The efficacy of potassium salts as agents for treating dentin hypersensitivity.
Formulations containing potassium salts (e.g., chloride, nitrate, citrate, oxalate) are widely used for treating dentin hypersensitivity (DH). The purpose of this review was to evaluate evidence for the clinical efficacy of potassium salts in reducing DH and also to consider the biologic basis for any effects. Literature searches were used to identify reports of clinical trials of potassium-containing preparations. Searches revealed 3 trials of potassium nitrate solutions or gels; 2 trials of mouthwashes containing potassium nitrate or citrate; 6 trials of potassium oxalates; and 16 double-blind randomized trials of toothpastes containing potassium nitrate, chloride, or citrate. The toothpaste studies provided quantitative data on treatment effects. These outcome measures were expressed as percentage reductions in sensitivity to cold air and mechanical stimulation and the patients' subjective reports. Trials of topically applied solutions yielded inconsistent results. Potassium-containing mouthwashes produced significant reductions in sensitivity. All potassium-containing toothpastes produced a significant reduction in sensitivity to tactile and air stimuli, as well as subjectively reported sensitivity. In most studies, the active agent (potassium) was superior to the minus-active control (placebo), but a few of the more recent trials have demonstrated significant placebo effects. It is postulated that potassium ions released from toothpastes diffuse along the dentinal tubules to inactivate intradental nerves. However, this principle has never been confirmed in intact human teeth. The mechanism of the desensitizing effects of potassium-containing toothpastes remains uncertain at present.


FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy.
Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcalphaRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcalphaRI-directed bispecific antibodies confirmed FcalphaRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcalphaRI x HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR-3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF-primed blood. Furthermore, bispecific antibodies, directed to FcalphaRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcalphaRI on neutrophils. They suggest FcalphaRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.


Clinical relevance of novel Otarine herpesvirus-3 in California sea lions (Zalophus californianus): lymphoma, esophageal ulcers, and strandings.
Herpesviruses have been recognized in marine mammals, but their clinical relevance is not always easy to assess. A novel otarine herpesvirus-3 (OtHV3) was detected in a geriatric California sea lion (Zalophus californianus), and using a newly developed quantitative PCR assay paired with histology, OtHV3 was associated with esophageal ulcers and B cell lymphoblastic lymphoma in this animal. The prevalence and quantities of OtHV3 were then determined among buffy coats from 87 stranded and managed collection sea lions. Stranded sea lions had a higher prevalence of OtHV3 compared to managed collection sea lions (34.9% versus 12.5%; p = 0.04), and among the stranded sea lions, yearlings were most likely to be positive. Future epidemiological studies comparing the presence and viral loads of OtHV3 among a larger population of California sea lions with and without lymphoid neoplasia or esophageal ulcers would help elucidate the relevance of OtHV3-associated pathologies to these groups.


Cognitive control and lexical access in younger and older bilinguals.
Ninety-six participants, who were younger (20 years) or older (68 years) adults and either monolingual or bilingual, completed tasks assessing working memory, lexical retrieval, and executive control. Younger participants performed most of the tasks better than older participants, confirming the effect of aging on these processes. The effect of language group was different for each type of task: Monolinguals and bilinguals performed similarly on working memory tasks, monolinguals performed better on lexical retrieval tasks, and bilinguals performed better on executive control tasks, with some evidence for larger language group differences in older participants on the executive control tasks. These results replicate findings from individual studies obtained using only 1 type of task and different participants. The confirmation of this pattern in the same participants is discussed in terms of a suggested explanation of how the need to manage 2 language systems leads to these different outcomes for cognitive and linguistic functions.


Comparison of pleurodesis by erythromycin, talc, doxycycline, and diazepam in a rabbit model.
Patients with malignant pleural effusion, recurrent spontaneous pneumothorax, and recurrent benign pleural effusions may have significant relief of their symptoms with chemical pleurodesis. Talc is the most frequently used chemical sclerosant; however, it has been known to induce Adult Respiratory Distress Syndrome (ARDS). Other agents such as doxycycline and erythromycin have documented efficacy as sclerosing agents in the pleura, but they are not in widespread clinical use and have significant documented adverse reactions. Diazepam may represent a potential sclerosing agent in the pleura, because of its local inflammatory profile in other tissues. Overall, 33 adult New Zealand White rabbits (Oryctolagus cuniculus) were randomized to 5 treatment groups. Each group received an intrapleural injection via 5 Fr silastic tubes of one of the following agents: 35-mg/kg erythromycin in 2 ml of saline, 70-mg/kg talc in 2 ml of saline, 10-mg/kg doxycycline in 2 ml of saline, 0.4-mg/kg diazepam in 2 ml of saline, or 2 ml of saline as a control. The animals were euthanized and necropsied 30 days after injection. The pleural surfaces were assessed for macroscopic and microscopic evidence of surrounding inflammation and fibrosis. Doxycycline resulted in severe pleural inflammation and fibrosis with pulmonary hemorrhage, whereas talc-treated animals had less effective fibrosis and granulomas. A trend toward higher mortality occurred in doxycycline-treated animals. Erythromycin demonstrated similar fibrosis (p=0.487) to doxycycline and had less inflammation (p<0.001). Diazepam treatment had little effect in the pleural cavity. This study demonstrates that erythromycin may be the ideal sclerosing agent. It had the advantage of maximal fibrosis with minimal inflammation. Although doxycycline was the most potent pleural sclerosant, it caused severe local tissue damage. Talc treatment resulted in only mild fibrosis, and diazepam was ineffective.


Exposure of C57BL/6J mice to long photoperiod during early life stages increases body weight and alters plasma metabolomic profiles in adulthood.
Perinatal photoperiod is an important regulator of physiological phenotype in adulthood. In this study, we demonstrated that postnatal (0-4 weeks old) exposure of C57BL/6J mice to long photoperiod induced persistent increase in body weight until adulthood, compared with the mice maintained under short photoperiod. The expression of peroxisome proliferator-activated receptor δ, a gene involved in fatty acid metabolism, was decreased in 10-week-old mice exposed to long photoperiod during 0-4 or 4-8 weeks of age. Plasma metabolomic profiles of adult mice exposed to a long photoperiod during the postnatal period (0-4 LD) were compared to those in the mice exposed to short photoperiod during the same period. Cluster analysis revealed that both carbon metabolic pathway and nucleic acid pathway were altered by the postnatal photoperiod. Levels of metabolites involved in glycolysis were significantly upregulated in 0-4 LD, suggesting that the mice in 0-4 LD use the glycolytic pathway for energy expenditure rather than the fatty acid oxidation pathway. In addition, the mice in 0-4 LD exhibited high levels of purine metabolites, which have a role in neuroprotection. In conclusion, postnatal exposure of C57BL/6J mice to long photoperiod induces increase in body weight and various changes in plasma metabolic profiles during adulthood.


Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms.
The dynamic patterns of pituitary-adrenocortical and sympatho-adrenal hormone responses to insulin hypoglycemia as well as the relative importance of central vs. peripheral control of hypoglycemia-induced ACTH secretion were evaluated. In conscious rats bearing indwelling cannulae, the changes in hormone concentrations after insulin injection were dependent on the changes in blood glucose levels with respect to both time course and magnitude. ACTH, corticosterone, epinephrine, and norepinephrine levels were found to be maximal at 60 min after 2.5 IU kg-1 insulin injected ip, whereas earlier (20 min) but smaller increases were obtained in response to 0.5 IU kg-1 insulin injected iv. In rats 6-7 days after lesions of the medial basal hypothalamus (MBH), the rise of ACTH during insulin hypoglycemia was markedly inhibited and corticosterone levels were significantly reduced. Simultaneously, the hypoglycemia-induced increase in plasma epinephrine was unchanged and that in plasma norepinephrine was significantly enhanced in rats with the MBH destroyed. The beta-adrenoreceptor blocker propranolol did not inhibit ACTH and corticosterone responses to hypoglycemia in either sham-operated or MBH-lesioned animals. We conclude that the main factors triggering ACTH release during insulin-induced hypoglycemia are of central rather than peripheral origin. The high concentrations of circulating catecholamines occurring during insulin hypoglycemia are not responsible for pituitary-adrenocortical activation by direct, beta-adrenoreceptor mediated action at the pituitary level.


Visualization of blebs using anterior-segment optical coherence tomography after glaucoma drainage implant surgery.
The current study investigated the internal structure of blebs using anterior-segment optical coherence tomography (AS-OCT) in patients who had undergone Ahmed glaucoma valve (AGV) (New World Medical Inc, Rancho Cucamonga, CA) implantation and compared the differences between successful and failed surgeries. Cross-sectional, observational study. A total of 76 patients who had undergone AGV implantation. The blebs after AGV implantation were examined using AS-OCT. The relationship between intraocular pressure (IOP) or the number of glaucoma medications and intrableb parameters was evaluated. Success was defined as IOP ≤ 21 mmHg with a maximum of 2 glaucoma medications, and the remaining cases were assigned to the "failed surgery group." Logistic regression was used to determine the predictive value of various bleb parameters measured by AS-OCT for bleb success. The bleb wall thickness (minimum and maximum) and the reflectivity of the bleb wall (mean, modal value, minimum, and maximum). Blebs from 46 successful (60.5%) and 30 failed (39.5%) AGV implantation surgeries were analyzed. The AS-OCT imaging of the intrableb configuration revealed a relatively regular surface and a homogeneous and hyperreflective bleb wall. The maximum and minimum bleb wall thicknesses were significantly different between the 2 groups (P<0.001, P<0.005). No significant differences were observed between the 2 groups in mean, modal, maximum, or minimum reflectivity of the bleb wall. The maximum and minimum bleb wall thicknesses were significantly correlated with the postoperative maximum IOP (r = 0.402, P<0.001; r = 0.280, P = 0.014). The maximum and minimum bleb wall thicknesses showed a significant correlation with the number of postoperative glaucoma eye drops (r = 0.452, P<0.001; r = 0.327, P = 0.004). Maximum bleb wall thickness was significantly associated with the success of AGV surgery by multivariate analysis (P<0.001). Anterior-segment OCT can be used for bleb imaging after glaucoma valve implantation. The AS-OCT results revealed that the maximum bleb wall was significantly thinner in successful AGV implant surgeries compared with unsuccessful AGV implant surgeries. This technique may facilitate the investigation of surgical outcomes and pathogenesis in patients receiving glaucoma valve implants. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


[Acute renal failure due to RAAS-inhibitors combined with dehydration].
Two men (61 and 81 years old) with mild impaired kidney function developed acute renal failure due to dehydration combined with the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS). After rehydration, correction of hyperkalaemia and stopping RAAS-inhibition and diuretics, they recovered completely. Many patients using RAAS-inhibitors have impaired renal function. In the case of dehydration due to gastroenteritis or prolonged fever they risk developing acute renal failure. The high risk groups are elderly patients, patients with atherosclerosis or heart failure and those with co-medication of diuretics or NSAIDs. The underlying mechanism is that the normal pathways to protect kidney perfusion in case of hypovolaemia are blocked by the use of RAAS-inhibitors or NSAIDs. In the case of dehydration in patients with chronic kidney disease using RAAS-inhibitors, serum creatinine and potassium levels should be monitored. Temporary discontinuation of RAAS-inhibitors or diuretics is often necessary.


Associations between child disabilities and caregiver discipline and violence in low- and middle-income countries.
Using nationally representative samples of 45,964 two- to nine-year-old children and their primary caregivers in 17 developing countries, this study examined the relations between children's cognitive, language, sensory, and motor disabilities and caregivers' use of discipline and violence. Primary caregivers reported on their child's disabilities and whether they or anyone in their household had used nonviolent discipline, psychological aggression, and physical violence toward the target child and believed that using corporal punishment is necessary. Logistic regression analyses supported the hypothesis that children with disabilities are treated more harshly than children without disabilities. The findings suggest that policies and interventions are needed to work toward the United Nations' goals of ensuring that children with disabilities are protected from abuse and violence.


Variability of inguinal hernia surgical technique: A survey of North American pediatric surgeons.
The tradition of learning from mentors is a unique aspect of surgical training. With this in mind, the authors sought to document our roots by analyzing the technical variability of how pediatric surgeons perform their most frequent operation, the inguinal hernia, and compare these data with the original description by Drs William Ladd and Robert Gross. A survey compiling the operative steps of an inguinal hernia repair as well as several key clinical situations involving hernias was mailed to pediatric surgeons in North America. These results then were compared with the original inguinal hernia technique by Drs Ladd and Gross. Results are recorded as the percent who concurred with their original description. A total of 447 of 640 (70%) surveys were returned. Geneologic data show that 81% of surgeons' hernia lineage could be traced to Drs Ladd and Gross. When compared with all respondents, Drs Ladd and Gross' hernia repair steps included incising Scarpa's fascia (61%), defining the external ring by pushing down with retractors (34%), incising the external oblique with scissors (18%), identifying the ileoinguinal nerve (81%), cleaning one underside of the external oblique (22%), bluntly spreading the cremasteric fibers (90%), elevating the sac with sharp dissection of the vessels (53%), opening the sac and inserting the forefinger into it (0%), bluntly dissecting the sac with forefinger and gauze (0%), ligating the sac with single ligature (22%) without twisting it (34%), leaving the distal sac untouched other than to drain fluid (78%), not inspecting the testicle (79%), performing a formal floor repair bringing external and internal oblique down to Poupart's ligament (10%), tightening the internal ring in both boys and girls (19% and 41%), using no local anesthetic (14%), closing Scarpa's fascia (94%), closing the skin with interrupted subcuticular sutures (49%), covering the incision with Collodion (48%), using the Stiles' dressing (0%), and only exploring the contralateral side if a hernia is suggested by history or physical examination (87% for boys, 60% for girls). The various other options surgeons use for their technique and their management decisions also are described. There is significant variability in the way pediatric surgeons perform inguinal herniorraphy. The differences from Drs Ladd and Gross' original description likely result from evolving techniques, experiences, and analysis of outcomes.


Public health and the radio frequency radiation emitted by cellphone technology, smart meters and WiFi.
This paper argues that the prevailing official narrative in New Zealand concerning the relationship between public health and the radio frequency emissions (RF) from cellphone technology, WiFi and electricity smart meters is scientifically and ethically flawed. The main regulatory document in the area, NZS2772.1:1999, is 20 years out of date and ignores existing laboratory evidence disproving its core assumption that the only biological effect of non-ionising radiation is tissue heating. This and further laboratory evidence for harmful effects of RF continues to be ignored, nominally on the contradictory grounds that (a) cellphone manufacturers say their products now emit less RF than early models, so early lab studies exposed tissue to RF levels higher than those now relevant (b) given the lack of actual data on population exposures either then or now, all laboratory evidence is unconvincing anyway. The offical narrative further opines that since there exist both laboratory and epidemiological studies concluding that RF is not biologically harmful, as well as studies concluding that RF is harmful, the appropriate response is to count up the number on each side, declare the "weight of evidence" to be such that "causation is not proven" and, pending unspecified further studies, continue exposing to unmonitored levels of RF the entire population of the country, none of whom has given informed consent to participate in the experiment. This approach is obviously unethical. It is also unacceptable scientifically. First, the algebraic model is flawed: studies that do find a harmful effect of RF are not invalidated by differently constructed studies that fail to find an effect. Secondly, while causation is relatively easy to study in the laboratory, it is difficult if not impossible to prove epidemiologically, given that (1) the very narrative under discussion has ensured that there is now no unexposed control group and (2) interpretation of timeline correlation studies is hampered by changes in the way new cancer registrations have been recorded over the years and the perennial problem of multiple possible causal factors. The present paper concludes that a precautionary approach is justified, and ends with a number of specific suggestions on how to start implementing such an approach.


Genes essential for early events in gonadal development.
The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. The basic underlying principle of sexual development is that genetic sex--determined at fertilization by the presence or absence of the Y chromosome--directs the embryonic gonads to differentiate into either testes or ovaries. Thereafter, hormones produced by the testes direct the developmental program that leads to male sexual differentiation. In the absence of testicular hormones, the female pathway of sexual differentiation occurs. Recent studies have defined key roles in gonadal development for two transcription factors: Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After presenting a brief overview of gonadal development and sexual differentiation, this chapter reviews the studies that led to the isolation and characterization of WT1 and SF-1, and then discusses how interactions between these two genes may mediate their key roles in a common developmental pathway.


Profound hypoglycemia with ecstasy intoxication.
Background. 3,4-Methylenedioxymethamphetamine (MDMA) or ecstasy is a synthetic drug that is commonly abused for its stimulant and euphoric effects. Adverse MDMA effects include hyperthermia, psychomotor agitation, hemodynamic compromise, renal failure, hyponatremia, and coma. However, endogenous hyperinsulinemia with severe persistent hypoglycemia has not been reported with MDMA use. Case Report. We report the case of a 29-year-old woman who remained severely hypoglycemic requiring continuous intravenous infusion of high-dose dextrose solutions for more than 24 hours after MDMA intoxication. Serum insulin and C-peptide levels confirmed marked endogenous hyperinsulinemia as the cause of the severe hypoglycemia. Why Should an Emergency Physician Be Aware of This? Immediate and frequent monitoring of blood glucose should be instituted in patients presenting with MDMA ingestion particularly if found to be initially hypoglycemic. Early recognition can help prevent the deleterious effects of untreated hypoglycemia that can add to the morbidity from MDMA use. Clinicians need to be aware of this side effect of MDMA so they can carefully monitor and treat it, especially in patients presenting with altered mental status.


Decreased retention of actinomycin D as the basis for cross-resistance in anthracycline-resistant sublines of P388 leukemia.
Sublines of P388 leukemia resistant to Adriamycin and daunorubicin were cross-resistant to actinomycin D in vivo and in vitro. The Adriamycin-resistant cell line was 1000-fold resistant to actinomycin D on 1-hr exposure in vitro and 370-fold resistant when exposed to the drug for 16 hr. The immediate binding of radioactive actinomycin D to sensitive and resistant cells was similar, and the uptake of the drug by the resistant cells was only about 27% less than the rate of uptake by sensitive cells. There was a dramatic difference in efflux of drug from sensitive and resistant sublines. Equivalent cytotoxicity of actinomycin D for the sensitive and resistant sublines was obtained at concentrations of the drug that resulted in approximately equivalent levels of net retention of actinomycin D (retained drug minus background levels of immediate binding of the drug to the cells). Incubation of cells in the presence of actinomycin D plus either Tween 80 or acridine orange incresed the rate of uptake and the percentage of actinomycin D retained by the resistant cells on short-term assays but did not reverse the resistance. It is concluded that these tumors must retain appreciable concentrations of actinomycin D for several hr in order to be killed. The anthracycline-resistant sublines are cross-resistant to actinomycin D by virtue of their inability to retain the drug.


Memory of learning facilitates saccadic adaptation in the monkey.
A motor learning mechanism called saccadic adaptation ensures accuracy of saccades throughout life despite growth, aging, and some pathologies of the oculomotor plant or nervous system. The present study investigates effects of preceding adaptation on the speed of subsequent adaptation during single experiments. Adaptive changes in gain (movement size divided by target eccentricity) were induced by intrasaccadic step (ISS) of the target. After the gain was altered (control block), we reversed the direction of ISS to bring the gain back to approximately 1.0 (recovery). We then reversed ISS direction again to induce another adaptation (test block). Analyses revealed that the gain changed at a higher rate in the early part of test adaptation than in the corresponding part of control. After approximately 100-300 saccades in the test block, adaptation slowed down. The gain value at which adaptation slowed was correlated with the gain achieved in the control. We further examined effects of a 30 min intervention inserted between recovery and test blocks. When zero-visual-error trials ( approximately 700 saccades) were repeated during this period, the rate of test adaptation was similar to that of control. In contrast, when the animal was deprived of visual inputs during this period, test adaptation was still influenced by preceding learning. We conclude that a memory of previous learning remains during recovery to facilitate subsequent adaptation and that such a memory does not disappear merely with time but is erased actively by repeated zero-error movements. Our results, which cannot be explained by a single mechanism, suggest that the saccadic system is equipped with more than one plasticity process.


Social appraisal in chronic psychosis: role of medial frontal and occipital networks.
Persons with schizophrenia often appraise other individuals as threatening or persecutory. To evaluate social appraisal in schizophrenia, we probed brain networks with a task in which subjects judged whether or not they liked face stimuli with emotional expressions. We predicted that appraising negative expressions would engage patients, more than controls, and negative faces would be related to higher levels of negative affect and produce increased activity in the medial frontal cortex, an area involved in social appraisal. Twenty-one stable outpatients with chronic non-affective psychosis (16 schizophrenic, 5 schizoaffective) and 21 healthy subjects underwent functional magnetic resonance imaging. Compared with the control subjects, patients were slower to respond, but particularly slow when they judged negatively-valenced faces, a slowness correlated with negative affect in the psychosis patients. Appraisal activated the medial prefrontal cortex (mPFC) across all face valences. For negative expressions, patients exhibited greater activation of the dorsal anterior cingulate cortex (dACC). A psychophysiological interaction analysis of the dACC revealed co-modulation of the mPFC in controls, significantly less in patients, and a trend for co-modulation of occipital cortex in the patients. Activity in occipital cortex correlated with poor social adjustment and impaired social cognition, and co-modulation of the occipital gyrus by the dACC was correlated with poorer social cognition. The findings link appraisal of negative affect with aberrant activation of the medial frontal cortex, while early sensory processing of this social cognitive task was linked with poor social function, reflecting either top-down or bottom-up influences.


[Inhibition of the COMPT with entacapone in the treatment of motor fluctuations in Parkinson disease].
Motor fluctuations are a common problem in the long-term treatment of Parkinson's disease (PD). Entacapone (Comtan) is a potent, peripherally acting, reversible and selective inhibitor of catechol-O-methyltransferase (COMT). Used as an adjuvant to levodopa therapy, entacapone slows the elimination of levodopa by decreasing peripheral conversion to 3-O-methyldopa, increasing central extracellular levodopa and striatal dopamine concentrations. Coadministered with levodopa/carbidopa or levodopa/benserazide, at doses of 200 mg 2 to 10 times daily in patients with end-of-dose fluctuations, entacapone may increase the duration of clinical response, both after the first single dose and after repeated dosing. At this dosage, it has a time to peak plasma concentration of 1.2 h and an elimination half life of 3.4 h. In two multicentric, long-term (24 weeks), parallel, randomized and placebo-controlled studies, entacapone increased the duration of 'on' time (by approximately 1 hour daily) and decreased the duration of 'off' time with a concomitant reduction in the mean daily levodopa dose. In these and other phase III studies, entacapone was generally well tolerated, with most adverse effects being dyskinesias and gastrointestinal disorders. Increased dyskinesia were generally controlled by reducing levodopa doses. Entacapone appears to be a useful adjunct in extending the benefit of each levodopa dose in PD patients with end-of-dose fluctuations.


An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.
Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.


Retrospective evaluation of shortened prothrombin time or activated partial thromboplastin time for the diagnosis of hypercoagulability in dogs: 25 cases (2006-2011).
To evaluate the relationship between shortened prothrombin time (PT) or activated partial thromboplastin time (aPTT) values, clinical findings associated with hypercoagulability, suspicion of pulmonary thromboembolism (PTE), D-dimer concentrations, and thromboelastogram (TEG) indices. Retrospective observational study from 2006 to 2011. University veterinary teaching hospital. Twenty-three dogs with TEG tracings and shortened PT or aPTT values and 23 control dogs with TEG tracings and normal PT and aPTT values. Parameters evaluated included signalment, coagulation testing results (PT, aPTT, D-dimer concentration), TEG measurements (R, K, α, maximal amplitude) and calculated clotting index, findings of clinical hypercoagulability (thrombosis of intravenous/intra-arterial catheters, vessel thrombosis, and suspected PTE). Dogs with shortened PT or aPTT had significantly more thrombus formation (P = 0.038), suspicion of PTE (P < 0.001), and increased D-dimer concentration (P < 0.001) compared to dogs with normal PT and aPTT values. There were no significant findings when compared to TEG values. A shortened PT or aPTT in dogs may be indicative of a hypercoagulable state as evidenced by an increased incidence of thrombosis, frequency of suspected PTE, and increased circulating D-dimers. A prospective study is warranted to further evaluate the use of PT and aPTT to diagnose hypercoagulable states.


Microphase separation in polymer solutions containing surfactants.
A microphase separation in solutions containing a polymer and a mixture of two solvents, one of which consists of amphiphilic molecules (surfactant), is considered theoretically in the weak-segregation regime. A surfactant molecule is described as a dimer consisting of hydrophobic and polar parts. The energy gain due to the orientation of surfactant molecules can lead to the appearance of non-homogeneities in the solution, where density fluctuations cause the orientational ordering of surfactant molecules. The difference in the interaction energies of hydrophobic and polar groups of a surfactant with solvent is considered as a main reason for orienting surfactant molecules. The free energy is calculated for various morphologies (lamellar, cylindrical hexagonal, spherical particles arranged at different cubic lattices). The phase diagrams are presented. With worsening the solvent quality, the transitions from disordered to a macro-separated state at low polymer and surfactant concentrations or to a body-centered-cubic, then hexagonal, and then lamellar structure at high polymer and surfactant concentrations are predicted. The amphiphilicity degree of surfactant molecules should exceed a certain critical value to make a microstructure formation possible. The period of the lamellar microstructure decreases with increasing the surfactant and polymer concentrations.


Evaluation of HIV voluntary counselling and testing services in Egypt. Part 1: client satisfaction.
HIV voluntary counselling and testing (VCT) services were launched in Egypt in 2005. A study of all functioning VCT centres in Egypt (7 mobile and 9 fixed) aimed to determine the profile of clients and their level of satisfaction to identify strengths and weaknesses in the service. In direct interviews with a sample of 928 clients, the main motive for seeking VCT was risky sexual behaviour (34.2%). More females than males sought services because of partners' risky sexual behaviour. More than 90% of the clients were satisfied with the counselling service. Only 41.4% were willing to discuss the test results with their partners. Male sex, higher education level and attendance at fixed VCT centres were associated with higher satisfaction.


[Complications of intracranial hemorrhage in full term newborns].
The incidence of various types of intracranial hemorrhage is different in full-term infants than those that occur in small premature infants. Consequently, the complications are for the most part different. The previous article described the types of hemorrhage occurring at term, as well as their signs and symptoms. This brief review will focus on the complications that may arise from these. Examples are given of superficially occurring hemorrhages and of those that arise deeper in the parenchyma of the brain. The actual bleed is the acute event that may become subacutely complicated by virtue of its position or by extension. This occurs as part of the natural process or as a result of injudicious intervention. There follow chronic complications: cerebral palsy, intellectual deficit and seizure disorder which remain for the patient's lifetime.


Discriminant component pruning. Regularization and interpretation of multi-layered back-propagation networks.
Neural networks are often employed as tools in classification tasks. The use of large networks increases the likelihood of the task's being learned, although it may also lead to increased complexity. Pruning is an effective way of reducing the complexity of large networks. We present discriminant components pruning (DCP), a method of pruning matrices of summed contributions between layers of a neural network. Attempting to interpret the underlying functions learned by the network can be aided by pruning the network. Generalization performance should be maintained at its optimal level following pruning. We demonstrate DCP's effectiveness at maintaining generalization performance, applicability to a wider range of problems, and the usefulness of such pruning for network interpretation. Possible enhancements are discussed for the identification of the optimal reduced rank and inclusion of nonlinear neural activation functions in the pruning algorithm.


An unusual presentation of post-traumatic pseudocyst of the spleen: case report.
Splenic pseudocysts are rare complications of abdominal trauma. Through rare, these lesions have been well-documented in the literature. According to current classification schemes, approximately 30% of all splenic cysts or pseudocysts result from direct abdominal trauma. The case report herein is an example of a splenic pseudocyst with an atypical presentation. The patient was evaluated and treated for progressive hypertension initially. Inability to control hypertension, and the appearance of symptoms suggesting intra-abdominal pathology prompted radiographic evaluation and surgical consultation. Prompt resolution of the hypertension followed operative resection of the splenic pseudocyst.


Sex-related communicative functions of voice spectral energy in human chorusing.
Music is a human communicative art whose evolutionary origins may lie in capacities that support cooperation and/or competition. A mixed account favouring simultaneous cooperation and competition draws on analogous interactive displays produced by collectively signalling non-human animals (e.g. crickets and frogs). In these displays, rhythmically coordinated calls serve as a beacon whereby groups of males 'cooperatively' attract potential female mates, while the likelihood of each male competitively attracting an actual mate depends on the precedence of his signal. Human behaviour consistent with the mixed account was previously observed in a renowned boys choir, where the basses-the oldest boys with the deepest voices-boosted their acoustic prominence by increasing energy in a high-frequency band of the vocal spectrum when girls were in an otherwise male audience. The current study tested female and male sensitivity and preferences for this subtle vocal modulation in online listening tasks. Results indicate that while female and male listeners are similarly sensitive to enhanced high-spectral energy elicited by the presence of girls in the audience, only female listeners exhibit a reliable preference for it. Findings suggest that human chorusing is a flexible form of social communicative behaviour that allows simultaneous group cohesion and sexually motivated competition.


Thermodynamic length for far-from-equilibrium quantum systems.
We consider a closed quantum system initially at thermal equilibrium and driven by arbitrary external parameters. We derive a lower bound on the entropy production which we express in terms of the Bures angle between the nonequilibrium and the corresponding equilibrium state of the system. The Bures angle is an angle between mixed quantum states and defines a thermodynamic length valid arbitrarily far from equilibrium. As an illustration, we treat the case of a time-dependent harmonic oscillator for which we obtain analytic expressions for generic driving protocols.


Nitrate reduction pathways in mycobacteria and their implications during latency.
Mycobacterial persistence has gained a lot of attention with respect to developing novel antitubercular drugs, which could drastically reduce the duration of tuberculosis (TB) therapy. A better understanding of the physiology of Mycobacterium tuberculosis, and of the metabolic state of the bacillus during the latent period, is a primary need in finding drug targets against persistent TB. Recent biochemical and genetic studies of nitrate reduction in mycobacteria have revealed the roles of distinct proteins and enzymes involved in the pathway. The differential degree of nitrate reduction among pathogenic and non-pathogenic mycobacterial species, and its regulation during oxygen and nutrient limitation, suggest a link between nitrate reduction pathways and latency. The respiratory and assimilatory reduction of nitrate in mycobacteria may be interconnected to facilitate rapid adaptation to changing oxygen and/or nitrogen conditions, increasing metabolic flexibility for survival in the hostile host environment. This review summarizes the nitrate metabolic pathways operative in mycobacteria to provide an insight into the mechanisms that M. tuberculosis has evolved to adapt successfully to the host environment.


The COVID-19 storm and the energy sector: The impact and role of uncertainty.
Prior research has shown that energy sector stock prices are impacted by uncertainty. The coronavirus (COVID-19) pandemic has given rise to widespread health and economic-related uncertainty. In this study, we investigate the magnitude and the timing of the impact of COVID-19 related uncertainty on returns and volatility for 20 national energy indices and a global energy index using ARCH/GARCH models. We propose a novel "overall impact of uncertainty" (OIU) measure, explained using a natural phenomenon analogy of the overall impact of a rainstorm, to gauge the magnitude and intensity of the impact of uncertainty on energy sector returns. Drawing upon economic psychology, COVID-19 related uncertainty is measured in terms of searches for information relating to COVID-19 as captured by Google search trends. Our results show that the energy sectors of countries further west from the outbreak of the virus in China are impacted to a greater extent by COVID-19 related uncertainty. A similar observation is made for net energy and oil exporters relative to importers. We also find that the impact of uncertainty on most national energy sectors intensified and then weakened as the pandemic evolved. Additional analysis confirms that COVID-19 uncertainty is part of the composite set of factors that drive energy sector returns over the COVID-19 period although its importance has declined over time.


[Allogeneic bone marrow transplantation in acute lymphoblastic leukemia of children. Analysis of prognostic factors. GEGMO (Bone Marrow Study Group) study].
Sixty-five children with acute lymphoblastic leukemia (ALL) underwent allogenic bone marrow transplantation (BMT) from an HLA identical donor, following cytoreduction with cyclophosphamide and total body irradiation (TBI): 15 were transplanted in 1st remission, 43 in 2nd and 7 in 3rd or in 4th. The Kaplan Meier estimate of surviving disease free at 4 years post BMT was 49.9% and the probability of continued remission at 4 years was 63.3%. Fourteen patients relapsed between 90 and 690 days (mean: 240 +/- 88) post BMT. The other causes of BMP failure included: graft versus host disease, veno-occlusive disease and sepsis. No interstitial pneumonitis has been reported. Patients who had a relapse while on chemotherapy had a higher probability of relapse than those who had a relapse while off therapy (p less than 0.01). We conclude that allogeneic BMT is the treatment of choice for children with ALL in second hematologic remission, the interval between diagnosis and first relapse being the most significant prognostic factor. Patients with poor prognosis might benefit from a more intensive chemotherapy/total body irradiation schedule or a BMT earlier in the course of their disease.


Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.
Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.


Acute management of croup in the emergency department.
Croup is one of the most common causes of upper airway obstruction in young children. It is characterized by sudden onset of barky cough, hoarse voice, inspiratory stridor and respiratory distress caused by upper airway inflammation secondary to a viral infection. Published guidelines for the diagnosis and treatment of croup advise using steroids as the mainstay treatment for all children who present to emergency department (ED) with croup symptoms. Dexamethasone, given orally as a single dose at 0.6 mg/kg, is highly efficacious in treating croup symptoms. Despite the evidence supporting the use of steroids as the cornerstone of croup treatment, there is significant practice variation among physicians treating croup in the ED. This practice point discusses evidence-based management of typical croup in the ED.


Assortative mating frames establishment in a young island bird population.
Successful island colonizations are key events to understand range dynamic processes, but studying a young population right after it reaches establishment is a rare opportunity in natural systems. The genetic structure of a recently established population may offer unique insights into its colonization history and demographic processes that are important for a successful colonization. Here, we studied the population genetics of a recently established island population of Eurasian blackbirds (Aves: Turdus merula) located on the island of Heligoland in the German North Sea. Using microsatellites, we genotyped the majority of the island population, including the nestlings, over a 4-year period between 2004 and 2007. We also genotyped high numbers of migrants on stopover and mainland individuals, as they are potential founders of the island population. We identified two genetic clusters that comply with the migrating and mainland birds. While most of the island birds belong to the mainland cluster, some breeding individuals and a low fraction of the offspring belong to the genetic cluster found in migrating individuals with almost no admixture between the two, pointing to assortative mating acting on the island population. We did not find any evidence for founder events and detected deviations from the Hardy-Weinberg equilibrium that disappeared in cohorts of older age that coincide with a lower number of siblings in older cohorts. The observed genetic patterns unravel a complex colonization history to which migratory and mainland birds have contributed and which is characterized by assortative mating. Further research will be directed towards habitat selection and phenotypic differences as potential drivers of assortative mating in this island population.


Effect of calcium ion on the maturation of cumulus-enclosed pig follicular oocytes isolated from medium-sized graafian follicles.
Porcine follicular oocytes from medium-sized follicles (3-5 mm in diameter) were cultured in modified Hank's balanced salts solution (MHBS) to which pyruvate, lactate, and glucose were added as an energy source. Bovine serum albumin (0.4%) was added as a protein source and the oocytes were cultured for 42 h at 37 degrees C in 5% CO2 in air. In this medium porcine oocytes underwent 80-90% nuclear maturation after 42 h. Oocytes were cultured in MHBS with various amounts of CaCl2 as well as in the presence of verapamil, a Ca2+ channel blocker, and the divalent cationophore A23187. It was found that the lowest concentration of Ca2+ required for oocyte maturation was around 0.0265-0.053 mM. Such a requirement for Ca2+ in the culture medium extended through metaphase II. If Ca2+ was omitted during the final 4 h of culture, the metaphase II chromosomes appeared extremely condensed or degenerated. Verapamil at a level of 0.2 mM inhibited germinal vesicle breakdown or resulted in degeneration, whereas lower concentrations did not affect oocyte maturation. In the presence of 0.02 mM verapamil, the maturation of cumulus-enclosed oocytes was not affected, whereas at the same dose of verapamil the maturation of denuded oocytes was inhibited. Less than 3.8 X 10(-7) M divalent cationophore did not inhibit oocyte maturation. Maturation was inhibited by 3.8 X 10(-7) and 3.8 X 10(-6) M divalent cationophore. In conclusion, maintenance of oocytes in a nondegenerated state also requires the constant presence of Ca2+ in the culture medium.


Multi-normal mode-splitting for an optical cavity with electromagnetically induced transparency medium.
We theoretically study the cavity transmission spectra with three-level atoms coupled by a coherent external control field in the superstrong coupling regime (atoms-cavity coupling strength g [square root] N is near or larger than the cavity free-spectral range DeltaFSR). When satisfying the superstrong coupling condition by increasing the number of the interaction atoms, more than one FSR cavity modes interact with atoms and each mode will split three peaks, which can be well explained by the linear dispersion enhancement of electromagnetically induced transparency medium due to the largely increased atomic density in the cavity.


In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy.
Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.


HIV and sexual risk behavior among commercial sex workers in the Netherlands.
In 2002-2005, a cross-sectional study to assess the potential for HIV transmission was carried out among 557 female and male-to-female transgender commercial sex workers (CSW) in three cities in the Netherlands. Female CSW (F-CSW), drug-using female CSW (DU), and transgender sex workers were recruited in street-based and establishment-based sites. An anonymous questionnaire was administrated by interviewers and a saliva sample was collected for HIV antibody testing. The overall HIV prevalence was 5.7% (31/547; 10 samples were excluded because of "intermediate" test results). HIV was more prevalent among transgender (18.8%, 13/69) and DU (13.6%, 12/88) sex workers than among F-CSW (1.5%, 6/390). Of the HIV positive CSW, 74% were unaware of their infection. Consistent condom use with clients was 81%. Regular condom failure with clients was reported by 39%. In multivariate analyses, transgender sex workers (OR = 22.9), drug-using CSW who ever injected drugs (OR = 31.1), African (OR = 19.0), and South European ethnicity (OR = 7.2) were independently associated with HIV. Condom failure (PRR = 2.0), anal sex (PRR = 2.1), and drug use (PRR = 3.8) were associated with inconsistent condom use with clients. There is a potential risk for further spread of HIV, through clients and (private) partners of sex workers, to the general population. Targeted health promotion activities are indicated for transgender sex workers and drug-using female CSW; active HIV testing must be continued.


The Annual American Men's Internet Survey of Behaviors of Men Who Have Sex With Men in the United States: 2017 Key Indicators Report.
The American Men's Internet Survey (AMIS) is an annual Web-based behavioral survey of men who have sex with men (MSM) who live in the United States. This Rapid Surveillance Report describes the fifth cycle of data collection (July 2017 to November 2017: AMIS 2017). The key indicators are the same as those previously reported for past AMIS cycles (December 2013 to May 2014: AMIS 2013; November 2014 to April 2015: AMIS 2014; September 2015 to April 2016: AMIS 2015; and September 2016 to February 2017: AMIS 2016). The AMIS methodology has not substantively changed since AMIS 2016. The MSM were recruited from a variety of websites using banner advertisements and email blasts. Additionally, participants from AMIS 2016 who agreed to be recontacted for future research were emailed a link to AMIS 2017. Men were eligible to participate if they were aged ≥15 years, resided in the United States, provided a valid US zone improvement plan code, and reported ever having sex with a man or identified as gay or bisexual. The analysis was limited to those who reported having oral or anal sex with a male partner in the past 12 months. We examined demographic and recruitment characteristics using multivariable regression modeling (P<.05) stratified by the participants' self-reported HIV status. The AMIS 2017 round of data collection resulted in 10,049 completed surveys from MSM representing every US state, Puerto Rico, and Guam. Participants were mainly non-Hispanic white, over the age of 40 years, living in the Southern United States and urban areas, and recruited from geospatial social networking websites. The plurality (4485/10,049, 44.6%) of participants was in the 40 years and older age group, followed by the youngest age group, 15 to 24 years (2726/10,049, 27.1%). Self-reported HIV prevalence was 9.6% (964/10,049). Compared with HIV-negative or unknown-status participants, HIV-positive participants were more likely to have had anal sex without a condom with a male partner in the past 12 months (adjusted odds ratio [aOR] 2.21, 95% CI 1.86-2.63) and more likely to have had anal sex without a condom with a serodiscordant or an unknown-status partner (aOR 3.13, 95% CI 2.71-3.62). The reported use of marijuana in the past 12 months was higher among HIV-positive participants than HIV-negative or unknown status participants (aOR 1.29, 95% CI 1.09-1.51). The reported use of methamphetamines and other illicit substances in the past 12 months was higher among HIV-positive participants than HIV-negative or unknown status participants (aOR 5.57, 95% CI 4.38-7.09 and aOR 1.93, 95% CI 1.65-2.27, respectively). Most HIV-negative or unknown status participants (7330/9085, 80.7%) reported ever taking an HIV test previously, and 60.6% (5504/9085) reported undergoing HIV testing in the past 12 months. HIV-positive participants were more likely to report testing and diagnosis of sexually transmitted infections than HIV-negative or unknown status participants (aOR 2.85, 95% CI 2.46-3.31 and aOR 2.73, 95% CI 2.29-3.26, respectively).


A comparison of the effects of two antiseptic agents on Staphylococcus epidermidis colony forming units at the peritoneal dialysis catheter exit site.
Peritonitis is the most common complication of peritoneal dialysis (PD). Staphylococcus epidermidis (S. epi), a common skin organism, is the microorganism that is identified is the majority of episodes of peritonitis. The PD catheter breaks the natural skin barrier and allows a periluminal migration of bacteria from the skin surface into the sterile peritoneal cavity. Exit site care is routinely performed to decrease the colony counts of microorganisms on the skin surrounding the PD catheter. Research data is limited to support any of the currently used protocols for exit site care. This study compared the effect of two antiseptic agents, povidone-iodine (P-I) and chlorhexidine gluconate (CG), on S. epi colony forming units (cfu) at the PD catheter exit site over a 24 hour period. Because the distribution of the research data was markedly non-normal, a descriptive approach was used to interpret the data. Results showed that there was no difference between P-I and CG immediately after exit site care. All patients had zero growth at Time I. One trend that emerged was that at 24 hours after exit site care with P-I, more patients (54%) had S. epi cfu than did patients (15%) cleaned with CG.


Testosterone modulates spatial recognition memory in male rats.
A growing body of research indicates that testosterone influences spatial cognition in male rats; however, the overwhelming majority of studies have been conducted on tasks motivated by either food deprivation or water escape. The hippocampus-dependent version of the Y-maze task, which characterizes spatial recognition memory, capitalizes on the propensity of rats to gravitate toward novel spatial environments and is not contingent upon either appetite or the stress associated with water escape, two factors also affected by testosterone. Accordingly, the aim of the current study was to examine the effects of orchidectomy and subsequent testosterone treatment on spatial recognition memory. Orchidectomy did not impact spatial recognition memory when the delay between the information and retention trials of the Y-maze task was 24h. Alternatively, on the second Y-maze task, which featured a 48-h delay between trials, orchidectomy reduced, and treatments that produced higher levels of testosterone restored, preference for the arm associated with the novel spatial environment. Importantly, there were no differences in activity levels as a function of orchidectomy or testosterone treatment on either of the two tasks. Consistent with previous findings, orchidectomy attenuated, and testosterone treatment restored, both body weight gain and the relative weight of the androgen-sensitive ischiocavernosus muscle, which confirmed the efficacy of orchidectomy and testosterone treatments on physiological outcomes. Therefore, testosterone influenced spatial cognition on a task that minimized the influence of non-mnemonic factors and took advantage of the innate preference of rodents to seek out novel spatial environments.


Pattern of emergence and the effects of temperature and light on the emergence and survival of heterophyid cercariae (Centrocestus formosanus and Haplorchis pumilio).
Production of the cercariae of Centrocestus formosanus and Haplorchis pumilio was not affected by a 10-day starvation of the snail host Melanoides tuberculata, and there was no circadian rhythm in the pattern of cercarial emergence. Daily average cercarial productions from each snail were 1,643 for C. formosanus and 689 for H. pumilio at 25 C and 500 lux illumination. The number of cercariae was moderately correlated with the size of snail host. The heaviest sheddings ever observed from 1 snail in 24 hr were 63,400 cercariae for C. formosanus and 3,470 cercariae for H. pumilio. The cercariae of C. formosanus could emerge in the dark, but the number was much less than in the light. In contrast, the cercariae of H. pumilio emerged equally well with or without light. Within the temperature range tested, the emergence of cercariae occurred at 15-35 C, but not at 10 C. Shedding of C. formosanus cercariae increased with the rise in ambient temperature, whereas the greatest shedding of H. pumilio cercariae occurred at 25 C. Life-span of the cercariae was temperature-dependent. The most favorable temperature for survival of C. formosanus was 15 C, at which some survived for 160 hr, and 20 C for H. pumilio, with the longest survival of 130 hr.


A review of 79 patients with malaria seen at a military hospital in Hawaii from 1979 to 1995.
The goal of our study was to determine the epidemiological and clinical features of imported malaria seen at our military hospital in Hawaii. We reviewed the records of malaria cases seen from January 1, 1979, to December 31, 1995, and compared our results with published reviews from civilian hospitals in North America. Seventy-nine patients were diagnosed with malaria by blood smears. All acquired malaria abroad, mostly in southeast Asia. Sixty-seven percent of cases were vivax malaria, 22% were falciparum malaria, and 11% were caused by undetermined species. Common symptoms were fever (100%), alternate day fever (41%), rigors (91%), headache (59%), nausea (41%), fatigue (39%), dark urine (32%), and vomiting (31%). Ninety-one percent had fever during hospitalization, but 39% were afebrile on admission. Splenomegaly was detected in 49% of cases. The white blood cell count was normal in 65%, low in 31%, and elevated in 4% of cases. Other laboratory findings were anemia (58%), thrombocytopenia (74%), and mild hyperbilirubinemia (64%). Military physicians initially considered the diagnosis of malaria in only 54% of patients. The epidemiological features of our patients differ from those described in the civilian hospitals. Most of our patients were nonimmune, U.S.-born, military personnel infected in southeast Asia, whereas patients described in reviews from U.S. civilian hospitals were usually foreign-born civilians who were infected in Africa or India. The clinical features of malaria, and the problems of initial misdiagnosis in our patients, were similar to those reported from civilian hospitals. Military physicians, like their civilian colleagues, need more training and experience in malaria.


Machine Learning-Assisted Automatically Electrochemical Addressable Cytosensing Arrays for Anticancer Drug Screening.
The high-throughput and accurate screening of anticancer drugs is crucial to the preclinical assessment of candidate drugs and remains challenging. Herein, an automatically electrochemical addressable cytosensor (AEAC) for the efficient screening of anticancer drugs is reported. This sensor consists of sectionalized laser-induced graphene arrays decorated by the rhombohedral TiO2 and spherical Pt nanoparticles (LIG-TiO2-Pt) with high electrocatalytic activity for H2O2 and a homemade Ag/Pt electrode couple fixed onto the robot arm. The immobilization of laminin on the surface of LIG-TiO2-Pt can promote its biocompatibility for the growth and proliferation of various tumor cells, which empowers the in situ monitoring of H2O2 directly released from these live cells for drug screening. A machine learning (ML) algorithm is employed to eliminate the possible random or systematic errors of AEAC, realizing rapid, high-throughput, and accurate prediction of different types of anticancer drugs. This ML-assisted AEAC provides a powerful approach to accelerate the evolution of sensing-served tumor therapy.


Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.
We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure. Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator. Crossed-validated area under the receiver operating characteristic curve was used to compare the prediction performance. Lipids with high crossed-validated area under the curve were identified. Lipid with mass-to-charge ratio of 372.31 was selected by all three methods comparing mesothelioma versus control. Lipids with mass-to-charge ratio of 1464.80 and 329.21 were selected by two models for asbestos exposure versus control. Different methods selected a similar set of serum lipids. Combining candidate biomarkers can improve prediction.


Catalytic activities of Werner protein are affected by adduction with 4-hydroxy-2-nonenal.
4-Hydroxy-2-nonenal (HNE) is a reactive α,β-unsaturated aldehyde generated during oxidative stress and subsequent peroxidation of polyunsaturated fatty acids. Here, Werner protein (WRN) was identified as a novel target for modification by HNE. Werner syndrome arises through mutations in the WRN gene that encodes the RecQ DNA helicase which is critical for maintaining genomic stability. This hereditary disease is associated with chromosomal instability, premature aging and cancer predisposition. WRN appears to participate in the cellular response to oxidative stress and cells devoid of WRN display elevated levels of oxidative DNA damage. We demonstrated that helicase/ATPase and exonuclease activities of HNE-modified WRN protein were inhibited both in vitro and in immunocomplexes purified from the cell extracts. Sites of HNE adduction in human WRN were identified at Lys577, Cys727, His1290, Cys1367, Lys1371 and Lys1389. We applied in silico modeling of the helicase and RQC domains of WRN protein with HNE adducted to Lys577 and Cys727 and provided a potential mechanism of the observed deregulation of the protein catalytic activities. In light of the obtained results, we postulate that HNE adduction to WRN is a post-translational modification, which may affect WRN conformational stability and function, contributing to features and diseases associated with premature senescence.


Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study.
The prevalence of obesity is increasing in many European countries and in the United States. This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospective Study and the relative effects of weight in middle age and self reported weight at 18 years. All men aged 45 to 59 years from the town of Caerphilly, South Wales and outlying villages were identified and 2512 men were examined for the first time between 1979 and 1983. Men were asked to recall their weight at 18 years of age (when the majority had been examined for National Service) so that weight then, weight at screening, and the difference could be related to their 14 year follow up from screening. A total of 2335 men could recall their weight at 18 years. By 14 years of follow up from screening 465 men had died and 382 had had coronary events. Mean body mass index in men who reported their weight at 18 years was 22.3 (SD 2.8) kg/m(2) and only 41 of these men (1.8%) were classified as obese (index >/= 30 kg/m(2)). The index did not predict all cause mortality when examined by quintile. For major ischaemic heart disease (non-fatal or fatal ischaemic heart disease) the relative odds was 1.73 (95% CI 1.21, 2.48) in the top fifth of the distribution (body mass index >/= 24.2 kg/m(2)) compared with the bottom fifth (body mass index <20.1 kg/m(2)). In men with an index >/= 30 kg/m(2) however, the relative odds were 2.03 (95% CI, 1.03, 4.01) for all cause mortality and 2.17 (95% CI, 1.08, 4.34) for major ischaemic heart disease, adjusted for age, smoking habit and social class. When men were recruited to the study, from 1979 to 1983; the mean body mass index had increased to 26.2 (SD 3.6), a mean increase of 3.9 kg/m(2) or 11. 2 kg; 299 men (12.1%) were classified as obese and showed significantly increased relative odds of both all cause mortality (1. 53 (95% CI 1.14, 2.06) and major ischaemic heart disease (1.55 (95% CI 1.13, 2.11)), adjusted for age, smoking habit and social class relative to the non-obese men. The effect of gain in weight from 18 years to recruitment was also examined; all cause mortality showed highest mortality in the fifth of the distribution who experienced weight loss or minimal weight gain. For major ischaemic heart disease an inconsistent, weak trend was shown, the relative odds rising to a maximum of 1.26 (0.89, 1.80) in the top fifth of weight gain compared with the bottom fifth. Weight gain showed strong associations with potential cardiovascular risk factors measured at recruitment; insulin, triglyceride, glucose, diastolic and systolic blood pressure and high density lipoprotein-cholesterol. Body mass at 18 years of age of 30 kg/m(2) or more conferred increased risk for all cause mortality and major ischaemic heart disease during 14 years of follow up of men aged 45 to 59 years. By the baseline examination the prevalence of obesity (body mass index >/=30) had increased from 1.8% to 12.1%; obese men also showed an excess risk of major ischaemic heart disease and overall mortality, but these risks were lower than those predicted from 18 years of age. Weight gain was strongly associated with smoking habit, the greatest weight gain being among ex-smokers and the least among light smokers. Weight gain from 18 years of age to baseline examination showed little relation with subsequent mortality and risk of major ischaemic heart disease when adjusted for age, smoking habit and social class. The lowest mortality rate occurred in the "fifth" of men who gained a mean weight of 16.1 kg. Weight gain is closely associated with some adverse cardiovascular risk factors; in particular with insulin, triglyceride, glucose and diastolic blood pressure.


Effects of Ocean Acidification on Transcriptomes in Asian Seabass Juveniles.
Ocean acidification is changing the fate of marine organisms. It is essential to predict the biological responses and evolutionary processes driven by ocean acidification, to maintain the equilibrium of the marine ecosystem and to facilitate aquaculture. However, how marine organisms, particularly the marine fish species, respond to ocean acidification, is still poorly understood. Consequences of ocean acidification on finfish aquaculture are largely not well known. We studied the effects of ocean acidification for 7 days on growth, behaviour and gene expression profiles in the brain, gill and kidney of Asian seabass juveniles. Results showed that growth and behaviour were not affected by short-term ocean acidification. We found tissue-specific differentially expressed genes (DEGs) involving many molecular processes, such as organ development, growth, muscle development, ion homeostasis and neurogenesis and development, as well as behaviours. Most of the DEGs, which were functionally enriched in ion homeostasis, were related to calcium transport, followed by sodium/potassium channels. We found that genes associated with neurogenesis and development were significantly enriched, implying that ocean acidification has also adversely affected the neural regulatory mechanism. Our results indicate that although the short-term ocean acidification does not cause obvious phenotypic and behavioural changes, it causes substantial changes of gene expressions in all three analysed tissues. All these changes of gene expressions may eventually affect physiological fitness. The DEGs identified here should be further investigated to discover DNA markers associated with adaptability to ocean acidification to improve fish's capability to adapt to ocean acidification.


Nanosilver and the microbiological activity of the particulate solids versus the leached soluble silver.
Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial nanoparticles with as yet, still unresolved cytotoxicity origins. To date, research efforts have mostly described the antimicrobial contribution from the leaching of soluble silver, while the undissolved solid Ag particulates are often considered as being microbiologically inert, serving only as source of the cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular oxidative stress in bacteria by the presence of the undissolved Ag particulates. The cytotoxicity characteristics are distinct from those arising from the leached soluble Ag, the latter being locked in organic complexes. The work also highlights the unique oxidative stress-independent bacterial toxicity of silver salt. Taken together, the findings advocate that future enquiries on the antimicrobial potency and also importantly, the environmental and clinical impact of Ag NPs use, should pay attention to the potential bacterial toxicological responses to the undissolved Ag particulates, rather than just to the leaching of soluble silver. The findings also put into question the common use of silver salt as model material for evaluating bacterial toxicity of Ag NPs.


Surface plasmon resonance based fiber optic detection of chlorine utilizing polyvinylpyrolidone supported zinc oxide thin films.
A highly sensitive chlorine sensor for an aqueous medium is fabricated using an optical fiber surface plasmon resonance (OFSPR) system. An OFSPR-based chlorine sensor is designed with a multilayer-type platform by zinc oxide (ZnO) and polyvinylpyrollidone (PVP) film morphology manipulations. Among all the methodologies of transduction reported in the field of solid state chemical and biochemical sensing, our attention is focused on the Kretschmann configuration optical fiber sensing technique using the mechanism of surface plasmon resonance. The optical fiber surface plasmon resonance (SPR) chlorine sensor is developed using a multimode optical fiber with the PVP-supported ZnO film deposited over a silver-coated unclad core of the fiber. A spectral interrogation mode of operation is used to characterize the sensor. In an Ag/ZnO/PVP multilayer system, the absorption of chlorine in the vicinity of the sensing region is performed by the PVP layer and the zinc oxide layer enhances the shift in resonance wavelength. It is, experimentally, demonstrated that the SPR wavelength shifts nonlinearly towards the red side of the visible region with an increase in the chlorine concentration in an aqueous medium while the sensitivity of the sensor decreases linearly with an increase in the chlorine concentration. As the proposed sensor utilizes an optical fiber, it possesses the additional advantages of fiber such as less signal degradation, less susceptibility to electromagnetic interference, possibility of remote sensing, probe miniaturization, probe re-usability, online monitoring, small size, light weight and low cost.


Gelsemine, a principal alkaloid from Gelsemium sempervirens Ait., exhibits potent and specific antinociception in chronic pain by acting at spinal α3 glycine receptors.
The present study examined the antinociceptive effects of gelsemine, the principal alkaloid in Gelsemium sempervirens Ait. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50% to 60% and ED50 values of 0.5 to 0.6 μg. Multiple daily intrathecal injections of gelsemine for 7 days induced no tolerance to antinociception in the rat model of bone cancer pain. Spinal gelsemine was not effective in altering contralateral paw withdrawal thresholds, and had only a slight inhibitory effect on formalin-induced acute nociception. The specific antinociception of gelsemine in chronic pain was blocked dose-dependently by the glycine receptor (GlyR) antagonist strychnine with an apparent ID50 value of 3.8 μg. Gelsemine concentration-dependently displaced H(3)-strychnine binding to the membrane fraction of rat spinal cord homogenates, with a 100% displacement and a Ki of 21.9μM. Gene ablation of the GlyR α3 subunit (α3 GlyR) but not α1 GlyR, by a 7-day intrathecal injection of small interfering RNA (siRNA) targeting α3 GlyR or α1 GlyR, nearly completely prevented gelsemine-induced antinociception in neuropathic pain. Our results demonstrate that gelsemine produces potent and specific antinociception in chronic pain states without induction of apparent tolerance. The results also suggest that gelsemine produces antinociception by activation of spinal α3 glycine receptors, and support the notion that spinal α3 glycine receptors are a potential therapeutic target molecule for the management of chronic pain.


Child marriage in the United States and its association with mental health in women.
Despite the devastating impact of child marriage (marriage before the age of 18 years) on health, no study has yet evaluated its impact on mental health in the general adult population. This article presents nationally representative data on the prevalence, sociodemographic correlates, and psychiatric comorbidity of child marriage among women in the United States. Data were drawn from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. We limited our analyses to the sample of women (N = 24 575) with a known age at first marriage, of whom 18 645 had been or were presently married. The prevalence of child marriage among women was 8.9%. Demographic factors associated with child marriage were black and American Indian/Alaska Native ethnicities, age at interview of >45 years, low educational level, low income, and living in the South and rural areas of the United States. The overall lifetime and 12-month rates of psychiatric disorders were higher for women who married as children, compared with women who married as adults. In addition, women who married as children were more likely to seek and access health services, compared with women who married in adulthood. Child marriage increases the risk of lifetime and current psychiatric disorders in the United States. Support for psychiatric vulnerabilities among women married in childhood is required.


The shrinking health advantage: unintentional injuries among children and youth from immigrant families.
Immigrants typically arrive in good health. This health benefit can decline as immigrants adopt behaviours similar to native-born populations. Risk of injury is low in immigrants but it is not known whether this changes with increasing time since migration. We sought to examine the association between duration of residence in Canada and risk of unintentional injury. Population-based cross-sectional study of children and youth 0 to 24 years in Ontario, Canada (2011-2012), using linked health and administrative databases. The main exposure was duration of Canadian residence (recent: 0-5 years, intermediate: 6-10 years, long-term: >10 years). The main outcome measure was unintentional injuries. Cause-specific injury risk by duration of residence was also evaluated. Poisson regression models estimated rate ratios (RR) for injuries. 999951 immigrants were included with 24.2% recent and 26.4% intermediate immigrants. The annual crude injury rates per 100000 immigrants were 6831 emergency department visits, 151 hospitalizations, and 4 deaths. In adjusted models, recent immigrants had the lowest risk of injury and risk increased over time (RR 0.79; 95% CI 0.77, 0.81 recent immigrants, RR 0.90; 95% CI 0.88, 0.92 intermediate immigrants, versus long-term immigrants). Factors associated with injury included young age (0-4 years, RR 1.30; 95% CI 1.26, 1.34), male sex (RR 1.52; 95% CI 1.49, 1.55), and high income (RR 0.93; 95% CI 0.89, 0.96 quintile 1 versus 5). Longer duration of residence was associated with a higher risk of unintentional injuries for most causes except hot object/scald burns, machinery-related injuries, non-motor vehicle bicycle and pedestrian injuries. The risk of these latter injuries did not change significantly with increasing duration of residence in Canada. Risk of drowning was highest in recent immigrants. Risk of all-cause and most cause-specific unintentional injuries in immigrants rises with increasing time since migration. This indicates the need to develop strategies for maintaining the immigrant health advantage over time while balancing the desire to support integration, active living, and healthy child development.


"Make it possible for more people to work at home!" representations of employee motivation and job satisfaction in Danish and Norwegian newspapers during the COVID-19 pandemic.
During the COVID-19 pandemic, many employees with task-based jobs were forced to work from home, while others were furloughed or laid off. The current study aims to investigate how Norwegian and Danish newspapers represent employee motivation and job satisfaction of remote workers in light of the COVID-19 pandemic. The study used a thematic analysis of five newspapers from Norway and Denmark with different daily distributions and political orientations. The findings suggest that the newspapers in the two countries represented the topic of interest from different perspectives, and this led to the use of two motivation theories: the self-determination theory (SDT) and Herzberg's two-factor theory. The SDT helps us understand why some employees feel motivated and are more productive while working from home. The need for autonomy, competence, and connectedness is being satisfied for some employees but not for all, which may affect the strength of employees' job motivation. Herzberg's theory helps explain physical and psychological issues as dissatisfiers, as these issues are the consequence of working in a home-based office. Furthermore, a hybrid model seems to be an optimal solution for the future job market, where employees with task-based jobs can feel motivated and job satisfied while working either from home or from the workplace. Finally, it is important for employers to look after both the physical and the psychosocial conditions if hybrid solutions are going to replace the traditional workplace.


CD28 controls the development of innate-like CD8+ T cells by promoting the functional maturation of NKT cells.
NK T cells(NKT cells) share functional characteristics and homing properties that are distinct from conventional T cells. In this study, we investigated the contribution of CD28 in the functional development of γδ NKT and αβ NKT cells in mice. We show that CD28 promotes the thymic maturation of promyelocytic leukemia zinc finger(+) IL-4(+) NKT cells and upregulation of LFA-1 expression on NKT cells. We demonstrate that the developmental defect of γδ NKT cells in CD28-deficient mice is cell autonomous. Moreover, we show in both wild-type C57BL/6 mice and in downstream of tyrosine kinase-1 transgenic mice, a mouse model with increased numbers of γδ NKT cells, that CD28-mediated regulation of thymic IL-4(+) NKT cells promotes the differentiation of eomesodermin(+) CD44(high) innate-like CD8(+) T cells. These findings reveal a previously unappreciated mechanism by which CD28 controls NKT-cell homeostasis and the size of the innate-like CD8(+) T-cell pool.


Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?
The relationship between a predisposition to obesity and the development of colitis is not well understood. Our aim was to characterize the adipokine response and the extent of colitis in diet-induced obese (DIO) rats. DIO and control, diet-resistant (DR) animals were administered either saline or trinitrobenzene sulfonic acid (TNBS) to induce colitis. Macroscopic damage scores and myeloperoxidase (MPO) activity were measured to determine the extent of inflammation. Trunk blood was collected for the analysis of plasminogen activator inhibitor-1 (PAI-1) as well as leptin, ghrelin, and adiponectin. Colonic epithelial physiology was assessed using Ussing chambers. DIO rats had a modestly increased circulating PAI-1 before TNBS treatment; however, during colitis, DR animals had more than a fourfold increase in circulating PAI-1 compared with DIO rats. Circulating leptin was higher in DIO rats compared with DR animals, in the inflamed and noninflamed states. These changes in TNBS-induced adipokine profile were accompanied by decreased macroscopic tissue damage score in DIO animals compared with DR tissues. Furthermore, TNBS-treated DR animals lost significantly more weight than DIO rats during active inflammation. Colonic epithelial physiology was comparable between groups, as was MPO activity. The factors contributing to the decreased colonic damage are almost certainly multifold, driven by both genetic and environmental factors, of which adipokines are likely to play a part given the increasing body of evidence for their role in modulating intestinal inflammation.


Augmentation of the maxillary sinus: a surgical technique.
Specific anatomic and physiologic differences between the maxillary and mandibular arches have presented challenges in restoring the fully or partially edentulous maxilla. These differences include the quality and quantity of available bone at the potential implant site. To address the limitations of the maxillary arch, attempts have been made during the last two decades to improve implant anchorage in this area. Bone grafting techniques and guided bone regeneration have been utilized to augment and improve the maxillary arch. The learning objective of this article is to review the important aspects related to the anatomy and physiology of the maxillary sinus, to discuss the use of various grafting materials, and to describe the technique and current status of the maxillary sinus augmentation procedures. Emphasis is placed upon presentation of the presurgical, surgical, and postsurgical protocol of maxillary sinus augmentation, as performed by the authors.


Thermoregulation of the testicle in response to exercise and subsequent effects on semen characteristics of stallions.
Stallions (n = 8) were implanted with a thermal sensory device in the muscle of the neck and the subcutaneous tissue of the scrotum and then assigned to either a nonexercise (Non-EX; n = 4) or exercise (EX; n = 4) group. A motorized equine exerciser was used to work EX stallions 30 min/d for 4 d/wk during a 12-wk period from July through October 2010. Temperatures (subcutaneous scrotal, intramuscular neck, and rectal) were recorded at 0, 22, and 30 min after the start of exercise, as well as 60 and 120 min post-exercise. Hourly ambient temperature and relative humidity data were also obtained. Semen was collected at 0, 4, 8, and 12 wk and analyzed for volume, sperm concentration, total sperm numbers, percentages of total and progressively motile sperm, sperm morphologic characteristics, and sperm DNA quality. No effect (P > 0.05) of exercise was observed on any of the measured semen variables. Implantation of thermal sensory devices had no demonstrable acute or chronic effects on the scrotal or neck tissue, indicating that the thermal sensory devices are a safe and effective way to measure subcutaneous scrotal and neck temperatures. At 22 and 30 min of exercise, rectal and neck temperatures increased (P < 0.0001) approximately 1.9 and 2.4°C, respectively, and scrotal temperatures simultaneously increased, although not significantly (P = 0.33), approximately 0.8°C. Correlations existed between scrotal, neck, rectal, and ambient temperatures, with the correlation between scrotal and rectal temperatures being greatest (r(s) = 0.76; P < 0.0001). Although moderate exercise for a short duration in extreme heat and humidity did significantly increase core body temperatures in stallions, scrotal temperatures did not significantly increase, and sperm parameters were unaffected.


The robust and independent nature of structural STS asymmetries.
The superior temporal sulcus (STS) is an important region for speech comprehension. The greater language network is known to exhibit asymmetries in both structure and function, and consistent with that theory are reports of STS structural asymmetry in MRI-based, morphological measures such as mean thickness and sulcal depth. However, it is not known how these individual STS structural asymmetries relate to each other, or how they interact with the broader language asymmetry that manifests in other brain regions. In this study, we assess the interrelations of STS asymmetries in the human brain in vivo, using four independent datasets to validate our findings. For morphological measurements, we identify STS laterality effects consistent between our datasets and with the literature: leftward for surface area, and rightward for sulcal depth and mean thickness. We then add two more measurements of STS asymmetry: in T1, a quantitative index of the tissue's underlying biophysical properties; and in the projections to the STS from the arcuate fasciculus, a left-lateralized white-matter bundle that connects temporal regions (including STS) with frontal regions (including Broca's area). For these two new measurements, we identify no effect for T1 and a leftward effect for arcuate projections. We then test for correlations between these STS asymmetries, and find associations mainly between measurements of the same type (e.g., two morphological measurements). Finally, we ask if STS asymmetry is preferentially related to Broca asymmetry, as these are both important language regions and connected via the arcuate fasciculus. Using a linear model with cross-validation, we find that random regions are as successful as Broca's area in predicting STS, and no indication of a hypothesized leftward asymmetry. We conclude that although these different STS asymmetries are robust across datasets, they are not trivially related to each other, suggesting different biological or imaging sources for different aspects of STS lateralities.


High-performance metabolic marker assessment in breast cancer tissue by mass spectrometry.
The identification of reliable markers for diagnosis of breast cancer has been thoroughly addressed by metabolic profiling using nuclear magnetic resonance (NMR) spectroscopy or imaging. Several clear diagnostic indicators have emerged using either in vitro analysis of tissue extracts, ex vivo analysis of biopsies or in vivo direct spectral observations. Most of the breast cancer characteristic metabolites could be assayed by mass spectrometry (MS) to exploit the superior sensitivity of this technique and therefore reduce the traumatic impact of current biopsy procedures. Following extraction, aqueous metabolite mixtures were obtained that were submitted to liquid-chromatography, electrospray-ionization, mass spectrometry (LC/ESI-MS) analysis to estimate the content of choline (Cho) and its phosphorylated derivatives, phosphocholine (PCho) and glycerophosphocholine (GPCho). The determinations were performed using 10 samples from breast tissue biopsies, surgical specimens and one single sample of a hepatic metastasis. In addition, some measurements were also repeated using high-resolution ¹H NMR spectroscopy to complement the mass spectrometry results. The contents of Cho, PCho and GPCho in breast tissue extracts were estimated by LC/ESI-MS based on standard compound calibration curves. Sharply increased ratios of phosphorylated-to-unphosphorylated metabolites, PCho/ Cho and (PCho+GPCho)/Cho, were observed in all tumor samples, although without discrimination between benign and malignant lesions, contrary to samples from healthy individuals and from those with fibrocystic disease. The assessment of breast cancer markers by LC/ESI-MS is feasible and diagnostically valuable. In addition to high sensitivity, the approach also shows a resolution advantage for assaying choline derivatives compared to NMR, and could complement the latter.


Giant right coronary artery aneurysm: the saphenous vein bridge technique.
A giant coronary artery aneurysm is defined as an irreversible dilation that is 1.5-times more than the diameter of a healthy adjacent coronary artery. It is a rare disease with an incidence of 0.2% to 4.9%. Coronary artery aneurysms are usually corrected with a coronary artery bypass graft. We describe how to perform a saphenous vein bridge to repair a giant coronary artery aneurysm. When applicable, this technique allows sparing of the coronary artery ostia and restores the coronary anatomy.


Recovery of proteins from corn and soybean extracts by membrane adsorption.
Efficient separation strategies for the recovery of high-value proteins (native or recombinant) from plant agriculture are an important aspect of many different processes, from biopharmaceuticals to byproduct recovery during biofuel production. Here we report the use of membrane adsorption for the recovery of proteins from soybean and corn extracts, and compare the results with packed bed adsorption. Two alternative operating modes were investigated, a flowthrough strategy and a bind and elute method. Overall, membrane adsorption provided faster throughput, and had equal or slightly higher dynamic binding capacities compared with resin beads, without compromising yield and purity of the chosen target. Soybean was found to be an ideal plant host when capturing native protein on an anion exchange medium. This provided an opportunity to capture a large percentage (>80%) of native protein as the product, and/or allowed for elevated enrichment factors (>20) during purification of a recombinant target with pI > 7.0, using a flowthrough approach. On the other hand, for corn, a single ion-exchange step was not able to capture more than 60% of the native protein. However, the bind and elute method with corn as the host for a recombinant product allowed for higher enrichment factors compared to soybean. In all cases, the concentration of a recombinant protein (as dictated by expression level) was found to play a significant role in the level of dynamic binding capacity, with higher concentration leading to elevated capacity. Likewise, a higher concentration of competing proteins was shown to decrease the overall capacity of a recombinant target.


Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus.
Visual cortex ablation in newborn rats determines the almost complete degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of the geniculo-cortical fibres. Death of dLGN neurons is massive and rapid, and occurs by apoptosis. We recently showed that exogenous administration of the neurotrophin brain-derived neurotrophic factor (BDNF) in the eye prevents the degeneration of dLGN neurons occurring after visual cortex lesion in newborn rats. To elucidate the molecular mechanisms of BDNF-mediated neuroprotection, we sought to identify novel genes regulated by BDNF in the rat dLGN after visual cortex lesion. By using mRNA fingerprinting, we isolated a cDNA fragment upregulated in the dLGN of lesioned rats treated with BDNF. This cDNA fragment shared 100% homology with the rat cytosolic branched chain aminotransferase (BCATc), a key enzyme of glutamate metabolism. Quantitative reverse transcription-polymerase chain reaction and in situ hybridization confirmed that BCATc mRNA is markedly overexpressed by exogenous supply of BDNF to axotomized dLGNs. Immunohistochemical analysis showed that upregulation of BCATc in the dLGN of lesioned rats treated with BDNF takes place in astrocytes. These results suggest that modulation of glutamate metabolism by astrocytes might play an important role in BDNF-mediated survival of axotomized dLGN neurons.