stable isotopes of H2O indicate that despite widespread use of imported water, meteoric recharge dominates shallow groundwater inputs with municipal sources contributing only 13-29% of discharge. These findings highlight the importance of understanding the hydrogeological setting to properly apportion contaminant sources and conveyances.


Spectral envelope coding in cat primary auditory cortex: linear and non-linear effects of stimulus characteristics.
Electrophysiological studies in mammal primary auditory cortex have demonstrated neuronal tuning and cortical spatial organization based upon spectral and temporal qualities of the stimulus including: its frequency, intensity, amplitude modulation and frequency modulation. Although communication and other behaviourally relevant sounds are usually complex, most response characterizations have used tonal stimuli. To better understand the mechanisms necessary to process complex sounds, we investigated neuronal responses to a specific class of broadband stimuli, auditory gratings or ripple stimuli, and compared the responses with single tone responses. Ripple stimuli consisted of 150-200 frequency components with the intensity of each component adjusted such that the envelope of the frequency spectrum is sinusoidal. It has been demonstrated that neurons are tuned to specific characteristics of those ripple stimulus including the intensity, the spacing of the peaks, and the location of the peaks and valleys (C. E. Schreiner and B. M. Calhoun, Auditory Neurosci., 1994; 1: 39-61). Although previous results showed that neuronal response strength varied with the intensity and the fundamental frequency of the stimulus, it is shown here that the relative response to different ripple spacings remains essentially constant with changes in the intensity and the fundamental frequency. These findings support a close relationship between pure-tone receptive fields and ripple transfer functions. However, variations of other stimulus characteristics, such as spectral modulation depth, result in non-linear alterations in the ripple transformation. The processing between the basilar membrane and the primary auditory cortex of broadband stimuli appears generally to be non-linear, although specific stimulus qualities, including the phase of the spectral envelope, are processed in a nearly linear manner.


Development of the international thymic malignancy interest group international database: an unprecedented resource for the study of a rare group of tumors.
Our knowledge of thymic malignancies has largely been derived from small, single-institution series. Recognition of the need for broad collaboration led to the creation of the International Thymic Malignancy Interest Group (ITMIG) and the development of a large, centralized database to advance knowledge of these rare tumors. A multidisciplinary Database Committee was convened to define a common set of data elements a priori. Retrospective data were solicited from ITMIG members and collated using standardized fields. Patients with thymoma, thymic carcinoma, or thymic carcinoid were included. Over a 6-month period, 47 institutions spanning 15 countries contributed a total of 6097 cases (mean, 129 [range, 10-1209]). The sex distribution was equal for thymomas, but there was a greater proportion of men with thymic carcinoma and thymic carcinoid (p < 0.0001). Nearly all cases (99%) were treated surgically. WHO type B2 was the most frequent histologic classification among thymomas, whereas squamous was the most common among thymic carcinomas. In total, 38% of patients with thymoma had myasthenia gravis compared with less than or equal to 5% for thymic carcinoma and thymic carcinoid. Median overall survival was 18.9 years (95% confidence interval [CI], 17.4-20.3) for thymoma, 6.8 years (95% CI, 5.5-7.9) for thymic carcinoma, and 7.5 years (95% CI, 6.5-8.5) for thymic carcinoid. The rapid creation of the ITMIG database demonstrates the feasibility of international collaboration for this rare set of malignancies and attests to the engagement of its membership. This database represents the largest collective data set ever assembled and provides an unprecedented resource for research of these tumors.


Contributions of Lateral and Orbital Frontal Regions to Abstract Rule Acquisition and Reversal in Monkeys.
The ability to learn and follow abstract rules relies on intact prefrontal regions including the lateral prefrontal cortex (LPFC) and the orbitofrontal cortex (OFC). Here, we investigate the specific roles of these brain regions in learning rules that depend critically on the formation of abstract concepts as opposed to simpler input-output associations. To this aim, we tested monkeys with bilateral removals of either LPFC or OFC on a rapidly learned task requiring the formation of the abstract concept of same vs. different. While monkeys with OFC removals were significantly slower than controls at both acquiring and reversing the concept-based rule, monkeys with LPFC removals were not impaired in acquiring the task, but were significantly slower at rule reversal. Neither group was impaired in the acquisition or reversal of a delayed visual cue-outcome association task without a concept-based rule. These results suggest that OFC is essential for the implementation of a concept-based rule, whereas LPFC seems essential for its modification once established.


Phenotypic variability in Townes-Brocks syndrome.
This is a report on a child with sensorineural deafness, imperforate anus with rectovaginal fistula, hypoplastic thumb, and congenital heart defect. This pattern of congenital anomalies is similar to that described in patients with the Townes-Brocks syndrome, although the present patient has characteristics that have not been reported previously in this syndrome. It is proposed that the clinical spectrum of the Townes-Brocks syndrome must be extended to include congenital heart defect, auricular changes differing from those previously described, and anomalies of other internal organs. The syndrome is an autosomal dominant trait. The present case may represent a de novo mutation.


Combined Na(+)/Ca(2+) exchanger and L-type calcium channel block as a potential strategy to suppress arrhythmias and maintain ventricular function.
L-type calcium channel (LTCC) and Na(+)/Ca(2+) exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate calcium and contractility. Although LTCC inhibition is negative inotropic, NCX inhibition has the opposite effect. Combined block may, therefore, offer an advantage for hemodynamics and antiarrhythmic efficiency, particularly in diseased hearts. In a model of proarrhythmia, the dog with chronic atrioventricular block, we investigated whether combined inhibition of NCX and LTCC with SEA-0400 is effective against dofetilide-induced torsade de pointes arrhythmias (TdP), while maintaining calcium homeostasis and hemodynamics. Left ventricular pressure (LVP) and ECG were monitored during infusion of SEA-0400 and verapamil in anesthetized dogs. Different doses were tested against dofetilide-induced TdP in chronic atrioventricular block dogs. In ventricular myocytes, effects of SEA-0400 were tested on action potentials, calcium transients, and early afterdepolarizations. In cardiomyocytes, SEA-0400 (1 μmol/L) blocked 66±3% of outward NCX, 50±2% of inward NCX, and 33±9% of LTCC current. SEA-0400 had no effect on systolic calcium, but slowed relaxation, despite action potential shortening, and increased diastolic calcium. SEA-0400 stabilized dofetilide-induced lability of repolarization and suppressed early afterdepolarizations. In vivo, SEA-0400 (0.4 and 0.8 mg/kg) had no effect on left ventricular pressure and suppressed dofetilide-induced TdPs dose dependently. Verapamil (0.3 mg/kg) also inhibited TdP, but caused a 15±8% drop of left ventricular pressure. A lower dose of verapamil without effects on left ventricular pressure (0.06 mg/kg) was not antiarrhythmic. In chronic atrioventricular block dogs, SEA-0400 treatment is effective against TdP. Unlike specific inhibition of LTCC, combined NCX and LTCC inhibition has no negative effects on cardiac hemodynamics.


Who should teach medical students surgery?
Medical schools are undergoing major curricular reform, partly in attempts to increase the number of graduates pursuing careers in the generalist disciplines. These reforms have often resulted in a shortening of the surgery clerkship, decreasing students' experiences in several domains important to the generalist. A seven-question survey of clerkship directors of US medical schools was administered to measure the magnitude of curriculum change during the past 5 years affecting the surgery and family practice clerkships. The survey also addressed attitudes about the purpose of the surgery clerkship. There was an 80% (103 of 129) response rate. Between 1989 and 1994, surgery clerkships decreased on average from 11 to 10.2 weeks (P <0.05) while family practice clerkships increased from 4.2 to 6.8 weeks (P <0.05). Ninety-one percent of clerkship directors felt the primary goal of the clerkship should be to train generalists. The length of the surgery clerkship has decreased at several institutions. In order to ensure an appropriate educational experience for medical students, surgeons must participate actively in curriculum reform within medical schools and highlight their unique role in training generalists.


"Vitelliform" lesions in adults.
Symmetric yellow ("vitelliform") foveal lesions are occasionally seen in adults. These patients should not be diagnosed as having Best's vitelliform dystrophy unless the EOG light/dark ratio is severely depressed and the family history reveals a dominantly-inherited maculopathy. Adult vitelliform lesions may vary in size from one third to several disc diameters, and may be present with or without drusen. More than one etiology may be involved, but many of these lesions seem to be degenerative changes related to drusen or pigment epithelial detachment.


The molecular basis of activity-induced muscle injury in Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is the most common of the human muscular dystrophies, affecting approximately 1 in 3500 boys. Most DMD patients die in their late teens or early twenties due to involvement of the diaphragm and other respiratory muscles by the disease. The primary abnormality in DMD is an absence of dystrophin, a 427 kd protein normally found at the cytoplasmic face of the muscle cell surface membrane. Based upon the predicted structure and location of the protein, it has been proposed that dystrophin plays an important role in providing mechanical reinforcement to the sarcolemmal membrane of muscle fibers. Therefore, dystrophin could help to protect muscle fibers from potentially damaging tissue stresses developed during muscle contraction. In the present paper, the nature of mechanical stresses placed upon myofibers during various forms of muscle contraction are reviewed, along with current lines of evidence supporting a critical role for dystrophin as a subsarcolemmal membrane-stabilizing protein in this setting. In addition, the implications of these findings for exercise programs and other potential forms of therapy in DMD are discussed.


Sephadex filtration and human serum albumin gradients do not select spermatozoa by sex chromosome: a fluorescent in-situ hybridization study.
Fluorescent in-situ hybridization (FISH) of decondensed sperm nuclei has been used directly to evaluate the enrichment efficiency of human sperm separation using Sephadex gel filtration and human serum albumin (HSA) gradients. Control and processed spermatozoa were fixed and their nuclei decondensed. In-situ hybridization was carried out with a Y-specific DNA probe (DYZ1). Sephadex filtration yielded 52.5% Y-chromosome-bearing spermatozoa, HSA separation resulted in 49.4% Y-chromosome-bearing spermatozoa and in the untreated control sample the percentage of Y spermatozoa was 49.3%. Statistical analysis revealed no significant differences between the selection methods employed and the controls, and no real enrichment for X- or Y-bearing spermatozoa was detected for any of the selection methods assayed. The usefulness of the protocols reported for selection of spermatozoa by sex chromosome in couples at risk for X-linked diseases is discussed.


Monitoring of seasonal variation in the water quality of Ubu river in Ekwusigo and Nnewi local government areas of Anambra State, Nigeria.
Investigation of the water quality of the Ubu river has been carried out. The upstream course of the river is slightly acidic (pH 5.45 +/- 0.23), and the acidity decreases along the lower courses of the river. Turbidity, surfactant, and iron content parameters of the river increased during the wet season, and these changes have been attributed to inputs from flood, leachates of soil erosion, and storm water runoff discharged into the river in increased quantities during the season. Concentrations of some metals were found to increase during the dry season because of absence of dilution of the river by storm water runoff. Most water quality parameters are within World Health Organization acceptable limits set for potable water, and they include most of the cationic and anionic constituents. Although there is no hydrocarbon or metal ion pollution, potability is reduced along the mid to downstream courses of the river by unacceptable levels of turbidity, surfactant concentration, and iron content, particularly during the wet season.


Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle.
The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules.


Causal evidence for the role of the sensory visual cortex in visual short-term memory maintenance.
The role of the sensory visual cortex during visual short-term memory (VSTM) remains controversial. This controversy is possibly due to methodological issues in previous attempts to investigate the effects of transcranial magnetic stimulation (TMS) on VSTM. The aim of this study was to use TMS, while covering previous methodological deficits. Sixty-four young adults were recruited to participate in two experiments (Experiment 1: n = 36; Experiment 2: n = 28) using a VSTM orientation change-detection task under TMS. Monocular vision was ensured using red-blue goggles combined with red-blue stimuli. Double-pulse TMS was delivered at different times (Experiment 1: 0, 200 or 1000 ms; Experiment 2: 200, 1000 ms) during a 2 s maintenance phase, on one side of the occipital hemisphere. In Experiment 2, a sham TMS condition was introduced. Decreased detection sensitivity (d') in the ipsilateral occipital hemisphere to visual hemifield, and in the real TMS (compared with sham TMS) condition indicated inhibitory TMS effects, and thus, a causal involvement of the sensory visual cortex during early (200 ms) and late (1000 ms) maintenance in VSTM. These findings are aligned with sensory recruitment, which proposes that both perceptual and memory processes rely upon the same neural substrates in the sensory visual cortex. The methods used in this study were preregistered and had received in-principle acceptance on 6 June 2022 (Stage 1 protocol can be found in: https://doi.org/10.17605/OSF.IO/EMPDT).


Cotton pillows: A novel field method for assessment of thirdhand smoke pollution.
Thirdhand smoke (THS) is the residue left behind by secondhand smoke (SHS) that accumulates in indoor environments. THS chemicals can persist long after smoking has ceased and can re-emit semivolatile compounds back into the air. Measuring tobacco smoke pollution in real-world field setting can be technically complex, expensive, and intrusive. This study placed pillows in homes of former smokers and examined how much nicotine adsorbed to them over a three-week period. Organic cotton pillows were placed in the homes of 8 former smokers following the first week after verified smoking cessation until the fourth week. For comparison, pillows were also placed in 4 homes of nonsmokers. Nicotine concentrations were determined in the pillow case, fabric, and cotton filling, using isotope-dilution liquid chromatography tandem mass spectrometry. Cotton pillows placed in homes of former smokers absorbed on average 21.5 μg of nicotine. Nicotine concentration per gram of material significantly differed between pillow components (p < 0.001) and was highest for the pillow case (257 ng/g), followed by the pillow fabric (97 ng/g), and the pillow filling (17 ng/g). Nicotine levels in pillows placed in nonsmokers' homes did not differ from laboratory blanks (p > 0.40), or between pillow components (p > 0.40). In the absence of any smoking activity, cotton pillows absorbed significant amounts of nicotine emitted from THS reservoirs in the homes of former smokers. Given the much higher concentrations of SHS in the homes of active smokers, fabrics found throughout the home of a smoker are likely to store a substantial mass of tobacco smoke toxicants. Cotton pillows present a novel method that could be of interest to researchers requiring robust and unobtrusive methods to examine tobacco smoke pollution in real-world field settings.