Comparative efficacy of the Colgate Actibrush battery-powered toothbrush vs Oral-B CrossAction toothbrush on established plaque and gingivitis: a 6-week clinical study.
The objective of this clinical program was to compare the efficacy of the Colgate Actibrush battery-powered toothbrush and the Oral-B CrossAction Toothbrush (full head, soft bristle) for the control of supragingival plaque and gingivitis. Two independent clinical studies were conducted: Study 1 (repeated 3 times) was a single-use, examiner-blind clinical study designed to measure the removal of plaque after 24 hours of no oral hygiene. Study 2 was a definitive 6-week, examiner-blind clinical study designed to determine plaque and gingivitis efficacy at 3 and 6 weeks. Sixty-one men and women, who had refrained from using oral hygiene procedures for 24 hours, were entered into the study and stratified into 2 balanced groups according to baseline (prebrushing) plaque and gingivitis scores. For Study 1, Modified Navy Plaque Index (Rustogi Refinement) scores were obtained prebrushing and after a 1-minute supervised brushing with the assigned toothbrush and a commercially available toothpaste. On 3 separate occasions, after 24 hours of no oral hygiene, the Colgate Actibrush battery-powered toothbrush removed significantly more plaque than did the CrossAction Toothbrush. For Study 2, subjects were instructed to brush their teeth twice daily for 1 minute with the assigned toothbrush. Plaque Index scores and Löe-Silness Gingival Index scores were assessed after 3 and 6 weeks. At the 6-week examination, the group using the Colgate Actibrush battery-powered toothbrush exhibited a statistically significant reduction in both supragingival plaque and gingivitis, compared with the group that used the CrossAction Toothbrush. The results of these clinical studies support the conclusion that the Colgate Actibrush battery-powered toothbrush is clinically superior for the control of both supragingival plaque and gingivitis, as compared with the Oral-B CrossAction manual toothbrush.


[Surgical treatment of patients with spinal infection].
The surgical treatment of spinal infection, relegated because of the development of more effective antibiotherapy and the fear of associated morbidity, is springing up again with the increase of new patients with weakening pathology. The clinical records of 27 patients submitted to surgery because of spinal infection between January 1990 and December 1999 at our service have been retrospectively studied. They were assessed with the Frankel and Karnofsky clinical scales, and the radiological angulation of the spine. Male (n = 17) and dorsal lesions (n = 14) predominate. Most of patients presented with pain, and 13 had neurological compromise. 29 operations were performed on the 27 patients. One of them was previously operated upon before the period considered, that procedure has been excluded. The total surgeries performed were 5 simple and 4 instrumented laminectomies, 6 simple corpectomies, 10 corpectomies with anterior instrumentation and 4 with posterior instrumentation. One patient died, there was not definitive morbidity and any patient deteriorated on clinical scales although radiology was not always improved. The aggressive treatment of spinal infection is indicated when conservative means are insufficient. Surgery permits a better recovery of the neurological deficit, and prevents spinal deformity and pain produced by the disease.


Melatonin Treatment Delays Senescence and Maintains the Postharvest Quality of Baby Mustard (Brassica juncea var. gemmifera).
The effect of melatonin treatment on the visual quality and content of health-promoting compounds in baby mustard (Brassica juncea var. gemmifera) at 20°C was investigated in this study. Application of 100 μmol L-1 melatonin was the most effective in prolonging the shelf life of baby mustard among all of the concentrations tested (1, 50, 100, and 200 μmol L-1). The 100 μmol L-1 melatonin treatment also delayed the increase in weight loss and the decrease in sensory parameter scores; retarded the decline of chlorophyll content; slowed the decline in antioxidant capacity by maintaining the content of carotenoids and ascorbic acid, as well as increasing the levels of total phenolics; and increased the content of individual and total glucosinolates in the lateral buds of baby mustard. These findings indicate that melatonin treatment is effective for maintaining the sensory and nutritional qualities of postharvest baby mustard.


Association between alcohol and Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by dense deposition of amyloid-β (Aβ) protein in the brain, failure of the memory and dementia. At present, there is no cure for AD and current treatments only provide a temporary reduction of symptoms. Thus, there is a need for effective preventive/curative strategic approaches. Accordingly, epidemiological studies have reported a reduction in the prevalence of AD in individuals ingesting low amounts of alcohol, while a moderate consumption of ethanol may protect against Aβ. These data are conflicting with other observations that assigned detrimental effects of heavy alcohol use on brain function, which are apparently similar to those observed in AD. These discrepancies questioned whether or not alcohol is a protective agent against the development of AD, whether the probable protective effects are influenced by the quantity and/or frequency of drinking. These issues are addressed in this review with the aim to suggest the real risk of alcohol for developing or preventing AD.


Oxygen delivery to children with hypoxaemia in small hospitals in developing countries.
Oxygen administration is one of the most important modalities of therapy for a patient with hypoxaemia to prevent death. This review summarises the methods of oxygen delivery applicable in small hospitals in developing countries, and evaluates information about their safety and efficacy. The following criteria were considered: cost and availability, efficiency/oxygen concentration achieved, tolerability/comfort of the method, requirement of humidification, demand for nursing care, and safety of the method and complications. In summary, it is concluded that all low-flow methods, i.e., nasopharyngeal catheters, nasal catheters and prongs, are effective in the oxygenation of sick children with severe pneumonia or bronchiolitis. Nasal prongs are the safest method of oxygen delivery, but nasopharyngeal catheters and nasal catheters are more easily available and less expensive. However, if they are used, they need close supervision to avoid serious complications. Nasal prongs are the method of choice for oxygen delivery in small hospitals in developing countries.


Seroprevalence to Rabies Virus in Wildlife in Brazil.
Serum samples of 638 free-ranging wild mammals from São Paulo state, Brazil, were tested for neutralizing antibodies against rabies virus by the rapid fluorescent focus inhibition test. Overall seroprevalence was 1.7% among 24 species surveyed, with individuals of six species having positive results indicating exposure to rabies virus.


CRISPR Loss-of-Function Screen Identifies the Hippo Signaling Pathway as the Mediator of Regorafenib Efficacy in Hepatocellular Carcinoma.
Regorafenib is used for hepatocellular carcinoma (HCC), but its response does not last long, partly due to chemoresistance acquisition. We performed a clustered regularly interspaced short palindromic repeats (CRISPR)-based loss-of-function genetic screen and aimed to discover molecules involved in regorafenib resistance in HCC. Xenograft tumors established from Cas9-expressing HCC cells with pooled CRISPR kinome libraries were treated with regorafenib or a vehicle. Sequencing analysis identified 31 genes, with the abundance of multiple guide RNAs increased in regorafenib-treated tumors compared to that in vehicle-treated tumors, including 2 paralogues, LATS2 and LATS1, core components of the Hippo signaling pathway. Notably, all eight designed guide RNAs targeting LATS2 increased in regorafenib-treated tumors, suggesting that LATS2 deletion confers regorafenib resistance in HCC cells. LATS2 knockdown significantly mitigated the cytotoxic and proapoptotic effects of regorafenib on HCC cells. LATS2 inhibition stabilized the Hippo signaling mediator YAP, leading to the upregulation of antiapoptotic Bcl-xL and the multidrug resistance transporter ABCB1. Among 12 hepatoma cell lines, the half maximal inhibitory concentration (IC50) values of regorafenib were positively correlated with any of YAP, Bcl-xL and ABCB1 levels. The inhibition of YAP or Bcl-xL in regorafenib-insensitive HCC cells restored their susceptibility to regorafenib. In conclusion, our screen identified the Hippo signaling pathway as the mediator of regorafenib efficacy in HCC.


The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model.
Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.


Tuning the optoelectronic properties of nonfullerene electron acceptors.
Broad spectral coverage over the solar spectrum is necessary for photovoltaic technologies and is a focus for organic solar cells. We report a series of small-molecule, nonfullerene electron acceptors containing the [(benzo[c][1,2,5]thiadiazol-4-yl)methylene]malononitrile unit as a high electron affinity component. The optoelectronic properties of these molecules were fine-tuned with the objective of attaining strong absorption at longer wavelengths by changing the low-ionization-potential moiety. The electron-accepting function of these materials was investigated with poly(3-n-hexylthiophene) (P3HT) as a standard electron donor. Significant photocurrent generation in the near infrared region, with an external quantum yield reaching as high as 22 % at 700 nm and an onset >800 nm was achieved. The results support efficient hole transfer to P3HT taking place after light absorption by the acceptor molecules. A Channel II-dominated power conversion efficiency of up to 1.5 % was, thus, achieved.


Unexplained swelling symptoms in women (idiopathic oedema) comprise one component of a common polysymptomatic syndrome.
Non-menstrually-related swelling symptoms (idiopathic oedema) are common in women. The community prevalence of such symptoms, their association with other symptoms, and their underlying aetiology, are uncertain. To determine the community prevalence of swelling symptoms and the independent contributions of major risk factors. Comparison of major risk factors in women with and without swelling symptoms. We assessed 196 women attending a menopause clinic, 201 women attending a fracture clinic and 201 women attending their general practitioner. Each documented family histories of swelling symptoms and diabetes mellitus, age, height and current weight. Women attending the menopause and fracture clinics also completed Visual Analogue Symptom (VAS) scales documenting the perceived severity of swelling symptoms, and of 20 affective, somatic and functional autonomic symptoms. The independent contributions of risk factors to swelling symptom risk were estimated by logistic regression analysis. Of those attending a fracture clinic or their general practitioner, 28% and 33%, respectively, experienced non-menstrually-related swelling symptoms in the month before interview. Severe (RR 43, 95%CI 16-112, p < 0.001) and moderate (RR 7.8, 95%CI 4-15, p < 0.001) affective symptoms, a family history of swelling symptoms (RR 4.5, 95%CI 2.3-8.8, p < 0.001) and a body mass index (BMI) >or=25 kg/m(2) (RR 4.8, 95%CI 2.5-8.9, p < 0.001) were significantly associated with the presence of mild to severe swelling symptoms (VAS 1-9). The prevalence of swelling symptoms increased from 8% in women with no risk factors to 100% in women with three risk factors, which included severe affective symptoms. Affective symptom severity provides the principal independent contribution to swelling symptom risk. BMI >or=25 and a family history of swelling symptoms provide smaller independent contributions. The nature of the mechanisms underlying these associations remains uncertain.


Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study.
This study aimed to assess the effect of the Microablative Fractional CO2 Laser (CO2-laser) therapy on vaginal pathophysiology and the symptoms of the Genitourinary Syndrome of Menopause (GSM). Postmenopausal women with moderate to severe symptoms of GSM underwent three sessions of CO2-laser therapy at monthly intervals. Participants were evaluated at baseline and 4 weeks after the last treatment. The primary outcomes were Vaginal Maturation Value (VMV) and Vaginal Health Index Score (VHIS). Secondary outcomes included symptoms of GSM, Female Sexual Function Index (FSFI), International Consultation on Incontinence Questionnaire of Female Urinary Tract Symptoms (ICIQ-FLUTS) and Urinary Incontinence Short Form (ICIQ-UI SF), Urogenital Distress Inventory (UDI-6) and King's Health Questionnaire (KHQ). Fifty-three postmenopausal women completed this study. VMV, VHIS and FSFI increased significantly. Dyspareunia, dryness, burning, itching, dysuria, frequency, urgency, urgency incontinence, stress incontinence and scores on the ICIQ-FLUTS, ICIQ-UI SF, UDI-6 and KHQ decreased significantly. Factors predicting for which women the CO2-laser therapy was more effective were not identified. This study suggests that intravaginal CO2-laser therapy for postmenopausal women with clinical signs and symptoms of GSM may be effective in improving both vaginal pathophysiology and reported symptoms.


Emergence of a diffusive metal state with no magnetic order near the Mott transition in frustrated pyrochlore-type molybdates.
The electron-correlation driven metal-insulator (Mott) transition in pyrocholore-type R2Mo2O7(R being rare-earth-metal ions) is accompanied by the change of the magnetic state from ferromagnetic to spin glass due to the competing double-exchange and superexchange interactions on the frustrated lattice. By application of high pressures on the compounds with Mott criticality, however, a new unique paramagnetic metal phase is observed to show up with nearly temperature-independent high resistivity close to the Ioffe-Regel limit. A possible non-Fermi-liquid character of this anomalously diffuse metallic state is argued in terms of the extended double-exchange model with the magnetically frustrated local S=1/2 spins.


The clock regulator Bmal1 protects against muscular dystrophy.
The muscle-intrinsic clock machinery is required for the maintenance of muscle growth, remodeling and function. Our previous studies demonstrated that the essential transcription activator of the molecular clock feed-back loop, Brain and Muscle Arnt-Like 1(Bmal1), plays a critical role in myogenic progenitor behavior to promote and regenerative myogenesis. Using genetic approaches targeting Bmal1 in the DMDmdx (mdx) dystrophic mouse model, here we report that the loss of Bmal1 function significantly accelerated dystrophic disease progression. In contrast to the mild dystrophic changes in mdx mice, the genetic loss-of-function of Bmal1 aggravated muscle damage in this dystrophic disease background, as indicated by persistently elevated creatine kinase levels, increased injury area and reduced muscle grip strength. Mechanistic studies revealed that markedly impaired myogenic progenitor proliferation and myogenic response underlie the defective new myofiber formation in the chronic dystrophic milieu. Taken together, our study identified the function of pro-myogenic clock gene Bmal1 in protecting against dystrophic damage, suggesting the potential for augmenting Bmal1 function to ameliorate dystrophic or degenerative muscle diseases.


Characteristics of gout patients according to the laterality of nephrolithiasis: A cross-sectional study using helical computed tomography.
To clarify the clinical and laboratory characteristics of nephrolithiasis in gout by computed tomography (CT). In 350 gout patients, unenhanced CT was performed at the 1st visit to hospital. Calculus density spots exceeding 1 mm in diameter with a CT value >120 Hounsfield units in the kidneys were defined as kidney stones. The association between laterality and the number of stones was investigated in each stone carrier. The 350 patients were classified into three groups (bilateral, unilateral and non-stone carriers). Then serum urate (Sua), renal function, uric acid metabolism, and the prevalence of metabolic syndrome (Mets) were compared among these groups by the Tukey-Kramer test or Fisher's exact test. Kidney stone(s) were detected in 108 (31%) of the 350 patients (bilateral in 58 and unilateral in 50). In 64 of the 108 patients (59%), there was no history of urolithiasis. Sua, serum creatinine and uric acid clearance were significantly higher (P = 0.001, P < 0.001, P = 0.043, respectively), while the estimated glomerular filtration rate was significantly lower (P = 0.039) in bilateral stone carriers than in non-stone carriers. No significant differences of uric acid metabolism or the prevalence of Mets were noted among the three groups. Approximately one-third of gout patients had kidney stones and more than half of the patients with stones were bilateral and multiple stone carriers. Elevation of Sua might increase the stone burden in gout, leading to more severe renal dysfunction. An association between nephrolithiasis and Mets was not demonstrated in gout patients.


Flow-cytometric isolation and enrichment of teleost type A spermatogonia based on light-scattering properties.
The transplantation of germ cells is a powerful tool both for studying their development and for reproductive biotechnology. An intraperitoneal germ cell transplantation system was recently developed for use in several teleost species. Donor germ cells transplanted into the peritoneal cavity of hatchlings migrated toward and were incorporated into the recipient's genital ridges, where they underwent gametogenesis. Among male germ cells, only type A spermatogonia were capable of colonizing the recipient gonads, unlike those at more advanced stages. The enrichment of type A spermatogonia is therefore important to achieve efficient donor-cell incorporation and subsequent donor-derived gametogenesis. Here we established a simple and rapid system of isolation and enrichment for fish type A spermatogonia, using flow cytometry. Type A spermatogonia were found to have distinctive forward and side light scatter properties compared to that with other types of testicular cell. Based on these characteristics, we were able to isolate and enrich type A spermatogonia by using flow cytometry. After intraperitoneal transplantation, the enriched type A spermatogonia could be successfully incorporated into the recipient genital ridges. This flow cytometry approach using forward and side light scatter was also found to be applicable to other salmonid and sciaenid species, suggesting that it could be a powerful tool for isolating and enriching transplantable type A spermatogonia in a wide range of teleosts. We expect this method to contribute significantly to germ cell biology and biotechnology.


Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter.
Transitional cell carcinoma of the upper urinary tract is a relatively uncommon malignancy. The role of adjuvant radiation therapy and chemotherapy is not well defined. We retrospectively reviewed the records of 31 patients who underwent surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy to determine overall outcome as well as impact of concurrent chemotherapy administration. Between 1970 and 1997, 31 patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (renal pelvis in 13, ureter in 15, and renal pelvis and ureter in 3) were treated with radiotherapy following attempted curative resection. Most patients (28 of 31) had T3/4 and/or N+ disease. The median radiation dose was 46.9 Gy. Nine patients received methotrexate, cisplatin and vinblastine chemotherapy for 2 to 4 cycles, followed by concurrent cisplatin with radiation. Median followup was 2.6 years in all patients and 8.5 years in survivors. Median survival in all patients was 2.4 years. Of the patients 16 (52%) experienced disease relapse, including 9 (29%) with distant metastases alone. Seven patients (23%) experienced locoregional failure with distant metastases developing in all except 1 within 8 months of locoregional failure diagnosis. Five-year actuarial overall survival, disease specific survival, locoregional control and metastasis-free survival rates were 39%, 52%, 67% and 48%, respectively. On univariate analysis patients had improved 5-year actuarial overall and disease specific survival with the administration of concurrent chemotherapy (27% vs 67%, p = 0.01 and 41% vs 76%, p = 0.06, respectively). Our series suggests that the addition of concurrent cisplatin to adjuvant radiotherapy improves the ultimate outcome in patients with resected, locally advanced upper tract urothelial malignancies. This regimen should be considered in patients with T3/4 and/or node positive upper tract transitional cell carcinoma.


Concomitant Trajectories of Internalising, Externalising, and Peer Problems Across Childhood: a Person-centered Approach.
This study investigated trajectories of concomitant internalising, externalising, and peer problems, and associated risk factors for group-membership, using a person-centered approach to better understand heterogeneity in subgroups identified. A cohort of 7,507 children in Ireland was followed from infancy to late childhood (50.3%, males; 84.9% Irish). The parent-version of the Strengths and Difficulties Questionnaire was used when children were 3, 5, 7 and 9 years of age. Information on antecedent risk factors was collected when children were 9 months. Group-based multi-trajectory modelling and multinomial logistic regression were used. Six subgroups of children with distinct profiles were identified, evidencing both homotypic and heterotypic comorbidity. No support of a 'pure' internalising, externalising or peer problems group was found in any identified trajectory group. Difficulties in one problem domain indicated the presence of difficulty in another problem domain for all children in elevated groups. Risk factors associated with group-membership were complex, with only three common factors across elevated groups: prenatal exposure to smoking, maternal education, and maternal stress. Specific risk factors for group-membership included low birth weight, sex, maternal age, maternal depression, family composition, social class, medical card status and quality of attachment. Despite some overlap in predictors, the combination of predictors specific to each group would suggest tailored programming. For children with the most acute problems, programming targets should include families with boys, born with low birth weight, exposed to smoking prenatally, with mothers who have lower levels of education, postnatal depression, increased stress and fewer financial resources.


Multicentric papillary-cystic neoplasm of the pancreas.
Two distinct papillary-cystic neoplasms were found in the pancreas of a young black woman. She presented to the hospital in her first trimester of pregnancy with the chief complaint of sharp right upper quadrant abdominal pain that radiated to the right shoulder. This was associated with jaundice, vomiting, and pruritus. On examination, a large, nontender, midepigastric abdominal mass was palpated. Serum liver enzyme levels were moderately to markedly elevated. An abdominal computed tomographic scan revealed a 9-cm solid and cystic mass located within the head of the pancreas with associated marked bile duct dilatation. A total pancreatectomy was performed. Gross examination of the specimen revealed two separate well-circumscribed tumors of unequal size. The larger one was found within the head of the pancreas and contained multiple hemorrhagic, cystic cavities. The smaller one, located within the tail, consisted primarily of solid tissue. Microscopic examination of both lesions revealed papillary-cystic neoplasms. To our knowledge, this is the first report of two synchronous papillary-cystic tumors of the pancreas and the first reported demonstration of the potential of this tumor for multicentricity.


Evaluating training effectiveness in psychotherapy: lessons for the AOD field.
Based on evaluations of effectiveness training on trainee and client outcome in the psychotherapy field, this paper presents a model and recommendations for the alcohol and other drug (AOD) field to consider when conducting investigations into training. Determining the effectiveness of training requires the consideration of a number of factors, including pre-existing trainee variables, methods of training and ability of trainers and the focus of training. The influence of each of these factors may be considered first in terms of proximal outcomes such as trainee satisfaction, improvements in clinical practice and knowledge, and secondly in terms of more distal outcomes, such as the impact that training may have on improving client outcome. The current literature regarding these factors pertaining to psychotherapy outcome is reviewed, and recommendations for evaluating training in the AOD field are made.


Generalizability of immune checkpoint inhibitor trials to real-world patients with advanced non-small cell lung cancer.
Based on data from randomized controlled trials (RCTs), immune checkpoint inhibitors (ICI) are standard-of-care in advanced non-small cell lung cancer (aNSCLC). However, trial eligibility criteria are restrictive, and participants and outcomes may not represent the wider population. We aim to assess the generalizability of key phase III RCTs to real-world patients. Among aNSCLC patients enrolled in the Embedding Research (and Evidence) in Cancer Healthcare (EnRICH) program between 26/6/17-18/2/21, we assessed the proportion of patients who fulfilled key trial eligibility criteria: performance status (PS) 0-1, normal laboratory results, no EGFR/ALK mutations, no exclusionary comorbidities (previous cancer, conditions necessitating steroid use, autoimmune diseases, HIV, hepatitis B/C, tuberculosis, interstitial lung disease, organ transplantation). We defined patients who met all assessed criteria as trial-typical and describe ICI uptake and overall survival (OS). Of 454 patients (median age 71 years, 42.1% female), 30% were trial-typical. Less than half received ICI (47.6%), with trial-typical patients more likely to receive ICI (69.1% vs 38.4%, adjusted odds ratio 3.77, 95% CI 2.40-5.91). Median OS was 10.2 and 5.4 months in patients receiving first- and second-line ICI, respectively. Rationalizing trial criteria to include patients with PS ≤ 2 and exclude those with targetable mutations, steroid use, autoimmune diseases, interstitial lung disease, tuberculosis or organ transplantation increased the proportion of trial-typical patients to 57.3%. Landmark phase III RCTs in aNSCLC have limited generalizability. OS of real-world patients receiving ICI is shorter than reported in trials. Novel ICI trials should consider broader eligibility criteria to improve their generalizability.


Combining population-dynamic and ecophysiological models to predict climate-induced insect range shifts.
Hundreds of species are shifting their ranges in response to recent climate warming. To predict how continued climate warming will affect the potential, or "bioclimatic range," of a skipper butterfly, we present a population‐dynamic model of range shift in which population growth is a function of temperature. We estimate the parameters of this model using previously published data for Atalopedes campestris. Summer and winter temperatures affect population growth rate independently in this species and therefore interact as potential range‐limiting factors. Our model predicts a two‐phase response to climate change; one range‐limiting factor gradually becomes dominant, even if warming occurs steadily along a thermally linear landscape. Whether the range shift accelerates or decelerates and whether the number of generations per year at the range edge increases or decreases depend on whether summer or winter warms faster. To estimate the uncertainty in our predictions of range shift, we use a parametric bootstrap of biological parameter values. Our results show that even modest amounts of data yield predictions with reasonably small confidence intervals, indicating that ecophysiological models can be useful in predicting range changes. Nevertheless, the confidence intervals are sensitive to regional differences in the underlying thermal landscape and the warming scenario.


The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome.
There is growing interest in deficit symptoms in studies of the course and treatment response of schizophrenia. However, existing clinical assessment instruments focus primarily on productive symptoms. The authors describe the Quality of Life Scale (QLS), a 21-item scale based on a semistructured interview designed to assess deficit symptoms and thereby fill an important gap in the range of instruments now available. Data regarding reliability and training in the use of the QLS are presented. A factor analysis of the items yields results compatible with the conceptual model on which the scale is based. The factor analysis was also performed separately by sex and was fundamentally similar for men and women.


Apparent repulsion between equally and oppositely charged spherical polyelectrolytes in symmetrical salt solutions.
Ion-mediated interactions are very important for the properties of colloids and biomacromolecules such as nucleic acids and proteins. In this work, the ion-mediated interactions between equally and oppositely charged spherical polyelectrolytes (SPEs) in symmetrical divalent electrolytes have been investigated by Monte Carlo simulations, and an unexpected apparent repulsion was observed at high divalent salt concentration. Our investigations also show that the effective repulsion becomes more pronounced for SPEs with higher charge densities and for counterions with larger sizes and was found to be tightly accompanied with the over-neutralization to SPEs by condensed counterions and their release upon the approach of SPEs. Such attractive interaction can be reproduced by our proposed modified Poisson-Boltzmann model and is mainly attributed to the increase in the electrostatic repulsion between on charged SPE and the over-neutralized counterions around the other oppositely SPE with the approach of the two SPEs.


Dynamics of the Acinetobacter baumannii inner membrane under exogenous polyunsaturated fatty acid stress.
Exogenous polyunsaturated fatty acids (PUFAs) are readily incorporated into the synthesis pathways of A. baumannii membrane phospholipids, where they contribute to reduced bacterial fitness and increased antimicrobial susceptibility. Here we examine the impact of PUFA membrane modification on membrane organisation and biophysical properties using coarse grained MARTINI simulations of chemically representative membrane models developed from mass-spectrometry datasets of an untreated, arachidonic acid (AA) treated and docosahexaenoic acid (DHA) treated A. baumannii membranes. Enzymatic integration of AA or DHA into phospholipids of the A. baumannii membrane resulted in modulation of membrane biophysical properties. Membrane thickness decreased slightly following PUFA treatment, concomitant with changes in the lateral area per lipid of each lipid headgroup class. PUFA treatment resulted in a decrease in membrane ordering and an increase in lipid lateral diffusion. Changes in lateral membrane organisation were observed in the PUFA treated membranes, with a concurrent increase in ordered cardiolipin domains and disordered PUFA-containing domains. Notably, separation between ordered and disordered domains was enhanced and was more pronounced for DHA relative to AA, providing a possible mechanism for greater antimicrobial action of DHA relative to AA observed experimentally. Furthermore, the membrane active antimicrobial, pentamidine, preferentially adsorbs to cardiolipin domains of the A. baumannii model membranes. This interaction, and membrane penetration of pentamidine, was enhanced following PUFA treatment. Cumulatively, this work explores the wide-ranging effects of PUFA incorporation on the A. baumannii membrane and provides a molecular basis for bacterial inner membrane disruption by PUFAs.


The Sequence and Three-Dimensional Structure Characterization of Snake Venom Phospholipases B.
Snake venom phospholipases B (SVPLBs) are the least studied enzymes. They constitute about 1% of Bothrops crude venoms, however, in other snake venoms, it is present in less than 1%. These enzymes are considered the most potent hemolytic agent in the venom. Currently, no structural information is available about these enzymes from snake venom. To better understand its three-dimensional structure and mechanisms of envenomation, the current work describes the first model-based structure report of this enzyme from Bothrops moojeni venom named as B. moojeni phospholipase B (PLB_Bm). The structure model of PLB_Bm was generated using model building software like I-TESSER, MODELLER 9v19, and Swiss-Model. The build PLB_Bm model was validated using validation tools (PROCHECK, ERRAT, and Verif3D). The analysis of the PLB_Bm modeled structure indicates that it contains 491 amino acid residues that form a well-defined four-layer αββα sandwich core and has a typical fold of the N-terminal nucleophile aminohydrolase (Ntn-hydrolase). The overall structure of PLB_Bm contains 18 β-strands and 17 α-helices with many connecting loops. The structure divides into two chains (A and B) after maturation. The A chain is smaller and contains 207 amino acid residues, whereas the B chain is larger and contains 266 amino acid residues. The sequence and structural comparison among homologous snake venom, bacterial, and mammals PLBs indicate that differences in the length and sequence composition may confer variable substrate specificity to these enzymes. Moreover, the surface charge distribution, average volume, and depth of the active site cavity also vary in these enzymes. The present work will provide more information about the structure-function relationship and mechanism of action of these enzymes in snakebite envenomation.


Augmenting recombinant antibody production in HEK293E cells: optimizing transfection and culture parameters.
Optimizing recombinant antibody production is important for cost-effective therapeutics and diagnostics. With impact on commercialization, higher productivity beyond laboratory scales is highly sought, where efficient production can also accelerate antibody characterizations and investigations. Investigating HEK293E cells for mammalian antibody production, various transfection and culture parameters were systematically analyzed for antibody light chain production before evaluating them for whole antibody production. Transfection parameters investigated include seeding cell density, the concentration of the transfection reagent and DNA, complexation time, temperature, and volume, as well as culture parameters such as medium replacement, serum deprivation, use of cell maintenance antibiotic, incubation temperature, medium volume, post-transfection harvest day, and common nutrient supplements. Using 2 mL adherent HEK293E cell culture transfections with 25 kDa linear polyethylenimine in the most optimized parameters, we demonstrated a ~2-fold production increase for light chain alone and for whole antibody production reaching 536 and 49 μg, respectively, in a cost-effective manner. With the addition of peptone, κ light chain increased by ~4-fold to 1032 μg, whereas whole antibody increased to a lesser extent by ~2.5-fold to 51 μg, with benefits potentially for antibodies limited by their light chains in production. Our optimized findings show promise for a more efficient and convenient antibody production method through transfection and culture optimizations that can be incorporated to scale-up processes and with potential transferability to other mammalian-based recombinant protein production using HEK293E.


Shoot organogenesis from root-derived callus of Rhinacanthus nasutus (L.) Kurz. and assessment of clonal fidelity of micropropagted plants using RAPD analysis.
An efficient regeneration system was established for an ethnomedicinal shrub Rhinacanthus nasutus from root-derived callus organogenesis. The root segments were cultured on MS medium supplemented with various concentrations of Kn (1.0-4.0 μM) alone or in combination with IBA (0.2-0.6 μM) or 2, 4-D (0.5-1.5 μM). The optimum frequency (94%) of callus induction was recorded on MS medium supplemented with 3.0 μM Kn and 0.4 μM IBA. For shoot regeneration from callus, MS medium supplemented with different concentrations (1.0-7.0 μM) of BA or TDZ alone or in combination with NAA (0.2-1.0 μm) was employed. The highest frequency of shoot regeneration (91%) and mean number of shoots (28.3) were observed on MS medium supplemented with 5.0 μM BA and 0.7 μM NAA. The shoots were excised and cultured on MS medium with 4.0 μM IBA produced 3.4 roots per shoot in 88% cultures. Of the 65 plants transferred to soil 54 survived (83%). The plants were transferred to field after successful hardening. RAPD analysis of the regenerated plants showed high similarity with the mother plant.


Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review.
Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment. We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization. Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse, hospitalization and suicide. Factors positively related to adherence were a good therapeutic relationship with physician and perception of benefits of medication. The most frequently reported driver and consequence were lack of insight and greater risk of hospitalization respectively. Improving adherence in schizophrenia may have a considerable positive impact on patients and society. This can be achieved by focusing on the identified multitude of factors driving nonadherence.


The role of the microbiome in scalp hair follicle biology and disease.
The skin surface microbiome and its role in skin diseases have received increasing attention over the past years. Beyond, there is evidence for a continuous exchange with the cutaneous immune system in healthy skin, where hair follicles (HFs) provide unique anatomical niches. Especially, scalp HFs form large tubular invaginations, which extend deeply into the skin and harbour a variety of microorganisms. The distinct immunology of HFs with enhanced immune cell trafficking in superficial compartments in juxtaposition to immune-privileged sites crucial for hair follicle cycling and regeneration makes this organ a highly susceptible structure. Depending on composition and penetration depth, microbiota may cause typical infections, but may also contribute to pro-inflammatory environment in chronic inflammatory scalp diseases. Involvement in hair cycle regulation and immune cell maturation has been postulated. Herein, we review recent insights in hair follicle microbiome, immunology and penetration research and discuss clinical implications for scalp health and disease.


Interaction of p38 and Sp1 in a mechanical force-induced, beta 1 integrin-mediated transcriptional circuit that regulates the actin-binding protein filamin-A.
Connective tissue cells in mechanically active environments survive applied physical forces by modifying actin cytoskeletal structures that stabilize cell membranes. In fibroblasts, tensile forces induce the expression of filamin-A, a mechanoprotective actin-binding protein, but the mechanisms and protein interactions by which force activates filamin-A transcription are not defined. We found that in fibroblasts, application of tensile forces through collagen-coated magnetite beads to cell surface beta(1) integrins induced filamin-A expression. This induction required actin filaments and selective activation of the p38 mitogen-activated protein kinase. Force promoted the redistribution of p38 to the integrin/bead locus and the nucleus as well as enhanced binding of the transcription factor Sp1 to proximal, regulatory domains of the filamin-A promoter. Force application increased association of Sp1 with p38 and phosphorylation of Sp1. Transcriptional activation of filamin-A in force-treated fibroblasts was subsequently mediated by Sp1-binding sites on the filamin-A promoter. These results provide evidence for a mechanically coupled transcriptional circuit that originates at the magnetite bead/integrin locus, activates p38, tethers p38 to actin filaments, promotes binding of p38 to Sp1 in the nucleus, and induces filamin-A expression.


Inner strength among HIV-infected women: nurses can make a difference.
The purpose of this qualitative study was twofold. First, the authors examined the phenomenon of inner strength as a resource that women infected with HIV use to cope with and manage their difficult lives. Second, the authors sought the women's views on the potential impact health care workers, specifically nurses, can have on the activation of inner strength. This study was phenomenologically informed and qualitatively structured. The goal was to construct an analytical understanding of inner strength as it is perceived, defined, experienced, and activated by women infected with HIV. Data were collected by means of 19 conversational, biographical interviews. These interviews were conducted with a stratified (by ethnicity and social class) sample of women infected with HIV. The data were elicited in terms of respondents' stories of living with HIV. The women listed a number of definitions for inner strength such as "the ability to fight" and "the motivation to go on and do better." The women recommended that nurses working with them be sensitive to the following patient concerns: validation, reality, sensitivity, and autonomy. The concept of inner strength can be of great scholarly and clinical value if it is defined as follows: Inner strength refers to the different ways women with serious illnesses experience and talk about the deepest, existential resources available to and used by them to manage severe risks to self-integrity. The recommendations, although somewhat critical of nurses, are plausible because they incorporate nurses' traditional approaches to caring for patients.


Insecticide resistance in indoor and outdoor-resting Anopheles gambiae in Northern Ghana.
Selection pressure from continued exposure to insecticides drives development of insecticide resistance and changes in resting behaviour of malaria vectors. There is need to understand how resistance drives changes in resting behaviour within vector species. The association between insecticide resistance and resting behaviour of Anopheles gambiae sensu lato (s.l.) in Northern Ghana was examined. F1 progenies from adult mosquitoes collected indoors and outdoors were exposed to DDT, deltamethrin, malathion and bendiocarb using WHO insecticide susceptibility tests. Insecticide resistance markers including voltage-gated sodium channel (Vgsc)-1014F, Vgsc-1014S, Vgsc-1575Y, glutathione-S-transferase epsilon 2 (GSTe2)-114T and acetylcholinesterase (Ace1)-119S, as well as blood meal sources were investigated using PCR methods. Activities of metabolic enzymes, acetylcholine esterase (AChE), non-specific β-esterases, glutathione-S-transferase (GST) and monooxygenases were measured from unexposed F1 progenies using microplate assays. Susceptibility of Anopheles coluzzii to deltamethrin 24 h post-exposure was significantly higher in indoor (mortality = 5%) than outdoor (mortality = 2.5%) populations (P = 0.02). Mosquitoes were fully susceptible to malathion (mortality: indoor = 98%, outdoor = 100%). Susceptibility to DDT was significantly higher in outdoor (mortality = 9%) than indoor (mortality = 0%) mosquitoes (P = 0.006). Mosquitoes were also found with suspected resistance to bendiocarb but mortality was not statistically different (mortality: indoor = 90%, outdoor = 95%. P = 0.30). Frequencies of all resistance alleles were higher in F1 outdoor (0.11-0.85) than indoor (0.04-0.65) mosquito populations, while Vgsc-1014F in F0 An. gambiae sensu stricto (s.s) was significantly associated with outdoor-resting behaviour (P = 0.01). Activities of non-specific β-esterase enzymes were significantly higher in outdoor than indoor mosquitoes (Mean enzyme activity: Outdoor = : 1.70/mg protein; Indoor = 1.35/mg protein. P < 0.0001). AChE activity was also more elevated in outdoor (0.62/mg protein) than indoor (0.57/mg protein) mosquitoes but this was not significant (P = 0.08). Human blood index (HBI) was predominantly detected in indoor (18%) than outdoor mosquito populations (3%). The overall results did not establish that there was a significant preference of resistant malaria vectors to solely rest indoors or outdoors, but varied depending on the resistant alleles present. Phenotypic resistance was higher in indoor than outdoor-resting mosquitoes, but genotypic and metabolic resistance levels were higher in outdoor than the indoor populations. Continued monitoring of changes in resting behaviour within An. gambiae s.l. populations is recommended.


Sequence of Chloroplast Degreening in Calamondin Fruit as Influenced by Ethylene and AgNO(3).
C(2)H(4) disrupts the internal membranes of the chloroplast and induces an increase in chlorophyllase activity in degreening calamondin [x Citrofortunella mitis (Blanco) Ingram and Moore] fruit. Whether the loss of chlorophyll in the peel is causally related to breakdown of the chloroplast and/or chlorophyllase activity is not readily apparent. Chlorophyllase levels were inversely related to chlorophyll content, but electron micrographs also showed that internal membranes of the chloroplasts were disrupted simultaneously with the decrease in chlorophyll content. Silver, a potent inhibitor of C(2)H(4)-mediated effects, retarded the loss of chlorophyll in calamondin rind, reduced the C(2)H(4)-induced increase in chlorophyllase level, and prevented the disruption of the chloroplast membranes. The results do not permit the proposal of a mechanism of C(2)H(4) metabolism in the degreening of calamondin fruit.


Adherence to recommended intake of pulses and related factors in university students in the UniHcos project.
Pulses such as peas, beans or lentils are one of the most complete foods at the nutritional level; however, they are one of the most often neglected foods in the diets of university students. Entrance to university translates into a major lifestyle change for many young people, and the habits acquired or cemented at this time will remain into adulthood. The objective of this study is to analyse the association between personal/sociodemographic factors, dietary intake of other food groups and the consumption of pulses in first-year university students. This cross-sectional study is part of the UniHcos project, a multicentre study of multipurpose prospective cohorts in eleven Spanish universities. Data from 9862 university students were collected through an online self-questionnaire completed by all students who met the selection criteria and agreed to participate in the project during the 2011-2018 academic years. Of students, 75·8 % presented an inadequate (≤2 times/week) consumption of pulses. Living outside the family home in either a student residence (OR 0·76; 95 % CI 0·69, 0·84) or rental (OR 0·81; 95 % CI 0·70, 0·95) decreased the compliance with recommendations on the consumption of pulses. Low consumption of pulses is seemingly not restricted to a specific profile or dietary pattern among university students, and no specific focus group for intervention can be identified. Policies promoting the consumption of pulses among the university population as a whole are necessary to increase compliance rates with the dietary recommendations.


Pictorial key to the common Indian species of Aedes (Stegomyia) mosquitoes.
The paper provides a simple pictorial key to differentiate common stegomyia species found in urban areas. This key will help medical officers and paramedical staff in demarcating the areas of influence of Aedes aegypti within a Dengue surveillance area.


Ceragenins and Antimicrobial Peptides Kill Bacteria through Distinct Mechanisms.
Ceragenins are a family of synthetic amphipathic molecules designed to mimic the properties of naturally occurring cationic antimicrobial peptides (CAMPs). Although ceragenins have potent antimicrobial activity, whether their mode of action is similar to that of CAMPs has remained elusive. Here, we reported the results of a comparative study of the bacterial responses to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. Using transcriptomic and proteomic analyses, we found that Escherichia coli responded similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Although traditional genetic approaches failed to identify genes that confer high-level resistance to ceragenins, using a Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) approach we identified E. coli essential genes that when knocked down modify sensitivity to these molecules. Comparison of the essential gene-antibiotic interactions for each of the CAMPs and ceragenins identified both overlapping and distinct dependencies for their antimicrobial activities. Overall, this study indicated that, while some bacterial responses to ceragenins overlap those induced by naturally occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action. IMPORTANCE The development of novel antibiotics is essential because the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. The development of naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors. The ceragenins are a family of synthetic CAMP mimics that kill a broad spectrum of bacterial species but are less expensive to produce, resistant to proteolytic degradation, and seemingly resistant to the development of high-level resistance. Determining how ceragenins function may identify new essential biological pathways of bacteria that are less prone to the development of resistance and will further our understanding of the design principles for maximizing the effects of synthetic CAMPs.


Microfluidic perfusion system for maintaining viable heart tissue with real-time electrochemical monitoring of reactive oxygen species.
A microfluidic device has been developed to maintain viable heart tissue samples in a biomimetic microenvironment. This device allows rat or human heart tissue to be studied under pseudo in vivo conditions. Effluent levels of lactate dehydrogenase and hydrogen peroxide were used as markers of damaged tissue in combination with in situ electrochemical measurement of the release of reactive oxygen species (ROS). The parameters for perfusion were optimized to maintain biopsies of rat right ventricular or human right atrial tissue viable for up to 5 and 3.5 hours, respectively. Electrochemical assessment of the oxidation current of total ROS, employing cyclic voltammetry, gave results in real-time that were in good agreement to biochemical assessment using conventional, off-chip, commercial assays. This proof-of-principle, integrated microfluidic device, may be exploited in providing a platform technology for future cardiac research, offering an alternative approach for investigating heart pathophysiology and facilitating the development of new therapeutic strategies.


Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins.
The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro.


Vascular protection of lacidipine in salt-loaded Dahl-S rats at nonsustained antihypertensive doses.
The aim of this study was to characterize the antihypertensive and vasoprotective properties of lacidipine in salt-loaded Dahl-S rats, a suitable animal model of malignant hypertension. After 9 weeks of a high (8%) sodium chloride (NaCl) diet, 80% of the untreated Dahl-S rats died (20% survival rate) whereas a 100% survival rate was observed with chronic treatment with lacidipine at doses of 0.1 (equivalent to the recommended dose in humans), 0.3, 1, and 10 mg/kg once daily by gastric gavage. The most interesting results included the following: (a) Only the highest dose tested (10 mg/kg once daily) was able to control the increase in blood pressure, which was measured 24 h after the preceding administration of drug, yet a 100% survival rate was maintained. (b) There appeared to be prevention of brain lesions, which is very likely the cause of the survival of all of the lacidipine-treated rats in this study. (c) A clear dose-related vascular protection was observed in other tissues. In conclusion, lacidipine protects against the vascular damage and concomitant increase in mortality of salt-loaded Dahl-S rats even at doses that do not adequately control the development of hypertension.


Radiographic assessment of overlengthening of the MoPyC radial head prosthesis: a cadaveric study.
The aim of this study was to evaluate a radiographic measurement method for assessment of overlengthening of the MoPyC radial head prosthesis. Seven cadaver specimens were studied in ten stages: native specimen (1), radial head resection (2), and implantation of the MoPyC radial head prostheses (Bioprofile, Tornier, Montbonnot-Saint-Martin, France) in four increasing length (correct length, overlengthening of 1.5 mm, 3 mm, and 5 mm) with an intact medial collateral ligament (MCL 3-6) and following transection of the MCL (7-10). The radiographic measurement method according to Athwal et al. was evaluated to detect overlengthening. Statistical analysis included calculation of the diagnostic accuracy of the radiographic method. The radiographic measurement method correctly determined the size of the radial head prosthesis within ± 1 mm in 224 of 336 scenarios (67%) and within ± 2 mm in 320 of 336 scenarios (95%). With a threshold value of ≥ 1 mm, the overall diagnostic sensitivity for detecting overlengthening when it was present and was 90% and the specificity was 79%. The sensitivity was higher with increasing size of the prosthesis: in cases with overlengthening of 1.5 mm, the sensitivity was 76%, with an overlengthening of 3 mm, the sensitivity was 95%, and with an overlengthening of 5 mm, the sensitivity was 100%. The radiographic measurement method of Athwal et al. can be used to estimate and to diagnose the magnitude overlengthening of the MoPyC radial head prosthesis. However, the sensitivity is limited (76%) in cases with a small amount of overlengthening of 1.5 mm.


[The integrated etiology and separate pathogenesis of atherosclerosis and atheromatosis. The differences of fatty acids transfer in lipoproteins of herbivorous and carnivorous animals.]
According phylogenetic theory of general pathology, overconsumption of meat food by herbivorous animals always results in atherosclerosis and atheromatosis of intima of arteries. The etiological factors of atherosclerosis, atheromatosis in vivo: a) absorption by cells of polyene fatty acids in anoB-100 lipoproteins of low density; b) impossibility of converting exogenous palmitic saturated fatty acids into mono-unsaturated oleic fatty acid; c) monocytes-macrophages in intima inactively hydrolyze polyene fatty acids esterified by alcohol cholesterol. The disorder of biological function of trophology (nutrition), biological reaction of exotrophy (external nutrition) and aphysiologically high content of palmitic unsaturated fatty acids and alcohol cholesterol in food become a pathogenic factors. The key stage of pathogenesis is formation in blood of non-ligand palmitic lipoproteins of very low density. At that: a) how to utilize in vivo non-ligand palmitic lipoproteins of very low density; it is possible under activation of biological function of endoecology, biological reaction of inflammation, formation of atheromatosis of intima of arteries and b) how to prolong function to cells at impossibility of of absorbing from inter-cellular medium polyene fatty acids; this is a foundation of atherosclerosis, disorders of biological function of adaptation, biological reaction of compensation. The primary prevention of myocardium infarction requires elimination of consumption of surplus amount of animal food. At low content of palmitic saturated fatty acids in food insulin forms optimal oleic alternative of metabolism of fatty acids supporting high "kinetic parameters" of organism and effective synthesis of ATP. According single pathogenesis of atherosclerosis and atheromatosis it is necessary to prevent development of non-ligand palmitic lipoproteins of very low density in blood. Without them no development of both atherosclerosis and atheromatosis is possible.


Genetic correlation between Prothrombin G20210A polymorphism and retinal vein occlusion risk.
The aim of this study was to perform an updated meta-analysis to quantitatively investigate the association between G20210A polymorphism of Prothrombin gene and the risk of retinal vein occlusion (RVO), based on the available publications with inconsistent results. We utilized the Stata software to perform the heterogeneity test, association test, Begg's and Egger's tests, and sensitivity analysis. We searched three on-line databases (PubMed, Embase, and WOS) and obtained a total of 422 articles. Based on our selection criteria, 24 case-control studies were finally enrolled in this overall meta-analysis; a subgroup analysis by the factors ethnicity, control source, and RVO type was done. Through the association test of overall meta-analysis, we did not observe a significant difference between RVO cases and controls under the A vs G (allele) (z=1.49, P=0.137), A vs G (carrier) (z=1.42, P =0.155), GA vs GG (z=1.50, P=0.135), and GA+AA vs GG (z=1.50, P=0.135). Furthermore, we observed similar negative results in the association test of subgroup analysis (all P>0.05). Heterogeneity, Begg's, and Egger's tests excluded the presence of high heterogeneity and publication bias. Statistically stable results were observed in the sensitivity analyses. Based on integrated analysis of the current evidence, Prothrombin gene G20210A polymorphism is likely unrelated to the risk of RVO.


The new physician role as employee.
Rapid and ongoing changes in the way in which medicine is practiced and health care services delivered have made employees of physicians who were once the very definition of entrepreneurs. If this new role is difficult for physicians, it is doubly difficult for those who must manage such employees. To be effective managers of other physicians, physician executives must be aware of the historical and sociological basis of the physician profession.


Sensory, cognitive, and linguistic factors in the early academic performance of elementary school children: The Benton-IU project.
Standardized sensory, perceptual, linguistic, intellectual, and cognitive tests were administered to 470 children, approximately 96% of the students entering the first grade in the four elementary schools of Benton County, Indiana, over a 3-year period (1995--1997). The results of 36 tests and subtests administered to entering first graders were well described by a 4-factor solution. These factors and the tests that loaded most heavily on them were reading-related skills (phonological awareness, letter and word identification); visual cognition (visual perceptual abilities, spatial perception, visual memory); verbal cognition (language development, vocabulary, verbal concepts); and speech processing (the ability to understand speech under difficult listening conditions). A cluster analysis identified 9 groups of children, each with a different profile of scores on the 4 factors. Within these groups, the proportion of students with unsatisfactory reading achievement in the first 2 years of elementary school (as reflected in teacher-assigned grades) varied from 3% to 40%. The profiles of factor scores demonstrated the primary influence of the reading-related skills factor on reading achievement and also on other areas of academic performance. The second strongest predictor of reading and mathematics grades was the visual cognition factor, followed by the verbal cognition factor. The speech processing factor was the weakest predictor of academic achievement, accounting for less than 1% of the variance in reading achievement. This project was a collaborative effort of the Benton Community School Corporation and a multidisciplinary group of investigators from Indiana University.


Toxoplasmosis complications and novel therapeutic synergism combination of diclazuril plus atovaquone.
Toxoplasmosis is a major cause of foodborne disease, congenital complication, and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: combination diclazuril plus atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes. Pregnant dams were treated with diclazuril and atovaquone monotherapy or combination therapy and infected i.p with Toxoplasma tachyzoites. Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p < 0.01) and to a lesser extent diclazuril (p < 0.05) protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (versus normal p < 0.05) with infiltration of inflammatory cells, degeneration and necrosis of pancreatic cells followed by the degeneration and loss of islets. Combination and monotherapy protected dams from these inflammatory and pathological aspects of pancreatitis. Infected dams exhibited severe colitis, and colonic tissues significantly shortened in length. Brush border epithelial cells were replaced with infiltration of lymphocytes, granulocytes, and microabscess formations into cryptic microstructures. Combination therapy synergistically preserved colonic structure and normalized pathological damages (p < 0.001) and to a lesser degree diclazuril monotherapy protected dams from colitis (p < 0.05) and gastrointestinal toxoplasmosis. Other complications included severe splenitis (p < 0.001) and hepatitis (p < 0.001) which were normalized with combination therapy. Combination diclazuril plus atovaquone was safe and with a novel therapeutic synergism protected dams and fetuses from toxoplasmosis.


Bright, noniridescent structural coloration from clay mineral nanosheet suspensions.
Structural colors originate by constructive interference following reflection and scattering of light from nanostructures with periodicity comparable to visible light wavelengths. Bright and noniridescent structural colorations are highly desirable. Here, we demonstrate that bright noniridescence structural coloration can be easily and rapidly achieved from suspended two-dimensional nanosheets of a clay mineral. We show that brightness is enormously improved by using double clay nanosheets, thus optimizing the clay refractive index that otherwise hampers structural coloration from such systems. Intralayer distances, and thus the structural colors, can be precisely and reproducibly controlled by clay concentration and ionic strength independently, and noniridescence is readily and effortlessly obtained in this system. Embedding such clay-designed nanosheets in recyclable solid matrices could provide tunable vivid coloration and mechanical strength and stability at the same time, thus opening a previously unknown venue for sustainable structural coloration.


Cultured skin for massive burns. A prospective, controlled trial.
The author compares the outcome of therapy in patients with massive burns with or without cultured autologous epithelial autografts. The use of cultured keratinocytes has been controversial because of poor take and fragility. There have been no prospective series comparing the use of this technology with standard burn wound coverage. During a 5-year period, 22 patients with an average burn size of 71.8% were treated with cultured keratinocytes and compared with a group of 42 controls with an average burn size of 61.6%. There was no significant difference in age, sex distribution, or third-degree component of the burn between the two groups. There was a significantly higher incidence of smoke inhalation in the cultured epithelial autograft group. There was a reduction in mortality in the cultured epithelial autograft group compared with controls, from 48% to 14% (p < 0.007). There was no difference between the two groups in other major complications, or in readmission for breakdown. Coverage of patients who sustain massive burns with cultured autologous epithelial cells is an important and significant advance in management.


Decree-Law guaranteeing the ownership of rural land to property grantees, 1987.
This Decree-Law provides that a buyer may become the owner of abandoned land by paying 10% of the land price to the Government of Equatorial Guinea. The buyer is required to present and carry out a five-year plan for cultivation and may not sell the land to a third person. If these conditions are not fulfilled, the land must be returned to the State, which will then distribute the land to villages.


Altered olfactory processing and increased insula activity in patients with obsessive-compulsive disorder: An fMRI study.
Obsessive-compulsive disorder (OCD) patients show increased insula activation to disgust-inducing images compared to healthy controls (HC). We explored whether this disgust reactivity was also present in the olfactory domain by conducting the first fMRI study of olfaction in OCD. Neural activation in response to pleasant and unpleasant odors (vs. unscented air) was investigated in 15 OCD and 15 HC participants using fMRI. OCD participants (vs. HC) had increased left anterior insula activation to unpleasant odors (vs. unscented air), which positively correlated with their disgust sensitivity and ratings of the unpleasantness and intensity of those odors. OCD participants (vs. HC) showed increased activation of caudate nucleus and left anterior and posterior insula to pleasant odors (vs. unscented air), which positively correlated with their OCD symptom severity, trait anxiety, frequency of feeling disgust, and odor intensity ratings. OCD participants had increased anterior insula activation to both pleasant and unpleasant odors, which correlated with their OCD symptoms, anxiety, disgust sensitivity, and frequency of feeling disgust. OCD patients might have a negative cognitive bias and experience all stimuli, regardless of valence, as being more unpleasant than healthy people. These findings further elucidate the neural underpinnings of OCD and may contribute to more effective treatments.


Pneumococcal antibodies in families with recurrent otitis media.
In a recent study it was found that children with recurrent acute otitis media (rAOM), in contrast to healthy children, frequently lack detectable antipneumococcal IgG antibodies against capsular types 6A and 19F. In children with rAOM, the concentrations of antibodies against type 6A polysaccharide remained low even after the period of rAOM had ceased. Antibody levels against various pneumococcal capsular polysaccharides were determined in otitis-prone and healthy members of 19 families. 25 children with a history of rAOM (mean age 7.2 years) and their parents, one of whom in each family had had rAOM during childhood, were investigated. Compared to the parents, the rAOM children had lower concentrations of IgG antibodies against the pneumococcal types 6A, 14, 19F and 23F and of IgA antibodies against type 23F. Compared to their parents, the rAOM children had higher concentrations of IgM antibodies against types 3 and 23F. 'Healthy parents' did not differ from 'rAOM parents' in IgG antibody levels against any of the pneumococcal capsular polysaccharides investigated. The findings indicate that rAOM occurs in individuals with a delayed rather than with a persisting inability to mount an adequate antibody response against the offending pneumococci.


Structure-guided microbial targeting of antistaphylococcal prodrugs.
Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in Staphylococcus aureus. Additionally, we determine the substrate specificities for FrmB and GloB and demonstrate the structural basis of these preferences. Finally, we establish the carboxy ester substrate specificities of human and mouse sera, ultimately identifying several promoieties likely to be serum esterase-resistant and microbially labile. These studies will enable structure-guided design of antistaphylococcal promoieties and expand the range of molecules to target staphylococcal pathogens.


Chemotherapeutic agent CPT-11 induces the new expression of the apoptosis initiator to the cytoplasm.
CPT-11, a derivative of camptothecin, induced apoptotic cell death characterized by chromosomal DNA fragmentation in human hepatoma PLC cells in vitro. Cell viability of PLC cells was significantly decreased by CPT-11 in a dose-dependent manner, and CPT-11-induced cytotoxic activity was completely prevented by an interleukin-1 beta converting enzyme-like protease inhibitor YVAD and a protein synthesis inhibitor cycloheximide. To examine the roles of the cytoplasm and the nucleus in CPT-11-induced apoptosis, we prepared cytoplasts from PLC cells and nuclei from rat hepatocytes (RHN). Apoptotic cell death as characterized by cell fragmentation was observed in whole PLC cells but not in PLC cytoplasts after incubation with CPT-11. In addition, CPT-11 could not induce chromosomal DNA fragmentation in RHN. In contrast, the extracts of CPT-11-treated PLC cells, which mainly contained cytosol proteins, induced chromosomal DNA fragmentation of RHN in a dose-dependent manner. These results indicate that CPT-11-induced apoptosis required the presence of both the cytoplasm and the nucleus and suggest that the apoptosis required the de novo synthesis of an apoptosis initiator.


Model-Independent Lens Distortion Correction Based on Sub-Pixel Phase Encoding.
Lens distortion can introduce deviations in visual measurement and positioning. The distortion can be minimized by optimizing the lens and selecting high-quality optical glass, but it cannot be completely eliminated. Most existing correction methods are based on accurate distortion models and stable image characteristics. However, the distortion is usually a mixture of the radial distortion and the tangential distortion of the lens group, which makes it difficult for the mathematical model to accurately fit the non-uniform distortion. This paper proposes a new model-independent lens complex distortion correction method. Taking the horizontal and vertical stripe pattern as the calibration target, the sub-pixel value distribution visualizes the image distortion, and the correction parameters are directly obtained from the pixel distribution. A quantitative evaluation method suitable for model-independent methods is proposed. The method only calculates the error based on the characteristic points of the corrected picture itself. Experiments show that this method can accurately correct distortion with only 8 pictures, with an error of 0.39 pixels, which provides a simple method for complex lens distortion correction.


Innovative Thin-Layer Chromatography/Fluorescence Detection Approach for Sensitive and Specific Determination of Ledipasvir in Rats' Feces and Pharmaceutical Dosage Form.
An innovative thin-layer chromatography method coupled with the fluorescence detection was developed for a specific estimation of ledipasvir. The separation was achieved on plates of silica gel 60 F254 using ethylacetate: hexane: acetonitrile: triethylamine; (6: 3.5: 1.5: 0.5, $\mathrm{v}/\mathrm{v}/\mathrm{v}/\mathrm{v}$) as a mobile phase system. The method involved the exposure of the developed thin-layer chromatography plate of ledipasvir to strong ultraviolet irradiation, resulting in a great enhancement in the fluorescence properties of ledipasvir. The irradiated plates were scanned after the excitation at 315 $\mathrm{nm}$. The method provided a sufficient separation of ledipasvir from sofosbuvir with ${R}_F$values of 0.28 and 0.36 for ledipasvir and sofosbuvir, respectively. The developed procedures were validated based on guidelines from the International Conference on Harmonization and Food and Drug Administration guidelines. The calibration curve was linear over the range of 5-50 $\mathrm{ng}/\mathrm{band}$. The excellent analytical features of the proposed method allow to the specific determination of ledipasvir in pharmaceutical tablets without interference from sofosbuvir or excipients. As the main elimination route for ledipasvir is via the fecal excretion (86%), the method was applied for the estimation of ledipasvir in fecal specimens with adequate recovery. In addition, the proposed method was applied for testing the content uniformity of ledipasvir in the pharmaceutical tablets.


Genetic determinants of growth hormone and GH-related phenotypes.
Higher fasting Growth Hormone (GH) has been associated with increased cardiovascular morbidity and mortality. Our objective was to find genetic determinants of fasting GH in order to facilitate future efforts of analyzing the association between fasting growth hormone and cardiovascular disease. A genome-wide association study (GWAS) was performed in a discovery cohort of 4134 persons (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH. Fifteen SNPs were replicated in an independent cohort of 5262 persons (28.9% females; age 56-85 yrs). The best performing SNP was analyzed vs GH-related variables in a third independent cohort (n = 24,047; 61% females; age 44-73 yrs). A candidate gene approach searched for significant SNPs in the genes GH1 and GHR in the discovery cohort and was replicated as previously described. In the GWAS, the minor allele of rs7208736 was associated with lower GH in the discovery cohort (p = 5.15*10^-6) and the replication cohort (p = 0.005). The GH reducing allele was associated with lower BMI (P = 0.026) and waist (P = 0.021) in males only. In the candidate gene approach rs13153388 in the GHR-gene was associated with elevated GH-levels (P = 0.003) in the discovery cohort only and reduced height (P = 0.003). In the first GWAS ever for GH, we identify a novel locus on chromosome 17 associated with fasting GH levels, suggesting novel biological mechanisms behind GH secretion and GH-related traits. The candidate gene approach identified a genetic variant in the GHR, which was associated with an elevation of fasting hs-GH and lower height suggesting reduced GHR ligand sensitivity. Our findings need further replication.


Changes in aqueous outflow after in vitro neodymium: yttrium aluminum garnet laser cyclophotocoagulation.
To examine the possible role of transscleral outflow routes, enucleated human and porcine eyes underwent noncontact neodymium:yttrium aluminum garnet (Nd:YAG) laser cyclophotocoagulation 3 mm posterior to the limbus. Pars plana lesions were verified histologically. The eyes were perfused with saline solution at 50 mm Hg perfusion pressure, placing the tip of the needle into the hyaloid orbicular space. The outflow facility was 0.072 microliter/min/mm Hg in paired controls and 0.105 microliter/min/mm Hg in human lasered eyes, a difference of 31%. In porcine eyes the difference was 43%. Since concepts of aqueous production, impaired circulation, and inflammation do not apply to enucleated eyes, the increase may be related to pars plana transscleral flow facilitated by disruption of the neuroepithelial barrier.


Which patients with headache do not seek medical attention?
To evaluate why patients do not discuss their headaches with their doctors and to compare these patients with those who seek medical assistance for headache. Cross-sectional study. A total of 200 consecutive patients attended by family doctors had their complaints registered. Those with headaches were interviewed. A semi-structured questionnaire, Headache Impact Test and Hospital Anxiety and Depression Scale were used. Fifty-two percent had headaches. Ten percent sought medical assistance for headache, 11% already had received some form of medical assistance for headache. There was no association between headache disability and seeking a doctor for headache. Patients that did not seek a doctor for headache had a higher prevalence of tension-type headache (59.6% vs. 22.1%; P < .01), a lower prevalence of migraine with aura (32.3% vs. 40.5%; P < .01), headache intensity (5.4 vs. 6.8; P = .01) and frequency (4.2 × 7.4 days/month; P < .01). Fifty-two percent of them needed preventive treatment. Most of them did not seek a doctor because their headaches were mild or received relief from painkillers. Patients who did not seek medical assistance for headache had more tension-type headache, less migraine with aura, lower headache intensity and frequency, but the same headache disability. Most of them needed preventive treatment and did not seek doctors because their headache was mild or received relief from painkillers.


Calorimetric measurement of postexercise net heat loss and residual body heat storage.
Previous studies have shown a rapid reduction in postexercise local sweating and blood flow despite elevated core temperatures. However, local heat loss responses do not illustrate how much whole-body heat dissipation is reduced, and core temperature measurements do not accurately represent the magnitude of residual body heat storage. Whole-body evaporative (H(E)) and dry (H(D)) heat loss as well as changes in body heat content (DeltaH(b)) were measured using simultaneous direct whole-body and indirect calorimetry. Eight participants cycled for 60 min at an external work rate of 70 W followed by 60 min of recovery in a calorimeter at 30 degrees C and 30% relative humidity. Core temperature was measured in the esophagus (T(es)), rectum (T(re)), and aural canal (T(au)). Regional muscle temperature was measured in the vastus lateralis (T(vl)), triceps brachii (T(tb)), and upper trapezius (T(ut)). After 60 min of exercise, average DeltaH(b) was +273 +/- 57 kJ, paralleled by increases in T(es), T(re), and T(au) of 0.84 +/- 0.49, 0.67 +/- 0.36, and 0.83 +/- 0.53 degrees C, respectively, and increases in T(vl), T(tb), and T(ut) of 2.43 +/- 0.60, 2.20 +/- 0.64, and 0.80 +/- 0.20 degrees C, respectively. After a 10-min recovery, metabolic heat production returned to pre-exercise levels, and H(E) was only 22.9 +/- 6.9% of the end-exercise value despite elevations in all core temperatures. After a 60-min recovery, DeltaH(b) was +129 +/- 58 kJ paralleled by elevations of T(es) = 0.19 +/- 0.13 degrees C, T(re) = 0.20 +/- 0.03 degrees C, T(au) = 0.18 +/- 0.04 degrees C, Tvl = 1.00 +/- 0.43 degrees C, T(tb) = 0.92 +/- 0.46 degrees C, and T(ut) = 0.31 +/- 0.27 degrees C. Despite this, H(E) returned to preexercise levels. Only minimal changes in H(D) occurred throughout. We confirm a rapid reduction in postexercise whole-body heat dissipation by evaporation despite elevated core temperatures. Consequently, only 53% of the heat stored during 60 min of exercise was dissipated after 60 min of recovery, with the majority of residual heat stored in muscle tissue.


Migration regions and interstate labor flows by occupation in the United States.
"This paper investigates the migration patterns of occupational groups [in the United States]. The results confirm previous analyses of the differences in movement behavior between occupations but, in addition, show that this variation is a function of the industrial sector of employment. The chief aim of the paper, however, is to uncover the geography of labor flows for different occupational groups using a principal components analysis of interstate flow matrices....Results indicate that migration regions vary by occupation and industry and we argue that these differences reflect job information flows and regional employment structure for various classes of labor." Data are from the Public Use Microdata Sample A taken from the 1980 census.


Skeletal identification using the frontal sinus region: a retrospective study of 39 cases.
The importance of identification using the frontal sinus has been previously demonstrated in case reports. In this study, 39 cases of identification using frontal sinus comparison from the Ontario Chief Coroner's Office were reviewed and differences between antemortem and postmortem radiographs examined. All cases involved decedents older than twenty years. Three cases were rejected due to poor antemortem and postmortem film quality. One subject had no frontal sinus. Thirty-five cases provided conclusive postmortem to antemortem pattern matches. Sixteen cases also yielded metric (quantitative) matches. Duration between antemortem and postmortem radiographic examinations, age, gender, and cause of death did not affect the ability to obtain a match. This is the largest study undertaken on actual cases and demonstrates the validity of frontal sinus pattern matching for forensic identification.


Complications after subclavian-cortical middle cerebral artery bypass.
Subclavian-cortical middle cerebral artery bypass by saphenous vein interposition is an uncommon recent revascularization technique used for immediate volume flow to the brain or when donor arteries are unavailable or inadequate. We used this technique in four cases of symptomatic common carotid artery occlusion. In the last two cases, severe, reversible neurological complications occurred. We think that these complications are due to this particular technique, and more cautious indications than for traditional extra-intracranial arterial bypass are recommended.


Not forgetting severe mental disorders in humanitarian emergencies: a descriptive study from the Philippines.
Severe mental disorders are often neglected following a disaster. Based on Médecins Sans Frontières' (MSF) experience of providing mental health (MH) care after the 2013 typhoon in the Philippines, we describe the monthly volume of MH activities and beneficiaries; characteristics of people seeking MH care; profile and outcomes of people with severe mental disorders; prescription of psychotropic medication; and factors facilitating the identification and management of individuals with severe mental disorders. A retrospective review of programme data was carried out. In total, 172 persons sought MH care. Numbers peaked three months into MSF's intervention and decreased thereafter. Of 134 (78%) people with complete data, 37 (28%) had a severe mental disorder, often characterised by psychotic symptoms (n=24, 64%) and usually unrelated to the typhoon (n=32, 86%). Four people (11%) were discharged after successful treatment, two (5%) moved out of the area, 20 (54%) were referred for follow-up on cessation of MSF activities and 10 (27%) were lost-to-follow-up. Psychotropic treatment was prescribed for 33 (75%) people with mental disorders and for 11 with non-severe mental disorders. This study illustrates how actors can play an important role in providing MH care for people with severe mental disorders in the aftermath of a disaster.


Effect of physicochemical anomalies of soda-lime silicate slides on biomolecule immobilization.
Glass microscope slides are considered by many as the substrate of choice for microarray manufacturing due to their amenability to various surface chemistry modifications. The use of silanes to attach various functional groups onto glass slides has provided a versatile tool for the covalent immobilization of many diverse biomolecules of interest. We recently noted a dramatic reduction in biomolecule immobilization efficiency on standard microscope slides prepared using a well-characterized silanization method. A survey of commercial soda-lime slides yielded the surprising result that slides purchased prior to 2008 had superior immobilization efficiencies when compared to those purchased after 2008. Characterization of the slides by X-ray photoelectron spectroscopy (XPS), contact angle measurements, and atomic force microscopy (AFM), revealed a significant correlation (R > 0.9) between magnesium content, surface roughness, and bioimmobilization efficiency. High performance slides had higher magnesium content and higher root-mean-square (rms) roughness (P < 0.005) than slides with lower bioimmobilization efficiencies. Although the exact mechanism of how magnesium content and surface roughness affect silane deposition has not yet been defined, we show that recent changes in the chemical and physical properties of commercial soda-lime slides affect the ability of these slides to be covalently modified.


Parametric Optimization of Electric Discharge Machining of Metal Matrix Composites Using Analytic Hierarchy Process.
The present study reports on the method used to obtain the reliable outcomes for different responses in electric discharge machining (EDM) of metal matrix composites (MMCs). The analytic hierarchy process (AHP), a multiple criteria decision-making technique, was used to achieve the target outcomes. The process parameters were varied to evaluate their effect on the material erosion rate (MER), surface roughness (SR), and residual stresses (σ) following Taguchi's experimental design. The process parameters, such as the electrode material (Cu, Gr, Cu-Gr), current, pulse duration, and dielectric medium, were selected for the analysis. The residual stresses induced due to the spark pulse temperature gradient between the electrode were of primary concern during machining. The optimum process parameters that affected the responses were selected using AHP to figure out the most suitable conditions for the machining of MMCs.


Case 1: isolated systolic hypertension.
Despite the prevalence of isolated systolic hypertension (ISH) in the elderly, many physicians are reluctant to treat the disorder. Recently identified as one of the major health challenges of the new millennium, ISH is the focus of this month's CME-accredited case study in hypertension, featured at www.CardiovascularEd. com.


Association of the fat mass and obesity-associated (FTO) gene variant (rs9939609) with dietary intake in the Finnish Diabetes Prevention Study.
A cluster of variants in the fat mass and obesity-associated (FTO) gene are associated with the common form of obesity. Well-documented dietary data are required for identifying how the genetic risk can be modified by dietary factors. The objective of the present study was to investigate the associations between the FTO risk allele (rs9939609) and dietary intake, and to evaluate how dietary intake affects the association between FTO and BMI in the Finnish Diabetes Prevention Study during a mean follow-up of 3·2 years. A total of 479 (BMI >25 kg/m2) men and women were genotyped for rs9939609. The participants completed a 3 d food record at baseline and before every annual study visit. The average intakes at baseline and during the years 1, 2 and 3 were calculated. At baseline, the FTO variant rs9939609 was not associated with the mean values of total energy intake, macronutrients or fibre. At baseline, a higher BMI by the FTO risk genotype was detected especially in those who reported a diet high in fat with mean BMI of 30·6 (sd 4·1), 31·3 (sd 4·6) and 34·5 (sd 6·2) kg/m2 for TT, TA and AA carriers, respectively (P =0·005). Higher BMI was also observed in those who had a diet low in carbohydrates (P =0·028) and fibre (P =0·015). However, in the analyses adjusted for total energy intake, age and sex, significant interactions between FTO and dietary intakes were not found. These findings suggest that the association between the FTO genotype and obesity is influenced by the components of dietary intake, and the current dietary recommendations are particularly beneficial for those who are genetically susceptible for obesity.


Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats.
The purpose of the present study was to establish a model of rats prone and resistant to intra-abdominal fat accumulation in response to ovariectomy (Ovx-P and Ovx-R) and to determine its relationship with molecular biomarkers. Two experiments were conducted in which female rats were either sham-operated (Sham) or ovariectomized (Ovx). In the first experiment, ovariectomized rats were stratified into three tertiles based on intra-abdominal adipose tissue mass. To strengthen the Ovx-P/Ovx-R model, we conducted a second experiment in which the numbers of rats in each group were extended and in which different molecular markers were measured. At the end of a 6-8-week period, ovariectomized rats that displayed the lower abdominal fat accumulation (lower tertile) were labelled as Ovx-R and those in the upper tertile as Ovx-P. Ovx-R rats displayed similar abdominal fat gain to Sham rats whereas Ovx-P rats depicted abdominal fat mass twice as high as that of Sham and Ovx-R rats. Despite the difference in abdominal adiposity, liver fat content was ~50% higher (p < 0.01) in both Ovx-R and Ovx-P rats compared to Sham rats. In addition, both Ovx-R and Ovx-P rats depicted higher HOMA-IR scores (p < 0.05) and lower (p < 0.01) hepatic gene expression of leptin receptor-b and -e, microsomal transfer protein (MTP), and diacylglycerol acyltransferase-2 (DGAT-2) compared to Sham rats. The present findings indicate that estrogen withdrawal-induced hepatic steatosis and associated insulin resistance may be dissociated from abdominal fat accumulation and suggest that a decrease in leptin action through a down-regulation of leptin receptors and a decrease in very low density lipoprotein production through a down-regulation of MTP and DGAT-2 may be factors responsible for this observation in the absence of peripheral fat gain.


Nitrosylation and nitration of mitochondrial complex I in Parkinson's disease.
Impairment of the mitochondrial electron transport chain has been suggested to be a critical factor in the neuropathogenesis of Parkinson's disease (PD), as inhibition of mitochondrial complex I (CI) activity is consistently detected in PD patients as well as in mitochondrial toxin models of the disorder. Increased levels of various reactive oxygen and nitrogen species appear to contribute to CI inhibition and mitochondrial dysfunction in PD. Reactive nitrogen species (RNS) such as nitric oxide (NO) and its metabolite peroxynitrite (PN) may inhibit CI activity via several different mechanisms including S-nitrosylation, nitration, and protein thiol formation. Studies using various cell and animal PD models have demonstrated that selective mitochondrial CI inhibition in dopaminergic cells may be due to both NO-mediated S-nitrosylation and nitration of CI sub-units. Strategies to modulate mitochondrial NO levels will therefore likely be a promising approach to enhance mitochondrial function and protect dopaminergic neurons against oxidative or nitrosative insult.


Myocardial adaptation to ischemia by oxidative stress induced by endotoxin.
In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induced by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats were killed, hearts were isolated, and the effects of ischemia-reperfusion were studied using an isolated working heart preparation. The development of oxidative stress was examined by assessing malonaldehyde production in the heart. The antioxidant defense system was studied by estimating antioxidant enzyme activities and ascorbate- as well as thiol-dependent antioxidant reserve. The results of our study indicated that endotoxin induced oxidative stress within 1 h of treatment; the stress was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thiol- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin provided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by endotoxin-induced adaptive modification of the antioxidant defense in the heart, thereby reducing ischemic-reperfusion injury.


Coordinated regulation of IL-4 and IL-13 expression in human T cells: 3C analysis for DNA looping.
Asthma is a chronic allergic disorder characterised by chronic inflammation. The balance of type I and type II (CD4+) T helper cells is of critical importance. In asthma there is an overexpression of T(H)2 cytokines, such as IL-4, IL-5 and IL-13. The genes encoding these cytokines are located together the same chromosomal region, 5q31.1 in humans. Here we confirm a central role for the transcription factors NFAT and GATA3 in the regulation of human IL-4 and IL-13. Chromatin Conformation Capture (3C) demonstrated the formation of specific ligation products containing spliced IL-4 and IL-13 DNA sequences in human T(H)2 polarised HuT-78 cells. This suggests that co-ordinate expression of T(H)2 cytokines, under the control of GATA3 and NFAT1 is due to the formation of a chromatin hub by DNA looping.