Endothelial dysfunction in heart failure: mechanisms and therapeutic approaches.
Endothelial dysfunction contributes to the development of impaired coronary and systemic perfusion as well as reduced exercise capacity in patients with congestive heart failure (CHF). Thereby endothelial dysfunction is assumed to have a fundamental impact on morbidity and potential mortality in this disease. Reduced bioavailability of nitric oxide (NO) and abundant formation of reactive oxygen species (ROS) within the vascular wall are the key determinants in endothelial dysfunction. The resulting imbalance between NO and ROS mainly results from neurohumoral activation associated with CHF. The excessive activation of the renin-angiotensin-aldosterone and endothelin systems plays a pivotal role. Treatment with ACE inhibitors, angiotensin-, aldosterone-, and endothelin-antagonists has been shown to beneficially modulate endothelial dysfunction in CHF. Furthermore, antioxidants, L-arginine, cofactors of endothelial NO-synthase, and exercise training positively modulate endothelial function. This article reviews the current knowledge of the pathophysiological events contributing to endothelial dysfunction in CHF as well as several treatment options to reverse those changes.


The functional morphology of the avian flight muscle M. Coracobrachialis posterior.
The extensive range of movement of the avian glenohumeral joint makes functional interpretation of any muscle that crosses the joint difficult. Multiple functional roles for the M. coracobrachialis posterior (CBP), an architecturally complex muscle that lies deep to the M. pectoralis, have been assigned on the basis of its anatomical position. The mechanical properties, neuromotor pattern during flight and the biochemical properties of the CBP in pigeons (Columba livia) were studied by in situ length/active tension and length/passive tension measurements, in vivo electromyography and muscle histochemistry. The action of the muscle was studied directly through in situ stimulation and measurement of humeral excursion in non-reduced preparations.


Fairness, accountability for reasonableness, and the views of priority setting decision-makers.
Fairness is a key goal of priority setting and 'accountability for reasonableness' has emerged as the leading framework for fair priority setting. However, it has not been shown acceptable to those engaged in priority setting. In particular, since it was developed in the context of a primarily privately funded health system, its applicability in a primarily publicly funded system is uncertain. In this paper, we describe elements of fairness identified by decision-makers engaged in priority setting for new technologies in Canada (a primarily publicly funded system). According to these decision makers, accountability for reasonableness is acceptable and applicable. Our findings also provide refinements to accountability for reasonableness.


Inspiratory muscle training at sea level improves the strength of inspiratory muscles during load carriage in cold-hypoxia.
Inspiratory muscle training (IMT) and functional IMT (IMTF: exercise-specific IMT activities) has been unsuccessful in reducing respiratory muscle fatigue following load carriage. IMTF did not include load carriage specific exercises. Fifteen participants split into two groups (training and control) walked 6 km loaded (18.2 kg) at speeds representing ∼50%V̇O2max in cold-hypoxia. The walk was completed at baseline; post 4 weeks IMT and 4 weeks IMTF (five exercises engaging core muscles, three involved load). The training group completed IMT and IMTF at a higher maximal inspiratory pressure (Pimax) than controls. Improvements in Pimax were greater in the training group post-IMT (20.4%, p = .025) and post-IMTF (29.1%, p = .050) compared to controls. Respiratory muscle fatigue was unchanged (p = .643). No other physiological or subjective measures were improved by IMT or IMTF. Both IMT and IMTF increased the strength of respiratory muscles pre-and-post a 6 km loaded walk in cold-hypoxia. Practitioner Summary: To explore the interaction between inspiratory muscle training (IMT), load carriage and environment, this study investigated 4 weeks IMT and 4 weeks functional IMT on respiratory muscle strength and fatigue. Functional IMT improved inspiratory muscle strength pre-and-post a loaded walk in cold-hypoxia but had no more effect than IMT alone. Abbreviations: ANOVA: analysis of variance; BF: breathing frequency; CON: control group; EELV: end-expiratory lung volume; EXP: experimental group; FEV1: forced expiratory volume in one second; FiO2: fraction of inspired oxygen; FVC: forced vital capacity; HR: heart rate; IMT: inspiratory muscle training; IMTF: functional inspiratory muscle training; Pemax: maximal expiratory pressure; Pimax: maximal inspiratory pressure; RMF: respiratory muscle fatigue; RPE: rate of perceived exertion; RWU: respiratory muscle warm-up; SaO2: arterial oxygen saturation; SpO2: peripheral oxygen saturation; V̇E: minute ventilation; V̇O2: rate of oxygen uptake.


Surveillance of Salmonella enterica serovar Typhi in Colombia, 2012-2015.
Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region.


Faecal retention: a common cause in functional bowel disorders, appendicitis and haemorrhoids--with medical and surgical therapy.
The present studies explored whether faecal retention in the colon is a causative factor in functional bowel disease, appendicitis, and haemorrhoids. Faecal retention was characterized by colon transit time (CTT) after radio-opaque marker ingestion and estimation of faecal loading on abdominal radiographs at 48 h and 96 h. Specific hypotheses were tested in patients (n = 251 plus 281) and in healthy random controls (n = 44). A questionnaire was completed for each patient, covering abdominal and anorectal symptoms and without a priori grouping. Patients with functional bowel disorders, predominantly women, had a significantly increased CTT and faecal load compared to controls. The CTT was significantly and positively correlated with segmental and total faecal loading. The faecal load was equal at 48 h and 96 h, mirroring the presence of permanent faecal reservoirs. In these first clinical studies to correlate bowel symptoms with CTT and colon faecal loading, abdominal bloating was significantly correlated with faecal loading in the right colon, total faecal load, and CTT. Abdominal pain was significantly and positively correlated to distal faecal loading and significantly associated with bloating. A new phenomenon with a high faecal load and a normal CTT was observed in a subset of patients (n = 90), proving faecal retention as hidden constipation. The CTT and faecal load were significantly higher in the right-side compared to the left and distal segments. Within the control group of healthy persons, the right-sided faecal load was significantly greater than the left and distal load. The CTT and faecal load significantly positively correlated with a palpable mass in the left iliac fossa and meteorism. Cluster analysis revealed that CTT and faecal load positively correlated with a symptom factor consisting of bloating, proctalgia and infrequent defecation of solid faeces. On the other hand, CTT and faecal load negatively correlated with a symptom factor comprising frequent easy defecations, repetitiveness, and incompleteness with solid or liquid faeces. The majority of patients with a heavy faecal load but normal CTT had repetitive daily defecation, mostly with ease and with altering faecal consistence. Flue-like episodes co-existed in symptom factors with abdominal pain and meteorism, and these symptoms together with a palpable right iliac fossa mass and tenderness, and in other factors with seldom and difficult defecation, and with epigastric discomfort and halitosis. Patients with seldom and difficult defecation of solid faeces experienced abdominal pain significantly more often and presented a palpable mass in the right iliac fossa with tenderness and meteorism. The CTT was significantly prolonged and faecal load significantly increased. In patients with a normal CTT and increased faecal load, only patients with abdominal pain had a significant correlation between faecal loading and bloating. CTT and faecal load were shown for the first time to increase significantly with the number of colonic redundancies (colon length), which also resulted in significantly increased bloating and pain. Intervention with a bowel stimulation regimen combining a fibre-rich diet, fluid, physical activity, and a prokinetic drug was essential to proving that abdominal symptoms and defecation disorders are caused by faecal retention, with or without a prolonged CTT. The CTT was significantly reduced, as was faecal load. Bloating and pain were reduced significantly. The defecation became easy with solid faeces, towards one per day and with significant reductions in incompleteness and repetitiveness. Proctalgia and flue-like episodes were significantly reduced. The intervention significantly reduced the presence of a tender palpable mass in the right fossa and rectal constipation. In patients with a normal CTT but increased faecal load, the intervention did not significantly change the CTT or load, but bloating and pain were significantly reduced, just as defecation improved overall. The novel knowledge of faecal retention in the patients does not explain why faecal retention occurs. However, it may be inferred from the present results that a constipated or irritable bowel may belong to the same underlying disease dimension, where faecal retention is a common factor. Thus, measuring CTT and faecal load is suggested as a guide to a positive functional diagnosis of bowel disorders compared to the constellation of symptoms alone. Thirty-five patients underwent surgery after being refractory to the conservative treatment for constipation. They had a significantly prolonged CTT and heavy faecal loading, which was responsible for the aggravated abdominal and defaecatory symptoms. The operated patients presented with a redundant colon (dolichocolon) significantly more often. These patients also had an extremely high rate of previous appendectomy. Twenty-one patients underwent hemicolectomy, and 11 patients had a subtotal colectomy with an ileosigmoidal anastomosis; three patients received a stoma. However, some patients had to have the initial segmental colectomy converted to a final subtotal colectomy because of persisting symptoms. Six more subtotal colectomies have been performed and the leakage rate of all colectomies is then 4.9 % (one patient died). After a mean follow-up of 5 years, the vast majority of patients were without abdominal pain and bloating, having two to four defecations daily with control and their quality of life had increased considerably. A faecalith is often located in the appendix, the occlusion of which is responsible for many cases of acute appendicitis, which is infrequent in all except white populations. An effort to trace the origin of the faecalith to faecal retention in the colon was made in a case control study (56 patients and 44 random controls). The CTT was longer and faecal load greater in patients with appendicitis compared to controls, though the difference was not significant. Power calculations showed that more patients were needed to reach statistical significance for these parameters. The presence of a faecalith was most often associated with a gangrenous or perforated appendix. No significant differences were found between the CTT and faecal load of patients who had or did not have a faecalith. However, the right-sided faecal load was significantly higher than the left and distal load. Haemorrhoids are often a consequence of constipation and defaecatory disorders and were found in every second patient with functional bowel disorders. The present studies are the first Danish reports of a novel operation to cure this disease, stapled haemorrhoidopexy (n = 40 and 258 patients). The majority of patients had prolapsed haemorrhoids, and the durability of procedure was confirmed with a follow-up of up to 5 years, meaning a normal anus. The operation time was short, post-operative pain was low, and recovery was rapid. No incontinence was observed, and patient satisfaction was high and significantly correlated with the appearance of a normal anus without prolapse. The cumulative risk of re-operation was greatest in the first 2 years after the stapled haemorrhoidopexy. Patients with persisting haemorrhoidal prolapse had the procedure repeated with results as good as those obtained in the rest of the patients. It was shown in a statistical model that the preoperative severity of haemorrhoidal disease and the immediate postoperative result contributed significantly to predicting the outcome that is the durability of the operation. The most frequent post-operative complication was bleeding requiring surgical haemostasis. One serious complication occurred after an anastomotic leak from a highly placed anastomosis, resulting in retro rectal, retro- and intra-peritoneal, and mediastinal gas. The patient recovered after conservative treatment and without surgical intervention. The stapling technique now used has revolutionized the surgical treatment of prolapsing haemorrhoids. Finally, a common cause may be suspected for diseases constantly associated with one another. Epidemiological evidence has recognized that constipation, diverticulosis and IBS increase the risk of colon cancer (and adenomas), diseases exceedingly rare in communities exempt from appendicitis. Haemorrhoids are a colonic co-morbidity as well. Notably, the patients with a functional bowel disorder had a much higher rate of a previous appendectomy than the background population. In addition, the patients who had previously had an appendectomy had a significantly longer CTT compared to patients, who had not. The data points to the involvement of faecal retention in the origin of faecaliths and, thus, acute appendicitis. Faecal reservoirs were shown in the right and left colon segments in both patients and controls, which are the same areas bearing the highest incidences of adenomateous polyps and malignancies. Familial colorectal cancer occurred significantly more often in patients who had a higher faecal load than the controls. Four malignancies and 25 adenomas were identified. An increased faecal load in the colon with or without delayed transit will increase bacterial counts and create a chronic inflammation of the colonic mucosa, which is a risk factor for cancer onset. A functional bowel disorder is then likely to occur with gradually transition from a primary functional disease into specific organic diseases. A diet rich in fibre and regular physical activity have a therapeutic and preventive effect on colorectal diseases associated with faecal retention. A "common cause" was earlier proposed for constipation, colon diverticula, cancer, appendicitis, and haemorrhoids. The actual results of the present studies support this unifying theory for these diet-related diseases, in which the functional retention of faeces maybe the common cause.


Impaired hepatocyte glucose transport protein (GLUT2) internalization in chronic pancreatitis.
Chronic pancreatitis (CP) is associated with impaired glucose tolerance and with reduced hepatic sensitivity to insulin. We have previously shown that in normal and sham-operated rats, insulin suppresses hepatic glucose production, and this suppression is associated with a decrease in the hepatocyte plasma membrane-bound quantity of the facilitative glucose transport protein GLUT2. The insulin-mediated reduction in membrane-bound GLUT2 is impaired in CP, and may play a role in the glucose intolerance associated with CP. To determine whether GLUT2 is actively internalized and whether this mechanism is disordered in CP, livers from fed and fasting rats in whom CP had been induced 2-3 months earlier by pancreatic duct oleic acid infusion, and in sham-operated (sham) rats, were fractionated to yield endosome (E)- and plasma membrane (PM)-enriched fractions. Forty-five minutes after duodenal intubation alone (fasting) or intubation plus duodenal feeding, livers were removed, homogenized and ultracentrifuged, and microsomal pellets were separated by sucrose density gradient ultracentrifugation. GLUT2 content of fractions was determined by Western blotting and scanning densitometry. The E:PM ratio of GLUT2 increased from 0.68 +/- 0.11 (mean +/- SEM) in fasting sham livers (n = 8) to 1.04 +/- 0.09 in fed sham livers (n = 8; p < 0.05). However, there was no change in the E:PM ratio of GLUT2 in CP livers after duodenal feeding (0.90 +/- 0.12 vs. 0.86 +/- 0.10; n = 8,8; p = NS). To test our findings using confocal laser scanning microscopy, liver specimens from fed and fasting CP and sham rats were minced, fixed in 4% paraformaldehyde, sectioned, and stained with rabbit antirat GLUT2 antibody followed by rhodamine-labeled secondary antibody. GLUT2 was quantified by mean pixel intensity in an 8 x 16-pixel area of PM and a 16 x 16-pixel area of cytosol (CYT) in each of 30 random cells/field (400x) in each of three rats per group. As in the fractionation study, duodenal feeding increased the CYT:PM ratio of GLUT2 from 0.75 +/- 0.01 in fasting sham liver to 0.86 +/- 0.01 in fed sham liver (p < 0.0001), while the CYT:PM ratio in CP remained unchanged. We conclude that feeding induces a shift in GLUT2 from the plasma membrane to the endosomal pool. The feeding-induced internalization of GLUT2 is absent in livers from rats with CP and may play a role in the glucose intolerance associated with CP.


What We Talk About When We Talk About Evolution.
Currently, the biologic sciences are a Tower of Babel, having become so highly specialized that one discipline cannot effectively communicate with another. A mechanism for evolution that integrates development and physiologic homeostasis phylogenetically has been identified-cell-cell interactions. By reducing this process to ligand-receptor interactions and their intermediate down-stream signaling partners, it is possible, for example, to envision the functional homologies between such seemingly disparate structures and functions as the lung alveolus and kidney glomerulus, the skin and brain, or the skin and lung. For example, by showing the continuum of the lung phenotype for gas exchange at the cell-molecular level, being selected for increased surface area by augmenting lung surfactant production and function in lowering surface tension, we have determined an unprecedented structural-functional continuum from proximate to ultimate causation in evolution. It is maintained that tracing the changes in structure and function that have occurred over both the short-term history of the organism (as ontogeny), and the long-term history of the organism (as phylogeny), and how the mechanisms shared in common can account for both biologic stability and novelty, will provide the key to understanding the mechanisms of evolution. We need to better understand evolution from its unicellular origins as the Big Bang of biology.


Presynaptic sympathetic mechanism in the insulinostatic effect of epinephrine in mouse pancreatic islets.
The catecholamines inhibit insulin release. It is not established whether presynaptic mechanisms contribute to this effect. We therefore examined the relative contribution of presynaptic and postsynaptic mechanisms to the insulinostatic effects of epinephrine and norepinephrine. Mice were injected with 6-hydroxydopamine (6-OHDA; 0.19 mmol/kg) or its vehicle. Islets were isolated after 48 h. Islets from vehicle-injected control animals contained numerous tyrosine hydroxylase (TH)-immunoreactive nerve terminals (marker for sympathetic nerves). In contrast, TH-immunoreactive nerves were not detected in islets from 6-OHDA-treated animals, indicating sympathetic denervation. Basal (5.6 mmol/l glucose) or glucose-stimulated (16.7 mmol/l) insulin secretion did not differ between incubated islets from vehicle-injected control animals and islets from 6-OHDA-treated animals. The insulinostatic effect of epinephrine, but not that of norepinephrine, was markedly impaired in islets from 6-OHDA-treated animals: the lowest effective insulinostatic concentration of epinephrine was 0.01 nmol/l in islets from vehicle-injected animals and 1 nmol/l in islets from 6-OHDA-treated animals. We conclude that in isolated mouse islets the insulinostatic effect of epinephrine, but not that of norepinephrine, partially depends on sympathetic nerve terminals, suggesting an important role for presynaptic mechanisms in epinephrine-induced inhibition of insulin secretion.


Neuroprotective Potential of Allium sativum against Monosodium Glutamate-Induced Excitotoxicity: Impact on Short-Term Memory, Gliosis, and Oxidative Stress.
This study evaluated the neuroprotective potential of Allium sativum against monosodium glutamate (MSG)-induced neurotoxicity with respect to its impact on short-term memory in rats. Forty male Wistar albino rats were assigned into four groups. The control group received distilled water. The second group was administered Allium sativum powder (200 mg/kg of body weight) orally for 7 successive days, then was left without treatment until the 30th day. The third group was injected intraperitoneally with MSG (4 g/kg of body weight) for 7 successive days, then left without treatment until the 30th day. The fourth group was injected with MSG in the same manner as the third group and was treated with Allium sativum powder in the same manner as the second group, simultaneously. Phytochemical analysis of Allium sativum powder identified the presence of diallyl disulphide, carvone, diallyl trisulfide, and allyl tetrasulfide. MSG-induced excitotoxicity and cognitive deficit were represented by decreased distance moved and taking a long time to start moving from the center in the open field, as well as lack of curiosity in investigating the novel object and novel arm. Moreover, MSG altered hippocampus structure and increased MDA concentration and protein expression of glial fibrillary acidic protein (GFAP), calretinin, and caspase-3, whereas it decreased superoxide dismutase (SOD) activity and protein expression of Ki-67 in brain tissue. However, Allium sativum powder prevented MSG-induced neurotoxicity and improved short-term memory through enhancing antioxidant activity and reducing lipid peroxidation. In addition, it decreased protein expression of GFAP, calretinin, and caspase-3 and increased protein expression of Ki-67 in brain tissues and retained brain tissue architecture. This study indicated that Allium sativum powder ameliorated MSG-induced neurotoxicity through preventing oxidative stress-induced gliosis and apoptosis of brain tissue in rats.


[Respiratory aid to patients with severe forms of suppurative meningitis].
The severity of acute respiratory failure (ARF) in patients with purulent meningitis (PM) depends on the severity of consciousness disorders. ARF is most expressed in comatose patients, whereas in PM involving no consciousness disorders there were no changes of the gaseous composition of the blood or acid-base status. After forced ventilation of the lungs is started, gaseous composition of the blood normalizes. Timely active respiratory care decreased by half the mortality in this patient population, this indicating that such patients are to be treated in intensive care wards for timely correction of disordered vital functions.


[Possible dependence of the results of phage typing Ps. aeruginosa strains on the presence of R plasmids].
The plasmid composition of 209 strains of Ps. aeruginosa was determined. The strains were isolated from patients, animals and environment in different geographical areas. The number of the plasmid-containing strains averaged 26.8 per cent. The molecular weights of the plasmids varied from less than 10 to more than 150 MD. 41 conjugative plasmids were transmitted to the recipients of Ps. aeruginosa RAO 303. 66 per cent of them had a restrictive effect on the development of phages used in genetic studies, epidemiological phage typing (Lindberg Collection), and medical practice. This resulted in the changing of the phage type of the host strain. Similar results were obtained in the studies with 10 standard R plasmids representing different incompatibility groups. No relation between the spectrum of the phage restriction, group specificity and the other properties of the plasmids was observed. About 50 per cent of the plasmids markedly lowered the sensitivity level of Ps. aeruginosa RAO 303 to the therapeutic pyocyanic phage. The systems of restriction and modification of DNA coded with plasmids were not detected. A possible changing of the phage type of Ps. aeruginosa strains under the effect of R plasmids should be considered in epidemiological assays and respective treatment measures.


[Fast neutrons in the treatment of malignant neoplasms].
More than 250 patients, mainly with locally advanced tumors of the head, neck and breast were treated with a I MeV beam of fast neutrons emitted from a BR-10 reactor. The fast neutron contribution to the total dose of the radical component of complex gamma-neutron therapy was 20-40%. Said modality was shown to improve the results of treatment for laryngeal and breast tumors. The 5-year actuarial survival following complex gamma-neutron therapy for laryngeal cancer was 89.25, while in controls--65.2% (p < 0.005). The 5-year actuarial overall survival in breast cancer patients treated with fast neutrons was 66.5%: gamma-neutron therapy alone--46.0% (p < 0.05).


Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure.
Mechanisms by which aniline exposure elicits splenotoxicity, especially a tumorigenic response, are not well-understood. Earlier, we have shown that aniline exposure leads to oxidative DNA damage and up-regulation of OGG1 and NEIL1/2 DNA glycosylases in rat spleen. However, the contribution of endonuclease III homolog 1 (NTH1) and apurinic/apyrimidinic endonuclease 1 (APE1) in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on examining whether NTH1 and APE1 contribute to the repair of oxidative DNA lesions in the spleen, in an experimental condition preceding tumorigenesis. To achieve this, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. By quantitating the cleavage products, the activities of NTH1 and APE1 were assayed using substrates containing thymine glycol (Tg) and tetrahydrofuran, respectively. Aniline treatment led to significant increases in NTH1- and APE1-mediated BER activity in the nuclear extracts of spleen of aniline-treated rats compared to the controls. NTH1 and APE1 mRNA expression in the spleen showed 2.9- and 3.2-fold increases, respectively, in aniline-treated rats compared to the controls. Likewise, Western blot analysis showed that protein expression of NTH1 and APE1 in the nuclear extracts of spleen from aniline-treated rats was 1.9- and 2.7-fold higher than the controls, respectively. Immunohistochemistry indicated that aniline treatment also led to stronger immunoreactivity for both NTH1 and APE1 in the spleens, confined to the red pulp areas. These results, thus, show that aniline exposure is associated with induction of NTH1 and APE1 in the spleen. The increased repair activity of NTH1 and APE1 could be an important mechanism for the removal of oxidative DNA lesions. These findings thus identify a novel mechanism through which NTH1 and APE1 may regulate the repair of oxidative DNA damage in aniline-induced splenic toxicity.


Morphological impairments in microglia precede age-related neuronal degeneration in senescence-accelerated mice.
The ageing brain is characterized by degenerative changes in both neurons and glia. Although neurons are known to lose dendritic complexity with ageing, age-related changes in the morphology of microglia have not been well documented. We investigated potential age-related changes in microglial morphology using mouse models. Senescence-accelerated mouse prone 10 (SAMP10) in which neuronal degeneration begins to appear around 8 months of age and becomes progressively remarkable with advancing age was used as a model of brain ageing. Senescence-accelerated mouse resistant 1 (SAMR1) in which age-related neuronal changes are inconspicuous was used as usual-ageing controls. Hippocampal sections prepared from 3-, 8- and 14-month-old SAMP10 and 3-, 8-, 14- and 24-month-old SAMR1 mice were stained immunohistochemically with anti-Iba-1 antibody to highlight microglia. Stick figures of individual microglia reflecting the length and complexity of cytoplasmic processes were made by camera lucida drawing. Parameters representing morphological features of microglia were quantified using an image analyzer: area of convex closure, cell body area, number of primary processes, maximal branch order, combined projection length, number of segments and number of tips. Pathological changes of processes such as beading and clusters of fragmented twigs were counted. In microglia of 3- and 8-month-old SAMP10 mice, combined projection length was shorter and numbers of segments and tips were smaller than those in age-matched SAMR1 mice. Similar changes were detected in SAMR1 mice at age 14 months and older. Microglia of SAMP10 mice at all ages were characterized by having frequent pathological changes in processes, which were not remarkable in SAMR1 mice at any age. These morphological abnormalities in microglia of SAMP10 mice preceded the onset of neuronal degeneration and may lead to making brain tissue less protective to neurons. We propose that preceding abnormalities in microglia may contribute to the vulnerability to age-related neuronal degeneration in SAMP10 mice.


[Lupus, corticosteroid treatment and opportunistic infection: 26 cases in Gabon].
Opportunistic infection is frequent in lupus patients. Susceptibility is inherent in the lymphopeniant nature of the disease and enhanced by the use of immune-suppressing agents (alone or in combination) for optimal disease control. The purpose of this retrospective series of lupus patients diagnosed based on the criteria of the American College of Rheumatology (ACR) was to assess the frequency of opportunistic infection in a high-risk epidemiological area. A total of 26 patients (24 women, 2 men) with a mean age of 28.8 years were identified. Systematic review carried infectious before the steroid and in light of the local endemicity (HBs Ag, hepatitis C serology, HIV + Rx Thorax IDR) coupled with blood cultures was non-contributory, without waking the tank or during the introduction treatment. With a mean follow-up of 3.6 years (range, 0.83 to 9.91), only one case of tuberculosis was observed with fatal outcome. Our study indicates that the prevalence of opportunistic infections in the Lupus under treatment in a high-risk area for infectious diseases was low. This finding suggests that the risk of infectious complications secondary to corticosteroid therapy in sub-Saharan zone is acceptable provided that surveillance is performed on a regular basis.


The phosducin-like protein PhLP1 impacts regulation of glycoside hydrolases and light response in Trichoderma reesei.
In the biotechnological workhorse Trichoderma reesei (Hypocrea jecorina) transcription of cellulase genes as well as efficiency of the secreted cellulase mixture are modulated by light. Components of the heterotrimeric G-protein pathway interact with light-dependent signals, rendering this pathway a key regulator of cellulase gene expression. As regulators of heterotrimeric G-protein signaling, class I phosducin-like proteins, are assumed to act as co-chaperones for G-protein beta-gamma folding and exert their function in response to light in higher eukaryotes. Our results revealed light responsive transcription of the T. reesei class I phosducin-like protein gene phlp1 and indicate a light dependent function of PhLP1 also in fungi. We showed the functions of PhLP1, GNB1 and GNG1 in the same pathway, with one major output being the regulation of transcription of glycoside hydrolase genes including cellulase genes in T. reesei. We found no direct correlation between the growth rate and global regulation of glycoside hydrolases, which suggests that regulation of growth does not occur only at the level of substrate degradation efficiency.Additionally, PhLP1, GNB1 and GNG1 are all important for proper regulation of light responsiveness during long term exposure. In their absence, the amount of light regulated genes increased from 2.7% in wild type to 14% in Δphlp1. Besides from the regulation of degradative enzymes, PhLP1 was also found to impact on the transcription of genes involved in sexual development, which was in accordance with decreased efficiency of fruiting body formation in Δphlp1. The lack of GNB1 drastically diminished ascospore discharge in T. reesei. The heterotrimeric G-protein pathway is crucial for the interconnection of nutrient signaling and light response of T. reesei, with the class I phosducin-like protein PhLP1, GNB1 and GNG1 acting as important nodes, which influence light responsiveness, glycoside hydrolase gene transcription and sexual development.


Cholesterol metabolism in pathogenesis of osteoarthritis disease.
Several lines of research indicate that osteoarthritis (OA) is not only a joint disorder associated with mechanical stress and aging but also a 'metabolic syndrome' in which several risk factors work together to contribute to disease initiation and/or development. One such metabolic risk factor could be high cholesterol levels in the body. Even though high cholesterol level is a well-known risk factor for cardiovascular disorders, its possible role in musculoskeletal diseases, particularly OA, is not clear. The authors discuss the fundamental viewpoints on cholesterol involvement in the pathogenesis of OA, stressing the need for understanding the molecular mechanisms behind this association. This is the area of research needed to provide knowledge on how one should live to prevent OA development as well as to suggest new targets for drug therapy.


[Lightning strike on a horse pasture - a diagnostic challenge?!]
During summer, permanent or temporary pasture keeping carries an increased risk of death caused by lightning strikes. Although - due to their body structure and pasture grazing - large animals are particularly susceptible to step voltage effects in consequence to a lightning strike to the ground there are only few published cases in the veterinary literature. Frequently in lightning-related accidents, a current flow through the heart occurs resulting in acute cardiac and circulatory failure. In the vast majority of cases, this is accompanied either by very unspecific lesions or even lacks any morphological alterations. Accordingly, the etiologic diagnosis in the absence of clear, lightning-related damage to the body represents a major diagnostic challenge. The evaluation of meteorological data as well as consideration of the pasture's location and positioning of the body when found may provide further key information in the clarification of fatalities caused by lightning strikes.This case report presents findings in a 7-year-old thoroughbred gelding found dead together with 3 other horses, all lying together in a group on the pasture. Pathological examination revealed a 2-3 mm wide line of singed, curled hair on the right front and hind limbs. Histologically, the pertaining skin areas displayed groups of elongated epithelial cells with herringbone-like elongation of the nuclei within the epidermis and the hair follicles. Coagulations of dermal proteins were present multifocally within the dermis.


Theory and modeling of stereoselective organic reactions.
Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometries of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions.


The rate of growth in scientific publication and the decline in coverage provided by Science Citation Index.
The growth rate of scientific publication has been studied from 1907 to 2007 using available data from a number of literature databases, including Science Citation Index (SCI) and Social Sciences Citation Index (SSCI). Traditional scientific publishing, that is publication in peer-reviewed journals, is still increasing although there are big differences between fields. There are no indications that the growth rate has decreased in the last 50 years. At the same time publication using new channels, for example conference proceedings, open archives and home pages, is growing fast. The growth rate for SCI up to 2007 is smaller than for comparable databases. This means that SCI was covering a decreasing part of the traditional scientific literature. There are also clear indications that the coverage by SCI is especially low in some of the scientific areas with the highest growth rate, including computer science and engineering sciences. The role of conference proceedings, open access archives and publications published on the net is increasing, especially in scientific fields with high growth rates, but this has only partially been reflected in the databases. The new publication channels challenge the use of the big databases in measurements of scientific productivity or output and of the growth rate of science. Because of the declining coverage and this challenge it is problematic that SCI has been used and is used as the dominant source for science indicators based on publication and citation numbers. The limited data available for social sciences show that the growth rate in SSCI was remarkably low and indicate that the coverage by SSCI was declining over time. National Science Indicators from Thomson Reuters is based solely on SCI, SSCI and Arts and Humanities Citation Index (AHCI). Therefore the declining coverage of the citation databases problematizes the use of this source.


Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury.
Susceptibility weighted imaging (SWI) is sensitive to deoxyhemoglobin and blood products such as hemosiderin in detecting microbleeds in the brain. However, there are no studies on SWI in the spine cord injury so far. The purpose of this study was to evaluate the role of SWI in detecting hemorrhage in acute cervical spinal cord injury (SCI). Twenty-three patients with a history of acute cervical spine trauma were studied. High-resolution SWI, gradient-echo (GRE) T2* weighted-image (T2*WI) and conventional magnetic resonance imaging (MRI) were performed on all patients within 15 days of the onset of injury. On the basis of the MRI findings, the patients were classified into four patterns: normal cord, spinal cord edema, spinal cord contusion and spinal cord hemorrhage. Quantitative analysis was performed by calculating and comparing the signal ratio of the hemorrhage to normal spinal cord on the same slice of T2*WI and SWI. All patients were clinically evaluated in follow-up. Twenty volunteers were also scanned as a control group. Out of 23 patients with a history of acute cervical spine trauma, 4 patients showed normal spinal cord on both conventional MRI and SWI, 8 had only spinal cord edema and 5 had contusion on conventional MRI, but SWI showed hemorrhage in 2 of the 5 patients with spinal contusion on conventional MRI; the other 6 patients had intraspinal hemorrhage on conventional MRI, and SWI proved hemorrhage in all these 6 patients. There was a significant difference between the signal ratios of hemorrhage to normal tissue on T2*WI and SWI (Z=2.34, P=.02). Susceptibility weighted imaging is more sensitive than conventional MRI in detecting hemorrhage in acute cervical SCI. This technique could prove to be a useful tool in the routine evaluation of cervical SCI patients.


Effects of entropy in real-world noise on speech perception in listeners with normal hearing and hearing lossa).
Hearing aids show more benefit in traditional laboratory speech-in-noise tests than in real-world noisy environments. Real-world noise comprises a large range of acoustic properties that vary randomly and rapidly between and within environments, making quantifying real-world noise and using it in experiments and clinical tests challenging. One approach is to use acoustic features and statistics to quantify acoustic properties of real-world noise and control for them or measure their relationship to listening performance. In this study, the complexity of real-world noise from different environments was quantified using entropy in both the time- and frequency-domains. A distribution of noise segments from low to high entropy were extracted. Using a trial-by-trial design, listeners with normal hearing and hearing loss (in aided and unaided conditions) repeated back sentences embedded in these noise segments. Entropy significantly affected speech perception, with a larger effect of entropy in the time-domain than the frequency-domain, a larger effect for listeners with normal hearing than for listeners with hearing loss, and a larger effect for listeners with hearing loss in the aided than unaided condition. Speech perception also differed between most environment types. Combining entropy with the environment type improved predictions of speech perception above the environment type alone.


On statistical analysis for placebo-challenging designs in clinical trials.
In clinical trials, appropriate designs are often chosen to address scientific/medical questions of particular interest to the investigator. For a chosen statistical design, however, standard statistical procedures may not be applicable owing to the nature of the design. In this paper we examine statistical methods for analysis of data collected from a placebo-challenging design which is often considered for assessment of the efficacy of drug products for indication of erectile dysfunction. An example concerning a clinical trial conducted with 120 male patients with erectile dysfunction is used to illustrate the derived statistical methods. Some recommendations to the randomization procedure for the study design of this kind are also made.


Duodenal erosions and ulcers in patients with pancreatobiliary obstruction.
In order to determine whether obstructive pancreatobiliary lesions increase the risk of duodenal erosions and ulcers, the duodenal mucosa of patients with these lesions were prospectively examined before endoscopic retrograde cholangiopancreatography (ERCP). During the study period, 133 patients underwent ERCP for various reasons in the Department of Medicine, The Aga Khan University Hospital. One hundred and twenty-three patients were eligible for final analysis. Sixty-five patients with bilirubin > or = 35 mumol/L and alkaline phosphatase > or = 2.5 times normal levels along with radiological evidence of pancreatobiliary obstruction were included in the obstruction group. Fifty-eight patients who did not fulfil these criteria were used in the control group. Acid peptic lesions, which included erosions and ulcers, were seen in 16 patients of the obstruction group and four patients of the control group (P = 0.016, odds ratio (OR) = 4.41). Patients with carcinoma of the pancreas had a greater number of lesions than the rest of the obstruction group (P = 0.001, OR = 8.75). Individual variables like age, sex, serum bilirubin, alanine aminotransferase, alkaline phosphatase, amylase levels, and duration of jaundice did not increase the vulnerability to acid peptic injury. The degree of obstruction multiplied by duration of jaundice (alkaline phosphatase x days) increased the susceptibility for duodenal disease (P = 0.047). From this data it was concluded that patients with obstructive pancreatobiliary lesions are more prone to acid peptic duodenal lesions.


Synthesis and properties of 2'-deoxy-2',4'-difluoroarabinose-modified nucleic acids.
We report the synthesis, thermal stability, and RNase H substrate activity of 2'-deoxy-2',4'-difluoroarabino-modified nucleic acids. 2'-Deoxy-2',4'-difluoroarabinouridine (2,'4'-diF-araU) was prepared in a stereoselective way in six steps from 2'-deoxy-2'-fluoroarabinouridine (2'-F-araU). NMR analysis and quantum mechanical calculations at the nucleoside level reveal that introduction of 4'-fluorine introduces a strong bias toward the North conformation, despite the presence of the 2'-βF, which generally steers the sugar pucker toward the South/East conformation. Incorporation of the novel monomer into DNA results on a neutral to slightly stabilizing thermal effect on DNA-RNA hybrids. Insertion of 2',4'-diF-araU nucleotides in the DNA strand of a DNA-RNA hybrid decreases the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage of the complement RNA strand compared to that for an all-DNA strand or a DNA strand containing the corresponding 2'-F-araU nucleotide units, consistent with the notion that a 4'-fluorine in 2'-F-araU switches the preferred sugar conformation from DNA-like (South/East) to RNA-like (North).


[pH-adjusted lidocaine HCl with or without epinephrine for epidural anesthesia].
Preparations of local anesthetics are prepared as acidic solutions of the salts to promote solubility and stability. In solution, these salts exist as both nonionized and ionized forms. The ratio depends on the pH of the solution, and it is only the non-ionized form that permeates the nerve membrane and sheath. This study of epidural analgesia was undertaken to determine the effect of increasing the pH of the lidocaine HCl by the addition of sodium bicarbonate. Parameters studied included the time of onset of analgesia (time between the completion of injection and the loss of scratch sensation at the left L1 dermatome), the spread of sensory blockade, the degree of motor block, and the blood pressure and heart rate. Eighty seven adult patients undergoing epidural anesthesia were divided into four groups. Group 1 patients were given 2% lidocaine HCl solution plus 1.5 mL normal saline per 10 mL of lidocaine (pH 5.55). Group 2 patients were given 2% lidocaine HCl solution plus 1.5 mL 7% sodium bicarbonate per 10 mL of lidocaine (pH 7.04). Group 3 received 2% lidocaine HCl solution with 1:200000 epinephrine plus 1.5 mL normal saline per 10 mL of lidocaine (pH 5.68). Group 4 received 2% lidocaine HCl solution with 1:200000 epinephrine plus 1.5 mL 7% sodium bicarbonate per 10 mL of lidocaine (pH 7.11). The time of onset of analgesia and the spread of sensory blockade were more rapid in groups 2 and 4. The degree of motor block was more pronounced in these two groups, as were the changes in blood pressure and heart rate.


Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee.
TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (kappa = 0.80). COPD-relatedness was reproduced 84% of the time (kappa = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.


3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine: a dual-signaling fluorescent reagent for optical sensing of aliphatic aldehydes.
A new optical chemical sensor for continuous monitoring of aliphatic aldehydes has been proposed based on the reversible chemical reaction between a new sensing reagent, 3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine (TMAB), and the analytes. TMAB, containing two receptors and two fluorescent reporters, can perform dual fluorescence responses corresponding to the reactions of hydrogen ion and carbonyl compound. When immobilized in a plasticized poly(vinyl chloride) membrane, TMAB extracts aliphatic aldehydes from aqueous solution into the bulk membrane phase and reacts with the analyte by forming a Schiff base. Since the extraction equilibrium and chemical reaction are accompanied by fluorescence increase of the sensing membrane, the chemical recognition process could be directly translated into an optical signal. At pH 3.20, the sensor exhibits a dynamic detection range from 0.017 to 4.2 mM n-butyraldehyde with a limit of detection of 0.003 mM. The forward response time (t95) of the sensor is 3-5 min, and the reverse response time is 5-7 min. The responses of the sensor toward different kinds of aldehydes and ketones depend on the lipophilicity and the reactivity of the analytes. Since the fluorescence enhancement of the sensing membrane at 296 nm/410 nm is only related to the formation of Schiff base, the measurement of aldehydes is independent of pH.


Impact of D-Dimer for Prediction of Incident Occult Cancer in Patients with Unprovoked Venous Thromboembolism.
Unprovoked venous thromboembolism (VTE) is related to a higher incidence of occult cancer. D-dimer is clinically used for screening VTE, and has often been shown to be present in patients with malignancy. We explored the predictive value of D-dimer for detecting occult cancer in patients with unprovoked VTE. We retrospectively examined data from 824 patients diagnosed with deep vein thrombosis or pulmonary thromboembolism. Of these, 169 (20.5%) patients diagnosed with unprovoked VTE were selected to participate in this study. D-dimer was categorized into three groups as: <2,000, 2,000-4,000, and >4,000 ng/ml. Cox regression analysis was employed to estimate the odds of occult cancer and metastatic state of cancer according to D-dimer categories. During a median 5.3 (interquartile range: 3.4-6.7) years of follow-up, 24 (14%) patients with unprovoked VTE were diagnosed with cancer. Of these patients, 16 (67%) were identified as having been diagnosed with metastatic cancer. Log transformed D-dimer levels were significantly higher in those with occult cancer as compared with patients without diagnosis of occult cancer (3.5±0.5 vs. 3.2±0.5, P-value = 0.009, respectively). D-dimer levels >4,000 ng/ml was independently associated with occult cancer (HR: 4.12, 95% CI: 1.54-11.04, P-value = 0.005) when compared with D-dimer levels <2,000 ng/ml, even after adjusting for age, gender, and type of VTE (e.g., deep vein thrombosis or pulmonary thromboembolism). D-dimer levels >4000 ng/ml were also associated with a higher likelihood of metastatic cancer (HR: 9.55, 95% CI: 2.46-37.17, P-value <0.001). Elevated D-dimer concentrations >4000 ng/ml are independently associated with the likelihood of occult cancer among patients with unprovoked VTE.


[Use of dibunol in treating radiation injuries to the skin and mucosa].
The authors present the results of the use of dibunol in the form of liniment (1-10%) for the treatment of radiation cystitis and rectitis resulting from radiation therapy of small pelvic tumors, epidermitis and epithelitis that develop in the course of treatment of skin and lower lip tumors. A high efficacy of the drug in the therapy of radiation injury has been shown in 212 patients.


Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep.
To investigate the effects of Nomega-mono-methyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on hemodynamics, oxygen transport, and regional blood flow in an ovine model of hyperdynamic sepsis and to compare these effects with the responses to norepinephrine. Prospective, nonrandomized, controlled experimental study with repeated measures. Investigational intensive care unit at a university medical center. Twenty-five female, healthy, adult sheep of the Merino breed, divided into three groups: nine control sheep; eight sheep treated with L-NMMA; and eight sheep treated with norepinephrine. All sheep were chronically instrumented. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) was started and maintained for the remainder of the experiment. After 24 hrs of sepsis, eight sheep received L-NMMA (7 mg/kg/hr), eight sheep received norepinephrine, and nine sheep received the vehicle alone (0.9% saline). The norepinephrine dosage was continuously and individually adjusted to achieve the same increase in blood pressure as was observed in a matched sheep of the L-NMMA group. After 24 hrs of sepsis, all sheep developed a hyperdynamic circulatory state with increased cardiac indices and reduced arterial pressures, and systemic vascular resistances. L-NMMA reversed the hyperdynamic circulation, causing an increase in arterial pressure by peripheral vasoconstriction. Norepinephrine led to an increase in blood pressure by augmenting cardiac indices, leaving the systemic vascular resistance unaffected. The norepinephrine dose needed to keep the blood pressure high had to be continuously increased, reflecting the reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unaffected by all treatment forms. Norepinephrine and L-NMMA led to a dramatic increase in urine production. Blocking the nitric oxide synthase with L-NMMA did not interfere with the host's pulmonary ability to clear bacteria, nor did treatment with norepinephrine. Blocking nitric oxide synthase had a marked vasoconstrictive effect. Both norepinephrine and L-NMMA increased arterial pressure without reducing renal blood flow, leading to an improved renal function.


Prognostic Significance of Diastolic Dysfunction With Multiple Comorbidities in Heart Failure Patients.
Background Heart failure poses a significant burden on health care and economy. In recent years, diastolic dysfunction has been increasingly recognized as a significant predictor of readmission in heart failure patients. Objectives We aimed to identify factors predicting readmission in patients with clinical heart failure at 30 days and six months. Methods A retrospective chart review was performed at a single urban medical center, including 208 patients in our final analysis. Results A higher Charlson comorbidity index (CCI) and moderate anemia (hemoglobin [Hb] < 10 g/dL) were significant predictors of readmission at both 30 days and six months. In addition, advanced chronic kidney disease (CKD) stage (4 or 5) and follow-up in a cardiology clinic were significant predictors at six months. During multivariate analysis, worsening diastolic dysfunction (grade 3 or 4) (OR: 2.09; 95% CI: 1.03 to 4.23), higher CCI (OR: 1.18; 95% CI: 1.03-1.36), and Hb < 10 g/dL (OR: 3.42; 95% CI: 1.44-8.13) were independent predictors of readmission at 30 days. Higher CCI (OR: 1.37; 95% CI: 1.19-1.58) and CKD stage 4 or 5 (OR: 3.05; 95% CI: 1.40-6.62) were independent predictors of readmission at six months. Conclusions Worse diastolic dysfunction (grade 3 or 4) was a significant predictor of all-cause readmission at 30 days post-discharge in heart failure patients. Higher CCI precisely predicted readmission as an independent variable at 30 days and six months. Anemia (Hb < 10 g/dL) and CKD stage 4 or 5 were significant predictors of readmission at 30-days and six months, respectively.


Functional MRI predicts post-surgical memory following temporal lobectomy.
Temporal lobectomy is an effective therapy for medically refractory temporal lobe epilepsy (TLE), but may be complicated by amnestic syndromes. Therefore, pre-surgical evaluation to assess the risk/benefit ratio for surgery is required. Intracarotid amobarbital testing (IAT) is currently the most widely used method for assessing pre-surgical memory lateralization, but is relatively invasive. Over the past decade functional MRI (fMRI) has been shown to correlate with IAT for language lateralization, and also for memory lateralization in a small number of patients. This study was carried out to compare fMRI during memory encoding with IAT testing for memory lateralization, and to assess the predictive value of fMRI during memory encoding for post-surgical memory outcome. Thirty-five patients with refractory TLE undergoing pre-surgical evaluation for temporal lobectomy and 30 normal subjects performed a complex visual scene-encoding task during fMRI scanning at 1.5 T using a 10-min protocol. Encoding performance was evaluated with subsequent recognition testing. Twenty-three patients also completed the same task again outside the scanner, an average of 6.9 months following surgery. A region of interest (ROI) analysis was used to quantify activation within hippocampal and a larger mesial temporal lobe ROI consisting of hippocampus, parahippocampus and fusiform gyrus (HPF) as defined by a published template. Normal subjects showed almost symmetrical activation within these ROI. TLE patients showed greater asymmetry. Asymmetry ratios (ARs) from the HPF ROI correlated significantly with memory lateralization by intracarotid amobarbital testing. HPF ARs also correlated significantly with memory outcome, as determined by a change in scene recognition between pre-surgical and post-surgical trials. When absolute activation within the HPF ROI was considered, a significant inverse correlation between activation ipsilateral to temporal lobectomy and memory outcome was observed, with no significant correlation in the contralateral HPF ROI. Although further technical improvements and prospective clinical validation are required, these results suggest that mesial temporal memory activation detected by fMRI during complex visual scene encoding correlates with post-surgical memory outcome and supports the notion that this approach will ultimately contribute to patient management.


Subclinical myopathy in patients affected with newly diagnosed colorectal cancer at clinical onset of disease: evidence from skeletal muscle biopsies.
To evaluate skeletal muscle biopsy from asymptomatic patients affected with newly diagnosed colorectal cancer and to identify pathological features which may be indicative of tumor-associated muscle disorders, potentially leading to cachexia. Patients affected with newly diagnosed colorectal cancer at clinical onset of disease underwent biopsy of the rectus abdominis muscle during elective laparoscopic tumor resection, before chemotherapeutic treatment. Morphometric analyses, ATPase histochemistry and immunohistochemical studies using antibodies directed to N-CAM and to MHC-emb, two sound makers of muscle denervation and injury-induced muscle regeneration, were performed on intraoperative muscle biopsies from ten patients. Muscle biopsies from rectus abdominis of seven subjects affected with non-neoplastic condition, which underwent laparoscopic surgery, were used as controls. In patients' biopsies, we observed a surprisingly high percentage of myofibers with internalized or central nuclei compared to controls (9.15 +/- 8.9 versus 0.6 +/- 0.9, p<0.0003). In addition, in the 30% of patients, small myofibers expressing the MHC-emb have been identified (0.4 +/- 0.5 positive fibers/mm(2)), while in 50% of patients, larger fibers positive for N-CAM have also been detected (0.7 +/- 1.1 positive fibers/mm(2)), suggesting that investigated muscle biopsies exhibit other evidence of muscle fiber injury/regeneration and/or denervation. Among the 10,000 analysed myofibers in control biopsies, no MHC-emb and N-CAM-positive muscle fibers have been detected. Thus, patients affected with newly diagnosed colorectal cancer at clinical onset of disease display early signs of a subclinical myopathy. Factors and mechanisms of this cancer-associated myopathy are yet unknown. The facts that the great majority of the abnormally nucleated myofibers are of the fast type and that regenerating myofibers are present, suggest a myogenic response to the colorectal cancer and not to the laparoscopic modalities of the biopsy harvesting. Follow-up of the patients will elucidate the clinical relevance of our observation, and further studies investigating the molecular mechanism underlying this early cancer-associated myopathy will hopefully provide some pathogenetic clues leading to the identification of potential specific targets for therapeutic intervention to prevent tumor cachexia.


The molecular biology of neuronal nicotinic acetylcholine receptors.
The molecular cloning of genes encoding neuronal nicotinic acetylcholine receptors (nAChRs) has made possible a better understanding of the pharmacology and toxicology of cholinergic compounds. Neuronal nAChRs are related in structure to the nAChRs present at the neuromuscular junction. They are composed of multiple subunits designated either alpha and beta. Eight alpha and three beta subunit genes have been cloned. The alpha subunits contain the ligand binding sites, whereas beta subunits are structural subunits that contribute to the function of the receptor. A large number of nAChRs can be formed from different combinations of alpha and beta subunits. Different combinations of alpha and beta subunits can produce receptors in vitro with distinct ion conducting properties. Each subunit gene is expressed in a distinct pattern in the nervous system. The expression of at least some of the nAChR subunit genes is regulated during development and by cell-cell interactions. Each neuronal nAChR subtype has a distinct pharmacology. Both alpha and beta subunits contribute to the pharmacological properties of each subtype. The expression of multiple nAChR subtypes may allow for precise control of neurotransmission mediated by acetylcholine in diverse populations of neurons.


A wireless laser displacement sensor node for structural health monitoring.
This study describes a wireless laser displacement sensor node that measures displacement as a representative damage index for structural health monitoring (SHM). The proposed measurement system consists of a laser displacement sensor (LDS) and a customized wireless sensor node. Wireless communication is enabled by a sensor node that consists of a sensor module, a code division multiple access (CDMA) communication module, a processor, and a power module. An LDS with a long measurement distance is chosen to increase field applicability. For a wireless sensor node driven by a battery, we use a power control module with a low-power processor, which facilitates switching between the sleep and active modes, thus maximizing the power consumption efficiency during non-measurement and non-transfer periods. The CDMA mode is also used to overcome the limitation of communication distance, which is a challenge for wireless sensor networks and wireless communication. To evaluate the reliability and field applicability of the proposed wireless displacement measurement system, the system is tested onsite to obtain the required vertical displacement measurements during the construction of mega-trusses and an edge truss, which are the primary structural members in a large-scale irregular building currently under construction. The measurement values confirm the validity of the proposed wireless displacement measurement system and its potential for use in safety evaluations of structural elements.


Health-Related Quality of Life at Admission Is Associated with Postdischarge Mortality, Functional Decline, and Institutionalization in Acutely Hospitalized Older Medical Patients.
To assess the independent association between health-related quality of life (HRQOL) at admission and mortality, functional decline, and institutionalization 3 and 12 months after admission in acutely hospitalized older adults. Post hoc analysis of data from prospective cohort study, 2006 to 2009, 12-month follow-up. Eleven medical wards in three hospitals in the Netherlands. Medical patients aged 65 and older acutely hospitalized for 48 hours or longer (N = 473). mortality, functional decline, and institutionalization, 3 and 12 months after admission. Main determinant was HRQOL (utility based on the EuroQol-5D at admission, reflecting the relative desirability of a particular health state and is measured on a scale from 0 (death) to 1 (full health). Some health states are regarded as being worse than death, resulting in negative utilities, with a minimum of -0.330). Participants were split into two groups based on median utility at admission. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using Cox and logistic regression analyses, adjusted for sociodemographic and health variables. Median utility was 0.775 (interquartile range 0.399-0.861). Utility greater than 0.775, indicating high HRQOL, was associated with lower risk of mortality (hazard ratio = 0.38, 95% CI = 0.18-0.83) and functional decline (OR = 0.47, 95% CI = 0.28-0.79) at 3 months in the adjusted models. At 12 months, these associations were statistically significant in the crude models but not in the adjusted models. Utility was not associated with risk of institutionalization at 3 or 12 months. Higher HRQOL at admission was associated with lower risk of mortality and functional decline 3 months after admission. In older, acutely hospitalized individuals, the EQ-5D may provide a means of risk stratification and may ultimately guide individuals, their families, and professionals in treatment decisions during hospitalization.


Content and Activities of UGT2B7 in Human Liver In Vitro and Predicted In Vivo: A Bottom-Up Approach.
UDP-glucuronosyltransferase 2B7 (UGT2B7) is one of the most significant isoforms of UGTs in human liver. This research measured UGT2B7 protein content and activities, including maximum velocity (Vmax) and intrinsic clearance (CLint), in human liver at isoform, microsomal, liver tissue, and liver levels and identified the factors that influence expression. We determined absolute protein content by liquid chromatography-tandem mass spectroscopy and activities using the probe drug zidovudine in 82 normal human liver microsomes. Using a bottom-up method for derivation, we showed UGT2B7 content at the microsomal, liver tissue, and liver levels, as well as activities at the isoform, microsomal, liver tissue, and liver levels in vitro, and predicted hepatic clearance in vivo, with median, range, variation, and 95% and 50% prediction intervals. With regard to the intrinsic activities, the maximum velocity (Vmax) had a median (range) of 7.5 (2-24) pmol/min per picomole of 2B7, and the CLint was 0.08 (0.02-0.31) μl/min per picomole of 2B7. Determinations at liver level showed larger variations than at microsomal level, so it was more suitable for evaluating individual differences. By analyzing factors that affect UGT2B7, we found that: 1) The content at the liver tissue and liver levels correlated positively with activities; 2) the mutant heterozygotes of -327G>A, -900A>G, -161C>T may lead to decreased protein content and increased intrinsic CLint; and 3) the transcription factor pregnane X receptor mRNA expression level was positively associated with the measured protein content. In all, we showed that protein content and activities at different levels and the factors that influence content provide valuable information for UGT2B7 research and clinically individualized medication.


More closely related plants have more distinct mycorrhizal communities.
Neighbouring plants are known to vary from having similar to dissimilar arbuscular mycorrhizal fungal (AMF) communities. One possibility is that closely related plants have more similar AMF communities than more distantly related plants, an indication of phylogenetic host specificity. Here, we investigated the structure of AMF communities among dominant grassland plants at three sites in the Northern Great Plains to test whether the pairwise phylogenetic distance among plant species was correlated with pairwise AMF community dissimilarity. For eight dominant and co-occurring grassland plant species, we reconstructed a phylogeny based on DNA data and characterized the AMF communities of their roots at each site. Community analyses revealed that AMF communities varied among sites and among plant species. Contrary to expectations for phylogenetic host specificity, we found that within a site more closely related plants had more distinct AMF communities despite their having similar phenologies. Associations with unique AMF communities may enhance the functional complementarity of related species and promote their coexistence.


Alternation between taxonomically divergent hosts is not the major determinant of flavivirus evolution.
Flaviviruses display diverse epidemiological and ecological features. Tick-borne and mosquito-borne flaviviruses (TBFV and MBFV, respectively) are important human pathogens that alternate replication in invertebrate vectors and vertebrate hosts. The Flavivirus genus also includes insect-specific viruses (ISFVs) and viruses with unknown invertebrate hosts. It is generally accepted that viruses that alternate between taxonomically different hosts evolve slowly and that the evolution of MBFVs and TBFVs is dominated by strong constraints, with limited episodes of positive selection. We exploited the availability of flavivirus genomes to test these hypotheses and to compare their rates and patterns of evolution. We estimated the substitution rates of CFAV and CxFV (two ISFVs) and, by taking into account the time-frame of measurement, compared them with those of other flaviviruses. Results indicated that CFAV and CxFV display relatively different substitution rates. However, these data, together with estimates for single-host members of the Flaviviridae family, indicated that MBFVs do not display relatively slower evolution. Conversely, TBFVs displayed some of lowest substitution rates among flaviviruses. Analysis of selective patterns over longer evolutionary time-frames confirmed that MBFVs evolve under strong purifying selection. Interestingly, TBFVs and ISFVs did not show extremely different levels of constraint, although TBFVs alternate among hosts, whereas ISFVs do not. Additional results showed that episodic positive selection drove the evolution of MBFVs, despite their high constraint. Positive selection was also detected on two branches of the TBFVs phylogeny that define the seabird clade. Thus, positive selection was much more common during the evolution of arthropod-borne flaviviruses than previously thought. Overall, our data indicate that flavivirus evolutionary patterns are complex and most likely determined by multiple factors, not limited to the alternation between taxonomically divergent hosts. The frequency of both positive and purifying selection, especially in MBFVs, suggests that a minority of sites in the viral polyprotein experience weak constraint and can evolve to generate new viral phenotypes and possibly promote adaptation to new hosts.


If patients are now "customers," what does that make physicians?
As patients become "members" and "customers," as physicians become "practitioners" and "providers," the practice of medicine becomes more complex and more demanding. The changes that have affected the daily lives of physicians across America will continue and will likely become even more dramatic in the future. There is much to mourn in the passing of the medical practice of the recent past, but there is every reason to celebrate the ongoing triumphs of medicine and its successes in improving the human condition. The job of being a physician is not becoming any less important. The job has just gotten tougher. Successful physicians will cope with the multitude of changes in which the health care field is engaged and make themselves effective agents of change within their organizations.


Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase.
Parathyroid hormone (PTH) is secreted from the parathyroid glands in response to low plasma calcium levels. Besides its classical actions on bone and kidney, PTH may have other important effects, including metabolic effects, as suggested for instance by increased prevalence of insulin resistance and type 2 diabetes in patients with primary hyperparathyroidism. Moreover, secondary hyperparathyroidism may contribute to the metabolic derangements that characterize states of vitamin D deficiency. PTH has been shown to induce adipose tissue lipolysis, but the details of the lipolytic action of PTH have not been described. Here we used primary mouse adipocytes to show that intact PTH (1-84) as well as the N-terminal fragment (1-37) acutely stimulated lipolysis in a dose-dependent manner, whereas the C-terminal fragment (38-84) was without lipolytic effect. The lipolytic action of PTH was paralleled by phosphorylation of known protein kinase A (PKA) substrates, i.e. hormone-sensitive lipase (HSL) and perilipin. The phosphorylation of HSL in response to PTH occurred at the known PKA sites S563 and S660, but not at the non-PKA site S565. PTH-induced lipolysis, as well as phosphorylation of HSL at S563 and S660, was blocked by both the PKA-inhibitor H89 and the adenylate cyclase inhibitor MDL-12330A, whereas inhibitors of extracellular-regulated kinase (ERK), protein kinase B (PKB), AMP-activated protein kinase (AMPK) and Ca(2+)/calmodulin-dependent protein kinase (CaMK) had little or no effect. Inhibition of phosphodiesterase 4 (PDE4) strongly potentiated the lipolytic action of PTH, whereas inhibition of PDE3 had no effect. Our results show that the lipolytic action of PTH is mediated by the PKA signaling pathway with no or minor contribution of other signaling pathways and, furthermore, that the lipolytic action of PTH is limited by simultaneous activation of PDE4. Knowledge of the signaling pathways involved in the lipolytic action of PTH is important for our understanding of how metabolic derangements develop in states of hyperparathyroidism, including vitamin D deficiency.


[Ten-year surveillance of nosocomial surgical site infections in an orthopedic surgery department].
Surveillance of nosocomial surgical site infections was instituted in our department in June 1991. We report our first nine years experience. This study concerned the first 9 years (June 1991-June 2000) of a surveillance program designed to monitor nosocomial surgical site infections in our orthopedic surgery department. During this period 9,696 patients underwent surgery, including 2745 for hip replacements and 1016 for knee replacements. The diagnosis of infection was based on the Centers of Disease Control criteria. Beginning in 1997, the program was widened to include all indications for prophylactic antibiotics, being limited before that time to indications for arthroplasty and spinal surgery. The overall rate of infection was 1.25%; 0.55% for hip arthroplasty and 1.77% for knee arthroplasty. The rate of infection among hip surgery patients over the last 5 years was much higher for prosthesis revision (2.37%) than for first-intention implantations (0.16%). The majority of the isolated strains were Gram-positive (84%) including Staphylococcus sp. found in 65% of the cases. Multiple-strains were found in 23% of the infections. The rate of infection improved very significantly over the last five years both for knee arthroplasty and spinal surgery. The rate remained unchanged for hip arthroplasty. This 10-year survey enabled us to analyze the difficulties encountered and pinpoint errors or insufficiencies in data recording. We were also able to identify measures to be taken concerning patient follow-up. The improvement in the rate of infection over time appears to be multifactorial, undoubtedly related to wider use of prophylactic antibiotics, progress in hygiene and sterilization methods with institution of a quality assurance program, and team awareness. Surveillance of nosocomial infections is a recommended practice. We have found that the information provided can be beneficial if the data is statistically sound, pointing out the need for progress in patient follow-up.


Health personnel retention strategies in a peri-urban community: an exploratory study on Epworth, Zimbabwe.
The need to retain health personnel is a policy challenge undermining health system reform of the 21st century. The need to resolve this global health workforce crisis resulted in the First Global Forum on Human Resources for Health in 2008 from which the Kampala Declaration and Agenda for Global Action was formulated. However, whilst there have been several studies exploring the retention of health personnel towards this end, available literature does not provide a detailed narrative on strategies used in peri-urban communities. The aim of this study was to explore retention strategies implemented in a Zimbabwean peri-urban community between 2009 and 2014 and implications for peri-urban communities towards the health system reform agenda. The study was carried out in Epworth, a peri-urban community in Harare, Zimbabwe. The research design was a cross-sectional survey, in which qualitative methods were used in sampling, data collection, reporting and analysis. Qualitative tools were used to collect data through in-depth interviews with purposively selected health personnel managers at 10 local clinics and sample interviews with purposively selected healthcare workers who included registered general nurses, state-certified nurses, midwives, environmental health technicians, nurse aids and community health volunteers at each clinic. Two focus group discussions were carried out with community health volunteers. Qualitative data was subjected to thematic analysis, with coding being performed manually. A programme-specific strategic partnership between the government and donor community contributed towards the mobilisation of more health personnel, health facilities, worker development and remuneration. To complement this, the Ministry of Health intervened through the review and payment of salaries, support towards post-basic training and development, and protection. The local board, mission and donors contributed through the payment of top-up allowances and provision of non-monetary incentives. The review of salaries, engagement of international strategic partners, payment of top-up allowances, support towards post-basic training and development, mobilisation of more health personnel, non-monetary incentives and healthcare worker protection were critical towards the retention of health personnel in the Epworth peri-urban community between 2009 and 2014.


Serological diagnosis and prevalence of HIV-1 infection in Russian metropolitan areas.
HIV infection is a major health problem in Russia. We aimed to assess HIV prevalence in different population groups and to compare the characteristics of 4th generation immunoassays from Abbott, Bio-Rad, Vector-Best, Diagnostic Systems, and Medical Biological Unit. The study included 4452 individuals from the general population (GP), 391 subjects at high risk of HIV infection (HR) and 699 with potentially interfering conditions. HIV positivity was confirmed by immunoblot and by HIV RNA, seroconversion and virus diversity panels were also used. HIV avidity was employed to assess recent infections. The prevalence in GP was 0.40%, higher in males (0.62%) and in people aged < 40 years (0.58%). Patients attending dermo-venereal centers and drug users had a high prevalence (34.1 and 58.8%). Recent infections were diagnosed in 20% of GP and in 4.2% of HR. Assay sensitivity was 100% except for one false negative (99,54%, MBU). Specificity was 99.58-99.89% overall, but as low as 93.26% on HR (Vector-Best). Small differences on early seroconversion were recorded. Only the Abbott assay detected all samples on the viral diversity panel. HIV infection rate in the high-risk groups suggests that awareness and screening campaigns should be enhanced. Fourth generation assays are adequate but performance differences must be considered.


Analysis of the needs for help of men who have sex with men and live with HIV.
To understand the needs for help of men who have sex with men and live with HIV in the light of a Prescriptive Theory. Descriptive and qualitative study, conducted with men who have sex with men and live with HIV who were treated in a Specialized Outpatient Service in a capital in Northeastearn Brazil, between the months of November 2017 and May 2018. The study used the analysis of the discourse of the collective subject. 49 men with HIV who self-identified as men who have sex with men participated in the study. Help was described as support, welcoming, psychosocial and family support. The desire to receive assistance was related to accepting and forgetting the diagnosis. The problems experienced were related to the acceptance of the diagnosis, fear and prejudice. Professionals and family members stood out as sources of support. Nursing care was cited as significant and the main help required was psychological. The needs for help identified were mainly related to psychological support coming from health professionals and family members. Participants were willing to receive help, especially to cope with the diagnosis.


[Biologically active substances of plant origin. Flavonols and flavones: prevalence, dietary sourses and consumption].
Flavonoids are the most numerous group of natural polyphenolic compounds, the secondary metabolites of plants that may play an important role in human health protection. Flavonols and flavones constitute the main two classes of flavonoids, whose antioxidant properties and high biological activity have been proofed both in vitro and in vivo. This review summarizes data, concerning the structure, occurrence and content of the main flavonols (quercetin, kaempherol, myricetin, isorhamnetin) and flavones (apigenin, luteolin) in some most widely consumed foodstuffs, including vegetables, fruits, berries, nuts, beverages and other products of plant origin. The products with high content of these biologically active food compounds--the major dietary sources of them--are noted. Forms of flavonols and flavones more often distributed among edible plants are characterized and some of their known glycosides occurred in foods are enumerated. Some peculiarities, characteristic to flavonol sand flavones glycosilation (O- and/or C-glycosides formation) are described. The data for flavonol and flavone glycosides composition (profiles) of some commonly consumed commodities rich by these flavonoids (onions, cabbage, apples at al.) are shown. Information about levels of daily dietary intake of total and individual flavonols and flavones in several countries is presented. The questions about dietary habits and lifestyle factors and the contribution of certain foods to flavonols and flavones in daily dietary consumption values are also discussed.


Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1) by extracts and polyphenols from apple reduces postprandial blood glucose levels in mice and humans.
There is a growing interest in food constituents that could reduce intestinal glucose absorption to prevent overshooting plasma glucose and insulin levels in patients with prediabetes and diabetes mellitus type 2. We here demonstrate that an extract and individual polyphenols from apple diminish sodium-coupled glucose transporter 1 (SGLT1) mediated glucose uptake in vitro and in vivo. Inhibition of transport of sugars by SGLT1 was shown in Xenopus oocytes and in mice jejunal segments. Strongest inhibition was observed for phlorizin with IC50 values for transport inhibition of 0.46 ± 0.19 and 4.1 ± 0.6 μM in oocytes and intestinal segments, respectively. An oral glucose tolerance test performed in volunteers with prior administration of the apple extract reduced venous blood glucose and plasma insulin levels, similar to findings obtained in C57BL/6N mice. Analysis of human urine samples revealed that the extract increased modestly renal glucose loss that is most likely a result of inhibition of renal glucose reabsorption by phloretin derivatives found in plasma of the volunteers. Although the apple extract substantially decreased intestinal glucose absorption in all test systems, the finding that there are systemic effects that relate to inhibition of glucose transport processes beyond the intestine addresses safety issues that need further exploitation.


Speed of information processing in traumatic brain injury: modality-specific factors.
To assess speed of information processing by two serial addition tests (one visual, one auditory) in individuals with moderate-to-severe traumatic brain injuries (TBIs) and in a healthy, normal control group (NC). The tasks were designed to equate and control for accuracy of performance across the TBI and NC groups, thus allowing for quantification of information processing speed. Performance across groups and tasks were compared using 2 x 2 repeated measure analyses of variance (ANOVAs). In addition, each individual's processing speed was used to adjust rate of stimulus presentation on a subsequent "rehabilitation" trial to determine further whether this adjustment equated accuracy of performance. Rehabilitation hospital. 22 outpatients with moderate-to-severe TBI (6 women, 16 men; mean age = 34.6 years; duration of loss of consciousness = 22.6 days) and 20 age- and education-matched healthy controls. Processing speed was slower in TBI subjects, relative to controls and was significantly related to measures of executive functioning for those with TBI. Relative to controls, speed of processing in the TBI group was disproportionately slower when information was presented in the auditory, relative to the visual, modality. Speed of information processing is a major impairment in those with TBI when unconfounded by performance accuracy. The modality-specific impairment observed in the TBI group may, in part, be due to a greater within-modality interference effect created by the auditory version of the task. By manipulating information at a pace customized for an individual through compensatory strategies and environmental modifications, information-processing performance of TBI participants can be enhanced significantly.


The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study.
This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6%) were significantly more likely to have SDB compared to women (5.6%), while women (42.4%) were significantly more likely to report DIMS than men (32.5%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.


A chromatographic technique to investigate the lability of copper complexes under steady-state conditions using high specific activity 64Cu
A novel chromatographic technique is described which has prospects for studying the lability of a metal complex in an aqueous system. It is based on interactions of metal species with an ion-exchange column under steady-state conditions. For this purpose, the column is equilibrated with the sample itself by using it as the mobile phase. With the aid of a high specific activity radiotracer, the characteristics of the metal species interaction with the ion-exchange column can be visualized in a radiochromatogram. Under particular experimental conditions, information regarding the dissociation kinetics of the metal complex can be extracted from this radiochromatogram. Erroneous results due to undesirable interactions of metal species with the chromatographic system are prevented, since the system remains in constant chemical equilibrium with the sample to be analyzed. The potential of this technique was investigated with copper complexes, using high specific activity 64Cu for labeling. Preliminary results obtained with four complexes (Cu-EDTA, Cu-NTA, Cu-citrate, and Cu-glycine) are discussed. For three complexes, dissociation rate constants could be determined: (6.2 +/- 0.3) x 10(-3) s(-1) for Cu-EDTA, (1.0 +/- 0.04) x 10(-2) s(-1) for Cu-NTA, and (3.1 +/- 0.2) x 10(-2) s(-1) for Cu-citrate. No dissociation rate constant could be determined for Cu-glycine owing to incompatible experimental conditions.


Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry.
About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and DA) are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both NA and DA contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection.


Optical transmission at oblique incidence through a periodic array of sub-wavelength slits in a metallic host.
Using the Bloch modes of a periodic, semi-infinite array of slits in a metallic host, we study the transmission of obliquely incident plane-waves through sub-wavelength slits. Matching the tangential E- and H-fields at the entrance facet of the periodic structure yields the complex amplitudes of the various Bloch modes, which exist and propagate within the slit array independently of each other. The computational scheme is robust, convergence is rapid, and a good match at the boundaries is obtained in every case. The regions examined in some detail include the vicinity of the Wood anomaly (where new diffraction orders appear/disappear on the horizon), the neighborhood of a point where surface plasmon polaritons (SPPs) are excited, and an ordinary situation in which the incidence angle is far from the angles that invoke Wood's anomaly or cause the excitation of SPPs. Field distributions and energy flow diagrams in and around the slits reveal the existence of transmission minima (and reflection maxima) at incidence angles associated with the excitation of SPPs.


Echocardiography Screening for Latent Rheumatic Heart Disease: What Can We Do in Indonesia?
Rheumatic heart disease (RHD), a sequela of acute rheumatic fever (ARF), is a preventable disease but remains a significant health problem, especially in developing countries. It causes disability, poor quality of life, early mortality, and national economic burden. The World Heart Federation (WHF) aimed to achieve a 25% reduction in premature deaths from ARF and RHD among individuals aged <25 years by 2025. Primordial and primary prophylaxis of RHD is aimed to prevent the occurrence of ARF, while the goal of secondary and tertiary prophylaxis is to limit the progression and reduce the consequences of RHD. Early recognition of RHD is important for early prophylaxis strategies to inhibit any progression to advanced stages. In 2012, WHF introduced the latest echocardiographic criteria to recognize the early stage of RHD. This includes the evaluation of pathological regurgitation jet and morphological features of RHD based on 2D, color, and spectral Doppler criteria. In remote areas, portable echocardiography is preferable for RHD screening. Previous portable devices were only capable of producing 2D and color images. Hence, a simplified echocardiographic criterion without spectral Doppler evaluation is needed in selected areas. Indonesia is a developing country, an archipelago with a population of over 250 million. Currently, there are no data on ARF incidence and RHD prevalence nationwide. The only data available are the number of patients in advanced stages who came to referral centers for further management. The screening program has to be introduced in Indonesia as part of national RHD prophylaxis.


ORFB is a subunit of F1F(O)-ATP synthase: insight into the basis of cytoplasmic male sterility in sunflower.
ORFB is the product of a gene that is conserved in plant mitochondrial genomes, and which, on the basis of sequence motif and structural similarity, is predicted to be the homologue of yeast and mammalian ATP8, part of the F(O) component of the F1F(O)-ATP synthase. We have shown that, in sunflower, orfB transcripts are edited, increasing the similarity of the predicted protein to ATP8 proteins from non-plant species. Blue-native polyacrylamide gel electrophoresis and peptide sequencing confirm that ORFB localizes to the ATP synthase complex. The predicted amino-terminal 19 amino acids of ORFB are identical to those in the chimeric mitochondrial ORF522 protein, which is associated with cytoplasmic male sterility (CMS) in sunflower. Assays comparing respiratory complexes from a male-sterile line expressing ORF522 with those from a male-fertile line show a specific decrease in ATP hydrolysis by the ATP synthase. These observations allow us to propose a mechanism underlying CMS that is associated with the expression of chimeric open reading frames containing part of the orfB gene.