Building the Arrow of Time… Over Time: A Sequence of Brain Activity Mapping Imagined Events in Time and Space.
When moving, the spatiotemporal unfolding of events is bound to our physical trajectory, and time and space become entangled in episodic memory. When imagining past or future events, or being in different geographical locations, the temporal and spatial dimensions of mental events can be independently accessed and manipulated. Using time-resolved neuroimaging, we characterized brain activity while participants ordered historical events from different mental perspectives in time (e.g., when imagining being 9 years in the future) or in space (e.g., when imagining being in Cayenne). We describe 2 neural signatures of temporal ordinality: an early brain response distinguishing whether participants were mentally in the past, the present or the future (self-projection in time), and a graded activity at event retrieval, indexing the mental distance between the representation of the self in time and the event. Neural signatures of ordinality and symbolic distances in time were distinct from those observed in the homologous spatial task: activity indicating spatial order and distances overlapped in latency in distinct brain regions. We interpret our findings as evidence that the conscious representation of time and space share algorithms (egocentric mapping, distance, and ordinality computations) but different implementations with a distinctive status for the psychological "time arrow."


Influence of L-dopa on subtle motor signs in heterozygous Parkin- and PINK1 mutation carriers.
A latent nigrostriatal deficit and its possible clinical consequences in asymptomatic heterozygous Parkin and PINK1 mutation carriers (AMC) have been a matter of investigation in recent years. Notably, mild Parkinsonian signs in heterozygous mutation carriers can be so subtle that they may be missed if not specifically investigated. We studied 15 heterozygous Parkin and PINK1 AMC and 18 age- and sex-matched mutation-negative controls using a standardized video, instructing the probands to perform relevant parts of the UPDRS III to investigate fine motor movements at baseline and after first-time L-Dopa administration. Additionally, available UPDRS III scores of mutation carriers from the past ten years were reviewed. AMC showed a reduced number of fine motor movements per second compared to controls at baseline (p = 0.04). L-Dopa improved motor performance numerically but non-significantly in AMC (p = 0.2301), but significantly in healthy controls (p = 6.1·10-5). Although none of the AMC reported symptoms, nine showed rigidity, bradykinesia, tremor, and postural instability when the UPDRS III was applied. Mean UPDRSIII scores significantly decreased after L-Dopa administration (p = 0.005), but did not increase over the past ten years. (i) Heterozygous AMC show subtle motor abnormalities when a detailed, specialized motor examination is applied and compared to mutation-negative matched control subjects. (ii) The mild motor deficit present in a subgroup of heterozygous Parkin and PINK1 AMC appears to be non-progressive and responsive to L-dopa administration. (iii) Evaluating motor changes, their progression, and treatment response in AMC can provide valuable insights into possible early disease stages and compensatory mechanisms.


Metabolic versatility of the Riftia pachyptila endosymbiont revealed through metagenomics.
The facultative symbiont of Riftia pachyptila, named here Candidatus Endoriftia persephone, has evaded culture to date, but much has been learned regarding this symbiosis over the past three decades since its discovery. The symbiont population metagenome was sequenced in order to gain insight into its physiology. The population genome indicates that the symbionts use a partial Calvin-Benson Cycle for carbon fixation and the reverse TCA cycle (an alternative pathway for carbon fixation) that contains an unusual ATP citrate lyase. The presence of all genes necessary for heterotrophic metabolism, a phosphotransferase system, and dicarboxylate and ABC transporters indicate that the symbiont can live mixotrophically. The metagenome has a large suite of signal transduction, defence (both biological and environmental) and chemotaxis mechanisms. The physiology of Candidatus Endoriftia persephone is explored with respect to functionality while associated with a eukaryotic host, versus free-living in the hydrothermal environment.


Plasma cell infiltration of the small bowel: lack of evidence for a non-secretory form of alpha-heavy chain disease.
Eight patients with diffuse plasma cell infiltration of the small bowel who had the clinical features of immunoproliferative small intestinal disease (IPSID), but whose serum was negative for free alpha-heavy chains, were investigated for evidence of a non-secretory form of alpha-chain disease (alpha-CD). Molecular sieving and immunoblotting of serum, immunoperoxidase staining of biopsy specimens, and in vitro protein synthesis studies utilising an immunoprecipitation technique and polyacrylamide gel electrophoresis, failed to detect any new cases of alpha-CD. Four of the eight cases were found to have diffuse intestinal lymphoma. The remaining four patients, who were unsuccessfully investigated for evidence of a significant abnormality in cellular immunity, have not developed detectable alpha-CD protein or lymphoma over a mean of 143 months. Despite continuing exposure to possible environmental stimuli, it is concluded that not all cases of IPSID elaborate detectable alpha-CD protein or evolve to lymphoma.


Baby food exchanges and feeding the diabetic infant.
Because of the dangers of hypoglycemia to the developing brain, the need to develop a lifelong positive attitude toward an eating pattern, the inherent communication difficulties, and the spontaneity of the very young, the diabetic infant presents a particular challenge to medical personnel. Baby and toddler foods in jar measurements and formula have been translated into the American Diabetes Association exchanges to help in teaching families with diabetic infants the effects of various foods on the infant's diabetes. The exchanges are taught as tools in maintaining metabolic balance rather than as a fixed diet. Caloric level is planned on the basis of diet history and the infant's current growth status. Flexibility of pattern and attitude is emphasized to minimize conflict over eating and to allow normal spontaneous activity without jeopardizing health.


Evaluation Of Mycotoxin Content In Soybean (Glycine max L.) Grown In Rwanda.
Soybean is a critical food and nutritional security crop in Rwanda. Promoted by the Rwandan National Agricultural Research System for both adults and as an infant weaning food, soybean is grown by approximately 40% of households. Soybean may be susceptible to the growth of mycotoxin-producing moulds; however, data has been contradictory. Mycotoxin contamination is a food and feed safety issue for grains and other field crops. This study aimed to determine the extent of mycotoxin contamination in soybean, and to assess people's awareness on mycotoxins. A farm-level survey was conducted in 2015 within three agro-ecological zones of Rwanda suitable for soybean production. Soybean samples were collected from farmers (n=300) who also completed questionnaires about pre-and post-harvest farm practices, and aflatoxin awareness. The concentration of total aflatoxin in individual soybean samples was tested by enzymelinked immunosorbent assay (ELISA) using a commercially-available kit. Other mycotoxins were analyzed using liquid chromatography-mass spectrometry (LCMS/MS) on 10 selected sub samples. Only 7.3% of the respondents were aware of aflatoxin contamination in foods, but farmers observed good postharvest practices including harvesting the crop when the pods were dry. Using enzyme-linked immunosorbent assay (ELISA), only one sample had a concentration (11 µg/kg) above the most stringent EU maximum permitted limit of 4 µg/kg. Multi-mycotoxins liquid chromatography-mass spectrometry (LC-MS/MS) results confirmed that soybeans had low or undetectable contamination; only one sample contained 13µg/kg of sterigmatocystine. The soybean samples from Rwanda obtained acceptably low mycotoxin levels. Taken together with other studies that showed that soybean is less contaminated by mycotoxins, these results demonstrate that soybean can be promoted as a nutritious and safe food. However, there is a general need for educating farmers on mycotoxin contamination in food and feed to ensure better standards are adhered to safeguard the health of the consumers regarding these fungal secondary metabolites.


The UCLA Cosmochemistry Database.
The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of California, Los Angeles (UCLA). The data collection includes elemental compositions of extraterrestrial materials analyzed by UCLA cosmochemists over the last five decades. The analytical techniques include atomic absorption spectrometry (AAS) and neutron activation analysis (NAA) at UCLA. The data collection is stored on the Astromaterials Data System (Astromat). We provide both interactive tables and downloadable datasheets for users to access all data. The UCLA Cosmochemistry Database archives cosmochemical data that are essential tools for increasing our understanding of the nature and origin of extraterrestrial materials. Future studies can reference the data collection in the examination, analysis, and classification of newly acquired extraterrestrial samples.


Status and recommendations for self-care instruction in US colleges and schools of pharmacy, 2006.
Teachers of pharmacy self-care courses have met annually since 1998 at the Nonprescription Medicines Academy (NMA) held in Cincinnati, Ohio. During these meetings, self-care faculty members discuss methods of enhancing the teaching of self-care in US colleges and schools of pharmacy. Self-care courses are taught using a variety of methods and content is woven into pharmacy curricula in many different ways. This manuscript sets forth the current state of self-care instruction in pharmacy curricula including the recommended core curriculum, instructional methodologies, course mechanics, existing standards, and assessment and curricular placement, and makes recommendations for the future.


Analysing the contributions of lower limb muscles to eccentric cycling using musculoskeletal modeling and simulation.
Eccentric (ECC) cycling, compared to traditional concentric cycling, has been shown to improve muscle strength and neuromuscular control at a lower metabolic cost. Despite the popularity of this exercise in the sports and rehabilitation contexts, there is a gap in our knowledge of which muscles are behaving eccentrically during ECC cycling. To this end, we used a musculoskeletal model and computer simulations to calculate joint kinematics and muscle lengths during ECC cycling. Movements were recorded using 3D motion capture technology while cycling eccentrically on a custom-built semi-recumbent ergometer. The software Opensim was used to calculate joint kinematics and muscle lengths from recorded movements. We found that among the primary knee extensors, it was predominantly the Vastii muscles that acted eccentrically in the ECC cycling phase, with other lower limb muscles showing mixed eccentric/concentric activation. Additionally, the muscle force-length and force-velocity factors in the ECC phase suggest that changes to the participant's pose and pedaling speed may elicit larger active muscle forces. Our work provides an interesting application of musculoskeletal modeling to ECC cycling, and an alternative way to help understand in-vivo muscle mechanics during this activity.


Zebrafish Tmem230a cooperates with the Delta/Notch signaling pathway to modulate endothelial cell number in angiogenic vessels.
During embryonic development, new arteries, and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles. Stalk and tip cellular responses are mediated in part by the interactions of components of the Delta/Notch and Vegf signaling pathways. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co-operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. Therefore, Tmem230a may have a modulatory role in vessel-network formation and growth. As the Tmem230 sequence is conserved in human, Tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis.


Periodontal status and dental behaviour of heart transplant recipients and healthy controls.
Objective: The aim of this study was to compare the periodontal status and dental behaviour of heart transplant recipients with systemically healthy controls.Material and Methods: Forty heart transplant recipients and 40 systemically healthy patients were included. A questionnaire was used to record demographic, systemic health and dental behaviour data, and the following clinical parameters were recorded: plaque index, bleeding on probing, probing depth, gingival recession, and clinical attachment level.Results: Mean probing depth (p = .045), mean gingival recession (p = .016), mean clinical attachment level (p = .021) and mean plaque index scores (p = .001) were higher in heart transplant recipients than the systemically healthy group. However, bleeding on probing was similar in both groups (p > .05). Tooth brushing frequency and number of participants who used dental floss/interdental brush was lower in the heart transplant group.Conclusion: Considering the poor oral hygiene and high clinical periodontal parameters of heart transplant recipients, periodontal evaluation should be done regularly before and after transplantation. The patient's daily oral hygiene regimens should be evaluated carefully in this evaluation session and modified based on their gingival health, manual skill and motivational levels. The importance of oral health and its effects on systemic health should also be explained to the transplant recipients in detail.


[Causes of death from breast cancer in Colombia].
Objective To review the direct causes of death from breast cancer in Colombia according to data from death certificates in 2008. Material and Methods We reviewed the direct causes of death in patients whose code of underlying cause of death was malignant tumor of the breast according to the National Statistics Department of Colombia's (DANE from Spanish initials) records of death in 2008. Distribution is evaluated by diagnostic code, age, educational level, marital status, social security and place of death. Results In women, the main direct causes of death were respiratory insufficiency or failure, cardiac arrest, multiple or multisystem organ failure, breast cancer and metastatic breast cancer. Most of the death codes were C509 and they were issued for women over 50 years. In men, the most common cause was respiratory failure. Conclusions The main denominations listed on death records as a direct cause of death from breast cancer were respiratory failure and arrest and cardiopulmonary arrest. However, it is evident that this arises from problems in the registry that are the result of not following the International Classification of Diseases (ICD-10). Improving the quality of death records is required so that all the information given by the death certificates can be used more effectively.


Recombinant Spider Silk Functionalized Silkworm Silk Matrices as Potential Bioactive Wound Dressings and Skin Grafts.
Silk is considered to be a potential biomaterial for a wide number of biomedical applications. Silk fibroin (SF) can be retrieved in sufficient quantities from the cocoons produced by silkworms. While it is easy to formulate into scaffolds with favorable mechanical properties, the natural SF does not contain bioactive functions. Spider silk proteins, on the contrary, can be produced in fusion with bioactive protein domains, but the recombinant procedures are expensive, and large-scale production is challenging. We combine the two types of silk to fabricate affordable, functional tissue-engineered constructs for wound-healing applications. Nanofibrous mats and microporous scaffolds made of natural silkworm SF are used as a bulk material that are top-coated with the recombinant spider silk protein (4RepCT) in fusion with a cell-binding motif, antimicrobial peptides, and a growth factor. For this, the inherent silk properties are utilized to form interactions between the two silk types by self-assembly. The intended function, that is, improved cell adhesion, antimicrobial activity, and growth factor stimulation, could be demonstrated for the obtained functionalized silk mats. As a skin prototype, SF scaffolds coated with functionalized silk are cocultured with multiple cell types to demonstrate formation of a bilayered tissue construct with a keratinized epidermal layer under in vitro conditions. The encouraging results support this strategy of fabrication of an affordable bioactive SF-spider silk-based biomaterial for wound dressings and skin substitutes.


Recommendations for treating depression in community-based older adults.
To present recommendations for community-based treatment of late-life depression to public health and aging networks. An expert panel of mental health and public health researchers and community-based practitioners in aging was convened in April 2006 to form consensus-based recommendations. When making recommendations, panelists considered feasibility and appropriateness for community-based delivery, as well as strength of evidence on program effectiveness from a systematic literature review of articles published through 2005. The expert panel strongly recommended depression care management-modeled interventions delivered at home or at primary care clinics. The panel recommended individual cognitive behavioral therapy. Interventions not recommended as primary treatments for late-life depression included education and skills training, comprehensive geriatric health evaluation programs, exercise, and physical rehabilitation/occupational therapy. There was insufficient evidence for making recommendations for several intervention categories, including group psychotherapy and psychotherapies other than cognitive behavioral therapy. This interdisciplinary expert panel determined that recommended interventions should be disseminated throughout the public health and aging networks, while acknowledging the challenges and obstacles involved. Interventions that were not recommended or had insufficient evidence often did not treat depression primarily and/or did not include a clinically depressed sample while attempting to establish efficacy. These interventions may provide other benefits, but should not be presumed to effectively treat depression by themselves. Panelists also identified primary prevention of depression as a much under-studied area. These findings should aid individual clinicians as well as public health decision makers in the delivery of population-based mental health services in diverse community settings.


The treatment of early (T1) glottic and supra-glottic carcinoma: does partial laryngectomy have a place?
A series of 900 patients with laryngeal carcinoma is described. Patients with glottic T1N0 tumours were treated by radiotherapy with a 5-year survival of 92%. Seven per cent of patients suffered recurrence and most were salvaged by surgery: vertical hemilaryngectomy was occasionally useful as a salvage procedure. Patients with supra-glottic T1N0 tumours were treated for the first 7 years by supra-glottic laryngectomy and prophylactic neck dissection and thereafter by radiotherapy. The results were equally good in both series: a 5-year survival of 75-80%. Salvage surgery for failed radiotherapy or surgery for supra-glottic carcinoma gave poor results.


Assessment of microbiological air quality in hemato-oncology units and its relationship with the occurrence of invasive fungal infections: an integrative review.
Worldwide aging of the human population has promoted an increase in the incidence of neoplasia, including hematological cancers, which render patients particularly vulnerable to invasive fungal infections. For this reason, air filtration in hematooncology units has been recommended. However, scarce literature has assessed the impact of microbiological air quality on the occurrence of fungal infections in this population. We performed an integrative review of studies in the MEDLINE database that were published between January 1980 and October 2012, using the following combinations of keywords: air × quality × HEPA, air × quality × hematology, and airborne fungal infections. The search yielded only 13 articles, suggesting that high-efficiency filtering of the ambient air in hemato-oncology units can prevent the incidence of invasive fungal infections. However, no randomized clinical trial was found to confirm this suggestion. Currently, there is no consensus about the maximum allowable count of fungi in the air, which complicates filtration monitoring, including filter maintenance and replacement, and needs to be addressed in future studies.


Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways.
The present study was designed to elucidate the protective effects of dietary apigenin (API) enrichment in a chronic colitis model induced by DSS in mice. Inflammatory mediators and the possible role of canonical and non-canonical NLRP3 inflammasome signaling pathways in the beneficial effects of API under chronic inflammatory conditions were also explored. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet (SD), and other two groups were fed with API at 0.1%. After 30days, all groups except sham received 3% DSS in drinking water for 5days followed by a regime of 21days of water. Our results revealed that dietary API supplementation decreased the macroscopic and microscopic damage signs of colitis; also, it was capable to down-regulate mPGES, COX-2 and iNOS enzyme colonic expressions and to decrease serum matrix metalloproteinase (MMP-3) levels. Similarly, API diet reduced IL-1β and TNF-α proinflammatory cytokine secretions in primary LPS-stimulated splenocytes. Furthermore, we demonstrated that API anti-inflammatory activity was related with an inhibition of both canonical and non-canonical NLRP3 inflammasome pathways by decreasing proinflammatory IL-1β and IL-18 cytokine levels as a consequence of regulation of cleaved caspase-1 and caspase-11 enzymes. We conclude that API supplement might provide a basis for developing a new dietary strategy for the prevention of chronic ulcerative colitis.


Peptides as potential virus inhibitors. Synthesis and bioassay of five respiratory syncytial virus peptide analogs with antimeasles activity.
Five carbobenzoxylated and D-amino acid containing-peptide analogs of the respiratory syncytial virus (RSV) F1 glycoprotein amino terminus were chemically synthesized by solution and FMOC-solid phase peptide synthesis methods. Several of these peptides, ranging from 3 to 6 residues in length, raised the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. None of these peptides were specific inhibitors of RSV or herpes simplex virus infection. Two of the series, CBZ-D-Phe-L-Leu-Gly-D-Phe-D-Leu-D-Leu and CBZ-D-Phe-L-Leu-Gly-D-Phe-D-Leu-D-Leu-Gly, were active in reducing measles virus-induced cytopathic effect at 62 micrograms/mL. Others in the series showed some activity at higher doses or activity simultaneously with some cell toxicity. These results support the view that membrane-stabilizing agents may have non-specific effects on membranes which are responsible for their antimeasles activity.


Unlabelled LRET biosensor based on double-stranded DNA for the detection of anthraquinone anticancer drugs.
Based on upconversion nanoparticles (UCNPs) as energy donor and herring sperm DNA (hsDNA) as molecular recognition element, an unlabelled upconversion luminescence (UCL) affinity biosensor was constructed for the detection of anthraquinone (AQ) anticancer drugs in biological fluids. AQ anticancer drugs can insert into the double helix structure of hsDNA on the surface of UCNPs, thereby shortening the distance from UCNPs. Therefore, the luminescence resonance energy transfer (LRET) phenomenon is effectively triggered between UCNPs and AQ anticancer drugs. Hence, AQ anticancer drugs can be quantitatively detected according to the UCL quenching rate. The biosensor showed good sensitivity and stability for the detection of daunorubicin (DNR) and doxorubicin (ADM). For the detection of DNR, the linear range is 1-100 μg·mL-1 with a limit of detection (LOD) of 0.60 μg·mL-1, and for ADM, the linear range is 0.5-100 μg·mL-1 with a LOD of 0.38 μg·mL-1. The proposed biosensor provides a convenient method for monitoring AQ anticancer drugs in clinical biological fluids in the future.


Effects of consanguineous marriage on reproductive outcome in an Arab community in Israel.
Intrafamilial marriage is favoured by the Arab community in Israel, almost all of whom live in villages populated by a few (< 20) founding families. A previous study in Taibe, a large Arab village located 30 km from Tel Aviv, showed a significantly high malformation rate among infants of consanguineous parents. The present study examines the reproductive consequences of parental consanguinity in 610 families from the same village, selected retrospectively through infants routinely seen in the local well baby clinic. All mothers were interviewed with regard to previous pregnancy outcomes, including abortions, stillbirths, and neonatal or infant deaths, as well as the degree of consanguinity. In addition, we analysed the anthropometric measurements of the probands. The incidence of infant deaths was significantly higher in the inbred group (p < 0.001). No significant increase in fetal loss between the inbred and outbred groups was observed. There were no differences in anthropometric features, except for a lower birth weight in the consanguineous group (p < 0.035). This study, combined with our previous studies of the same population, indicates a prominent public health problem associated with consanguineous marriage in the Arab community and a need for specific genetic counselling.


Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the β-lactam antibiotic, ceftriaxone, in mice.
Recently, it has been indicated that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Furthermore, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids. Since cannabinoid tolerance is known to be similar to opioids, our purpose was to examine the effect of ceftriaxone on the development of tolerance to WIN 55,212-2, a cannabinoid agonist. The tail flick test, a rectal thermometer, and the ring test were used for evaluating the degree of tolerance to the analgesic, hypothermic, and cataleptic effects of WIN 55,212-2, respectively. Within one week, animals became completely tolerant to analgesic, hypothermic and cataleptic effects of WIN 55,212-2 (6mg/kg). Ceftriaxone, with its higher doses (100-200mg/kg), attenuated the development of tolerance to the analgesic and hypothermic effects of WIN 55,212-2, but had no effect on its cataleptic action. Dihydrokainic acid (10mg/kg), a GLT-1 transporter inhibitor, prevented this effect of ceftriaxone. Our results suggest that repeated treatment with ceftriaxone prevents the development of tolerance to the analgesic and hypothermic effects of cannabinoids, and GLT-1 activation appears to play a key role in this preventive effect of beta-lactam antibiotics.


Rural health centres, communities and malaria case detection in Zambia using mobile telephones: a means to detect potential reservoirs of infection in unstable transmission conditions.
Effective malaria control depends on timely acquisition of information on new cases, their location and their frequency so as to deploy supplies, plan interventions or focus attention on specific locations appropriately to intervene and prevent an upsurge in transmission. The process is known as active case detection, but because the information is time sensitive, it is difficult to carry out. In Zambia, the rural health services are operating effectively and for the most part are provided with adequate supplies of rapid diagnostic tests (RDT) as well as effective drugs for the diagnosis and treatment of malaria. The tests are administered to all prior to treatment and appropriate records are kept. Data are obtained in a timely manner and distribution of this information is important for the effective management of malaria control operations. The work reported here involves combining the process of positive diagnoses in rural health centres (passive case detection) to help detect potential outbreaks of malaria and target interventions to foci where parasite reservoirs are likely to occur. Twelve rural health centres in the Choma and Namwala Districts were recruited to send weekly information of rapid malaria tests used and number of positive diagnoses to the Malaria Institute at Macha using mobile telephone SMS. Data were entered in excel, expressed as number of cases per rural health centre and distributed weekly to interested parties. These data from each of the health centres which were mapped using geographical positioning system (GPS) coordinates were used in a time sensitive manner to plot the patterns of malaria case detection in the vicinity of each location. The data were passed on to the appropriate authorities. The seasonal pattern of malaria transmission associated with local ecological conditions can be seen in the distribution of cases diagnosed. Adequate supplies of RDT are essential in health centres and the system can be expanded throughout the country to support strategic targeting of interventions by the National Malaria Control Programme. Participation by the health centre staff was excellent.


Expression of the Saccharomyces cerevisiae PIS gene and synthesis of phosphatidylinositol in Escherichia coli.
Expression of the Saccharomyces cerevisiae PIS gene encoding phosphatidylinositol synthase in Escherichia coli was achieved by inserting its coding sequence into lacZ on pUC8. The fused gene encoded a phosphatidylinositol synthase whose amino-terminal three amino acids had been replaced by the amino-terminal five amino acids of E. coli beta-galactosidase. E. coli cells bearing this recombinant plasmid produced a significant level of phosphatidylinositol synthase in the presence of a lacZ inducer, isopropylthio-beta-D-galactopyranoside. When the culture medium was supplemented with myo-inositol and isopropylthio-beta-D-galactopyranoside, the cells accumulated a substantial amount of phosphatidylinositol in their membranes. When a saturating level of myo-inositol was added, phosphatidylinositol constituted about 4% of the total phospholipids. Phosphatidylinositol accumulation occurred at the expense of phosphatidylglycerol. The ratio of phosphatidylethanolamine to total acidic phospholipids remained constant. The growth rate of phosphatidylinositol-containing E. coli cells did not differ significantly from that of cells with the normal phospholipid composition.


Metabolites and Biological Activities of Thymus zygis, Thymus pulegioides, and Thymus fragrantissimus Grown under Organic Cultivation.
Thymus plants are marketed for diverse usages because of their pleasant odor, as well as high nutritional value and wealth of health-promoting phytochemicals. In this study, Thymuszygis, Thymuspulegioides, and Thymusfragrantissimus grown under organic cultivation regime were characterized regarding nutrients and phenolic compounds. In addition, the antioxidant and antibacterial properties of these species were screened. The plants were particularly notable for their high K/Na ratio, polyunsaturated fatty acids content and low omega-6/omega-3 fatty acids ratios, which are valuable features of a healthy diet. Caffeic acid and/or its derivatives, mainly rosmarinic acid and caffeoyl rosmarinic acid, represented the majority of the phenolic constituents of these plants, although they were less representative in T. pulegioides, which in turn was the richest in flavones. The latter species also exhibited the highest antioxidant capacity (DPPH● EC50 of 9.50 ± 1.98 μg/mL and reducing power EC50 of 30.73 ± 1.48 μg/mL), while T. zygis was the most active towards Gram-positive and Gram-negative bacteria. Overall, the results suggest that the three thyme plants grown in organic farming are endowed with valuable metabolites that give them high commercial value for applications in different industries.


Clinically relevant effect of rupatadine 20 mg and 10 mg in seasonal allergic rhinitis: a pooled responder analysis.
Different clinical trials showed the superior efficacy of rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Data from 1470 patients were analyzed: 332 treated with placebo, 662 with rupatadine 10 mg and 476 with rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in rupatadine groups compared to the placebo group across the visits. Among rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the rupatadine 20 mg group than in the rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. This responder analysis confirms the superior efficacy of rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group.


The viability of external electrical stimulation as a therapeutic modality.
This study indicates that external electrical stimulation is a valuable tool for control of acute pain in about 80 percent of patients but, for significant relief of pain, in only about 25 percent of patients with chronic pain. The author recognizes that in order to increase its use, a system for delivery of this therapy under a doctor's prescription, rather than having to teach each individual practitioner the technique for using the device, must be developed. In chronic-pain patients when external electrical stimulation is inadequate, a more aggressive and comprehensive program of operant conditioning, progressive physical exercise, drug withdrawal, autogenic training, and biofeedback is advised.


[Criteria for evaluating the severity of craniocerebral trauma in children].
The article discusses the total results of multifactorial analysis of observations over 16,000 children with isolated and more than 400 with combined craniocerebral trauma (CCT) in the light of the peculiarities of the child age and the current trends in studying the problem in the Soviet Union and other countries. From these standpoints, the author first gives a clinicomorphological characterization of CCT types in children, deals with the methods and prospects of objectivication of the evaluation of the severity of isolated and combined CCT, extracranial local injuries in polytrauma, totally determining the severity of the general condition and the efficacy and prognosis of the diagnostic and therapeutic measures. Original methods for quantitative evaluation of the degree of severity of the trauma, which were developed in the clinic, are described. A variety of the clinical CCT forms and the possible variants of the concomitant injuries are systematized in a CCT classification approximated maximally to the solution of practical problems under different conditions, including extreme conditions in mass injuries. For this purpose, the author uses conventional designations for the main gradients of the pathophysiological reactions of the child's organism depending on the location and severity of the concrete damages and the general condition, making a coded recording of the diagnosis possible, which makes easier the sorting out and registration of the patients and orientation as regards the order in which aid should be given and the volume of the therapeutic and diagnostic programs with the use of computers. The patients were subjected to general clinical examination and laboratory tests, as well as special methods of examination (radiography, ultrasonic study, angiography, circulography, computed tomography, etc.). Importance was attached to the results of histological study and the reports of the forensic medical examination committee.


Characteristics and Outcomes in Primary Aldosteronism Patients Harboring Glucocorticoid-Remediable Aldosteronism.
The clinical characteristics and surgical prognosis of glucocorticoid-remediable aldosteronism (GRA, also known as familial hyperaldosteronism type 1, FH-I) have not been widely studied. Using data from the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry retrospectively, we describe the associated clinical factors for GRA and clinical predictors of surgical outcomes among identified GRA patients. We found 79 GRA-positive (51.2 ± 13.8 years; women 39 (49.4%)) and 114 GRA-negative primary aldosteronism (PA) patients matched with age, gender, and body mass index. Lower plasma aldosterone concentrations (PACs) and aldosterone-renin ratios were found among GRA-positive individuals. Multivariable logistic regression demonstrated that a PAC ≤ 40 ng/dL could predict concealed GRA individuals (OR 0.523, p = 0.037). Low serum potassium (OR 0.285, p = 0.008), but not the presence of GRA, was associated with hypertension-remission. Of note, PRA (OR 11.645, p = 0.045) and hypokalemia (OR 0.133, p = 0.048) were associated with hypertension-remission in GRA patients. Unilateral primary aldosteronism patients harboring concomitant GRA were not associated with inferior hypertension-remission after an adrenalectomy. Low serum potassium and high PRA were positively associated with hypertension-remission in GRA patients.


Ghrelin suppresses migration of macrophages via inhibition of ROCK2 under chronic intermittent hypoxia.
Migration of macrophages and atherosclerosis result in various diseases, including coronary heart disease. This study aimed to clarify the roles that ghrelin and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) play in migration of macrophages under chronic intermittent hypoxia (CIH). A rat model of CIH was constructed and changes in ghrelin and ROCK2 protein expression were measured by western blot assay. The migratory ability of macrophages was determined by the transwell assay. Hematoxylin and eosin staining was applied to detect the changes in intima-media thickness. We found that CIH enhanced migration of macrophages, and this effect was attenuated by exogenous ghrelin. Additionally, the facilitative effect of CIH on migration of macrophages was strengthened or decreased by upregulation or downregulation of ROCK2, respectively. This phenomenon indicated that ROCK2 was involved in CIH-induced migration in macrophages. Furthermore, western blot and transwell assays showed that ghrelin inhibited CIH-induced migration via ROCK2 suppression in macrophages. In summary, the present study shows that ghrelin inhibits CIH-induced migration via ROCK2 suppression in macrophages. Our research may help lead to identifying a new molecular mechanism for targeted therapy of atherosclerosis and its associated coronary artery diseases under intermittent hypoxia.


Staphyloma and other risk factors in axial myopia.
Posterior staphyloma, associated exclusively with axial myopia, is progressive and often results in visual loss. Five types of primary staphyloma have been described anatomically and in terms of sequelae. Mechanical and physiological factors in axial myopia can lead to potentially sight-threatening abnormalities which affect central or peripheral vision. Some are easily detectable while others require a thorough evaluation of the peripheral retina. This report consists of a review of fundus changes associated with axial myopia, the types of staphyloma, and a case report. Emphasis is placed on identification and management of patients at risk from the sequelae of axial myopia.


Biomechanical analysis of skull trauma and opportunity in neuroradiology interpretation to explain the post-concussion syndrome: literature review and case studies presentation.
Traumatic head injuries are one of the leading causes of emergency worldwide due to their frequency and associated morbidity. The circumstances of their onset are often sports activities or road accidents. Numerous studies analysed post-concussion syndrome from a psychiatric and metabolic point of view after a mild head trauma. The aim was to help understand how the skull can suffer a mechanical deformation during a mild cranial trauma, and if it can explain the occurrence of some post-concussion symptoms. A multi-step electronic search was performed, using the following keywords: biomechanics properties of the skull, three-dimensional computed tomography of head injuries, statistics on skull injuries, and normative studies of the skull base. We analysed studies related to the observation of the skull after mild head trauma. The analysis of 23 studies showed that the cranial sutures could be deformed even during a mild head trauma. The skull base is a major site of bone shuffle. Three-dimensional computed tomography can help to understand some post-concussion symptoms. Four case studies showed stenosis of jugular foramen and petrous bone asymmetries who can correlate with concussion symptomatology. In conclusion, the skull is a heterogeneous structure that can be deformed even during a mild head trauma.


Methane production during storage of anaerobically digested municipal organic waste.
Anaerobic digestion of source-separated municipal organic waste is considered feasible in Denmark. The limited hydraulic retention in the biogas reactor (typically 15 d) does not allow full degradation of the organic waste. Storage of anaerobically digested municipal organic waste can therefore be a source of methane (CH4) emission that may contribute significantly to the potential global warming impact from the waste treatment system. This study provides a model for quantifying the CH4 production from stored co-digested municipal organic waste and estimates the production under typical Danish climatic conditions, thus quantifying the potential global warming impact from storage of the digested municipal organic waste before its use on agricultural land. Laboratory batch tests on CH4 production as well as temperature measurements in eight full-scale storage tanks provided data for developing a model estimating the CH4 production in storage tanks containing digested municipal organic waste. The temperatures measured in separate storage tanks on farms receiving digested slurry were linearly correlated with air temperature. In storage tanks receiving slurry directly from biogas reactors, significantly higher temperatures were measured due to the high temperatures of the effluent from the reactor. Storage tanks on Danish farms are typically emptied in April and have a constant inflow of digested material. During the warmest months the content of digested material is therefore low, which limits the yearly CH4 production from storage.


Naked mole-rats: behavioural phenotyping and comparison with C57BL/6 mice.
Naked mole-rats (NMR) live underground in large eusocial colonies in East Africa. They are extremely long-lived, some individuals having a lifespan of over 30 years. This has attracted research into longevity and possibly neurodegenerative disorders. However, very little is known about their basic behaviour, particularly in tests commonly used to characterise the behaviour of the laboratory rat and mouse, for which there is an enormous database. Recently the authors carried out comprehensive behavioural phenotyping on NMRs, comparing them on most tasks directly with C57BL/6 mice, the strain for which there is the largest behavioural database. The NMR colony had been obtained from the wild originally, but housed in an animal facility for about two years. Large inter-species differences in behaviour were seen between the mice and the NMRs. The latter had generally poor sensorimotor function, including cutaneous sensation, strength and even grasp reflexes. They were often reluctant to enter or head-dip into small holes that mice readily entered. Their vision (generally considered to be very poor) was sufficient to distinguish the two zones of a light-dark box. Although, as expected, the NMRs were capable of burrowing and digging, when individually housed they did not shred cotton material to make nests. Shredding was seen in a colony cage containing a queen, but no nests were made there even when a nesting box was provided. In cognitive testing, although, unlike mice and rats, they did not spontaneously alternate in a T-maze, they learnt rewarded alternation and a cued position task well. This study demonstrates how behaviour uniquely reflects the natural environment in which these unusual animals have evolved and live, and provides baseline data for future work.


A method for the control of multigrasp myoelectric prosthetic hands.
This paper presents the design and preliminary experimental validation of a multigrasp myoelectric controller. The described method enables direct and proportional control of multigrasp prosthetic hand motion among nine characteristic postures using two surface electromyography electrodes. To assess the efficacy of the control method, five nonamputee subjects utilized the multigrasp myoelectric controller to command the motion of a virtual prosthesis between random sequences of target hand postures in a series of experimental trials. For comparison, the same subjects also utilized a data glove, worn on their native hand, to command the motion of the virtual prosthesis for similar sequences of target postures during each trial. The time required to transition from posture to posture and the percentage of correctly completed transitions were evaluated to characterize the ability to control the virtual prosthesis using each method. The average overall transition times across all subjects were found to be 1.49 and 0.81 s for the multigrasp myoelectric controller and the native hand, respectively. The average transition completion rates for both were found to be the same (99.2%). Supplemental videos demonstrate the virtual prosthesis experiments, as well as a preliminary hardware implementation.


Amygdala 5-HTT Gene Network Moderates the Effects of Postnatal Adversity on Attention Problems: Anatomo-Functional Correlation and Epigenetic Changes.
Variations in serotoninergic signaling have been related to behavioral outcomes. Alterations in the genome, such as DNA methylation and histone modifications, are affected by serotonin neurotransmission. The amygdala is an important brain region involved in emotional responses and impulsivity, which receives serotoninergic input. In addition, studies suggest that the serotonin transporter gene network may interact with the environment and influence the risk for psychiatric disorders. We propose to investigate whether/how interactions between the exposure to early life adversity and serotonin transporter gene network in the amygdala associate with behavioral disorders. We constructed a co-expression-based polygenic risk score (ePRS) reflecting variations in the function of the serotonin transporter gene network in the amygdala and investigated its interaction with postnatal adversity on attention problems in two independent cohorts from Canada and Singapore. We also described how interactions between ePRS-5-HTT and postnatal adversity exposure predict brain gray matter density and variation in DNA methylation across the genome. We observed that the expression-based polygenic risk score, reflecting the function of the amygdala 5-HTT gene network, interacts with postnatal adversity, to predict attention and hyperactivity problems across both cohorts. Also, both postnatal adversity score and amygdala ePRS-5-HTT score, as well as their interaction, were observed to be associated with variation in DNA methylation across the genome. Variations in gray matter density in brain regions linked to attentional processes were also correlated to our ePRS score. These results confirm that the amygdala 5-HTT gene network is strongly associated with ADHD-related behaviors, brain cortical density, and epigenetic changes in the context of adversity in young children.


Bilirubin or plasminogen--which is better in the assessment of the severity of viral hepatitis?
The purpose of the present paper was to asses the values of plasminogen (PLg) as severity index in viral hepatitis (VH). The results were compared with serum bilirubin (SB) and prothrombin time. The following groups of patients were investigated: I- VH (n-672); II- Fulminant hepatitis (FH)(n-53); III-Liver cirrhosis (n-52); IV- Cholangiohepatitis (21); Toxic hepatitis (n-22); V- Gall stone (n-56) VI- Neoplasms with jaundice (n-56); VII- Healthy subjects (n-137). PLg was found to be diminished in parenchymal liver diseases, especially in VH's patients according to the severity and the stage of the diseases. The most impressive decline was observed in FH--more than 50% of the tests showed Plg activity less than 10% (reverence values 83-126% activity). In VH, PLg was superior to SB and prothrombin time when evaluating the severity of the disease at the time of admission in the hospital. We proposed PLg as valuable criterion for the severity of VH. The range being as follows: Light forms of VH- PLg activity above 70%; Medium forms-from 69 to 50%; Severe forms-from 49 to 20% and patients with high risk of liver coma-PLg activity below 20%.


Low-Dose Tacrolimus Prevents Dysregulated Peri-Conceptional Ovarian and Systemic Immune Cellular Homeostasis in Subjects with PCOS.
Polycystic ovary syndrome (PCOS) is characterized by failure of ovulation and is associated with obesity and chronic inflammation. Recent evidence suggests that anomalous activation of ovarian macrophages and numerical and functional deficits in the Th17 (CD4+IL17A+) and the CD4+CD25+CD127low Tregs plays crucial role in PCOS. We have shown that the pre-pregnancy use of tacrolimus prevents adverse reproductive outcomes in a mouse model of PCOS. Here we used the HFD-NONcNZO mice to test a hypothesized beneficial use of tacrolimus relative to metformin in favorably influencing the ovarian and systemic immune milieux conducive to gestational success in subjects with PCOS. Compared to normative controls, our data revealed an aberrant peri-conceptional suppression of the CD4+CD25+CD127low Tregs together with an overexpression of the Th17 T cells and lack of coordinated activation of ovarian macrophages in untreated HFD-dNONcNZO mice. Significant variances in treatment outcomes favoured the use of tacrolimus over metformin in treated mice. Consistent with the human fertility studies, this investigation reveals a beneficial systemic use of tacrolimus (0.1 mg/kg) in promoting early pregnancy in individuals with PCOS and suggests the need for further research into the selective inhibition of IL17A as a plausibly alternative immunotherapeutic approach in the clinical management of infertile individuals with PCOS.


Allograft tendons are a safe and effective option for revision ACL reconstruction: a clinical review.
Revision anterior cruciate ligament reconstruction remains a challenge, especially optimising outcome for patients with a compromised knee where previous autogenous tissue has been used for reconstruction. Allograft tissue has become a recognized choice of graft for revision surgery but questions remain over the risks and benefits of such an option. Allograft tendons are a safe and effective option for revision ACL reconstruction with no higher risk of infection and equivalent failure rates compared to autografts provided that the tissue is not irradiated, or any irradiation is minimal. Best scenarios for use of allografts include revision surgery where further use of autografts could lead to high donor site morbidity, complex instability situations where additional structures may need reconstruction, and in those with clinical and radiologic signs of autologous tendon degeneration. A surgeon needs to be able to select the best option for the challenging knee facing revision ACL reconstruction, and in the light of current data, allograft tissue can be considered a suitable option to this purpose.Level of evidence IV.


Biomolecular Changes and Cortical Neurodegenerative Lesions in Trichinella Spiralis Infected BALB/c Mice: A Preliminary Study Elucidating a Potential Relationship Between Systemic Helminthic Infections and Idiopathic Parkinson's.
Idiopathic Parkinson's (IP) is a neurodegenerative disease that is suspected to be due to exposure to infections during early life. Toxoplasmosishas been the only suspected parasitic infection in IP (Celik et al., 2010). Recently, some non-central nervous system bacterial and viral infections have been incriminated in IP (Çamcı & Oğuz, 2016). So in the current study, we tried to explore if the systemic inflammatory reactions triggered by some helminths like Trichinella spiralis can induce Parkinsonian lesions in the brain, especially that the cerebral complications have been reported in 10-20% of Trichinella spiralis infected patients . An experimental study was designed to assess the neurodegenerative and biomolecular changes that may occur in Trichinella spiralis infected BALB/C mice in comparison to rotenone induced PD model and apparently healthy ones. The motor affection was significantly lesser in the Trichinella infected mice than the Parkinson's model, but when the catalepsy score was calculated (through the grid and bar tests) it was found to be significantly higher in the infected mice than in the healthy ones. A significant increase in the blood advanced oxidative protein products (AOPP), IFN-γ, TGF-β, and brain DNA fragmentation was also detected in the Trichinella spiralis infected mice. After histopathological examination, a significant increase in the cortical apoptotic neurons and Lewy's body were observed in the Trichinella infected and the rotenone induced Parkinson's model sections. A significant decrease in the immunohistochemical expression of the tyrosine hydroxylase expression in the brain sections and the ELISA measured dopamine level in the brain homogenate was also reported in the infected mice group. This study findings may collectively suggest that the systemic inflammatory reactions and the oxidative stresses associated with some systemic helminthic infections like trichinellosis are possible to precipitate neurodegenerative lesions and biomolecular changes in the brain , and manifest with IPD later in life.


Structure-activity studies of aplysiatoxin-type tumor promoters.
The cellular activities and responses of aplysiatoxin in vitro and in vivo are very similar to those of the diterpene 12-O-tetradecanoylphorbol-13-acetate (TPA) and the indole aklaloids teleocidin B and lyngbyatoxin A. Even though aplysiatoxin, TPA, and teleocidin B are chemically and structurally quite distinct from one another, all three compounds produce essentially the same plethora of biological effects by apparently binding to the same receptor on the cell membrane, the so-called phorboid receptor. Several aplysiatoxin-type compounds have been studied in three test systems for evaluating potential tumor-promoting activity, viz. mouse ear skin for irritation, murine dorsal skin for the induction of ornithine decarboxylase (ODC) activity, and an epidermal particulate fraction of dorsal mouse skin for the inhibition of specific binding of [3H]-TPA. Some of the compounds were tested in a 30-week two-step carcinogenesis experiment in mice. In most cases the results of the 30-week test correlated with the activities of the three preliminary tests. The overall study indicated that the hydroxyl groups on C-3, C-20, and C-30 are essential for maximum activity. Inspection of Dreiding models showed that the oxygens on C-27, C-3, and C-30 of aplysiatoxin are aligned with the oxygens on C-3, C-4, and C-20 of TPA, respectively. The latter oxygens are in functional groups that are known to be necessary for the high activity of TPA.


Diverse roles for the Drosophila fructose sensor Gr43a.
The detection of nutrients, both in food and within the body, is crucial for the regulation of feeding behavior, growth, and metabolism. While the molecular basis for sensing food chemicals by the taste system has been firmly linked to specific taste receptors, relatively little is known about the molecular nature of the sensors that monitor nutrients internally. Recent reports of taste receptors expressed in other organ systems, foremost in the gastrointestinal tract of mammals and insects, has led to the proposition that some taste receptors may also be used as sensors of internal nutrients. Indeed, we provided direct evidence that the Drosophila gustatory receptor 43a (Gr43a) plays a critical role in sensing internal fructose levels in the fly brain. In addition to the brain and the taste system, Gr43a is also expressed in neurons of the proventricular ganglion and the uterus. Here, we discuss the multiple potential roles of Gr43a in the fly. We also provide evidence that its activation in the brain is likely mediated by the neuropeptide Corazonin. Finally, we posit that Gr43a may represent only a precedent for other taste receptors that sense internal nutrients, not only in flies but, quite possibly, in other animals, including mammals.


The effectiveness and cost-effectiveness of acupressure for the control and management of chemotherapy-related acute and delayed nausea: Assessment of Nausea in Chemotherapy Research (ANCHoR), a randomised controlled trial.
Chemotherapy-induced nausea and vomiting remain difficult symptoms to manage in clinical practice. As standard antiemetic drugs do not fully eliminate these symptoms, it is important to explore the adjuvant role of non-pharmacological and complementary therapies in antiemetic management approaches. Acupressure is one such treatment showing highly suggestive evidence so far of a positive effect, meriting further investigation. The primary objective was to assess the effectiveness and cost-effectiveness of self-acupressure using wristbands compared with sham acupressure wristbands and standard care alone in the management of chemotherapy-induced nausea. Secondary objectives included assessment of the effectiveness and cost-effectiveness of the wristbands in relation to vomiting and quality of life and exploration of any age, gender and emetogenic risk effects. Randomised three-arm sham-controlled trial (Assessment of Nausea in Chemotherapy Research or ANCHoR) with an economic evaluation. Arms include the wristband arm, the sham wristband arm and the standard care only arm. Randomisation consisted of minimisation with a random element balancing for gender, age (16-24, > 24-50, >50 years) and three levels of emetogenic chemotherapy (low, moderate and high). Qualitative interviews were incorporated to shed more light on the quantitative findings. Outpatient chemotherapy clinics in three regions in the UK involving 14 different cancer units/centres. Chemotherapy-naive cancer patients receiving chemotherapy of low, moderate and high emetogenic risk. The intervention was acupressure wristbands pressing the P6 point (anterior surface of the forearm). The Rhodes Index for Nausea/Vomiting, the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool and the Functional Assessment of Cancer Therapy - General (FACT-G). At baseline participants completed measures of anxiety/depression, nausea/vomiting expectation and expectations from using the wristbands. In total, 500 patients were randomised in the study arms (166 standard care, 166 sham acupressure and 168 acupressure) and data were available for 361 participants for the primary outcome. The primary outcome analysis (nausea in cycle 1) revealed no statistically significant differences between the three arms, although the median nausea experience in patients using wristbands (both real and sham ones) was somewhat lower than that in the antiemetics only group (median nausea experience scores for the four cycles: standard care arm 1.43, 1.71, 1.14, 1.14; sham acupressure arm 0.57, 0.71, 0.71, 0.43; acupressure arm 1.00, 0.93, 0.43, 0). A gender effect was evident (p= 0.002), with women responding more favourably to the use of sham acupressure wristbands than men (odds ratio 0.35 for men and 2.02 for women in the sham acupressure group; 1.27 for men and 1.17 for women in the acupressure group). This suggests a placebo effect. No significant differences were detected in relation to vomiting outcomes, anxiety and quality of life. Some transient adverse effects were reported, including tightness in the area of the wristbands, feeling uncomfortable when wearing them and minor swelling in the wristband area (n= 6).There were no statistically significant cost differences associated with the use of real acupressure bands (£70.66 for the acupressure group, £111.13 for the standard care group and £161.92 for the sham acupressure group). In total, 26 subjects took part in qualitative interviews. The qualitative data suggested that participants perceived the wristbands (both real and sham) as effective and helpful in managing their nausea during chemotherapy. There were no statistically significant differences between the three arms in terms of nausea, vomiting and quality of life, although apparent resource use was less in both the real acupressure arm and the sham acupressure arm compared with standard care only; therefore; no clear conclusions can be drawn about the use of acupressure wristbands in the management of chemotherapy-related nausea and vomiting. However, the study provided encouraging evidence in relation to an improved nausea experience and some indications of possible cost savings to warrant further consideration of acupressure both in practice and in further clinical trials. ISRCTN87604299. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 26. See the HTA programme website for further project information.


Interstitial lung disease: state of the clinical art.
Interstitial lung diseases pose a great challenge to the clinician because of the indolent and variably active nature of these disorders and the limited number of therapeutic options. Adjunctive therapy includes supplemental oxygen in hypoxic patients, bronchodilators in patients with an obstructive lung component, and aggressive use of antibiotics in febrile patients on potent immunosuppressive therapy and suspected or confirmed infections. In younger patients who present late in their illness or deteriorate on therapy, lung transplantation is the only option. Recent advances in our knowledge of the cellular and molecular mechanisms operating in ILD and techniques which include gene amplification and cloning promise to yield more effective treatments for these diseases which currently produce a high incidence of morbidity and mortality.


Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.
OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.


Transplant nephrectomy: what are the surgical risks?
Whether or not to remove a failed renal graft has been the subject of much debate. One reason for a cautious approach to graft removal is its high morbidity and mortality rates. We analyzed the morbidity, mortality, and risk factors of transplant nephrectomy at our center. We included 157 cases of transplant nephrectomy in 143 patients, performed between January 2000 and May 2012 at the Academic Medical Center, Amsterdam. Patient data were collected retrospectively. A total of 32 surgical complications occurred after transplant nephrectomy (20%) and 16 patients needed surgical re-intervention (10%). Hemorrhage and infection are the most frequent causes of surgical complications (14%). The mortality rate was 3.2%. There were no significant differences in characteristics and timing of transplant nephrectomy between the group with surgical complications and the group without. A total of 59 re-transplantations were performed in 57 patients (38%). Transplant nephrectomy is associated with high morbidity and mortality rates. We found no significant risk factors for surgical complications following transplant nephrectomy and no significant association between timing of transplant nephrectomy and surgical complications. Steps to reduce these complications need further investigation.


Acid proteinase secreted by Candida tropicalis: functional analysis of preproregion cleavages in C. tropicalis and Saccharomyces cerevisiae.
The 40 kDa secreted aspartyl proteinase (Sapt1) of Candida tropicalis is a pepsin-like enzyme encoded by the SAPT1 gene. According to the deduced amino acid sequence. Sapt1 has a putative preproregion of 60 amino acids preceding the mature enzyme. Maturation and processing of Sapt1 was analysed in C. tropicalis and Saccharomyces cerevisiae strains expressing wild-type or mutated forms of SAPT1. In S. cerevisiae, the glycosylated 46 kDa proenzyme was converted to the mature 40 kDa form of Sapt1 by KEX2-dependent proteolytic cleavage following the Lys59-Arg60 sequence. The replacement of Lys59-Arg60 by Lys59-Gly60 revealed that the precursor can be processed by an autocatalytic cleavage. This alternative processing pathway to produce mature Sapt1 is less efficient than the Kex2-mediated pathway. Finally, it was shown that in C. tropicalis and S. cerevisiae the removal of the proregion was a prerequisite for the secretion of Sapt1.


Unilateral hippocampal sclerosis with contralateral temporal scalp ictal onset.
To investigate the clinical characteristics and surgical outcomes in patients with unilateral hippocampal sclerosis whose scalp ictal EEG recordings localize to the opposite temporal lobe. We retrospectively reviewed the data of all adult patients who had undergone depth electrode implantation for suspected temporal lobe epilepsy (TLE) at UCLA (1993-2000) or the Montreal Neurological Institute (1991-1998) to identify patients who had (a) unilateral hippocampal atrophy, and (b) surface ictal recordings in which the majority of seizures appeared to initiate in the opposite temporal lobe, with few or none that were concordant with the hippocampal atrophy. Of 109 patients with suspected TLE who underwent depth electrode study at the two centers, five patients met the aforementioned criteria. Four of these five had very severe hippocampal atrophy, whereas the fifth had mild atrophy but extensive signal change on magnetic resonance imaging (MRI). Depth electrode recordings in four of the five patients yielded clear ictal onset in the mesial temporal lobe ipsilateral to the imaging abnormality (contralateral to apparent scalp ictal onset). One patient had an unusual bitemporal onset pattern, which was nonetheless suggestive of onset in the sclerotic hippocampus. No patient had intracranial ictal onset contralateral to the imaging abnormality. All patients underwent resection of the structurally abnormal temporal lobe. After follow-up of > or = 2 years, four (80%) of five patients were seizure free, while the fifth showed lesser improvement (class III). Some patients with severe hippocampal sclerosis (sometimes called a "burned-out hippocampus") have atypical spread of ictal discharges, resulting in apparent gross discordance between imaging and scalp ictal recordings. These patients nonetheless have excellent surgical outcomes on the whole. Whether such patients may forego intracranial recordings requires further study.


Biological basis for vertical ramus osteotomies--a study of bone healing and revascularization in adult rhesus monkeys.
Fifteen adult rhesus monkeys were used as experimental models to investigate revascularization and bone healing associated with pedicled and nonpedicled vertical ramus osteotomies and to elucidate the problem of vascular ischemia of the proximal segment and healing of the osteotomized bone. Microangiographic and histologic studies of vertical ramus osteotomies in which the proximal segment was not pedicled to soft tissue showed intraosseous necrosis, vascular ischemia, and delayed healing. Similar studies of pedicled vertical ramus osteotomies showed early osseous union, minimal osteonecrosis, and minimal vascular ischemia. The results indicate that continuous circulation to the proximal segment is necessary to retain osseous viability and to support the clinical practice of pedicling the proximal condylar segment to the articular capsule and lateral pterygoid muscle.


Barrier and spermicidal contraceptive methods and risk of invasive cervical cancer.
The effects of barrier and spermicidal methods of contraception on cervical cancer risk were examined by studying 479 cases of histologically confirmed invasive cervical cancer cases and 788 random digit dialing controls. In addition to a detailed history of contraceptive practices, information was available on numerous potential confounders, including demographic characteristics, sexual behavior, reproductive factors, Pap smear screening history, and smoking. After adjustment for relevant confounders, diaphragm and condom use were found not to be significantly associated with risk of cervical cancer. Although there was a small reduction in risk (OR = 0.8) associated with long-term use (5+ years) of the diaphragm, the effect appeared to relate to concomitant spermicide use, since there was evidence of further decreases in risk for women using spermicides alone for extended periods (OR = 0.7 for 5+ years). Effects were only seen among subjects of higher income and education levels, suggesting that patterns of usage may be important. The potential ability of spermicides to reduce cervical cancer risk by neutralizing viral agents warrants further attention.


Usability and Acceptability of the QDACT-PC, an Electronic Point-of-Care System for Standardized Quality Monitoring in Palliative Care.
Few resources exist to support collaborative quality monitoring in palliative care. These tools, if proven efficient through technology-enabled methods, may begin to routinize data collection on quality during usual palliative care delivery. Usability testing is a common approach to assess how easily and effectively users can interact with a newly developed tool. We performed usability testing of the Quality Data Collection Tool for Palliative Care (QDACT-PC) a novel, point-of-care quality monitoring tool for palliative care. We used a mixed methods approach to assess community palliative care clinicians' evaluations of five domains of usability. These approaches included clinician surveys after recording mock patient data to assess satisfaction; review of entered data for accuracy and time to completion; and thematic review of "think aloud" protocols to determine issues, barriers, and advantages to the electronic system. We enrolled 14 palliative care clinicians for the study. Testing the electronic system vs. paper-based methods demonstrated similar error rates and time to completion. Overall, 68% of the participants believed that the electronic interface would not pose a moderate or major burden during usual clinical activities, and 65% thought it would improve the care they provided. Thematic analysis revealed significant issues with paper-based methods alongside training needs for future participants on using novel technologies that support the QDACT-PC. The QDACT-PC is a usable electronic system for quality monitoring in palliative care. Testing reveals equivalence with paper for data collection time, but with less burden overall for electronic methods across other domains of usability.


Pain-related fear and catastrophizing predict pain intensity and disability independently using an induced muscle injury model.
Timing of assessment of psychological construct is controversial and results differ based on the model of pain induction. Previous studies have not used an exercise-induced injury model to investigate timing of psychological assessment. Exercise-induced injury models may be appropriate for these investigations because they approximate clinical pain conditions better than other experimental stimuli. In this study we examined the changes of psychological constructs over time and determined whether timing of assessment affected the construct's association with reports of pain intensity and disability. One-hundred twenty-six healthy volunteers completed the Fear of Pain Questionnaire (FPQ-III), Pain Catastrophizing Scale (PCS), and Tampa Scale of Kinesiophobia (TSK) prior to inducing muscle injury to the shoulder. The PCS and TSK were measured again 48 and 96 hours postinjury induction. Pain intensity and disability were collected at 48 and 96 hours and served as dependent variables in separate regression models. Results indicated that the FPQ-III had the strongest prediction of pain intensity from baseline to 96 hours. After baseline the PCS and TSK were stronger predictors of pain intensity and disability, respectively. These data provide support for the use of psychological constructs in predicting outcomes from shoulder pain. However, they deviate from the current theoretical model indicating that fear of pain is a consequence of injury and instead suggests that fear of pain before injury may influence reports of pain intensity. The current study provides evidence that fear of pain can be assessed prior to injury. Furthermore, it supports that after injury pain catastrophizing and kinesiophobia are independently associated with pain and disability. Overall these data suggest that timing of psychological assessment may be an important consideration in clinical environments.


Mothers' reflections about infant irritability and postpartum tobacco use.
Recent research has shown that most women who stop or substantially reduce cigarette smoking during pregnancy return to previous levels of tobacco use soon after delivery. The determinants of postpartum tobacco use have not been adequately identified. To address this gap, the present study examined one potential contributor to postpartum smoking, namely, unexplained infant crying and fussiness. The purpose of this study was to describe mothers' reflections about perceived infant irritability and postpartum tobacco use. A qualitative descriptive approach was applied to the responses of low-income women who participated in a mixed methods study of smoking relapse among mothers of infants. The subset of mothers for the present study (n = 86) was composed of women who intended to be nonsmokers after delivery. Thematic content analysis was conducted of the texts from their interviews. Four major themes were identified with respect to perceptions of infant irritability and postpartum tobacco use: not knowing what to do, seeking renewal, seeking relief, and evaluating self. The reflections of the study participants suggest that the challenges of handling infant irritability often trigger thoughts of smoking or smoking behavior. Health practitioners may strengthen cessation interventions by using strategies to help mothers cope with this experience, which is unique to the first few months after delivery.


Clinical application of 3D printing technology to the surgical treatment of atlantoaxial subluxation in small breed dogs.
Atlantoaxial instability (AAI)/subluxation commonly occurs in small breed dogs. Ventral stabilization techniques using screws and/or pins and a plate or, more commonly, polymethylmethacrylate are considered to provide the most favorable outcome. However, the implantation of screws of sufficient sizes for long-term stability becomes challenging in toy breed dogs (e.g. <2 kg). We herein report the application of 3D printing technology to implant trajectory planning and implant designing for the surgical management of AAI in 18 dogs. The use of our patient-specific drill guide templates resulted in overall mean screw corridor deviations of less than 1 mm in the atlas and axis, which contributed to avoiding iatrogenic injury to the surrounding structures. The patient-specific titanium plate was effective for stabilizing the AA joint and provided clinical benefits to 83.3% of cases (15/18). Implant failure requiring revision surgery occurred in only one case, and the cause appeared to be related to the suboptimal screw-plate interface. Although further modifications are needed, our study demonstrated the potential of 3D printing technology to be effectively applied to spinal stabilization surgeries for small breed dogs, allowing for the accurate placement of screws and minimizing peri- and postoperative complications, particularly at anatomical locations at which screw corridors are narrow and technically demanding.


The C-terminal region of the movement protein of Cowpea mosaic virus is involved in binding to the large but not to the small coat protein.
Cowpea mosaic virus (CPMV) moves from cell to cell as virus particles which are translocated through a plasmodesmata-penetrating transport tubule made up of viral movement protein (MP) copies. To gain further insight into the roles of the viral MP and capsid proteins (CP) in virus movement, full-length and truncated forms of the MP were expressed in insect cells using the baculovirus expression system. Using ELISA and blot overlay assays, affinity purified MP was shown to bind specifically to intact CPMV virions and to the large CP, but not to the small CP. This binding was not observed with a C-terminal deletion mutant of the MP, although this mutant retained the capacity to bind to other MP molecules and to form tubules. These results suggest that the C-terminal 48 amino acids constitute the virion-binding domain of the MP.


[Nosography in child psychiatry].
There is an important jeopardizing factor for all nosological classificatory systems, in general Psychiatry as well as in child Psychiatry: the lack of a universally valid basis for defining concepts of "normal" and "pathological". Both stem from social patterns, values, culture and organization. Thus, they vary widely in different countries and communities. In order to attain the much needed general nosological criteria, the starting point is to our mind, a scientific comprehensive conception of man in the midst of a social environment. Pathological phenomena are usually located either in biological, psychological or sociological domains, but they are all-pervading and affect man in the whole. Taking into account that the same can be said about children, we discuss in this paper one classificatory system proposed by Telma Reca M. D. and modified by the author. Following the gravitation of the main aethiological factors, four categories are proposed: a. Psychogenetical diseases: regular or reactive developmental disturbances; acute anxiety; neurotic traits; fully developed neurosis, and psychosomatic disturbances of neurotic origin; speech disturbances of a pure psychological nature, etc. b. Psychical disorders derived from physical diseases: acute confusional or delusional states; mental retardation; epilepsy; minimal cerebral disfunction; learning difficulties derived from injuries or/and genetic deficiencies, etc. c. Psychical disorders derived from social problems: bad nourishment, disturbed sleep, faulty or disorderly sexual behaviour; poor or disturbed performance at school or in social groups, etc. d. Disorders caused by several factors: psychotic traits; psychosis; psychopathic behaviour; lack of maturity according to chronological age; congenital personality disorders, etc.


[Ticks of the Ixodidae family as reservoir of arboviruses in the Republic of Guinea. II. Arboviruses].
From 1978 to 1985, 96,167 Ixodidae family were collected, from which 79 strains of the following arboviruses were isolated, i.e. 4 Bhanja strains, 9 CHF-Congo, 20 Dugbe, 24 Jos (viruses ecologically related to ticks), 10 Abadina, 7 Bluetongue, 1 Bunyamwera, 1 Chikungunya, (related to ticks for the first time), 1 Kindia and 2 Forecariah (new viruses). The main sources for arbovirus isolation were ticks of the Amblyomma variegatum genus (78.5%) followed by ticks of the Boophilus (12.6%), Rhipicephalus (7.6%) and Haemaphysalis (1.3%) genera. According to experimental data obtained in the laboratory and in the field involvement of A. variegatum as reservoir host for Abadina virus was established. The seasonal dynamics characteristics of the propagation of this virus and its pathogenicity for cattle were also noticed. Serological surveys on cattle (i.e. on about 7000 sera) showed that Abadina, Bluetongue, CHF-Congo, Dugbe viruses spread more actively, with 24-35% positive sera. The rate of positive sera against Bhanja, Forecariah, Jos and RVF viruses did not exceed 0.9%. During the study period, the arboviruses isolated from ticks did not play any important epidemiological role in human pathology of the Republic of Guinea.


The PRE and PQ box are functionally distinct yeast pheromone response elements.
Saccharomyces cerevisiae mating pheromones function by binding to cell surface receptors and activating signal transduction processes which regulate gene expression. In this report, we have analyzed the minimum sequence requirements for conferring both a and alpha mating pheromone inducibilities onto a heterologous promoter. Here we show that the repetitive pheromone response element (PRE) which binds to STE12 protein is sufficient to confer pheromone responsiveness only when present in multiple copies. Moreover, by itself, it is preferentially responsive to alpha factor in a cells. In contrast, a single copy of the PQ box of the STE3 upstream activation sequence (UAS) is sufficient to confer a-factor responsiveness in alpha cells. The PQ box binds both MCM1 and MAT alpha 1 in a cooperative manner, and neither the P nor Q site alone is sufficient to confer a-factor responsiveness. In a cells, however, even multiple copies of the PQ box fail to confer alpha-factor responsiveness. Therefore, the PRE and the PQ box are functionally distinct pheromone-responsive elements with opposite cell type specificities. Moreover, these results indicate that the MCM1 protein functions in a signal transduction pathway in a manner analogous to that of its mammalian homolog, the serum response factor, which regulates the expression of the c-fos proto-oncogene in mammals.


Targeting the bacteria-host interface: strategies in anti-adhesion therapy.
Bacterial infections are a major cause of morbidity and mortality worldwide and are increasingly problematic to treat due to the rise in antibiotic-resistant strains. It becomes more and more challenging to develop new antimicrobials that are able to withstand the ever-increasing repertoire of bacterial resistance mechanisms. This necessitates the development of alternative approaches to prevent and treat bacterial infections. One of the first steps during bacterial infection is adhesion of the pathogen to host cells. A pathogen's ability to colonize and invade host tissues strictly depends on this process. Thus, interference with adhesion (anti-adhesion therapy) is an efficient way to prevent or treat bacterial infections. As a basis to present different strategies to interfere with pathogen adhesion, this review briefly introduces general concepts of bacterial attachment to host cells. We further discuss advantages and disadvantages of anti-adhesion treatments and issues that are in need of improvement so as to make anti-adhesion compounds a more broadly applicable alternative to conventional antimicrobials.


Preparation and emission characteristics of ethanol-diesel fuel blends.
The preparation of ethanol-diesel fuel blends and their emission characteristics were investigated. Results showed the absolute ethanol can dissolve in diesel fuel at an arbitrary ratio and a small quantity of water(0.2%) addition can lead to the phase separation of blends. An organic additive was synthesized and it can develop the ability of resistance to water and maintain the stability of ethanol-diesel-trace amounts of water system. The emission characteristics of 10%, 20%, and 30% ethanol-diesel fuel blends, with or without additives, were compared with those of diesel fuel in a direct injection (DI) diesel engine. The experimental results indicated that the blend of ethanol with diesel fuel significantly reduced the concentrations of smoke, hydrocarbon (HC), and carbon monoxide (CO) in exhaust gas. Using 20% ethanol-diesel fuel blend with the additive of 2% of the total volume, the optimum mixing ratio was achieved, at which the bench diesel engine testing showed a significant decrease in exhaust gas. Bosch smoke number was reduced by 55%, HC emission by 70%, and CO emission by 45%, at 13 kW/1540 r/min. However, ethanol-diesel fuel blends produced a few ppm acetaldehydes and more ethanol in exhaust gas.


Organic carbonates as alternative solvents for palladium-catalyzed substitution reactions.
Organic carbonates, such as propylene carbonate, butylene carbonate, and diethyl carbonate, were tested in the Pd-catalyzed asymmetric allylic substitution reactions of rac-1,3-diphenyl-3-acetoxy-prop-1-ene with dimethyl malonate or benzylamine as nucleophiles. Bidentate diphosphanes were used as chiral ligands. The application of monodentate phosphanes capable of self-assembling with the metal was likewise tested. In the substitution reaction with dimethyl malonate, enantioselectivities up to 98% were achieved. In the amination reaction, the chiral product was obtained with up to 83% ee. The results confirm that these "green solvents" can be advantageously used for this catalytic transformation as an alternative to those solvents usually employed which run some risk of being harmful to the environment.


Performance of grain sorghum hybrids under drought stress using GGE biplot analyses.
The objective of this study was to estimate the adaptability and stability of grain sorghum hybrids grown under post-flowering water stress and non-stress conditions. The trials were carried out in Nova Porteirinha-MG during the season of 2014 and 2015, and in Teresina-PI in the 2014 season. Twenty-nine-grain sorghum hybrids were evaluated, in a randomized complete block design, with three replications. Plots consisted of four lines with 3 m long. The grain yield data were submitted to the individual variance analysis, having considered the effects of the hybrids as fixed and the other effects as random. The joint analysis was carried out, and when the interaction genotypes x environments was significant, the grain yield data were submitted to the adaptability and stability analysis by the GGE biplot method. A substantial reduction in the grain yield in environments with water stress was found. The highest yielding hybrids under water stress conditions in Nova Porteirinha-MG were 50A50, AG1080, AG1090, DKB550, DKB590, Jade, and BM737, and the highest yielding hybrids under the water stress in Teresina-PI were 1G282, 1G244, and A9721R. Considering all environments, the highest yielding hybrids were 1G282, DKB540, A9721R, 1G100, and AG1090.


Characterization of the five replication factor C genes of Saccharomyces cerevisiae.
Replication factor C (RFC) is a five-subunit DNA polymerase accessory protein that functions as a structure-specific, DNA-dependent ATPase. The ATPase function of RFC is activated by proliferating cell nuclear antigen. RFC was originally purified from human cells on the basis of its requirement for simian virus 40 DNA replication in vitro. A functionally homologous protein complex from Saccharomyces cerevisiae, called ScRFC, has been identified. Here we report the cloning, by either peptide sequencing or by sequence similarity to the human cDNAs, of the S. cerevisiae genes RFC1, RFC2, RFC3, RFC4, and RFC5. The amino acid sequences are highly similar to the sequences of the homologous human RFC 140-, 37-, 36-, 40-, and 38-kDa subunits, respectively, and also show amino acid sequence similarity to functionally homologous proteins from Escherichia coli and the phage T4 replication apparatus. All five subunits show conserved regions characteristic of ATP/GTP-binding proteins and also have a significant degree of similarity among each other. We have identified eight segments of conserved amino acid sequences that define a family of related proteins. Despite their high degree of sequence similarity, all five RFC genes are essential for cell proliferation in S. cerevisiae. RFC1 is identical to CDC44, a gene identified as a cell division cycle gene encoding a protein involved in DNA metabolism. CDC44/RFC1 is known to interact genetically with the gene encoding proliferating cell nuclear antigen, confirming previous biochemical evidence of their functional interaction in DNA replication.


[Effect of the addition of sorghum and molasses on the fermentation of bovine colostrum].
In this study, ground sorghum (7.5%) and molasses (10%) were added to fresh bovine colostrum. The two mixtures and the fresh colostrum, used as control, were allowed to ferment for 21 days. Significant differences (P less than 0.05) were found by analysis of variance, comparing lactic acid production in the control fermented colostrum (0.399 g/100 ml) and molasses (0.504 g/100 ml), as well as ground sorghum fermented colostrums (0.649 g/100 ml). The lowest amino acids degradation occurred in the sorghum fermented colostrum, while the control colostrum revealed the greatest degradation. No significant differences were found by analysis of variance comparing pH, crude protein percentage, and moisture of the two treatments and of the control. It is concluded that the addition of ground sorghum to fresh bovine colostrum increases the lactic acid content post-fermentation. It also reduces the amino acids degradation, resulting in an improved product for feeding calves.


In vivo protection of the marjoram (Origanum majorana Linn.) essential oil in the cutaneous sporotrichosis by Sporothrix brasiliensis.
Thirty Wistar rats subcutaneously infected by an itraconazole-resistant Sporothrix brasiliensis received the oral daily treatment (n = 10, each) of control (CTL, saline solution), itraconazole (ITZ, 10 mg/kg) and marjoram essential oil (MRJ, 80 mg/kg) for 30 days. Weekly, the clinical evaluation and euthanasia for histopathology and fungal burden were performed. Only animals from MRJ evolved to the remission of the cutaneous lesion with a mild to absent presence of yeasts in footpad, besides decreased the fungal burden in the systemic organs compared to CTL and ITZ (p < 0.05), preventing the fungal spread, mainly in the liver and spleen. The antifungal activity may have been attributed to the majority composition of terpinen-4-ol (34.09%), γ-terpinene (14.28%) and α-terpinene (9.6%), which the mode of action was at the level of ergosterol complexation. These findings highlighted the antifungal and the systemic protective effects of MRJ, supporting the promising use in the treatment of cutaneous sporotrichosis.


Increased antidepressant use in patients prescribed beta-blockers.
Little information exists on the epidemiology of central nervous system side effects in patients taking antihypertensive medications. We examined prevalence rates of tricyclic antidepressant (TCA) use among a random sample (N = 143,253) of Medicaid recipients. The TCA use was compared for patients taking any of seven antihypertensive agents and for those prescribed insulin or oral hypoglycemic agents. Use of TCA was significantly higher in patients taking beta-blockers (23% over two years) than for patients taking hydralazine or hypoglycemics (both 15%) or methyldopa or reserpine (both 10%). Prevalence rate ratios revealed a risk of being prescribed a TCA of 1.5 (95% confidence interval, 1.4 to 1.7) for patients receiving beta-blockers relative to patients receiving hydralazine or hypoglycemics. beta-Blocker use may be an important cause of iatrogenic depression among hypertensive patients.


Frequency of metabolic syndrome and the food intake patterns in adults living in a rural area of Brazil.
Metabolic syndrome (MetS), a risk factor for atherosclerosis and coronary heart disease, is related to an inadequate food intake pattern. Its incidence is increasing among Brazilian adults, including those living in rural areas. Our aim was not only to describe the frequency of MetS in adults with or without MetS but also to compare their food intake pattern as assessed by the healthy eating index (HEI) and serum albumin and C reactive protein (CRP) levels. Men and women (n = 246) living in a small village in Brazil were included. MetS was characterized according to the adult treatment panel (ATP III) criteria. Groups were compared by chi-square, student t or Mann-Whitney tests. MetS was diagnosed in 15.4% of the cases. The MetS group showed higher CRP (1.8±1.2 vs. 1.0±0.9 mg/dl) and lower albumin (4.3±0.3 vs. 4.4±0.3 g/dl) serum levels compared to the control group. Additionally, the MetS group showed lower scores (median[range]) in the HEI compared to the control group (53.5[31.2-78.1] vs 58[29.7-89.5], respectively). The MetS group also had decreased scores for total fat and daily variety of food intake. The results suggest that adults with MetS displayed chronic mild inflammation and a poorer food intake pattern than the control group.