Vaccination Using Gene-Gun Technology.
DNA vaccines against infection with Plasmodium have been highly successful in rodent models of malaria and have shown promise in the very limited number of clinical trials conducted so far. The vaccine platform is highly attractive for numerous reasons, such as low cost and a very favorable safety profile. Gene gun delivery of DNA plasmids drastically reduces the vaccine dose and does not only have the potential to make vaccines more accessible and affordable, but also simplifies (a) the testing of novel antigens as vaccine candidates, (b) the testing of antigen combinations, and (c) the co-delivery of antigens with molecular adjuvants such as cytokines or costimulatory molecules. Described in this chapter are the preparation of the inoculum (i.e., DNA plasmids attached to gold particles, coating to the inside of plastic tubing also referred to as gene gun "bullets" or cartridges), the gene gun vaccination procedure, and the challenge of mice with Plasmodium berghei parasites to test the efficacy of the experimental vaccine.


Objectification of cranial vault correction for craniosynostosis by three-dimensional photography.
Correction of craniosynostosis is necessary in predominant cases. Surgical planning usually requires a preoperative CT to estimate the bony and intracerebral structures. A postoperative CT scan would involve a significant dose of radiation, which carries an elevated risk of malignant tumor development in later life. This study was performed to demonstrate the quality of three-dimensional (3D) photogrammetry when objectifying perioperative changes in craniofacial surgery. Twenty-eight patients with different premature craniosynostoses were analyzed photogrammetrically before and after surgical correction. 3D changes in cranial distances, symmetry and volumes were evaluated. A statistical covariance analysis excluded changes in cranial shape caused by physiological head growth. The Cephalic Index in Scaphocephaly changed from 75.1% to a median value of 77.4%. The anterior symmetry ratio for coronal synostoses improved from 0.943 to 0.949 (a value of 1.0 represents perfect symmetry). The posterior symmetry ratio improved from 0.733 to 0.808 postoperatively in one single lambdoidal synostosis. In trigonocephaly, the median anterior skull volume rose from 528 to 601 ml. 3D photogrammetry has great potential to track and objectify the clinical course of surgical correction of craniosynostoses. Craniofacial changes become highly reproducible and demonstrate clinical utility based on this technology.


An improved procedure for flow-based turbidimetric sulphate determination based on a liquid core waveguide and pulsed flows.
An improved flow-based procedure is proposed for turbidimetric sulphate determination in waters. The flow system was designed with solenoid micro-pumps in order to improve mixing conditions and minimize reagent consumption as well as waste generation. Stable baselines were observed in view of the pulsed flow characteristic of the systems designed with solenoid micro-pumps, thus making the use of washing solutions unnecessary. The nucleation process was improved by stopping the flow prior to the measurement, thus avoiding the need of sulphate addition. When a 1-cm optical path flow cell was employed, linear response was achieved within 20-200mgL(-1), described by the equation S=-0.0767+0.00438C (mgL(-1)), r=0.999. The detection limit was estimated as 3mgL(-1) at the 99.7% confidence level and the coefficient of variation was 2.4% (n=20). The sampling rate was estimated as 33 determinations per hour. A long pathlength (100-cm) flow cell based on a liquid core waveguide was exploited to increase sensitivity in turbidimetry. Baseline drifts were avoided by a periodical washing step with EDTA in alkaline medium. Linear response was observed within 7-16mgL(-1), described by the equation S=-0.865+0.132C (mgL(-1)), r=0.999. The detection limit was estimated as 150microgL(-1) at the 99.7% confidence level and the coefficient of variation was 3.0% (n=20). The sampling rate was estimated as 25 determinations per hour. The results obtained for freshwater and rain water samples were in agreement with those achieved by batch turbidimetry at the 95% confidence level.


Observational study of peripheral intravenous catheter outcomes in an internal medicine department.
In elderly patients hospitalised in internal medicine departments, risk factors, preferable placement area and methods of securement of short peripheral venous catheters (SPVC) a unclear. To determine the incidence and risk factors of adverse events using a transparent bordered dressing for securement in the dorsum of the hand or cubital fossa in consecutive patients hospitalised in an internal medicine department. In a prospective observational study of patients admitted to a regional hospital with a SPVC, the dependent variable was the need to replace the catheter because of an adverse event (phlebitis, accidental removal, infiltration/occlusion). The independent variables were age, gender, disorientation, placement area, intravenous antibiotic therapy and indwelling time. Risk factors were determined by Cox regression model analysis. There were 709 catheters placed in 499 patients. Per catheter placed the mean age was 75 ± 17 years. Accidental removal, infiltration/obstruction and phlebitis occurred in 21.5, 16.2 and 15.0 events per 1000 days respectively. There was a significantly increased risk on Day 3 compared to Days 2 and 4. An older age, intravenous antibiotics and disorientation increased the hazard for accidental displacement, whereas phlebitis was associated only with intravenous antibiotics and occlusion/infiltration only with age. The observed low rates of adverse events suggests that placement in the dorsum of the hand or cubital fossa secured by a transparent dressing is acceptable. It is important to consider the indwelling catheter time when studying adverse events, and elderly patients, disoriented patients and/or patients receiving intravenous antibiotics deserve special attention.


Metabolic engineering of Lactobacillus casei for production of UDP-N-acetylglucosamine.
UDP-sugars are used as glycosyl donors in many enzymatic glycosylation processes. In bacteria UDP-N-acetylglucosamine (UDP-GlcNAc) is synthesized from fructose-6-phosphate by four successive reactions catalyzed by three enzymes: Glucosamine-6-phosphate synthase (GlmS), phosphoglucosamine mutase (GlmM), and the bi-functional enzyme glucosamine-1-phosphate acetyltransferase/N-acetylglucosamine-1-phosphate uridyltransferase (GlmU). In this work several metabolic engineering strategies, aimed to increment UDP-GlcNAc biosynthesis, were applied in the probiotic bacterium Lactobacillus casei strain BL23. This strain does not produce exopolysaccharides, therefore it could be a suitable host for the production of oligosaccharides. The genes glmS, glmM, and glmU coding for GlmS, GlmM, and GlmU activities in L. casei BL23, respectively, were identified, cloned and shown to be functional by homologous over-expression. The recombinant L. casei strain over-expressing simultaneously the genes glmM and glmS showed a 3.47 times increase in GlmS activity and 6.43 times increase in GlmM activity with respect to the control strain. Remarkably, these incremented activities resulted in about fourfold increase of the UDP-GlcNAc pool. In L. casei BL23 wild type strain transcriptional analyses showed that glmM and glmU are constitutively transcribed. By contrast, glmS transcription is down-regulated with a 21-fold decrease of glmS mRNA in cells cultured with N-acetylglucosamine as the sole carbon source compared to cells cultured with glucose. Our results revealed for the first time that GlmS, GlmM, and GlmU are responsible for UDP-GlcNAc biosynthesis in lactobacilli.


Correlations between MTP and ROS Levels of Peripheral Blood Lymphocytes and Readmission in Patients with Chronic Heart Failure.
Peripheral blood lymphocytes exhibit changes that parallel those in failing cardiomyocytes. We hypothesised that mitochondrial transmembrane potential (MTP) and reactive oxygen species (ROS) levels of lymphocytes are associated with serum NT-proBNP and short-term prognosis in patients with chronic heart failure (CHF). Fifty-four CHF patients and 30 controls were enrolled in this prospective study. Mitochondrial transmembrane potential and ROS levels of lymphocytes were evaluated by flow cytometry and reported as the JC-1 fluorescence ratio and DCF fluorescence intensity, respectively. Serum NT-proBNP levels and biochemical parameters were also examined. All the participants received follow-up to evaluate clinical end-points after eight months. Chronic heart failure patients had higher levels of DCF fluorescence intensity of lymphocytes and serum NT-proBNP, as well as lower levels of JC-1 fluorescence ratios compared with those of controls (all P<0.05). A closer relationship was found between Lg(DCF fluorescence intensity of lymphocytes) or JC-1 fluorescence ratio of lymphocytes and Lg(NT-proBNP) (both P<0.05) in CHF patients. During the eight-month follow-up period, 14 CHF patients (25.9%) were readmitted for severe HF, but none died. A logistic regression analysis showed that both ROS level and MTP of the lymphocytes were independent predictors (B=7.03, P=0.006; B= - 0.32, P=0.029, respectively) of readmission of CHF patients. In CHF patients at low risk, MTP and ROS levels of the lymphocytes showed a significant change that is associated with serum NT-proBNP and patient readmission.


Phytoestrogens and phytoestrogen metabolites differentially modulate immune parameters in human leukocytes.
Phytoestrogens (PE) including isoflavones and lignans, are a group of substances of plant origin which can act as estrogen agonists or antagonists. While the immunomodulatory effects of isoflavones have been studied, little is known about the impact of lignans and other PE metabolites on the immune system. The aim of the present study was to assess whether PE and their metabolites modulate human leukocyte functions in vitro. We investigated the effects of genistein, daidzein, matairesinol, and secoisolariciresinol, including metabolites such as equol, O-desmethylangolensin, enterodiol, and enterolactone on natural killer cell activity, proliferation, cytokine secretion, as well as apoptotic and necrotic rate of human leukocytes. Genistein, daidzein, and its metabolite equol were the most potent inhibitors of leukocyte functions. Ten micromolars of genistein decreased proliferation, lytic activity of natural killer cells, and cytokine secretions. The latter proved to be the most sensitive marker of immune functions. Lignans and their metabolites had minor effects on the immune system. The antiestrogens Tamoxifen and Fulvestrant did not block the inhibition of cytokine secretion by genistein and equol. In conclusion, while physiological concentrations of isoflavones have minor effects on cytokine secretion, lignans including their major metabolites do not modulate human leukocyte functions in vitro.


Quality of life with antihypertensive medication.
Mild to moderate hypertension is often an asymptomatic disease, but it is strongly associated with increased risk of cardiovascular, renal and central nervous system morbidity and mortality. Because of the chronic nature of the disease, treatment involves the reduction of blood pressure without functional impairment. Since the adverse effects of pharmacological agents greatly reduce compliance, it is of prime importance not only to control blood pressure but also to preserve the patient's quality of life. Previous studies have demonstrated the adverse effects observed in patients treated with antihypertensive medications, but few have attempted to analyse the impact on the quality of life. Therefore, a multicentre trial was carried out to investigate the quality of life in hypertensive patients before and after treatment with the beta-adrenergic blocker propranolol or the calcium channel blocker nitrendipine. Both treatments were effective in the reduction of blood pressure. Preliminary results indicated that patients taking nitrendipine were more vigorous (P less than 0.01) and less fatigued (P less than 0.05) than those taking propranolol. In addition, patients in the propranolol group perceived a decrease in a partner's sexual satisfaction (P less than 0.05). No other major negative impacts on the quality of life were caused by either drug. These preliminary data indicate that nitrendipine and propranolol reduced blood pressure equally, but that nitrendipine caused less of a negative impact on the quality of life than propranolol.


Evaluation of the effectiveness and comfort of incisive nerve anesthesia given inside or outside the mental foramen.
Thirty volunteer subjects were given bilateral injections of one-half carpule of 2% Xylocaine with 1:100,000 epinephrine to anesthetize the incisive nerve. Injections were given either inside or outside the mental foramen. Success (80/80 reading) and duration of anesthesia were verified with the Analytic Technology pulp tester. Pain and preference for either injection type were evaluated via questionnaire. The mental foramen could be located in 1 min 56.6% of the time. There was a significantly greater chance of success for injections given inside the foramen for the second bicuspid (p = 0.0422) and the canine (p = 0.015). There was no statistically significant difference in success for either type injection for the first bicuspid (p = 0.184). There was no significant difference in duration of anesthesia whether given inside or outside the foramen and no difference in pain of injection with either type. Patients had no clear-cut preference for either injection type.


[The role of specialized treatment in school's substance use and misuse].
As it is the case in other European countries, substance use and misuse is increasing among teenagers in Switzerland. This fact is worrying, and requires the application of specific primary and secondary prevention programs to this population, particularly in schools. The pilot-study DEPART makes available to network professionnals, as well as to adolescents (12 to 20 years old) and their family, an interdisciplinary team that provides specific support for substance use and misuse among teenagers. Thus, this pilot-study, which is currently being carried out in and around the city of Lausanne, aims at the early identification and treatment of adolescents in schools (secondary prevention).


Fish oil fatty acid esters of phytosterols alter plasma lipids but not red blood cell fragility in hamsters.
In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil FA, plant sterols have recently been esterified to fish oil n-3 PUFA. The objective of this study was to determine the effects of plant sterols esterified to n-3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters were fed diets varying in cholesterol and plant sterol content: (i) Non-cholesterol (semipurified diet with no added cholesterol or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols), or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols). The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P = 0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters fed nonesterified plant sterols (P < 0.0001). Despite higher (P < 0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of plant sterols exert no detrimental effect on erythrocyte fragility.


Sensory innervation of the rat portal vein and the hepatic artery.
Several neuroanatomical and neurophysiological experiments suggest that the hepatic portal vein is not only richly innervated with sympathetic efferents, but also it is an important source of afferent information. By combining retrograde tracing (with True Blue as a marker) and immunological techniques, the cell bodies for the substance P-containing nerves that surround the portal vein and the hepatic artery of the rat have been localized to the spinal sensory ganglia (T8-T13). Since dorsal root rhizotomy abolished all substance P immunoreactive material from nerve fibres that surround these blood vessels, and since no double-labelled cells were detected in the nodose ganglia, an exclusive spinal origin for the substance P-containing sensory nerves is suggested.


Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells.
Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBChR-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study on the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBChR-8-5 cells or anti-MDR activity.


Association between 11beta-hydroxysteroid dehydrogenase type 1 gene polymorphisms and metabolic syndrome in Bosnian population.
The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of the hormonally inactive cortisone to active cortisol, thus facilitating glucocorticoid receptor activation in target tissues. Increased expression of 11beta-HSD1 in adipose tissue has been associated with obesity and insulin resistance. In this study, we investigated the association of two 11beta-HSD1 gene (HSD11B1) polymorphisms with the metabolic syndrome (MetS) and its characteristics in the Bosnian population. The study included 86 participants: 43 patients diagnosed with MetS and 43 healthy controls. Subjects were genotyped for two HSD11B1 gene polymorphisms: rs846910: G > A and rs45487298: insA, by the high resolution melting curve analysis. Genotype distribution and an influence of genotypes on clinical and biochemical parameters were assessed. There was no significant difference in the mutated allele frequencies for the two HSD11B1 gene polymorphisms between MetS patients and controls. In MetS patients, no significant associations between disease-associated traits and rs45487298: insA were found. Regarding rs846910: G > Avariant, heterozygous patients (G/A) had significantly lower systolic (P = 0.017) and diastolic blood pressure (P = 0.015), lower HOMA-IR index (P = 0.011) and higher LDL-cholesterol levels (P = 0.049), compared to the wild-type homozygotes. In the control group, rs45487298: insA polymorphism was associated with lower fasting plasma insulin levels (P = 0.041), lower homeostasis model assessment insulin resistance (HOMA-IR) index (P = 0.041) and lower diastolic blood pressure (P = 0.048). Significant differences between rs846910: G > A genotypes in controls were not detected. Haplotype analysis confirmed the association of rs45487298: insA with markers of insulin resistance in the control subjects. Our results indicate that a common rs45487298: insA polymorphism in HSD1181 gene may have a protective effect against insulin resistance.


Lung recruitment maneuvers in acute respiratory distress syndrome.
In the experimental setting, repeated derecruitments of the lungs of ARDS models accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate the injury. In the clinical setting, recruitment manuevers that use a continuous positive airway pressure of 40 cmH2O for 40 secs improve oxygenation in patients with early ARDS who do not have an impairment in the chest wall. High intermittent positive end-expiratory pressure (PEEP), intermitent sighs, or high-pressure controlled ventilation improves short-term oxygenation in ARDS patients. Both conventional and electrical impedance thoracictomography studies at the clinical setting indicate that high PEEP associated with low levels of pressure control ventilation recruit the collapsed portions of the ARDS lungs and that adequate PEEP levels are necessary to keep the ARDS lungs opened allowing a more homogenous ventilation. High PEEP/low tidal volume ventilation was seen to reduce inflammatory mediators in both bronchoalveolar lavage and plasma, compared to low PEEP/high tidal volume ventilation, after 36 hours of mechanical ventilation in ARDS patients. Recruitment maneuvers that used continuous positive airway pressure levels of 35-40 cmH2O for 40 secs, with PEEP set at 2 cmH2O above the lower inflection point of the pressure-volume curve, and tidal volume < 6 mL/kg were associated with a 28-day intensive care unit survival rate of 62%. This contrasted with a survival rate of only 29% with conventional ventilation (defined as the lowest PEEP for acceptable oxygenation without hemodynamic impairment with a tidal volume of 12 mL/kg), without recruitment manuevers (number needed to treat = 3; p < 0.001). In the near future, thoracic computed tomography associated with high-performance monitoring of regional ventilation may be used at the bedside to determine the optimal mechanical ventilation of the ARDS keeping an opened lung with a homogenous ventilation.


Geographic enrolment of the top 100 in athletics running events from 1996 to 2012.
It is widely accepted in the literature that athletes of West African origins achieve the best sprint performances, while athletes originating from East Africa are the most efficient at long distances. So far, no study has measured the evolution of these groups' contribution from 100 m to the marathon. Speed, morphology and geographic origin of the top 100 male and female athletes (from 100 m to the marathon) were collected and analyzed over the 1996-2012 period. The amount of male sprinters (100, 200 and 400 m) originating from West Africa increased from 57.7% in 1996 to 72.3% in 2012, while female sprinters from West Africa increased from 55% to 65% over the same period. This contribution gradually increases from 400 m to 100 m for both sexes. For long-distance runs (3000 m, 10,000 m and marathon), male athletes from East Africa represented 32% in 1996 ; this proportion increased to 65.7% in 2012. It also increased over the same period from 9% to 39% for women. In addition, male and female sprinters originating from West Africa have a significantly higher Body Mass Index (BMI, P<0.05) than athletes of other geographic origin. Conversely, long distances runners' with an East African origin have a significantly lower BMI (P<0.05). Running best performances are dominated by a few groups including runners with West African ancestry for the sprint distances and East African runners for the long distances. This dominance strengthened from 1996 to 2012 for both sexes in parallel with a reduction of Caucasian and Asian athletes contribution and in relation to muscle mass repartition.


Cloning and expression analysis of chicken phospholipid-hydroperoxide glutathione peroxidase.
Phospholipid-hydroperoxide glutathione peroxidase (GPX4 or PHGPX) is a unique selenium dependent glutathione peroxidase that reduces phospholipid, cholesterol, and cholesteryl ester hydroperoxides. Phospholipid-hydroperoxide glutathione peroxidase has been shown to exist as both a 197 amino acid mitochondrial targeting protein and as a 170 amino acid non-mitochondrial protein. The cDNA encoding the non-mitochondrial chicken GPX4 (cGPX4) has been isolated from an immortalized DF-1 chicken embryonic fibroblast (CEF) cell line cDNA library. The nucleotide sequence of cGPX4 was 802 bp in length with an open reading frame (ORF) that encoded 170 amino acids but lacked the N-terminal domain that encoded the mitochondrial leader sequence (MLS). Chicken non-mitochondrial GPX4 was highly expressed in brain and stromal tissues. Surprisingly, it was found that ovarian stromal tissue cGPX4 expression is regulated quite differently according to the reproductive status of the bird, suggesting that GPX4 may play an important role in reproduction in response to steroid hormones, in addition to its general antioxidant functions.


Self-reported sleep quality and depression in post myocardial infarction patients attending cardiology outpatient clinics in Oman.
This study aimed to examine the sleep quality and prevalence of depression in post myocardial infarction patients attending cardiology outpatient clinics of selected hospitals in Oman. A descriptive cross-sectional design was used to collect data from patients (n = 180) who were at least 4 weeks post myocardial infarction diagnosis and receiving follow-up care in the outpatient clinic. The Arabic version of the Pittsburgh Sleep Quality Index and Patient Health Questionnaire-9 were used to assess sleep quality and depressive symptoms, respectively. The sample mean age was 62.0 ± 11.3 years. Poor sleep quality affected 61.1% of the participants. The significant predictors of poor sleep quality were gender (P ≤ 0.05), body mass index (P ≤ 0.05), and self-reported regular exercise (P ≤ 0.01). The most impacted domains of sleep quality were sleep latency, sleep duration, and sleep disturbances. The prevalence of major depression was low (5%) and the rate of re-infarction was 27.2%. The prevalence of minimal to mild major depression with a potential of transitioning into major depression overtime was very high. Self-reported regular exercise (P ≤ 0.01) was the only significant predictor of depressive symptoms. The sleep quality of post myocardial infarction patients was poor and the prevalence of depression was low. There was no significant relationship between sleep quality or depression with re-infarction.


Juvenile hormone III, hydroprene and a juvenogen as soldier caste differentiation regulators in three Reticulitermes species: potential of juvenile hormone analogues in termite control.
The efficacy of juvenile hormone III (JH III) and two JH-mimicking compounds was compared in laboratory experiments with Reticulitermes lucifugus (Rossi), R. santonensis Feytaud and R. virginicus (Banks). Induction of presoldier, soldier and/or soldier-worker intercaste differentiation was taken as positive response to the treatment. The novel juvenogen, a fatty acid ester of a juvenoid alcohol, induced greatest soldier differentiation in all species tested, followed by hydroprene. JH III was less effective. Representatives of three Reticulitermes species showed similar trends in soldier induction rates. Differences in mortality in treatments of termites of the same species from different colonies with the same compound were observed and evidently were caused by differences in the conditions of respective colonies.


Structure, synthetic methods, magnetic properties and biomedical applications of ferrofluids.
This paper is aimed at conducting a survey of the synthetic methods and magnetic properties of nanoparticles as ferrofluids used in biomedicine. As compared with other works in the field, the distinctive feature of the current work is the systematic study of recent advances in ferrofluids utilized in hyperthermia and magnetic resonance imaging (MRI). The most important feature for application of ferrofluids is super-paramagnetic behavior of magnetic cores with relatively high saturation magnetization. Although Fe3O4 nanoparticles have traditionally been used in medicine; the modified Mn-ferrite has recently received special attention due to its higher saturation magnetization and r2-relaxivity as a contrast agent in MRI. Co-ferrite nanoparticles are also good candidates for hyperthermia treatment because of their high coercivity and magnetocrystalline anisotropy. The thermal decomposition and hydrothermal methods are good candidates for obtaining appropriate super-paramagnetic particles.


Outcomes for acute type A aortic dissection: effects of previous cardiac surgery.
The standard of performing emergent surgical repair for acute aortic dissection type A has been questioned in patients with previous cardiac surgery. The effects of previous cardiac surgery on the presentation and operative outcome of these patients is understudied. Between 1998 and 2010, 190 patients were operated on for acute type A aortic dissection; there were 159 first cardiac operations (FCO) and 31 redo operations (REDO). Stepwise logistic regression analysis identified independent predictors of hospital mortality. Propensity score-matching yielded 31 FCOs who matched the REDOs with respect to age, sex, hypertension history, chronic obstructive pulmonary disease, and renal failure. The presentation, operative outcome, and complications were compared between the two groups. Hospital mortality rate was 16.8% (32 of 190). Regression analysis identified mental status change (odds ratio [OR] = 5.9), hypertension (OR = 4.6), concomitant coronary artery bypass grafting (OR = 3), reoperation (OR = 2.9), and age of 70 years or older (OR = 2.8) as predictors of hospital mortality. After matching there was no difference between REDO and FCO groups in the presenting symptoms, but REDOs had a higher incidence of aortic rupture (29% [9 of 31] versus 3.2% [1 of 31]; p = 0.012). Cardiac tamponade was present in 3.2% (1 of 31) of REDOs versus 16.1% of FCOs (5 of 31; p = 0.195). Patients in the REDO group required more intraoperative blood transfusion, and had longer cardiopulmonary bypass time. Major complications occurred similarly between the two groups, except REDOs had worse renal function and a higher rate of sudden cardiac arrest (14.3% [4 of 28] versus 0; p = 0.045). Although hospital mortality is higher among REDOs, it is still lower than the reported mortality for medical management, and major complications occurred at a rate similar to that of FCOs; hence, emergent surgery remains the prudent treatment.


Extracellular cysteine disulfide bond break at Cys122 disrupts PIP2-dependent Kir2.1 channel function and leads to arrhythmias in Andersen-Tawil Syndrome.
Andersen-Tawil Syndrome Type 1 (ATS1) is a rare heritable disease caused by mutations in the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys122-to-Cys154 disulfide bond in the Kir2.1 channel structure is crucial for proper folding, but has not been associated with correct channel function at the membrane. We tested whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing the open state of the channel. We identified a Kir2.1 loss-of-function mutation in Cys122 (c.366 A>T; p.Cys122Tyr) in a family with ATS1. To study the consequences of this mutation on Kir2.1 function we generated a cardiac specific mouse model expressing the Kir2.1C122Y mutation. Kir2.1C122Y animals recapitulated the abnormal ECG features of ATS1, like QT prolongation, conduction defects, and increased arrhythmia susceptibility. Kir2.1C122Y mouse cardiomyocytes showed significantly reduced inward rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking ability and localization at the sarcolemma and the sarcoplasmic reticulum. Kir2.1C122Y formed heterotetramers with wildtype (WT) subunits. However, molecular dynamic modeling predicted that the Cys122-to-Cys154 disulfide-bond break induced by the C122Y mutation provoked a conformational change over the 2000 ns simulation, characterized by larger loss of the hydrogen bonds between Kir2.1 and phosphatidylinositol-4,5-bisphosphate (PIP2) than WT. Therefore, consistent with the inability of Kir2.1C122Y channels to bind directly to PIP2 in bioluminescence resonance energy transfer experiments, the PIP2 binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch-clamping the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing PIP2 concentrations. The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential to channel function. We demonstrated that ATS1 mutations that break disulfide bonds in the extracellular domain disrupt PIP2-dependent regulation, leading to channel dysfunction and life-threatening arrhythmias.


An accurate and rapid inflation device for pneumatic cuffs.
A simple and inexpensive semiautomatic device was constructed and calibrated for rapid and accurate inflation of limb pneumatic cuffs. An automatic timer was designed for use in cuff inflation requiring repetition or exact timing.


Safety and efficacy of superior turbinate biopsies as a source of olfactory epithelium appropriate for morphological analysis.
There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function. In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence. Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants. Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.


AKT-dependent and -independent pathways mediate PTEN deletion-induced CNS axon regeneration.
Phosphatase and tensin homolog (PTEN) acts as a brake for the phosphatidylinositol 3-kinase-AKT-mTOR complex 1 (mTORC1) pathway, the deletion of which promotes potent central nervous system (CNS) axon regeneration. Previously, we demonstrated that AKT activation is sufficient to promote CNS axon regeneration to a lesser extent than PTEN deletion. It is still questionable whether AKT is entirely responsible for the regenerative effect of PTEN deletion on CNS axons. Here, we show that blocking AKT or its downstream effectors, mTORC1 and GSK3β, significantly reduces PTEN deletion-induced mouse optic nerve regeneration, indicating the necessary role of AKT-dependent signaling. However, AKT is only marginally activated in PTEN-null mice due to mTORC1-mediated feedback inhibition. That combining PTEN deletion with AKT overexpression or GSK3β deletion achieves significantly more potent axonal regeneration suggests an AKT-independent pathway for axon regeneration. Elucidating the AKT-independent pathway is required to develop effective strategies for CNS axon regeneration.


Prevalence of malocclusion and orthodontic treatment needs among 12-15 years old school children in Patna, Eastern India.
The people around the world are concerned about the aesthetic oral-facial structures as it is more important in interpersonal interactions and dictates vocal, physical, and emotional communication. The present study was conducted to assess the severity of malocclusion and orthodontic treatment need among 12-15-year-old school children of Patna, Eastern India. A cross-sectional study design was used to assess the severity of malocclusion using Dental Aesthetic Index (DAI) index among 12-15-year-old school-going children. A specially prepared and pretested format, exclusively designed for recording all the required and relevant general information and other clinical findings was used in the study. The sample size consisted of 902 children from middle schools (Government and Private) in Patna. Chi-square test was done for the categorical data to compare differences between two independent groups. Data were presented as Mean ± SD and "P" value of less than 0.05 was accepted as indicating significance. Around 5.3% had a DAI score of ≤25 which signifies that there is "no abnormality or may have minor malocclusion"; 15.3% had a DAI score of 26-30 which signifies that there is "definite malocclusion"; 6% had a DAI score of 31-35 which signifies that there is "severe malocclusion" and 4% had a DAI score of ≥36 which signifies that there is "very severe or handicapping malocclusion". The finding was more commonly seen among 14 years age group. It can be concluded from the present study that the prevalence of malocclusion is reasonable high in this part of the region, and it is very important to bring in more awareness at the school level as primary prevention can be the most effective tool in control this menace.


Pulmonary hypertension and systemic hypotension as limitations to exercise in chronic heart failure.
The authors have previously shown that the resistance ratio (RR) is increased in patients with congestive heart failure (CHF), and that the patients with the highest RRs have an increased mortality. The authors hypothesized that CHF patients with the lowest maximum oxygen consumption and the most impaired Weber functional classification would have the highest RR. Eighty-four patients with chronic CHF underwent seated ergometric exercise to exhaustion. Hemodynamic and respiratory gas exchange parameters were measured at rest and peak exercise. Weber functional classifications (A through E) were determined from maximum oxygen consumptions, and patients were stratified to evaluate the RR. The RR increased progressively across Weber classifications at rest (A vs E; P < .001) and with maximum exercise (A vs E; P < .002). At rest, elevation in the RR was related to an increase in the pulmonary pressure gradient (A vs E; P < .002) secondary to increased mean pulmonary arterial pressures. With peak exercise, this elevation was secondary to a decrease in the systemic pressure gradient (A vs E; P < .001). Further analysis revealed that the progressive decrease in the systemic pressure gradient was due to progressively lower mean arterial pressures (A vs E; P < .001). Elevation of the RR, both at rest and peak exercise, predicts a more impaired exercise functional status in patients with chronic CHF. Increases in the RR at peak exercise were related to decreases in mean arterial pressure, most likely limiting perfusion to exercising skeletal muscle. The mechanism of poor exercise blood pressure response in these patients is unclear. Possible explanations include abnormal systemic baroreceptor function with inappropriate vascular adaptation, and a poor cardiac output response to a relative increase in right ventricular afterload in systemic vasodilation seen with exercise.


Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment.
To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.


Test-Retest Reliability of the Self-Reported Impairments in Persons With Late Effects of Polio (SIPP) Rating Scale.
A new 13-item rating scale, the Self-Reported Impairments in Persons with Late Effects of Polio (SIPP), has been developed. The SIPP has been analyzed using the Rasch method and has shown good construct validity and internal consistency. To establish its clinical utility, further evaluation of its psychometric properties is needed. To evaluate the test-retest reliability of the SIPP and to define limits for the smallest change that indicates a real change, both for a group of persons and a single individual. A postal survey. University Hospital. Fifty-one persons (31 men and 20 women; mean age, 72 years) with clinically verified late effects of polio. Not applicable. The participants completed the SIPP twice, 2 weeks apart. The response frequencies at test occasion 1 (T1) and test occasion 2 (T2) were calculated. Test-retest reliability was analyzed using the percentage agreement of each item, the intraclass correlation coefficient, and the mean difference between the test occasions (đ), together with the 95% confidence intervals for đ, the standard error of measurement, the smallest real difference, and a Bland-Altman plot. The percentage agreement (ie, the same scoring at both test occasions) was >70% for 10 of 13 items. The mean score (standard deviation) was 27.9 (5.7) points at T1 and 28.2 (6.0) points at T2, with no systematic difference between the test occasions. The intraclass correlation coefficient was 0.88, the standard error of measurement (the smallest change for a group of persons) was 2.0 points, and the smallest real difference (the smallest change for a single individual) was 5.6 points, respectively. The SIPP is a reliable rating scale in persons with late effects of polio and can be used to evaluate effects of rehabilitation interventions and changes of perceived impairments over time both for a group of persons and for a single individual.


Abdominal radical trachelectomy: a safe and feasible option for fertility preservation in developing countries.
This study aimed to report on a series of patients with early-stage cervical cancer who underwent an abdominal radical trachelectomy to preserve their fertility. We performed a retrospective review of all patients who underwent an abdominal radical trachelectomy in 2 centers of gynecologic oncology in Argentina. Data collected included patient's age, stage, histologic subtype, tumor grade, tumor size, evidence of lymph vascular space invasion, number of lymph nodes removed, perioperative complications, as well as oncologic and obstetrical outcomes. Thirty patients were selected for radical trachelectomy. Five of these patients were excluded from the study: 3 for compromised margins, 1 for lymph node involvement, and 1 for vesicovaginal space involvement. Twenty-five patients underwent the procedure and were included in this report. Median age was 31 years (range = 22-40 years). Nineteen patients had stage IB1, and 6 patients had stage IA2 cervical cancer. Median tumor size was 1.2 cm (range = 0.4-3.5 cm). Median number of pelvic lymph nodes removed was 21 (range = 11-33). Median surgical time was 240 minutes (range = 210-270 minutes), and median length of hospital stay was 3.5 days (range = 3-5 days). Estimated blood loss was 350 mL (range = 200-700 mL). No intraoperative complications were reported. There were 6 postoperative complications. Three patients (12%) were able to get pregnant spontaneously with 3 live births by cesarean delivery. No recurrences were reported with a median follow-up of 29.6 months. Abdominal radical trachelectomy with pelvic lymphadenectomy is a feasible procedure and a viable option for women wishing to preserve their fertility in developing countries.


The radiographic patterns of acute mycoplasma pneumonitis.
Twenty-two cases of serologically proven pulmonary mycoplasma infection have been reviewed. All showed abnormality on plain chest radiographs. A definitive diagnosis could not be made on initial or individual films. However, studies of sequential films enabled diagnostic patterns to be distinguished.


Failure of seminal plasma to enter the uterus and oviducts of the rabbit following artificial insemination.
Twelve adult does in estrus were artificially inseminated with 1 ml of semen from bucks that had received injections of 3H-thymidine 22 to 32 days previously. The ejaculates contained radioactive seminal plasma and unlabeled sperm. The reproductive tracts of the does were removed at selected intervals after insemination, divided into segments of no more than 300 mg, and processed for scintillation counting. Significant levels of radioactivity were never detected in any uterine or oviductal segment. The technique was capable of detecting as little as 1.5 X 10(-4) ml of semen in a segment. These results demonstrate that seminal plasma is not transported from the vagina into the uterus or oviducts in the rabbit, emphasizing the importance of the motility of spermatozoa in their passage to the site of fertilization.


Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.
The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity.


Delivering sensitive health care information: challenging the taboo of women's sexual health after pelvic radiotherapy.
The aim of this study was to elicit current practice with regard to the content and delivery of patient education for women undergoing pelvic radiotherapy. A 38-item questionnaire was sent to all radiotherapy departments (n=65) and a convenience sample of specialist gynaecological oncology nurses (n=166), with response rates of 62% (n=40) and 42% (n=52), respectively. Data analysis of 32 different patient education leaflets from individual cancer units, cancer networks and vaginal dilator manufacturers was conducted. Content was evaluated on the inclusion and accuracy of the key knowledge women should receive before completing pelvic radiotherapy. Patient education focused on the technical aspects of vaginal dilation with minimal content on psychosocial 6% (n=2) or sexual health components 44% (n=14). It was evident from the information leaflets reviewed and questionnaire responses that there was duplication of verbal and written information provision in the clinical setting as opposed to using different information strategies to provide more comprehensive coverage of knowledge gaps in post-treatment sexual rehabilitation. Results suggest the provision of vaginal dilation advice and sexual health information may benefit from being placed in the wider context of assessing treatment impact on women's health. It is important to analyse the management of sensitive content, within both written information materials and verbal consultations, to determine the most effective information provision strategies that support sexual health interventions in cancer practice.


Identification of novel lncRNA by reanalysis of RNA-seq data in Zika Virus Infected hiNPCs.
The Zika Virus (ZIKV) infection is a serious, public health concern with no vaccines or antiviral treatments. This study aims to identify the differentially expressed long non-coding RNAs (lncRNAs) in ZIKV infected human-induced neuroprogenitor cells (hiNPCs). Though lncRNA is well-known for its role in gene regulation, its role in ZIKV infection remains unclear. Thus, taking advantage of publicly available transcriptome data, BioProject PRJNA551246 was analysed. Performed the gene ontology and pathway analysis of differentially expressed lncRNAs were functionally interpreted based on the neighbouring protein-coding genes (100 kb upstream and downstream of each lncRNAs). The study revealed 19 novels and 237 differentially expressed lncRNAs in ZIKV infected hiNPCs. They are found to be significantly enriched in type I interferon signalling pathway, negative regulation of viral genome replication, defense response to the virus, pathways involved in Influenza A and Herpes simplex infection, tumor necrosis factor signalling pathway, and apoptosis. In ZIKV, associated microcephaly type I interferon act as potential modulating factors. Type-I interferon inhibits ZIKV replication in many human cell types. The results support future studies on understanding the structure and function of the novel lncRNAs and experimental approaches to determine the role of the lncRNAs in ZIKV induced infection. The online version contains supplementary material available at 10.1007/s13337-022-00771-1.


Quantitative microspectrophotometrical determination of protein thiols and disulfides with 2,2'-dihydroxy-6,6'-dinaphthyldisulfide (DDD). The variety of DDD-staining methods demonstrated on Ehrlich ascites tumor cells.
2,2'-dihydroxy-6,6'-dinaphthyldisulfide (DDD) reacts with both protein thiol groups and with protein disulfides (Nöhammer 1977). By varying the pH of the DDD-reaction, as well as the reaction times, the complex reaction became specific with respect to the histochemical demonstration of protein-SH groups. Furthermore, the application of the histochemical DDD-reaction following quantitative blockade of the protein-SH groups enabled the demonstration of distinctive DDD-reactive disulfides. The specificity and the extent of the different histochemical DDD-staining methods were investigated by comparing macroscopically determined values of the protein-SH-contents, and the contents of the different kinds of disulfides in Ehrlich-ascites-tumor cells (EATC) (Modig 1968; Hofer 1975), with microspectrometrical values determined with the MCN-method of Nöhammer et al. (1981), and with microspectrometrical values measured on EATC after staining with the modified DDD-methods. Also, the method for the histochemical demonstration of protein-SH with DDD after the reduction of the disulfides with thioglycolate was investigated and conditions were found by which the protein-SH content could be determined quantitatively with DDD and Fast blue B after the reduction of the disulfides. With the aid of the MCN-method (Nöhammer et al. 1981), the intracellular disulfide interchange reaction was investigated, leading to pH-dependent changes of the SH-SS-ratio of fixed cells during their incubation in aqueous media. In addition the possibility of protein loss during the long incubation times of the fixed cells in the DDD-solutions was investigated. For the quantitative microscpecrometrical determination of the protein content of EATC the so-called tetrazonium-coupling method, optimized by Nöhammer (1978) and calibrated by Nöhammer et al. (1981), was used.


Study on improvement of chiral separation of capillary electrophoresis based on cyclodextrin by deep eutectic solvents.
For the first time, the mechanism of deep eutectic solvents (DESs) improving chiral separation by capillary electrophoresis has been studied. The capillary electrophoresis chiral separation has been improved by using DESs as the auxiliary additive. Taking tropicamide, homatropine hydrochloride, ofloxacin, atenolol and propranolol hydrochloride as model chiral separation targets and cyclodextrin (CD) as the chiral selector, and the effects of DESs on the chiral separation resolution were investigated on the basis of optimized conditions. The results of fluorescence spectrophotometry and non-aqueous capillary electrophoresis showed that DESs can improve the resolution of the enantiomers, and the coordination mechanism of DESs was also explored. After DESs were added, the resolution of the above enantiomers increased from 1.26, 1.70, 5.10, 1.90, 2.02 to 3.02, 4.10, 6.86, 2.84 and 5.51 respectively, and the binding constant of CD with propranolol hydrochloride increased from 23 M-1 to 142 M-1. The results showed that DESs is an effective auxiliary additive to improve the separation efficiency of capillary electrophoresis with CD as a basic chiral additive.


Disrupted thalamic resting-state functional connectivity in patients with minimal hepatic encephalopathy.
Little is known about the role of thalamus in the pathophysiology of minimal hepatic encephalopathy (MHE). The purpose of this study was to investigate whether the thalamic functional connectivity was disrupted in cirrhotic patients with MHE by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty seven MHE patients and twenty seven age- and gender- matched healthy controls participated in the rs-fMRI scans. The functional connectivity of 11 thalamic nuclei were characterized by using a standard seed-based whole-brain correlation method and compared between MHE patients and healthy controls. Pearson correlation analysis was performed between the thalamic functional connectivity and venous blood ammonia levels/neuropsychological tests scores of patients. The ventral anterior nucleus (VAN) and the ventral posterior medial nucleus (VPMN) in each side of thalamus showed abnormal functional connectivities in MHE. Compared with healthy controls, MHE patients demonstrated significant decreased functional connectivity between the right/left VAN and the bilateral putamen/pallidum, inferior frontal gyri, insula, supplementary motor area, right middle frontal gyrus, medial frontal gyrus. In addition, MHE patients showed significantly decreased functional connectivity with the right/left VPMN in the bilateral middle temporal gyri (MTG), temporal lobe, and right superior temporal gyrus. The venous blood ammonia levels of MHE patients negatively correlated with the functional connectivity between the VAN and the insula. Number connecting test scores showed negative correlation with the functional connectivity between the VAN and the insula, and between the VPMN and the MTG. MHE patients had disrupted thalamic functional connectivity, which mainly located in the bilateral ventral anterior nuclei and ventral posterior medial nuclei. The decreased connectivity between thalamus and many cortices, and basal ganglia indicated reduced integrity of thalamic RSN in MHE.


Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation.
Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically, Ezh2 functions through its SANT2 domain to maintain the enrichment of H3K27 acetylation in the promoter region of the long noncoding RNA (lncRNA) Neat1, thereby promoting chromatin accessibility and facilitating p65-mediated transcription of Neat1, which is a critical mediator of inflammasome assembly and activation. In addition, the tumour suppressor protein p53 competes with Ezh2 for the same binding region in the Neat1 promoter and thus antagonises Ezh2-induced Neat1 transcription and inflammasome activation. Therefore, loss of Ezh2 strongly promotes the binding of p53, which recruits the deacetylase SIRT1 for H3K27 deacetylation of the Neat1 promoter and thus suppresses Neat1 transcription and inflammasome activation. Overall, our study demonstrates an epigenetic mechanism involved in modulating inflammasome activation through an Ezh2/p53 competition model and highlights a novel function of Ezh2 in maintaining H3K27 acetylation to support lncRNA Neat1 transcription.


Cloning and sequence analysis of an XbaI fragment of rainbow trout mitochondrial DNA.
A 2.4 kbp XbaI fragment of rainbow trout mitochondrial DNA was cloned into pTZ18R. DNA sequence analysis reveals that this segment of the genome encodes URF3, tRNA(Arg), URF4L and URF4 in the same orientation as other vertebrate mitochondrial genomes. Comparison of these segments of the rainbow trout mitochondrial genome with the corresponding sequences in human mitochondrial DNA shows that approximately 60% of the nucleotides are the same in both species.


Fame through surprise: How fame-seeking mass shooters diversify their attacks.
Mass shootings are becoming more frequent in the United States, as we routinely learn from the media about attempts that have been prevented or tragedies that destroyed entire communities. To date, there has been limited understanding of the modus operandi of mass shooters, especially those who seek fame through their attacks. Here, we explore whether the attacks of these fame-seeking mass shooters were more surprising than those of others and clarify the link between fame and surprise in mass shootings. We assembled a dataset of 189 mass shootings from 1966 to 2021, integrating data from multiple sources. We categorized the incidents in terms of the targeted population and shooting location. We measured "surprisal" (often known as "Shannon information content") with respect to these features, and we scored fame from Wikipedia traffic data-a commonly used metric of fame. Surprisal was significantly higher for fame-seeking mass shooters than non-fame-seeking ones. We also registered a significant positive correlation between fame and surprisal controlling for the number of casualties and injured victims. Not only do we uncover a link between fame-seeking behavior and surprise in the attacks but also we demonstrate an association between the fame of a mass shooting and its surprise.


Diabetic kidney disease and immune modulation.
Immune modulation is now known to contribute to the development of glomerulosclerosis, tubulointerstitial fibrosis and end-stage renal disease in a large number of kidney diseases. Similarly, diabetic nephropathy is increasingly considered an inflammatory disease, with immune modulation being involved in both the development and progression of the disease. Infiltration of immune cells including macrophages, T cells, B cells and mast cells into the kidney has been reported. A number of pro-inflammatory cytokines and chemokines also play a major role in pathogenesis of diabetic nephropathy. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease.


tert-Butyl 4-{5-[3-(tri-fluoro-meth-oxy)phen-yl]-1,2,4-oxa-diazol-3-yl}piperazine-1-carboxyl-ate.
In the title compound, C18H21F3N4O4, the piperazine ring adopts a chair conformation and the dihedral angle between the oxa-diazole and benzene rings is 6.45 (14)°. The C atoms and their attached H atoms in the piperazine ring are disordered, with site-occupation factors of 0.576 (12) and 0.424 (12). In the crystal, mol-ecules are linked through weak C-H⋯O inter-actions, generating an R 2 (2)(12) motif. Further, secondary C-H⋯O inter-molecular inter-actions link the mol-ecules into C(6) chains along [100].


Cumulative success rate and marginal bone loss for immediate and early loading protocols in a single implant-supported crown: A randomized controlled split-mouth clinical trial.
New loading protocols with reduced treatment time have gained popularity because of their advantages. However, whether the success rate with immediate loading (IL) is worse than with early loading (EL) is still unclear. The purpose of this randomized controlled trial with a split-mouth design was to evaluate the marginal bone loss and the cumulative success rate (CSR) 1 year after an IL protocol in single implant-supported crowns. The test groups were loaded after less than 24 hours (test group) and EL at 60 days (control group). Seventeen participants received 34 implants. The recall appointments were at baseline, 30 days, 60 days, and 1 year. The outcome measures evaluated were pain, implant clinical mobility, probing depth measurements, peri-implant disease, marginal bone loss, implant insertion torque, implant stability quotient (ISQ) value, and the CSR. A 2-way repeated measures ANOVA identified the significant differences for probing depth and ISQ. A 3-way repeated measures ANOVA followed by a pairwise t test analyzed marginal bone loss, and a nonparametric Wilcoxon test analyzed insertion torque (α=.05). No differences were found between the insertion torque, ISQ, and marginal bone loss values (P>.05). When analyzing probing depth, no differences were found when comparing IL versus EL at baseline, 30 days, and 1 year (P>.05). The global CSR was 91.17%, 88.23% for the IL group and 94.11% for the EL group. When analyzing marginal bone loss, the groups were similar. The global CSR was 91.17%, 88.23% for the IL group, and 94.11% for the EL group.


Prevalence of Chlamydia trachomatis among women attending an antenatal clinic in Bangkok.
Cervical swabs from 140 Thai pregnant women were cultured for Chlamydia trachomatis twice during the first and the third trimester. Serum samples for antichlamydial antibodies was also studied from 126 women; 12 of women were culture positive on both occasions. Chlamydia was isolated from 24% of women aged 20-24 years, compared to only 9% of women 25-30 years. Antibody were detected to the genital serotypes (D-K) in 31 (25%) of 126 women who were tested. 70% of women who were culture positive had antibody titer greater than or equal to 1:64 compared to 7% of women who were culture negative.


The pharmacokinetics of single and multiple doses of tiaprofenic acid in elderly patients with arthritis.
We have studied the single dose and steady-state pharmacokinetic of tiaprofenic acid in ten elderly arthritic patients living in the community (5 men and 5 women) taking 200 mg tid for 8 days. The mean area under the plasma concentration-time curves to 8 h (AUC (0-8)) did not alter significantly from day 1 to day 8 (77.25 to 79.61 micrograms X ml-1 X h). The mean terminal phase half-life (t1/2) was 2.05 h and 2.25 h on Days 1 and 8 respectively in patients in whom the calculations were possible (7 patients on Day 1 and 6 patients on Day 8). The median observed time of maximum concentration (tmax) and the mean observed maximum plasma concentration (Cmax) of 100 min and 21.3 micrograms X ml-1 respectively on Day 1 were not significantly different from the values obtained on Day 8 (tmax 120 min; Cmax 20.7 micrograms X ml-1). The kinetic data suggest that there should be no significant accumulation of tiaprofenic acid in elderly ambulant people suffering from arthritis.


Genetic Code Expansion Facilitates Position-Selective Labeling of RNA for Biophysical Studies.
Nature relies on reading and synthesizing the genetic code with high fidelity. Nucleic acid building blocks that are orthogonal to the canonical A-T and G-C base-pairs are therefore uniquely suitable to facilitate position-specific labeling of nucleic acids. Here, we employ the orthogonal kappa-xanthosine-base-pair for in vitro transcription of labeled RNA. We devised an improved synthetic route to obtain the phosphoramidite of the deoxy-version of the kappa nucleoside in solid phase synthesis. From this DNA template, we demonstrate the reliable incorporation of xanthosine during in vitro transcription. Using NMR spectroscopy, we show that xanthosine introduces only minor structural changes in an RNA helix. We furthermore synthesized a clickable 7-deaza-xanthosine, which allows to site-specifically modify transcribed RNA molecules with fluorophores or other labels.


[Biochemical and serologic characteristics of Campylobacter jejuni/coli strains causing diarrhea in children].
One hundred strains of Campylobacter jejuni/coli isolated from faeces of children with diarrhoea were characterised. Frequency of isolation of these microorganisms from faeces of children with enterocolitis symptoms was evaluated. In this group Campylobacter jejuni/coli constituted 11.4% of all isolates, being the dominant etiologic agent of these infections. Biotype pattern of 100 Campylobacter jejuni/coli strains was determined. Biotype I C.jejuni prevailed and C. coli constituted as much as 35% of all isolated strains. All isolated strains were characterised serologically according to typing scheme of Lior. Seventy four strains were typed and 22 were untypable, out of which four were rough. Two new serotypes were isolated: LIO 71 and LIO 72, LIO 4 and LIO 72 serotypes were the most frequently isolated. Frequency of isolation of Campylobacter jejuni/coli strains were also determined in the period from january 1985 to august 1987.


Tip-porous microneedle: A highly stable sensing platform for direct determination of labile metals in natural seawater.
Nanomaterial-functionalized voltammetric microsensors are promising tools for detecting trace metals at low concentrations in the complex environment of natural seawater. However, the sensitivity reduction caused by the loss of modified nanomaterials in the detection process has always been a major problem. Herein, to fabricate a highly stable sensing platform, a microneedle electrode with a hierarchical porous tip was prepared through electrochemical etching technology to firmly embed nanoparticles. Using copper (Cu) as a model trace metal, a micro-cluster needle sensor based on a gold nanoparticle (AuNP)-embedded tip-porous microneedle electrode (P-MNE) was fabricated for the direct voltammetric determination of labile Cu in natural seawater. The porous structure of P-MNE not only provided a larger specific surface area and active sites for AuNPs which had excellent electrocatalytic performance for Cu2+ determination, but also protected from their loss during the detection process in seawater. Therefore, this novel micro-cluster needle sensor exhibited significantly improved stability with a relative standard deviation (RSD) of 1.5% for 30 detections. The linear range of Cu2+ on this micro-cluster needle sensor was from 0.1 to 1000 nM with a detection limit of 0.03 nM. More importantly, this micro-cluster needle sensor was successfully used for directly detecting labile Cu in natural seawater samples without any preaccumulation treatment or reagent addition to obtain the contribution proportions of the labile fraction in total dissolved Cu. Furthermore, this sensing platform might also be extended to the reliable determination of other labile metals in seawater by changing the functional nanoparticles embedded in the nanopores.


Extrathermodynamic interpretation of retention equilibria in reversed-phase liquid chromatography using octadecylsilyl-silica gels bonded to C1 and C18 ligands of different densities.
The retention behavior on silica gels bonded to C18 and C1 alkyl ligands of different densities was studied in reversed-phase liquid chromatography (RPLC) from the viewpoints of two extrathermodynamic relationships, enthalpy-entropy compensation (EEC) and linear free energy relationship (LFER). First, the four tests proposed by Krug et al. were applied to the values of the retention equilibrium constants (K) normalized by the alkyl ligand density. These tests showed that a real EEC of the retention equilibrium originates from substantial physico-chemical effects. Second, we derived a new model based on the EEC to explain the LFER between the retention equilibria under different RPLC conditions. The new model indicates how the slope and intercept of the LFER are correlated to the compensation temperatures derived from the EEC analyses and to several parameters characterizing the molecular contributions to the changes in enthalpy and entropy. Finally, we calculated K under various RPLC conditions from only one original experimental K datum by assuming that the contributions of the C18 and C1 ligands to K are additive and that their contributions are proportional to the density of each ligand. The estimated K values are in agreement with the corresponding experimental data, demonstrating that our model is useful to explain the variations of K due to changes in the RPLC conditions.


Wrong gas/liquid partition data by gas chromatography.
In a paper published in 1992 [K.S. Reddy, J.-Cl. Dutoit, E.sz. Kováts, Pair-wise interactions by gas chromatography. I. Interaction free enthalpies of solutes with non-associated primary alcohol groups, J. Chromatogr. 609 (1992) 229] retention indices and standard chemical potential differences (SPOT-s) are given for about 160 solutes on a liquid branched paraffin hydrocarbon of the carbon number, z = 78. For the temperature dependence of the SPOT-s the proposal of Kirchhoff was accepted i.e. that at higher temperatures the molar heat capacity difference of the solute between the gas phase and the solution is nearly constant in a broad temperature range. The data were determined under conditions where the effect of adsorption could be neglected. By comparing the published data with those determined on another branched paraffin of the carbon number, z = 87 [F. Riedo, D. Fritz, G. Tarján, E.sz. Kováts, A tailor-made C87 hydrocarbon as a possible non-polar standard stationary phase for gas chromatography, J. Chromatogr. 126 (1976) 63] it is shown that the reported thermodynamic constants of solutes determined experimentally at higher temperatures (the group "H") are wrong on C78. In the present paper, the method of correction and the resulting corrected data are given. In later papers retention data are given on eight polar derivatives of the hydrocarbon C78 relative to those measured on the nonpolar standard [R. Cloux, G. Défayes, K. Fóti, J.-Cl. Dutoit, E.sz. Kováts, Pair-wise interactions by gas chromatography. III. Synthesis of isosteric stationary phases for gas chromatography, Synthesis (1993) 909; G. Défayes, K.S. Reddy, A. Dallos, E.sz. Kováts, Pair-wise interactions by gas chromatography. V. Interaction free enthalpies of solutes with primary chloro- and bromo-alkanes, J. Chromatogr. A 699 (1995) 131; K.S. Reddy, E.sz. Kováts, Pair-wise interactions by gas chromatography. II. Sociation free enthalpies of some hydrogen bonding solutes with non-associated primary alcohol groups, Chromatographia 34 (1992) 249; K.S. Reddy, R. Cloux, E.sz. Kováts, Pair-wise interactions by gas chromatography. IV. Interaction free enthalpies of solutes with trifluoromethyl-substituted alkanes, J. Chromatogr. A 673 (1994) 181; K.S. Reddy, R. Cloux, E.sz. Kováts, Pair-wise interactions by gas chromatography. VI. Interaction free enthalpies of solutes with primary methoxyalkane, cyanoalkane and alkanethiol groups, J. Chromatogr. A 704 (1995) 387; A. Dallos, A. Sisak, Z. Kulcsár, E.sz. Kováts, Pair-wise interactions by gas chromatography. VII. Interaction free enthalpies of solutes with secondary alcohol groups, J. Chromatogr. A 904 (2000) 211]. Obviously, the same data which are wrong in the nonpolar standard are also wrong in these solvents. The corrected data in the polar solvents are given in supplementary tables.


[Ocular proprioception and developmental dyslexia. Sixty clinical observations].
The objective of this study is to assess proprioception anomalies in postural deficiency syndrome in a group of children suffering from reading impairment. Sixty male patients with an average age of 11 years and 9 months were included in the study. Initially, they were given a standardized neuropsychological examination, which confirmed the diagnosis of reading impairment. Then after filling out a questionnaire seeking a proprioceptive anomaly, the patients were subjected to a clinical ocular and postural examination consisting of nine precisely described steps. All of the patients recruited for the study presented clinical signs confirming a proprioception disorder found as a part of postural deficiency syndrome. This study opens a new direction for research concerning the origin and treatment of at least some reading-impaired children.


[Human papillomavirus vaccine. Efficacy and safety].
Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases.


Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells.
The IFN-induced double-stranded RNA (dsRNA)-activated protein kinase PKR is one of the key molecules in the antiviral effects of IFN. To clarify the effects of hepatitis C virus nonstructural protein 5A (NS5A) on antiviral activity of IFN, in particular on PKR kinase activity, in mammalian cells, we established inducible NS5A-expressing cell lines derived from human osteosarcoma (Saos-2). The cells expressing NS5A derived from an IFN-resistant clone (NS5A-lb) that interacted with endogenous PKR in vitro, showed a suppressive effect on IFN function as determined by interference with vesicular stomatitis virus (VSV) infection, whereas NS5A (NS5A-2a) from an IFN-sensitive clone did not block the antiviral effect of IFN. A mutant with deletion of the IFN sensitivity determining region (ISDR) in NS5A-1b (NS5A-AISDR) also interacted with PKR and suppressed its activity in vitro. However, neither NS5A-2a nor the C-terminal truncated mutant of NS5A-1b (NS5A-deltaC) blocked PKR activity. These observations confirmed the previous report that the inhibitory effect of NS5A on IFN activity is mediated at least in part by the repression of PKR. In addition, we showed that IFN sensitivity was determined not only by the ISDR but that the involvement of the C-terminal region of NS5A-1b is important for the suppression of PKR activity.


Effects of caffeine on diaphragmatic activity in preterm infants.
Caffeine is the first-choice drug for the treatment for apnea of prematurity (AOP) in preterm infants and it has been reported that it improves the diaphragm activity. The aim of this study was to evaluate by ultrasound possible changes in diaphragm contractility and motility induced by caffeine. We studied 26 preterm infants with gestational age ≤34 weeks treated with caffeine for the prevention or treatment of AOP. Diaphragmatic ultrasound was performed 15 min (T0 ) before and 60 min (T60 ) after the loading (20 mg/kg) or maintenance (5 mg/kg) dose of caffeine. Diaphragmatic excursion (DE) and thickness at the end of inspiration (DT-in) and expiration (DT-ex), as well as peak velocity of the excursion at the end of inspiration (DT-in) and expiration (DT-ex) increased after administration of both loading and maintenance dose of caffeine. Ultrasounds confirmed that caffeine improves the activity of diaphragm in preterm infants improving its thickness, amplitude of excursions, and contraction velocity. These results are consistent with the effectiveness of caffeine in treating AOP and decreasing the risk of failure of noninvasive respiratory support in preterm infants with respiratory distress syndrome (RDS).


A computerized version of EBIS evaluation chart and its opportunities in the rehabilitation program of TBI patients.
The need of rehabilitation programs for severely traumatic brain injured (TBI) patients is great and is growing, but these programs are long, costly and it would be very useful if we could demonstrate and quantify the benefits of our approaches. We think that scarcity of literature in this field is a consequence of the well known and real difficulty in this kind of investigations (too many variability factors, groups of population not homogeneous, ethical problems for double blind studies and so on). It is our opinion that EBIS Protocol could be a very useful instrument for the evaluation of rehabilitation programs benefits, provided that the protocol is used regularly for a long time after the acute phase and in many different TBI centres: in this way it would be possible to compare and to elaborate data concerning a large number of patients. This instrument could also become an opportunity for a continuous and more coordinated collaboration between rehabilitation centres of different countries. We think that this target is realistic only if we dispose of a commonly accepted computerized version of EBIS Protocol with a data exchange via Internet. Since 1996 we have been using a computerized version of the EBIS protocol for data archivation and follow up of TBI patients treated in our centre. The data bank concerns actually n. 341 TBI patients. Objective of the present research is the presentation of a computerized version of EBIS protocol. This program is freely available and it could contribute to a more common use of this evaluation tool. We thank particularly Prof. Truelle and Prof. Brooks who gave us the permission for the use of EBIS document.


A neonate with the Pelger-Huët anomaly, cleft lip and palate, and agenesis of the corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12.
We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the corpus callosum, slightly small penis, hypoglycemia, and what initially appeared to be a marked leukocyte 'left shift' on complete blood count, but which was actually a Pelger-Huët anomaly. A chromosomal microdeletion was identified at1q41-42.12.


Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.
10-formyltetrahydrofolate dehydrogenase (ALDH1L1) is a major folate enzyme, which is usually underexpressed in malignant tumors and competes with tumors for the same folate substrate. However, the specific role and mechanisms of ALDH1L1 in oral squamous cell carcinoma (OSCC) remainsobscure. The expression level of ALDH1L1 in paired OSCC tissues and adjacent noncancerous tissues were detected by quantitative realtime PCR, Western blot and immunohistochemistry. The relationship between ALDH1L1 expression and clinical characteristics was analyzed. Besides, CCK8, EdU staining, colony formation, wound healing, transwell invasion, apoptosis, cell cycle assays and nude mice tumor bearing experiments were employed to assess the role of ALDH1L1 in OSCC. To explore the underlying mechanisms of these effects, cell cycle-related markers were examined. In this study, we revealed that ALDH1L1 expression was significantly reduced in OSCC, and its downregulation was associated with the malignancy of the tumor and poor prognosis of patients. In vivo and in vitro experiments, downregulation of ALDH1L1 in OSCC significantly inhibited the occurrence of NADP+ -dependent catalytic reactions and facilitated tumor cell growth, migration, invasion, survival, cell cycle progression, and xenograft tumor growth. On the contrary, re-expression of ALDH1L1 plays a similar role to anti-folate therapy, promoting NADPH production and suppressing the progression of OSCC. Furthermore, ALDH1L1 overexpressing obviously inhibited the expression of PI3K, p-Akt, CDK2, CDK6, Cyclin D1, Cyclin D3, and Rb in OSCC cells, and promoted the expression of p27. LY294002 and 740 Y-P were used to confirm the inhibitory effects of ALDH1L1 on OSCC progression through PI3K/Akt/Rb pathway. Our findings highlight the clinical value of ALDH1L1 as a prognostic marker and the potential of a new target for anti-folate therapy.


High-performance liquid chromatographic determination of phenytoin and hydroxyphenytoin in human urine.
Simple and rapid quantitative analysis utilizing high-performance liquid chromatography was performed to determine the concentration of the antiepileptic agent phenytoin, and its main metabolite hydroxyphenytoin, in human urine. For the purposes of simple and rapid determination, the commercially available Extrelut columns were used with diethyl ether and chloroform as extraction solvents. High-performance liquid chromatography was performed on a LiChrosorb RP-8 column, with a mobile phase of methanol-0.02% ammonium acetate (1:1). The internal standard was 5-(4-methylphenyl)-5-phenylhydantoin. The method was applied to patients' urine, to examine the influence of concomitant drugs. Also, the results obtained using the commercially available enzymatic immunoassay method were compared with those from the present method, and it was concluded that a simple and rapid microanalysis is possible with a high extraction ratio.


Multicystic lateral periodontal cyst and botryoid odontogenic cyst. Multifactorial analysis of previously unreported series and review of literature.
A series of six cases of botryoid odontogenic cyst (BOC) are presented, and their clinical, radiographic, histologic and follow-up data are analyzed. A review of the English language literature revealed an additional 60 cases of BOC, bringing the total number of cases to 66.


Management of blunt liver trauma in a tertiary referral centre.
In recent years, several reports from North America have highlighted the success of conservative treatment in patients with blunt liver trauma. The aim of this study was to identify trends in the management of blunt liver trauma in a UK tertiary referral centre dealing with both adults and children over a 10-year period. A retrospective case note review was performed on 71 consecutive patients (58 male patients) of median age 25 years admitted to the hepatobiliary unit over the 10-year period from 1992 to 2001 with blunt liver trauma. Data relating to referring source, severity of liver injury, initial and subsequent management and outcome were collected using a standard pro forma. Sixty-two of the 71 patients were referred from other surgical units. Of these, 14 had undergone laparotomy at the referring hospital, with ten having perihepatic packing; the other 48 were managed conservatively. Of the 62 patients transferred to the authors' unit, 12 required surgical intervention for the liver injury. The mean number of patients with blunt liver trauma increased between the first second 5-year periods, from 3.2 to 11.0 patients per year. There was a significant reduction in the proportion of patients requiring surgery for the liver injury in both the authors' unit (from seven of 16 patients in 1992-1996 to seven of 55 in 1997-2001; P = 0.017, chi(2) test) and referring hospitals (from six of 12 to eight of 50; P = 0.014, chi(2) test). The reduction in the mortality rate, from two (12.5 per cent) of 16 in the first period to four (7.3 per cent) of 55 in the second, was not significant (P = 0.880, chi(2) test). This study demonstrated a marked increase in the number of patients with blunt liver trauma referred to a regional hepatobiliary centre in recent years. It has confirmed that the majority of such patients can be treated successfully without surgery.


Cup-cage construct for acute fractures of the acetabulum, re-defining indications.
Acetabular fractures in the elderly are challenging injuries. The use of a trabecular metal acetabular cage was investigated as the treatment option in a series of elderly patients with acetabular fractures. At a 2-year follow up, 6 elderly patients were found to have mimimum pain, increased function, and increased scores using the Merle d'Aubigné and Postel system modified by Charnley. Radiographically, the areas of morsellised autograft that surrounded the cups were seen to have incorporated uniformly well, and the acetabular fractures were healed within six months after surgery. No mechanical failure, screw breakage, loosening, or migration was noticed. This novel indication of the cup-cage construction that uses revision techniques, for selected patients and fractures, to achieve an acute stable reconstruction, should be considered as an alternative reconstruction option in elderly patients presenting with acetabular fractures.


Automated assessment of blood pressure using BpTRU compared with assessments by a trained technician and a clinic nurse.
To determine the accuracy and reproducibility of a new automated blood pressure manometer (BpTRU) relative to auscultatory blood pressure assessed by a research nurse and to that assessed by a clinic nurse. Firefighters in a cohort study had blood pressure assessed on up to five occasions with BpTRU and by a trained research technician. Patients in an internal medicine clinic had blood pressure assessed by the clinic nurse and by BpTRU. The absolute values of blood pressure, reproducibility and effect on hypertension classification were compared with the different methods. The research technician readings were higher than the BpTRU readings at visit 1 (3.0/2.7 mmHg, P<0.0001) but the readings converged by visits 4-5 because of a greater reduction in the research nurse readings. The BpTRU readings had similar reproducibility and classification of hypertension as the research technician but did not exhibit terminal digit preference while the research technician readings did. The BpTRU had substantially lower readings (8/7 mmHg) and fewer hypertensive readings than those of the nurse in the internal medicine clinic. This preliminary study found that the BpTRU had desirable characteristics that suggest that it would be a suitable replacement for auscultatory assessment of blood pressure in clinical practice. A large confirmatory study performed in a usual clinic setting is required.


In vivo H-2K and H-2D antigen expression in two allogeneic mouse tumours of low immunogenicity.
The B16 melanoma of C57BL/6 mice immunizes very poorly, even against its own major histocompatibility complex (MHC) antigens. B16 cells expressed both H-2K and H-2D antigens in vitro as judged by binding of monoclonal antibodies to these antigens in indirect immunofluorescence staining. The in vivo MHC antigen expression of B16 was examined and compared with that of a second C57BL/6 tumour, the Lewis lung carcinoma (3LL), whose defective immunogenicity has been attributed to a selective deficiency in H-2K antigen expression. We found that 125I-labelled cells of both tumours expressed sufficient allo-antigen in vivo to be lysed in BALB/c mice which had been pre-immunized with C57BL/6 lymphoid cells. 125I-B16 cells were also lysed in MHC-recombinant mice which had been immunized against either H-2Kb or H-2Db, indicating that B16 cells express both of these MHC antigens in vivo. This contrasted with our findings with 125I-3LL cells which were destroyed in mice immunized against H-2Db but not in those immunized against H-2Kb. Thus, B16 illustrates a different deficiency in tumour cell immunogenicity which appears not to be attributable to an absence of either of the class I MHC antigens.


Rhinoplasty in Middle Eastern Patients.
Rhinoplasty in patients of Middle Eastern origin requires complete understanding of nasal morphology and an individualized approach to create a racially congruent and aesthetically pleasing outcome. In this article, common anatomic features and characteristics and detailed steps, surgical techniques, and operative maneuvers that can lead to predictable outcome in rhinoplasty of Middle Eastern patients are discussed.


What predicts influenza vaccination status in older Americans over several years?
To examine the correlates of repeat influenza vaccination and determine whether there are age-group (50-64, > or =65) differences in decision-making behavior. Longitudinal survey study. Two community health centers in Pittsburgh, Pennsylvania. Two hundred fifty-three patients aged 50 and older in 2001 who visited one of the health centers and completed telephone surveys in 2002 and 2003 after the respective influenza seasons. Influenza vaccination status, demographic characteristics, and decision-making behavior were self-reported. Vaccination status was identified for three seasons: 2000-2001, 2001-2002, and 2002-2003. A three-level outcome was defined as unvaccinated all 3 years, vaccinated one to two times over 3 years, and vaccinated all 3 years. Factor analysis identified three decision-making behaviors. Predictors of being vaccinated across 3 years included being older, the belief that social forces influence vaccination behavior, and disagreement with the view that vaccine is detrimental. National educational efforts should be intensified to dispel the myths about alleged adverse events, including contracting influenza from inactivated influenza vaccine. Physicians should continue to share their personal experiences of treating patients with influenza, including the incidence of hospitalization and death.


Peroxiredoxin 4 secreted by cumulus cells ameliorates the maturation of oocytes in vitro.
Peroxiredoxin 4 (Prdx4) in the endoplasmic reticulum (ER) is the only secretory member of the antioxidant Prdx family. Our previous studies demonstrated that Prdx4 in cumulus cells (CCs) ameliorated the maturation of oocytes in vitro and enhanced oocyte developmental competence by preventing CCs apoptosis caused by oxidative stress (OS) through gap junctions. In this study, we aimed to determine whether Prdx4 released by CCs can repair meiotic defects in mouse oocytes by co-culturing immature (germinal vesicle) oocytes with CCs from mature oocytes in the absence of gap junctions. The OS-induced meiotic defects in mouse oocytes were impeded by co-culture with CCs, as evidenced by the increased first polar body (PB1) extrusion rate and decreased ROS level. CCs increased Prdx4 expression and lowered IRE1α, Bip expression in H2O2-treated oocytes. After knockdown of Prdx4 expression in CCs, the rate of PB1 extrusion in the oocytes was significantly reduced to the level detected in H2O2 group, and ER stress was not alleviated. CO-IP and immunofluorescence co-localization experiments demonstrated that Prdx4 interacted with PDIA6 in the oocytes and the Pearson's R value was 0.69 calculated using ImageJ. Cumulus cells can promote the maturation of oocytes in vitro by secreting Prdx4 in a paracrine manner and serve as a promising therapeutic antioxidant for improving the quality of oocytes, especially aging oocytes, in clinical in vitro maturation (IVM).


Unequal expectations? Testing decisional mechanisms for secondary effects of social origin.
It is a common research practice to decompose the effect of social origin on an educational expectation into a primary effect, via academic performance, and a secondary effect, computed as the inequality that survives the control of performance. In this paper, I examine how specific decisional mechanisms described in the Cultural Capital and Rational Action theories contribute to explain the inequalities that survive the control of performance in the configuration of educational expectations. Cultural Capital Theory argues that participation in the dominant culture at schools, the endowment of educational resources and the development of skill-generating habits contribute to holding ambitious expectations over and above performance. In Rational Action Theory, students form expectations at each level of performance by gathering information, pondering benefits and costs, and evaluating the risk of academic failure and social demotion, which in turn might account for the secondary effect of social origin. Relying on Spanish data from 2018 PISA, I observe that Cultural Capital and Rational Action mechanisms are compatible in the explanation of the secondary effects of social origin, although two-thirds of that inequality remain unexplained. Nonetheless, I find differences in how those mechanisms perform in vertical (whether to enrol an educational level) and horizontal expectations (what alternative is preferred in that educational level).


Baseline severity of parent-perceived inattentiveness is predictive of the difference between subjective and objective methylphenidate responses in children with attention-deficit/hyperactivity disorder.
The purpose of this study was to find potential variables associated with the difference between subjective and object treatment responses in children with attention-deficit/hyperactivity disorder (ADHD) treated with OROS-methylphenidate (MPH). We conducted a post-hoc analysis of data from a multicenter, open-label, 12 week trial of OROS-MPH in Korean children with ADHD. The subjective outcome measurement was the parent version of the ADHD Rating Scale-IV (ARS-P), and the objective outcome measurement was the Continuous Performance Test (CPT). We compared the children's demographic and disease-related variables among four groups, classified according to whether they showed subjective or objective improvement after MPH treatment. Higher baseline inattentive scores on the ARS-P were associated with a significantly higher probability of subjective treatment response among objective nonresponders (p=0.033). Lower baseline inattentive scores on the ARS-P were associated with a significantly higher probability of subjective nonresponse among objective responders (p=0.045). Lower baseline omission errors (p=0.006) and response time variability scores (p=0.011) on the CPT were associated with a significantly higher probability of both objective and subjective responses, compared with both types of nonresponse to treatment. The baseline severity of parent-perceived inattentive symptoms was predictive of differences in subjective and objective treatment responses, and the baseline severity of neuropsychological deficit (inattention and inconsistency of attention) was predictive of responses, using both subjective and objective measurements.


Antigenotoxic role of Centella asiatica L. extract against cyproterone acetate induced genotoxic damage in cultured human lymphocytes.
The majority of the Indian population use traditional natural preparations derived from plant material for the treatment of various diseases, and for that reason it becomes necessary to assess the mutagenic potential or modulating action of plants extract when associated with other substances. The genotoxicity testing provides human a risk assessment. Earlier in vitro and in vivo studies reveal that the plant extracts from various parts of the plant play a modulating role in xenobiotic effects. Identification and characterization of some active principles may lead to the development of the strategies to reduce the risk for developing cancer in humans. Cyproterone acetate (CPA), a synthetic progestin is not only a genotoxic agent but also a tumor initiating agent. It is used in oral contraceptives formulations and also in the treatment of various sexual and metabolic disorders. In this context, the antigenotoxic effect of Centella asiatica L. extract was studied against the genotoxic effect induced by CPA on human lymphocytes using chromosomal aberrations and sister chromatid exchanges as parameters. The treatment of the two doses of CPA, i.e. 20 and 30 microM was given along with the C. asiatica extract at the dosages of 1.075 x 10(-4), 2.125 x 10(-4), 3.15 x 10(-4) and 4.17 x 0(-4)g/ml of culture medium. A clear dose dependent decrease in the genotoxic damage of CPA was observed, suggesting a protective role of C. asiatica extract during CPA therapy. The results of the present study suggest that the plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of CPA on human lymphocytes in vitro.