Sound frequency affects speech emotion perception: results from congenital amusia.
Congenital amusics, or "tone-deaf" individuals, show difficulty in perceiving and producing small pitch differences. While amusia has marked effects on music perception, its impact on speech perception is less clear. Here we test the hypothesis that individual differences in pitch perception affect judgment of emotion in speech, by applying low-pass filters to spoken statements of emotional speech. A norming study was first conducted on Mechanical Turk to ensure that the intended emotions from the Macquarie Battery for Evaluation of Prosody were reliably identifiable by US English speakers. The most reliably identified emotional speech samples were used in Experiment 1, in which subjects performed a psychophysical pitch discrimination task, and an emotion identification task under low-pass and unfiltered speech conditions. Results showed a significant correlation between pitch-discrimination threshold and emotion identification accuracy for low-pass filtered speech, with amusics (defined here as those with a pitch discrimination threshold >16 Hz) performing worse than controls. This relationship with pitch discrimination was not seen in unfiltered speech conditions. Given the dissociation between low-pass filtered and unfiltered speech conditions, we inferred that amusics may be compensating for poorer pitch perception by using speech cues that are filtered out in this manipulation. To assess this potential compensation, Experiment 2 was conducted using high-pass filtered speech samples intended to isolate non-pitch cues. No significant correlation was found between pitch discrimination and emotion identification accuracy for high-pass filtered speech. Results from these experiments suggest an influence of low frequency information in identifying emotional content of speech.


[THE SECOND VICTIM: TREATING THE HEALTH CARE PROVIDERS].
During their professional careers, physicians and other health care providers are repeatedly exposed to emotional stress. This is usually secondary to coping with the results of a medical error or complicated medical event. Generally, in the above cases, the patient and his/her family are in the center of the medical system, being "the first victim" of such an event, while the involved caregiver, who provided the medical service, is categorized as the "second victim". "Second victims" may feel anxiety, fear, guilt or anger and experience social withdrawal, which may lead to troubling memories, depression and insomnia. Over the years, this situation may lead to deterioration in his/her work and personal life and, in rare circumstances, may lead to pharmaceutical and even alcohol consumption. In the literature there are even some rare case reports of "second victims" who have committed suicide. To meet these challenges, several leading institutions in western countries have developed formal support programmes that allow health care providers to cope with their emotional distress by obtaining timely support in an emphatic, confidential, non-judgmental environment. The above scheme of support is not meant to disrupt any correct medical investigation or to stand between the "second victim" and his superiors, but rather to allow them to cope with these events. We believe that the time has come to develop national support programs appropriate to our culture and behavioural circumstances. Local health care organizations should build a supporting scheme for the "second victims", helping them to cope with these events, thereby assisting them to return to their daily work and former routine.


Let's reach all of the market for health administration education: design, development, and delivery issues in distance delivery.
Web-based distance learning is an up and coming form of education. Web-based education delivered via a Web browser through the Internet has been found to be less expensive, more efficient, and sometimes more effective than classroom training. In the distance learning environment, the traditional "lecture and chalkboard" classroom pedagogy is completely absent. The virtual classroom becomes an "active learning" environment in which students, while utilizing technology, are able to discuss health administration concepts, analyze cases, work exercises, and discuss and share these interactively with both the instructor and fellow classmates. This method of Health Administration Education encourages students to learn from each other and promotes the open exchange of ideas and experiences. It does not require working students to put their careers on hold while they continue their studies. In this paper, we explore the opportunities and challenges of delivering web-based Health Administration courses via the Internet. Included is a discussion of the design, development, and delivery of a distance learning, web-based Health Administration Education system.


Absorption, metabolism, and excretion of [14C]evogliptin tartrate in male rats and dogs.
The objective of this study was to determine the absorption, excretion, and metabolism of a novel, oral antihyperglycemic drug, evogliptin, in male rats and dogs. Plasma, urine, feces, and expired air samples were collected after a single oral dose administration of [14C]evogliptin, samples were analyzed by measuring overall radioactivity levels using high-performance liquid chromatography (HPLC), and radioactivity levels were measured by utilizing LC-tandem mass spectrometry (LC-MS/MS). The total amounts of radioactivity excreted in urine, feces, and expired air up to 168 h after administration of [14C]evogliptin tartrate to rats (30 mg evogliptin/kg) and dogs (10 mg evogliptin/kg) were 96.7% and 96.8% of initial doses administered, respectively. The extent of urinary and fecal excretion in the rat up to 168 h constituted 29.7% and 66.5% of the given dose, respectively; and in dog was 43.3% and 53.5%, respectively. A total of 23 possible metabolites were detected with radiochromatograms of plasma, urinary, and fecal samples, but only the structures of 12 metabolites were identified via LC-MS/MS analysis. Evogliptin was the major component. Regarding the total radiochromatographic peak areas, peaks 9 (evogliptin acid) and 11 (hydroxyevogliptin) were the major metabolites in rats, and peaks 8 [4(S)-hydroxyevogliptin glucuronide], 15 [4(S)-hydroxyevogliptin], and 17 [4(R)-hydroxyevogliptin] were the predominant metabolites in dogs. Data demonstrated that evogliptin was the major component excreted in urine and feces of rats and dogs, but the metabolite profiles varied between species.


Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.
The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.


A further cold agglutinin, F1, recognizing a N-acetylneuraminic acid-determined antigen.
A cold agglutinin, F1, reacted with an erythrocyte antigen, which was inactivated by neuraminidase. It resembled anti-I antibodies in reacting more strongly with erythrocytes of adults than with cord blood cells. However, unlike I, this 'new' antigen is destroyed by neuraminidase treatment. This antigen is also distinct from Pr, Gd and Sa type antigens which are equally expressed on cord and adult erythrocytes.


Antihypertensive efficacy and orthostatic tolerance of bunazosin vs nitrendipine: a multicentre double-blind randomized controlled study.
A multicentre double-blind randomized controlled study was conducted in 358 patients with mild to moderate essential hypertension. The goal was to compare the antihypertensive efficacy, tolerability, and in particular postural hypotension of the alpha 1-adrenoreceptor blocker bunazosin with the calcium channel blocker nitrendipine. Both treatment groups had comparable baseline blood pressure (BP) values, namely diastolic BP (DBP) of 103.8 +/- 5.6 mm Hg in the bunazosin group, and 103.4 +/- 6.0 mm Hg in the nitrendipine group, respectively. Baseline systolic BPs (SBP) were 149.7 +/- 14.4 mm Hg (bunazosin) and 149.2 +/- 14.3 mm Hg (nitrendipine). After 12 weeks of therapy, reduction of DBP (-6.1 +/- 11.7 mm Hg on bunazosin vs -6.9 +/- 9.9 mm Hg on nitrendipine; P = n.s.), and SBP (-4.4 +/- 14.3 mm Hg on bunazosin vs -7.0 +/- 14.4 mm Hg on nitrendipine; P = n.s.) was similar in both groups. During a provocative orthostatic tolerance test after the first dose, the incidence of prae-collapses (ie termination of the test due to orthostatic complaints) was higher on bunazosin (17 vs 2; P < 0.05) but orthostatic dysregulation symptoms (symptom score 1.37 on bunazosin vs 0.95 on nitrendipine; n.s.) and collapses (four on bunazosin vs one on nitrendipine; n.s.) occurred to a similar extent in both treatment groups. Three and 9 weeks after treatment, no increased susceptibility to orthostatic stress compared to baseline could be found in either group. Under daily life conditions, the frequency of orthostatic dysregulation was identical in both groups (0.8%). Bunazosin, however, was far better tolerated with 43.8% of the patients complaining of adverse events as opposed to 63.6% on nitrendipine (P < 0.001). The rate of early discontinuations due to adverse events was only 1.3% on bunazosin compared to 13.6% on nitrendipine (P < 0.001). In conclusion, bunazosin has a similar antihypertensive efficacy as nitrendipine. Despite an initially higher susceptibility to orthostatic stress under a provocative manoeuver, bunazosin evoked the same low incidence of orthostatic dysregulation symptoms as nitrendipine under daily life conditions, but was significantly better tolerated than nitrendipine.


The "dependent viscera" sign in CT diagnosis of blunt traumatic diaphragmatic rupture.
The objective of our study was to describe the "dependent viscera" sign and determine its usefulness at CT in the diagnosis of diaphragmatic rupture after blunt abdominal trauma. The study sample consisted of 28 consecutive patients (19 men, nine women) between 17 and 74 years old (mean age, 31 years) who had undergone abdominal CT and subsequent emergency laparotomy after a blunt trauma. Ten patients had a diaphragmatic rupture (six, right-sided; four, left-sided) at laparotomy. An experienced radiologist unaware of the surgical findings retrospectively reviewed the CT scans, and then a second radiologist reviewed the scans to provide interobserver agreement. Note was made of discontinuity of the diaphragm, intrathoracic herniation of abdominal contents, and waistlike constriction of bowel (the collar sign). Also noted was whether the upper one third of the liver abutted the posterior right ribs or whether the bowel or stomach lay in contact with the posterior left ribs. Either of these findings was termed the "dependent viscera" sign. The radiologists' detection rate of diaphragmatic rupture on the CT scans via observance of the dependent viscera sign was determined. Interobserver agreement was assessed using Cohen's kappa statistic. The dependent viscera sign was observed on the CT scans of 100% of the patients with a left-sided diaphragmatic rupture and of 83% of the patients with right-sided diaphragmatic rupture. Both observers missed one case of right-sided diaphragmatic rupture. The radiologists' overall rate of detecting diaphragmatic rupture was 90% using the dependent viscera sign. We found excellent interobserver agreement (kappa = 1) for detection of the dependent viscera sign and for the diagnosis of diaphragmatic tear on CT scans. The dependent viscera sign increases the detection at CT of acute diaphragmatic rupture after blunt trauma.


Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1.
Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin.


Purification and biochemical analysis of native AMPA receptors from three different mammalian species.
The majority of fast, excitatory synaptic transmission in the central nervous system (CNS) is mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), which are glutamate-activated ion channels integral to synaptic plasticity, motor coordination, learning, and memory. Native AMPARs are multiprotein assemblies comprised of a tetrameric receptor core that co-assembles with a broad range of peripheral auxiliary proteins which shape subcellular localization and signaling properties of the resulting complexes. Structure determination of AMPARs has traditionally relied on recombinant expression systems; however, these methods are not well suited to elucidate the diverse array of AMPAR assemblies that are differentially expressed in mammalian brains. While recent studies of native receptor complexes have advanced our understanding of endogenous assemblies, receptors thus far have only been isolated from rodent brain tissue. Here, we employed an immunoaffinity purification strategy to isolate native AMPARs from the brains of three different mammals-pigs, sheep, and cows. Compared to rodents, pigs, sheep, and cows are ungulate mammals, animals with closer genomic identity with humans. Here we determined the molecular size, overall yield, and purity of native AMPARs isolated from these three mammals, thereby demonstrating that structural determination and biochemical analysis is possible from a clade of mammals evolutionarily distinct from rodents.


Nutrition and somatomedin. I. Effect of fasting and refeeding on serum somatomedin activity and cartilage growth activity in rats.
The relationship between nutrition, somatomedin, and growth was studied in young male rats which were fasted for 72 h, and then refed. Cartilage growth activity was measured by the incorporation of SO4 by costal cartilage incubated in vitro. Serum somatomedin activity was measured by the ability of sera to stimulate the incorporation of SO4 in vitro by cartilage from hypophysectomized rats or normal young pigs. Cartilage growth activity was unchanged after 24 h of fasting, but decreased significantly to hypopituitary levels after 72 h. The decrease in cartilage growth activity could not be attributed to a decrease in the ability of cartilage to respond to somatomedin, since fasted rat cartilage incubated in vitro had significantly greater stimulation from the addition of normal rat serum (normal somatomedin) than from the addition of hypophysectomized rat serum (low somatomedin). A decrease in serum somatomedin preceded the decrease in growth activity; somatomedin was significantly decreased after 24 h of fasting, and fell to hypopituitary levels after 72 h of fasting. The decrease in somatomedin could not be attributed to growth hormone deficiency, since treatment with bGH did not prevent the fall in somatomedin. The direct addition of fasted rat serum to normal rat serum did not inhibit the somatomedin activity of the normal serum. The refeeding of 72h-fasted rats was associated with an increase in serum somatomedin which was significant after 6 h, and comparable to control levels after 24 h of refeeding. The increase in somatomedin was followed by an increase in cartilage growth activity, which was significant after 12 h, and comparable to control levels after 48 h of refeeding. We conclude that adequate food intake appears to be required for the maintenance of normal levels of somatomedin; the processing of nutrients may modulate the generation of somatomedin.


The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
The c-Abl tyrosine kinase protein is implicated in the signaling pathway as well as in transcription, DNA repair, apoptosis, and several other vital biological processes essential for cell proliferation or differentiation. The interaction of c-Abl with DNA is important for some of these functions, but the exact nature of this interaction is still a matter of controversy. The present study addresses the DNA-binding properties of the human c-Abl protein. Using CASTing experiments, the consensus binding site 5'-AA/CAACAAA/C was determined. The central highly conserved AAC triplet appears to constitute the crucial core element in the binding sequences of the c-Abl protein. The c-Abl DNA-binding domain recognizes specific sequences and interacts with deformed DNA structures such as four-way junctions and bubble DNA containing a large single-stranded loop, as determined by electromobility shift assay, melting temperature studies, and binding to specific oligonucleotides covalently linked to beads. Additional competition experiments suggest that the interaction mainly involves contacts within the minor groove of the double helix. The DNA-binding properties of c-Abl are reminiscent of those of high-mobility group (HMG)-like proteins such as LEF-1 and SRY. However, the circular permutation and ring closure assays and DNA unwinding experiments reveal that, unlike HMGs, c-Abl does not bend its target sequence. In addition, it is shown that the protein potentiates the DNA relaxation activity of topoisomerase I. These findings indicate that the interaction of c-Abl with DNA is both sequence-selective and structure-dependent.


Amphetamine and methamphetamine differentially affect dopamine transporters in vitro and in vivo.
The psychostimulants d-amphetamine (AMPH) and methamphetamine (METH) release excess dopamine (DA) into the synaptic clefts of dopaminergic neurons. Abnormal DA release is thought to occur by reverse transport through the DA transporter (DAT), and it is believed to underlie the severe behavioral effects of these drugs. Here we compare structurally similar AMPH and METH on DAT function in a heterologous expression system and in an animal model. In the in vitro expression system, DAT-mediated whole-cell currents were greater for METH stimulation than for AMPH. At the same voltage and concentration, METH released five times more DA than AMPH and did so at physiological membrane potentials. At maximally effective concentrations, METH released twice as much [Ca(2+)](i) from internal stores compared with AMPH. [Ca(2+)](i) responses to both drugs were independent of membrane voltage but inhibited by DAT antagonists. Intact phosphorylation sites in the N-terminal domain of DAT were required for the AMPH- and METH-induced increase in [Ca(2+)](i) and for the enhanced effects of METH on [Ca(2+)](i) elevation. Calmodulin-dependent protein kinase II and protein kinase C inhibitors alone or in combination also blocked AMPH- or METH-induced Ca(2+) responses. Finally, in the rat nucleus accumbens, in vivo voltammetry showed that systemic application of METH inhibited DAT-mediated DA clearance more efficiently than AMPH, resulting in excess external DA. Together these data demonstrate that METH has a stronger effect on DAT-mediated cell physiology than AMPH, which may contribute to the euphoric and addictive properties of METH compared with AMPH.


Safe and uncomplicated inguinal hernia surgery in the elderly - message from anesthesiologists to general surgeons.
Introduction Elderly patients are often discouraged from surgery due to the risk of complications that increases with age. Aim We wanted to assess mortality, morbidity, and complications in patients older than 75 years who underwent elective or emergency inguinal hernia repair in a single center. Methods All patients older than 75 years who were operated on because of inguinal hernia in the Department of General and Colorectal Surgery, Medical University of Lodz between 2003 and 2015 were analyzed. Detailed information was collected with regard to patient demographics, mode of admission, comorbidities, type of intervention, applied anesthesia, and 30-day outcomes. Postoperative outcomes included medical and surgical complications, readmissions, and survival status. Results One hundred thirty-two patients older than 75 years were operated on for inguinal hernia, 16 (12.1%) in an emergency setting and 116 (87.9%) in an elective setting. Eighteen patients (13.6%) developed complications, 8 (50%) in the emergency group, and 10 (8.6%) in the elective group. In the emergency group, severe medical complications (Clavien-Dindo 4) were frequent, whereas in the elective group, severity of surgical and medical complications was not significantly different (Clavien-Dindo median score 2, p=0.6084), and these complications were classified as mild (Clavien-Dindo 1-2). One death occurred in the emergency group. Conclusion Inguinal hernia surgery in the elderly may be safe and effective in an elective setting and if regional anesthesia is used. Careful examination of patients before surgery and identification of potential risk factors associated with co-existing diseases are vital for reducing the risk of complications. Key point: Hernia surgery in patients older than 65 years is a low-risk intervention, if carried out in an elective setting.


Antibody Validation by Immunoprecipitation Followed by Mass Spectrometry Analysis.
We describe a mass spectrometry-based approach for validation of antibody specificity. This method allows validation of antibodies or antibody fragments, against their endogenous targets. It can assess if the antibody is able to bind to its native antigen in cell lysates among thousands of other proteins, DNA, RNA, and other cellular components. In addition, it identifies other proteins the antibody is able to immunoprecipitate allowing for the assessment of antibody specificity and selectivity. This method is easily scalable, adaptable to different cell lines and conditions and has been shown to be reproducible between multiple laboratories.


Stimulation of lymphocytes in vitro by Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis sonicates.
The present study was designed to assess whether the in vitro stimulation of lymphocytes by sonicates of Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis is antigen specific or non-specific. In addition, the role of T and B lymphocytes in these responses was assessed. Peripheral blood lymphocytes obtained from healthy volunteers were cultured in the presence of these bacterial preparations and the proliferative response was measured. In similar experiments the response of umbilical cord blood lymphocytes did not exceed background values. In limiting dilution experiments only 1:4000, 1:6800, and 1:8200 of the lymphocytes initially reacted to B. intermedius, which strongly argues for the antigen-specificity of the response. Purified T cells, in the presence of monocytes, proliferated when stimulated with B. intermedius and B. gingivalis. As for B cell stimulation, the bacterial extracts were capable of inducing IgM production, which appeared to be T cell dependent. These findings support the notion that B. intermedius and B. gingivalis induce specific T cell activation; secondarily, a T cell dependent, polyclonal B cell activation may occur.


Function of the airway epithelium in asthma.
Asthma is traditionally defined as a chronic disease characterized by bronchial hyper-responsiveness and lung inflammation. The airway inflammation and remodelling together likely explain the clinical manifestations of asthma. The mechanisms by which the external environmental cues, together with the complex genetic actions, propagate the inflammatory process that characterizes asthma are beginning to be understood. There is also an evolving awareness of the active participation of structural elements, such as the airway epithelium, airway smooth muscle, and endothelium, in this process; these structural elements within the lung and the bone marrow serve as reservoirs for and the source of inflammatory cells and their precursors. Although often viewed as separate mechanistic entities, so-called innate and acquired immunity often overlap in the propagation of the asthmatic response. This review examines the newer information on the pathophysiologic characteristics of asthma and focuses on the role of airway epithelium in the exacerbation of the disease.


Ultraviolet irradiation of trans-resveratrol and HPLC determination of trans-resveratrol and cis-resveratrol in Romanian red wines.
A reversed-phase high-performance liquid chromatography method with diode array detection was developed for the determination of trans- and cis-resveratrol in red wines. Separation was achieved after direct injection by the use of a BDS Hypersil C18 column (250 × 4.6 mm) with gradient elution (solvent A: acetic acid 2%, solvent B: acetonitrile). Detection of trans- and cis-resveratrol was performed at 306 and 286 nm, respectively. The retention times of trans- and cis-resveratrol were 22.2 and 26.1 min, respectively. Good linearity and precision were obtained for the two isomers. Detection limits of 0.004 mg/L for trans-resveratrol and 0.02 mg/L for cis-reveratrol were obtained. The developed method was applied to determine cis- and trans-resveratrol in 30 red wines produced in Oltenia (southwestern Romania). The wines came from different vineyards harvested in various vintages. The concentration of trans-resveratrol ranged from 0.287 to 7.188 mg/L, while the content of cis-resveratrol ranged from 0.718 to 6.587 mg/L. The highest amount of trans-resveratrol was found in Merlot from Vanju Mare, Mehedinti (7.188 mg/L), followed by Sirah from Corcova, Mehedinti (4.738 mg/L), both from the 2010 harvest. The paper also approaches the study of the transformation of trans-resveratrol into the cis form after ultraviolet irradiation through glass and quartz. At the irradiation of a trans-resveratrol solution through quartz, the formation of another two compounds apart from cis-resveratrol was observed.


Twelve cases of hydronephrosis in utero diagnosed by ultrasonography.
Twelve examples of hydronephrosis in utero, seven of which were bilateral, were seen at the Johns Hopkins Hospital. Unexpected findings on sonographic examination were: 1) two cases of transient hydronephrosis of moderate severity, persisting over several examinations, which disappeared spontaneously; 2) only two of six examples of ureteropelvic junction obstruction were detected by palpation by competent neonatologists at the time of delivery; 3) polyhydramnios in association with bilateral ureteropelvic junction obstruction was observed in one case and had been reported twice previously (two cases of the prune belly syndrome, however, were associated with oligohydramnios); 4) two examples of a mixed pattern of hydronephrosis and multicystic kidney were seen.


Recombinant interferon-gamma induces interleukin 2 receptors on human peripheral blood monocytes.
The present report describes the inducibility of IL 2 receptors on human peripheral blood monocytes. Although freshly isolated monocytes are IL 2 receptor negative, approximately one-third of the cells react with the anti-Tac antibody within 18 hr of culture. IFN-gamma is found to double both the number of positive cells and the number of binding sites, whereas IL 2 has no influence on the IL 2 receptor expression on monocytes. Anti-Tac precipitates from monocyte lysates several protein bands of similar m.w. to those previously found with activated T and B cells. Finally, IFN-gamma-induced, but not resting, monocytes are found to bind recombinant IL 2. We conclude that IFN-gamma induces peripheral blood monocytes to express IL 2 receptors similar in structure to those found on activated T and B lymphocytes.


Reliability of self-reports: data from the Canadian Multi-Centre Osteoporosis Study (CaMos).
Reliable questions enhance study design. We assessed the reliability of questions that gather demographic, sun exposure, reproductive history, and physical activity information. Subjects were participants in the Canadian Multicentre Osteoporosis Study (CaMos), a cohort study of Canadian adults recruited January 1996 to September 1997 in nine cities, stratified by sex, age, and location. Following personal interviews, 367 subjects were re-administered part of the questionnaire by telephone. Reliability was assessed using kappa and intra-class correlation. Reliability was excellent for employment status, reproductive history, weight and height (0.91 to 0.97), not differing greatly when stratified by age group or sex. Physical activity and sun exposure were reported with fair to good reliability (0.44 to 0.58), except for moderate activity (kappa = 0.30, 95% confidence interval 0.23, 0.37). Stratification by body mass index did not show significant differences. Many items can be reported reliably, especially those of height, weight, employment status and reproductive history, and, to a lesser extent, physical activity and sun exposure. Similar questions might be used reliably in future studies.


Calcium homeostasis disorder during and after neonatal extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) is used during pediatric resuscitation in case of refractory hypoxemia or septic shock under maximum therapy. Previous studies describe calcium homeostasis dysregulation. The aim of this study was to confirmed of calcium homeostasis dysregulation in neonates under ECMO and supposed news explanation. From November 2012 to July 2013, we performed a prospective single center observational study. Eleven neonatal patients were included. Blood was obtained before and during ECMO (day 7, 14 and 21) for parathyroid hormone (PTH), protein adjusted serum calcium, ionized calcium, magnesium, and calcitriol levels. All surviving patients underwent a consultation up to 6 months after ECMO weaning. During ECMO PTH was inadequately high with normal serum calcium on day 7 (PTH: 73.54 ± 40 ng/l; calcemia: 2.33 ± 0.21 mmol/l), day 14 (PTH: 57.63 ± 29.57 ng/l; calcemia: 2.44 ± 0.43 mmol/l) and day 21 (PTH: 54.93 ± 8.43 ng/l; calcemia: 2.13 ± 0.09 mmol/l). The absence of correlation between serum calcium and PTH levels seem to confirm the dysregulation of PTH - serum calcium metabolism during ECMO. Six months after ECMO weaning, we noticed hypercalcemia with normal PTH. We confirmed the existence of severe disturbances of calcium homeostasis in neonates on ECMO and supposed the possible damage of calcium regulation. We did not succeed in finding clear explanations of these disturbances.


Biofilm Formation Mechanisms of Pseudomonas aeruginosa Predicted via Genome-Scale Kinetic Models of Bacterial Metabolism.
A hallmark of Pseudomonas aeruginosa is its ability to establish biofilm-based infections that are difficult to eradicate. Biofilms are less susceptible to host inflammatory and immune responses and have higher antibiotic tolerance than free-living planktonic cells. Developing treatments against biofilms requires an understanding of bacterial biofilm-specific physiological traits. Research efforts have started to elucidate the intricate mechanisms underlying biofilm development. However, many aspects of these mechanisms are still poorly understood. Here, we addressed questions regarding biofilm metabolism using a genome-scale kinetic model of the P. aeruginosa metabolic network and gene expression profiles. Specifically, we computed metabolite concentration differences between known mutants with altered biofilm formation and the wild-type strain to predict drug targets against P. aeruginosa biofilms. We also simulated the altered metabolism driven by gene expression changes between biofilm and stationary growth-phase planktonic cultures. Our analysis suggests that the synthesis of important biofilm-related molecules, such as the quorum-sensing molecule Pseudomonas quinolone signal and the exopolysaccharide Psl, is regulated not only through the expression of genes in their own synthesis pathway, but also through the biofilm-specific expression of genes in pathways competing for precursors to these molecules. Finally, we investigated why mutants defective in anthranilate degradation have an impaired ability to form biofilms. Alternative to a previous hypothesis that this biofilm reduction is caused by a decrease in energy production, we proposed that the dysregulation of the synthesis of secondary metabolites derived from anthranilate and chorismate is what impaired the biofilms of these mutants. Notably, these insights generated through our kinetic model-based approach are not accessible from previous constraint-based model analyses of P. aeruginosa biofilm metabolism. Our simulation results showed that plausible, non-intuitive explanations of difficult-to-interpret experimental observations could be generated by integrating genome-scale kinetic models with gene expression profiles.


The Solvent Induced Inter-Dimensional Phase Transformations of Cobalt Zeolitic-Imidazolate Frameworks.
Studying inter-dimensional phase transitions of zeolitic-imidazolate frameworks (ZIFs) is essential for developing strategies in controlling morphology and properties. Herein, the inter-dimensional topotactic phase transformations of 3D ZIF-67 to 2D ZIF-L are investigated in detail by employing a simple and efficient solvent-induced growth method. In addition to ZIF-67 and ZIF-L, a series of novel core-shell composites of ZIF-67@ZIF-L, with unprecedented morphologies, are also obtained and well-defined. The different behaviors of the amine hydrogen of 2-MIM in the solvents play a pivotal role for inter-dimensional phase transformations, and in combination with the concentration of 2-MIM, the 2D to 3D phase transformations are also revealed. The findings are very beneficial for morphological design of the ZIFs, along with exploration of the corresponding properties. Impressively, Co-ZIFs exhibit interesting tunable CO2 adsorption behaviors with the phase evolution, which might bring broader understanding for designing CO2 detection and adsorption devices.


Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice.
We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse-induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.


Resistance training and bone mineral density during growth.
This study examined the efficacy of two different resistance training programs in enhancing bone modeling and bone mineral density (BMD) in maturating rats. One exercise mode involved lifting a lighter weight with more repetitions (LI), while the other regimen involved lifting a heavier weight with fewer repetitions (HI) where the total volume of work between exercise programs was equivalent by design. Twenty-three male rats were randomly divided into control (Con, n = 8), LI (n = 7), and HI (n = 8) groups. The LI and HI groups were conditioned to climb a vertical ladder with weights appended to their tail 4 days/wk for 6 wks. After training, serum osteocalcin (OC) was significantly (p < 0.05) higher in both HI (45.2 +/- 1.7 ng/ml) and LI (39.1 +/- 2.2 ng/ml) when compared to Con (29.9 +/- 0.9 ng/ml). Left tibial BMD was significantly (p < 0.05) greater for HI (0.231 +/- 0.004 g/cm (2)) when compared to both LI (0.213 +/- 0.003 g/cm (2)) and Con (0.206 +/- 0.005 g/cm (2)) with no significant difference between LI and Con. The results indicate that both HI and LI are effective in elevating serum OC, implicating an osteogenic response; however, only HI resulted in a significant elevation in BMD.


Fasting blood glucose levels and initiation of insulin therapy in gestational diabetes.
To determine whether an initial fasting blood glucose determination will predict which pregnant women will need insulin in addition to dietary measures to maintain fasting glucose levels during gestation. All women referred for management of gestational diabetes received dietary counseling and instructions for self-monitoring of blood glucose levels during fasting and at 2 hours after each meal. Insulin therapy was initiated if the fasting blood glucose value exceeded 5.8 mmol/L (105 mg/dL) on more than one occasion, the 2-hour postprandial glucose exceeded 8.3 mmol/L (150 mg/dL), or the 2-hour postprandial glucose exceeded 6.7 mmol/L (120 mg/dL) three times in a week. The use of diet alone or diet plus insulin therapy was determined by review of medical records. Fifty-two pregnant women with fasting blood glucose levels of less than 5.8 mmol/L (105 mg/dL) and with two or more elevated blood glucose values on a 3-hour glucose tolerance test underwent follow-up at least through the 36th week of gestation. In 21 patients, insulin therapy was initiated in addition to diet. Two of five women with an initial fasting glucose level of less than 4.4 mmol/L (80 mg/dL) required insulin, and 8 of 24 women with fasting levels of 5.3 to 5.8 mmol/L (96 to 105 mg/dL) eventually needed insulin. The height of the fasting blood glucose level in women with gestational diabetes does not separate those who will maintain blood glucose levels in the targeted therapeutic range on diet alone from those who will need insulin. Therefore, all women with gestational diabetes need to participate in self-monitoring of blood glucose levels.


[The prevention of delirium].
Delirium is a disturbance of consciousness, cognition and perception that occurs frequently in medically ill patients. Although it is associated with increased morbidity and mortality, it is often not recognised. Predisposing factors are believed to have multiplicative effects and include dementia, advanced age and male gender. Recently developed models allow for the estimation of the risk of developing delirium during a hospitalisation, based on predisposing factors and acute additional stressors. Although it has been shown to be efficacious, the prevention of delirium is underutilised. Prevention consists of aggressive management of known risk factors and early detection. The intervention had not always significant effect on the severity of delirium or on recurrence rates; this finding suggests that primary prevention of delirium is probably the most effective treatment strategy.


Evaluation of the ability of the trypsin-like peptidase activity assay to detect severe periodontitis.
N-benzoyl-DL-arginine peptidase (trypsin-like peptidase) is specifically produced by certain strains of periodontitis-associated bacteria. We aimed to examine the effectiveness of an objectively quantified trypsin-like peptidase activity assay (TLP-AA) for detecting severe periodontitis. The study population included 347 adults (108 men and 239 women; average age, 43.3 years) who underwent a full-mouth periodontal examination. Specimens for the TLP-AA were obtained using tongue swabs. Using a color reader, the TLP-AA results were obtained as a* values, with higher positive a* values indicating an increased intense enzymatic activity. The predictive validity of the TLP-AA results for severe periodontitis was assessed using receiver operating characteristic curve analysis and the periodontitis case definition provided by the Centers for Disease Control and Prevention/American Academy of Periodontology as the gold standard. Furthermore, multivariable logistic regression analyses were performed to predict severe periodontitis using the TLP-AA results and health characteristics, as the exposure variables. Severe periodontitis was observed in 5.2% of the participants. TLP-AA had high diagnostic accuracy for severe periodontitis, with an area under the curve of 0.83 (95% confidence interval [CI]: 0.75-0.92). The cut-off score for the a* value that best differentiated individuals with severe periodontitis was 0.09, with a sensitivity of 83% and specificity of 77%. Multivariable logistic regression analyses revealed that the TLP-AA results were significantly associated with severe periodontitis after adjusting for health characteristics (adjusted odds ratios: 1.90 [95% CI: 1.37-2.62] for the a* value). Objectively quantified TLP-AA results are potentially useful for detecting severe periodontitis in epidemiological surveillance.


Delirium after coronary artery bypass graft surgery and late mortality.
Delirium is common after cardiac surgery, although under-recognized, and its long-term consequences are likely underestimated. The primary goal of this study was to determine whether patients with delirium after coronary artery bypass graft (CABG) surgery have higher long-term out-of-hospital mortality when compared with CABG patients without delirium. We studied 5,034 consecutive patients undergoing CABG surgery at a single institution from 1997 to 2007. Presence or absence of neurologic complications, including delirium, was assessed prospectively. Survival analysis was performed to determine the role of delirium in the hazard of death, including a propensity score to adjust for potential confounders. These analyses were repeated to determine the association between postoperative stroke and long-term mortality. Individuals with delirium had an increased hazard of death (adjusted hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.38-1.97) up to 10 years postoperatively, after adjustment for perioperative and vascular risk factors. Patients with postoperative stroke had a HR of 2.34 (95% CI, 1.87-2.92). The effect of delirium on subsequent mortality was the strongest among those without a prior stroke (HR 1.83 vs HR 1.11 [with a prior stroke] [p-interaction = 0.02]) or who were younger (HR 2.42 [<65 years old] vs HR 1.49 [>/=65 years old] [p-interaction = 0.04]). Delirium after cardiac surgery is a strong independent predictor of mortality up to 10 years postoperatively, especially in younger individuals and in those without prior stroke. Future studies are needed to determine the impact of delirium prevention and/or treatment in long-term patient mortality.


Primary mycobacterial infection of the uvula.
Tuberculosis, and non-tuberculous mycobacterial infections are becoming more common thus it is more likely that otolaryngologists will encounter these conditions. We describe an otherwise well patient, with symptoms and signs from chronic uvular inflammation, who proved to have a primary mycobacterial infection. This is an unique presentation in the literature and reminds clinicians of the need, where uncertainty exists in diagnosis, to consider mycobacterial infections.


Behaviors and Risks for Cardiovascular Disease Among Muslim Women in the United States.
Purpose: This study examines statistical associates of cardiovascular disease risk factors, as defined by the American Heart Association's Life's Simple Seven, among Muslim women who reside in the United States. Methods: Data collected nationally through the 2015 Muslim Women's Health project were analyzed (N=373). Logistic regression models estimated associations between sample characteristics and diet, exercise, alcohol consumption, blood pressure, cholesterol, and weight. Results: Over half of respondents reported exercising regularly (64%) and maintaining a healthy diet (85%); 20% consumed alcohol. About 5% reported having high cholesterol, 4% had high blood pressure, and 42% reported being overweight. Perceived and experienced stigma were associated with alcohol use (odds ratio [OR]=1.085, p<0.001) and being overweight (OR=0.938, p<0.001). Married respondents had 42% lower odds of exercising and 83% lower odds of drinking alcohol. Compared to foreign-born respondents, U.S.-born respondents had 2.9 higher odds of drinking alcohol and 2.7 higher odds of having high cholesterol (OR=2.931, p<0.001; OR=2.732, p<0.01, respectively). Significant effects were also found when examining the statistical impact of of age, Islamic sect, and education on cardiovascular disease risk factors. Conclusion: With increasing focus on precision medicine, personalized healthcare, and patient-centered medical homes (all interventions designed to promote disease prevention and assist in managing chronic health conditions) better understanding the health of understudied populations is imperative to the success of these interventions. Our findings suggest countervailing forces may affect the health of American Muslim women; therefore, additional studies with this hard-to-reach population are warranted and will be informative to improving overall population health in the United States, an overarching priority for both public health practitioners and medical providers.


Within-patient fluctuation of brain volume estimates from short-term repeated MRI measurements using SIENA/FSL.
Measurements of brain volume loss (BVL) in individual patients are currently discussed controversially. One concern is the impact of short-term biological noise, like hydration status. Three publicly available reliability MRI datasets with scan intervals of days to weeks were used. An additional cohort of 60 early relapsing multiple sclerosis (MS) patients with MRI follow-ups was analyzed to test whether after 1 year pathological BVL is detectable in a relevant fraction of MS patients. BVL was determined using SIENA/FSL. Results deviating from zero in the reliability datasets were considered as within-patient fluctuation (WPF) consisting of the intrinsic measurement error as well as the short-term biological fluctuations of brain volumes. We provide an approach to interpret BVL measurements in individual patients taking the WPF into account. The estimated standard deviation of BVL measurements from the pooled reliability datasets was 0.28%. For a BVL measurement of x% per year in an individual patient, the true BVL lies with an error probability of 5% in the interval x% ± (1.96 × 0.28)/(scan interval in years)%. To allow a BVL per year of at least 0.4% to be identified after 1 year, the measured BVL needs to exceed 0.94%. The median BVL per year in the MS patient cohort was 0.44%. In 11 out of 60 MS patients (18%) we found a BVL per year equal or greater than 0.94%. The estimated WPF may be helpful when interpreting BVL results on an individual patient level in diseases such as MS.


Electronic monitoring of dental implant osseointegration.
The methods for evaluating dental implant osseointegration can be limited in their effectiveness. The authors developed a new noninvasive electronic instrument to test implant stability and improve the assessment process. Using the new instrument, which was based on impulse testing and fast Fourier transform, or FFT, technology, the authors tested implant stability under real-time clinical conditions. The clinical procedure involved a weekly test of two placed implants, from the first-stage insertion point to the completion of the integration. This longitudinal monitoring spanned eight months. The authors verified clinical implant integration electronically and that it closely matched mathematical predictions. They also observed changes in implant stability during the integration process. Implant stability can be monitored electronically using FFT testing. A theoretical integration prediction also can be formulated. Like a "dental electrocardiogram," integration is assessed by waveform shape analysis. Electronic measurement of implant stability may help clinicians noninvasively diagnose the suitability of implants for restoration and aid in postrestorative monitoring.


Changes in cyclic 3'5'-adenosine monophosphate tissue concentration and net fluid transport in the cat's small intestine elicited by cholera toxin, arachidonic acid, vasoactive intestinal polypeptide and 5-hydroxytryptamine.
We have analysed tissue cyclic 3'5'-adenosine monophosphate (cAMP) concentration in different fractions of the cat's small intestinal mucosa during secretion elicited in vivo by four different secretagogues: cholera toxin (administered intraluminally), vasoactive intestinal polypeptide (VIP; given i.a.), arachidonic acid (AA; administered intraluminally) and 5-hydroxytryptamine (5-HT; given i.a.). Cholera toxin was found to increase cAMP concentration in the villi but not in the crypts. The VIP, AA and 5-HT did not influence tissue cAMP concentration despite a profuse net fluid secretion. Hexamethonium inhibited secretion elicited by cholera toxin and AA but did not significantly influence tissue cAMP concentration. There is strong evidence for the view that villus and crypt regions of the small intestinal mucosa have different functions, secretion taking place in the crypts and absorption in the villi. However, the lack of cAMP increase in the crypts reported in this study suggests that cholera toxin in this model does not reach the crypts. The results are not in agreement with a role for cAMP in mediating secretion from the crypts, but are compatible with a role of cAMP in inhibiting absorption in the villi. It is suggested that the observed fluid secretion from the crypts elicited by cholera toxin, AA and 5-HT is to a major part mediated by intramural enteric reflexes.


Novel non-neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia.
Mitochondria produce adenosine triphosphate (ATP) for energy requirements via the mitochondrial oxidative phosphorylation (OXPHOS) system. One of the hallmarks of cancer is the energy shift toward glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Mitochondria have their own genome (mitochondrial DNA [mtDNA]) encoding for 13 essential subunits of the OXPHOS enzyme complexes. We studied mtDNA in childhood acute lymphoblastic leukemia (ALL) to detect potential pathogenic mutations in OXPHOS complexes. The whole mtDNA from blood and bone marrow samples at diagnosis and follow-up from 36 ALL patients were analyzed. Novel or previously described pathogenic mtDNA mutations were identified in 8 out of 36 patients. Six out of these 8 patients had died from ALL. Five out of 36 patients had an identified poor prognosis genetic marker, and 4 of these patients had mtDNA mutations. Missense or nonsense mtDNA mutations were detected in the genes encoding subunits of OXPHOS complexes, as follows: MT-ND1, MT-ND2, MT-ND4L and MT-ND6 of complex I; MT-CO3 of complex IV; and MT-ATP6 and MT-ATP8 of complex V. We discovered mtDNA mutations in childhood ALL supporting the hypothesis that non-neutral variants in mtDNA affecting the OXPHOS function may be related to leukemic clones.


Staphylococcus aureus and Candida albicans infection (animal experiments).
During a certain period of the course of infection in white mice inoculated intraperitoneally with the pure culture of a proteolysing strain of Candida albicans, Staphylococcus aureus and C. albicans both, were isolated simultaneously from the peritoneal abscesses, especially those adhering to the stomach, duodenum, pancreas and the upper part of small intestine. This concommitant occurrence of the two pathogens was further corroborated by histopathological examination which revealed large number of staphylococci present in the close neighbourhood of Candida cells, usually in the center of the granulomata caused by the fungus. In view of the facts that the proteolytic end-products of C. albicans can offer a good substratum for the growth of S. aureus and the latter may be isolated from the intestinal tract of apparently healthy mice, possibly as a constituent of the transient microflora, the co-existence of these two important aetiologic agents of endogenous infections as encountered during this study appears to be of great clinical interest. Furthermore, these observations also demonstrate the importance of controlling the bacterial flora of mice for pure mycological studies.


Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis: a magnetic resonance study.
Patients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine if patients with SSc have lower global myocardial perfusion (MP) at rest or during adenosine stress, compared to healthy controls, quantified with CMR. Nineteen SSc patients (17 females, 61 ± 10 years) and 22 controls (10 females, 62 ± 11 years) underwent CMR. Twelve patients had limited cutaneous SSc and 7 patients had diffuse cutaneous SSc. One patient had pulmonary arterial hypertension (PAH). MP was quantified using coronary sinus flow (CSF) measurements at rest and during adenosine stress, divided by left ventricular mass (LVM). There was no difference in MP at rest between patients and controls (1.1 ± 0.5 vs. 1.1 ± 0.3 ml/min/g, P = 0.85) whereas SSc patients showed statistically significantly lower MP during adenosine stress (3.1 ± 0.9 vs. 4.2 ± 1.3 ml/min/g, P = 0.008). Three out of the 19 SSc patients showed fibrosis in the right ventricle insertion points despite absence of PAH. None had signs of myocardial infarction. Patients with SSc have decreased MP during adenosine stress compared to healthy controls. Thus hypoperfusion at stress may be a sensitive marker of cardiac disease in SSc patients possibly signifying microvascular myocardial disease.


Direct restoration of anterior teeth: review of the clinical technique and case presentation.
Direct composite resin bonding procedures are growing in popularity as conservative and predictable restorative treatment alternatives. An understanding of the fundamental layering, contouring, and polishing principles is paramount to the success of any direct composite restoration; this awareness can be subsequently applied to indirect restorations and significantly enhance laboratory/clinician communication. This article presents a clinical technique that describes the incremental placement of direct resin veneers on a typodont and demonstrates the application of these procedures on an actual clinical case.


Did the Addition of Olive Cakes Obtained by Different Methods of Oil Extraction in the Finishing Diet of Bísaro Pigs Affect the Volatile Compounds and Sensory Characteristics of Dry-Cured Loin and "Cachaço"?
This study was conducted to determine the effects of different types of olive cake in the basal diet of Bísaro pigs on the volatile compounds and sensory characteristics of dry-cured loin and "cachaço". A total of 40 Bísaro breed animals were allocated to four treatments, along with a control group (T1-control, T2-crude olive cake, T3-centrifugation two phases, T4-exhausted, and T5-exhausted with 1% of olive). Various extraction methods (centrifugation, pressing, and exhaustion) were employed for the olive cake used. Furthermore, the extracted olive cake was supplemented with 1% olive oil. Eighty compounds were identified and grouped into eight chemical classes: hydrocarbons, aldehydes, esters, alcohols, ketones, acids, furans, and other compounds. Aldehydes and alcohols were the major groups of compounds, representing 57.06-66.07% and 68.67-75.61% for the loin and "cachaço", respectively. There were no significant differences between treatments for any of the volatile compounds identified. The major aldehydes were hexanal, heptanal, pentanal, and propanal. These compounds were significantly higher (p < 0.001) in "cachaço". This significant difference between the two types of dry-cured products was directly related to the amount of total fat content. The major alcohols were 2.3-butanediol, 1-octen-3-ol, 1-butanol, 3-methyl, 1-hexanol, benzyl-alcohol, and glycidol. Except for compounds 2,3-butanediol and benzyl-alcohol, the majority in this group were significantly different in terms of the type of dry-cured product. As for the sensory evaluation, for both dry-cured products, the trained tasters did not detect significant differences between the different treatments. The results showed that the olive cake obtained by different methods of oil extraction did not negatively affect the sensory and volatile components of the processed meat products; thus, they maintained their appeal to the consumer.


Development and application of a new scheme for typing Campylobacter jejuni and Campylobacter coli by PCR-based restriction fragment length polymorphism analysis.
A molecular typing approach for Campylobacter jejuni and Campylobacter coli was developed with restriction fragment length polymorphism analysis of a 9.6-kb PCR-amplified portion of the lipopolysaccharide gene cluster. Sixty-one Penner serotype reference strains were analyzed with this new genotyping scheme, and 32 genogroups were found. Eleven additional genogroups were obtained from 87 clinical C. jejuni strains tested. This molecular typing method shows a correlation with the Penner heat-stable serotyping method, a phenotypic typing method based on lipopolysaccharide structures that is often used as a "gold standard" for subtyping Campylobacter spp. This strong correlation suggests that the data obtained can be directly compared with epidemiological data collected in the past by classical serotyping of C. jejuni and C. coli. In contrast to the high percentage of nontypeability by phenotyping, this molecular typing method results in 100% typeability and provides a superior alternative to serotyping.


A direct interview family study of obsessive-compulsive disorder. I.
This and the companion paper present two sequential family studies of obsessive-compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome. In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total "combined" samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two "blinded" senior clinicians who reviewed all diagnostic materials including proband informant data about relatives. Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation. These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.


Comparative analysis of ultrasound diagnosis and pathological characteristics of external jugular venous aneurysm.
This study aimed to investigate the diagnosis of the external jugular venous aneurysm on color Doppler ultrasound and its relationship with pathological characteristics. A retrospective analysis of 17 patients with external jugular venous aneurysm admitted to the Provincial Hospital Affiliated with Shandong First Medical University from May, 2010, to June, 2020, was performed. The color Doppler ultrasound characteristics of 17 patients with external jugular vein aneurysms were analyzed and summarized, which were then compared with postoperative pathological outcomes. All 17 patients with external jugular venous aneurysms were presented with cystic structures adjacent to and communicated with the external jugular vein. Color Doppler flow imaging showed a bidirectional venous flow signal in the communication between the cystic structure and the external jugular vein. Among the 17 patients, ultrasound diagnosis showed true venous aneurysm due to degenerative changes in the venous wall in 8 cases, venous pseudoaneurysm in 4 cases, and external jugular venous aneurysm in 5 cases, and postoperative pathology indicated degenerative changes in the venous wall in all 17 patients. Bidirectional blood flow at the communication between the cystic lesion and the external jugular vein on color Doppler ultrasound should not be the criterion for the diagnosis of external jugular venous pseudoaneurysm, which requires pathological support.


The nursing process--a method of collecting evidence?
This paper questions whether or not the nursing process can be a valid method of collecting evidence on which to base nursing care. The author asserts that it can, but only if the service user is involved in the entire process.


Endocrine disruption, oxidative stress, and testicular damage induced by 4-nonylphenol in Clarias gariepinus: the protective role of Cydonia oblonga.
Exposure to xenoestrogens like 4-nonylphenol (NP) is recognized by disrupting endocrine functions and causes reproductive dysfunction in male fish. The present study aimed at investigating the 4-nonylphenol propensity to induce oxidative stress and hormonal disturbances in male catfish and at studying the protective role of quince (Cydonia oblonga). To fulfill this aim, catfish Clarias gariepinus were exposed to pure 100 μg/L 4-NP and to quince the leaf extract added to 4-NP, both for 15 days. The 4-NP exposure induced a marked increase in 17ß-estradiol (E2), LH, and cortisol, while thyroid hormone (TSH, T3), testosterone (T), and FSH levels noticeably decreased; however, 4-NP had no effect on T4 level. Moreover, 4-NP exposure was accompanied by histological impairments in testes. Existence of 4-NP was associated with oxidative damage as evidenced by the significant increase (p < 0.05) of the enzymes, superoxidase dismutase (SOD), catalase (CAT), acetylcholinesterase (AchE), glutathione s-transferase, total antioxidant capacity (TAC), and malondialdehyde (MDA). Adding quince was effective to neutralize hormonal levels and to repair the testicular histological alterations. In response to quince remedy, the enzymes AchE and MDA reduced significantly (p < 0.05), while limited or no response was detected for other tested enzymes. Our results concluded that quince can antagonize 4-NP toxicity in catfish, confirming that quince leaf extract displayed antioxidant activities against the toxicity of hazardous chemicals.


The clinical aspects of newborn screening: importance of newborn screening follow-up.
The aim of newborn screening is to identify presymptomatic healthy infants that will develop significant metabolic or endocrine derangements if left undiagnosed and untreated. The goal of ultimately reducing or eliminating irreversible sequelae is reached by maximizing test sensitivity of the primary newborn screening that measures specific analytes by a number of methodologies. Differentiation of true from false negatives is accomplished by the test specificity. This review discusses disorders for which, in general, there are available therapies and that are detected by routine and expanded newborn screening. Recommendations are presented for evaluation by a primary care physician, with confirmation by a metabolic or endocrinology specialist. Disorders are organized in tabular format by class of pathway or analyte, with attention to typical clinical presentations, confirmatory biochemical and molecular tests, and therapies. There are numerous challenges in clinical follow-up, including diagnosis and appropriate understanding of the consequences of the disorders. The data required to meet these challenges can be acquired only by large scale longitudinal comprehensive studies of outcome in children identified by newborn screening. Only with such data can newborn screening fully serve families.


Are there reliable changes in memory and executive functions after cognitive behavioural therapy in patients with obsessive-compulsive disorder?
Patients with obsessive-compulsive disorder (OCD) have impaired memory and executive functions, but it is unclear whether these functions improve after cognitive behavioural therapy (CBT) of OCD symptoms. The primary aim of this study was to investigate whether memory and executive functions change after CBT in patients with OCD. We assessed 39 patients with OCD before and after CBT with neuropsychological tests of memory and executive functions. To correct for practice effects, 39 healthy controls (HCs) were assessed at two parallel time intervals with the neuropsychological tests. There were no changes in memory and executive functions after CBT in patients with OCD when results were corrected for practice effects. Patients performed worse on a test of visuospatial memory and organisational skills (Rey complex figure test [RCFT]) compared to HCs both before and after CBT (ps = .002-.036). The finding of persistent poor RCFT performances indicates that patients with OCD have impaired visuospatial memory and organisational skills that may be trait-related rather than state-dependent. These impairments may need to be considered in treatment. Our findings underline the importance of correcting for practice effects when investigating changes in cognitive functions.


Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China.
Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.


Pressor and hormonal responses to angiotensin I infusion in healthy subjects of different angiotensin-converting enzyme genotypes.
The effects of incremental infusion of angiotensin I on pressor and hormonal responses in relation to the angiotensin-converting enzyme (ACE) genotype were compared in healthy men of genotype DD (n = 8) and II (n = 8). The R(d)25 was the rate of angiotensin I infusion required to achieve a 25-mm Hg increase in diastolic pressure, and the R(s)25, that which caused a 25-mm Hg increase in systolic pressure. Changes in heart rate (HR25) were analysed at the time the R(d)25 was achieved. Serum ACE activity and plasma renin, angiotensin II, and aldosterone concentrations were measured at the start and end of the angiotensin I infusion. Serum ACE activity differed significantly between the genotypes with significantly higher mean values in DD subjects (46.3 +/- SEM 5.2 U/L) than II subjects (12.3 +/- 1.4 U/L; p < 0.001). Age, weight, and baseline blood pressure, heart rate, urinary sodium excretion, plasma renin, angiotensin II, and aldosterone concentrations did not differ between genotypes. The geometric mean infusion rates of angiotensin I required to achieve R(d)25 were 2.53 micrograms/min in II subjects and 2.67 micrograms/min in DD subjects (ratio of infusion rates, 0.95; 95% CI, 0.44-2.02; p > 0.05). The corresponding infusion rates for systolic blood pressure (R(s)25) were 4.47 micrograms/min in II subjects and 3.39 micrograms/min in DD subjects (ratio, 1.32; 95% CI, 0.49-3.55; p > 0.05). At the time of R(d)25, changes in heart rate from baseline were +1.2 beats/min for DD subjects and -9.5 beats/min for II subjects (diff II-DD = 10.7 beats/min; 95% CI, 6.7-14.8; p = 0.01). There were no differences in plasma renin, angiotensin, and aldosterone responses to angiotensin I infusion between the DD and II genotypes. We showed no difference in blood pressure or renin-angiotensin-aldosterone system responses to infusion of angiotensin I related to the deletion or insertion allele of the ACE gene polymorphism, but the study has insufficient power to exclude with certainty such differences. There was a significant difference between II and DD subjects in the chronotropic response to angiotensin I infusion.


Cytokine kinetics profiling in pediatric renal transplant recipients.
Pediatric renal transplant recipients experience side effects of immunosuppression. Few immunoassays exist which can assess the adequacy of immunosuppression. We developed a CKT, whereby cytokine levels are measured in a five-day mixed lymphocyte reaction. We describe the in vitro cytokine responses to donor and third-party antigen in a pilot study of nine children after living-donor renal transplantation. The CKT identified five patterns of IFN-gamma secretion relative to donor and third-party alloantigen: no response to alloantigen (n = 2), hypo-response to donor (n = 3), equal response (n = 1), hyper-response to donor (n = 1), and intermediate response (n = 2). IL-2 and IL-13 patterning correlated with IFN-gamma expression. Two of nine subjects had acute rejection, which correlated with intermediate and hyper-responsive profiles. No rejection occurred during immunosuppression or donor-specific hypo-responsiveness. Significant immunosuppression was universal early after transplantation. Two of four children showed strong pretransplant responses to donor, which were regained three months post-transplant, and associated with rejection in one subject. The CKT reflects the level of immunosuppression and may offer a method to assess the adequacy of immunosuppression. A pattern of complete non-responsiveness or hypo-responsiveness correlated with lack of acute rejection. The CKT may prove useful in titrating immunosuppression and in improving live donor selection.


[Cor triatriatum sinistrum in adults (case report)].
A case is presented of cor triatriatum sinistrum , which has been diagnosed in an adult. The findings of invasive and noninvasive studies have resulted in a diagnosis, which can be confirmed by using two-dimensional echocardiography.


Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management.
Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.


Methyl/ethyl differentiation in diastereoselective hydride addition to [Tp'W(CO)(PhCCMe)(NH=CMeEt)][BAr'(4)].
Hydride addition to either an 80:20 or a 93:7 E/Z isomer ratio of coordinated imine complex 2a occurs with high diastereoselectivity. The high diastereoselectivity regardless of the reagent E/Z ratio is explained by a difference between the relative kinetic acidities of the E and Z isomers of the imine complex. The kinetic acidities of related isopropylimine and 3-pentylimine complexes were used in explaining these results.


Evaluation of the oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population.
Type 2 diabetes mellitus is a polygenic metabolic disorder resulting from oxidative stress, the root cause of insulin resistance, β-cell dysfunction and impaired glucose tolerance. The aim of this study was to investigate the role of oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO in type 2 diabetes mellitus susceptibility in the Chinese Han population. A total of 396 type 2 diabetes mellitus patients and 678 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222, GPX1 rs1050450, GPX3 rs3828599 and MPO rs2107545 gene polymorphisms were genotyped. We found one single-nucleotide polymorphism in the MPO gene was associated with type 2 diabetes mellitus susceptibility [rs2107545: odds ratio = 1.563 (1.166-2.096); p = 0.003], after adjusting for covariates. Furthermore, we also considered the likely complexity of effects of genetic and conventional risk factors in type 2 diabetes mellitus-related vascular complications, such as carotid plaques. Our analysis revealed that the GPX1 rs1050450 and MPO rs2107545 were significantly associated with increased risk of carotid plaques in type 2 diabetes mellitus patients. Our study presents novel evidence for main effects of MPO gene on type 2 diabetes mellitus susceptibility. Furthermore, our study supported the association between variants of oxidative stress-related genes ( GPX1 and MPO) and carotid plaques in type 2 diabetes mellitus patients, which indicated a modulation of type 2 diabetes mellitus-related vascular complication susceptibility by genetic predisposition.


Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies.
Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a 1D sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods.


Effectiveness of midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial).
Initial treatment of vasovagal syncope (VVS) consists of advising adequate fluid and salt intake, regular exercise, and physical counterpressure manoeuvres. Despite this treatment, up to 30% of patients continue to experience regular episodes of VVS. We investigated whether additional Midodrine treatment is effective in these patients. In our study, patients with at least three syncopal and/or severe pre-syncopal recurrences during non-pharmacological treatment were eligible to receive double-blind cross-over treatment starting either with Midodrine or placebo. Treatment periods lasted for 3 months with a wash-out period of 1 week in-between. At baseline and after each treatment period, we collected data about the recurrence of syncope and pre-syncope, side effects, and quality of life (QoL). Twenty-three patients (17% male, mean age 32) included in the cross-over trial received both Midodrine and placebo treatment. The proportion of patients who experienced syncopal and pre-syncopal recurrences did not differ significantly between Midodrine and placebo treatment (syncope: 48 vs. 65%, P= 0.22; pre-syncope: 74 vs. 78%, P> 0.99). The median number of syncopes and pre-syncopes per 3 months were also not significantly different during Midodrine and placebo treatment (0 vs. 1; P= 0.57; and 6 vs. 8; P= 0.90). The occurrence of side effects was similar during Midodrine and placebo treatment (48 vs. 57%; P= 0.75). Also, QoL did not differ significantly. Our findings indicate that additional Midodrine treatment is less effective in patients with VVS not responding to non-pharmacological treatment than reported as first-line treatment.


Post-trial access to tested interventions: the views of IRB/REC chair, investigators, and research participants in a multinational HIV/AIDS study.
Controversy exists regarding an ethical requirement to make products proven effective in research available after the trial. Little is known about the views of several stakeholders. Phone or self-administered questionnaires were completed by 65 IRB/REC chairs, 117 investigators, and 500 research participants in a multinational HIV trial to assess their views about posttrial access to interventions proven effective in the study. A total of 83% of research participants, 29% of IRB/REC chairs, and 42% of researchers (p = 0.046) thought IL-2 should be guaranteed for every HIV-infected person in the world if proven effective. Most European and Latin American research participants thought IL-2 should be provided free, while North American, Australian, and Thai participants commonly said at a price the average person could afford (p < 0.001). Most IRB/REC chairs and researchers thought the CIOMS "reasonable availability" requirement applied to people in the country where the study was conducted and meant a drug should be available at a price the average person could afford and that host country governments had primary responsibility for making it available. Most research participants believe an HIV drug proven effective in research should be made available to everyone in the world who needs it. IRB/REC chairs and researchers were less expansive both in who and how they thought a drug should be guaranteed.


Permeability Prediction of Nanoscale Porous Materials Using Discrete Cosine Transform-Based Artificial Neural Networks.
The permeability of porous materials determines the fluid flow rate and aids in the prediction of their mechanical properties. This study developed a novel approach that combines the discrete cosine transform (DCT) and artificial neural networks (ANN) for permeability analysis and prediction in digital rock images, focusing on nanoscale porous materials in shale formations. The DCT effectively captured the morphology and spatial distribution of material structure at the nanoscale and enhanced the computational efficiency, which was crucial for handling the complexity and high dimensionality of the digital rock images. The ANN model, trained using the Levenberg-Marquardt algorithm, preserved essential features and demonstrated exceptional accuracy for permeability prediction from the DCT-processed rock images. Our approach offers versatility and efficiency in handling diverse rock samples, from nanoscale shale to microscale sandstone. This work contributes to the comprehension and exploitation of unconventional resources, especially those preserved in nanoscale pore structures.


Fabrication and Characterization of Zn Particle Incorporated Fibrous Scaffolds for Potential Application in Tissue Healing and Regeneration.
Zinc (Zn) metal and its alloys have received a lot of interest in biomedical applications due to their biodegradability, biocompatibility, antimicrobial activity, and ability to stimulate tissue regeneration. Bulk Zn has been successfully utilized in a variety of implant applications, most notably as bioabsorbable cardiac stents and orthopedic fixation devices, where it provides adequate mechanical properties while also releasing helpful Zn ions (Zn2+) during degradation. Such beneficial ions are dose-dependent and, when released in excess, can induce cellular toxicity. In this study, we hypothesize that embedding Zn metal particles into a polymer nanofibrous scaffold will enable control of the degradation and time release of the Zn2+. We designed and fabricated two polymer scaffolds, polycaprolactone (PCL) and polycaprolactone-chitosan (PCL-CH). Each scaffold had an increasing amount of Zn. Several physicochemical properties such as fiber morphology, crystallinity, mechanical strength, hydrophilicity, degradation and release of Zn2+, thermal properties, chemical compositions, and so forth were characterized and compared with the PCL fibrous scaffold. The biological properties of the scaffolds were evaluated in vitro utilizing direct and indirect cytotoxicity assays and cell viability. All the data show that the addition of Zn changed various physical properties of the PCL and PCL-CH scaffolds except their chemical structure. Further investigation reveals that the PCL-CH scaffolds degrade the Zn particles relatively faster than the PCL because the presence of the hydrophilic CH influences the faster release of Zn2+ in cell culture conditions as compared to the PCL fibrous scaffold. The combined advantages of CH and Zn in the PCL scaffold enriched 3T3 fibroblast cells' survival and proliferation except the ones with the higher concentration of Zn particles. These new composite scaffolds are promising and can be further considered for tissue healing and regeneration applications.


Use of Ethibloc in the treatment of cystic and venous angiomas in children. 19 cases.
The authors report the use of Ethibloc in the treatment of cystic lymphangiomas and venous angiomas in 19 children. This embolizing product is injected by puncture in situ. Ten cystic lymphangiomas were treated, including 7 of the cervico-facial region. Of these ten, 8 were embolized initially using Ethibloc, and 2 after surgery. The diagnosis was always confirmed by echography and in some cases also by scanner. Six were completely cured and 2 had partial but satisfactory results requiring further injections. The final 2 cases when Ethibloc was administered after surgery, gave very disappointing results as the residual lesion was microcystic and thus difficult to access for the Ethibloc injection. The 9 venous angiomas involved various regions, including 5 facial lesions. These angiomas required a more extensive blood-clotting and radiologic assessment: standard radiography to detect the clot, Doppler echography and M.R.I. precisely clarifying the exact extension in depth. For 6 patients the cure was complete, for 2 others the results were good. Finally, in 1 case Ethibloc embolization was carried out prior to surgery, allowing definitive cure. In all, this technique resulted in a complete cure in 2/3 of the cases and its simplicity makes it a seemingly interesting alternative to surgery.


Involvement of neuroleptic drugs in selenium deficiency and sudden death of cardiac origin: study and human post-mortem examination.
The involvement of psychotropic drugs in sudden deaths has been highlighted. The objective of this work was to establish a link between selenium levels in heart tissue, psychotropic treatment and sudden death. Selenium levels were measured by electrothermal atomic absorption spectroscopy post-mortem in heart, brain and liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A significant reduction of myocardial selenium levels compared to controls was seen in patients treated with neuroleptic drugs or meprobamate. No changes in brain or liver selenium levels were seen. These results suggest that selenium deficiency can facilitate sudden death in patients on psychotropic drugs. The reduced activity of glutathione peroxidase due to selenium deficiency can result in augmented oxidative stress in myocardial cells and myocardiopathy leading to sudden death.


Assessment of social communication skills in preschoolers.
This paper orients the reader to social communication assessment and reviews methods for assessing social communication behavior in children from toddlerhood through the preschool years. Most standardized, normed tests of language in this age range focus on morpho-syntactic and semantic comprehension and production abilities. While social communication is perhaps one of the most important skills for peer acceptance, these skills are often overlooked in language evaluation with children. However, there are a number of caregiver questionnaires, interviews, or direct social-communication sampling methods that are available to assist clinicians or researchers in documenting social-communication skills or behaviors. Since assessment of social communication is essential in clinical work with children with an autism spectrum disorder, some of the tools described below are outgrowths of autism research or provide autism-related scores. While many children receiving social communication assessments do not have autism, the need to assess social communication skills in children with language impairment is highlighted by the growing literature documenting social and pragmatic difficulties in this population (Bishop 2000 Causes, Characteristics, Intervention, and Outcome. Hove, UK: Psychology press). Regardless of whether the measures presented herein were initially designed for children with autism or not, they will provide insights into the social communicative behaviors or tendencies in young children.


Tracking hierarchical processing in morphological decomposition with brain potentials.
One important debate in psycholinguistics concerns the nature of morphological decomposition processes in visual word recognition (e.g., darkness = {dark} + {-ness}). One theory claims that these processes arise during orthographic analysis and prior to accessing meaning (Rastle & Davis, 2008), and another argues that these processes arise through greater temporal overlap between the activation of orthographic and semantic information (Feldman, O'Connor, & Moscoso del Prado Martín, 2009). This issue has been the subject of intense debate in studies using masked priming but has yet to be resolved unequivocally. The present study takes another approach to resolving this controversy by examining brain potentials as participants made lexical decisions to unprimed morphological (darkness), pseudomorphological (corner), and nonmorphological (brothel) stimuli. Results revealed a difference from ∼190 ms between the nonmorphological condition and the other 2 conditions (which showed no differentiation), a likely correlate of morphological processing reliant exclusively on orthography. Only 60-70 ms later was there evidence of the activation of semantic information, when the pseudomorphological condition diverged from the other 2 conditions. These results provide unambiguous support for a hierarchical model of morphological processing whereby decomposition is based initially on orthographic analysis and is only later constrained by semantic information. (PsycINFO Database Record (c) 2012 APA, all rights reserved).


The drug cost gap and the diagnosis-prescription connection.
Although the rise in pharmacy benefit costs continues to outpace overall medical cost inflation, the gap is narrowing. Employers can improve cost and employee wellness even further with an innovative technique for drug therapy compliance called the Diagnosis-Prescription (Dx-Rx) approach. This article reports results from a 2007 national employer survey on pharmacy benefits and describes how the Dx-Rx innovation can keep patients and their doctors on track when it comes to controlling disease and driving down overall medical costs.


Radiation-induced glioblastoma multiforme in two adult baboons (Papio cynocephalus anubis).
A diagnosis of glioblastoma multiforme (GBM) was made for cerebral masses found at necropsy in two baboons (Papio cynocephalus anubis). Case 1 was an adult (6.18 years old) male baboon that suddenly died during a physical examination as part of a clinical evaluation for a leg lameness. Case 2 was an adult (5.95 years old) female baboon that stopped breathing during anesthesia for an magnetic resonance imaging to evaluate lethargy, weight loss, inappetence, and dilated pupils. Both animals had undergone total body irradiation with cobalt during a research protocol. The incidence of spontaneous brain tumors in nonhuman primates is low, but radiation-induced GBM lesions in rhesus macaques (Macaca mulatta) have been reported. A definitive diagnosis was made in these cases, using histopathologic criteria of cellular pleomorphism, high mitotic rate, regions of coagulation necrosis, and endothelial proliferation.


The outcome of a test-treat package versus routine outpatient care for Ghanaian children with fever: a pragmatic randomized control trial.
Over-diagnosis of malaria among African children results in mismanagement of non-malaria infections. Limited laboratory capacity makes it difficult to implement policies that recommend pre-treatment confirmation of infections so a new approach with a package for on-the-spot management of fevers was evaluated. Febrile children presenting to outpatient clinic were randomized to receive either a 'test-treat' package (history with clinical examination; point-of-care tests; choice of artesunate-amodiaquine, co-amoxiclav and/or paracetamol) or routine outpatient care in a secondary health care facility in Kumasi, Ghana. A diagnosis of malaria, bacterial, viral or mixed malarial and bacterial infections was made using pre-defined criteria. Outcome was resolution of all symptoms including fever on day 7. The median age of the patients was 37.5 months (IQR: 19 to 66 months), with 56.7% being males. Compared to routine care the test-treat package resulted in less diagnoses of malaria, (37.2% vs 46.2%, p = 0.190) and mixed malaria and bacterial infections (14.0% vs 53.8%, p < 0.001) but more diagnoses of viral (33.1% vs 0.0%, p < 0.001) and bacterial infections only (15.7% vs 0.0%, p < 0.001). Less anti-malarials (51.2% vs 100.0%, p < 0.001) and antibiotics (29.7% vs 48.7%, p < 0.001), were prescribed in the test-treat group on completion of study, more test-treat package patients were clinically well (99.2% vs 80.7%, p < 0.001) and febrile (0.8% vs 10.1%, p = 0.001) and less were admitted for inpatient care (0.0% vs 8.4% p = 0.001) compared to the routine care group. Test-treat package improves the effectiveness of outpatient diagnosis and treatment of children with fever and reduces inappropriate prescribing of anti-malarials and antibiotics. The package provides clinicians with the option for immediate diagnosis and treatment of non-malaria fevers. The test-treat package now needs to be evaluated in other settings including primary health care facilities.


Using Low-Calorie Orange Juice as a Dietary Alternative to Alkali Therapy.
Purpose: The pursuit of a dietary source to increase urine pH and citrate in stone formers has been ongoing for >30 years. Early evidence showed that orange juice (OJ) contains alkali and citrate, but high sugar and ascorbic acid content limited the use of OJ as a viable daily source of alkali. Recently, novel low-calorie OJs have emerged and could potentially be a better option. Methods: Beverages with high concentrations of alkali citrate and malate were identified using ion chromatography. Two low-calorie OJ beverages, in addition to crystal light lemonade beverage (CLLB), were chosen. Healthy volunteers (5 men, 5 women) drank 1 L of OJ or CLLB with 1 L water daily for 7 days, and then completed a 24-hour urinalysis. A washout week was instituted between trial weeks. The study design is a prospective randomized crossover control trial. A paired analysis using comparison of means was used to evaluate low-calorie OJ and CLLB. Volunteers had no prior history of kidney stones and maintained a journal with beverage compliance, side effect (SE), and dietary consumption data. Results: Tropicana 50 (TRP50), Kroger low-calorie OJ (KLCO), and CLLB were found to have a total alkali content of 56.60, 47.9, and 17.3 mEq/L, respectively, based on ion chromatography. Consumption of all three beverages raised urinary citrate (116.6 [-118 to 373, 177.9 [-3 to 359], 155.6 [-4 to 237] ▵mg/day 95% confidence interval) and urinary pH (0.25 [0.08-0.53], 0.74 [0.41-1.07 p < 0.05], 0.25 [0.25-0.64]), respectively, compared with water phase. Based on journal entries by volunteers, TRP50 had the most SEs (90% participants) felt to be a result of the artificial sweetener (Stevia®). Conclusion: Low-calorie OJs, and to a lesser extent CLLB, have alkali and citrate based on ion chromatography. Daily consumption by healthy volunteers of KLCO can raise urinary pH.


High throughput genotyping technologies.
A comprehensive genetic map containing several hundred microsatellite markers resulted from a large microsatellite mapping project. This was the first real study that introduced high throughput methods to the genetic community. This map and the concurrent technological advances, which will briefly be reviewed, led to further numerous mapping investigations of simple and complex diseases. The annotated draft sequence of approximately three billion base pairs (bp) of the human genome has been completed much sooner than many imagined, due to considerable technological advancements and the international enterprise that resulted. This was a major development for the genetics community, but is only the precursor to the next phase of studying and understanding the variation within the human genome. The awareness of the differences may help us understand the effects on the genetics of the variation between individuals and disease. It is these variations at the nucleotide level that determine the physiological differences, or phenotypes of each individual, including all biological functions at the cellular and body level. Single nucleotide polymorphisms (SNPs) will provide the next high density map, and be the genetic tool to study these genetic variations. There are many sources of SNPs and exhaustive numbers of methods of SNP detection to be considered. The focus in this paper will be on the merits of selected, varied SNP typing methodologies that are emerging to genotype many individuals with the required huge number of SNPs to make the study of complex diseases and pharmacogenomics a practical and economically viable option.