The Effectiveness of Serious Games for Alleviating Depression: Systematic Review and Meta-analysis.
Depression is a common mental disorder characterized by disturbances in mood, thoughts, or behaviors. Serious games, which are games that have a purpose other than entertainment, have been used as a nonpharmacological therapeutic intervention for depression. Previous systematic reviews have summarized evidence of effectiveness of serious games in reducing depression symptoms; however, they are limited by design and methodological shortcomings. This study aimed to assess the effectiveness of serious games in alleviating depression by summarizing and pooling the results of previous studies. A systematic review of randomized controlled trials (RCTs) was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The search sources included 6 bibliographic databases (eg, MEDLINE, PsycINFO, IEEE Xplore), the search engine "Google Scholar," and backward and forward reference list checking of the included studies and relevant reviews. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. Results of the included studies were synthesized narratively and statistically, as appropriate, according to the type of serious games (ie, exergames or computerized cognitive behavioral therapy [CBT] games). From an initial 966 citations retrieved, 27 studies met the eligibility criteria, and 16 studies were eventually included in meta-analyses. Very low-quality evidence from 7 RCTs showed no statistically significant effect of exergames on the severity of depressive symptoms as compared with conventional exercises (P=.12). Very low-quality evidence from 5 RCTs showed a statistically and clinically significant difference in the severity of depressive symptoms (P=.004) between exergame and control groups, favoring exergames over no intervention. Very low-quality evidence from 7 RCTs showed a statistically and clinically significant effect of computerized CBT games on the severity of depressive symptoms in comparison with no intervention (P=.003). Serious games have the potential to alleviate depression as other active interventions do. However, we could not draw definitive conclusions regarding the effectiveness of serious games due to the high risk of bias in the individual studies examined and the low quality of meta-analyzed evidence. Therefore, we recommend that health care providers consider offering serious games as an adjunct to existing interventions until further, more robust evidence is available. Future studies should assess the effectiveness of serious games that are designed specifically to alleviate depression and deliver other therapeutic modalities, recruit participants with depression, and avoid biases by following recommended guidelines for conducting and reporting RCTs. PROSPERO International Prospective Register of Systematic Reviews CRD42021232969; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=232969.


Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.
Calcium (Ca2+ ) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.


Cardiovascular comorbidities among public health clinic patients with diabetes: the Urban Diabetics Study.
We sought to determine the frequency and distribution of cardiovascular comorbidities in a large cohort of low-income patients with diabetes who had received primary care for diabetes at municipal health clinics. Outpatient data from the Philadelphia Health Care Centers was linked with hospital discharge data from all Pennsylvania hospitals and death certificates. Among 10,095 primary care patients with diabetes, with a mean observation period of 4.6 years (2.8 after diabetes diagnosis), 2,693 (14.3%) were diagnosed with heart disease, including 270 (1.4%) with myocardial infarction and 912 (4.8%) with congestive heart failure. Cerebrovascular disease was diagnosed in 588 patients (3.1%). Over 77% of diabetic patients were diagnosed with hypertension. Incidence rates of new complications ranged from 0.6 per 100 person years for myocardial infarction to 26.5 per 100 person years for hypertension. Non-Hispanic whites had higher rates of myocardial infarction, and Hispanics and Asians had fewer comorbid conditions than African Americans and non-Hispanic whites. Cardiovascular comorbidities were common both before and after diabetes diagnosis in this low-income cohort, but not substantially different from mixed-income managed care populations, perhaps as a consequence of access to primary care and pharmacy services.


Long-term changes in quality of life after surgery for pediatric obstructive sleep apnea.
To study long-term changes in quality of life in children after adenotonsillectomy for obstructive sleep apnea (OSA) documented by polysomnography. Prospective study of children with OSA at the University of New Mexico Children's Hospital, Albuquerque. Children who met inclusion criteria underwent adenotonsillectomy. Caregivers were asked to complete the OSA-18 quality of life survey prior to surgery (survey 1), within 7 months after surgery (short-term) (survey 2), and between 9 and 24 months after surgery (long-term) (survey 3). Scores from the preoperative and postoperative surveys were compared using the paired t test. The study population included 34 children, 27 (79%) of whom were male. The mean age of the children at the time of inclusion in the study was 6.7 years (range, 3.0-16.8 years). The mean total score for survey 1 (76.7) was significantly higher (P<.001) than the mean total score for survey 2 (32.0) or for survey 3 (40.9). However, the domains of sleep disturbance and physical suffering were significantly lower (P<or=.005) in survey 2 than in survey 3. The differences in the domains of emotional distress, daytime problems, and caregiver concerns between survey 2 and survey 3 were not statistically significant. Caregivers perceive a long-term improvement in quality of life after adenotonsillectomy for OSA although these improvements are more pronounced in the short-term than in the long-term and are not uniform across all domains of the OSA-18 survey.


Life-cycle biological efficiency of Bos indicus x Bos taurus and Bos taurus crossbred cow-calf production to weaning.
A deterministic model was developed that accounted for all biological inputs and outputs for a theoretical herd of F1 females at age equilibrium mated to produce three-way terminal-cross calves and for the required proportion of straightbred cows needed to produce replacements. Two Bos indicus x Bos taurus vs two Bos taurus x Bos taurus types of crossbred cows were compared in the production environment of south-central Nebraska. The four types of F1 females were from Hereford (H) or Angus (A) dams and by H or A (HA), Pinzgauer (Pz), Brahman (Bm), or Sahiwal (Sw) sires. The crossbred females were assumed mated to Red Poll (R) sires for their first calving and to Simmental (S) sires thereafter. Two evaluations of efficiency for each of the four breeding systems were total cow and calf feed energy input 1) per unit of only weaned calf weight output (CALFEFF, Mcal/kg) and 2) per unit of weaned calf plus .55 x cull cow weight output (TVALEFF, Mcal/kg). Results for a terminal age of 7 yr in systems using HA, Pz, Bm, and Sw crossbred cows, respectively, were 64.9, 64.5, 60.9, and 59.3 Mcal/kg for CALFEFF and 45.7, 46.4, 44.1, and 43.7 Mcal/kg for TVALEFF. Changing terminal age to 11 yr reduced CALFEFF about 6% but increased TVALEFF about 7%, because total inputs increased more than output value (10 vs 3%) from 7 to 11 yr terminal ages. These results suggest differences in efficiency among these breed crosses favoring the Bos indicus crossbred cows by over 4% in this particular environment.


The effect of donor graft type on survival after liver transplantation for hepatoblastoma in children.
Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatoblastoma (HBL). Although post-transplant outcomes have improved in the contemporary era, the impact of donor graft type on survival remains unclear. Using the United Network for Organ Sharing database (02/2002-06/2021), demographics, clinical characteristics, and patient and graft survival were analyzed in children (<18 years) who underwent LT for HBL according to donor graft type. The Kaplan-Meier method, log-rank tests, and Cox regression modeling were used to evaluate the effect of whole, partial, and split deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) on patient and graft survival. A total of 590 pediatric HBL LT recipients (344 whole graft DDLT; 62 partial graft DDLT; 139 split graft DDLT; 45 LDLT) were included. During 2012-2021 the proportion of LDLTs for HBL decreased to about 5% compared with about 11% during 2002-2011. No significant differences were identified by donor graft type in either patient survival (log-rank test, p = .45) or graft survival (log-rank test, p = .69). The results remained similar during the 2002-2011 era, while during the 2012-2021 era, split graft DDLT was associated with decreased graft loss risk versus whole graft DDLT (hazard ratio: 0.48, 95% confidence interval: 0.23-0.99, p = .046) without any other significant between-group differences. Utilizing non-whole liver grafts can increase access to LT in children with unresectable HBL while ensuring favorable outcomes. LDLT is underutilized in children with HBL in the United States, and efforts to explore LDLT options should be undertaken.


Improved learning of Riemannian metrics for exploratory analysis.
We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping).


Semi-Supervised Medical Image Segmentation with Co-Distribution Alignment.
Medical image segmentation has made significant progress when a large amount of labeled data are available. However, annotating medical image segmentation datasets is expensive due to the requirement of professional skills. Additionally, classes are often unevenly distributed in medical images, which severely affects the classification performance on minority classes. To address these problems, this paper proposes Co-Distribution Alignment (Co-DA) for semi-supervised medical image segmentation. Specifically, Co-DA aligns marginal predictions on unlabeled data to marginal predictions on labeled data in a class-wise manner with two differently initialized models before using the pseudo-labels generated by one model to supervise the other. Besides, we design an over-expectation cross-entropy loss for filtering the unlabeled pixels to reduce noise in their pseudo-labels. Quantitative and qualitative experiments on three public datasets demonstrate that the proposed approach outperforms existing state-of-the-art semi-supervised medical image segmentation methods on both the 2D CaDIS dataset and the 3D LGE-MRI and ACDC datasets, achieving an mIoU of 0.8515 with only 24% labeled data on CaDIS, and a Dice score of 0.8824 and 0.8773 with only 20% data on LGE-MRI and ACDC, respectively.


The Effects of Adding a Gel-Alike Curcuma longa L. Suspension as Color Agent on Some Quality and Sensory Properties of Yogurt.
Color is an important characteristic of food products. This characteristic is related to consumer acceptability. To use the entire rhizome of Curcuma longa (CL) as a food colorant, a novel gel alike stable suspension (CLS) was previously developed using cellulose nanofibers (CNFs). Therefore, the present study was conducted to evaluate the CLS as a color additive on a stirred yogurt. Three concentrations of CLS were studied (0.1, 0.125, and 0.15 wt. %) and compared to yogurt without CLS. The obtained yogurts were characterized through the determination of pH, titratable acidity, syneresis, color and curcumin content after 1, 7, 14, and 21 days of storage. Additionally, rheological and sensory measurements were performed on the samples after one day of storage. Results show that the addition of CLS does not affect the pH and titratable acidity of the samples, but all the yogurts showed an increase in their syneresis during the storage time, showing a breakdown of the gel structure. Furthermore, the CLS suspension has the ability to impart a yellow color to yogurts, a characteristic that was stable during storage. Finally, the addition of 1 wt. % or 1.25 wt. % of CLS allows the development of a yogurt with adequate sensory perception.


Post-infectious inflammation, autoimmunity, and OCD: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Disorder (PANS).
Post-infectious neuroinflammation has been implicated in multiple models of acute onset obsessive-compulsive disorder (OCD) including Sydenham's chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by an infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.


Effects of an applied voltage on direct interspecies electron transfer via conductive materials for methane production.
Direct interspecies electron transfer (DIET) between exoelectrogenic bacteria and methanogenic archaea via conductive materials is reported as an efficient method to produce methane in anaerobic organic waste digestion. A voltage can be applied to the conductive materials to accelerate the DIET between two groups of microorganisms to produce methane. To evaluate this hypothesis, two sets of anaerobic serum bottles with and without applied voltage were used with a pair of graphite rods as conductive materials to facilitate DIET. Initially, the methane production rate was similar between the two sets of serum bottles, and later the serum bottles with an applied voltage of 0.39V showed a 168% higher methane production rate than serum bottles without an applied voltage. In cyclic voltammograms, the characteristic redox peaks for hydrogen and acetate oxidation were identified in the serum bottles with an applied voltage. In the microbial community analyses, hydrogenotrophic methanogens (e.g. Methanobacterium) were observed to be abundant in serum bottles with an applied voltage, while methanogens utilizing carbon dioxide (e.g., Methanosaeta and Methanosarcina) were dominant in serum bottles without an applied voltage. Taken together, the applied voltage on conductive materials might not be effective to promote DIET in methane production. Instead, it appeared to generate a condition for hydrogenotrophic methanogenesis.


Bilateral diaphragmatic weakness: a late complication of radiotherapy.
Brachial plexus neuropathy is an unfortunate complication that sometimes follows radiotherapy to the axillary and supraclavicular regions. A patient is described who, 30 years after radiotherapy for Hodgkin's disease and more than 10 years after the development of radiation-induced bilateral brachial plexus neuropathy, presented with bilateral diaphragmatic weakness secondary to bilateral phrenic nerve weakness. Previous radiotherapy was the most probable cause of the condition.


Identification of Compounds with Efficacy against Malaria Parasites from Common North American Plants.
Some of the most valuable antimalarial compounds, including quinine and artemisinin, originated from plants. While these drugs have served important roles over many years for the treatment of malaria, drug resistance has become a widespread problem. Therefore, a critical need exists to identify new compounds that have efficacy against drug-resistant malaria strains. In the current study, extracts prepared from plants readily obtained from local sources were screened for activity against Plasmodium falciparum. Bioassay-guided fractionation was used to identify 18 compounds from five plant species. These compounds included eight lupane triterpenes (1-8), four kaempferol 3-O-rhamnosides (10-13), four kaempferol 3-O-glucosides (14-17), and the known compounds amentoflavone and knipholone. These compounds were tested for their efficacy against multi-drug-resistant malaria parasites and counterscreened against HeLa cells to measure their antimalarial selectivity. Most notably, one of the new lupane triterpenes (3) isolated from the supercritical extract of Buxus sempervirens, the common boxwood, showed activity against both drug-sensitive and -resistant malaria strains at a concentration that was 75-fold more selective for the drug-resistant malaria parasites as compared to HeLa cells. This study demonstrates that new antimalarial compounds with efficacy against drug-resistant strains can be identified from native and introduced plant species in the United States, which traditionally have received scant investigation compared to more heavily explored tropical and semitropical botanical resources from around the world.


A Comparative Study between Indigenous Low Cost Negative Pressure Wound Therapy with Added Local Oxygen versus Conventional Negative Pressure Wound Therapy.
The incidence of compound fractures and severe soft tissue loss has increased manifolds due to high speed traffics. Negative Pressure Wound Therapy (NPWT) is a treatment modality for managing soft tissue aspect of such injuries. It reduces the need of flap coverage. However, many patients from developing countries cannot afford a conventional NPWT. We developed an indigenous low cost NPWT for our patients and supplemented it with Topical Pressurised Oxygen Therapy (TPOT). We conducted this study to compare its treatment outcome with the use of conventional NPWT. The study was conducted from 2018 to 2020 at a tertiary care teaching hospital. A total of 86 patients were treated with NPWT and their results were assessed for various parameters like reduction in wound size, discharge, infection, etc. We included patients with acute traumatic wounds as well as chronic infected wounds, and placed them in three treatment groups to receive either conventional NPWT, Indigenous NPWT and lastly NPWT with supplement TPOT. We observed a significant reduction of wound size, discharge and infection control in all three groups. The efficacy of indigenous NPWT is at par with conventional NPWT. Only six patients who had several comorbidities required flap coverage while in another four patients we could not achieve desired result due to technical limitations. Indigenous NPWT with added TPOT is a very potent and cost effective method to control infection and rapid management of severe trauma seen in orthopaedic practice. It also decreases the dependency on plastic surgeons for management of such wounds.


Thresholds for thermal damage to normal tissues: an update.
The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002-2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time-temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.


Does prophylactic antidepressant treatment boost interferon-alpha treatment completion in HCV?
Depression is often a side effect of interferon-alpha treatment for hepatitis C, and is recognized as a cause for treatment discontinuation. When detected, antidepressant treatment begins promptly. In contrast to this rescue approach, prophylactic antidepressant treatment has been considered as a superior approach. While studies indicate that depression is lower with prophylaxis, no study has prospectively evaluated the degree that treatment completion might be boosted by the prophylactic strategy. A structured literature search was conducted to discover all trials of antidepressant prophylaxis for patients undergoing antiviral treatment for chronic hepatitis C. Selection criteria included: antidepressant prophylaxis study; report of depression treatment outcome; report of numbers discontinuing and reason for discontinuation (including any of the following: discontinuation data for medical side effects (i.e., thrombocytopenia); discontinuation due to lack of antiviral response; discontinuation due to lack of antidepressant effect; discontinuation due to antidepressant side effects; discontinuation due to patient preference; discontinuation due to loss to follow-up; or unspecified discontinuation). Across the studies, total enrollees were determined for the prophylaxis arms and the rescue arms, and then, again across studies, those discontinuing for reasons other than lack of antiviral response or medical side effect were summed for each of these two arms. Twelve studies were discovered. One was a retrospective chart review, one was an uncontrolled trial, and ten were controlled trials. Discontinuation of antiviral therapy was not less common in the prophylaxis arms: of the 396 patients treated by the prophylaxis strategy, 47 (11.9%) discontinued; of the 380 patients in the rescue strategy, 45 (11.8%) discontinued. While the prophylaxis strategy seems to manage depression symptoms, it does not seem to boost treatment completion. Rescue was a very successful strategy when indicated. While antidepressant prophylaxis has benefit in antiviral treatment, it should not generally be valued for boosting the likelihood of treatment completion.


Regulation of rat biliary cholesterol secretion by agents that alter intrahepatic cholesterol metabolism. Evidence for a distinct biliary precursor pool.
Propensity for cholesterol gallstone formation is determined in part by biliary cholesterol content relative to bile salts and phospholipid. We examined the hypothesis that the rate of biliary cholesterol secretion can be controlled by availability of an hepatic metabolically active free cholesterol pool whose size is determined in part by rates of sterol synthesis, as reflected by activity of the primary rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and of sterol esterification, as reflected by the activity of the enzyme acyl coenzyme A/cholesterol acyltransferase (ACAT). Rats were prepared with biliary, venous, and duodenal catheters. The enterohepatic circulation of biliary lipids was maintained constant by infusion of a bile salt, lecithin, cholesterol replacement solution. Administration of 25-hydroxycholesterol decreased HMG CoA reductase activity, increased ACAT activity, and decreased biliary cholesterol output 26% by 1 h. By 2 h, ACAT activity and biliary cholesterol secretion were at control levels. Administration of mevinolin, a competitive inhibitor of HMG CoA reductase, had no effect on ACAT activity and decreased biliary cholesterol secretion 16%. Administration of progesterone, an inhibitor of ACAT, had no effect on HMG CoA reductase and increased biliary cholesterol output 32% at 1 h. By 2 h, all parameters were near control levels. None of these agents had any significant effect on biliary bile salt or phospholipid secretion. Thus, acutely altering rates of esterification and/or synthesis can have profound effects on biliary cholesterol secretion independent of the other biliary lipids. These experiments suggest the existence of a metabolically active pool of free cholesterol that serves as a precursor pool for biliary cholesterol secretion. Furthermore, the size of this precursor pool is determined in part both by rates of cholesterol synthesis and esterification and is a key determinant of biliary cholesterol secretion.


Fat overload with a 10% soybean oil emulsion.
A 10% soybean oil emulsion (Intralipid) has been demonstrated to be an effective means of delivering an adequate caloric intake via a peripheral vein. This emulsion has generally been considered safe and free of significant complications. This is a report of a child who initially thrived on this intravenously administered fat emulsion, then suddenly developed a lifethreatening intolerance to the infusion, which appeared to be the "fat overload syndrome." This syndrome, seen frequently with earlier fat emulsions, has not been reported previously as a complication of the 10% soybean oil emulsion.


Narrow-linewidth chirped frequency comb from a frequency-shifted feedback Ti:sapphire laser seeded by a phase-modulated single-frequency fiber laser.
Frequency-shifted feedback (FSF) lasers have emerged as powerful tools for precision distance metrology. At the output of a Michelson interferometer, the detected rf spectra of the FSF laser light contain a length-dependent heterodyne beat signal whose linewidth ultimately limits the achievable accuracy of length measurements. Here, we demonstrate a narrow-linewidth chirped frequency comb from an FSF Ti:sapphire ring laser seeded by a phase-modulated, ultra-low-phase-noise, single-frequency fiber laser. We experimentally investigate the influence of the seed laser linewidth on the resulting width and shape of the length-dependent rf beat signal. An ultranarrow heterodyne beat linewidth of <20 Hz is observed.


High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission.
We explored the combination of busulfan/cyclophosphamide/etoposide as conditioning regimen prior to bone marrow transplantation in 31 patients with acute myeloid leukemia (AML) in first complete remission. The preparative regimen consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25 patients are alive in continuous complete remission. Estimated disease-free survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft-versus-host disease and cytomegalovirus infection, graft-versus-host disease and pneumonia, sepsis and mucositis, respectively). None of the patients have relapsed. As demonstrated by the results of this analysis, the conditioning regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in patients with AML in first complete remission. Main nonhematological toxicities were mucositis and hepatotoxicity. The low mortality and relapse rate appears to justify allogeneic bone marrow transplantation for patients with AML in first complete remission who have an HLA-identical donor. Whether this regimen offers a substantial improvement in disease-free and overall survival over presently used regimens warrants further investigation.


Dysnatremia on intensive care unit admission is a stronger risk factor when associated with organ dysfunction.
Dysnatremia present at the time of intensive care unit (ICU) admission is associated with mortality. In this study, we investigated the epidemiology of dysnatremia present on ICU admission and the impact of organ dysfunction on the association between dysnatremia and mortality. We hypothesized that dysnatremia comorbid with organ dysfunction is associated with higher risk of mortality. This retrospective study was conducted on all patients admitted to the International Hospital General ICU in Istanbul over a period of 6 years (2006-2011). Patients were classified, according to the most abnormal serum sodium values measured within 24 hours after ICU admission, into 7 groups as follows: normonatremia (135≤Na≤145 mmol/L), borderline hyponatremia (130≤Na<135 mmol/L), mild hyponatremia (125≤Na<130 mmol/L), severe hyponatremia (Na <125 mmol/L), borderline hypernatremia (145<Na≤150 mmol/L), mild hypernatremia (150<Na≤155 mmol/L), and severe hypernatremia (Na >155 mmol/L). The total admitting patient were 1657. A total of 1060 patients' data were analyzed in this study. Sodium levels were normal in 637 (60.1%), hyponatremic in 367 (34.6%) and hypernatremic in 56 (5.3%) patients. Multivariate analysis showed that only SAPS II was associated with increased mortality (OR, 1.05 [95% confidence interval, 1.02-1.09]). The odds ratio (95% CI) of dysnatremia (Na <125 mmol/L and >150 mmol/L) for mortality was 4.37 (2.29-8.36) in patients with organ dysfunction (number of dysfunctional organs ≥1) (P<0.001). Below 125 and above 150 mmol/L sodium levels at ICU admission are risk factors for higher mortality rates in patients with comorbid organ dysfunction. The effect of dysnatremia on mortality is observed when organ dysfunction is present.


Palmoplantar Dermatoses- A Clinical Study of 300 Cases.
Dermatoses affecting palms and soles are among the most difficult of all dermatological therapeutic problems. Many previous studies have focused on the specific diseases of palmoplantar dermatoses. However, none of them have included a comprehensive study of palmoplantar dermatoses. To study the epidemiological aspects like age distribution, sex distribution, the dermatoses affecting the palms & soles and the frequency of involvement of palms, soles or both palms & soles, in patient with palmoplantar dermatoses. This cross sectional study was conducted in the Department of Dermatology between October 2011 to September 2013. First 300 cases attending the department of dermatology primarily with complaints pertaining to palms and soles were enrolled in the study. After taking consent a detailed history and clinical examination pertaining to the aim of the study was recorded and analysed, which included inspection of morphology and distribution of lesions and palpation of any swelling. Direct microscopic examination of scrapings, wet mounted with 10% potassium hydroxide was done for cases with scaly lesions. Those who had a pustule, gram staining was done. Patch testing using Indian Standard Battery Series was done for those cases of eczema. A sample for biopsy was taken when diagnosis could not be arrived clinically, and subjected to histopathological examination. In our study of 300 patients with palmoplantar dermatoses, 164 were females and 136 were males, the ratio observed being 1.2:1. The peak incidence was found in the age group 21-30 years, with 41 females (25%) and 35 males (25.7%). Most frequently affected individuals in this study were housewives (30%). The most common five diseases of palmoplantar dermatoses were palmoplantar psoriasis (20.7%), moniliasis (19%), palmoplantar hyperhidrosis (7%), keratolysis exfoliativa (6%) and pitted keratolysis (6%). Majority of patients had involvement of both palms and soles (44.3%) as compared to patients with involvement of only palm (28%) and only sole (27.3%). The commonest palmoplantar dermatoses with only palm involvement was keratolysis exfoliativa (16.7%), with only sole involvement was moniliasis (41%) and with both palms and soles involvement was palmoplantar psoriasis (41.4%). Associated nail changes were seen in 80 cases (26.6%), with maximum incidence in palmoplantar psoriasis (62.5%). Associated dermatological conditions were observed in 43 patients (14.3%). Palmoplantar dermatoses are frequently encount-ered in the dermatologic field. Further investigation with a wider and larger population is necessary to understand the epidemiology, based on which accurate diagnosis and proper treatment could be achieved.


Locomotion in ornithischian dinosaurs: an assessment using three-dimensional computational modelling.
Ornithischian dinosaurs were primitively bipedal with forelimbs modified for grasping, but quadrupedalism evolved in the clade on at least three occasions independently. Outside of Ornithischia, quadrupedality from bipedal ancestors has only evolved on two other occasions, making this one of the rarest locomotory transitions in tetrapod evolutionary history. The osteological and myological changes associated with these transitions have only recently been documented, and the biomechanical consequences of these changes remain to be examined. Here, we review previous approaches to understanding locomotion in extinct animals, which can be broadly split into form-function approaches using analogy based on extant animals, limb-bone scaling, and computational approaches. We then carry out the first systematic attempt to quantify changes in locomotor muscle function in bipedal and quadrupedal ornithischian dinosaurs. Using three-dimensional computational modelling of the major pelvic locomotor muscle moment arms, we examine similarities and differences among individual taxa, between quadrupedal and bipedal taxa, and among taxa representing the three major ornithischian lineages (Thyreophora, Ornithopoda, Marginocephalia). Our results suggest that the ceratopsid Chasmosaurus and the ornithopod Hypsilophodon have relatively low moment arms for most muscles and most functions, perhaps suggesting poor locomotor performance in these taxa. Quadrupeds have higher abductor moment arms than bipeds, which we suggest is due to the overall wider bodies of the quadrupeds modelled. A peak in extensor moment arms at more extended hip angles and lower medial rotator moment arms in quadrupeds than in bipeds may be due to a more columnar hindlimb and loss of medial rotation as a form of lateral limb support in quadrupeds. We are not able to identify trends in moment arm evolution across Ornithischia as a whole, suggesting that the bipedal ancestry of ornithischians did not constrain the development of quadrupedal locomotion via a limited number of functional pathways. Functional anatomy appears to have had a greater effect on moment arms than phylogeny, and the differences identified between individual taxa and individual clades may relate to differences in locomotor performance required for living in different environments or for clade-specific behaviours.


Right or wrong, familiar or novel in pictorial list discrimination learning.
The interaction between nonassociative learning (presentation frequencies) and associative learning (reinforcement rates) in stimulus discrimination performance was investigated. Subjects were taught to discriminate lists of visual pattern pairs. When they chose the stimulus designated as right they were symbolically rewarded and when they chose the stimulus designated as wrong they were symbolically penalised. Subjects first learned one list and then another list. For a "right" group the pairs of the second list consisted of right stimuli from the first list and of novel wrong stimuli. For a "wrong" group it was the other way round. The right group transferred some discriminatory performance from the first to the second list while the control and wrong groups initially only performed near chance with the second list. When the first list involved wrong stimuli presented twice as frequently as right stimuli, the wrong group exhibited a better transfer than the right group. In a final experiment subjects learned lists which consisted of frequent right stimuli paired with scarce wrong stimuli and frequent wrong stimuli paired with scarce right stimuli. In later test trials these stimuli were shown in new combinations and additionally combined with novel stimuli. Subjects preferred to choose the most rewarded stimuli and to avoid the most penalised stimuli when the test pairs included at least one frequent stimulus. With scarce/scarce or scarce/novel stimulus combinations they performed less well or even chose randomly. A simple mathematical model that ascribes stimulus choices to a Cartesian combination of stimulus frequency and stimulus value succeeds in matching all these results with satisfactory precision.


Pregnancy anxiety and prenatal cortisol trajectories.
Pregnancy anxiety is a potent predictor of adverse birth and infant outcomes. The goal of the current study was to examine one potential mechanism whereby these effects may occur by testing associations between pregnancy anxiety and maternal salivary cortisol on 4 occasions during pregnancy in a sample of 448 women. Higher mean levels of pregnancy anxiety over the course of pregnancy predicted steeper increases in cortisol trajectories compared to lower pregnancy anxiety. Significant differences between cortisol trajectories emerged between 30 and 31 weeks of gestation. Results remained significant when adjusted for state anxiety and perceived stress. Neither changes in pregnancy anxiety over gestation, nor pregnancy anxiety specific to only a particular time in pregnancy predicted cortisol. These findings provide support for one way in which pregnancy anxiety may influence maternal physiology and contribute to a growing literature on the complex biological pathways linking pregnancy anxiety to birth and infant outcomes.


Anticoagulation therapy in pediatric patients with sinovenous thrombosis: a cohort study.
To assess the use of anticoagulant therapy in a consecutive cohort study of children with sinovenous thrombosis (SVT). A single institutional pilot study of anticoagulant therapy was conducted from January 1992 to December 1996 at the Hospital for Sick Children, Toronto, Ontario. Consecutive children with the diagnosis of SVT, made by computed tomography, magnetic resonance imaging (MRI), MRI with venography, ultrasonography, nuclear brain scanning, or conventional angiography were eligible for anticoagulant therapy. RADIOGRAPHIC EVALUATION: Most children underwent multiple radiographic tests for evaluation of the central nervous system. Of the 32 episodes of SVT, CT was performed in 30, MRI with or without venography in 26, ultrasonography in 11, and nuclear brain scanning in 5. The majority of the SVTs were located at the superior sagittal sinus (50%) and right lateral sinus complex (44%). There were 30 consecutive children with 32 episodes of SVT during the 5-year study (2 girls had recurrent SVT). The median age was 6.2 years (age range, 3 days to 18 years), and the sex of the patients was evenly distributed (15 girls and 15 boys). The primary associated clinical conditions consisted of systemic lupus erythematosus (n = 5), renal disease (n = 3), perinatal distress (n = 2), congenital heart disease (n = 1), cerebral arteriovenous malformation (n = 1), and neurosurgery for refractory seizures (n= 1). The remainder were previously healthy children older than 1 month (n = 10) and newborns (n = 7). Eight children were ineligible for anticoagulant therapy because of an associated intracranial hemorrhage (n = 6), a postoperative bleeding risk after neurosurgery (n = 1), or a prolonged delay from the diagnosis to the time of referral (n = 1). Ten children received standard heparin, and 12 children received low-molecular-weight heparin (LMWH) (enoxaparin sodium). Eighteen children were treated with oral anticoagulants for 3 months after initial heparin therapy, and 4 patients received LMWH for the entire course of treatment. There was no intracranial hemorrhage in the 12 patients treated with LMWH, but there was 1 case of clinically silent bleeding in the standard heparin group. The results of this pilot study suggest that anticoagulant therapy, in particular LMWH, is safe and may have a role in the treatment of children with SVT. A randomized controlled trial is warranted.


On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes.
The regulation of body axis specification in the common ancestor of bilaterians remains controversial. BMP signaling appears to be an ancient program for patterning the secondary, or dorsoventral, body axis, but any such program for the primary, or anteroposterior, body axis is debated. Recent work in invertebrates indicates that posterior Wnt/beta-catenin signaling is such a mechanism and that it evolutionarily predates the cnidarian-bilaterian split. Here, I argue that a Cartesian coordinate system of positional information set up by gradients of perpendicular Wnt and BMP signaling is conserved in bilaterians, orchestrates body axis patterning and contributes to both the relative invariance and diversity of body forms.


Action of sodium deoxycholate on subcutaneous human tissue: local and systemic effects.
Phosphatidylcholine injections have been used as a nonsurgical alternative to the surgical removal of undesired fat. Studies in cell culture suggest that sodium deoxycholate (SD) has a detergent action in fat reduction. The objective was to study SD in subcutaneous human tissue. Thirty volunteers underwent four sessions of subcutaneous abdominal injections of diluted 2.5 or 1% SD stock solutions or placebo. Clinical, hematologic, and ultrasonographic evaluations were performed for 3 months and histology at 3 and 6 months. Both concentrations of SD induced an inflammatory response at the injection site, with dose-dependent adipocyte lysis. Patients reported mild, localized heat, erythema, swelling, and intense pain. Microscopic evaluation revealed necrosis of adipose tissue with adipocyte lysis, fat dissolution, acute lymphomononuclear inflammatory reaction, and intense phagocytosis of fat cells by macrophages. Fibrosis was observed only at the 6-month biopsy. Nodules at the injection sites, compatible with areas of inflammation, were detected by ultrasonography 2 weeks after the first injection. Placebo injections induced no histologic changes. SD induces an inflammatory reaction in subcutaneous human fat and dose-dependent adipocyte lysis with acute pain and fibrosis. No systemic effects were detected. Further studies will establish the best dose-result ratio, frequency of application, and long-term safety.


Adult outcomes of three newborns with a combined weight of 1100 grams.
To present the short- and long-term (20 years) growth and developmental outcomes of four micropremies (birth weight of less than 500 grams). Retrospective review of medical records and prospective assessment/interview with patients and their families. One infant was lost at long-term follow-up. The other three showed a quite satisfactory health status and life style in early adulthood. Despite extreme low birth weight (less than 500 grams) normal outcomes are possible. In the case of micropremies, gestational age appears to be of greater importance than birth weight as well as female gender in the decision-making process regarding initiation of resuscitation.


Protein and lipid deposition rates in male broiler chickens: separate responses to amino acids and protein-free energy.
Two experiments of similar design were conducted with male broiler chickens over two body weight ranges, 200 to 800 g in Experiment 1 and 800 to 1,600 g in Experiment 2. The data were used to test the hypothesis that protein deposition rate increases (linearly) with increasing amino acid intake, until energy intake becomes limiting for protein deposition rate. Additional amino acid intake above this point would be deposited less efficiently. An increase in energy intake would increase lipid deposition rate, but should, at low amino acid intakes, not affect protein deposition rate. Each experiment consisted of 18 treatments: two levels of protein-free energy (energy(pf)) intake, combined with nine amino acid to energypf ratios. Protein was balanced for amino acid content and lysine was the first limiting amino acid in the diet. Protein deposition rate increased with additional amino acid intake. No evidence was found that energy(pf) intake limited protein deposition rate at high amino acid intake. Extra intake of energy(pf) increased lipid deposition rate, which was independent of amino acid intake. Where amino acid intake was limiting, additional intake of energy(pf) had generally no effect on protein deposition rate. The marginal efficiency of amino acid utilization for protein deposition did not depend on body weight. The facts are relevant to the modeling of the growth of broiler chickens.


Fibrils Emerging from Droplets: Molecular Guiding Principles behind Phase Transitions of a Short Peptide-Based Condensate Studied by Solid-State NMR.
Biochemical reactions occurring in highly crowded cellular environments require different means of control to ensure productivity and specificity. Compartmentalization of reagents by liquid-liquid phase separation is one of these means. However, extremely high local protein concentrations of up to 400 mg/ml can result in pathological aggregation into fibrillar amyloid structures, a phenomenon that has been linked to various neurodegenerative diseases. Despite its relevance, the process of liquid-to-solid transition inside condensates is still not well understood at the molecular level. We thus herein use small peptide derivatives that can undergo both liquid-liquid and subsequent liquid-to-solid phase transition as model systems to study both processes. Using solid-state nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM), we compare the structure of condensed states of leucine, tryptophan and phenylalanine containing derivatives, distinguishing between liquid-like condensates, amorphous aggregates and fibrils, respectively. A structural model for the fibrils formed by the phenylalanine derivative was obtained by an NMR-based structure calculation. The fibrils are stabilised by hydrogen bonds and side-chain π-π interactions, which are likely much less pronounced or absent in the liquid and amorphous state. Such noncovalent interactions are equally important for the liquid-to-solid transition of proteins, particularly those related to neurodegenerative diseases.


Sperm whale long-range echolocation sounds revealed by ANTARES, a deep-sea neutrino telescope.
Despite dedicated research has been carried out to adequately map the distribution of the sperm whale in the Mediterranean Sea, unlike other regions of the world, the species population status is still presently uncertain. The analysis of two years of continuous acoustic data provided by the ANTARES neutrino telescope revealed the year-round presence of sperm whales in the Ligurian Sea, probably associated with the availability of cephalopods in the region. The presence of the Ligurian Sea sperm whales was demonstrated through the real-time analysis of audio data streamed from a cabled-to-shore deep-sea observatory that allowed the hourly tracking of their long-range echolocation behaviour on the Internet. Interestingly, the same acoustic analysis indicated that the occurrence of surface shipping noise would apparently not condition the foraging behaviour of the sperm whale in the area, since shipping noise was almost always present when sperm whales were acoustically detected. The continuous presence of the sperm whale in the region confirms the ecological value of the Ligurian sea and the importance of ANTARES to help monitoring its ecosystems.


[Algorithms for constructing phylogenetic trees of maximum topological similarity].
The paper concerns the practical realization of the maximum topologic similarity principle for phylogenetic reconstruction. This novel principle is described in the accompanying paper. Two algorithms that were embodied in the computer program allow one to find out the unique tree in case when source data admit the existence of such tree. In case if numerous parallel mutations make such precise realization impossible, algorithms allow one to obtain approximations to the maximum topologic similarity trees with a high computation efficiency. Examples illustrating use of these algorithms, as well as discussion of biological consistency of the novel concept are presented.


Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use.
Toll-like receptors (TLRs) are a major class of pattern recognition receptors, which mediate the responses of innate immune cells to microbial stimuli. To systematically determine the roles of proteins in canonical TLR signaling pathways, we conducted an RNA interference (RNAi)-based screen in human and mouse macrophages. We observed a pattern of conserved signaling module dependencies across species, but found notable species-specific requirements at the level of individual proteins. Among these, we identified unexpected differences in the involvement of members of the interleukin-1 receptor-associated kinase (IRAK) family between the human and mouse TLR pathways. Whereas TLR signaling in mouse macrophages depended primarily on IRAK4 and IRAK2, with little or no role for IRAK1, TLR signaling and proinflammatory cytokine production in human macrophages depended on IRAK1, with knockdown of IRAK4 or IRAK2 having less of an effect. Consistent with species-specific roles for these kinases, IRAK4 orthologs failed to rescue signaling in IRAK4-deficient macrophages from the other species, and only mouse macrophages required the kinase activity of IRAK4 to mediate TLR responses. The identification of a critical role for IRAK1 in TLR signaling in humans could potentially explain the association of IRAK1 with several autoimmune diseases. Furthermore, this study demonstrated how systematic screening can be used to identify important characteristics of innate immune responses across species, which could optimize therapeutic targeting to manipulate human TLR-dependent outputs.


[An activity of nonspecific esterases in homogenates of Lymnaea stagnalis and Lymnaea tumida snails (Gastropoda: Pulmonata) infected by trematode cercariae Echinoparyphium aconiatum and Moliniella anceps (Echinostomatidae)].
The comparative analysis of esterase changes in homogenates of the snails Lymnaea stagnalis and L. tumida bodies was carried out. Juvenile snails with shell size 2 mm, 3-4 mm, 5-6 mm and 7-8 mm were exposed to cercariae of the trematodes Echinoparyphium aconiatum and/or Moliniella anceps. The esterase activity was detected spectrofotometrically. The highest level of esterase activity in noninfected L. stagnalis was registered in snails with shell size 3-4 mm. The invasion of snails by trematode cercariae results in a change of esterase activity in the tissues of infected snails. The activity of easterases was increased in the infected L. stagnalis snails with shell size 5-8 mm at 2 days post invasion in comparison with control. The decrease of esterase activity in tissues of infected snails L. stagnalis (3-4 mm) and L. tumida (4 mm) was observed at 26 days post invasion by E. aconiatum only. The host size and parasite species was influenced on esterase activity in the snails.


Absolute consistency: individual versus population variation in annual-cycle schedules of a long-distance migrant bird.
Flexibility in scheduling varies throughout an organism's annual cycle, reflecting relative temporal constraints and fitness consequences among life-history stages. Time-selection can act at different scales, either by limiting the range of alternative strategies in the population, or by increasing the precision of individual performance. We tracked individual bar-tailed godwits Limosa lapponica baueri for two full years (including direct observation during non-breeding seasons in New Zealand and geolocator tracking of round-trip migrations to Alaska) to present a full annual-cycle view of molt, breeding, and migration schedules. At both population and individual scales, temporal variation was greater in post-breeding than pre-breeding stages, and greater in molts than in movements, but schedules did not tighten across successive stages of migration toward the breeding grounds. In general, individual godwits were quite consistent in timing of events throughout the year, and repeatability of pre-breeding movements was particularly high (r = 0.82-0.92). However, we demonstrate that r values misrepresent absolute consistency by confounding inter- and intra-individual variation; the biological significance of r values can only be understood when these are considered separately. By doing so, we show that some stages have considerable tolerance for alternative strategies within the population, whereas scheduling of northbound migratory movements was similar for all individuals. How time-selection simultaneously shapes both individual and population variation is central to understanding and predicting adaptive phenological responses to environmental change.


Decreasing trends in cardiovascular mortality in Turkey between 1988 and 2008.
Cardiovascular disease (CVD) mortality increased in developed countries until the 1970s then started to decline. Turkey is about to complete its demographic transition, which may also influence mortality trends. This study evaluated trends in coronary heart disease (CHD) and stroke mortality between 1988 and 2008. The number of deaths by cause (ICD-8), age and sex were obtained from the Turkish Statistical Institute (TurkStat) annually between 1988 and 2008. Population statistics were based on census data (1990 and 2000) and Turkstat projections. European population standardised mortality rates for CHD and stroke were calculated for men and women over 35 years old. Joinpoint Regression was used to identify the points at which a statistically significant (p < 0.05) change of the trend occurred. The CHD mortality rate increased by 2.9% in men and 2.0% in women annually from 1988 to 1994, then started to decline. The annual rate of decline for men was 1.7% between 1994-2008, whilst in women it was 2.8% between 1994-2000 and 6.7% between 2005-2008 (p < 0.05 for all periods).Stroke mortality declined between 1990-1994 (annual fall of 3.8% in both sexes), followed by a slight increase between 1994-2004 (0.6% in men, 1.1% in women), then a further decline until 2008 (annual reduction of 4.4% in men, 7.9% in women) (p < 0.05 for all periods). A decrease in CVD mortality was observed from 1995 onwards in Turkey. The causes need to be explored in detail to inform future policy priorities in noncommunicable disease control.


Managing diet quality for cheddar cheese manufacturing milk. 2. Pasture v. grain supplements.
The effects of supplementing a basal diet of silage and hay with increasing amounts of harvested spring pasture, or with lupin and wheat, on the composition of milk and the consequent effects on cheese composition and yield were investigated in an indoor feeding study. Milk was collected from five groups of eight cows in mid lactation offered different diets and manufactured into Cheddar cheese on a pilot scale. Milk from cows given the lupin-wheat (LW) and the high pasture level (HP) diets produced low moisture cheese. Cheese produced with milk from cows given the control diet was high in moisture content compared with that made with milk from cows offered the LW diet. Cheese yields from the milk of cows offered the HP and LW diets were greater than from the milk of cows on the control diet, and were associated with the higher casein concentrations of these milks. Casein number was higher in milk from diets supplemented with pasture but was not an indicator of the functional properties of milk that affected cheese moisture. The proportion of beta-casein in milk from cows offered the HP diet was higher and that of gamma-casein lower than in milk from cows given the LW supplement, although cheese moisture content was similar with both diets. Milk from cows offered the HP diet had a greater inorganic P concentration than that from cows given the LW diet, although the dietary intake of P was higher for the LW diet. The significance of the effect of dietary P intake on the concentration of inorganic P in milk and hence its suitability for cheesemaking was apparent when dietary P intake was low, as shown in milk produced by cows offered the control diet.


Muscular subunits transplantation for facial reanimation.
To present an alternative technique for reconstruction of musculocutaneous damages in the face transferring innervated subsegments (subunits) of the latissimus dorsi flap for replacement of various facial mimetic muscles. One clinical case of trauma with skin and mimetic muscles damage is described as an example of the technique. The treatment was performed with microsurgical transfer of latissimus dorsi muscle subunits. Each subunit present shape and dimensions of the respective mimetic muscles replaced. The origin, insertions and force vectors for the mimic muscle lost were considered. Each subsegment has its own arterial and venous supply with a motor nerve component for the muscular unit. Pre and one year postoperative photos registration of static and dynamic mimic aspects, as well as digital electromyography digital data of the patients were compared. The transplanted muscular units presented myoelectric activity, fulfilling both the functional and cosmetic aspect. This technique seems to be a promising way to deal with the complex musculocutaneous losses of the face as well as facial palsy.


Current advances in the therapy of sinus disease.
Recent technological advances in the diagnosis and treatment of sinus disease have had a significant impact on the way we handle this common condition. As a result of new technologies, we have gained an improved understanding of the pathophysiology of sinus disease. The functional endoscopic sinus surgery (FESS) procedure provides the latest approach to diagnose and aid in the treatment of patients with sinus disease. This endoscopic procedure improves diagnosis and assists in the evaluation of medical and surgical treatment modalities. Should surgery be indicated, a more functional technique can be performed. This includes the meticulous postoperative observation and care of the surgical site. This paper discusses these latest advances in endoscopic diagnosis, medical treatment, and functional surgery for the treatment of sinus diseases. It also outlines the team approach to physician care and management of these patients.


The Intersections of Race, Gender, Age, and Socioeconomic Status: Implications for Reporting Discrimination and Attributions to Discrimination.
This study employed an intersectional approach (operationalized as the combination of more than one social identity) to examine the relationship between aspects of social identity (i.e., race, gender, age, SES), self-reported level of mistreatment, and attributions for discrimination. Self-reported discrimination has been researched extensively and there is substantial evidence of its association with adverse physical and psychological health outcomes. Few studies, however, have examined the relationship of multiple demographic variables (including social identities) to overall levels self-reported mistreatment as well the selection of attributions for discrimination. A diverse community sample (N = 292; 42.12% Black; 47.26% male) reported on experiences of discrimination using the Everyday Discrimination Scale. General linear models were used to test the effect of sociodemographic characteristics (i.e., race, gender, age, SES) on total discrimination score and on attributions for discrimination. To test for intersectional relationships, we tested the effect of two-way interactions of sociodemographic characteristics on total discrimination score and attributions for discrimination. We found preliminary support for intersectional effects, as indicated by a significant race by age interaction on the selection of the race attribution for discrimination; gender by SES on the age attribution; age by gender on the education attribution; and race by SES on the economic situation attribution. Our study extends prior work by highlighting the importance of testing more than one factor as contributing to discrimination, particularly when examining to what sources individuals attribute discrimination.


The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial.
Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, β-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. One hundred thirty-two participants were randomized to 30,000 IU vitamin D weekly for 6 months. Participants underwent oral glucose tolerance test (OGTT) at 3-month intervals to determine the change in plasma glucose concentration at 2 h after 75 g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), β-cell function (HOMA-β, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0 ng/ml and 14.9 ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-β significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in β-cell function in both groups. Additionally, HOMA-β was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in β-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. NCT02098980, 28/03/2014 (www.clinicaltrials.gov).


Restoring Nonvital Premolars with Composite Resin Onlays: Effect of Different Fiber-reinforced Composite Layers on Marginal Adaptation and Fracture Load.
To evaluate the marginal adaptation and fracture load of composite resin onlays reinforced with different substructures. Thirty-two extracted, caries-free premolars were selected for this study and endodontically treated. Group 1 was used as the control group, and the teeth were restored only with as-manufactured composite resin overlays. Group 2 teeth were restored with composite resin overlays with 3 fiber-reinforced composite (FRC) layers placed horizontally on the bottom of the restoration. Group 3 teeth were restored with composite resin overlays with 6 fiber-reinforced composite (FRC) layers placed as in group 2. Group 4 teeth were restored with composite resin overlays and FRC placed with an anatomical design. All specimens underwent SEM evaluation of their marginal adaptation before and after thermocycling and cyclic mechanical loading. All specimens were then subjected to a fracture test, recording the value for the initial (IF) and final (FF) failure. Differences in the means were compared using matched-pairs t-tests and one-way ANOVA. The level of significance was set at α = 0.05. No statistically significant difference between the four groups in terms of marginal adaptation was observed at the tooth/luting composite and luting composite/overlay interfaces before and after loading. The fracture loads of IF and FF, from most to least resistant were: group 4 (1431.8 ± 294.3 N/1710.1 ± 326.6 N), group 3 (1428.1 ± 251.4 N/1467.9 ± 242.4 N), group 2 (852.6 ± 413.5 N/1058.1 ± 251.5 N) and group 1 (899.8 ± 352.7 N/923.5 ± 318.8 N). Significant differences (p = 0.026) were observed comparing group 1 to groups 2 and 3, and group 1 to 4. Three irreparable fractures were found in group 3, four in group 2, and five in groups 1 and 4. The presence or absence of reinforcement and the different configuration of the reinforcement fibers affect fracture strength but only partially the failure modality. The presence or absence of reinforcement does not alter marginal adaptation.


Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro.
Acetylsalicylic acid (aspirin) is one of the most widely used drugs worldwide, due mainly to its broad therapeutic spectrum with anti-inflammatory, antipyretic, antithrombotic and analgesic effects. However, the exact mechanisms by which aspirin influences inflammation, pain and immune system activation are only partly understood. Within activation of the cellular immune system, Th1-type cytokine interferon (IFN)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma induces enzyme GTP-cyclohydrolase I, which gives rise to neopterin production by activated human macrophages. Similarly, tryptophan degradation and neopterin formation increase during several disease states involving Th1-type immune activation. Using stimulated human peripheral blood mononuclear cells (PBMC), the effect of aspirin on tryptophan degradation and neopterin production was investigated. Stimulation of PBMC with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen induced significant tryptophan catabolism as was reflected by a decline in tryptophan levels and a parallel increase in kynurenine concentrations compared with unstimulated cells. In parallel, neopterin production was enhanced. Treatment of stimulated PBMC with increasing doses of 1-5 mM aspirin significantly decreased stimulation-induced tryptophan degradation and neopterin production as well. All the effects of aspirin were dose-dependent. The parallel influence of aspirin on both biochemical pathways implies that there was no direct inhibitory effect of aspirin on IDO; rather, it inhibits production of IFN-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect.


Identification of Cystatin SN as a novel tumor marker for colorectal cancer.
The goal of this study was to investigate Cystatin SN, a cysteine protease inhibitor, as a novel tumor marker for colorectal cancer (CRC). Gene expression profiles of mRNA from normal tissues and cancer cell lines were performed. Twenty-eight monoclonal antibodies for Cystatin SN were generated and serum Cystatin SN was quantified using ELISA in sera from 159 patients with CRC and 40 healthy controls. Cystatin SN was highly expressed in colon cancer cells. Employing a receiver-operating characteristic curve, we obtained an area under the curve of 0.708 for Cystatin SN, 0.819 for carcinoembryonic antigen (CEA) and 0.703 for carbohydrate antigen 19-9 (CA19-9). The combination assay of Cystatin SN, CEA and CA19-9 showed 62.9% sensitivity and 90.0% specificity. Especially, the sensitivity of the combination assay in stages I and II detection, in which stages curative operation would be possible, was improved over that of the assay testing only for CEA and CA19-9 (from 37.5 to 42.5% in stage I, from 49.0 to 60.8% in stage II). Furthermore, Western blot analysis revealed that Cystatin SN was increased in the urine from patients with CRC. Our results suggest the possibility of utilizing this novel tumor marker that can be tested in urine samples. These observations suggest that Cystatin SN in combination with CEA and CA19-9 is a useful tumor marker for detecting early stage CRC and that it is a unique urinary excretory protein, suggesting that Cystatin SN might be a novel candidate for use in mass screening for CRC.


Gli2 activator function in preosteoblasts is sufficient to mediate Ihh-dependent osteoblast differentiation, whereas the repressor function of Gli2 is dispensable for endochondral ossification.
Signaling of Indian hedgehog (Ihh), one of the key regulators of endochondral ossification is mediated by transcription factors of the Gli family, Gli1, Gli2, and Gli3. Gli3 and to a lesser extent Gli2 can be proteolytically processed into short repressor proteins. Upon Ihh signaling, processing is inhibited and the full-length proteins function as activators of transcription. Gli3 has been shown to mainly act as a repressor of Ihh target genes in chondrocytes, but the role of other Gli isoforms is less clear. Analyzing mouse mutants deficient for Ihh;Gli2 or Gli3;Gli2, we show here that the Gli2 repressor has no detectable function in chondrocyte or osteoblast differentiation. Instead, Gli2 seems to act as an activator to fully induce the expression of Ihh target genes in skeletal tissues. Furthermore, we show that, in the absence of Gli3, the activator function of Gli2 is sufficient to induce Ihh-dependent osteoblast differentiation.


Design of experiments as a tool for LC-MS/MS method development for the trace analysis of the potentially genotoxic 4-dimethylaminopyridine impurity in glucocorticoids.
The present study reports on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development strategy supported by design of experiments (DoE) for the trace analysis of 4-dimethylaminopyridine (DMAP). The conventional approaches for development of LC-MS/MS methods are usually via trial and error, varying intentionally the experimental factors which is time consuming and interactions between experimental factors are not considered. The LC factors chosen for the DoE study include flow (F), gradient (G) and injection volume (V(inj)) while cone voltage (E(con)) and collision energy (E(col)) were chosen as MS parameters. All of the five factors were studied simultaneously. The method was optimized with respect to four responses: separation of peaks (Sep), peak area (A(peak)), length of the analysis (T) and the signal to noise ratio (S/N). A quadratic model, namely central composite face (CCF) featuring 29 runs was used instead of a less powerful linear model since the increase in the number of injections was insignificant. In order to determine the robustness of the method a new set of DoE experiments was carried out applying robustness around the optimal conditions was evaluated applying a fractional factorial of resolution III with 11 runs, wherein additional factors - such as column temperature and quadrupole resolution - were considered. The method utilizes a Phenomenex Gemini NX C-18 HPLC analytical column with electrospray ionization and a triple quadrupole mass detector in multiple reaction monitoring (MRM) mode, resulting in short analyses with a 10min runtime. Drawbacks of derivatization, namely incomplete reaction and time consuming sample preparation, have been avoided and the change from SIM to MRM mode resulted in increased sensitivity and lower LOQ. The DoE method development strategy led to a method allowing the trace analysis of DMAP at 0.5 ng/ml absolute concentration which corresponds to a 0.1 ppm limit of quantification in 5mg/ml mometasone furoate glucocorticoid. The obtained method was validated in a linear range of 0.1-10 ppm and presented a %RSD of 0.02% for system precision. Regarding DMAP recovery in mometasone furoate, spiked samples produced %recoveries between 83 and 113% in the range of 0.1-2 ppm.


STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB.
The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new software tool STOCHSIMGPU that exploits graphics processing units (GPUs) for parallel stochastic simulations of biological/chemical reaction systems and show that significant gains in efficiency can be made. It is integrated into MATLAB and works with the Systems Biology Toolbox 2 (SBTOOLBOX2) for MATLAB. The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU). Using our software does not require any changes to the user's models, since it acts as a direct replacement of the stochastic simulation software of the SBTOOLBOX2. The software is open source under the GPL v3 and available at http://www.maths.ox.ac.uk/cmb/STOCHSIMGPU. The web site also contains supplementary information. email@example.com Supplementary data are available at Bioinformatics online.


Vaccinations Against COVID-19 May Have Averted Up To 140,000 Deaths In The United States.
COVID-19 vaccination campaigns continue in the United States, with the expectation that vaccines will slow transmission of the virus, save lives, and enable a return to normal life in due course. However, the extent to which faster vaccine administration has affected COVID-19-related deaths is unknown. We assessed the association between US state-level vaccination rates and COVID-19 deaths during the first five months of vaccine availability. We estimated that by May 9, 2021, the US vaccination campaign was associated with a reduction of 139,393 COVID-19 deaths. The association varied in different states. In New York, for example, vaccinations led to an estimated 11.7 fewer COVID-19 deaths per 10,000, whereas Hawaii observed the smallest reduction, with an estimated 1.1 fewer deaths per 10,000. Overall, our analysis suggests that the early COVID-19 vaccination campaign was associated with reductions in COVID-19 deaths. As of May 9, 2021, reductions in COVID-19 deaths associated with vaccines had translated to value of statistical life benefit ranging between $625 billion and $1.4 trillion.


Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma.
Autotaxin (ATX) is a tumour cell motility-stimulating factor originally isolated from melanoma cell supernatants. ATX is identical to lysophospholipase D, which produces a bioactive lipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine. ATX is overexpressed in various malignancies, including Hodgkin lymphoma, and ATX may stimulate tumour progression via LPA production. The present study measured the serum ATX antigen levels in patients with haematological malignancies using a recently developed automated enzyme immunoassay. The serum ATX antigen levels in patients with B-cell neoplasms, especially follicular lymphoma (FL), were higher than those in healthy subjects. Serum ATX antigen levels in FL patients were associated with tumour burden and changed in parallel with the patients' clinical courses. The serum ATX antigen levels were little affected by inflammation, unlike the soluble interleukin-2 receptor and beta2-microglobulin levels. As expected, the plasma LPA levels in FL patients were correlated with the serum ATX antigen levels. Given that leukaemic tumour cells from FL patients expressed ATX, the shedding of ATX from lymphoma cells probably leads to the elevation of serum ATX antigen levels. Our results suggest that the serum ATX antigen level may be a promising and novel marker for FL.


Classification of acute pancreatitis and the role of prognostic factors in assessing severity of disease.
Clinical assessment of acute pancreatitis by experts is as accurate as any of the individual approaches which have been recommended. What is important in a hospital setting is for one or more of these systems to be applied in individual hospitals so that forewarning is given, especially to the less experienced clinicians, of the patient who is likely to run into difficulties and requires high dependency or intensive care. One practical approach which can be personally recommended is to employ the Glasgow scoring system plus C-reactive protein levels and also to take into account body mass index. Any patient with three positive Glasgow factors, or CRP > 150 mg/l or BMI > 30 kg/m2 has severe acute pancreatitis. More refined systems may ultimately be developed but we are still some way from a single substance in blood or urine being easily and cheaply measured and representing an accurate prognostic indicator of severe acute pancreatitis. Part of the journey has been completed but there is still considerable potential to make the rest of the journey an improvement for both clinicians and patients.


A mathematical approach for the analysis of data obtained from the monitoring of biocides leached from treated materials exposed to outdoor conditions.
Leaching processes are responsible for the release of biocides from treated materials into the environment. Adequate modeling of emission processes is required in order to predict emission values in the framework of the risk assessment of biocidal products intended for long-term service life. Regression approaches have been applied to data obtained from the long-term monitoring of biocide emissions in experiments involving semi-field conditions. Due to the complex interaction of different underlying mechanisms such as water and biocide diffusion and desorption, however, these attempts have proven to be of limited usefulness - at least, for the available biocide emission data. It seems that the behavior of the biocide emission curve depends to a considerable extent on whichever underlying mechanism is slowest at a given point in time, thus limiting the amount of biocide available for release. Building on results obtained in the past few years, the authors propose a criterion for determining which mechanism controls the leaching process at a given point in time based on the slope of the log-log emission curve. In addition, a first-order approximation of this slope value is presented which displays advantages both in terms of computability and interpretability. Finally, an algorithm for the determination of breakpoints in the slope of the log-log emission curve is presented for the demarcation of phases within which one mechanism acts as a limiting factor.


[Autocrine growth mechanisms of cholesteatoma epithelium].
Transforming growth factor alpha (TGF alpha) and interleukin 1 alpha (IL-1 alpha) are known to be produced by normal human keratinocytes stimulating their proliferation. The distribution and expression of TGF alpha and IL-1 alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody against TGF alpha and a polyclonal one against IL-1 alpha. Normal retroauricular skin was stained for comparison. Staining for TGF alpha was consistently stronger in cholesteatoma epithelium than in normal epidermis, and encompassed all epithelial cell layers. Immune cells occurring in the stroma of cholesteatoma also reacted positively for TGF alpha. The intensity of staining for IL-1 alpha was markedly stronger in cholesteatoma tissue than in normal epidermis. All cellular layers of the squamous epithelium of cholesteatoma stained strongly and uniformly for IL-1 alpha, whereas the keratin layer was negative for IL-1 alpha. In the connective tissue beneath the cholesteatoma epithelium intensely positive cells were scattered between negative stromal cells. These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF alpha and IL-1 alpha as well as with a paracrine stimulation by immune cells. Both factors contribute to the unrestrained growth of cholesteatoma in the middle ear cavity.


[Average of the PCDFs value in blood in patients with Yusho in the 2001 to 2003 fiscal year and comparison between the clinical features and PCDFs].
Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth, general fatigue, headaches, and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001. The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15 years previously. The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well, the blood PeCDF level was related to PCB level, hexachlorobiphenyl level, urinary sugar, erythrocyte sedimetation rate (ESR) (2-hour), thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988. However, PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions.


Socioeconomic position and mental health problems in pre- and early-adolescents: the TRAILS study.
Family socioeconomic position (SEP) is known to be associated with adolescent mental health. Whether the relationship is different for different mental health dimensions is unknown. Using a cross-sectional design, we investigated the differential effects of family SEP on multiple mental health dimensions in preadolescents (N = 2230, baseline age 10-12, 49% boys) using reports from multiple informants (parent, self, and teachers). A score equal to or higher than the 85th percentile (averaged across informants) defined mental health problems. SEP was inversely associated with all dimensions. Compared to high SEP, the odds ratios (OR) for externalizing problems were 3.88 (95% confidence interval (CI): 2.56, 5.90) and 2.05 (CI: 1.34, 3.14) for low and intermediate SEP, respectively. For internalizing problems, they were 1.86 (CI: 1.28, 2.70) and 1.37 (CI: 0.94, 2.00), respectively. When adjusted for externalizing problems, SEP effects on internalizing problems materially attenuated (OR: 1.47, CI: 0.78, 1.68 and OR: 1.34, CI: 0.91, 1.96) while the converse was less pronounced (OR: 3.39, CI: 2.24, 5.15) and (OR: 1.91, CI: 1.25, 2.94). In early adolescence, the risk of mental health problems increases with decreasing SEP, particularly for externalizing problems. Further, the SEP-internalizing problems relationship is partly explained by shared aspects with externalizing problems.


Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis.
In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.


Cadmium-mediated rescue from ER-associated degradation induces expression of its exporter.
Cadmium is a highly toxic environmental contaminant that has been implicated in various disorders. A major mechanism for cadmium detoxification in the yeast Saccharomyces cerevisiae relies on extrusion via Pca1, a P-type ATPase. While an N-terminal degron targets Pca1 for degradation before its secretion to the plasma membrane, cadmium in the growth media rapidly up-regulates Pca1 by preventing its turnover. Here we show that the endoplasmic reticulum-associated degradation (ERAD) system, known for its role in quality control of secretory proteins, is unexpectedly responsible for the regulation of Pca1 expression by cadmium. Direct cadmium sensing at the ER by a degron in Pca1 leads to an escape of Pca1 from ERAD. This regulated conversion of an ERAD substrate to a secretory competent state in response to a cellular need illustrates a mechanism for expressional control of a plasma membrane protein. Yeast has likely evolved this mode of regulation for a rapid response against cadmium toxicity at the expense of constant synthesis and degradation of Pca1. ERAD of a portion of secretory proteins might occur via signal-dependent regulatory mechanisms as demonstrated for Pca1.


Predictors of Quitting Smoking in Cardiac Rehabilitation.
Quitting smoking and participation in cardiac rehabilitation (CR) are effective strategies in reducing morbidity and mortality. However, little is known about the predictors of quitting smoking in those who attend CR. This study aimed to determine the sociodemographic and clinical factors associated with the likelihood of CR attendees who are quitting smoking. Data from the UK National Audit of Cardiac Rehabilitation (NACR) database, between April 2013 and March 2016, were used. Smoking status is categorized as smokers and quitters, assessed by patient self-report. The study used patient demographics, cardiovascular risk factors, comorbidities, and physical and psychosocial health measures. Binary logistic regression was performed to identify the predictors of quitting smoking among CR attendees. Of the 3290 patients who started CR and were entered into the NACR database, 2052 were continued smokers (mean age 58.59 ± 10.49 years, 73.6% men) and 1238 were quitters (mean age 57.63 ± 10.36 years, 75.8% men). The median duration of CR was 9 weeks. Compared to smokers, the quitters were younger, weighed more, were less anxious and depressed, and were more likely to be employed. Single patients had 0.60 times lower odds (95% CI 0.43 to 0.82) of quitting smoking than patients with partners, and low-risk patients had 1.71 times higher odds (95% CI 1.12 to 2.62) of quitting smoking than high-risk patients. Increasing number of comorbidities and depression scores were associated with decreasing likelihood of quitting. This study highlights the routine factors that determine smoking cessation outcomes, which could inform the delivery of CR to better help patients to quit smoking.


Hamiltonian of a homogeneous two-component plasma.
The Hamiltonian of one- and two-component plasmas is calculated in the negligible radiation Darwin approximation. Since the Hamiltonian is the phase space energy of the system its form indicates, according to statistical mechanics, the nature of the thermal equilibrium that plasmas strive to attain. The main issue is the length scale of the magnetic interaction energy. In the past a screening length lambda=1/square root of r(e)n], with n number density and r(e) classical electron radius, has been derived. We address the question whether the corresponding longer screening range obtained from the classical proton radius is physically relevant and the answer is affirmative. Starting from the Darwin Lagrangian it is nontrivial to find the Darwin Hamiltonian of a macroscopic system. For a homogeneous system we resolve the difficulty by temporarily approximating the particle number density by a smooth constant density. This leads to Yukawa-type screened vector potential. The nontrivial problem of finding the corresponding, divergence free, Coulomb gauge version is solved.


[Fever of unknown origin. A study of 100 cases (author's transl)].
This report concerns the analysis of 100 cases of fever of unknown origin, defined according to the criteria of Petersdorf and Beeson. An etiological diagnosis could be reached in 77 cases, distributed as follows: infections, 32 cases; tumors, 14 cases; collagen diseases, 13 cases; various etiologies, 18 cases; and idiopathic, 23 cases of whom 20 had selflimited fever. There were 51 male and 49 female. The incidence of infectious diseases was significantly higher below age 40 when compared with the group of collagen diseases. Recurrent fever was common (43 cases) while continuous fever was unusual (3 cases). Recurrent fever was most frequent in neoplastic diseases, the difference in relation to the other groups being statistically significant (p less than 0.05). Chills, diffuse perspiration and myalgia were more frequent in infectious diseases (p less than 0.01) than in the other groups. Collagen diseases had significantly higher (p less than 0.05) white blood cell counts than neoplastic diseases, while the latter had significantly higher (p less than 0.01) serum lactic-dehydrogenase and alpha 2 globulin levels than infectious and collagen diseases. Hepatosplenomegaly was present more frequently in neoplastic than in infectious diseases. When evaluating diagnostic procedures it was noted that invasive techniques (arteriography, biopsy, laparoscopy, laparotomy) were essential to arrive to the final diagnosis in 47 cases, while noninvasive procedures (serological and immunological tests, bacteriology, conventional radiology, clinical course, and response to therapy) were sufficient in 22 cases. In eight cases the etiology of the fever could only be determined by post-mortem examination.


Chemical genetics unveils a key role of mitochondrial dynamics, cytochrome c release and IP3R activity in muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. The subcellular mechanisms of DMD remain poorly understood and there is currently no curative treatment available. Using a Caenorhabditis elegans model for DMD as a pharmacologic and genetic tool, we found that cyclosporine A (CsA) reduces muscle degeneration at low dose and acts, at least in part, through a mitochondrial cyclophilin D, CYN-1. We thus hypothesized that CsA acts on mitochondrial permeability modulation through cyclophilin D inhibition. Mitochondrial patterns and dynamics were analyzed, which revealed dramatic mitochondrial fragmentation not only in dystrophic nematodes, but also in a zebrafish model for DMD. This abnormal mitochondrial fragmentation occurs before any obvious sign of degeneration can be detected. Moreover, we demonstrate that blocking/delaying mitochondrial fragmentation by knocking down the fission-promoting gene drp-1 reduces muscle degeneration and improves locomotion abilities of dystrophic nematodes. Further experiments revealed that cytochrome c is involved in muscle degeneration in C. elegans and seems to act, at least in part, through an interaction with the inositol trisphosphate receptor calcium channel, ITR-1. Altogether, our findings reveal that mitochondria play a key role in the early process of muscle degeneration and may be a target of choice for the design of novel therapeutics for DMD. In addition, our results provide the first indication in the nematode that (i) mitochondrial permeability transition can occur and (ii) cytochrome c can act in cell death.


The spin excitation spectrum in superconducting YBa(2)Cu(3)O(6.85)
A comprehensive inelastic neutron scattering study of magnetic excitations in the near optimally doped high-temperature superconductor YBa(2)Cu(3)O(6.85) is presented. The spin correlations in the normal state are commensurate with the crystal lattice, and the intensity is peaked around the wave vector characterizing the antiferromagnetic state of the insulating precursor, YBa(2)Cu(3)O(6). Profound modifications of the spin excitation spectrum appear abruptly below the superconducting transition temperature T(c), where a commensurate resonant mode and a set of weaker incommensurate peaks develop. The data are consistent with models that are based on an underlying two-dimensional Fermi surface, predicting a continuous, downward dispersion relation connecting the resonant mode and the incommensurate excitations. The magnetic incommensurability in the YBa(2)Cu(3)O(6+)(x) system is thus not simply related to that of another high-temperature superconductor, La(2-)(x)Sr(x)CuO(4), where incommensurate peaks persist well above T(c). The temperature-dependent incommensurability is difficult to reconcile with interpretations based on charge stripe formation in YBa(2)Cu(3)O(6+x) near optimum doping.


Comparison of gastric fundus invagination and gastric greater curvature plication for weight loss in a rat model of diet-induced obesity.
Gastric fundus invagination (GFI) is a novel weight loss procedure. The gastric fundus is invaginated inside the gastric lumen and anastomosed to the gastric antrum. In gastric plication (GP), the greater curvature is plicated inside the gastric lumen leaving a narrow gastric channel for food passage. This study compares GFI to GP in a diet-induced obesity rat model. Twenty Long-Evans male rats were fed a 60% high fat diet for 6 weeks. At 14 weeks of age, the rats underwent either GFI (N = 10) or GP (N = 10) surgery. Body weight and food intake were measured for 6 weeks. Serum adipokines and ghrelin hormone were assayed. Six weeks after surgery, all rats were euthanized and the stomachs examined. The two-sample t test was used to compare the results between the two groups. All GFI rats had an intact fundus invagination at 6 weeks following surgery. The greater curvature plication unfurled in three out of ten GP rats. Part of the fundus herniated through the plication suture line in one GP rat. There was no significant difference between the mean percent weight change for the GFI (4.2 ± 4.1%) and GP (8.8 ± 6.0%) groups. There was no difference in food intake between both groups. GFI was associated with a significant lower fasting ghrelin levels (101.1 ± 13.1 versus 137.3 ± 27.4; p = 0.044) compared with GP. GFI offers a more effective and more durable surgical alternative for weight loss than GP.