Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice.
It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated thermogenesis, obesity phenotypes were determined in C57BL6/J.(+)/(+) (WT) and C57BL6/J.Ucp1.(-)/(-) mice (Ucp1-KO) housed at TN and fed a HFD with or without 0.5% (wt/wt) cholic acid (CA) for 9 wk. CA in a HFD reduced adiposity and hepatic lipogenesis and improved glucose tolerance in WT but not in Ucp1-KO mice and was accompanied by increases in food intake and energy expenditure (EE). In iBAT, CA increased Ucp1 mRNA and protein levels 1.5- and twofold, respectively, and increased DIO2 and TGR5 protein levels in WT mice. Despite enhanced Dio2 expression in Ucp1-KO and Ucp1-KO-CA treated mice, this did not enhance the ability of BAs to reduce obesity. By comparing the effects of BAs on WT and Ucp1-KO mice at TN, our study showed that BAs suppress diet-induced obesity by increasing EE through a mechanism dependent on Ucp1 expression, which is likely independent of adrenergic signaling.


Neutrophil-to-Lymphocyte Ratio Better Than High-Sensitivity C-Reactive Protein in Predicting Stroke-Associated Pneumonia in Afebrile Patients.
To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) without fever and to clarify whether NLR has an advantage over high-sensitivity C-reactive protein (hs-CRP) in predicting SAP. A total of 434 patients with AIS without fever were assessed in this study. Multivariable analysis was used to evaluate the relationship between NLR and SAP, and the receiver operating characteristic (ROC) curve was used to compare the predictive value of NLR and hs-CRP. Among the total patients, 18 (4.1%) developed SAP. After adjusting for confounders, NLR (adjusted odds ratio [aOR] = 1.60; 95% confidence interval [CI], 1.30-1.96; p < 0.001) remained independently associated with an increased risk of SAP. In addition, the area under the curve (AUC) of NLR (0.862 [0.826-0.893]) was higher than that of hs-CRP (0.738 [0.694-0.779]). We found that compared with hs-CRP, NLR was significantly associated with the occurrence of SAP in patients with AIS without fever and showed a more effective predictive value for SAP.


Clinical and Confocal Microscopy Study of Plasma Exeresis for Nonsurgical Blepharoplasty of the Upper Eyelid: A Pilot Study.
Plasma exeresis is an evolving technique for nonsurgical treatment of several skin conditions. Reflectance confocal microscopy (RCM) is a noninvasive tool that allows the "in vivo" imaging of the skin. To evaluate the clinical improvement and collagen remodeling of the upper eyelid dermatochalasis after plasma exeresis. Ten patients were subjected to 3 interventions of plasma exeresis. Photographic and RCM images were acquired at T0 (baseline) and T1 (4-6 weeks after final plasma exeresis). Eyelid dermatochalasis was rated as absent, mild, moderate, and severe according to the facial laxity rating scale, at clinical images at T0 and T1. An expert RCM evaluator classified collagen according to the predominant pattern of reticulated, coarse, huddled, or curled at T0 and T1. Clinical improvement of 2.6 ratings was observed at clinical evaluation. Collagen was classified as long straight fibers in all cases, according to RCM images. Plasma exeresis in this pilot study shows promising remodeling effects on the collagen of the upper eyelid, as viewed by RCM, and clinically improved appearance for the patient cohort, without any serious adverse events. This study suggests that plasma exeresis could be a valid solution for eyelid dermatochalasis, but further studies are required.


Pomegranate Seed Oil Mitigates Liver and Kidney Damage in an Experimental Colitis Model: Modulation of NF-κB Activation and Apoptosis.
Pomegranate seed oil, extracted from pomegranate seeds, is a slightly fragrant yellow oil with a mild odor. Pomegranate seed oil is the main source of punicic acid (conjugated linolenic acid). Punicic acid is a long-chain omega-5 polyunsaturated fatty acid and a conjugated α-linolenic acid molecule. This acid is thought to provide many health benefits. This study evaluated the potential of pomegranate seed oil to attenuate damage to liver and kidney tissues in an acetic acid-induced colitis model. 32 male Sprague-Dawley rats were divided into 4 groups: control, colitis, 0.4ml/kg, and 0.8ml/kg pomegranate seed oil treatment after colitis. At the end of the experiment, histopathological and immunohistochemistry analyses of liver and kidney tissues were performed. Pomegranate seed oil treatment reduced damage in liver and kidney tissues, suppressed NF-κB activation, and regulated apoptosis. These findings support the potential effects of pomegranate seed oil against extraintestinal symptoms of colitis through its anti-inflammatory, and anti-apoptotic properties.


Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China.
To investigate the molecular epidemiology and genetic variation of human adenovirus type 7 (HAdV-7) in children with acute respiratory infections (ARI) in China. HAdV-7-positive respiratory samples collected from children with ARI in Beijing, Shijiazhuang, Wenzhou and Guangzhou from 2014-2018 were selected for gene amplification and sequence analysis. Fifty-seven HAdV-7 clinical strains with hexon, penton base and fiber gene sequences were obtained. Meanwhile 17 strains were selected randomly from different cities for whole genome sequencing. Phylogenetic and variation analyses were performed based on the obtained sequences, HAdV-7 prototype strain Gomen (AY594255), vaccine strains (AY495969 and AY594256) and representative sequences of strains. The phylogenetic trees constructed based on whole genome sequences, major capsid protein genes (hexon, penton base and fiber) and the early genes (E1, E2, E3 and E4) were not completely consistent. The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980s to the present. Compared with the HAdV-7 prototype strain Gomen (AY594255), some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed. Recombination analysis showed that partial regions of 55 kDa protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3, respectively. Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention, control and vaccine development of HAdV-7.


A systematic review of studies measuring health-related quality of life of general injury populations: update 2010-2018.
Studies examining the impact of injury on health-related quality of life (HRQL) over time are necessary to understand the short- and long-term consequences of injury for population health. The aim of this systematic review was to provide an evidence update on studies that have measured HRQL over time in general injury populations using a generic (general) health state measure. Studies conducted between 2010 and 2018 that assessed HRQL at more than one time point among general injury populations were eligible for inclusion. Two reviewers independently extracted information from each study on design, HRQL measure used, method of HRQL measure administration, timing of assessment(s), predictive variables, ability to detect change, and findings. Quality appraisals of each study were also completed by two reviewers using items from the RTI Item Bank on Risk of Bias and Precision of Observational Studies and the Guidelines for the Conduction of Follow-up Studies Measuring Injury-Related Disability. Twenty-nine studies (44 articles) that met the inclusion criteria were identified. HRQL was measured using 14 different generic measures; the SF-36, SF-12, and EQ-5D were used most frequently. A varying number of follow-up assessments were undertaken, ranging from one to five. Follow-up often occurred 12 months post-injury. Fewer studies (n = 11) examined outcomes two or more years post-injury, and only one to 10 years post-injury. While most studies documented improvements in HRQL over time since the injury event, study populations had not returned to pre-injury status or reached general population norm HRQL values at post-injury follow-ups. Since 2010 there has been a substantial increase in the number of studies evaluating the HRQL of general injury populations. However, significant variability in study design continues to impede quantification of the impact of injury on population health over time. Variation between studies is particularly evident with respect to timing and number of follow-up assessments, and selection of instruments to evaluate HRQL.


Prevalence and patient awareness of medical comorbidities in an urban AIDS clinic.
Mortality in HIV-positive persons is increasingly due to non-HIV-related medical comorbidities. There are limited data on the prevalence and patient awareness of these comorbid conditions. Two hundred subjects at an urban HIV clinic were interviewed in 2005 to assess their awareness of 15 non-HIV-related medical comorbidities, defined as medical problems that are neither AIDS-defining by standard definitions, nor a direct effect of immune deficiency. Medical charts were subsequently reviewed to establish prevalence and concordance between self-report and chart documentation. Eighty-four percent of subjects self-reported at least 1 of 15 medical comorbidities and 92% had at least 1 condition chart-documented. The top 5 chart-documented conditions were hepatitis C (51.5%), pulmonary disease (28.5%), high blood pressure (27%), high cholesterol (24.5%), and obesity (22.5%). In multivariate analysis, higher number of non-HIV-related medical comorbidities was associated with older age, female gender, and intravenous drug use as route of HIV transmission. Across self-reported non-HIV-related medical comorbidities, the absolute concordance rate ranged from 67% to 96%, the sensitivity ranged from 0% to 79%; the positive predictive value ranged from 0% to 100%. While the vast majority of largely urban minority HIV-positive subjects were diagnosed with non-HIV-related medical comorbidities, there is significant room for improvement in patient awareness. In order to help patients optimally access and adhere to medication and medical care for these non-HIV-related medical comorbidities, interventions and educational campaigns to improve patient awareness that take cultural background, literacy, and educational level into account should be developed, implemented, and evaluated.


Constitutive high expression of interleukin-4/13A and GATA-3 in gill and skin of salmonid fishes suggests that these tissues form Th2-skewed immune environments.
Rainbow trout and Atlantic salmon interleukin-4/13A (IL-4/13A) genes were identified. They were found expressed at high level in thymus, gill, and skin, in concert with the transcription factor gene GATA-3. High expression levels of IL-4, IL-13, and GATA-3 were also detected in murine thymus, suggesting similar importance of the fish and mammalian homologues for early T cell development. In mammals, combined high expression of IL-4/13 and GATA-3 in tissues other than thymus is mostly indicative of Th2 responses. Th2-skewage may protect fish skin and gill from parasites and from damage by inflammatory Th1 and Th17 responses. The immune milieus of fish gill and skin are relevant to aquaculture, because these tissues are preferred sites for vaccine administration. The similarities between the immune milieus of fish gill and thymus may reflect an evolutionary relationship, since these tissues map close together lining the gill cavity. Expression patterns of IL-4/13A and interferon gamma (IFN-γ) in isolated trout gill cells and pronephrocytes were consistent with Th2 identity of IL-4/13A.


Extensive sequence variation exists among isolates of murine cytomegalovirus within members of the m02 family of genes.
Murine cytomegalovirus (MCMV) is a widely used model for human cytomegalovirus (HCMV) and has facilitated many important discoveries about the biology of CMVs. Most of these studies are conducted using the laboratory MCMV strains Smith and K181. However, wild-derived isolates of MCMV, like HCMV clinical isolates, exhibit genetic variation from laboratory strains, particularly at the ends of their genomes in areas containing known or putative immune-evasion and tropism genes. This study analysed the nucleotide sequence of the m02-m05 region, within the m02 gene family, of a number of laboratory and wild-derived MCMV isolates, and found a large degree of variation in both the sequence and arrangement of genes. A new open reading frame (ORF), designated m03.5, was found to be present in a number of wild isolates of MCMV in place of m03. Two distinct isolates, W8 and W8211, were found to possess both m03 and m03.5. Both m03 and m03.5 had early transcription kinetics and the encoded proteins could be detected on the cell surface, consistent with a possible role in immune evasion through binding to host-cell proteins. These data show that gene duplication and sequence variation occur within different isolates of MCMV found in the wild. As this variation among strains may alter the function of genes, these findings should be considered when analysing gene function or host-virus interactions in laboratory models.


CT Findings and Patterns of e-Cigarette or Vaping Product Use-Associated Lung Injury: A Multicenter Cohort of 160 Cases.
e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown. What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior? CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ2 test, and multivariable analyses were used for statistical analysis. A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC. EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding.


Recurrent Body Rash Warranted Second Desensitization With Acyclovir in a Myeloma Patient: A Case Report.
A 75-year-old woman developed a moderately severe rash about a week and a half after the start of bortezomib (Btb)-based chemotherapy for IgG lambda multiple myeloma; at the time, she was also receiving acyclovir as antiviral prophylaxis in addition to herpes zoster (HZ) vaccination. HZ reactivation rate is high in Btb recipients; therefore, the timing of antiviral prevention is critical in relation to Btb. Attempts were made to identify the offending agent based on the timing of drugs administered and the appearance of skin lesions in relation to other drugs. Both Btb and acyclovir were potential culprits. However, the timing of rash presented on days 9 - 10 revealed the offending agent when the corticosteroid was weaned off while acyclovir continued. A decision was made to administer acyclovir rapid desensitization program (RDP) for our patient.


Defined nuclear changes accompany the reprogramming of the microspore to embryogenesis.
The switch of the gametophytic developmental program toward pollen embryogenesis to form a haploid plant represents an important alternative for plant breeding. In the present study, the switch of the gametophytic developmental program toward a sporophytic pathway, "embryogenesis," has been studied in three different plant species, Brassica, tobacco, and pepper. The switch has been induced by stress (heat shock) at the very responsive stage of the microspore, which is the vacuolate period. As a result, the cell nucleus undergoes striking structural changes with regard to late gametophytic development, including alterations of biosynthetic activities and proliferative activity. An enrichment in HSP70 heat-shock protein and in the presence of Ntf6-MAP kinase was observed after inductive treatment in the nuclei during early embryogenesis. This apparently reflected the possible roles of these proteins, specifically the protective role of HSP70 for the nuclear machinery, and signal transduction of Ntf6-MAPK for the entry of cells into proliferation. Importantly, the observed nuclear changes were similar in the three species investigated and represented convenient markers for early monitoring of embryogenesis and selection purposes for obtaining double-haploid plants in plant breeding.


Race/ethnicity and validity of self-reported pneumococcal vaccination.
National and state surveys show large disparities in pneumococcal vaccination status among Whites, Blacks and Latinos aged >/= 65. The purpose of this study is to determine whether there is any difference in the validity of self-report for pneumococcal vaccination by race/ethnicity that might contribute to the substantial disparities observed in population-level coverage estimates. Self-reported vaccination status was compared with medical record documentation for samples of White, Black, and Latino members of a large health plan to examine whether differences in validity of self-report contribute to observed disparities. Sensitivity was significantly lower for Blacks (0.849, 95% CI 0.818-0.876) and Latinos (0.869, 95% CI 0.847-0.889) than for Whites (0.931 95% CI 0.918-0.942). Specificity was somewhat higher for Blacks than for Latinos and Whites, but the differences were not statistically significant. Coverage for Whites, Blacks and Latinos, respectively, was 84.3%, 73.5%, and 82.3% based on self-report, but 74.8%, 71.9%, and 84.2% based on medical records. The results of this study suggest that differential self-report error, i.e., summative effect of over-reporting and under-reporting within a race-ethnic group, may contribute to the size and direction of race-ethnic disparities in pneumococcal vaccination observed in surveys.


Endovascular Treatment for Stroke in a Single Center in a Developing Country: Permanent Training is the Key.
In Mexico, the systematic implementation of mechanical thrombectomy has been delayed due to several factors, such as the conditions of the healthcare system. The objective of this report is to explain the experience in our center going through these circumstances, how we have overcome them, our results, and our pending challenges. This is a single-center, independent, and retrospective study of prospectively collected data destined to record consecutive patients treated with endovascular techniques at a Mexican hospital that implemented a mechanical thrombectomy program for large vessel occlusion (LVO). Patient selection began in February 2017 and ended in January 2020. Patients selected were between the ages of 18 and 80, and could be treated within 8 hours after onset of symptoms. The timeline of the analysis was divided in half (i.e., 18 months). We prognosticate that our concept of permanent training could have an impact on clinical outcomes. In all, 73 patients gathered, of which 60.3% were women and 39.7% were men, with an average patient age of 62 years old. The average Onset-Door time was 248 minutes, and mean Door-Recanalization time was 91.7 minutes, where 29.6% (27.2 min) were used in the endovascular procedure per se. The results obtained were as follows: five (6%) patients with a thrombolysis in cerebral infarction (TICI) <2B and nine patients (12.3%) with a TICI 2B. TICI 2C and 3 were considered optimal results and found in 59 (80.8%) patients. It was found that 17 (23%) patients treated in the first 18 months had favorable outcomes (modified Ranking Scale [mRS] <3), and in the last 18 months, 45 (33%) patients had favorable outcomes (p = 0.0001). Developing countries such as Mexico usually present particular conditions that are not part of the algorithms generated in developed countries. Nevertheless, with logistic adaptation, creativity, and above all, permanent training, similar results to those in other parts of the world can be achieved.


Scrotal ulceration as a consequence of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia.
Induction therapy with all-trans-retinoic acid (ATRA), an oral vitamin A derivative, has been shown to improve the short and long-term outcome of patients with acute promyelocytic leukemia (APML). Common side effects include headache, fever, dry skin, and bone pain, and approximately 25% of treated patients experience ATRA syndrome, which includes fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions. Scrotal ulcerations due to ATRA are rare with 16 previously documented cases, most of whom were Asian. We report a Caucasian male with APML who developed scrotal ulceration during ATRA induction therapy and review the previously reported cases. Physicians and patients should be aware of this disturbing, but self-limited, dermatologic complication of ATRA.


Sustainment of Lean Redesigns for Primary Care Teams.
Quality improvements are notoriously followed by "backsliding" or relapse to the status quo. This mixed-methods study examined the sustainment of Lean workflow redesigns for primary care teams several years after being implemented in a large, ambulatory care delivery system. We conducted qualitative interviews of 57 leaders and frontline providers, and fielded post-Lean implementation surveys to 1164 physicians and staff in 17 primary care clinics across the system. We analyzed interviews and conducted independent sample t tests to identify key factors that facilitated the sustainment of new workflows among primary care teams. All analyses were conducted after Lean redesigns were implemented and scaled across the system in 3 consecutive phases. Adherence to Lean redesigns was highest in the pilot clinic, despite having the longest postdesign measurement period. Members of the pilot clinic reported greatest participation in designing workflows, were most highly engaged in quality improvement efforts, and held most favorable beliefs about Lean changes. Adherence to redesigns was lowest among clinic members in the second phase of implementation; these members also reported highest levels of burnout. Staff participation in Lean redesign is a key to facilitating buy-in and adherence to changes. Change ownership and continued availability of time for improvement activities are also critical to the long-term success of Lean implementation in primary care.


A Blueprint for the Conduct of Large, Multisite Trials in Telemedicine.
Recent literature supports the efficacy and efficiency of telemedicine in improving various health outcomes despite the wide variability in results. Understanding site-specific issues in the implementation of telemedicine trials for broader replication and generalizability of results is needed. Lessons can be learned from existing trials, and a blueprint can guide researchers to conduct these challenging studies using telemedicine more efficiently and effectively. This viewpoint presents relevant challenges and solutions for conducting multisite telemedicine trials using 7 ongoing and completed studies funded by the Patient-Centered Outcomes Research Institute portfolio of large multisite trials to highlight the challenges in implementing telemedicine trials. Critical issues of ensuring leadership and buy-in, appropriate funding, and diverse and representative trials are identified and described, as well as challenges related to clinical, informatics, regulatory, legal, quality, and billing. The lessons learned from these studies were used to create a blueprint of key aspects to consider for the design and implementation of multisite telemedicine trials.


Introducing quality management into primary health care services in Uganda.
In 1994, a national quality assurance programme was established in Uganda to strengthen district-level management of primary health care services. Within 18 months both objective and subjective improvements in the quality of services had been observed. In the examples documented here, there was a major reduction in maternal mortality among pregnant women referred to Jinja District Hospital, a reduction in waiting times and increased patient satisfaction at Masaka District Hospital, and a marked reduction in reported cases of measles in Arua District. Beyond these quantitative improvements, increased morale of district health team members, improved satisfaction among patients, and greater involvement of local government in the decisions of district health committees have been observed. At the central level, the increased coordination of activities has led to new guidelines for financial management and the procurement of supplies. District quality management workshops followed up by regular support visits from the Ministry of Health headquarters have led to a greater understanding by central staff of the issues faced at the district level. The quality assurance programme has also fostered improved coordination among national disease-control programmes. Difficulties encountered at the central level have included delays in carrying out district support visits and the failure to provide appropriate support. At the district level, some health teams tackled problems over which they had little control or which were overly complex; others lacked the management capacity for problem solving.


Microflora of black and red pepper.
Dilution cultures of 30 samples of ground black pepper yielded an average of 39,000 colonies of fungi per g, with a range of 1,700 to 310,000 per g. Total numbers of colonies of bacteria from 11 samples averaged 194,000,000 per g, with a range from 8,300,000 to 704,000,000 per g. A variety of fungi grew from nearly all surface-disinfected whole peppercorns that were cultured. Thirteen samples of ground red pepper from the United States yielded an average of 1,600 colonies of storage fungi per g and an equal number of other fungi; five samples from India yielded an average of 78,900 colonies of storage fungi per g and 169,400 colonies of other fungi per g. Among the fungi from both black and red pepper were Aspergillus flavus and A. ochraceus, some isolates of which, when grown for 8 to 10 days on moist autoclaved corn and fed to white rats or to 2-day-old Pekin ducklings, were rapidly lethal to them. Aflatoxin B(1) was isolated from one of the samples of corn on which A. flavus from black pepper was grown. Among the bacteria isolated from ground black pepper were Escherichia coli, E. freudii, Serratia sp., Klebsiella sp., Bacillus sp., Staphylococcus sp., and Streptococcus sp. No cultures of Shigella or Salmonella were found.


Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part II--vitamin D, vitamin A, iron, zinc, iodine, essential fatty acids.
Part II of this review considers additional micronutrients. Vitamin D is a fat soluble vitamin found in foods of animal origins (fatty fish, liver oil) or fortified products (milk, cheese). Vitamin D deficiency is common in African-American women living in northern latitudes. Vitamin D supplementation may be needed to reach desired 25-(OH)D3 concentrations of >50 nmol/L. In foods of animal origin, preformed Vitamin A is present; in plants (fruits and vegetables) vitamin A precursors (β-carotenoids) are present. Vitamin A supplementation is usually not warranted, and in developing countries should not exceed 3000 μg (10,000 IU)/day. Iron in the form of haem-iron is found in meat, fish and poultry; non-haem (inorganic) iron is found in vegetables, fruits and grains. Iron supplementation may be necessary in the third trimester, earlier in pregnancy or in non-pregnant states if serum ferritin is <20 μg/L or haemoglobin <10.9 g/dL. Zinc is available in red meat, seafood including oysters and unpolished grains; supplementation is not necessary. To assure adequate iodine, food is fortified worldwide with iodated salt. If urinary iodine levels are low, supplementation is needed. Essential fatty acids requirements can be met by one to two portions of fish per week.


The softening of human bladder cancer cells happens at an early stage of the malignancy process.
Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young's modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force.


Methods for the detection and assembly of novel sequence in high-throughput sequencing data.
Large insertions of novel sequence are an important type of structural variants. Previous studies used traditional de novo assemblers for assembling non-mapping high-throughput sequencing (HTS) or capillary reads and then tried to anchor them in the reference using paired read information. We present approaches for detecting insertion breakpoints and targeted assembly of large insertions from HTS paired data: BASIL and ANISE. On near identity repeats that are hard for assemblers, ANISE employs a repeat resolution step. This results in far better reconstructions than obtained by the compared methods. On simulated data, we found our insert assembler to be competitive with the de novo assemblers ABYSS and SGA while yielding already anchored inserted sequence as opposed to unanchored contigs as from ABYSS/SGA. On real-world data, we detected novel sequence in a human individual and thoroughly validated the assembled sequence. ANISE was found to be superior to the competing tool MindTheGap on both simulated and real-world data. ANISE and BASIL are available for download at http://www.seqan.de/projects/herbarium under a permissive open source license.


Risk Factor for Vital Signs Fluctuation during Colonoscopy under Conscious Sedation Consisting of Midazolam and Meperidine.
Sedatives or analgesics are widely used to relieve a patient's discomfort during colonoscopy (CS). Although cardiopulmonary adverse events are sometimes experienced during the examination, the risk factors for vital signs fluctuation (VSF) have not been fully elucidated. This study thus aimed to identify the risk factors for VSF during the examination, as well as to evaluate the frequency and the degree of VSF. A total of 755 consecutive subjects who received CS under endoscopist-administrated sedation using midazolam, meperidine, or combination of both were retrospectively analyzed. We assessed the distribution of vital signs during the procedure and frequency of VSF. To identify independent risk factors, we analyzed the association between VSF and subjects' characteristics and procedure information using the multivariate logistic regression model. Consequently, VSF was observed in 17% of all; hypotension and oxygen desaturation was observed in 13 and 5%, respectively. However, we could achieve the purpose of all procedure and, no one required hospitalization or extension of hospital stay. Multivariate analysis revealed that age (OR 1.05 [95% CI 1.04-1.07]), being female (OR 1.78 [95% CI 1.19-2.70]), and use of midazolam (OR 5.06 [95% CI 3.18-8.08]) were independent risk factors for VSF.


A case-control study of diet and lung cancer in northeast China.
A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates for tumor removal by surgery. Controls were selected among hospitalized patients with non-neoplastic and non-lung disease. The overall male lung-cancer risks associated with cigarette smoking were similar to those reported in other Chinese studies but quite low compared to risks in Western countries. However, the subjects in this study were relatively young (average age 53.2), had started to smoke on average at a relatively old age (21.3 years), and only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not strongly associated with any of the nutrients examined, when all cases were compared to all controls. However, the data were suggestive of differences in the relationship of diet to risk among smokers and non-smokers. Cautious interpretation is required because of the wide confidence intervals due to limited sample size. Among the smokers, only higher beta-carotene was associated with estimates suggesting a lowered risk. Among non-smokers, the evidence suggested that increased vegetable consumption might reduce risk, consumption of any fruit might reduce risk but beta-carotene was unrelated to risk. The differences observed in the relationship of diet to lung-cancer risk between Chinese smokers and non-smokers warrant further study.


Analysis and experimental assessment of an optimized SERS substrate used to detect thiabendazole in apples with high sensitivity.
Pesticides that linger in the environment and ecosystems for an extended period can cause severe and dangerous health problems in humans. To detect pesticides in foods, the development of high-sensitivity and quick screening technologies was required. This research investigated the performance of Au@Ag NPs with varying thicknesses of the silver shell for detecting trace quantities of thiabendazole (TBZ) in apples using surface-enhanced Raman spectroscopy (SERS). The Au@Ag NPs were synthesized by coating 32 nm gold seeds with different thicknesses of silver shell ranging from 2.4 to 8.7 nm, achieved by adjusting the incorporation of AgNO3 and ascorbic acid. The optimized Au@Ag NPs with a 7.3 nm silver shell demonstrated outstanding SERS activity, high sensitivity, and a detection limit of 0.05 μg/mL for TBZ. The R2 values, representing the goodness of fit, were found to be 0.990 and 0.986 for standard and real TBZ samples, respectively, indicating a strong correlation between the measured signal and the TBZ concentration. The recovery analysis showed a reliable and accurate detection capability (96 to 105%), suggesting good reliability and accuracy of the SERS-based detection using the optimal Au@Ag NPs. Overall, this research highlights the potential of SERS with optimal Au@Ag NPs for rapid and effective monitoring of pesticides in the food industry.


Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device.
High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.


Interspecific hybridization and restricted trans-Pacific gene flow in the Tropical Eastern Pacific Pocillopora.
Coral reefs in the Tropical Eastern Pacific (TEP) are among the most isolated in the world. This isolation has resulted in relatively low species diversity but comparatively high endemism. The dominant reef-building corals of the TEP are the Pocillopora corals, a ubiquitous Indo-Pacific genus commonly regarded as inferior reef-builder. In addition to being the dominant reef-builders in the TEP, the Pocilloporids have undergone a reproductive shift from internally brooding larvae through most of their Indo-Pacific range to free-spawning in the TEP. Using genetic data from the internally transcribed spacer (ITS) regions of the nuclear ribosomal DNA gene cluster, we show here that this apparent reproductive shift coincides with interspecific hybridization among TEP Pocillopora species. We document a pattern of one-way gene flow into the main TEP reef builder P. damicornis from one or both of its TEP congeners - P. eydouxi and P. elegans. Our data provide preliminary evidence that trans-Pacific gene flow in P. damicornis between the Central and Eastern Pacific is restricted as well (Phi(ST) = 0.419, P < 0.0001). In combination, these results suggest that Eastern Pacific corals exist in relative isolation from their Central Pacific counterparts and interact with each other differently via hybridization.


[Current standing of forensic psychotherapy in Germany].
Although treatment of inmates already has got a long tradition in Germany, forensic psychotherapy is - especially outside the so-called German "Massregelvollzug" - only at its beginnings, and consistent theories about delinquency and treatment programmes have not yet been established. While international studies show high prevalence of mental disorders in prisons (up to 60 - 70 %), in Germany even basic epidemiological data about the prevalence of mental disorders among inmates is still missing. Thus, the need for psychotherapy can only be roughly estimated. Ethical implications regarding the self-image, an ambivalent assignment for treatment (given by society) and a recent tightening of German law create a difficult framework for forensic psychotherapy, complicating the establishment as well as the evaluation of new treatment programmes, especially since many people still doubt the efficiency of forensic psychotherapy for delinquents despite convincing counter-evidence. It seems obvious that in Germany much research has to be done in the fields of epidemiology as well as in forensic psychotherapy in order to gain basic data and to be then able to provide effective psychotherapeutic treatment facilities aiming at the needs of mentally disturbed offenders.


Response of the sulfate-reducing community to the re-establishment of estuarine conditions in two contrasting soils: a mesocosm approach.
We studied the response of the sulfate-reducing prokaryote (SRP) communities to the experimental variation of salinity and tide in an outdoor mesocosm setup. Intact soil monoliths were collected at two areas of the Haringvliet lagoon (The Netherlands): one sampling location consisted of agricultural grassland, drained and fertilized for at least the last century; the other of a freshwater marshland with more recent sea influence. Two factors, i.e., "salinity" (freshwater/oligohaline) and "tide" (nontidal/tidal), were tested in a full-factorial design. Soil samples were collected after 5 months (June-October). Dissimilatory (bi)sulfite reductase beta subunit-based denaturing gradient gel electrophoresis (dsrB-DGGE) analysis revealed that the SRP community composition in the agricultural grassland and in the freshwater marshland was represented mainly by microorganisms related to the Desulfobulbaceae and the Desulfobacteraceae, respectively. Desulfovibrio-related dsrB were detected only in the tidal treatments; Desulfomonile-related dsrB occurrence was related to the presence of oligohaline conditions. Treatments did have an effect on the overall SRP community composition of both soils, but not on the sulfate depletion rates in sulfate-amended anoxic slurry incubations. However, initiation of sulfate reduction upon sulfate addition was clearly different between the two soils.


An integrated individual-level trait-based phytoplankton dataset from transitional waters.
Functional trait-based approaches have undergone an extraordinary expansion in phytoplankton ecology. Morpho-functional traits have been shown to vary both within and between populations and species, potentially affecting individual fitness and the network of inter-individual relationships. Here we integrate six fully harmonized phytoplankton morpho-functional trait datasets, characterized by a fine data grain, reporting individual-level data over a large biogeographical area. Datasets refer to transitional water ecosystems, from five biogeographical areas: Northern Atlantic Ocean (Scotland), South-Western Atlantic Ocean (Brazil), South-Western Pacific Ocean (Australia), Indo Pacific Ocean (Maldives) and Mediterranean Sea (Greece and Turkey). The integrated dataset includes 127311 individual phytoplankton records with sampling locations, taxonomic and morphometric information according to Darwin Core standards and semantic annotations. The six FAIR datasets are openly available in the LifeWatch Italy data portal. The datasets have already been used for morpho-functional analyses and hypothesis testing on phytoplankton guilds at different levels of data aggregation and scale, from local to global.


Antimicrobial and cytotoxicity properties of Plumeria alba flower extract against oral and periodontal pathogens: A comparative in vitro study.
Plumeria alba, commonly known as frangipani or West Indian jasmine, is a traditional and ancient folklore medicine known for its antimicrobial, anti-inflammatory, and antioxidant properties. The extracts from P. alba obtained from the leaves, bark, and flowers, are commonly used to manage bacterial, fungal, and viral infections such as herpes, scabies, and fungal infections. The constituents of the P. alba plant have shown promising antihelmintic, antipyretic, and antirheumatic properties. Although studies have confirmed that extracts from Plumeria species are effective against microbial infections and cancer, its role in managing oral diseases, particularly the chronic inflammatory disease of the gums (gingivitis and periodontitis), has never been explored. Therefore, the current study aimed to explore the antimicrobial and cytotoxic properties of the P. alba flower extract against oral and periodontal pathogens compared to chlorhexidine and doxycycline. This was an in vitro study. The ethanolic extract was prepared from the freshly plucked P. alba flowers. The antimicrobial properties of the extract were evaluated by testing the minimal inhibitory concentration, minimal bactericidal concentration, and well-diffusion assay against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, Tannerella forsythia, Streptococcus mutans, Actinomyces viscosus, Streptococcus salivarius, and Candida albicans. The results were compared to chlorhexidine and doxycycline. The cytotoxicity was checked by the against human-derived gingival fibroblast and keratinocytes. One-way ANOVA for the mean zones of inhibition against all the microorganisms was done. P. alba extract inhibited the growth for all the tested oral and periodontal pathogens at 25 μg/ml. The well-diffusion assay of P. alba extract was comparable to chlorhexidine but was not statistically significant compared to doxycycline. P. alba can be used as a promising alternative to chlorhexidine for the management of oral and periodontal infections.


Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects.
Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population. Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P < or = 0.05). Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.


The role of cytochrome P-450 in cholesterol biogenesis and catabolism.
1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [(14)C]acetate or [(14)C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7alpha-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7alpha-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.


Ag-Au-Cu Trimetallic Alloy Microflower: A Highly Sensitive SERS Substrate for Detection of Low Raman Scattering Cross-Section Thiols.
Trimetallic Ag-Au-Cu alloy microflowers (MFs) with various surface compositions were synthesized on a glass coverslip and used as efficient surface-enhanced Raman spectroscopy (SERS) substrates for highly sensitive label-free detection of smaller Raman scattering cross-section molecules, namely, L-cysteine and toxic thiophenols. MFs of different compositions were synthesized via appropriate mixing of metal-alkyl ammonium halide precursors followed by a single-step thermolysis at 350 °C. While the Ag percentage was kept constant at 90% for all the substrates, the composition of Au and Cu was varied between 1 and 9% sequentially. The synthesized MFs were thoroughly characterized by using field emission scanning electron microscopy (FE-SEM), wide-angle X-ray scattering, X-ray photoelectron spectroscopy (XPS), and X-ray fluorescence techniques. FE-SEM studies revealed that the MFs were present throughout the substrate, and the average size varied from 20 to 40 μm. XPS studies showed that the top surface of the alloy substrates was rich in either Au or Cu atoms, while Ag remained underneath. The performance of the trimetallic MFs as SERS substrates was evaluated using Rhodamine 6G as a probe molecule, which showed that the MFs with Ag-Au-Cu compositions 90-7-3 and 90-3-7 were found to be the best and of equal SERS efficiency. The SERS enhancement factor (EF) of both these MFs was found to be the same, approximately 9 × 107, when calculated using 1,2,3-benzatriazole as the probe molecule. Between the two, the trimetallic substrate with a higher Au percentage (Ag-Au-Cu as 90-7-3) was used for the sensitive SERS-based detection of thiols to exploit the strong Au-S binding interaction. By virtue of the high EF of the substrate, the inherently low Raman scattering cross-sections of the probe molecules were greatly enhanced in SERS mode. The 'limit of quantification (LOQ)' values were found to be 1 nM for aliphatic L-Cysteine and 1-0.1 pM for aromatic thiols using the trimetallic SERS sensor.


Managing prescription drug costs: a case study.
Pharmacy costs in most private insurance companies and public concerns have risen over the past several years. To address the problem of increased expenditures in its government employee pharmacy program, the State of New York sought bids from outside vendors to help it control pharmaceutical costs. The following is a case study of the tools the state employed in that effort. Over time, both prescription drug coverage and mental health and substance abuse benefits were carved out of the medical plan and are now provided under free-standing programs. In order to participate, an independent pharmacy must accept a discount of 10% off the average wholesale price of brand name drugs and 25% off the average generic price of generic drugs.


Force-length properties in stable skeletal muscle fibers--theoretical considerations.
Differences in the force-length (F-L) properties between sarcomeres and fibers have been associated with the supposed unstable nature of the sarcomere F-L relation on the descending limb (i.e. at sarcomere lengths greater than optimal length). Recently, it has been suggested that sarcomere behavior in a fiber is stable during contractions on the descending limb of the F-L relation; therefore, a factor other than sarcomere instability must be responsible for the observed differences in the F-L relations of sarcomeres and fibers. The purpose of this study was to determine theoretically the F-L relation of a muscle fiber when sarcomeres were at a stable, steady-state length. Three models of muscle fibers are presented; each model contains sarcomeres with different mechanical properties which have been observed experimentally. Results of these theoretical considerations demonstrate that sarcomeres with the classic F-L properties as measured by Gordon et al. (J. Physiol. 184, 170-192, 1966) cannot predict the F-L relation exhibited by fibers. The addition of cross-bridge stiffness properties to the classic sarcomere F-L relation still does not explain the differences between the sarcomere and fiber F-L relations. However, if history dependent sarcomere properties are used, the fiber F-L relation exhibits an elongated plateau and greater forces on the descending limb compared to the classic sarcomere F-L relation; and the fiber F-L relation corresponds qualitatively to experimental findings.


Evaluation of concentric left ventricular geometry in humans: evidence for age-related systematic underestimation.
There might be limitations in identifying concentric left ventricular (LV) geometry by ratio of diastolic posterior wall thickness (WT(p)) to cavity radius, defined as relative wall thickness (RWT(p)). This study has been designed to evaluate age effects on RWT(p). WT(p), mean of septal thickness and WT(p) (WT(m)), and cavity radius were cross-sectionally evaluated in 766 1- to 85-year-old, normotensive, nonobese subjects and 331 hypertensive Italians (used as a test series). RWT(p) > or =0.43 defined "traditional" concentric LV geometry. The ratios WT(m)/radius (RWT(m)) and RWT(p) increased by 0.005 and 0.006 per year of age in the age stratum up to 17 years and by 0.002 in the older age stratum (18 years or older; all P<0.0001). Thus, RWT(m) and RWT(p) were normalized to average age in both age strata (10 and 46 years) by age-specific regression coefficients. The 90th and 95th percentiles of age-normalized RWT(p) or RWT(m) were 0.40 and 0.42 or 0.41 and 0.43, respectively, in adults and 0.36 and 0.39 or 0.36 and 0.38, respectively in young subjects. In hypertensive subjects, traditional RWT(p) cutoff identified 74 subjects (22%) with concentric LV geometry; by 95th or 90th normal percentiles, normalized RWT(m) identified 112 (34%), or 149 (45%) subjects with concentric LV geometry, and normalized RWT(p) 29% and 39%, respectively (all P<0.0001 versus unadjusted RWT(p)). Thus, prevalence of concentric LV geometry increases with age-normalized RWT. Accordingly, we suggest that concentric LV hypertrophy be defined by coexistence of high LV mass with age-normalized RWT(m) >0.41 or RWT(p) >0.40. Further studies are required to establish prognostic implications of our findings.


Phenotype-defining functions of multiple non-coding RNA pathways.
One of the surprising revelations of the initial stage of the ENCODE project was the conclusion that more than 90% of human genome is transcribed. A major component of this vast transcriptional output is represented by highly heterogeneous families of transcripts defined as short non-coding RNAs (sncRNAs) with no or limited protein-coding potentials. Here we carried out the sequence homolog profiling of the 2301 human sncRNAs with confirmed sequence identities [including 943 transintrons; 235 expressed distal intergenic sequences (EDIS); and 1005 piRNAs] as well as >1000 hypothetical transcripts derived from allelic variants of human SNP sequences with strong associations to human diseases or linkages to phenotypes established in genome-wide association studies. Unexpectedly, this analysis reveals a structural feature common for approximately 85% of analyzed sncRNA sequences and 488 human microRNAs. This structural feature common for multiple seemingly unrelated sncRNA pathways points to a multitude of potential functional and regulatory implications involving mechanisms of gene expression regulation, control of biogenesis, stability and bioactivity of microRNAs, sncRNA-guided macromolecular interactions, and transcriptional basis of self/non-self discrimination by immune system. Our analysis implies that hundreds thousands of non-protein-coding transcripts are contributing to phenotype-defining regulatory and structural features of a cell. Therefore, definitions of genes as structural elements of a genome contributing to phenotypes should be expanded beyond the physical boundaries of mRNA-encoding units. We propose an information-centered model of a cell suggesting that informasomes (the RNP complexes of sncRNAs and Argonaute proteins) represent the intracellular structures which provide the increasingly complex structural framework of genomic regulatory functions in higher eukaryotes to facilitate the stochastic (random and probabilistic) rather than deterministic mode of choices in a sequence of regulatory events defining the phenotype.


Electrochemical scanning tunneling microscopic observation of the preoxidation process of CO on Pt(111) electrode surface.
Presented are sequential images of CO on Pt(111), observed with electrochemical scanning tunneling microscopy, during its electrochemical preoxidation process. In the course of the well-known phase transition from the (2 x 2)-3CO-alpha structure to the (radical 19 x radical 19)R23.4 degrees-13CO structure, various structures were observed: (2 x 2)-3CO-beta (Chem. Comm. 2006, 2191-2193), (1 x 1)-CO, and (radical 13 x radical 13)R46.1 degrees-9CO. Based on an analysis of the populations of the structures averaged over imaging time and imaged location at the preoxidation potential range (0-0.25 V vs Ag/AgCl), the structures of CO domains changed sequentially in the order of (2 x 2)-3CO-alpha, (2 x 2)-3CO-beta, (1 x 1)-CO, (radical 13 x radical 13)R46.1 degrees-9CO, and (radical 19 x radical 19)R23.4 degrees-13CO as the potential shifted from 0 to 0.25 V. Such a sequential structural change demonstrates that the structures of (2 x 2)-3CO-beta, (1 x 1)-CO, and (radical 13 x radical 13)R46.1 degrees-9CO are transient ones during the preoxidation of CO on Pt(111). Discussed are the transient structures in terms of various aspects, such as the absence of CO in solution and the origin of compressed structures.


Parthenolide inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in colorectal cancer cells.
Transforming growth factor-β1 (TGF-β1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently metastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-β1-induced EMT in CRC cell lines. HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The induction of EMT by TGF-β1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting. TGF-β1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-β1 did not induce apoptosis in HT-29 and SW480 cells. PT attenuates TGF-β1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-β1-induced cell migration and cell invasion. In addition, other EMT markers such as β-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT. Our findings show that PT inhibits TGF-β1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-β1-induced EMT.


Dynamics of monocyte surface receptors after burns: a pilot study.
Previous studies suggested that monocytes may play a vital role in infection and sepsis following burn injury. The aim of this study was to determine whether burn injury had any effect on the levels of expression of monocyte cell-surface receptors at different phases post burn injury. Ten adult burn victims with burns of >25% of the total body surface area were included in this study. Blood samples were collected on the first, third and seventh day post burn injury. The peripheral blood mononuclear cells were extracted, with or without lipopolysaccharide stimulation. The monocyte phenotypes of CD14, CD16, HLA-DR, CD163, TLR2 and TLR4 were characterized by flow cytometry. Six healthy volunteers were recruited as controls. The percentage of expressed CD14+ monocytes increased during the first day, and then decreased on the third and seventh day after burn injury. The percentages of CD14+ cells expressing CD16 and HLA-DR decreased on the first day, followed by an increase on the third and seventh day post burn. In comparison, the percentage of CD14+ monocytes expressing TLR2 and TLR4 was higher on the first day in burn patients than that of control participants, followed by no change on the third and seventh day post burn injury. There was no significant difference in the percentages of CD14+ expressing CD163 between the two groups. This study showed that the expression of the specific receptors on the surface of monocyte is affected by burn injury. The changes in the expression levels of these receptors may contribute to burn-induced infection susceptibility.


The influence of satellite populations of emerald ash borer on projected economic costs in U.S. communities, 2010-2020.
The invasion spread of the emerald ash borer (Agrilus planipennis Fairmaire) (Coleoptera: Buprestidae) is characterized by the formation of satellite populations that expand and coalesce with the continuously invading population front. As of January 2010, satellite infestations have been detected in 13 states and two Canadian provinces. Understanding how newly established satellite populations may affect economic costs can help program managers to justify and design prevention and control strategies. We estimate the economic costs caused by EAB for the 10-yr period from 2010 to 2020 for scenarios of fewer EAB satellite populations than those found from 2005 to 2010 and slower expansion of satellite populations found in 2009. We measure the projected discounted cost of treatment, removal, and replacement of ash trees (Fraxinus spp.) growing in managed landscapes in U.S. communities. Estimated costs for the base scenario with the full complement of satellites in 2005-2010 and no program to mitigate spread is $12.5 billion. Fewer EAB satellites from 2005 to 2010 delay economic costs of $1.0 to 7.4 billion. Slower expansion of 2009 satellite populations delays economic costs of $0.1 to 0.7 billion. Satellite populations that are both distant from the core EAB infestation and close to large urban areas caused more economic costs in our simulations than did other satellites. Our estimates of delayed economic costs suggest that spending on activities that prevent establishment of new satellite EAB populations or slow expansion of existing populations can be cost-effective and that continued research on the cost and effectiveness of prevention and control activities is warranted.


Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β-catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide.
Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/β-catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2+ oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28-day septic rats. The number of PLP+ and MBP+ cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g-ratios were higher. This was coupled with an increase in number of NG2+ cells and decreased number of CC1+ cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above-mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/β-catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/β-catenin signaling pathway, which would contribute ultimately to axonal hypomyelination.


Comparison of Vitamin D Serum Values between Rheumatoid Arthritis and Lupus Populations: An Observational Study.
In recent years, the role of Vitamin D (VitD), as an immunomedulator in autoimmune diseases, has been evaluated in basic science and practice. There is a considerable volume of data on the effect of VitD position in lupus and rheumatoid arthritis exacerbation. This study aims to compare VitD serum values in lupus (SLE) and Rheumatoid Arthritis (RA) in the geographical region of northeastern Iran. Lupus and RA Patients were selected with various disease activity levels. All the patients received an equal amount of VitD supplementation and were selected by the same inclusion and exclusion criteria. VitD serum values were measured by a commercial ELISA kit. Data were analyzed in SPSS-15. A total of 148 SLE and 156 RA patients were studied. VitD serum levels were 66.54±41.2 nmol/l in the SLE group and 83.74±46.45 nmol/l in the RA group. Statistical analysis showed that VitD serum levels were lower in lupus patients than RA ones (p=0.006). VitD serum values were lower in lupus patients than RA ones. Since VitD deficiency is very common in Iran, physiologic doses of VitD supplementation in patients lead to higher serum levels of VitD. Lower VitD values in lupus patients compared with RA ones may stem from intestinal malabsorption, higher doses of corticosteroid therapy, renal involvement and proteinuria, different polymorphisms of VitD receptors, and more sun protection strategies in lupus patients.


Myotoxin-3 from the Pacific Rattlesnake Crotalus oreganus oreganus Venom Is a New Microtubule-Targeting Agent.
Microtubule targeting agents (MTA) are anti-cancer molecules that bind tubulin and interfere with the microtubule functions, eventually leading to cell death. In the present study, we used an in vitro microtubule polymerization assay to screen several venom families for the presence of anti-microtubule activity. We isolated myotoxin-3, a peptide of the crotamine family, and three isoforms from the venom of the Northern Pacific rattlesnake Crotalus oreganus oreganus, which was able to increase tubulin polymerization. Myotoxin-3 turned out to be a cell-penetrating peptide that slightly diminished the viability of U87 glioblastoma and MCF7 breast carcinoma cells. Myotoxin 3 also induced remodeling of the U87 microtubule network and decreased MCF-7 microtubule dynamic instability. These effects are likely due to direct interaction with tubulin. Indeed, we showed that myotoxin-3 binds to tubulin heterodimer with a Kd of 5.3 µM and stoichiometry of two molecules of peptide per tubulin dimer. Our results demonstrate that exogenous peptides are good candidates for developing new MTA and highlight the richness of venoms as a source of pharmacologically active molecules.


Violation of US regulations regarding online marketing and sale of e-cigarettes: FDA warnings and retailer responses.
The aim of this study was to characterise all 2018 Food and Drug Administration (FDA) warning letters specific to e-cigarette products and to evaluate whether online retailers complied with FDA requested actions. All 2018 FDA e-cigarette warning letters issued by the Center for Tobacco Products to online retailers were reviewed and characterised. Date of issuance, name, type, and location of the retailer, and violation type were recorded. Retailer websites were rechecked a minimum of 30 days after the issuance of the warning letter to assess compliance with enforcement actions. One hundred and thirteen of 124 letters met the inclusion criteria; one duplicate letter and 10 letters unrelated to e-cigarettes were excluded. One manufacturer was cited for associating their e-liquid with prescription drugs, and when analysed, the e-liquid was found to contain phosphodiesterase inhibitors. A majority of violations, 98.2% (111/113), pertained to the sales of an e-cigarette product to a minor and/or use of marketing that appeals to children. The majority of websites (63.7%, 72/113) resolved all violations. However, 19.5% (22/113) inactivated their website, and 16.8% (19/113) did not fully correct all violations. Sales of e-cigarette products to minors and the purposeful marketing of e-liquids in a manner that appeals to children and adolescents continues to be problematic. While the warning letters were successful in getting a majority of online retailers to correct the stated violation, many sold other products that would be considered a violation of marketing to minors. The appearance of e-liquids that contain prescription medications is also alarming. Comprehensive and continued enforcement of online e-cigarette retailers is urgently needed.


Rural Africa: modernization, equity, and long-term development.
Prospects for rural development in sub-Saharan Africa appear to be much poorer than in the rest of the developing world, especially since the oil price increases. If present trends continue, African dependence on food imports will increase. Despite the rhetorical acknowledgment of the importance of the agricultural and rural sector, most African countries are not giving that sector the needed priority in their policies and budgets. Indeed, the rural sector is heavily taxed for the support of urban modernization. Large investments by foreign donors in the rural sector have had little overall effect. Donors need to adopt a longer perspective on development and to make greater efforts to promote indigenous capacities for policy, planning, and administration. Their investments need to be geared more to broad-based higher education and training and to transport and communications.


Differences in cell density associated with differences in lung-colonizing ability of B16 melanoma cells.
The B16 melanoma-derived low lung-colonizing variant B16-F1 and the high lung-colonizing variant B16-F10 retained their differential lung-colonizing abilities throughout at least 35 serial s.c. transplant generations. The majority of the cells originating from solid B16-F1 tumors had a higher density than did cells originating from solid B16-F10 tumors. Cell suspensions of unselected solid B16 melanomas contained two major subpopulations differing in their cell density. The subpopulation with the lower cell density was more efficient in lung tumor colony formation, following i.v. administration, than was the high-density subpopulation. Cloned tumors from low-density B16 cells were more efficient in lung colony formation than were cloned tumors from high-density cells.


Bioengineered bioreactors: a review on enhancing biomethane and biohydrogen production by CFD modeling.
Computational fluid dynamics (CFD) is numerical strategy developed for simulating the behavior of liquid and gas flow. CFD may be applied starting from aerospace, engine design, vehicle aerodynamics, power plants and chemical industries for analyzing and solving relevant system design and process issues. Biogas produced during anaerobic digestion (AD) is sustainable and renewable alternative to fossil fuels. AD may improve the controlled production of biogas and offers significant environmental benefits. This review focuses on research outcomes relevant for enhanced biogas production by exploring the possible applications of CFD in AD technology. CFD-related research performed in AD conditions in order to improve mixing performance, reduce power consumption, and understand the effects of total solid (TS) concentrations on flow behavior have been discussed. In addition, the use of AD for bio-hydrogen production, wastewater treatment, and sludge treatment are looked in. This review also identifies novel areas for AD technology advancement where there is potential for economic improvement in renewable energy production. Finally, future research needs have been identified, focusing on the opportunities to integrate conceptual and mathematical models for advancing CFD simulations for bioenergy.


Suppression of T lymphocyte activity by lupeol isolated from Crataeva religiosa.
Lupeol has been shown to possess antiarthritic activity through possible suppression of the immune system. As seen in the following studies, it was found to suppress various immune factors such as the phagocytic (cell-killing) activity of macrophages, T-lymphocyte activity that included CD4+T cell mediated cytokine generation. Assessment of T cells and their intracellular content of cytokines was carried out by flow cytometric analysis in Balb/c mice. Oral administration of lupeol at doses of 12.5-200 mg/kg p.o. inhibited CD4+ T and CD8+ T cell counts and cytokines IL-2, IFN-gamma (Th1) and IL-4 (Th2). Cytometric bead array (CBA) technology was applied to carry out simultaneous measurement of multiple serum cytokines. The oral LD(0) in mice was more than 2 g/kg body weight.


Ribavirin in the treatment of hepatitis C.
The hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, with approximately 170-200 million people infected. The HCV virus is transmitted by blood and blood products and such transmission occurs primarily through drug use by injection, sex with an infected partner and occupational exposure. The severity of the disease varies widely from mild chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC). Nowadays, the reference treatment is combination therapy of pegylated interferon and ribavirin, which is an inosine monophosphate dehydrogenase inhibitor and immunomodulator. Efficacy of treatment in our clinical trials is 87% in patients infected by HCV genotypes 2 or 3, whereas in patients infected by HCV genotype 1 response to treatment is 66%. The current combination treatment has significant side-effects and sometimes is poorly tolerated. HCV genotypes 2 or 3 can be treated with a lower dose of ribavirin and a shorter course of therapy, 24 weeks vs 48 weeks for patients with genotype 1. There is a growing consensus that acute control of HCV infection is associated with a vigorous intrahepatic antiviral CD4+ and CD8+ T-cell response, enhanced Th1 and natural killer activity. Pretreatment genotype and response to therapy measured at weeks 12 and 24 of treatment have been identified as key determinants in decisions about continuing treatment. Elevated serum ferritin levels and hepatic iron deposition as well as hepatic steatosis and high ALT levels with chronic hepatitis C are risk factors for HCC development. Heterozygosityfor the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C. Ribavirin could cause dose-dependent reversible haemolytic anaemia, which can be managed with dose reductions or with administration of epoetin alpha at 40,000 IU once weekly without sacrificing the optimal dosing of ribavarin. Among patients who received ribavirin alone, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels and hepatic fibrosis scores were not changed significantly from baseline. For HCV-HIV co-infected patients, treatment is given when blood CD4 counts are above 350/ml and before antiretroviral (ART) treatment is needed.


Beyond DNA and RNA: The Expanding Toolbox of Synthetic Genetics.
The remarkable physicochemical properties of the natural nucleic acids, DNA and RNA, define modern biology at the molecular level and are widely believed to have been central to life's origins. However, their ability to form repositories of information as well as functional structures such as ligands (aptamers) and catalysts (ribozymes/DNAzymes) is not unique. A range of nonnatural alternatives, collectively termed xeno nucleic acids (XNAs), are also capable of supporting genetic information storage and propagation as well as evolution. This gives rise to a new field of "synthetic genetics," which seeks to expand the nucleic acid chemical toolbox for applications in both biotechnology and molecular medicine. In this review, we outline XNA polymerase and reverse transcriptase engineering as a key enabling technology and summarize the application of "synthetic genetics" to the development of aptamers, enzymes, and nanostructures.


Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.


Perspective: gene divergence, population divergence, and the variance in coalescence time in phylogeographic studies.
Molecular methods as applied to the biogeography of single species (phylogeography) or multiple codistributed species (comparative phylogeography) have been productively and extensively used to elucidate common historical features in the diversification of the Earth's biota. However, only recently have methods for estimating population divergence times or their confidence limits while taking into account the critical effects of genetic polymorphism in ancestral species become available, and earlier methods for doing so are underutilized. We review models that address the crucial distinction between the gene divergence, the parameter that is typically recovered in molecular phylogeographic studies, and the population divergence, which is in most cases the parameter of interest and will almost always postdate the gene divergence. Assuming that population sizes of ancestral species are distributed similarly to those of extant species, we show that phylogeographic studies in vertebrates suggest that divergence of alleles in ancestral species can comprise from less than 10% to over 50% of the total divergence between sister species, suggesting that the problem of ancestral polymorphism in dating population divergence can be substantial. The variance in the number of substitutions (among loci for a given species or among species for a given gene) resulting from the stochastic nature of DNA change is generally smaller than the variance due to substitutions along allelic lines whose coalescence times vary due to genetic drift in the ancestral population. Whereas the former variance can be reduced by further DNA sequencing at a single locus, the latter cannot. Contrary to phylogeographic intuition, dating population divergence times when allelic lines have achieved reciprocal monophyly is in some ways more challenging than when allelic lines have not achieved monophyly, because in the former case critical data on ancestral population size provided by residual ancestral polymorphism is lost. In the former case differences in coalescence time between species pairs can in principle be explained entirely by differences in ancestral population size without resorting to explanations involving differences in divergence time. Furthermore, the confidence limits on population divergence times are severely underestimated when those for number of substitutions per site in the DNA sequences examined are used as a proxy. This uncertainty highlights the importance of multilocus data in estimating population divergence times; multilocus data can in principle distinguish differences in coalescence time (T) resulting from differences in population divergence time and differences in T due to differences in ancestral population sizes and will reduce the confidence limits on the estimates. We analyze the contribution of ancestral population size (theta) to T and the effect of uncertainty in theta on estimates of population divergence (tau) for single loci under reciprocal monophyly using a simple Bayesian extension of Takahata and Satta's and Yang's recent coalescent methods. The confidence limits on tau decrease when the range over which ancestral population size theta is assumed to be distributed decreases and when tau increases; they generally exclude zero when tau/(4Ne) > 1. We also apply a maximum-likelihood method to several single and multilocus data sets. With multilocus data, the criterion for excluding tau = 0 is roughly that l tau/(4Ne) > 1, where l is the number of loci. Our analyses corroborate recent suggestions that increasing the number of loci is critical to decreasing the uncertainty in estimates of population divergence time.


Expression pattern of ATM and cyclin D1 in ductal carcinoma, normal adjacent and normal breast tissues of Iranian breast cancer patients.
ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. Cyclin D1 acts in regulating the G1 phase of the cell cycle. Experimental and clinical studies suggest them to be involved in transformation and tumour progression. To elucidate the role of ATM and cyclin D1 expression in sporadic breast cancer, we investigated the possible link between their RNA expression levels in ductal carcinoma and normal adjacent versus normal breast tissues measured by Taqman real-time PCR in 119 breast tissues. Results showed that cyclin D1 over-expressed in 51.4% of breast tumours, whereas ATM expression was down regulated in 55% of breast tumours compared to both normal adjacent and normal controls (P ≤ 0.01). Cyclin D1 expression in adjacent normal and normal tissues was not significantly differed, whereas ATM expression in normal adjacent was lower than normal control (P ≤ 0.01). Over-expression of cyclin D1 correlated with ER(+) and/or PR(+) (oestrogen/progesterone receptor) status, whereas it mostly under-expressed in HER2(+) (human epidermal growth factor 2) tumours. ATM under-expression was more observed in triple-negative tumours (ER(-), PR(-) and HER2(-)). Our results indicated that reduced expression of the ATM and aberrant cyclin D1 expressions may contribute to the development and/or malignant progression of breast carcinomas also the latter could be involved in the regulation of hormone sensitivity associated with ER and PR.


Protein-energy malnutrition delays small-intestinal recovery in neonatal pigs infected with rotavirus.
Infectious diarrheal diseases and protein-energy malnutrition (PEM) are major causes of child morbidity and mortality worldwide. In the present study, PEM was superimposed on rotavirus infection in neonatal pigs to simulate chronic small intestinal stress in malnourished infants with viral gastroenteritis. Two-day-old cesarean-derived pigs (n = 39) were allotted to three treatment groups: 1) noninfected, full-fed; 2) infected, full-fed; and 3) infected, malnourished. Two days postinfection, severe diarrhea and weight loss (11%) were accompanied by reductions in villus height (60%) and lactase activity (78%) and increased crypt depth (32%) in infected full-fed compared with noninfected pigs (P < 0.05). Malnutrition blunted (P < 0.05) increases in crypt depth elicited by rotavirus. By 9 d postinfection, body weight was 59% less, villus height and lactase activity remained lower (50%), and crypt depth remained greater (62%) in infected full-fed compared with noninfected pigs (P < 0.05). However, diarrhea began to clear in infected full-fed, but not in infected malnourished pigs. Plasma insulin-like growth factor-I (IGF-I) was reduced 68% and crypt depth was reduced 19% in infected-malnourished compared with infected full-fed pigs (P < 0.05). Sixteen days postinfection, full-fed pigs had recovered from rotaviral infection; however, in infected-malnourished pigs, diarrhea and growth stasis persisted, and plasma IGF-I, villus height and alkaline phosphatase activity remained reduced compared with infected full-fed pigs (P < 0.05). Overall, PEM prolonged diarrhea and delayed small-intestinal recovery, indicating that nutritional status during diarrhea is essential for recovery from rotaviral enteritis.


Staging laparotomy for Hodgkin's disease in 69 patients.
Sixty-nine patients with biopsy-proven Hodgkin's disease were subjected to laparotomy, splenectomy, liver biopsy, bone biopsy, and para-aortic nodal biopsies between October 1970 and December 1975, and have now been followed for 5 years. There were no major short-term surgical complications. There was one death from septicemia in a splenectomized adolescent. Laparotomy with splenectomy provides more precise delineation of intraabdominal disease than other methods. In difficult or equivocal cases, staging laparotomy can help choose the best treatment regimen.


Lichens: unexpected anti-prion agents?
The prion diseases sheep scrapie and cervid chronic wasting disease are transmitted, in part, via an environmental reservoir of infectivity; prions released from infected animals persist in the environment and can cause disease years later. Central to controlling disease transmission is the identification of methods capable of inactivating these agents on the landscape. We have found that certain lichens, common, ubiquitous, symbiotic organisms, possess a serine protease capable of degrading prion protein (PrP) from prion-infected animals. The protease functions against a range of prion strains from various hosts and reduces levels of abnormal PrP by at least two logs. We have now tested more than twenty lichen species from several geographical locations and from various taxa and found that approximately half of these species degrade PrP. Critical next steps include examining the effect of lichens on prion infectivity and cloning the protease responsible for PrP degradation. The impact of lichens on prions in the environment remains unknown. We speculate that lichens could have the potential to degrade prions when they are shed from infected animals onto lichens or into environments where lichens are abundant. In addition, lichens are frequently consumed by cervids and many other animals and the effect of dietary lichens on prion disease transmission should also be considered.


[Correction of vestibular disorders in patients with otitis media purulenta chronica complicated by labyrinthitis].
A vestibulogic examination was made in 66 patients with otitis media purulenta chronica complicated with labyrinthitis. The patients were divided into two groups: group 1 received surgical treatment in an acute period of labyrinthitis, group 2 was treated conservatively with delayed operation. The patients were examined at admission, 2 weeks, 1, 3, 6 and 12 months after the treatment. It was found that compensation of the vestibular function in group 1 took place 6 months after temporal bone surgery, in group 2-9 months after delayed operation, i.e. 1 years after hospitalization.


Imaging studies for evaluating impact of position sampling techniques in PET scanners.
Previously we have evaluated two crystal calibration techniques that can be applied to pixelated detector designs to improve system spatial resolution without detector motion. The inter-crystal positioning technique utilizes sub-sampling in the crystal flood map to better sample the Compton scatter events in the detector. The Compton scatter rejection technique, on the other hand, rejects those events that are located further from individual crystal centers in the flood map. Here we performed imaging studies with a Mini Deluxe hot rod phantom and a hot sphere phantom (sphere diameters of 4.95 and 7.86-mm with 6:1 uptake relative to background) using the standard crystal calibration technique, as well as the inter-crystal and Compton rejection calibration techniques. Our results show improved separation of 1.6-mm diameter hot rods with the two new crystal calibration techniques that is consistent with improved spatial resolution. For the hot sphere phantom the contrast recovery is improved with both the inter-crystal and Compton rejection calibration techniques over the standard calibration technique. The only drawback of the inter-crystal calibration technique is the increase in the number of possible lines-of-response (LORs) (factor of 16) that may slow image reconstruction. With the Compton rejection calibration technique, loss of counts leads to increased noise in the images.


Determining myocardial viability in chronic ischemic left ventricular dysfunction: a prospective comparison of rest-redistribution thallium 201 single-photon emission computed tomography, nitroglycerin-dobutamine echocardiography, and intracoronary myocardial contrast echocardiography.
Detection of viable myocardium (VM) has important therapeutic implications for chronic ischemic left ventricular (LV) systolic dysfunction. We compared the ability of nitroglycerin-dobutamine echocardiography (NTG-DE), intracoronary myocardial contrast echocardiography (MCE), and rest-redistribution thallium 201 single-photon emission computed tomography (RRT-SPECT) to detect VM in this setting. Patients with LV ejection fraction (LVEF) <40% and multivessel coronary disease suitable for revascularization underwent NTG-DE, MCE, RRT-SPECT, and radionuclide ventriculography to determine baseline LVEF. Myocardial contrast echocardiography was performed using intracoronary injection of Albunex. Patients who underwent revascularization had 3-month postprocedural radionuclide ventriculography and transthoracic echocardiography to assess functional recovery. Of 512 myocardial segments in the 32 patients studied, 309 were akinetic or dyskinetic at baseline. Nitroglycerin alone increased regional thickening in 20% of segments with contractile reserve. By RRT-SPECT, 93% of nitroglycerin-responsive segments were viable. Myocardial contrast echocardiography had up to 85% sensitivity and 74% specificity for detection of VM diagnosed by RRT-SPECT. In the 23 patients who underwent revascularization, 54% of akinetic segments showed improved contractility, and mean LVEF increased from 32% to 37% (P = .04). Sensitivities and specificities for detecting functional recovery were 95% and 37% for RRT-SPECT, up to 87% and 48% for MCE, and 63% and 83% for a biphasic response during NTG-DE. In patients with chronic ischemic LV dysfunction, RRT-SPECT had the highest sensitivity, and NTG-DE, the best specificity for detection of VM. Nitroglycerin facilitated detection of VM and may be a useful adjunct to dobutamine stimulation.


Quartz crystal microbalance immunosensors for environmental monitoring.
This paper presents discussion of quartz crystal microbalance (QCM) immunosensors for environmental monitoring. Factors limiting the practical application of antibodies to analytical problems are also presented. Among several candidates for the QCM immunosensor device, selected QCM devices and oscillating circuits were tested thoroughly and developed to obtain highly stable and sensitive frequency signals. The biointerface of QCM immunosensor was designed and controlled to immobilize antibody on the QCM surface, to reduce non-specific binding and to suppress denaturation of immobilizing antibody by self-assembled monolayer technique and artificial phospholipid (2-methacryloyloxyethyl phosphorylcholine (MPC)) polymer. MPC polymer as a antibody-stabilizing reagent was added to reduce non-specific binding of the antigen solution and stabilize the immunologic activity of the antibody-immobilized QCM. In addition, it provides examples for detection and quantitation of environmental samples using QCM immunosensors. The analytical results for fly ash extracted samples of dioxins using the QCM immunosensor indicated a good relationship with GC/MS methods. The integrating protocols of the competitive immunoassay and signal-enhancing step are for detecting low molecular analytes with extremely low detection limits using an QCM immunosensor. Furthermore, its detect limitation was extended from 0.1 to 0.01 ng/ml by the signal-enhancing step when the anti-bisphenol-A antibody conjugated MPC polymeric nanoparticles was used. The QCM immunosensor method has demonstrated its effectiveness as an alternative screening method for environmental monitoring because these results were compared with results obtained through environmental monitoring methods such as ELISA and GC/MS.


Exploring the determinants of fracture risk among individuals with spinal cord injury.
In this cross-sectional study, we found that areal bone mineral density (aBMD) at the knee and specific tibia bone geometry variables are associated with fragility fractures in men and women with chronic spinal cord injury (SCI). Low aBMD of the hip and knee regions have been associated with fractures among individuals with chronic motor complete SCI; however, it is unclear whether these variables can be used to identify those at risk of fracture. In this cross-sectional study, we examined whether BMD and geometry measures are associated with lower extremity fragility fractures in individuals with chronic SCI. Adults with chronic [duration of injury ≥ 2 years] traumatic SCI (C1-L1 American Spinal Cord Injury Association Impairment Scale A-D) reported post injury lower extremity fragility fractures. Dual-energy X-ray absorptiometry (DXA) was used to measure aBMD of the hip, distal femur, and proximal tibia regions, while bone geometry at the tibia was assessed using peripheral quantitative computed tomography (pQCT). Logistic regression and univariate analyses were used to identify whether clinical characteristics or bone geometry variables were associated with fractures. Seventy individuals with SCI [mean age (standard deviation [SD]), 48.8 (11.5); 20 females] reported 19 fragility fractures. Individuals without fractures had significantly greater aBMD of the hip and knee regions and indices of bone geometry. Every SD decrease in aBMD of the distal femur and proximal tibia, trabecular volumetric bone mineral density, and polar moment of inertia was associated with fracture prevalence after adjusting for motor complete injury (odds ratio ranged from 3.2 to 6.1). Low knee aBMD and suboptimal bone geometry are significantly associated with fractures. Prospective studies are necessary to confirm the bone parameters reported to predict fracture risk in individuals with low bone mass and chronic SCI.