Use of tracheal ultrasound combined with clinical parameters to select left double-lumen tube size: A prospective observational study.
Left double-lumen tubes (LDLTs) are used in thoracic surgery to allow one-lung ventilation. Their size is usually chosen on the basis of clinical parameters (height, sex). Double-lumen endobronchial tubes are frequently undersized/oversized, risking tube displacement or tracheal trauma. A correlation between ultrasound tracheal diameter and left main bronchus dimension has been demonstrated. We hypothesised that the insertion of undersized/oversized double-lumen tubes is frequent when the size is selected using standard criteria, and that the use of ultrasound to estimate tracheal diameter may help to reduce the frequency of insertion of oversized tubes. Two-step prospective observational study. The operating room of a French University hospital from January 2016 to February 2017. We enrolled 102 and 50 consecutive patients undergoing elective thoracic surgery in Steps 1 and 2 (males 63.7 and 60.0%, age 63 (13) and 63 (11) years, height 170 (13) and 169 (9) cm, respectively). In Step 1, the size of the LDLT inserted was selected on the basis of clinical parameters. Ultrasound data about tracheal diameter were collected to determine cut-off points associating height and tracheal diameter. Cut-off values for ultrasound tracheal diameter were applied retrospectively to test their capability to reduce the insertion rate of oversized tube. In Step 2, the LDLT size was chosen according to the determined combined cut-off values. LDLT size was considered adequate if the bronchial cuff volume required for isolation of the lung (i.e. no difference between inspiratory and expiratory lung volumes) was 0.5 to 2.5 ml of air; undersized and oversized tubes required more than 2.5 ml and less than 0.5 ml, respectively. In Step 1, LDLT size was appropriate/undersized/oversized in 40 (39.2%)/23 (22.6%)/39 (38.6%) of patients. Cut-off values derived from ultrasound measurements would have reduced the use of oversized tubes by 20.6% (P < 0.001). In Step 2, the frequency of use of adequately sized tubes increased (86.0 vs. 39.2%, P < 0.001), and the frequency of insertion of oversized and undersized tubes decreased (6.0 vs. 38.2% and 8.0 vs. 22.6%, both P < 0.001). Combining ultrasound measurement of tracheal diameter and clinical parameters improves the choice of LDLT size.


LIGHT-SENSITIVE VISUALIZATION OF MULTIMODAL DATA FOR NEUROSURGICAL APPLICATIONS.
We present a technique for enhancing multimodal visualizations for image-guided neurosurgery in the presence of adverse lighting conditions. In the surgical environment, images used for real time navigation are displayed in suboptimal conditions due to the varying lighting conditions. Our approach actively monitors the incoming light on the display and appropriately enhances the visualization based on the change in light. Based on the results of a user study to evaluate our approach, we found that our enhanced visualization techniques were mostly preferred over regular visualizations.


Effects of massage & use of oil on growth, blood flow & sleep pattern in infants.
The present study was undertaken to investigate if massage with oils commonly used in the community for massage in infancy is beneficial. Full term born healthy infants (n = 125), 6 +/- 1 wk of age, wt > 3000 g were randomly divided into five groups. Infants received (i) herbal oil, (ii) sesame oil, (iii) mustard oil, or (iv) mineral oil for massage daily for 4 wk. The fifth group did not receive massage and served as control. The study tools were anthropometeric measurements; microhaematrocrit; serum proteins, creatinine and creatine phosphokinase; blood flow using colour doppler and sleep pattern. Massage improved the weight, length, and midarm and midleg circumferences as compared to infants without massage. However, in the group with sesame oil massage increase in length, midarm and midleg circumferences by 1.0, 0.9 and 0.7 cm, respectively was significant (P < 0.05, < 0.01 & < 0.05). There was no change in microhaematocrit, serum: proteins, albumin, creatinine and creatine phosphokinase between both the groups. The femoral artery blood velocity, diameter and flow improved significantly by 12.6 cm/sec, 0.6 cm and 3.55 cm3/sec respectively in the group with sesame oil massage as compared to the control group. Massage improved the post massage sleep, the maximum being 1.62 h in the sesame oil group (P < 0.0001). Massage in infancy improves growth and post-massage sleep. However, only sesame oil showed significant benefit.


Brooke-Spiegler syndrome: report of 10 patients from 8 families with novel germline mutations: evidence of diverse somatic mutations in the same patient regardless of tumor type.
Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma (cribriform trichoblastoma). BSS patients have various mutations in the CYLD gene, a tumor suppressor gene located on chromosome 16q. Our search of the literature revealed 51 germline CYLD mutations reported to date. Somatic CYLD mutations have rarely been investigated. We studied 10 patients from 8 families with BSS. Analysis of germline mutations of the CYLD gene was performed using either peripheral blood or nontumorous tissue. In addition, 19 formalin-fixed paraffin-embedded tumor samples were analyzed for somatic mutations, including loss of heterozygosity studies. A total of 38 tumors were available for histopathologic review. We have identified 8 novel germline mutations, all of which consisted of substitutions, deletions, and insertions/duplications and all except one led to premature stop codons. The substitution mutation in a single case was also predicted to disrupt protein function and seems causally implicated in tumor formation. We demonstrate for the first time that somatic events, loss of heterozygosity, or sequence mutations may differ among multiple neoplasms even of the same histologic type, occurring in the same patient.


Schisandra chinensis acidic polysaccharide partialy reverses acetaminophen-induced liver injury in mice.
Schisandra chinensis is a hepatoprotective herb that has been used for centuries in China. Polysaccharide is one of the major active components in S. chinensis, which has been reported to improve liver injuries induced by carbon tetrachloride, alcohol, or high-fat diet. In this study, we observed the effects and corresponding mechanisms of the secondary component of Schisandra polysaccharide (acidic polysaccharide, SCAP) on a murine model of severe acute liver injury induced by acetaminophen (APAP). SCAP significantly decreased the serum alanine aminotransferase (ALT), aspartate aminotransferas (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels, and was found to alleviate hepatic pathological alterations in the mouse model. Meanwhile, SCAP revealed a protective effects on the liver injury-related enzymes and factors, such as significantly diminished malondialdehyde (MDA) levels and glutathione (GSH) depletion, reduced ratio of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2, prohibited cleaved caspase-3 expression, and elevated the expression of p-AMPK, p-Akt, p-glycogen synthase kinase 3β (GSK 3β), nuclear factor erythroid 2-derived-like 2 (Nrf 2) and heme oxygenase-1 (HO-1) proteins in the liver tissues of the mouse model. In conclusion, we speculated that the protective activities of SCAP on the APAP-induced mouse model of acute liver injury might be related to its antioxidation, anti-inflammation and anti-apoptosis properties.


Comparison of In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycle Outcome in Patients with and without Polycystic Ovary Syndrome: A Modified Poisson Regression Model.
Polycystic ovary syndrome (PCOS) is a frequent condition in reproductive age women with a prevalence rate of 5-10%. This study intends to determine the relationship between PCOS and the outcome of assisted reproductive treatment (ART) in Tehran, Iran. In this historical cohort study, we included 996 infertile women who referred to Royan Institute (Tehran, Iran) between January 2012 and December 2013. PCOS, as the main variable, and other potential confounder variables were gathered. Modified Poisson Regression was used for data analysis. Stata software, version 13 was used for all statistical analyses. Unadjusted analysis showed a significantly lower risk for failure in PCOS cases compared to cases without PCOS [risk ratio (RR): 0.79, 95% confidence intervals (CI): 0.66-0.95, P=0.014]. After adjusting for the confounder variables, there was no difference between risk of non-pregnancy in women with and without PCOS (RR: 0.87, 95% CI: 0.72-1.05, P=0.15). Significant predictors of the ART outcome included the treatment protocol type, numbers of embryos transferred (grades A and AB), numbers of injected ampules, and age. The results obtained from this model showed no difference between patients with and without PCOS according to the risk for non-pregnancy. Therefore, other factors might affect conception in PCOS patients.


Crystallization and preliminary X-ray diffraction studies of a surface mutant of the middle domain of PB2 from human influenza A (H1N1) virus.
In the last hundred years, four influenza pandemics have been experienced, beginning with that in Spain in 1918. Influenza A virus causes severe pneumonia and its RNA polymerase is an important target for drug design. The influenza A (H1N1) virus has eight ribonucleoprotein complexes, which are composed of viral RNA, RNA polymerases and nucleoproteins. PB2 forms part of the RNA polymerase complex and plays an important role in binding to the cap structure of host mRNA. The middle domain of PB2 includes a cap-binding site. The structure of PB2 from H1N1 complexed with m(7)GTP has not been reported. Plate-like crystals of the middle domain of PB2 from H1N1 were obtained, but the quality of these crystals was not good. An attempt was made to crystallize the middle domain of PB2 complexed with m(7)GTP using a soaking method; however, electron density for m(7)GTP was not observed on preliminary X-ray diffraction analysis. This protein has hydrophobic residues on its surface and is stable in the presence of high salt concentrations. To improve the solubility, a surface double mutant (P453H and I471T) was prepared. These mutations change the surface electrostatic potential drastically. The protein was successfully prepared at a lower salt concentration and good cube-shaped crystals were obtained using this protein. Here, the crystallization and preliminary X-ray diffraction analysis of this mutant of the middle domain of PB2 are reported.


Short communication: Effects of changing teatcup removal and vacuum settings on milking efficiency of an automatic milking system.
The aim of this experiment was to assess strategies to reduce milking time in a pasture-based automatic milking system (AMS). Milking time is an important factor in automatic milking because any reductions in box time can facilitate more milkings per day and hence higher production levels per AMS. This study evaluated 2 end-of-milking criteria treatments (teatcup removal at 30% and 50% of average milk flowrate at the quarter-level), 2 milking system vacuum treatments (static and dynamic, where the milking system vacuum could change during the peak milk flowrate period), and the interaction of these treatment effects on milking time in a Lely Astronaut A4 AMS (Maassluis, the Netherlands). The experiment was carried out at the research facility at Teagasc Moorepark, Cork, Ireland, and used 77 spring-calved cows, which were managed on a grass-based system. Cows were 179 DIM, with an average parity of 3. No significant differences in milk flowrate, milk yield, box time, milking time, or milking interval were found between treatments in this study on cows milked in an AMS on a pasture-based system. Average and peak milk flowrates of 2.15 kg/min and 3.48 kg/min, respectively, were observed during the experiment. Small increases in maximum milk flowrate were detected (+0.09 kg/min) due to the effect of increasing the system vacuum during the peak milk flow period. These small increases in maximum milk flowrate were not sufficient to deliver a significant reduction in milking time or box time. Furthermore, increasing the removal setting from 30% of the average milk flowrate to 50% of the average milk flowrate was not an effective means of reducing box time, because the resultant increase in removal flowrate of 0.12 kg/min was not enough to deliver practical or statistically significant decreases in milking time or box time. Hence, to make significant reductions in milking time, where cows have an average milk flow of 2 kg/min and yield per milking of 10 kg, end-of-milking criteria above 50% of average milk flowrate at the quarter level would be required.


Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).
Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care.


Neuromuscular fatigue and recovery in elite female handball players.
The purpose of this study was to investigate the degree of neuromuscular fatigue and recovery from fatigue, following handball training and handball matches at elite level. The focus was specifically on changes in physical performance when playing three matches over the course of 3 days, which simulates a sequence in international championships. Female players from the Norwegian national handball team were tested during a 5-day training camp (seven players) and a 3-day international tournament (eight players). Testing was done before and after training sessions and matches. Neuromuscular fatigue was measured as changes in voluntary isokinetic knee extensions, jump height in counter-movement jumps, and 20 m sprint time. The results showed a significant reduction by 2-6% in all three performance tests during the training camp and by 4-7% during the tournament (sprint and jump test) (P<0.05). Slow recovery was indicated by incomplete restoration of performance between matches and training sessions. The paper discusses the insufficient recovery measured related to handball performance. Because of changes in the rules of the game and strategic tendencies towards higher speed in play, the physical demands in elite handball seems to be increasing. The results of the study indicate that coaches should consider physical loading and recovery time available when distributing playing time between individual players in international tournaments.


Estimation of beef marbling in the Longissimus muscle with computer image analysis of ultrasonic pictures of the Iliocostalis muscle area.
This study investigated an objective method for estimating beef marbling using ultrasonic images of the Iliocostalis muscle and the Lomgissimus muscle area sections. Thirty-one Japanese Black cattle steers were used in this study. The end of the left side shoulder blade bone was scanned using an ultrasonic device. Ultrasonic images were captured of the Longissimus muscle area and that around the Iliocostalis muscle area. Twenty items were measured in the two images using computer image analysis software. The level of beef marbling was measured according to the Beef Marbling Standard (BMS) for carcass grading, and the percentage of ether-extractable fat content in the Longissimus muscle (EE). The difference in the gray level between the Iliocostalis muscle and intermuscular fat (X10) was used to estimate the BMS and the EE, which were highly correlated (r(2) = 67.72% and 61.30%). An equation was developed using four parameters from the two ultrasonic images, which could estimate the BMS (r(2) = 85.88%). This equation could also estimate the EE (r(2) = 68.98%). The equations used to estimate beef marbling were based on one to four parameters that included X10. Thus, ultrasonic images of the Iliocostalis muscle area section are important for estimating beef marbling.


Motor enrichment and the induction of plasticity before or after brain injury.
Voluntary exercise, treadmill activity, skills training, and forced limb use have been utilized in animal studies to promote brain plasticity and functional change. Motor enrichment may prime the brain to respond more adaptively to injury, in part by upregulating trophic factors such as GDNF, FGF-2, or BDNF. Discontinuation of exercise in advance of brain injury may cause levels of trophic factor expression to plummet below baseline, which may leave the brain more vulnerable to degeneration. Underfeeding and motor enrichment induce remarkably similar molecular and cellular changes that could underlie their beneficial effects in the aged or injured brain. Exercise begun before focal ischemic injury increases BDNF and other defenses against cell death and can maintain or expand motor representations defined by cortical microstimulation. Interfering with BDNF synthesis causes the motor representations to recede or disappear. Injury to the brain, even in sedentary rats, causes a small, gradual increase in astrocytic expression of neurotrophic factors in both local and remote brain regions. The neurotrophic factors may inoculate those areas against further damage and enable brain repair and use-dependent synaptogenesis associated with recovery of function or compensatory motor learning. Plasticity mechanisms are particularly active during time-windows early after focal cortical damage or exposure to dopamine neurotoxins. Motor and cognitive impairments may contribute to self-imposed behavioral impoverishment, leading to a reduced plasticity. For slow degenerative models, early forced forelimb use or exercise has been shown to halt cell loss, whereas delayed rehabilitation training is ineffective and disuse is prodegenerative. However, it is possible that, in the chronic stages after brain injury, a regimen of exercise would reactivate mechanisms of plasticity and thus enhance rehabilitation targeting residual functional deficits.


TGF-β-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases.
Fibrotic diseases are characterized by net accumulation of extracellular matrix proteins in affected organs leading to their dysfunction and ultimate failure. Myofibroblasts have been identified as the cells responsible for the progression of the fibrotic process, and they originate from several sources, including quiescent tissue fibroblasts, circulating CD34⁺ fibrocytes and the phenotypic conversion of various cell types into activated myofibroblasts. Several studies have demonstrated that endothelial cells can transdifferentiate into mesenchymal cells through a process termed endothelial- mesenchymal transition (EndMT) and that this can give rise to activated myofibroblasts involved in the development of fibrotic diseases. Transforming growth factor β (TGF-β) has a central role in fibrogenesis by modulating the fibroblast phenotype and function, inducing myofibroblast transdifferentiation and promoting matrix accumulation. In addition, TGF-β by inducing EndMT may further contribute to the development of fibrosis. Despite extensive investigation of the pathogenesis of fibrotic diseases, no effective treatment strategies are available. Delineation of the mechanisms responsible for initiation and progression of fibrotic diseases is crucial for the development of therapeutic strategies for the treatment of the disease. In this review, we summarize the role of the TGF-β signaling pathway and EndMT in the development of fibrotic diseases and discuss their therapeutic potential.


Long-term performance of single-connector (DF4) implantable defibrillator leads.
Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.


Prevalence of dermatological complaints in patients undergoing treatment for breast cancer.
Internal malignancies such as breast cancer, as well as their treatment can often result in skin changes. To assess the prevalence of dermatological complaints in patients who are undergoing oncological treatment for breast cancer in a hospital in Tubarão, Santa Catarina, Brazil. Observational, cross-sectional study, from October 2015 to February 2016 in which 152 patients with the diagnosis of breast cancer, undergoing treatment with chemotherapy, radiotherapy, hormone therapy and/or surgery, were interviewed and completed a research protocol developed by the author. The treatment of breast cancer was associated with dermatological complaints in 94.1% of the interviewed, being with hair loss the most frequent, present in 79.6% of the sample, followed by nail changes (56%). Patients with lighter skin phototypes (I, II and III) had a lower risk (p=0.045) of developing skin changes when compared to darker phototypes. Radiation therapy (p=0.011) and oncological surgery (pFisher=0.004) were statistically significant when related to skin changes. Inherent to the design of the study, as well as recall bias. It was found that most patients diagnosed with breast cancer showed dermatologic manifestations during the proposed cancer treatment. Patients undergoing radiotherapy and surgery showed skin changes with greater statistical significance.


Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract.
Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.


Autoimmune Encephalitis in Critical Care: Optimizing Immunosuppression.
Autoimmune diseases affecting the nervous systems are a common cause of admission to the intensive care unit (ICU). Although there exist several well-described clinical syndromes, patients more commonly present with progressive neurologic dysfunction and laboratory and radiographic evidence of central nervous system (CNS) inflammation. In the critical care setting, the urgency to intervene to prevent permanent damage to the nervous system and secondary injury from the systemic manifestations of these syndromes often conflicts with diagnostic uncertainty. Furthermore, treatment is limited by current therapeutic agents that remain non-specific for individual diseases, especially for those whose pathophysiology remains unclear. Primary autoimmune, paraneoplastic, parainfectious, and iatrogenic neurologic disorders all share the common underlying pathophysiology of an adaptive immune response directed against an antigen within the nervous system. Several different mechanisms of immune dysfunction are responsible for pathogenesis within each of these categories of disease, and it is at this level of pathophysiology that the most effective and appropriate therapeutic decisions are made. In this review, we outline the basic diagnostic and therapeutic principles in the management of autoimmune diseases of the nervous system in the ICU. We approach these disorders not as lists of distinct clinical syndromes or molecular targets of autoimmunity but rather as clusters of syndromes based on these common underlying mechanisms of immune dysfunction. This approach emphasizes early intervention over precise diagnosis. As our understanding of the immune system continues to grow, this framework will allow for a more sophisticated approach to the management of patients with these complex, often devastating but frequently reversible, neurologic illnesses.


Cross-cultural adaptation of the CRS-PRO questionnaire into French.
Chronic rhinosinusitis (CRS), encompasses many different clinical patterns with variable response to treatment. Precise criteria specifying disease severity and control are lacking in the current literature. Our aim was to perform a cross-cultural adaptation of the CRS-PRO, creating a French version for use as a routine questionnaire in the assessment of patients with CRS. The CRS-PRO questionnaire was translated according to the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) through a three-step procedure including a backward translation. Seven of 12 items were initially discordant between the three translators before achieving consensus (Step 1). Two of 12 items were discordant between the backward translation and the initial CRS-PRO version regarding the word "mucus"(Step 2). Step 3 allowed the creation of a French proof-read version of the CRS-PRO questionnaire. Thirty patients were included for initial validation, mean age of 49.2 ± 15 years and 63.3% (19/30) male. It took them 67 ± 23 s to complete the questionnaire without any patients requiring more than 2 min. This study presents the French version of the CRS-PRO questionnaire-an adapted, validated, and well-accepted instrument to evaluate the CRS symptoms in the French speaking population.


Relation of breast cancer with passive and active exposure to tobacco smoke.
Studies on passive smoking have consistently shown a tendency toward an increased risk of breast cancer, while studies an active smoking have failed to demonstrate an association. This apparent contradiction may stem from not separating passive smokers from the unexposed when assessing the effect of active smoking. a population based case-control study was conducted in Geneva, Switzerland, between January 1992 and October 1993 to determine the relation of passive and active smoking to breast cancer when the referent unexposed category consisted of women unexposed to active and passive smoke. The 244 patients with breast cancer (cases) were compared with 1.032 women free of breast cancer (controls). The lifetime history of active and passive smoking was recorded year by year, between the age of 10 and the date of the interview. The adjusted odds of breast cancer for ever active smokers, compared with women unexposed to either passive or active smoke, were 2.2 (95% confidence interval (CI) 1.0-4.4) for an average lifetime consumption of 1-9 cigarettes per day, 2.7% (95% CI 1.4-5.4) for 10-19 cigarettes per day, and 4.6 (95% CI 2.2-9.7) for 30 or more cigarettes per day. Among passive smokers, the adjusted odds ratio was 3.2 (95% CI 1.6-6.3) for being exposed for the equivalent of 2 hours per day for 25 years. The odds ratios were adjusted for known or postulated risk factors of breast cancer, including alcohol and saturated fat intake. There was no evidence of strong selection, detection, or recall biases. Active and passive exposure to tobacco smoke may increase the risk of breast cancer. Additional studies are needed to decide whether the association is causal. Further elucidation of this relation would benefit not only the prevention of breast cancer but also the the prevention of other smoking-related diseases in women.


Involvement of rho-kinase activation in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in patients with coronary artery disease.
Activation of Rho-kinase plays a central role in the pathogenesis of drug-eluting stents (DES)-induced coronary hyperconstricting responses in pigs in vivo has been previously demonstrated. In the present study, Rho-kinase activation involved in those responses in patients with coronary artery disease (CAD) is examined. In 24 patients with CAD who underwent coronary intervention with either DES or bare-metal stents (BMS), coronary vasomotor responses to intracoronary acetylcholine (ACh) before and after intracoronary pre-treatment with a Rho-kinase inhibitor, fasudil was examined. Coronary vasomotor responses by quantitative coronary angiography (QCA) and coronary vascular structure by optical coherence tomography (OCT) was evaluated. QCA showed that the coronary vasoconstricting responses to ACh were significantly enhanced in the DES group compared with the BMS group both at the proximal and the distal segments adjacent to the stents (proximal: BMS -13.0±10.7% vs. DES -25.4±14.3%, P=0.036; distal: BMS -24.4±12.2% vs. DES -43.8±14.7%, P=0.003). Importantly, fasudil markedly attenuated the enhanced vasoconstricting responses to ACh in the DES group (proximal 10.2±11.7%, distal 14.4±10.5% vs. before fasudil, both P<0.01). In the OCT imaging analysis, there was no significant correlation between intimal thickness and coronary vasoconstriction to ACh. These results indicate that Rho-kinase activation is substantially involved in the pathogenesis of the DES-induced coronary hyperconstricting responses in patients with CAD, suggesting the therapeutic importance of Rho-kinase pathway.


Valvular and coronary artery surgery.
This brief review supplements recent extensive discussion of valvular and coronary artery surgery in this journal. It includes 1) ultrasonic decalcifications of stenotic aortic valves, a technique once more found wanting because of induced aortic incompetence; 2) the concept of prosthesis-specific anticoagulation, adjusting the level of anticoagulant control for individual prosthetic valves to minimize thromboembolic and hemorrhagic complications; 3) the use of homograft aortic roots to treat aortic prosthetic valve endocarditis; and 4) a new approach to the repair of postinfarction ventricular septal defects, supported by excellent results.


[Cytotoxic properties of pancreatic ribonuclease, modified by the surface active substance oxanol KD-6].
Pancreatic RNase modified by the surface active substance oxanole KD-6 (OxRNase) was studied in respect to its cytotoxic action on cells. The studies included in vitro and in vivo tests with intravital staining of the cells by neutral red and the 3H uridine label, as well as the test with the preparation action on fusion of lysosomes and phagosomes. It was shown that in all the tests the hydrophobised RNase had a higher cytotoxic action versus the native enzyme. The analysis of the experimental data suggested that the cytotoxicity of the hydrophobised RNase was due to its action on the cell membrane structures including the lysosome membranes.


Attentional cartography: mapping the distribution of attention across time and space.
Decades of research have shown that the orienting of attention follows a reliable pattern of facilitation and then inhibition following a peripheral cue. However, the literature lacks a high-resolution spatiotemporal map of this pattern. Moreover, the use of visual placeholders to highlight potential stimulus locations is inconsistent. This is puzzling, given attention's well-known predilection for objects. In this article, we remedy these outstanding issues with a large-scale investigation charting the spatiotemporal distribution of attention. Participants detected targets presented at 121 possible locations 100, 200, 400, or 800 ms following an uninformative peripheral cue. The cued locations were presented with or without placeholders. With placeholders, the classic pattern of early facilitation and late inhibition was observed for targets appearing within the placeholders, and the spread of inhibition was severely limited to within the placeholders. Without placeholders, we observed inhibition shortly after cue presentation, upsetting the famously reliable effect of facilitation following a cue. Moreover, inhibition spread from the cued location, unlike when placeholders were present. This investigation has produced an eminently detailed spatiotemporal map of attentional orienting and illustrated the consequences of placeholder stimuli, with surprising results.


Purification and characterization of the Sjögren's syndrome A and B antigens.
In sera from patients with systemic lupus erythematosus and Sjögren's syndrome (SS), antibodies are present in high titres to small cellular proteins which may be involved in RNA processing. In this study we used affinity chromatography with antibodies isolated from patients sera to purify two cellular antigens; SS-A (Ro) from human spleen and SS-B (La) from rabbit thymus. Both antigens co-purified as a molecular complex from human thymus. The protein components were acidic though SS-A was resistant, and SS-B sensitive to trypsin. On polyacrylamide gel electrophoresis SS-A migrated as a single 55K polypeptide and SS-B as 40-45K polypeptides with a 29K degradation product. All of these polypeptides were reactive in the western blot with their respective antibodies from characterized sera and similar components in SS-B were demonstrated in tissue extracts from a range of mammalian species. These purified antigens represent important reagents for the investigation of the aetiology of some types of autoimmunity.


[Trial of detection of female carriers for the ornithine-carbamyltransferase deficiency by the urine assay of crotic acid. Apropos of a family study].
Studies on the detection of female carriers of the gene responsible for ornithine carbamoyl transferase deficiency are reported. The method used was that described by Goldstein and is based on provoked acidemia after an oral protein overload. Transmission of the disease as a sex linked dominant was confirmed. The heterogeneity of the metabolic disorder is discussed.


Significance of the Reverse Halo Sign in Immunocompromised Patients.
OBJECTIVE. The purpose of this study is to assess the most common causes of the reverse halo sign (RHS) in immunocompromised patients and to identify clinicoradiologic features that help in achieving a specific diagnosis. MATERIALS AND METHODS. This retrospective study included 70 patients with hematologic malignancy, neutropenia, or history of solid organ transplant or stem cell transplant who had the RHS at chest CT. Absolute neutrophil count, imaging features of the RHS, and presence of pleural effusions were noted and correlated with the specific diagnosis. A decision tree was constructed from predictive imaging features and compared with radiologist assessment for infectious versus noninfectious cause. RESULTS. Infection, including fungal and bacterial pneumonia, was the most common cause of the RHS (66%), followed by organizing pneumonia (26%). Noninfectious causes such as organizing pneumonia were more likely in the solid organ transplant group, whereas infections were more likely in patients with hematologic malignancy and stem cell transplant. Among fungal pneumonias, aspergillosis (20%) was as common as mucormycosis (19%). In univariate analysis, neutropenia, rim thickness, central ground-glass attenuation, and lesion diameter correlated with infectious cause. A decision tree using neutropenia, rim thickness, central ground-glass attenuation, and pleural effusion could differentiate infectious from noninfectious cause with accuracy of 78%, compared with radiologist accuracy of 81%. CONCLUSION. Infections are more likely to cause RHS than noninfectious processes in immunocompromised patients, and aspergillosis may be as likely overall as mucormycosis because of its higher frequency in these patients. A decision tree using clinical and imaging features can help differentiate infectious from noninfectious causes of RHS.


Implementation of an integrated longitudinal curricular activity for graduating pharmacy students.
To evaluate whether a novel integrated longitudinal curricular activity to prepare graduating doctor of pharmacy (PharmD) students for 2 comprehensive examinations was successful, and to assess whether it engaged other pharmacy students in curricular discussion and learning. Thirty-eight of 91graduating third-year (P3) students in a PharmD program formed 11 teams to create and present pharmacotherapeutic posters to their peers. The impact of the novel activity on graduating students' performance on the North American Pharmacist Licensure Examination (NAPLEX) and a comprehensive commercial examination was assessed. All first-year (P1), second-year (P2), and P3 students reviewed and discussed the content of each poster. Participants in the integrated longitudinal curricular activity performed better than nonparticipants on the commercial examination (p=0.023) and NAPLEX (p=0.033). However, regardless of participation, commercial examination scores predicted a significant amount of variance (ie, 34%) in NAPLEX scores. The P3 participants (83%) believed the curricular activity assisted them in their NAPLEX preparation, while 75% of P1 students, 79% of P2 students, and 80% of P3 students agreed that poster review provided an effective summary of different disease states. Ninety percent of faculty poster evaluators reported that the posters were professional, and all evaluators agreed that participants effectively conveyed their message to the intended audience. The integrated longitudinal curricular activity provided a positive learning environment for all pharmacy students and may have better prepared graduating students' for the NAPLEX.


ADHD in college students.
According to the American Psychiatric Association, 3% to 7% of the school-age population has ADHD and many children continue to display significant symptoms throughout adolescences and adulthood. Relative to the childhood literature, less is known about ADHD in adults, especially college students with ADHD. The principle purpose of this review articles is to summarize the major research findings concerning ADHD in the college student population with regard to prevalence of symptoms, neuropsychological and psychological functioning. Overall, findings suggest that college students with ADHD are at greater risk for academic and psychological difficulties, and they perform similar to non-ADHD controls on many neuropsychological tasks. These findings are preliminary, however, and are tempered by the small number of studies that have been conducted as well as the methodological limitations of these studies. Future research using larger sample sizes, rigorous assessment criteria, and a longitudinal design is needed to better understand the psychological, academic, and neuropsychological functioning of college students with ADHD. Studies are also needed to elucidate the effects of pharmacological and nonpharmacological effects of treatment on the functioning of college students with this disorder.


T-2 Toxin Induces Kidney Fibrosis via the mtROS-NLRP3-Wnt/β-Catenin Axis.
T-2 toxin causes kidney fibrosis. Wnt/β-catenin signaling promotes kidney fibrosis when sustained and activated. However, whether T-2-induced kidney fibrosis involves Wnt/β-catenin signaling activation has not been explored yet. T-2 toxin causes renal mitochondrial damage, leading to mitochondrial reactive oxygen species (mtROS) overproduction and NLRP3-inflammasome activation. The activated NLRP3-inflammasome can mediate fibrosis. However, whether the NLRP3-inflammasome can be mediated by mtROS and further regulate T-2-induced kidney fibrosis through Wnt/β-catenin signaling is unclear. In this study, first, we confirmed that T-2 toxin caused Wnt/β-catenin signaling activation in mice kidneys and HK-2 cells. Second, we confirmed that mtROS activated the NLRP3-inflammasome in T-2-exposed mice kidneys and HK-2 cells. Third, we confirmed that the NLRP3-inflammasome regulated the Wnt/β-catenin signaling in T-2 toxin-exposed mice kidneys and HK-2 cells. Finally, we confirmed that Wnt/β-catenin signaling regulated fibrosis in T-2 toxin-exposed mice kidneys and HK-2 cells. The above results confirm that T-2 toxin induces kidney fibrosis via the mtROS-NLRP3-Wnt/β-catenin axis.


The immune response against Francisella tularensis live vaccine strain in Lps(n) and Lps(d) mice.
The impact of Lps gene on the course of immune response against subcutaneous infection of mice with Francisella tularensis live vaccine strain was studied. Production and specificity of antibodies, cytotoxic responses of macrophages and NK-cells, spontaneous production ex vivo of cytokines IL-1 alpha, IL-2, IL-4, IL-6, IL-10, IFN-gamma, and TNF-alpha in spleen cell cultures in C3H/HeJ (Lps(d)) mice in comparison with C3H/HeN (Lps(n)) mice were tested. The value of LD(50) was significantly different in the two strains of mice (8.0 x 10(5) cfu for C3H/HeJ versus 4.61 x 10(3) cfu for C3H/HeJ mice after subcutaneous inoculation). The production of NO(2) is also impaired in C3H/HeJ mice in the early intervals after infection. Thus, the defective Lps gene of C3H/HeJ mice influences both the level of innate resistance of mice to F. tularensis live vaccine strain infection and the process of induction and regulation of immune response against this intracellular bacterial pathogen.


Analysis of factors associated with injury severity in crashes involving young New Zealand drivers.
Young people are a risk to themselves and other road users, as motor vehicle crashes are the leading cause of their death. A thorough understanding of the most important factors associated with injury severity in crashes involving young drivers is important for designing well-targeted restrictive measures within youth-oriented road safety programs. The current study estimates discrete choice models of injury severity of crashes involving young drivers conditional on these crashes having occurred. The analysis examined a comprehensive set of single-vehicle and two-vehicle crashes involving at least one 15-24 year-old driver in New Zealand between 2002 and 2011 that resulted in minor, serious or fatal injuries. A mixed logit model accounting for heterogeneity and heteroscedasticity in the propensity to injury severity outcomes and for correlation between serious and fatal injuries proved a better fit than a binary and a generalized ordered logit. Results show that the young drivers' behavior, the presence of passengers and the involvement of vulnerable road users were the most relevant factors associated with higher injury severity in both single-vehicle and two-vehicle crashes. Seatbelt non-use, inexperience and alcohol use were the deadliest behavioral factors in single-vehicle crashes, while fatigue, reckless driving and seatbelt non-use were the deadliest factors in two-vehicle crashes. The presence of passengers in the young drivers' vehicle, and in particular a combination of males and females, dramatically increased the probability of serious and fatal injuries. The involvement of vulnerable road users, in particular on rural highways and open roads, considerably amplified the probability of higher crash injury severity.


A comparative study on peripheral blood lymphocyte subpopulations in different kinds of warts.
Peripheral blood T-cell subpopulations were evaluated in 36 patients with clinically different types of warts, subdivided in 4 groups (common, genital, flat and plantar warts). A significant decrease was found in OKT3 and OKT4 subsets total count and in OKT4/OKT8 ratio in patients with common and genital warts as compared with controls. Only in common and genital warts did we also observe a significant decrease of percentage of OKT4 subset. No significant difference of considered parameters was observed in flat and plantar warts as compared to controls, apart from a significant increase in number of OKT8 subset in flat warts. We then discuss this different status of C.M.I. in patients with different clinical warts, stressing the importance of various types of HPV.


Assessment of sex-specific genetic and environmental effects on bone mineral density.
Although it is widely accepted that genes contribute significantly to the variation in bone mineral density (BMD), the nature of the genetic contribution is poorly defined. There are large gender differences in BMD, although whether sex-specific genetic effects influencing variation in BMD contribute to these differences is not known. To address this issue, we studied 929 subjects from large families participating in the Amish Family Osteoporosis Study. Bone mineral density was measured at the hip and spine by dual energy X-ray absorptiometry (DXA). We used variance decomposition procedures to partition variation in BMD into genetic and environmental effects common to both sexes and to men and women separately. After accounting for covariate effects, the heritability of BMD ranged from 0.63 to 0.72 in men and 0.80 to 0.87 in women. The residual environmental variance in BMD at the spine, but not hip, was significantly higher in men than in women (P < 0.05), reflecting a greater variance in BMD due to unexplained non-genetic factors in men. In contrast, there were no significant differences between men and women in the magnitude of the genetic variance in BMD, nor did the genetic correlation in BMD between men and women differ significantly from one. Overall, these analyses do not provide evidence for sex-specific genetic effects, suggesting that many of the genes influencing variation in BMD should be detectable in both men and women.


The treatment of acute vertigo.
Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière's disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v., 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or triethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internuclear inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20 degrees. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different interpretation of PPV etiopathogenesis, the maneuvers described by Semont, Epley, or Lempert and their modifications are undoubtedly effective. For this reason the first therapeutic approach in acute provoked vertigo must be by means of one of these kinds of treatments.


Plasma power controlled deposition of SiOx with manipulated Si Quantum Dot size for photoluminescent wavelength tailoring.
Plasma power controlled PECVD of SiO(x) under SiH(4)/N(2)O gas mixture with manipulated Si quantum dot (Si-QD) size for tailoring photoluminescent (PL) wavelength is demonstrated. The incomplete decomposition of N(2)O at high plasma power facilitates Si-rich SiO(x) deposition to enlarge O/Si composition ratio and to shrink Si-QD size. As RF plasma power increases from 20 to 70 W, the O/Si ratio is increased from 1 to 1.6 and the average Si-QD size is reduced from 4.5 to 1.7, which increases Si-QD density from 3.2 x 10(17) to 3.02 x 10(18) cm(-3) and blue-shifts PL wavelength from 780 to 380 nm.


A 6-month follow-up of an RCT on behavioral and neurocognitive effects of neurofeedback in children with ADHD.
To assess the long-term effects of neurofeedback (NFB) in children with attention deficit hyperactivity disorder (ADHD), we compared behavioral and neurocognitive outcomes at a 6-month naturalistic follow-up of a randomized controlled trial on NFB, methylphenidate (MPH), and physical activity (PA). Ninety-two children with a DSM-IV-TR ADHD diagnosis, aged 7-13, receiving NFB (n = 33), MPH (n = 28), or PA (n = 31), were re-assessed 6-months after the interventions. NFB comprised theta/beta training on the vertex (cortical zero). PA comprised moderate to vigorous intensity exercises. Outcome measures included parent and teacher behavioral reports, and neurocognitive measures (auditory oddball, stop-signal, and visual spatial working memory tasks). At follow-up, longitudinal hierarchical multilevel model analyses revealed no significant group differences for parent reports and neurocognitive measures (p = .058-.997), except for improved inhibition in MPH compared to NFB (p = .040) and faster response speed in NFB compared to PA (p = .012) during the stop-signal task. These effects, however, disappeared after controlling for medication use at follow-up. Interestingly, teacher reports showed less inattention and hyperactivity/impulsivity at follow-up for NFB than PA (p = .004-.010), even after controlling for medication use (p = .013-.036). Our findings indicate that the superior results previously found for parent reports and neurocognitive outcome measures obtained with MPH compared to NFB and PA post intervention became smaller or non-significant at follow-up. Teacher reports suggested superior effects of NFB over PA; however, some children had different teachers at follow-up. Therefore, this finding should be interpreted with caution. Clinical trial registration Train your brain and exercise your heart? Advancing the treatment for Attention Deficit Hyperactivity Disorder (ADHD), Ref. no. NCT01363544, https://clinicaltrials.gov/show/NCT01363544 .


Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition.
Regulation of epithelial and endothelial permeability is essential for proper function of compartmentalized organisms, and tyrosine phosphorylation plays an important role in this process. We analyzed the impact of protein tyrosine phosphatase (PTP) inhibition on the structure of endothelial junctional proteins. In human umbilical vein endothelial cells (HUVECs) the PTP inhibitors phenylarsine oxide (PAO) and pervanadate induced proteolysis of the tight junction protein occludin. Occludin proteolysis was inhibited by the metalloproteinase inhibitor 1,10-phenanthroline (PHEN), but not by inhibitors against other types of proteases. The junctional proteins ZO-1, cadherin and beta-catenin were not cleaved. Under conditions of occludin proteolysis, PAO treatment elevated permeability for FITC-dextran. Simultaneous incubation of HUVECs with PAO and PHEN inhibited the rise in permeability by more than 60%. PAO treatment lead to progressive disappearance of occludin from the cell periphery. In contrast, ZO-1, cadherin and beta-catenin retained their positions at the sites of intercellular contact. Simultaneous administration of PAO and PHEN greatly prevented the redistribution of occludin. These results demonstrate a selective cleavage of occludin by a metalloproteinase and suggest that this process can contribute to the control of paracellular permeability in endothelial cells.


PCR/SSCP detects reliably and efficiently DNA sequence variations in large scale screening projects.
A simple and fast method with high reliability is necessary for the identification of mutations, polymorphisms and sequence variants (MPSV) within many genes and many samples, e.g. for clarifying the genetic background of individuals with multifactorial diseases. Here we review our experience with the polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis to identify MPSV in a number of genes thought to be involved in the pathogenesis of multifactorial neurological disorders, including autoimmune diseases like multiple sclerosis (MS) and neurodegenerative disorders like Parkinson s disease (PD). The method is based on the property of the DNA that the electrophoretic mobility of single stranded nucleic acids depends not only on their size but also on their sequence. The target sequences were amplified, digested into fragments ranging from 50-240 base pairs (bp), heat-denatured and analysed on native polyacrylamide (PAA) gels of different composition. The analysis of a great number of different PCR products demonstrates that the detection rate of MPSV depends on the fragment lengths, the temperature during electrophoresis and the composition of the gel. In general, the detection of MPSV is neither influenced by their location within the DNA fragment nor by the type of substitution, i.e., transitions or transversions. The standard PCR/SSCP system described here provides high reliability and detection rates. It allows the efficient analysis of a large number of DNA samples and many different genes.


Matrix metalloproteinase-2: mechanism and regulation of NF-kappaB-mediated activation and its role in cell motility and ECM-invasion.
Matrix metalloproteinases belong to a family of enzymes that degrade the extracellular matrix (ECM) components and play an important role in tissue repair, tumor invasion, and metastasis. ECM proteins, cytokines, and certain other factors regulate MMP activity. OPN, an ECM protein, has been found to be overexpressed in various cancers, and it has been shown to correlate with the metastatic potential. Although such reports indicate that OPN plays an important role in the ability of tumor cells to survive and metastasize to secondary sites, the mechanism by which OPN regulates these processes is yet to be understood. In this study we report that native purified human OPN can induce cell migration and ECM invasion. Increased invasiveness and migration correlates with enhanced expression and activation of MMP-2. Our study provides evidence showing that OPN increases gelatinolytic activity by inducing MT1-MMP expression via activation of the NF-kappaB pathway. Suppression of MMP-2 by ASMMP-2 reduces the OPN-induced cell migration and ECM invasion. Curcumin blocks OPN-induced MT1-MMP expression and pro-MMP-2 activation. Curcumin, a known anti-inflammatory and anticarcinogenic compound, suppresses OPN-induced cell migration, invasion and induces apoptotic morphology in OPN-treated cells. The mechanism by which curcumin suppresses the OPN-induced effects has also been delineated. Curcumin inhibits MT1-MMP gene expression by blocking signals leading to IKK activation. This in turn inhibits IkappaBalpha phosphorylation and NF-kappaB activation.


Modelling future impacts of air pollution using the multi-scale UK Integrated Assessment Model (UKIAM).
Integrated assessment modelling has evolved to support policy development in relation to air pollutants and greenhouse gases by providing integrated simulation tools able to produce quick and realistic representations of emission scenarios and their environmental impacts without the need to re-run complex atmospheric dispersion models. The UK Integrated Assessment Model (UKIAM) has been developed to investigate strategies for reducing UK emissions by bringing together information on projected UK emissions of SO2, NOx, NH3, PM10 and PM2.5, atmospheric dispersion, criteria for protection of ecosystems, urban air quality and human health, and data on potential abatement measures to reduce emissions, which may subsequently be linked to associated analyses of costs and benefits. We describe the multi-scale model structure ranging from continental to roadside, UK emission sources, atmospheric dispersion of emissions, implementation of abatement measures, integration with European-scale modelling, and environmental impacts. The model generates outputs from a national perspective which are used to evaluate alternative strategies in relation to emissions, deposition patterns, air quality metrics and ecosystem critical load exceedance. We present a selection of scenarios in relation to the 2020 Business-As-Usual projections and identify potential further reductions beyond those currently being planned.


Improving Euro-Collins flushing solution's ability to protect kidneys from normothermic ischemia.
In this investigation, we describe a modification of Euro-Collins flushing solution which enables this solution to be effective in preventing normothermic postischemic acute renal failure. The left kidneys of Sprague-Dawley rats were briefly flushed in situ by vascular perfusion with Euro-Collins solution and the renal pedicle clamped to render the kidney ischemic and hold the flushing solution in the kidney. Following 1 h of in situ normothermic ischemia, the pedicle clamp was removed and a contralateral nephrectomy of the right kidney performed. In two other groups of rats the same experimental protocol was followed using Euro-Collins solution in which the dextrose in this solution was replaced with a similar osmolal contribution of either sucrose (64 g/l) or mannitol (35 g/l). Rats with kidneys flushed with the standard Euro-Collins solution containing dextrose (n = 24) exhibited significantly higher postischemic daily serum creatinine levels, a greater degree of tubular necrosis, and a higher mortality (75, versus 31%) than unflushed ischemic controls (n = 22). Rats with kidneys flushed with Euro-Collins, containing either sucrose (n = 25) or mannitol (n = 22) in place of dextrose, all survived, exhibited only focal tubular damage as observed by electron microscopy, and most returned to normal serum creatinine levels within 72 h following ischemia. These findings, together with other reports that mannitol- and sucrose-based flushing solutions provide excellent protection during prolonged cold ischemia, strongly argue for the substitution of sucrose, mannitol or other similar protective impermeant agents for dextrose in flushing solutions such as Euro-Collins.


Real-World Performance of the American Thyroid Association Risk Estimates in Predicting 1-Year Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study of 2000 Patients.
Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.


Association of Job Expectations Among High School Students With Early Death During Adulthood.
Deaths from self-injury are increasing. Understanding the sources of risk is important for prevention and treatment. To estimate the risks of suicide and drug poisoning deaths among adult men whose adolescent occupational expectations were not met in adulthood. This cohort study included a sample of men interviewed as part of the High School and Beyond study, a nationally representative study of US high school sophomores and seniors in 1980, who were interviewed every 2 years through 1986; those who were sophomores in 1980 were reinterviewed in 1992. Men who survived to 1992 and reported occupational expectations were included in the present study. Death records prior to 2018 were linked to mortality databases and released in 2019. Data analysis was conducted from May to October 2020. Occupational expectations. Survival or death by suicide, drug poisoning, chronic liver disease, heart disease, cancer, or some other cause, categorized from International Classification of Diseases, Ninth Revision and Tenth Revision codes. Competing risk Fine-Gray survival models regressed cause of death on adolescent occupational expectations and covariates. The 11 680 men in the High School and Beyond cohort study had a median (interquartile range) age of 29 (28-30) years in 1992, when the analysis of their future mortality began. Most men survived until 2015 (11 060 [weighted percentage, 95.0%]). Reported causes of death were suicide (60 [weighted percentage, 0.5%]), drug poisoning (40 [weighted percentage, 0.4%]), chronic liver disease (20 [weighted percentage, 0.2%]), heart disease (130 [weighted percentage, 1.0%]), cancer (100 [weighted percentage, 1.0%]), and other (280 [weighted percentage, 2.0%]). Subhazard ratios for death by suicide and drug poisoning were 2.91 (95% CI, 1.07-7.88; P = .04) and 2.62 (95% CI, 1.15-5.94; P = .02) times higher, respectively, among those who in 1980 expected to hold a subbaccalaureate occupation that later declined in labor market share compared with those with professional occupational expectations. The actual job held by men did not attenuate the hazards of deaths from suicide and drug poisoning. In this cohort study, men whose occupational expectations were not met because of labor market declines were at a higher risk of death from suicide or drug poisoning than men with different occupational expectations. Interventions to mitigate labor market changes should account for individuals' expectational ideals.


Switching species tropism: an effective way to manipulate the feline coronavirus genome.
Feline infectious peritonitis virus (FIPV), a coronavirus, is the causative agent of an invariably lethal infection in cats. Like other coronaviruses, FIPV contains an extremely large positive-strand RNA genome of ca. 30 kb. We describe here the development and use of a reverse genetics strategy for FIPV based on targeted RNA recombination that is analogous to what has been described for the mouse hepatitis virus (MHV) (L. Kuo et al., J. Virol. 74:1393-1406, 2000). In this two-step process, we first constructed by targeted recombination a mutant of FIPV, designated mFIPV, in which the ectodomain of the spike glycoprotein was replaced by that of MHV. This switch allowed for the selection of the recombinant virus in murine cells: mFIPV grows to high titers in these cells but has lost the ability to grow in feline cells. In a second, reverse process, mFIPV was used as the recipient, and the reintroduction of the FIPV spike now allowed for selection of candidate recombinants by their regained ability to grow in feline cells. In this fashion, we reconstructed a wild-type recombinant virus (r-wtFIPV) and generated a directed mutant FIPV in which the initiation codon of the nonstructural gene 7b had been disrupted (FIPV Delta 7b). The r-wtFIPV was indistinguishable from its parental virus FIPV 79-1146 not only for its growth characteristics in tissue culture but also in cats, exhibiting a highly lethal phenotype. FIPV Delta 7b had lost the expression of its 7b gene but grew unimpaired in cell culture, confirming that the 7b glycoprotein is not required in vitro. We establish the second targeted RNA recombination system for coronaviruses and provide a powerful tool for the genetic engineering of the FIPV genome.


Excited state engineering for efficient reverse intersystem crossing.
Reverse intersystem crossing (RISC) from the triplet to singlet excited state is an attractive route to harvesting electrically generated triplet excitons as light, leading to highly efficient organic light-emitting diodes (OLEDs). An ideal electroluminescence efficiency of 100% can be achieved using RISC, but device lifetime and suppression of efficiency roll-off still need further improvement. We establish molecular design rules to enhance not only the RISC rate constant but also operational stability under electrical excitation. We show that the introduction of a second type of electron-donating unit in an initially donor-acceptor system induces effective mixing between charge transfer and locally excited triplet states, resulting in acceleration of the RISC rate while maintaining high photoluminescence quantum yield. OLEDs using our designed sky-blue emitter achieved a nearly 100% exciton production efficiency and exhibited not only low efficiency roll-off but also a marked improvement in operational stability.


Superior sensitivity of computed tomographic scanning to magnetic resonance imaging in metastatic neoplasia: two case reports.
A case of carcinoma of the breast and a case of melanoma metastatic to the brain were evaluated by both magnetic resonance imaging (MRI) and enhanced computed tomography (CT). In these two cases, enhanced CT was more sensitive and more clearly delineated the extent of disease. Does diagnostic imaging of central nervous system metastatic disease require both MRI and enhanced CT?


Polyphasic evidence for the reclassification of Rhodothermus obamensis Sako et al. 1996 as a member of the species Rhodothermus marinus Alfredsson et al. 1988.
DNA-DNA reassociation studies, 16S rRNA gene sequence comparisons and fatty acid analysis were used to reassess the taxonomic status of the type strain of Rhodothermus obamensis and several strains of the genus Rhodothermus isolated from widely distributed shallow marine hot springs. The results show that the type strain of R. obamensis, JCM 9785T, has a DNA-DNA reassociation value of 78% with the type strain of R. marinus, DSM 4252T. The other strains examined had DNA-DNA reassociation values that varied between about 68 and 94% with R. marinus. The 165 rRNA gene sequence was determined for the type strain of R. obamensis and found to share 99.5% similarity with the type strain of R. marinus. The fatty acid composition of R. obamensis was slightly different from that of the other strains examined, but indicated that this strain is very closely related to the other strains examined in this study. On the basis of DNA-DNA reassociation values, 16S rRNA gene sequence comparison and fatty acid profiles, it was concluded that R. obamensis and R. marinus represent the same species and that the name Rhodothermus obamensis should be regarded as a junior synonym of Rhodothermus marinus.


[A home exercise training program after acute coronary syndrome and/or endovascular coronary intervention: efficiency and a patient motivation problem].
To analyze the impact of a home exercise training (ET) program on quality of life, motor activity (MA), dietary habit, functional and biochemical parameters, and clinical course of the disease in patients who have experienced acute coronary syndrome (ACS) and/or endovascular coronary intervention (ECI). The trial included 100 patients after ECL who were randomized into 2 groups: those who had gone through Patient School (PS) and received a 6-week course of controlled ET (a study group (Group S)) and those who had gone through PS only (a control group (Group C). The patients of both groups were recommended a home ET program and, according to its implementation, they formed 2 subgroups: Subgroup A (home ET+) comprising 51 patients who had trained themselves at home) and Subgroup B (home ET-) consisting of 46 patients who had not. The follow-up lasted 1 year. Quality of life, risk factors, lifestyle and clinical parameters were assessed. As time elapsed, the patients' motivation to perform home ET; and, accordingly, the proportion of those who had trained themselves decreased in Group S to 67 and 61% and in Group C to 39 and 40% after 6 and 12 months, respectively. Among the reasons for refusal to perform home ET, disease was reported by only 5.6% of the patients (by all from Group C). The comprehensive physical rehabilitation program (RP) (controlled ET in combination with home ET) produced the best effect in raising the level of daily MA, exercise performance with a 21.3-fold increase in cardiac performance (p < 0.05) and a 14.3-fold decrease in heart rate increment in response to exercises. Group C patients who had refused the home ET program, as compared to those in the same group who had trained themselves at home, showed the worst daily MA levels, none body mass index reduction, and a rise in the low-density lipoprotein cholesterol (by 20.3%; p < 0.05) and in the number of angina attacks (by 1.9 times; p < 0.05). RP in the early-stage, which encompasses an educational program (PS), a short-term course of controlled ET and home ET used in patients with ACS, including in those after ECI, has clear clinical benefits. The participation of patients with coronary heart disease (CHD) in the home ET programs increases their motivation and, hence, the proportion of those who participate in therapeutic and rehabilitation measures. Home patient physical rehabilitation is one of the important components of different rehabilitation and prevention programs in patients with CHD after ACS and ECI.


[Continuous renal replacement therapy: management of acute renal insufficiency in critical care units].
Acute renal insufficiency is characterized by a sudden decrease in renal function. Various causes are implicated and the physiopathological mechanisms are quite complex. When kidney failure is associated with other organ or system failure, the patient is usually treated in an intensive care unit. Such "critical status" patients are characterized by severe cardiovascular, respiratory and metabolic unstability that may make conventional methods of dialysis (intermittent hemodialysis and peritoneal dialysis) impossible or inadvisable. Continuous methods of renal replacement include 24-hour extracorporeal blood filtration for an indefinite period of time. Such aspects of renal function as electrolyte regulation of nitrogenated products, inflammatory mediators and so forth are replaced or supplemented by various continuous modes available. In this review we discuss the functions and indications for the continuous renal replacement techniques available. The components of each technique are studied exhaustively with a view to obtaining benefit.


Curcumin supplementation protects from genotoxic effects of arsenic and fluoride.
The present study was aimed to evaluate curcumin as a potential natural antioxidant to mitigate the genotoxic effects of arsenic (As) and fluoride (F) in human peripheral blood lymphocytes. The study was divided into nine groups consisting of negative control, positive control treated with ethyl methane sulphonate (EMS; 1.93 mM) and curcumin control with only curcumin (1.7 microM) in blood culture. As (1.4 microM) and F (34 microM) were added alone as well as in combination, to the cultures, with and without curcumin. Cultures were analysed for chromosomal aberrations (both structural and numerical) and primary DNA damage via comet assay as the genotoxic parameters after an exposure duration of 24h. Results revealed that curcumin efficiently ameliorates the toxic effect of As and F by reducing the frequency of structural aberrations (>60%), hypoploidy (>50%) and primary DNA damage. In conclusion, curcumin mitigates the genotoxic effects of the two well known water contaminants (As and F) effectively and efficiently at the given concentration in vitro.


Genetic variation for upper thermal tolerance diminishes within and between populations with increasing acclimation temperature in Atlantic salmon.
Populations may counteract lasting temperature changes or recurrent extremes through plasticity or adaptation. However, it remains underexplored how outbreeding, either naturally, unintentionally, or facilitated, may modify a local response potential and whether genotype-by-environment interactions or between-trait correlations can restrict this potential. We quantified population differences and outbreeding effects, within-population genetic variation, and plasticity of these, for thermal performance proxy traits using 32 pedigreed wild, domesticated, and wild-domesticated Atlantic salmon families reared under common-garden conditions. Following exposure to ambient cold (11.6 °C) or ~4° and ~8° warmer summer temperatures, populations differed notably for body length and critical thermal maximum (CTmax) and for thermal plasticity of length, condition, and CTmax, but not for haematocrit. Line-cross analysis suggested mostly additive and some dominant outbreeding effects on means and solely additive outbreeding effects on plasticity. Heritability was detected for all traits. However, with increasing acclimation temperature, differences in CTmax between populations and CTmax heritability diminished, and CTmax breeding values re-ranked. Furthermore, CTmax and body size were negatively correlated at the genetic and phenotypic levels, and there was indirect evidence for a positive correlation between growth potential and thermal performance breadth for growth. Thus, population differences (including those between wild and domesticated populations) in thermal performance and plasticity may present a genetic resource in addition to the within-population genetic variance to facilitate, or impede, thermal adaptation. However, unfavourable genotype-by-environment interactions and negative between-trait correlations may generally hamper joint evolution in response to an increase in average temperature and temporary extremes.


Apolipoprotein A-IV as a novel gene associated with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder, affecting 6-10% of women of reproductive age. The etiology remains poorly understood. To investigate the differentially expressed proteins from PCOS patients versus healthy women, the protein expression in follicular fluid was analyzed using two-dimensional electrophoresis (2-DE). Since follicular fluid contains a number of secretory proteins required for oocyte fertilization and follicle maturation, it is possible that follicular fluid can be used as a provisional source for identifying pivotal proteins associated with PCOS. In this study, six overexpressed proteins [kininogen 1, cytokeratin 9, antithrombin, fibrinogen γ-chain, apolipoprotein A-IV (apoA-IV) precursor and α-1-B-glycoprotein (A1BG)] in follicular fluids from PCOS patients were identified with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) and nano LC-MS/MS. Western blot analysis confirmed that the protein expression levels of apoA-IV precursor and A1BG were increased in follicular fluid from PCOS patients compared with those from normal controls. The analysis of protein expression for other proteins revealed individual variation. These results facilitate the understanding of the molecular mechanisms of PCOS and provide candidate biomarkers for the development of diagnostic and therapeutic tools.


Environmental and Economic Assessment of Electrothermal Swing Adsorption of Air Emissions from Sheet-Foam Production Compared to Conventional Abatement Techniques.
A life-cycle assessment (LCA) and cost analysis are presented comparing the environmental and economic impacts of using regenerative thermal oxidizer (RTO), granular activated carbon (GAC), and activated carbon fiber cloth (ACFC) systems to treat gaseous emissions from sheet-foam production. The ACFC system has the lowest operational energy consumption (i.e., 19.2, 8.7, and 3.4 TJ/year at a full-scale facility for RTO, GAC, and ACFC systems, respectively). The GAC system has the smallest environmental impacts across most impact categories for the use of electricity from select states in the United States that produce sheet foam. Monte Carlo simulations indicate the GAC and ACFC systems perform similarly (within one standard deviation) for seven of nine environmental impact categories considered and have lower impacts than the RTO for every category for the use of natural gas to produce electricity. The GAC and ACFC systems recover adequate isobutane to pay for themselves through chemical-consumption offsets, whereas the net present value of the RTO is $4.1 M (20 years, $0.001/m(3) treated). The adsorption systems are more environmentally and economically competitive than the RTO due to recovered isobutane for the production process and are recommended for resource recovery from (and treatment of) sheet-foam-production exhaust gas. Research targets for these adsorption systems should focus on increasing adsorptive capacity and saturation of GAC systems and decreasing electricity and N2 consumption of ACFC systems.


Scan patterns during the processing of facial expression versus identity: an exploration of task-driven and stimulus-driven effects.
Perceptual studies suggest that processing facial identity emphasizes upper-face information, whereas processing expressions of anger or happiness emphasizes the lower-face. The two goals of the present study were to determine (a) if the distributions of eye fixations reflect these upper/lower-face biases, and (b) whether this bias is task- or stimulus-driven. We presented a target face followed by a probe pair of morphed faces, neither of which was identical to the target. Subjects judged which of the pair was more similar to the target face while eye movements were recorded. In Experiment 1 the probe pair always differed from each other in both identity and expression on each trial. In one block subjects judged which probe face was more similar to the target face in identity, and in a second block subjects judged which probe face was more similar to the target face in expression. In Experiment 2 the two probe faces differed in either expression or identity, but not both. Subjects were not informed which dimension differed, but simply asked to judge which probe face was more similar to the target face. We found that subjects scanned the upper-face more than the lower-face during the identity task but the lower-face more than the upper-face during the expression task in Experiment 1 (task-driven effects), with significantly less variation in bias in Experiment 2 (stimulus-driven effects). We conclude that fixations correlate with regional variations of diagnostic information in different processing tasks, but that these reflect top-down task-driven guidance of information acquisition more than stimulus-driven effects.


Determinants of spring migration departure decision in a bat.
Migratory decisions in birds are closely tied to environmental cues and fat stores, but it remains unknown if the same variables trigger bat migration. To learn more about the rare phenomenon of bat migration, we studied departure decisions of female common noctules (Nyctalus noctula) in southern Germany. We did not find the fattening period that modulates departure decisions in birds. Female noctules departed after a regular evening foraging session, uniformly heading northeast. As the day of year increased, migratory decisions were based on the interactions among wind speed, wind direction and air pressure. As the migration season progressed, bats were likely to migrate on nights with higher air pressure and faster tail winds in the direction of travel, and also show high probability of migration on low-pressure nights with slow head winds. Common noctules thus monitor complex environmental conditions to find the optimal migration night.


Non-telecentric two-photon microscopy for 3D random access mesoscale imaging.
Diffraction-limited two-photon microscopy permits minimally invasive optical monitoring of neuronal activity. However, most conventional two-photon microscopes impose significant constraints on the size of the imaging field-of-view and the specific shape of the effective excitation volume, thus limiting the scope of biological questions that can be addressed and the information obtainable. Here, employing a non-telecentric optical design, we present a low-cost, easily implemented and flexible solution to address these limitations, offering a several-fold expanded three-dimensional field of view. Moreover, rapid laser-focus control via an electrically tunable lens allows near-simultaneous imaging of remote regions separated in three dimensions and permits the bending of imaging planes to follow natural curvatures in biological structures. Crucially, our core design is readily implemented (and reversed) within a matter of hours, making it highly suitable as a base platform for further development. We demonstrate the application of our system for imaging neuronal activity in a variety of examples in zebrafish, mice and fruit flies.


Tunable surface plasmon polaritons and ultrafast dynamics in 2D nanohole arrays.
High-quality and unique surface plasmon resonance (SPR) with a narrow linewidth and controllable resonance energy plays a key role in wide applications including ultrahigh-resolution spectroscopy, on-chip sensing, optical modulation, and solar cell technology. In this work, the response of surface plasmon polariton (SPP) modes in Au nanohole arrays has been effectively tuned by properly adjusting the sample orientation without changing the geometrical parameters, and a very narrow linewidth down to 8 nm is achieved via the strong interference of two (0, -1) and (-1, 0) SPP modes in the Γ-M direction under transverse magnetic polarization. These results have been validated excellently by finite-element-method numerical simulations. More importantly, we have quantitatively investigated the contribution of conduction-band electron distribution to the SPP intensity of the array within a 20 ps timescale with ultrahigh sensitivity by utilizing home-built femtosecond transient absorption spectroscopy, and observed the minimum SPP intensity at ∼700 fs following excitation with a 0.2 μJ pulse. This study may help enhance the understanding toward the intrinsic micromechanism of SPR, thus offering opportunities for potential applications in strong coupling and new-style optical wave manipulations.


Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats.
Previous work indicates that female rats initiate cocaine use sooner than male rats and reach significantly higher break points (BPs) for a single injection of cocaine under a progressive ratio (PR) schedule compared to male rats. The present study extends previous work examining sex differences to the acquisition of methamphetamine (METH) (0.02 mg/kg) and maintenance of METH-maintained responding under a PR schedule. An automated priming procedure that has previously been shown to be sensitive to sex differences was used for the acquisition of drug self-administration. A PR schedule that has been shown to be sensitive in detecting sex differences in maintenance levels of cocaine-reinforced responding was used for the maintenance phase of the experiment. A greater percentage of female rats met the acquisition criterion for METH (0.02 mg/kg) self-administration compared to male rats (55.6% versus 11.1%, respectively), and they did so at a significantly faster rate. Under stable fixed-ratio 1 (FR1) conditions (after acquisition and 5 days before the PR schedule) female rats responded for significantly more METH (0.02 mg/kg) infusions compared to males. Dose-response curves obtained under the PR schedule during maintenance indicated that female rats self-administered significantly more METH infusions compared to male rats. These data suggest that female rats are more vulnerable to the acquisition of METH self-administration, and they are more motivated to self-administer METH compared to male rats under a PR schedule during the maintenance phase.


Induction of demyelination by a temperature-sensitive mutant of the coronavirus MHV-A59 is associated with restriction of viral replication in the brain.
The neurovirulence of eight temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59 in 4-week-old BALB/c mice was investigated. Whereas a dose of 100 p.f.u. of wild-type virus killed mice within a week, a 1000-fold higher dose of ts mutants did not. Three ts mutants induced demyelinating disease in the central nervous system (CNS). The pathology of the demyelinating disease caused by one mutant, designated ts-342, was studied in detail. Pathological changes, starting 3 days post-inoculation (p.i.), were characterized by inflammation and demyelination in the CNS. Antibody responses directed against all virus-specific structural proteins were present at 7 days p.i. No virus particles were observed by electron microscopy at 14 days p.i. However, macrophages and lymphocytes were abundant in the areas of demyelination. The growth kinetics in vivo of wild-type virus, ts-342 and a revertant of ts-342 were compared. Wild-type virus and the revertant replicated rapidly in the brain and spread to the liver causing a lethal hepatitis. Ts-342, however, replicated to a much lesser extent within the brain and could not be detected in the blood or liver. The ts lesion in the genome of ts-342 seems, therefore, to determine the outcome of the infection.


Integrating genetic and imaging investigations into the clinical management of congenital hyperinsulinism.
Congenital Hyperinsulinism (CHI) is a rare but important cause of hypoglycaemia in infancy. CHI is a heterogeneous disease, but has a strong genetic basis; a number of genetic causes have been identified with CHI in about a third of individuals, chiefly in the genes that code for the ATP sensitive K(+) channels (KATP ) in the pancreatic β-cells. Rapid KATP channel gene testing is a critical early step in the diagnostic algorithm of CHI, with paternal heterozygosity correlating with the occurrence of focal lesions. Imaging investigations to diagnose and localize solitary pancreatic foci have evolved over the last decade with (18)F-DOPA PET-CT scanning as the current diagnostic tool of choice. Although clinical management of CHI has improved significantly with the application of genetic screening and imaging investigations, much remains to be uncovered. This includes a better understanding of the molecular mechanisms for dysregulated insulin release in those patients without known genetic mutations, and the development of biomarkers that could characterize CHI, including long-term prognosis and targeted treatment planning, i.e. 'personalised medicine'. From the perspective of pancreatic imaging, it would be important to achieve greater specificity of diagnosis not only for focal lesions but also for diffuse and atypical forms of the disease.


Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy.
The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.


Serum leptin during recovery following maximal incremental and prolonged exercise.
This study investigated the delayed circulating leptin response to maximal and prolonged treadmill exercise. Six healthy untrained males performed three sessions after an overnight fast: control, maximal exercise, and prolonged exercise at 50% of maximal oxygen consumption. Blood samples were collected prior to exercise, at the end of exercise, and at 60, 120, 180, and 240 min following exercise and control sessions. Blood samples were analyzed for serum leptin, insulin, glucose, free fatty acids, and glycerol. Hemoglobin and hematocrit were measured to correct for plasma volume changes. Resting energy expenditure (REE) and body fat (BF) were also assessed. Immediately at the end of maximal and prolonged exercise, and during the 4 hours of recovery, serum leptin levels did not change significantly compared to their respective baseline values. At 240 min of recovery serum leptin decreased 7% and 9% (p>0.05) from the baseline in the maximal and prolonged sessions, respectively. In the control experiment serum leptin decreased 27% from the baseline at 240 min of the recovery (p < 0.05). No significant differences were found in leptin values between the control and exercise sessions. Control serum leptin was positively correlated (p < 0.05) to BF (r = 0.88) and glucose (r=0.96), and negatively correlated to REE (r= -0.81). In conclusion, maximal or prolonged exercise do not appear to have an influence on circulating serum leptin in the delayed (4 hr) post exercise recovery period.


Acceptability and potential impact on uptake of using different risk stratification approaches to determine eligibility for screening: A population-based survey.
Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. An online population-based survey of 668 adults in the UK aged 45-79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. We used multi-level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. Two members of the public contributed to the development of the survey and have commented on this paper.


Clostridium difficile: isolation and characteristics.
Clostridium difficile can be grown readily in Reinforced Clostridial Medium (RCM) containing 0-1-0-4% of o-, m- or p-cresol, or phenol. We recommend 0-2% of phenol or p-cresol in RCM for the isolation of this organism. The characteristic "cornfield" growth in RCM in 25-ml Universal containers is described. Glucose, fructose, galactose, mannose, raffinose, aesculin and mannitol are fermented with production of acid and gas; maltose, sucrose, glycogen, soluble starch and sorbitol are fermented with production of acid only. Lactose and rice starch are not fermented by any strain, and DL-methionine is not attacked. Nitrate is reduced to nitrite. Hydrogen sulphide and indole are not produced. Gelatin is attacked by all strains, but in some cases prolonged incubation is required. Hyaluronidase is produced, but not deoxyribonuclease. A lethal toxin appears to be produced. Strains possess shared and strain-specific antigens.