Mild to moderate sleep respiratory events: one negative night may not be enough.
Reports on the reproducibility of apnea-hypopnea indexes (AHIs) across sequential polysomnography (PSG) sessions are conflicting, leading to a lack of clear recommendations on the optimal use of this technique: is one night of monitoring sufficient or is a second night required in order to safely reject the diagnosis? Retrospective comparison of two consecutive nights. Sleep unit of a tertiary-care facility. Two hundred forty-three subjects with suspected sleep apneas. Two sequential PSG sessions in a sleep unit. Using analysis of covariance for repeated measures, with age and body mass index as covariates and gender as a cofactor, a classic first-night effect was found for sleep variables. In addition, a night effect was demonstrated for sleep respiratory variables. Moreover, the high variability of AHIs showed that many patients had their condition diagnosed on only one of the two nights, and more often on the second night than on the first. The gain in detection by adding a second night when the results of testing on the first were negative was between 15% and 25%, according to the AHI obtained on night 1. Considering the disability associated with sleep apnea/hypopnea syndrome, as well as its global cost for society, the present study shows that it is worth performing two consecutive PSG sessions or at least a second one when the result of the first one is negative in all patients admitted for apnea detection.


Predictability of FEV1 after pulmonary resection for bronchogenic carcinoma.
The aim of this study was to review the reliability of prediction of postoperative FEV1 in patients with bronchogenic carcinoma using a Tc-99m perfusion scan and simple spirometry. Over a 27-month period, 40 patients without known recurrent disease had their FEV1 measured. One quarter of the postoperative values for FEV1 differed from predicted values by less than 5% (2/11 pneumonectomies, 5/23 lobectomies, 3/6 segmental resections) and half differed by no more than 10% of predicted FEV1 (4/11 pneumonectomies, 12/23 lobectomies, 3/6 segmentectomies). One tenth of the predicted values differed by more than 30% and up to 760 mls (1/11 pneumonectomies, 2/23 lobectomies, 1/6 segmentectomy). Disease recurrence, phrenic nerve paralysis, exacerbation of obstructive pulmonary disease and poor collaboration during spirometry explained the most severe erroneous results. Age, preoperative smoking, tumour stage and histology, absence of symptoms at the time of diagnosis and adjuvant radiotherapy showed no statistically significant effect on predictability. Twenty-one patients had a postoperative Tc-99m pulmonary scan simultaneous to the spirometric control. Overestimation of postoperative FEV1 was associated with heterogeneous distribution of ventilation and perfusion.


Serial measurements of bone density at the lumbar spine do not predict fracture risk after liver transplantation.
Bone disease has emerged as a serious and complex complication after liver transplantation. The purpose of this study is to determine risk factors for fracture and bone loss after liver transplantation. Dual-energy x-ray absorptiometry (DEXA) of the lumbar spine was performed routinely pretransplantation, 6 months posttransplantation, and at yearly intervals thereafter at our center. We followed up patients who underwent transplantation in the past 10 years and compared bone mineral density (BMD) and fracture rate with known risk factors for bone loss in primary transplant recipients who met the inclusion criteria of a pretransplantation DEXA and at least one follow-up DEXA scan postoperatively (n = 153). We observed a 15% (n = 23) prevalence of symptomatic fractures at a mean of 2.2 +/- 1.8 years after transplantation. Change in BMD was greatest from pretransplantation to 6 months posttransplantation (-4.2%; P =.006), then increased at a rate of 1.4% per year. Logistic regression analysis showed an association of fracture risk with several factors, including number of acute rejection episodes (P =.045), smoking (P =.02), and female sex (P =.02). Stepwise logistic regression analysis reported female sex (P =.004) as the only factor associated with fracture after transplantation. Age, time listed for transplantation, race, menopause, chronic renal insufficiency, loss of height, family history of osteoporosis, BMD, and T score did not predict fracture or bone loss after transplantation. In conclusion, serial measurements of BMD at the lumbar spine do not appear to predict fracture risk; however, data suggest that female sex is the strongest predictor of fracture after liver transplantation.


Traumatic rupture of a descending thoracic aortic homograft.
My colleagues and I report an unusual case of traumatic aortic injury in an 18-year-old woman who had undergone multiple prior surgical procedures for repair of a type B interrupted aortic arch. Her most recent procedure included replacement of the proximal descending thoracic aorta with a 19-mm homograft at age 11 years. Seven years later, she was involved in a motor vehicle collision after a syncopal episode. Imaging studies revealed rupture of the body of the aortic homograft with formation of a pseudoaneurysm. The injury was successfully repaired with a Dacron graft by using hypothermic circulatory arrest.


Apparent foveofugal drift of counterphase gratings.
Counterphase gratings, and several other stimuli which consist of equal components of motion in both directions, appeared to drift foveofugally, rather than foveopetally, when presented to the retinal periphery. This 'foveofugal drift effect' was demonstrated by descriptive and nulling techniques and its magnitude was shown to vary across subjects. The effect was fairly brief under continuous fixation. Several lines of evidence suggested that eye movements were not responsible for the effect. The phenomenon implies a directional asymmetry in the human visual system which may be related to our consistent exposure to expanding patterns of visual flow.


Toxicity and inhibition assessment of ionic liquids by activated sludge.
Toxicity of 13 ionic liquids (ILs) corresponding to different families were studied by inhibition respiration assays (15 min) using activated sludge. Toxicity increased as increasing the number of carbons in the alkyl-chain of imidazolium-based ILs, with EC50 values from 4.19 to 0.17 for 1-ethyl-3-methylimidazolium chloride ([Emim][Cl]) and 1-octyl-3-methylimidazolium chloride ([Omim][Cl]), respectively. An increase in toxicity was observed for aromatic-based ILs (pyridinium- and imidazolium-based ILs) due to the hydrophobic character of the head groups in comparison with linear structures as phosphonium and ammonium cations. Among to the anions studied fixing [Emim]+ as cation, [HSO4]- and [NTf2]- presented low EC50 values (0.34 mM and 1.69 mM, respectively) while [Cl]- and [EtSO4]- were considered harmless anions due to the hydrophilic character of chloride and the organic nature of [EtSO4]-. ILs toxicity/inhibition was determined by adding a biodegradable compound and measuring the sludge response after being in contact with the ILs for at least 15 h. The exposure of sewage sludge to ILs for more than 15 min used in short inhibition assays caused more toxic effect on microorganisms, even for [Choline][NTf2], previously defined as practically harmless (EC50 = 2.79 mM). Biodegradability assays confirmed the biodegradable nature of choline cation, related with TOC conversion of 40%, only due to cation consumption. No oxygen consumption or even lysis of microbial cells was observed for Tetrabutylammonium bis(trifluoromethylsulfonyl)imide and for 1-Ethyl-3-methylimidazolium hydrogensulphate due to the presence of anions previously defined as hazardous ([NTf2]- and [HSO4]-), maintaining their recalcitrant character to sewage systems.


Further studies on rabies postexposure prophylaxis in mice: a comparison of vaccine with interferon and vaccine.
Mice were inoculated in the left hind footpad with street rabies virus, and 24 h later various types of rabies vaccine were administered intramuscularly in the right leg. The vaccines alone were ineffective in reducing mortality, but when an interferon inducer, polyriboinosinic acid-polyribocytidylic acid complexed to poly-L-lysine (polyICLC), was given along with the vaccines, a marked reduction resulted. The polyICLC-vaccine combination was effective even when it was injected 5 days after infection, suggesting that effective postexposure treatment in man might be successful when given at a comparable late time.


Pulse rate and blood pressure changes during low-irradiance PDT compared with conventional PDT in the treatment of facial actinic keratoses: A retrospective study.
Conventional photodynamic therapy (c-PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low-irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li-PDT on the BP and pulse (PR) during therapy and the incidence of post-interventional hypertension compared with c-PDT. We retrospectively analyzed the treatment data of 79 patients (39 c-PDT and 40 li-PDT). BP and PR measurements were performed in all patients before PDT, at mid-exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale. Patients treated with li-PDT reported significantly lower pain than those receiving c-PDT (p < .0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p < .0005, ∆DBP: p = .015) and overall lower absolute BP values (SBP: p < .0005, DBP: p = .008) compared with c-PDT. They were also significantly less likely to develop post-interventional hypertension (p = .037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c-PDT (p = .013). Li-PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post-interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history).


Influences of culture temperature on the growth, lipid content and fatty acid composition of Aurantiochytrium sp. Strain mh0186.
The growth, lipid content, and fatty acid composition of Aurantiochytrium sp. strain mh0186 at different temperatures were investigated. Strain mh0186 grew well at 15-30 degrees C, but weakly at 10 degrees C. The biomass at 15-30 degrees C was significantly higher than at 10 and 35 degrees C, and the total lipid at 15-35 degrees C was significantly higher than that at 10 degrees C. The amount of DHA in the total fatty acid was highest at 10 degrees C and decreased in response to temperature increase. The content of DHA (mg/g-dry cell weight) at 15-30 degrees C were significantly higher than those at 35 degrees C and those at 15-25 degrees C were significantly higher than those at 10 and 35 degrees C. The DHA yield at 15-35 degrees C was significantly higher than those at 10 and 35 degrees C. Unsaturation of fatty acid was regulated by temperature and was enhanced in response to temperature decrease. The ratio of DHA to DPA varied at different temperatures.


Incorporating patterns of disperser behaviour into models of seed dispersal and its effects on estimated dispersal curves.
The processes determining where seeds fall relative to their parent plant influence the spatial structure and dynamics of plant populations and communities. For animal dispersed species the factors influencing seed shadows are poorly understood. In this paper we test the hypothesis that the daily temporal distribution of disperser behaviours, for example, foraging and movement, influences dispersal outcomes, in particular the shape and scale of dispersal curves. To do this, we describe frugivory and the dispersal curves produced by the southern cassowary, Casuarius casuarius, the only large-bodied disperser in Australia's rainforests. We found C. casuarius consumed fruits of 238 species and of all fleshy-fruit types. In feeding trials, seeds of 11 species were retained on average for 309 min (+/-256 SD). Sampling radio-telemetry data randomly, that is, assuming foraging occurs at random times during the day, gives an estimated average dispersal distance of 239 m (+/-207 SD) for seeds consumed by C. casuarius. Approximately 4% of seeds were dispersed further than 1,000 m. However, observation of wild birds indicated that foraging and movement occur more frequently early and late in the day. Seeds consumed early in the day were estimated to receive dispersal distances 1.4 times the 'random' average estimate, while afternoon consumed seeds received estimated mean dispersal distances of 0.46 times the 'random' estimate. Sampling movement data according to the daily distribution of C. casuarius foraging gives an estimated mean dispersal distance of 337 m (+/-194 SD). Most animals' behaviour has a non-random temporal distribution. Consequently such effects should be common and need to be incorporated into seed shadow estimation. Our results point to dispersal curves being an emergent property of the plant-disperser interaction rather than being a property of a plant or species.


Tolerability of prophylactic aerosolized liposomal amphotericin-B and impact on pulmonary function: data from a randomized placebo-controlled trial.
Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability. Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in a placebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks. Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1s (FEV(1)) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmB patients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmB patients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared. Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects.


Haptoglobin polymorphism and the immune response after hepatitis B vaccination.
One hundred healthy Caucasian medical students (age 22 +/- 1 years) were vaccinated with a recombinant hepatitis B vaccine and their haptoglobin types were determined. A relationship between haptoglobin type and immune response to the vaccine was observed. Subjects with a 2-2 haptoglobin phenotype produced significantly lower hepatitis B antibody titres than those having a 1-1 or 2-1 haptoglobin phenotype. The haptoglobin phenotypes not only influenced the magnitude but also the kinetics of the anti-HBs response. For all haptoglobin types, haptoglobin concentration and immune response to the vaccine behaved independently.


Acetate ester formation in wine by mixed cultures in laboratory fermentations.
Two non-Saccharomyces wine yeast strains, Hanseniaspora guilliermondii 11104 and Pichia anomala 10590, selected as good producers of acetate esters when grown on synthetic microbiological medium, have been tested in wine fermentations as mixed cultures together with Saccharomyces cerevisiae. Wines produced using mixed cultures showed levels of acetaldehyde, acetic acid, glycerol and total higher alcohols within the ranges described for wine, whereas an increase in acetate ester concentrations was found. Ethyl acetate was the main ester produced, and isoamyl acetate and 2-phenylethyl acetate made up the next largest group of ester compounds in the wines analysed. H. guilliermondii 11104 was found to be a strong producer of 2-phenylethyl acetate in both pure and mixed cultures whereas S. cerevisiae was the best producer of ethyl esters. Mixed cultures did not influence ethyl ester levels at all.


Relationship between HLA-DP gene polymorphisms and clearance of chronic hepatitis B virus infections: case-control study and meta-analysis.
Hepatitis B virus (HBV) infection is a serious public health problem worldwide. Two common genetic variants (rs3077 and rs9277535) of human leukocyte antigen DP (HLA-DP) have been reported to be associated with persistent HBV infection in populations of Japan and Thailand. To confirm whether the association can be replicated in Chinese populations, an independent case-control study were conducted, and two polymorphisms (rs3077 and rs9277535) were genotyped using the TaqMan SNP genotyping assay in 282 persistent chronic HBV carriers and 64 spontaneously HBV recovered carriers. To provide a more definitive conclusion, a meta-analysis combining and summarizing five studies was performed by random-effects model using the DerSimonian and Laird's method. By using logistic regression analysis with adjustment for covariates, including age, sex, and alcohol consumption, the results of our independent case-control study showed that the minor allele's homozygote (AA genotype) of rs3077 and rs9277535 was significantly associated with decreasing risk/protection of HBV persistent chronic infection (for rs3077: P=0.0017, OR=0.29, 95% CI=0.13-0.62; for rs9277535, P=0.0004, OR=0.26, 95% CI=0.12-0.54). The results of meta-analysis pooling all eligible studies also showed that rs3077-A and rs9277535-A alleles were associated with an increased clearance rate to HBV infection (rs3077: OR=0.57, 95% CI=0.44-0.75; rs9277535: OR=0.56, 95% CI=0.47-0.63). These results further confirmed the strong influence of HLA-DP gene variants on risk of spontaneous HBV clearance from persistent HBV infection. Both A alleles of HLA-DP SNP rs3077 and rs9277535 showed strong protective effects for spontaneous HBV clearance from persistent HBV infection in the Han Chinese population.


Mechanobiology of the Mitotic Spindle.
The mitotic spindle is a microtubule-based assembly that separates the chromosomes during cell division. As the spindle is basically a mechanical micro machine, the understanding of its functioning is constantly motivating the development of experimental approaches based on mechanical perturbations, which are complementary to and work together with the classical genetics and biochemistry methods. Recent data emerging from these approaches in combination with theoretical modeling led to novel ideas and significant revisions of the basic concepts in the field. In this Perspective, we discuss the advances in the understanding of spindle mechanics, focusing on microtubule forces that control chromosome movements.


Water Poverty Index: a Tool for Water Resources Management in Jordan.
In terms of water resources, Jordan is considered one of the poorest countries in the world. Water resources management is one of the available options to decrease the gap between demand and resources. Water resources management requires optimum use of the available water resources taking into consideration resources availability, resources reliability, water use pattern, in addition to the socioeconomic issues. One of the most important aspects is human behaviour which has a strong impact on water management and on the ecosystem. Therefore, there is a need to follow a sustainable approach to improve the management and the understanding of the difficulties of water issues by integrating the physical, social, economic, and environmental aspects, as well as linking water issues to poverty indicator. In this paper, Water Poverty Index (WPI) will be used as a tool for water resources management. WPI was calculated based on five parameters: resources, access to water, capacity, use, and the environment. The Jordanian water strategy targets will be used to forecast the water situation in 2025 and calculate WPI. In 2002, the WPI was calculated and found at 46.3%, in comparison with higher figures for other countries. WPI was calculated for the year 2018, and the results showed a value of 50.7%. If the national water strategy targets and improvements will be successfully implemented, by 2025, the value is expected to be increased to 56.38%. Water resources are the most sensitive component of WPI. COVID-19 increased the rate of unemployment and poverty ratio which will affect WPI negatively. It's concluded that WPI could be used as a valuable indicator to help evaluate the running plans and monitor the management performance.


Public support for smoke-free laws in rural communities.
There has been an upward trend in smoke-free laws in countries, states, and municipalities in recent years. However, these laws are more likely to be enacted in urban areas. The purpose of this study was to examine public opinion of smoke-free laws and to determine if there was a difference in support for these laws between urban and rural dwellers. A series of random-digit-dialed phone surveys was conducted in 2005-2006 with 3672 adult Kentucky residents living in rural and urban communities without smoke-free laws. In addition to demographics, respondents were asked whether they would support a local law prohibiting smoking in public places. Responses were weighted to adjust for an over-representation of women in the sample relative to the population. Logistic regression was used to test for a rural/urban difference in support; data analysis was conducted in 2007. Respondents were primarily women, Caucasian, with at most a high school education, and nonsmokers; the average age was 49.3 years. About half lived in rural communities. More than half (59.6%) supported a local smoke-free law. Controlling for age, gender, ethnicity, education, and smoking status, there was a significant difference in the level of support for a smoke-free law between rural and urban respondents. Compared to urban dwellers, rural residents were more likely to support these laws (OR=1.21; 95% CI=1.03, 1.42). When controlling for demographic differences between groups, rural residents were more likely than those in urban settings to support a law for local smoke-free public places.


Effects of Palonosetron, a 5-HT3 Receptor Antagonist, on Mechanical Allodynia in a Rat Model of Postoperative Pain.
5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 µg intrathecally; 0.5 µg intraplantarly) was administered and the thresholds were observed for 4 hours. Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 µg and 0.1 µg) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 µg) also did not change the paw withdrawal threshold. Intrathecal and intraplantar palonosetron (0.5 µg) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.


Lung ultrasound in outpatient approach to children with suspected COVID 19.
Children with COVID 19 infection (CV19) generally have a mild disease whose main symptoms are fever and cough. Dyspnoea and hypoxemia are rarely reported and few data are available on the frequency and extent of lung involvement in children with CV19. In addition, due to the limited availability of diagnostic tests in Italy during the pandemic period and the relative reliability of the test results, the diagnostic suspicion of CV19 infection in most of the children was difficult to confirm. The aim of this study is to evaluate if lung ultrasound (LUS) was able to highlight typical interstitial lung lesions in children with persistent cough and suspected CV19, providing corroborating evidence of CV19 infection. We retrospectively analysed the data of 32 children who came consecutively to our outpatient observation in the period between March 1st and April 30th, 2020 because of the presence of persistent cough for at least 3 days and with suspected CV19. All the children undergone clinical examination, oximetry measurement and LUS. Twenty over thirty-two children had US lesions compatible with the presence of CV19, many of them without clinical signs of respiratory distress. LUS is much more sensitive than clinical examination to detect lung injury in children with suspected CV19. In the absence of reliable, highly sensitive diagnostic tests or when nasal swab is unworkable or there are too many requests to be performed quickly due to the pandemic, LUS should be used in children with persistent cough for whom a CV19 is suspected because it can highlight undiagnosed interstitial lung lesions and reinforce the diagnostic suspicion of CV19 This approach can be very useful in outpatient settings and in areas with limited medical resources such as developing countries.


The isolation and fluorometric determination of 3-methoxytyramine in urine and in tissues.
A fluorometric methods is described for determination of cardiac and urinary 3-methoxytyramine, a metabolite of dopamine. Methoxy metabolites were isolated on Amberlite CG-50 resin and oxidation to emitter form was performed with K3Fe(CN)6. Good specificity and sensitivity of determination, and a high recovery of 3-MT were obtained.


Clinicopathologic studies in childhood pancreatitis.
In a review of pediatric autopsies from 1951 to 1985, we identified 40 cases in which pancreatitis was diagnosed pathologically. Twenty-six of these patients were under 4 years of age, and the male-to-female ratio was 1.5. Six groups of patients were identified: 10 with hepatobiliary disease, including 9 with biliary atresia; 7 with immunosuppressive therapy for tumors (n = 2), leukemia (n = 4) and aplastic anemia (n = 1); 6 with viral infections; 8 with congenital anomalies, including congenital heart disease (n = 3); and 9 with miscellaneous problems. Several patients had surgery and various intercurrent complications. Clinical features attributable to the pancreatitis included vomiting or excessive nasogastric drainage (60%), pleural effusions (40%), and abdominal pain (25%). However, the diagnosis was suspected clinically in only 5 of 40 patients. Our findings suggest several pathogenic mechanisms exist for childhood pancreatitis: biliary obstruction, infections, drug toxicity, immunosuppression (acting in synergy with drug toxicity, trauma, and low-flow states resulting from shock, heart failure, and vasculopathy.


Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes.
Nitric oxide (NO) can directly modulate cardiac contractility by accelerating relaxation and reducing diastolic tone. The intracellular mechanisms underlying these contractile effects are poorly understood. Here we investigate the role of cyclic GMP-dependent protein kinase (PKG) in the contractile response to exogenous NO in rat ventricular myocytes. Isolated ventricular myocytes were stimulated electrically and contractility was assessed by measuring cell shortening. Some cells were loaded with the fluorescent Ca(2+) probe indo-1 AM for simultaneous assessment of the intracellular Ca(2+) transient. The NO donor diethylamine NONOate (DEA/NO, 10 microM) significantly increased resting cell length, reduced twitch amplitude and accelerated time to 50 % relaxation (to 100.8 +/- 0.2, 83.7 +/- 3.0 and 88.9 +/- 3.7 % of control values, respectively). The contractile effects of DEA/NO occurred without significant changes in the amplitude or kinetics of the intracellular Ca(2+) transient, suggesting that the myofilament response to Ca(2+) was reduced. These effects were abolished by inhibition of either guanylyl cyclase (with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ, 10 microM) or PKG (with Rp-8-Br-cGMPs, 10 microM) suggesting that, at the concentration investigated, the effects of DEA/NO were mediated exclusively by PKG, following activation of guanylyl cyclase and elevation of cGMP. Direct activation of PKG with 8-pCPT-cGMP (10 microM) mimicked the effects of DEA/NO (resting cell length and time to 50 % relaxation were 100.6 +/- 0.1 and 90.5 +/- 1.5 % of control values, respectively).The reduced myofilament Ca(2+) responsiveness was not attributable to an intracellular acidosis since the small reduction in pH(i) induced by DEA/NO was found to be uncoupled from its contractile effects. However, hearts treated with DEA/NO (10 microM) showed a significant increase (1.4-fold; P < 0.01) in troponin I phosphorylation compared to control, untreated hearts. These results suggest that the reduction in myofilament Ca(2+) responsiveness produced by DEA/NO results from phosphorylation of troponin I by PKG.


New members of the Escherichia coli sigmaE regulon identified by a two-plasmid system.
A previously established method, based on a two-plasmid system, was used to identify promoters recognized by RNA polymerase containing the extracytoplasmic stress response sigma factor sigmaE in Escherichia coli. In addition to previously identified rpoE-dependent promoters, 11 new promoters potentially directing the expression of 15 genes were identified that were active only after over-expression of rpoE. The promoters were confirmed and transcriptional start points of the promoters were determined by primer extension analysis and S1-nuclease mapping. All the promoters contained sequences similar to the consensus sequence of rpoE-dependent promoters. The new rpoE-dependent promoters governed expression of genes encoding proteins involved in primary metabolism (fusA, tufA, recR), phospholipid and lipopolysaccharide biosynthesis (psd, lpxP), signal transduction (sixA), proposed inner or outer membrane proteins (bacA, sbmA, smpA, yeaY), and proteins with unknown function (ybaB, yaiW, yiiS, yiiT, yfeY).


[Degos atrophic malignant papulosis. Not always malignant!].
A patient developed malignant atrophic papulosis with only cutaneous manifestation. Repeated coloscopy uncovered no malignant papules in the colon. Referring to the literature, the value of permanent anticoagulant therapy is discussed. In contrast to the term "malignant" atrophic papulosis, there also seems to be a variant with a benign clinical course.


The effect of electrical stimulation on colonic transit following spinal cord injury in cats.
The effect of direct electrical stimulation on colinic transit and manometric recordings following spinal cord injury were assessed in five adult male cats. Intra-colonic catheters were surgically placed, stimulating electrodes were sutured to the colonic serosa and a laminectomy with spinal cord clamping at a T4 level was done to induce spinal cord injury (SCI). Twenty radiopaque markers were inserted through an intra-colonic catheter located 1 cm distal to the cecum and were monitored with daily fluoroscopy as a measure of colonic transit. Transit measurements were compared before SCI, after SCI and after SCI with electrical stimulation of 40 pps, 1 ms, and 0-50 mA. Colonic transit following SCI was significantly prolonged (P<0.05) when compared to the transit before SCI. Electrical stimulation following SCI improved colonic transit to values not significantly different from those before SCI. Spontaneous colonic phasic motor activity was similar both before and after SCI. Manometric defection patterns were also observed to be similar before SCI and after SCI with electrical stimulation. Based on our scoring criteria, the most frequent response to electrical stimulation was an abdominal contraction. These findings demonstrate that colonic transit is prolonged following SCI and that direct electrical stimulation of the colon following SCI improves colonic transit in an animal model.


Potential influencing factor on health-related quality of life in Japanese with knee osteoarthritis: the Locomotive syndrome and Health outcome in Aizu cohort Study (LOHAS).
Several studies have investigated the factors that influence health-related quality of life in patients with knee osteoarthritis (KOA). This study aimed to identify and investigate the degree of involvement of potential factors influencing health-related quality of life (HRQOL) in an aged population with or without KOA. This multi-centered study included 651 participants who underwent health checkups in rural areas of Japan in 2010. The association between three component summary score of short-form 12 (physical component summary; PCS, mental component summary; MCS, and role-social component summary; RCS) and covariates were investigated using multiple linear regression model and calculated the scaled estimated regression coefficient. Decreasing mobility, severity of knee pain, high pain-related self-efficacy (PSE), older age, high functional self-efficacy (FSE), and female gender had significant effect on PCS (p < 0.05). However, radiographic KOA had no influence on PCS. Presence of depression and body mass index had a significant influence on the MCS (p < 0.05). Decreasing mobility, presence of depression, PSE and older age had significant influence on the RCS (p < 0.05). Our study results showed that physical, mental, and role/social QOL were affected by different influencing factors. Physical QOL was strongly influenced by subjective pain, physical performance, and self-efficacy, whereas radiographic KOA had no such effect. Depressive mood is associated with both mental and role/social QOL. The role/social QOL was predominantly affected by physical function and pain-related self-efficacy. Taking measure to improving functional ability and mental status might be the key factor to improve HRQOL in patient with KOA. Level 3: Epidemiologic cross-sectional study (prognostic study).


Synthesis and preliminary evaluation of the new water-soluble radioactive platinum(IV) complexes.
A novel class of water-soluble Pt(IV) complexes with histamine (Hist) and radioiodinated histamine ([(125)I/(131)I]Hist) has been synthesised with the goal of potential application for concomitant anticancer radio-chemotherapy of solid tumours. The prepared complex of 1:2 metal:ligand stoichiometry ([Pt(IV)(Hist)(2)(OH)(2)]Cl(2)) was characterised by microanalysis, mass spectrometry, and chromatographic methods. Cytotoxic/cytostatic activities of the complex were examined by flow cytometry method using the MCF-7 cells line. A slightly lower cytotoxicity of the Pt(IV) complex comparing to cisplatin was found (IC(50) 59 and 48 microM, respectively). Both cisplatin and the histamine complex show a cytostatic activity by blocking MCF-7 cells in S-phase of cell cycle. Biodistribution studies in normal rats revealed the highest accumulation of the (131)I-labelled complex in liver and kidneys (41.3% and 12.4% ID after 24 h post-intravenous injection (p.i.v.)). The similar pharmacokinetics was observed in tumour-bearing C3H/W mice, however, a lower accumulation in liver was observed following an intraperitoneal comparing to an intravenous administration. A concentration of the complex in tumour increased with time post-intraperitoneal injection (1.2 and 2.5%ID/g after 2 and 24 h (p.i.), respectively). An increasing tumour/muscle ratio was also observed (2.2 and 4.5 after 2 and 24 h p.i., respectively), and that suggests a penetration of the complex into the tumour cells, and a permanent binding with some cellular components, probably with the DNA.


The genetics of exceptional longevity: Insights from centenarians.
As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs).


Partial destabilization of native structure by a combination of heat and denaturant facilitates cold denaturation in a hyperthermophile protein.
Cold denaturation is a phenomenon seen in many different proteins. However, there have been no reports so far of its occurrence in hyperthermophile proteins. Here, using a recombinant triosephosphate isomerase (PfuTIM) from the hyperthermophile archaeon, Pyrococcus furiosus, we show that the heating of this protein through the low temperature side of its thermal unfolding transition in the presence of guanidinium hydrochloride (GdmCl) results in the formation of partially-disordered conformational ensembles that retain considerable native-like secondary and tertiary structure. Unlike PfuTIM itself, these thermochemically obtained partially-disordered PfuTIM ensembles display cold denaturation as they are cooled to room temperature. The protein thus shows hysteresis, adopting different structural states in a manner dependent upon the nature of the heating and cooling treatment, rather than upon the initial and final conditions of temperature and GdmCl concentration, indicating that some sort of a kinetic effect influences structure adoption and retention. The structure lost through cooling of partially-disordered PfuTIM is found to be regained through heating. The ability of GdmCl to thus apparently destabilize the highly thermodynamically and kinetically stable structure of PfuTIM (sufficiently, to cause it to display observable cold-denaturation and heat-renaturation transitions, in real-time, with cooling and heating) offers support to current ideas concerning the how hyperthermophile proteins achieve their high kinetic stabilities, and suggests that desolvation-solvation barriers may be responsible for high kinetic stability.


Fenugreek attenuation of diabetic nephropathy in alloxan-diabetic rats: attenuation of diabetic nephropathy in rats.
Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. To prevent the development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In this paper, the efficacy of fenugreek to restore the kidney function of diabetic rats via its antioxidant and anti-inflammatory activities has been studied. Novel data showing the efficacy of fenugreek to attenuate progression of diabetic nephropathy and production of interleukin-6 (IL-6) in rats compared with a diabetic untreated group were obtained. Rats were classified into five groups; control, diabetic untreated, and three diabetic groups treated with fenugreek, rosiglitazone, and metformin. Treatment with fenugreek has been continued for 12 weeks. Fenugreek was found to significantly reduce the high levels of glucose, urea, creatinine, sodium, potassium, and IL-6 in serum compared with the diabetic untreated group. In addition, levels of malondialdehyde and IL-6 in the kidney homogenate were significantly reduced as a result of the fenugreek treatment compared with the diabetic untreated group. Moreover, concentration of GSH and the activity of both superoxide dismutase and catalase were considerably increased in the diabetic treated groups compared with the diabetic untreated group. Furthermore, glomerular mesangial expansion was reduced in the treated animal groups. These findings suggest a therapeutic potential of fenugreek against diabetic nephropathy, explain its antioxidative/anti-inflammatory properties and provide a direction for future research.


Complications of tracheotomy in patients with mucopolysaccharidoses type II (Hunter syndrome).
To investigate the complication rate of tracheotomy in patients with mucopolysacchridoses (MPS) type II (Hunter syndrome). From 2004 to 2005, seven tracheotomy procedures were performed for the airway management in three patients with MPS type II. The complications for each procedure were analyzed, which included the stomal narrowing, granulation formation, infrastomal tracheal stenosis, and wound infection. All tracheotomies in patients with MPS type II resulted in tracheotomy-related complications, though these procedures secured a safe airway. Infrastomal tracheal stenosis was the most frequent complication (85.7%) and stomal narrowing also occurred frequently (71.4%) after each tracheotomy. These complications caused cannula care to be difficult, with revision frequently required. Of the complications observed after tracheotomy, infrastomal tracheal stenosis and stomal narrowing are frequent in patients with MPS type II. Therefore, tracheotomy procedures should be cautiously applied to the MPS type II patients, and the complications associated with tracheotomy should be discussed with caregivers preoperatively.


The effect of ferriprotoporphyrin IX and chloroquine on phospholipid monolayers and the possible implications to antimalarial activity.
Ferriprotoporphyrin IX intercalates into phospholipid membranes, as evidenced from its effect on the surface pressure of monolayers composed of different phospholipids. Ferriprotoporphyrin intercalation is enhanced by membrane hydrophobicity and decreased by negative surface potential. Chloroquine enhances the effect of ferriprotoporphyrin in relatively hydrophobic membranes but reduces it in monolayers composed of highly unsaturated phospholipids. These results are consistent with the differential effect of chloroquine on ferriprotoporphyrin-induced lysis of erythrocytes and of malarial parasites, thus supporting the membrane-lesion hypothesis of antimalarial action.


Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes.
Investigate the potential application of corosolic acid (CA) in the treatment of diseases causing retinal neovascularization. CA cytotoxicity effect was evaluated in ARPE-19 cells by sulforhodamine B colorimetric method, and antiangiogenic activity was studied using chorioallantoic membrane (CAM) assay. An amount of 0.01 mL of CA formulations at 5, 10 and 25 µM was injected in the right eyes of Wistar rats, and the contralateral eyes received the vehicle to verify the safety of ophthalmic use. Electroretinography (ERG) was performed before, 7 and 15 days after CA administration. Animals were killed on the 15th day, and the histological analysis of retina was carried out under light microscopy. CA did not present cytotoxicity at concentrations below 35.5 μM after 48 h of treatment. The antiangiogenic activity was confirmed by CAM assay, since CA (range from 5 to 25 µM) induced a significant reduction in vascularity without any signs of toxicity. ERG recordings and histological evaluation did not show any signs of retinal toxicity. CA was effective in reducing vascularity in a CAM model and was found to be safe for potential ophthalmic use.


Asymmetric labeling of amino lipids in liposomes.
Fluorescamine and trinitrobenzenesulfonate were used as chemical probes to differentially label amino phospholipids in liposomes. At low concentrations, fluorescamine reacts primarily with amino lipids on the external half of the bilayer. Further increase in fluorescamine concentration resulted in a linear increase of labeling indicating penetration and reaction with the internal half of the bilayer. Because of the pH requirements of the fluorescamine reaction, internal labeling was eliminated with a H+ gradient: inside acidic/outside alkaline. Differential labeling was also achieved with trinitrobenzenesulfonate, which is normally not permeable but which can be transported by valinomycin-K+ complex and react with internal amines. Thus, either half of the bilayer can be labeled with the same or different reagents. When liposomes were double-labeled, the fluorescence of fluorescamine was quenched by the trinitrobenzenesulfonate label. This quenching was reversed by solubilizing the liposomes with acidic ethanol. No quenching occurred when fluorescamine-labeled liposomes were mixed with trinitrobenzenesulfonate-reacted liposomes (or trinitrophenylated methylamine) suggesting close proximity of two labels is required for quenching. Conditions which promoted vesicular fusion promptly produced quenching. These differential labeling procedures can be usefully applied to quantitate aminolipids on internal and external vesicular surface, monitor vesicular fusion, and assess liposomal structure.


Comparison of trans-nasal laryngoscopic office based biopsy of laryngopharyngeal lesions with traditional operative biopsy.
The objectives of this study are to compare the pathological results from office-based biopsy (OBB) and operative biopsy (ORB) of laryngopharyngeal lesions from 26 patients. Lesion location, specimen concordance, efficacy, cost savings, and patient management are discussed. OBB can provide a sample of laryngopharyngeal tissue that can be used to diagnose lesions in these sites. This study design is retrospective review and involved retrospective analysis and chart review of 26 cases of patients who had an OBB followed by and ORB of the same site; oropharyngeal or laryngopharyngeal lesion. CPT 31576 was to identify patients. Twenty six patients had both OBB and operative biopsy performed of a lesion within the oropharynx and laryngopharynx. All OBB attempts resulted in diagnostic tissue samples. Vocal fold biopsy (69 %) was most common. The most common OBB diagnosis was squamous cell carcinoma or moderate-to-severe dysplasia (54 %). OBB and ORB pathological results were the same in 81 % of patients. Of the benign samples obtained by OBB, 83 % of the ORB were deemed benign. Of the non-benign samples obtained via OBB, 80 % of the ORB were deemed non-benign in the operating room samples. Office-based biopsy is a simple procedure that can be performed in an outpatient setting, avoiding an operating room and the need for general anesthesia. Comparison of results from OBB to ORB together with patient characteristics resulted in very reliable results that can help to guide further patient management.


Induction of umu gene expression in Salmonella typhimurium TA1535/pSK1002 by dimethyl sulfoxide (DMSO).
The genotoxicity of dimethyl sulfoxide (DMSO) was demonstrated by the umu test using Salmonella typhimurium TA1535/pSK1002 carrying the umuC-lacZ fusion gene. The level of beta-galactosidase activity which shows umu gene expression in the test system was dependent on the concentration of DMSO in the culture medium. The maximum beta-galactosidase activity was approximately 3.5 times as high as the background level with 10% of DMSO in the culture medium. The lowest concentration of DMSO required for a response of over twice the background level was approximately 5%. Four structurally related chemicals (acetone, di-n-butylsulfoxide, dimethylsulfide, methylphenylsulfoxide) did not show umu gene expression at their non-toxic doses.


Sesquiterpene lactones from Achillea chrysocoma and Achillea coarctata.
The aerial parts of A. chrysocoma and A. coarctata afforded 22 and 9 sesquiterpene lactones, respectively. All the compounds described are new for the studied species. The lactones 5, 6 and 12 are new for the genus Achillea.


A Luminex Approach to Develop an Anti-Tumor-Associated Antigen Autoantibody Panel for the Detection of Prostate Cancer in Racially/Ethnically Diverse Populations.
(1) Background: Autoantibodies to tumor-associated antigens (TAAs) have emerged as promising cancer biomarkers. Luminex technology offers a powerful approach for the simultaneous detection of multiple anti-TAA autoantibodies. (2) Methods: We aimed to utilize Luminex technology to evaluate and optimize a panel of anti-TAAs autoantibodies for detecting prostate cancer (PCa), which included autoantibodies to fourteen TAAs. A total of 163 serum samples (91 PCa, 72 normal controls) were screened to determine the levels of the autoantibodies using the Luminex assay. (3) Results: Twelve autoantibodies exhibited significantly high frequencies ranging from 19.8% to 51.6% in the PCa group. Receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values ranging from 0.609 to 0.868 for the twelve autoantibodies individually. We further confirmed the performance of the HSP60 autoantibody by using an enzyme-linked immunosorbent assay (ELISA) in a larger sample comprising 200 PCa sera, 20 benign prostatic hyperplasia (BPH) sera, and 137 normal control sera. The results obtained from the Luminex assay were consistent with the ELISA findings. We developed a panel consisting of three autoantibodies (p16, IMP2, and HSP60) which achieved an impressive AUC of 0.910 with a sensitivity of 71.4% and a specificity of 95.8%. The panel was also evaluated in PCa patients from different races/ethnicities with the best performance observed in distinguishing the Hispanic American patients with PCa from normal controls. (4) Conclusions: We developed an anti-TAA autoantibody panel for the detection of PCa that exhibits promising performance. This panel holds significant potential as a high-throughput tool to facilitate PCa detection.


Surfactant proteins in pediatric interstitial lung disease.
Children's interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD. Levels of SP-B and SP-C in BALF from 302 children with chILD and in controls were quantified using western blotting. In a subset, single-nucleotide polymorphisms (SNPs) in the SFTPC promoter were genotyped by direct sequencing. While a lack of dimeric SP-B was found only in the sole subject with hereditary SP-B deficiency, low or absent SP-C was observed not only in surfactant dysfunction disorders but also in patients with other diffuse parenchymal lung diseases pathogenetically related to the alveolar surfactant region. Genetic analysis of the SFTPC promoter showed association of a single SNP with SP-C level. SP-B levels may be used for screening for SP-B deficiency, while low SP-C levels may point out diseases caused by mutations in TTF1, SFTPC, ABCA3, and likely in other genes involved in surfactant metabolism that remain to be identified. We conclude that measurement of levels of SP-B and SP-C was useful for the differential diagnosis of chILD, and for the precise molecular diagnosis, sequencing of the genes is necessary.


The compatibility heuristic in non-categorical hypothetical reasoning: inferences between conditionals and disjunctions.
A new theory explains how people make hypothetical inferences from a premise consistent with several alternatives to a conclusion consistent with several alternatives. The key proposal is that people rely on a heuristic that identifies compatible possibilities. It is tested in 7 experiments that examine inferences between conditionals and disjunctions. Participants accepted inferences between conditionals and inclusive disjunctions when a compatible possibility was immediately available, in their binary judgments that a conclusion followed or not (Experiment 1a) and ternary judgments that included it was not possible to know (Experiment 1b). The compatibility effect was amplified when compatible possibilities were more readily available, e.g., for 'A only if B' conditionals (Experiment 2). It was eliminated when compatible possibilities were not available, e.g., for 'if and only if A B' bi-conditionals and exclusive disjunctions (Experiment 3). The compatibility heuristic occurs even for inferences based on implicit negation e.g., 'A or B, therefore if C D' (Experiment 4), and between universals 'All A's are B's' and disjunctions (Experiment 5a) and universals and conditionals (Experiment 5b). The implications of the results for alternative theories of the cognitive processes underlying hypothetical deductions are discussed.


Energy partitioning in three species of nematode from polysaprobic environments.
The partitioning of energy in three species of nematode, Paroigolaimella bernensis, Diplogasteritus nudicapitatus and Rhabditis curvicaudata, from a polysaprobic environment is considered. Temperature was shown to have a profound impact on the rate at which these organisms obtained food resources and on the partitioning of energy into growth, reproduction and maintenance. Declining temperature resulted in a reduction in energy consumption and in production and maintenance costs. Absorption efficiencies were relatively low, rarely exceeding 20% and lying on average between 5-15%. Net production efficiencies varied throughout the life-cycle, but attained maximum levels of 70-80%. Females achieved higher net production efficiency than males. The physiology and ecological implications are discussed.


Construction and characterization of BsGDH-CatIB variants and application as robust and highly active redox cofactor regeneration module for biocatalysis.
Catalytically active inclusion bodies (CatIBs) are known for their easy and cost efficient production, recyclability as well as high stability and provide an alternative purely biological technology for enzyme immobilization. Due to their ability to self-aggregate in a carrier-free, biodegradable form, no further laborious immobilization steps or additional reagents are needed. These advantages put CatIBs in a beneficial position in comparison to traditional immobilization techniques. Recent studies outlined the impact of cooperative effects of the linker and aggregation inducing tag on the activity level of CatIBs, requiring to test many combinations to find the best performing CatIB variant. Here, we present the formation of 14 glucose dehydrogenase CatIB variants of Bacillus subtilis, a well-known enzyme in biocatalysis due to its capability for substrate coupled regeneration of reduced cofactors with cheap substrate glucose. Nine variants revealed activity, with highest productivity levels for the more rigid PT-Linker combinations. The best performing CatIB, BsGDH-PT-CBDCell, was characterized in more detail including long-term storage at -20 °C as well as NADH cofactor regeneration performance in repetitive batch experiments with CatIB recycling. After freezing, BsGDH-PT-CBDCell CatIB only lost approx. 10% activity after 8 weeks of storage. Moreover, after 11 CatIB recycling cycles in repetitive batch operation 80% of the activity was still present. This work presents a method for the effective formation of a highly active and long-term stable BsGDH-CatIB as an immobilized enzyme for robust and convenient NADH regeneration.


Quantification of tissue property and perfusion uncertainties in hyperthermia treatment planning: Multianalysis using polynomial chaos expansion.
Hyperthermia treatment planning (HTP) tools can guide treatment delivery, particularly with locoregional radiative phased array systems. Uncertainties in tissue and perfusion property values presently lead to quantitative inaccuracy of HTP, leading to sub-optimal treatment. Assessment of these uncertainties would allow for better judgement of the reliability of treatment plans and improve their value for treatment guidance. However, systematically investigating the impact of all uncertainties on treatment plans is a complex, high-dimensional problem and too computationally expensive for traditional Monte Carlo approaches. This study aims to systematically quantify the treatment-plan impact of tissue property uncertainties by investigating their individual contribution to, and combined impact on predicted temperature distributions. A novel Polynomial Chaos Expansion (PCE)-based HTP uncertainty quantification was developed and applied for locoregional hyperthermia of modelled tumours in the pancreatic head, prostate, rectum, and cervix. Patient models were based on the Duke and Ella digital human models. Using Plan2Heat, treatment plans were created to optimise tumour temperature (represented by T90) for treatment using the Alba4D system. For all 25-34 modelled tissues, the impact of tissue property uncertainties was analysed individually i.e., electrical and thermal conductivity, permittivity, density, specific heat capacity and perfusion. Next, combined analyses were performed on the top 30 uncertainties with the largest impact. Uncertainties in thermal conductivity and heat capacity were found to have negligible impact on the predicted temperature ( < 1 × 10-10 °C), density and permittivity uncertainties had a small impact (< 0.3 °C). Uncertainties in electrical conductivity and perfusion can lead to large variations in predicted temperature. However, variations in muscle properties result in the largest impact at locations that could limit treatment quality, with a standard deviation up to almost 6 °C (pancreas) and 3.5 °C (prostate) for perfusion and electrical conductivity, respectively. The combined influence of all significant uncertainties leads to large variations with a standard deviation up to 9.0, 3.6, 3.7 and 4.1 °C for the pancreatic, prostate, rectal and cervical cases, respectively. Uncertainties in tissue and perfusion property values can have a large impact on predicted temperatures from hyperthermia treatment planning. PCE-based analysis helps to identify all major uncertainties, their impact and judge the reliability of treatment plans.


Structure-activity relationships (SAR) of triazine derivatives: Promising antimicrobial agents.
The emergence of drug resistance has created unmet medical need for the development of new classes of antibiotics. Innovation of new antibacterial agents with new mode of action remains a high priority universally. Triazines are six-membered, nitrogen-containing heterocyclic scaffold with a wide range of pharmaceutical properties such as antibacterial, antifungal, anticancer, antioxidants, antitubercular, antimalarial, anti-HIV, anticonvulsant, anti-inflammatory, antiulcer, and analgesic activities. The present review focuses on the recent developments in the area of medicinal chemistry to discover various chemical structures as potential antimicrobial agents and their structure-activity relationships (SAR) studies are also discussed for further rational design of this kind of derivatives.


Long-term effects of triethylenemelamine exposure on mouse testis cells and sperm chromatin structure assayed by flow cytometry.
The toxic and potentially mutagenic actions of triethylenemelamine (TEM) on mouse body and testis weights, testicular cell kinetics, sperm production, sperm head morphology, and sperm chromatin structure were assessed in two experiments. The first experiment examined effects of four dose levels of TEM, assayed 1, 4, and 10 wk after toxic exposure. In the second study, effects from five dosage levels were measured at 1, 4, and 10 wk, and the highest dosage level was evaluated over 44 wk. TEM produced an expected dose related loss of spermatogenic activity and subsequent recovery as determined by dual-parameter (DNA, RNA) flow cytometry (FCM) measurements of testicular cells. Both testicular weights and caudal sperm reserves remained generally below controls after 44 wk recovery following exposure to the highest (1.0 mg/kg daily x 5) dosage. Chromatin structure alterations, defined as increased susceptibility to DNA denaturation in situ, and sperm head morphology were highly correlated (.87-.93, P less than .001) with dose and with each other. Data obtained from the sperm chromatin structure essay (SCSA) on fresh sperm was highly correlated with measurements of aliquots of the same sample collected over 44 wk, frozen, and then measured on the same day. Sperm head morphology and sperm chromatin structure remained abnormal at 44 wk for the 1.0 mg/kg TEM dosage, suggesting that the abnormalities, present long after the initial toxic response, may be a result of mutation. This study demonstrates that flow cytometry provides a unique, rapid, and efficient means to measure effects of reproductive toxins and potential mutagens.


Contributions of cytoplasmic domains of desmosomal cadherins to desmosome assembly and intermediate filament anchorage.
To examine the potential of cytoplasmic portions ("tails") of desmosomal cadherins for assembly of desmosome plaque structures and anchorage of intermediate filaments (IFs), we transfected cultured human A-431 carcinoma cells, abundant in desmosomes and cytokeratin IFs, with constructs encoding chimeric proteins in which the transmembranous region of connexin 32 had been fused with tails of desmocollin (Dsc) or desmoglein (Dsg). The results show that the tail of the long splice form a of Dsc, but not its shorter splice form b, contains sufficient information to recruit desmoplakin and plakoglobin to connexon membrane paracrystals (gap junctions) and to form a novel kind of plaque at which cytokeratin IFs attach. By contrast, chimeras containing a Dsg tail, which accumulated in the plasma membrane, showed a dominant-negative effect: they not only were unable to form gap junction structures and plaques but also led to the disappearance of all endogenous desmosomes and the detachment of IFs from the plasma membrane.


Non-mammalian vertebrate models and the endocannabinoid system: relationships with gonadotropin-releasing hormone.
Endocannabinoids, via cannabinoid receptors (CB1 and CB2), affect reproductive functions at both local and central level. Due to the high complexity of the endocannabinoid system, to the widespread distribution outside the nervous system and to the high degree of evolutionary conservation, a deep CB1 molecular characterization among species may be useful to elucidate the activity of endocannabinoids at multiple levels. In this review we report CB1 characterization in non-mammalian animal models and, in particular, in the anuran amphibian, the frog, Rana esculenta; we also describe its expression during the annual sexual cycle. Moreover, since reproductive functions are under control of gonadotropin releasing hormone (GnRH), cb1 mRNA and protein expression profile in the forebrain has been compared to those of GnRH-I, the mammalian form primarily involved in gonadotropin release.


Associations between the chemical composition of PM2.5 and gestational diabetes mellitus.
Fine particulate matter (PM2.5) is a complex mixture of fine particulates with large spatiotemporal heterogeneities in chemical compositions. While PM2.5 has been associated with gestational diabetes mellitus (GDM), little is known about the relationship between specific chemical components of PM2.5 and GDM. We examined the associations between GDM and pregnancy exposures to PM2.5 and its compositions, including sulfate (SO42-), ammonium (NH4+), nitrate (NO3-), organic matter (OM), black carbon (BC), mineral dust (DUST), and sea-salt (SS), and to identify critical windows of exposure. We used data from the 2005-2015 Florida Vital Statistics Birth Records. A well-validated geoscience-derived model was used to estimate women's pregnancy exposures to PM2.5 and its compositions. Distributed lag models were used to examine the associations and to identify the critical windows of exposure. A total of 2,078,669 women were included. In single-pollutant models, after controlling for potential confounders, positive associations between PM2.5 and GDM were observed during the second trimester of pregnancy. We found positive associations between SO42-, NH4+, NO3-, OM and BC, with largest effect sizes observed in the 21-24 weeks of pregnancy. Negative associations were observed for DUST and SS. Consistent results for NH4+, OM, DUST and SS were observed in the multi-pollutant models. Exposures to PM2.5 and its compositions (mainly NH4+, OM) during the second trimester are positively associated with GDM, especially for exposures during the 21-24 weeks of pregnancy. Further studies are needed to confirm the findings and examine the underlying mechanisms.


Bilateral mastocytic and fibroblastic nodular proliferative dermatosis affecting ear margins in three domestic cats.
This case series describes the clinical appearance, histopathological findings and therapeutic trials of proliferative nodular lesions on bilateral ear margins of three domestic cats including two littermates. All therapeutic trials were unsuccessful. While the aetiology remains unclear, this report highlights different hypotheses in presenting this unusual inflammatory and fibroblastic dermatosis in cats.


[Enzyme arrangement of various tissues in swine. 3. Studies of pre- and postnatal activities of various enzymes (ATPase, GOT, GPT, leucine aminopeptidase, acid and alkaline phosphatases, aldose reductase, glucuronate reductase, sorbitol dehydrogenase) in various tissues].
The crude protein levels as well as the activities of various enzymes were studied in certain tissues of fetuses (80th through 114th days of development), piglets of different age groups, and pigs for slaughter. In most of the tissues tested the postnatal activities of Na-K-ATPase were beyond those recorded from fetuses. The highest GOT activities were recorded from the liver, myocardium, and kidneys. Activities were found to rise sizeably in some tissues after birth. The activity of GPT, too, exhibited age-dependent variations. The activity of leucine-aminopeptidase increased strongly after birth in liver and kidneys. Acid phosphatase activity was less markedly influenced by development phases. Those enzymes which are involved in the formation of fructose and glucose (aldolreductase, glucuronate-reductase, and sorbite-dehydrogenase) had their highest activities, all age-dependent, in liver and kidneys.


Treating age-related multimorbidity: the drug discovery challenge.
Advanced age is the major risk factor for multimorbidity. Current clinical practice treats the individual age-related diseases, resulting in polypharmacy. Thus, targeting the biological processes that drive ageing could prevent both multimorbidity and polypharmacy.


APOBEC3G has the ability to programme T cell plasticity.
Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-κB, CCL5, IL-6, IL-4, IFN-γ, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number. On the basis of these findings, we propose that APOBEC3G has the ability to induce T cell plasticity and modulate immune response.


A rapid colorimetric method for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage form.
Two new rapid reproducible and economical spectrophotometric methods are described for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage forms. Both methods are based on the formation of an orange-red and orange ion-pair complex due to the action of Calmagite (CT) and Orange-II (O-II) on Losartan potassium in acidic medium (pH 1.2). Under optimised conditions, they show an absorption maxima at 491 nm (CT) and 486 nm (O-II), with molar absorptivities of 1.74 x 10(3) and 1.75 x 10(3) l mol(-1) cm(-1) and Sandell's sensitivities of 0.2649 and 0.2637 per 0.001 absorbance unit for CT and O-II, respectively. The colour is stable for 5 min after extraction. In both cases Beer's law is obeyed between 10 and 100 microg ml(-1). The proposed method was successfully extended to synthetic mixture for solid dosage forms.


The effects of ginsenosides to amyloid fibril formation by RCMκ-casein.
When not incorporated into the casein micelle, isolated κ-casein spontaneously forms amyloid fibrils under physiological conditions, and is a convenient model for researching generic aspects of fibril formation. Ginsenosides have recently attracted much research interest because of the effects on aging diseases, which are always associated with amyloid fibril formation, for example, Alzheimer's, Parkinson's, and Huntington's diseases. In addition, the mechanism remains unclear that ginsenosides exert the effects against aging diseases. To address these aspects, we have investigated the ability of ginsenoside Rb1, Rc, Rg1, and Re influencing fibril formation by RCMκ-casein (reduced and carboxymethylated κ-casein), with the methods of Thioflavin T fluorescence assay, transmission electron microscopy (TEM), and intrinsic fluorescence spectroscopy. The results showed that ginsenoside Rb1 and Rg1 inhibited obviously RCMκ-CN fibrillation in both the initial rate and final level of ThT fluorescence. On the contrary, ginsenoside Re had a few effect on promoting RCMκ-CN fibril formation, proved by thick and larger fibrils observed frequently in TEM. While Rc did not influence RCMκ-CN fibrillation. It is demonstrated that Rg1 prevent RCMκ-CN fibril formation by stabilising RCMκ-CN in its native like state. Additional chemical structure difference of ginsenosides and the effects on fibril formation are also implicated.


Human receptor for activated protein kinase C1 associates with polyglutamine aggregates and modulates polyglutamine toxicity.
Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer's and Parkinson's diseases.


Changes in U.S. girls' participation in high school sports: implications for injury awareness.
The number of female athletes has grown exponentially since Title IX. However, little data exists on the proportion of women and girls who play each sport. To quantify changes in female sports participation in high school sports from 1973 to 2018. Retrospective analysis of data from the National Federation of State High School Associations Participation Survey. US high schools. US high school athletes from 1973 to 2018. Percentage of female participation for each high school sport in 5-year intervals; and changes in rates of participation by player gender and sport at designated intervals. From 1973 to 2018, the percentage of high school sports played by girls increased from 24.2% to 42.9% ([95%CI, 18.6,18.8], p < 0.0001). In the 14 sports included in our study, all had an increase in the percentage of female participation between 1973 and 2018. >80% of the increases occurred between 1973 and 1998 for all sports except lacrosse, ice hockey, football, and wrestling. Between 1998 and 2018, the percentage of girls playing each sport increased by less than 5% in all sports, except for ice hockey (11.5%, 95% CI 11.0, 12.0, p < 0.001) and wrestling (7.1%, 95% CI 6.9, 7.1, p < 0.001). Girls' participation in high school sports continues to grow not only in numbers but in the types of sports played. Between 1998 and 2018, the greatest increases were noted in ice hockey and wrestling, which had fewer than 1% female participation before 1998. Physicians providing care for female athletes should be aware of these changes and understand the potential injuries associated with these sports.


Variable interference with interferon signal transduction by different strains of porcine reproductive and respiratory syndrome virus.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-sense single-strand RNA virus that has contributed to substantial losses to the swine industry. The objective of this study was to examine the interference of interferon (IFN)-activated signaling by PRRSV viral proteins and compare the effects of several PRRSV strains on the IFN signaling. Three non-structural proteins (nsp 1β, 7 and 12) and two structural proteins (GP3 and N) of VR-2385 were found to significantly inhibit the expression of IFN-stimulated response element (ISRE) luciferase reporter. Nsp1β and N showed robust inhibition and their-encoding sequences from the six PRRSV strains (VR-2385, Ingelvac PRRS MLV, VR-2332, NVSL97-7895, MN184, and Lelystad) were cloned for further characterization. The nsp1βs of all the strains except MLV inhibited expression of IFN-induced ISRE reporter, interferon-stimulated gene 56 (ISG56) and signal transducer and activator of transcription 2 (STAT2). The N proteins inhibited the IFN-induced ISRE reporter expression and STAT2 elevation and blocked nuclear translocation of STAT1. In MARC-145 cells, all the six PRRSV strains with the exception of MN184 blocked the activity of exogenous IFN-α. In primary porcine pulmonary alveolar macrophages (PAMs), only MLV and NVSL failed to inhibit the activity of IFN-α. These results indicate that some PRRSV strains, such as NVSL and MN184, have variable effects on IFN-activated signaling in the two types of cells.


Pathogenic HER3 dimerization domain mutations create a structural bias towards un-conventional EGFR-HER3 signalling axis in breast cancer.
Among the EGFR family of receptors, HER3 is considered as a pseudo-kinase which primarily interacts with HER2 in presence of heregulin-1β. We identified two hotspot mutations i.e. G284R and D297Y and one double mutant HER2-S310F/HER3-G284R in breast cancer patients. Long term MDS (7.5 μs) revealed that HER3-D297Y and HER2-S310F:HER3-G284R do not allow the interaction with HER2 as these mutations cause dramatic conformational changes in its flanking regions. This results in formation of an unstable HER2-WT:HER3-D297Y heterodimer, thereby abrogating the downstream signalling by AKT. We found that His228 and Ser300 of HER3-D297Y form stable interactions with Glu245 and Tyr270 of EGFR-WT, in the presence of either EGF or heregulin-1β. Applying TRIM-ing mediated direct knockdown of endogenous EGFR protein, specificity of the unconventional EGFR:HER3-D297Y interaction was validated. Due to this unusual ligand mediated interaction, cancer cells were found susceptible to EGFR targeted therapeutics i.e. Gefitinib and Erlotinib. Further, in TCGA analysis, BC patients harbouring HER3-D297Y mutation showed increased p-EGFR levels as compared to the patients harbouring HER3-WT and HER3-G284R mutations. For the first time, this comprehensive study showed the importance of specific hotspot mutations in HER3 dimerization domain can defy the Trastuzumab therapy, rather cells become susceptible to the EGFR inhibitors.


The distribution of serotonin, met-enkephalin and beta-lipotropin-like immunoreactivity in neuronal perikarya of the cat brainstem.
The distribution of methionine-enkephalin, serotonin and beta-lipotropin-containing neurones has been mapped immunohistochemically in the brainstem of the cat after local colchicine injections. Serotonin-containing neurons were found in th raphe in nucleus raph magnus (NRM), nucleus raphe pallidus (NRP) and nucleus raphe obscurus (NRO) and in a band extending cross the ventral reticular formation into nucleus paragigantocellularis lateralis (PGL) and nucleus lateralis reticularis (LRM). Enkephalin-positive cell bodies were also found in these raphe nuclei and in most divisions of the caudal reticular formation. Double labelling studies established that enkephalin and serotonin co-exist within some neurons in NRM and NRP. beta-Lipotropin-positive cell bodies were found principally within NRP and within the ventrolateral reticular formation in PGL and LRM.


From organ preservation to selective surgery: How immunotherapy changes colorectal surgery?
The emergence of immunotherapy has revolutionized the traditional treatment paradigm of colorectal cancer (CRC). Among them, immune checkpoint blockade has become the first-line treatment for metastatic colorectal cancer (mCRC) and has made significant progress in the treatment of locally advanced colorectal cancer (LACRC). We reviewed a series of clinical trials that have made breakthrough progress. We will emphasize the breakthrough progress in achieving organ preservation in patients with high microsatellite instability or DNA mismatch repair deficiency (MSI-H/dMMR), and based on this, we propose the concept of selective surgery, which includes selectively removing or preserving lymph nodes, with the aim of proving our idea through more research in the future.


[Rectal Mucosa-associated Lymphoid Tissue Lymphoma Treated with Endoscopic Resection].
A primary extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct clinical-pathological entity that develops in diverse anatomic locations. However, colorectal involvement is rare. The authors encountered a case of a MALT lymphoma of the rectum in a 69-year-old woman who complained of up to 3 kg weight loss during 3 months. A colonoscopy demonstrated a 1.0×1.0 cm sized subepithelial tumor (SET) at the lower rectum. The patient underwent an endoscopic mucosal resection with ligation for the SET. Pathological analysis revealed marked small to medium-sized lymphocytic infiltration. Immunohistochemistry revealed neoplastic cells positive for CD20 and bcl-2. A polymerase chain reaction detected immunoglobulin H gene rearrangement. Finally, rectal MALT lymphoma was diagnosed. Computed tomography and positron emission tomography scans showed that there was no lymph node metastasis or other organ involvement. A bone marrow biopsy was found to be negative for any neoplastic process. Therefore, the Ann Arbor stage was IeB. Helicobacter pylori (H. pylori) was not detected in the gastric biopsy specimens. Thus far, she has had no relapse since the endoscopic resection. The incidence of rectal MALT is very rare, and treatment is unclear. This paper reports a case of rectal MALT lymphoma treated successfully with only an endoscopic resection.


Higher risk of recurrent ischemic events in patients with intracranial in-stent restenosis.
Reliable data concerning prognosis of patients with intracranial in-stent restenosis (ISR) is lacking. We prospectively studied long-term outcomes of patients with and without a catheter angiography-verified ISR. Between September 2001 and May 2009, 540 consecutive patients with symptomatic intracranial atherosclerosis received stenting treatment at our institute. Of them, 226 patients with 233 stented arteries had catheter angiography follow-up after stenting and were enrolled into this study. They were clinically followed up until the end of December 2011. Primary end point was ischemic stroke or transient ischemic attack in the territory of the stented artery after the catheter angiography follow-up. ISR was defined as a catheter angiography-verified stenosis of ≥50% within or immediately adjacent (within range of 3 mm) to the implanted stent. During a mean follow-up of 38.9 months, 27 (11.6%, 27/233) primary end point events were recorded. The risk of primary end point in ISR group was higher compared with non-ISR group (21.1% [12/57] versus 8.5% [15/176]; hazard ratio, 2.94; 95% confidence interval, 1.37-6.30; P=0.005). Multivariable analysis showed that the ISR was an independent risk factor for the primary end point (hazard ratio, 2.79; 95% confidence interval, 1.20-6.49; P=0.017). The median occurrence time of primary end point was 9.9 (interquartile range, 5.0, 21.1) months in ISR group, earlier than that in non-ISR group (26.6 [13.1, 52.9] months; P=0.01). In-stent restenosis after stenting of intracranial atherosclerosis is significantly associated with an increased risk and an earlier occurrence of recurrent ischemic events in the territory of the stented intracranial artery.


Some effects of delayed auditory feedback on dyspraxia of speech.
This investigation was designed to determine if delayed auditory feedback (DAF) might have a facilitating effect on dyspraxic speech. Five subjects with dyspraxia of speech and minimal aphasic involvement were used. Two reading tasks were administered under conditions of DAF and no DAF. Reading tasks were constructed of 24 monosyllabic words with initial consonant clusters and 10 polysyllabic words. Three experienced judges scored word production, consonant cluster production, and 12 types of production errors. Temporal duration of word productions was measured in both conditions. No significant differences between the conditions were found in any of the measured parameters. There was no demonstrable improvement of dyspraxia of speech errors under DAF. Contrary to earlier research, distortions rather than phonemic substitutions were found to be the most frequently occurring articulatory errors.


Plasma concentration of local anaesthetic agents in regard to absorption, distribution and elimination, with special reference to bupivacaine.
Absorption from the injection site, tissue distribution, metabolism and urinary excretion are the factors determining the plasma concentration of local anaesthetic agents. Other factors such as physico-chemical properties of these drugs may have important influences on these processes. An example of this is the difference in tissue distribution and plasma/erythrocyte ratio as well as an increase in plasma concentration of bupivacaine seen in acidosis. The importance for the plasma concentration, of protein binding, vasoactivity and the effect of depressed circulation are discussed.


Mercury free operation of the Coulter counter MultiSizer II sampling stand.
Electronic particle counters have gained widespread acceptance as a means to measure osmotic properties of cell membranes. Because most current instruments do not allow for the collection of true volume as a function of time data, investigators use older models such as the MultiSizer II sampling stand. A significant drawback to this and other older models is that they rely on mercury to maintain a constant pressure and to connect electrodes. The presence of mercury is a human health hazard that is exacerbated by the sometimes irregular vacuum pressures that cause mercury spills inside of the machine. To eliminate this hazard, we have determined that the MultiSizer II model can be simply and easily modified to function and collect temporal volume data without the use of mercury.


Reliability and validity of the Incontinence Quiz-Turkish version.
The aim of this study was to investigate the reliability and validity of the Turkish version of the Incontinence Quiz, which was developed by Branch et al. (1994), to assess women's knowledge of and attitudes toward urinary incontinence. Comprehensibility of the Turkish version of the 14-item Incontinence Quiz, which was prepared following translation-back translation procedures, was tested on a pilot group of eight women, and its internal reliability, test-retest reliability and construct validity were assessed in 150 women who attended the gynecology clinics of three hospitals in İçel, Turkey. Physical and sociodemographic characteristics and presence of incontinence complaints were also recorded. Data were analyzed at the 0.05 alpha level, using SPSS version 22. The scale had good reliability and validity. The internal reliability coefficient (Cronbach α) was 0.80, test-retest correlation coefficients were 0.83-0.94; and with regard to construct validity, Kaiser-Meyer-Olkin coefficient was 0.76 and Barlett sphericity test was 562.777 (P = 0.000). Turkish version of the Incontinence Quiz had a four-factor structure, with Eigenvalues ranging from 1.17 to 4.08. The Incontinence Quiz-Turkish version is a highly comprehensible, reliable and valid scale, which may be used to assess Turkish-speaking women's knowledge of and attitudes toward urinary incontinence.


Seasonal variation in fitness parameters in competitive athletes.
In many sports, training for successful competition has become virtually a year-round endeavour. To assist in better preparation, a competitor's year may be divided into phases such as off-season and in-season, indicating reduced or increased competition commitments, respectively. A number of studies have described the effects of seasons or periods of competition, training, detraining and reduced training on aspects of physical fitness. Depending on performance level, the type of sport and the fitness parameter in question, the swings in fitness variables reported may be as high as 18% from one season to another. In elite competitors, anaerobic parameters, heart frequencies, subcutaneous fat, flexibility and haemoglobin levels remain relatively unchanged throughout the year. Aerobic metabolism and muscular strength may demonstrate noticeable (mostly unfavourable) changes, and plasma hormonal levels normally follow changes in training intensities. Aspects related to long term fatigue and genetics, and to appropriate training are just a few explanations for these observations. It is still not known whether greater fitness gains attainable with longer off-season training programmes can be successfully maintained over the duration of the competition season. However, the consensus would seem to be that specialised training (based on technique and competition tactics only) is inadequate for fitness maintenance and/or improvements. This is perhaps supported by the general trends found in the literature regarding muscular strength: while supervised off-season conditioning programmes may result in significant improvements for both recreational and competitive athletes, no such changes are normally observed after competition seasons. These findings may reflect, amongst other factors, a lack of optimal training intensity to bring about strength increases during in-season periods. In novices and in athletes at low competitive levels, training seasons may lead to considerable functional improvements of the cardiorespiratory system, coupled with occasional increases in muscular strength and decreases in body fat. Relatively low fitness levels at the beginning of training have been put forward as an explanation for these improvements. Seasons of training and competition result in no significant changes in flexibility measurements. Similar changes to those found in novices and in athletes at low competitive levels may also be seen in children and adolescents engaged in sport, although their fitness improvements are consistent with normal patterns of growth and development. No differences have been identified between male and female athletes participating at different competition levels.


HLA-A, -B, and -DRB1 genotyping and haplotype frequencies among Filipinos living in the National Capital Region of the Philippines.
In this report, HLA polymorphisms (A, B, and DRB1 loci) were determined in 51 unrelated Filipinos. Molecular genotyping was carried out by sequence-based typing (Sanger sequencing). Data were analyzed by HLA-net GENE[RATE] tools. HLA-A, -B and -DRB1 genotype frequencies were at Hardy-Weinberg equilibrium. A*11, B*15, and DRB1*15 were the most frequent allele groups, while A*11-B*15-DRB1*15 was the most frequent HLA-A-B-DRB1 haplotype. HLA data are available in the Allele Frequencies Net Database (AFND: 3690) under the population name "Philippines National Capital Region".


Cryopreservation of zygotes and early cleaved human embryos.
Zygotes and 2- to 5-cell human embryos were frozen in 1,2-propanediol and sucrose; results of the first 50 cycles (45 patients) are presented. A total of 41 zygotes (17 attempts at thawing) were thawed, resulting in six singleton clinical pregnancies (15% per embryo; 35% per cycle), of which three delivered, one aborted, and two are ongoing. Fifty-seven cleaved embryos were thawed in 33 other cycles, resulting in four singleton and one twin pregnancy (11% per embryo; 15% per cycle), of which four delivered and one is ongoing. Depending on the cell stage, 61% to 81% of embryos survived cryostorage, but 2-cell embryos did not implant. One fifth of cryoinjury was due to the formation of cracks in the zona pellucida. The incidence of implantation was not enhanced when more than one freeze/thawed embryo was replaced, most pregnancies being obtained from single embryo replacements. At least 8% more births are expected in addition to conventional in vitro fertilization methods when the current policy of replacing three fresh embryos and freezing the remainder using this technique is applied. This method will result in two to four times more pregnancies per spare embryo, compared with other cryopreservation methods using older embryos.


Suspected or known neonatal sepsis and neurodevelopmental delay by 5 years.
Evaluate impact of known and suspected neonatal sepsis in the term and preterm infant on neurodevelopmental delay by 5 years. Included infants were born in 2009-2010 and followed for 5 years. Diagnostic codes and at least 5 days of antibiotic use identified suspected sepsis. Laboratory results confirmed known sepsis. Diagnostic codes stratified developmental delay by sub-type. Logistic regression analysis determined odds of developmental delay for sepsis and suspected sepsis. Of 65,938 included infants, 190 had sepsis and 3449 had suspected sepsis. After adjustment for known developmental risk factors, sepsis and suspected sepsis were associated with increased risk for any developmental delay, (1.48 (1.05-2.09) and 1.09 (1.01-1.18)), respectively, and multiple developmental delay sub-types. Neonatal sepsis and suspected sepsis are associated with neurodevelopmental delay by 5 years of age.


A simple and flexible model to calculate annual merit raises for health sciences faculty.
The objective of this study was to develop and implement a simple and flexible mathematical model to generate merit-based salary increases as a percentage of the faculty base salaries, with the flexibility to choose the range of merit raises. Annual faculty performance scores, faculty base salaries, and available salary increase pool were used in a relatively simple linear model to determine the individual faculty merit raises as a percentage of their base salary. The core model allows the selection of a slope value that determines how steeply the merit raise changes with a change in the performance score. The application of the method to different scenarios, including random and non-random distribution of salaries and performance scores, was also tested. More advanced versions of the core model, where the slope value is calculated based on various criteria, are presented in an appendix. The models were incorporated into spreadsheets, which automatically calculate percent merit raises for different input scenarios. The developed method successfully estimates percent merit raises for individual faculty to precisely match the available merit pool fund. Additionally, merit raises simulated for scenarios with different slopes indicate that the range of distribution of percent merit raise is directly proportional to the slope, i.e., doubling the slope doubles the difference in the percent merit raises for the faculty with the lowest and highest performance scores. The application of the method to different scenarios indicates that the method is robust and independent of the available merit raise pool or distribution patterns of the salaries and performance scores among faculty. Faculty merit raises may be easily calculated using a relatively simple model, which may be applied to a variety of cases where flexibility in the degree of distribution of raises is desired.


Hidden food allergens.
This review summarizes recent advances and findings in the area of 'hidden' food allergens, i.e. allergenic foods that can either contaminate other foods, or be 'disguised' as part of a food, and cause allergic reactions. Newly emerging allergenic foods of increasing importance, recently developed methods for the detection of allergenic residues, the potential allergenicity of genetically engineered foods, and some unexpected sources of food allergens are described.


Antiarrhythmic activity of four pteridine compounds in ouabain intoxication.
The antiarrhythmic effects of 4 pteridine analogues, 2 of which are potassium-sparing diuretics, triamterene (2, 4, 7-triamino-6-phenylpteridine) and [2-phenyl-4, 7 diaminopteridine-6-(N-diethylaminoethyl) carboxamide] and 2 of which have no diuretic effects [2-phenyl-4, 7-diaminopteridine-6-(N-2-hydroxyethyl) carboxamide], on ouabain-induced ventricular tachycardia in intact pentobarbital-anesthetized dogs were investigated. Ouabain was given as a continuous infusion 2 mug/kg/min intravenously until 5 min after the onset of a sustained ventricular tachycardia. It was found that both 6-(N-dimethylaminopropyl) and 6-(N-diethylaminoethyl) carboxamide derivates of the pteridine had a significant protective effect against ouabain-induced ventricular tachycardia in dogs that had been pretreated with a dose of 5 mg/kg intravenously. At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain-induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia.


Oxidative DNA damage is associated with intense noise exposure in the rat.
Increasing evidence suggests that noise-induced hearing loss may be reduced or prevented with antioxidant therapy. Biochemical markers of reactive oxygen species (ROS)-induced damage can help elucidate possible treatment timing constraints. This study examined the time course of ROS damage following a 2-h, broad-band noise exposure resulting in permanent threshold shift in 35 Long-Evans rats. Cochlea, brain, liver, serum and urine were analyzed at 1, 3, 8, 72, and 672 h (28 days) after exposure. Oxidative DNA damage was assessed by measuring 8-hydroxy-2'-deoxyguanosine (8OHdG) by high performance liquid chromatography with electrochemical detection. Lipid peroxidation was measured via the thiobarbituric acid-reactive substances (TBARS) colorimetric assay for detection of aldehydes (e.g., malondialdehyde). Auditory brainstem response and distortion product otoacoustic emission thresholds showed progressive elevation for the 3- and 8-h groups, then notable recovery for the 72-h group, and some worsening for the 672-h group. 8OHdG was significantly elevated in cochlea in the 8-h group, and in brain and liver for the 72-h group. TBARS were significantly elevated in serum for the 72-h group. Based upon oxidative DNA damage present in cochlea following intense noise, we postulate that the first 8 h following exposure might be a critical period for antioxidant treatment.


GDNF is important for striatal organization and maintenance of dopamine neurons grown in the presence of the striatum.
Glial cell line-derived neurotrophic factor (GDNF) exerts neuroprotective and neurorestorative effects on neurons and GDNF plays a significant role in maintenance of the dopamine neurons utilizing grafting to create a nigrostriatal microcircuit of Gdnf knockout (Gdnf(-/-)) tissue. To further evaluate the role of GDNF on organization of the nigrostriatal system, single or double grafts of ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) with mismatches in Gdnf genotypes were performed. The survival of single grafts was monitored utilizing magnetic resonance imaging (MRI) and cell survival and graft organization were evaluated with immunohistochemistry. The results revealed that the size of VM single grafts did not change over time independent of genotype, while the size of the LGE transplants was significantly reduced already at 2 weeks postgrafting when lacking GDNF. Lack of GDNF did not significantly affect the survival of tyrosine hydroxylase (TH)-positive neurons in single VM grafts. However, the survival of TH-positive neurons was significantly reduced in VM derived from Gdnf(+/+) when co-grafted with LGE from the Gdnf(-/-) tissue. In contrast, lack of GDNF in the VM portion of co-grafts had no effect on the survival of TH-positive neurons when co-grafted with LGE from Gdnf(+/+) mice. The TH-positive innervation of co-grafts was sparse when the striatal co-grafts were derived from the Gdnf(-/-) tissue while dense and patchy when innervating LGE producing GDNF. The TH-positive innervation overlapped with the organization of dopamine and cyclic AMP-regulated phosphoprotein-relative molecular mass 32,000 (DARPP-32)-positive neurons, that was disorganized in LGE lacking GDNF production. In conclusion, GDNF is important for a proper striatal organization and for survival of TH-positive neurons in the presence of the striatal tissue.