The Predictive Value of Tagalog Voice Morphology in Filler-Gap Dependency Formation.
Research has shown that when processing filler-gap dependencies, comprehenders do not wait until they encounter all of the bottom-up information in the input. Instead, they use various types of linguistic information to predictively posit a gap that would allow the dependency to be resolved. They can use syntactic (Traxler and Pickering, 1996), lexical (Trueswell et al., 1994), morphological (Kamide et al., 2003), and prosodic (Nagel et al., 1994) information. Here we examine whether Tagalog comprehenders use the language's voice morphology to guide their incremental interpretations. We hypothesized that voice allows comprehenders to commit to an interpretation upon encountering the verb, since they have information about the event structure at this point in time and by virtue of the voice morphology, the thematic role of the filler. In experiment 1, using an acceptability judgment study, we found that comprehenders differed in how they used the different voices in different filler-gap contexts to detect the licitness of displacements. These differences may have consequences for how voice is used in real-time. In experiments 2 and 3, using the stops-making-sense paradigm (Boland et al., 1990), we found that comprehenders used voice as a cue to actively associate the filler with the gap. However, in experiment 3, the way in which they used voice varied by type and varied across types of filler-gap dependencies. We argue that comprehenders were using construction-specific cue validities when processing filler-gap dependencies. However, they also engaged with other classes of linguistic information, including (but not limited to) information about the structural similarities and the thematic complexity of the dependencies involved, and the relative frequency of the different types of voices in the language. These interactions resulted in processing asymmetries.


Plasma levels of thrombin activatable fibrinolysis inhibitor antigen in active and inactive inflammatory bowel disease.
The clinical course of patients with inflammatory bowel disease (IBD) is frequently complicated by thromboembolic events and may involve the arterial and venous systems. Although not uniformly documented, several studies document substantial alterations in markers of coagulation and fibrinolysis in patients with IBD. 45 patients with IBD (31 UC,14 CD) were included in the study. Age and sex matched 16 volunteers were used as a control group. TAFI antigen was determined using an ELISA kit VisuLiseTM for quantitative measurement. Inflammatory parameters such as white blood cell, platelet levels, erythrocyte sedimentation rate, C-reactive protein were found to be significantly higher in active disease group compared to inactive patients. Coagulation parameters of prothrombin time, activated partial thromboplastin time and d-dimer levels showed no significant difference between active and inactive IBD. Fibrinogen levels were significantly higher in clinically active IBD patients. Plasma TAFI levels demonstrated no significant difference between active and control, inactive and control as well as active and inactive groups. We observed no significant changes in levels of β-TG and PF-4 between active and inactive disease group. We studied plasma TAFI levels in IBD. In conclusion, plasma TAFI levels does not appear to represent to be a marker of activation in IBD in contrast to literature. So further studies covering more patients with different clinic and disease activity status might improve the perspective on this issue.


Mercury in tunas and blue marlin in the North Pacific Ocean.
Models and data from the North Pacific Ocean indicate that mercury concentrations in water and biota are increasing in response to (global or hemispheric) anthropogenic mercury releases. In the present study, we provide an updated record of mercury in yellowfin tuna (Thunnus albacares) caught near Hawaii that confirms an earlier conclusion that mercury concentrations in these fish are increasing at a rate similar to that observed in waters shallower than 1000 m. We also compiled and reanalyzed data from bigeye tuna (Thunnus obesus) and blue marlin (Makaira nigricans) caught near Hawaii in the 1970s and 2000s. Increases in mercury concentrations in bigeye tuna are consistent with the trend found in yellowfin tuna, in both timing and magnitude. The data available for blue marlin do not allow for a fair comparison among years, because mercury concentrations differ between sexes for this species, and sex was identified (or reported) in only 3 of 7 studies. Also, mercury concentrations in blue marlin may be insensitive to modest changes in mercury exposure, because this species appears to have the ability to detoxify mercury. The North Pacific Ocean is a region of both relatively high rates of atmospheric mercury deposition and capture fisheries production. Other data sets that allow temporal comparisons in mercury concentrations, such as pacific cod (Gadus macrocephalus) in Alaskan waters and albacore tuna (Thunnus alalunga) off the US Pacific coast, should be explored further, to aid in understanding human health and ecological risks and to develop additional baseline knowledge for assessing changes in a region expected to respond strongly to reductions in anthropogenic mercury emissions. Environ Toxicol Chem 2017;36:1365-1374. © 2017 SETAC.


Cancer preventive properties of ginger: a brief review.
Ginger, the rhizome of Zingiber officinalis, one of the most widely used species of the ginger family, is a common condiment for various foods and beverages. Ginger has a long history of medicinal use dating back 2500 years. Ginger has been traditionally used from time immemorial for varied human ailments in different parts of the globe, to aid digestion and treat stomach upset, diarrhoea, and nausea. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory activities, and some of them exhibit cancer preventive activity in experimental carcinogenesis. The anticancer properties of ginger are attributed to the presence of certain pungent vallinoids, viz. [6]-gingerol and [6]-paradol, as well as some other constituents like shogaols, zingerone etc. A number of mechanisms that may be involved in the chemopreventive effects of ginger and its components have been reported from the laboratory studies in a wide range of experimental models.


Clinical manifestations of head and neck cancer in pediatric patients, an analysis of 253 cases in a single Brazilian center.
Pediatric head and neck cancer (PHNC) is rare and its nonspecific clinical manifestations may often lead to delayed diagnosis. We aimed to describe the signs, symptoms, and clinicopathological characteristics of PHNC. Medical records were retrospectively reviewed for all PHNC cases diagnosed from 1986 to 2016 affecting patients aged 19-years and younger from a tertiary referral center in Brazil. Demographic variables, anatomical site of primary tumors, histopathological diagnoses, signs and symptoms, and patterns of misdiagnosis were collected and interpreted by statistical and descriptive analysis. A total of 253 PHNC cases were included. The mean age was 9.3 years and male patients were more frequently affected (60.9%). Burkitt lymphoma (23.7%), nasopharyngeal carcinoma (15.8%), and rhabdomyosarcoma (15.4%) were the most common cancer types. The nasopharynx (28.9%), cervical/lymph node region (25.3%), and craniofacial bones (8.3%) were the predominant anatomical sites. Tumor/swelling (68.4%), was the clinical finding often presented. The univariable analysis showed association between tumor histology and clinical variables such as sex (p=0.022), age (p<0.0001), anatomical location (p<0.0001) tumor/swelling (p=0.034), pain (p=0.031), systemic/general manifestations (p=0.004), nasal/breathing alterations (p=0.012), orbital/ocular alterations (p<0.0001). Misdiagnosis such as tonsillitis, otitis, and abscess were frequent. Although the clinical findings of PHNC are often unspecific, this study provided signs and symptoms with significant correlations between tumor histology. The suspicion of malignancy should be considered when the main signs and symptoms reported here appear and persist, in order to conduct a timely diagnosis.


The Synucleinopathies: Twenty Years On.
In 2017, it is two hundred years since James Parkinson provided the first complete clinical description of the disease named after him, fifty years since the introduction of high-dose D,L-DOPA treatment and twenty years since α-synuclein aggregation came to the fore. In 1998, multiple system atrophy joined Parkinson's disease and dementia with Lewy bodies as the third major synucleinopathy. Here we review our work, which led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp-Lantos bodies, as well as what has happened since. Some of the experiments described were carried out in collaboration with ML Schmidt, JQ Trojanowski and VMY Lee.


Toward a Wirelessly Powered On-Lens Intraocular Pressure Monitoring System.
This paper presents a wireless on-lens intraocular pressure monitoring system, comprising a capacitance-to-digital converter and a wirelessly powered radio-frequency identification (RFID)-compatible communication system, for sensor control and data communication. The capacitive sensor was embedded on a soft contact lens of 200 μm thickness using commercially available biocompatible lens material, to improve compliance and reduce user discomfort. The sensor chip was shown to achieve effective number of bits greater than 10 over a capacitance range up to 50 pF while consuming only 64-μW power. The on-lens capacitive sensor could detect dielectric variation caused by changes in water content from a distance of 2 cm by using incident power from an RFID reader at 20 dBm. The maximum detectable distance was 11 cm with 30-dBm incident RF power. The rise in eye tissue temperature under 30-dBm RF exposure over an interval of 1 s was simulated and found to be less than 0.01°C.


[Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives bearing dithiocarbamate chains].
A series of 4(3H)-quinazolinone derivatives bearing dithiocarbamate side chains have been synthesized through the reaction of 6-bromomethyl-2-methyl-4(3H)-quinazolinone with CS2 and various amines in the presence of anhydrous K3PO4, and their structures were confirmed with ESI-MS, H NMR, elemental analysis or HRMS. The target compounds 8a -8q were tested for their in vitro antitumor activity against human myelogenous leukaemia K562 and human Hela cell lines by means of colorimetric MTT assay. Among the tested compounds, 8q exhibited in vitro inhibitory activity against K562 and Hela cells with IC50 values of 0.5 and 12.0 micromol x L(-01), respectively. Therefore, compound 8q is worthy to be a lead compound for the design and synthesis of new antitumor agents.


The effect of carrier technetium in the preparation of 99mTc-human serum albumin.
Accumulation of daughter 99Tc in 99Mo-99mTc generator systems may adversely affect the preparation of certain 99mTc radiopharmaceuticals. In a study of the effect of "carrier" technetium on the radiochemical purity of 99mTc-human serum albumin, varying amounts of 99Tc were added to a commercially available electrolytic kit. The maximum amount of 99Tc that could be added to such a kit and still maintain radiochemical purity above 90% was about 3 X 10(15) atoms. When kits containing 10(16) 99Tc atoms were electrolyzed for the conventional 42 sec, the radiochemical purity was only 50.8%. However, when the electrolysis time was varied, it was found that electrolysis for 80 sec yielded a product with greater than 90% radiochemical purity. Four solutions to the problem created by the 99Tc carrier effect are described.


High-energy, high-resolution x-ray imaging on the Trident short-pulse laser facility.
With the completion of the Trident laser facility upgrade, 200 TW high-energy laser pulses are now capable of producing x-ray pulses with energies in the range of 15-40 keV, which will be used for high-spatial resolution radiography. A diagnostic suite is being developed on the laser system to investigate and characterize the x-ray emission from high-Z targets. This includes charge coupled device based single-photon counters, imaging plates, a high-energy electronic imager, spectral diagnostics, and optical and x-ray spot size diagnostics. We describe recent x-ray results from a commissioning campaign as well as describe the development and design of a high-energy spectrometer. X-ray radiographs taken at 22 keV with a spatial resolution of 25 mum are a first demonstration on this facility of high-energy, high-spatial resolution capability.


[Biological role of insulin: transformation of carnivores leaving in the ocean into herbivores living on the dry land. Development of the biological function of locomotion and kinetic parameters of the body.]
Phylogenetic theory of general pathology draws researchers' attention to the following aspects of the biological effects of insulin. 1. Phylogenetically, in vivo insulin is primarily involved in the metabolism of fatty acids (FA) and only in the second turn in glucose metabolism; regulation of FA metabolism in cells started millions of years earlier than that of glucose metabolism. Phylogenetically late insulin blocks lipolysis only in phylogenetically late insulin-dependent subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. 2. Biological role of insulin consists in the formation of the biological function of locomotion, i.e., movement arising from contraction of striated myocytes provided with substrates (FA and glucose) for energy production as macroergic ATP. 3. Biological destiny of phylogenetically late insulin is transformation of carnivorous (fish-eating) animals living in the ocean into herbivores living on the dry land. 4. Insulin has formed in vivo highly efficient oleic variant of FA metabolism instead of phylogenetically early less efficient palmitic variant. 5. Biologically, insulin is destined for providing cells with energy and perfection of physical activity and kinetic parameters of the organism. According to phylogenetic theory of general pathology and basic principles of endocrinology, clinical cases should be regarded as: 1. rare structurally-related insulindeficient type I diabetes mellitus, 2. rare structurally-related (receptor pathology) hyperinsulinemic type II diabetes mellitus, and 3. a great number of patients with functional disorders in the hormone activity, insulin resistance syndrome, metabolic syndrome and obesity. We believe that the food of herbivores should contain palmitic acid in the amounts that hepatocytes can esterify into oleic very low density lipoproteins and cells can internalize as ligand oleic by apoЕ/В-100 endocytosis without formation of low density lipoproteins.


Development of a preoperative questionnaire to improve satisfaction with hallux valgus repair: A Delphi study.
Satisfaction with hallux valgus repair is often poor, despite good surgical outcomes. Many tools have been developed to assess the outcome of the procedure; however none evaluate the association between the initial motive for repair and the reasons for post-surgical dissatisfaction. The aim of this study was to develop a new tool to analyse the subjective and objective expectations of individuals during a pre-operative consultation for hallux valgus repair in order to improve post-surgical satisfaction. We first collected the reasons for dissatisfaction with repair from the medical files of dissatisfied individuals. Then, a steering committee of 4 French experts in the management of hallux valgus designed a questionnaire based on the reasons for dissatisfaction. We then used the DELPHI method to validate the questionnaire: we submitted the questionnaire to a panel of 34 francophone experts in hallux valgus repair for rating in 4 rounds. The medical files of 853 individuals were reviewed and a 52-item questionnaire relating to expectations from hallux valgus surgery was drafted. After the 4 rounds, a final 44 item questionnaire reached consensus. Thirteen items related to clinical and psychological profile, 5 to pain, 9 to physical activity, 4 to aesthetics and 13 to footwear. This tool should facilitate gathering of individuals' expectations from hallux valgus repair to ensure realistic goals and reduce post-surgical dissatisfaction.


Inhibitory effects of Olea ferruginea crude leaves extract against some bacterial and fungal pathogen.
This work aimed to evaluate the inhibitory effects of Olea ferruginea crude leaves extract that are commonly used as remedy to cure infections in the tribal (Khyber Agency) areas of Pakistan against some of bacterial and fungal pathogens. The crude n-hexane fraction was appreciably active against both gram positive and negative microorganisms (MIC ranged from 7.5 to 15 mg/ml) followed by butanol fraction (MIC 15 to 30 mg/ml). Conversely least biological activity was shown by chloroform (30mg/ml) and methanol (15 to 30mg/ml) crude fractions. The MBC observed for all crude fractions was same or 2 times higher when compared with MIC for all crude extract fractions. Likewise all the fractions showed activity against Aspergillus niger and maximum zones of inhibition were shown by the n-hexane fraction (14 ± (0.02), butanol (13 ± (0.02) followed by methanol (9 ± (0.05) and chloroform fractions (7 ± (0.02). These results clearly imitate the antibacterial and antifungal potential of Olea ferruginea and hence we recommend the whole plant for further futuristic studies.


Can open label placebos improve pain and gluten tolerance via open label placebos in fibromyalgia patients? A study protocol for a randomised clinical trial in an outpatient centre.
Fibromyalgia syndrome (FMS) is defined as a medical condition with chronic widespread musculoskeletal pain accompanied by mood disorders, fatigue and sleep disturbances. Treatment of this condition can often be challenging. As nutrition in general and nutritional interventions in the context of illness management become more and more important, current research also focuses on the relevance of diets for FMS, including gluten as field of interest. To date, there is no clear evidence that a gluten-free diet or other nutritional interventions are significantly important for the reduction of pain in the context of FMS. Only a very few studies show that FMS patients respond to a gluten-free diet and that cytokine production (also in FMS) can be reduced through the change. However, these studies have not investigated whether and to what extent cognitive factors, such as the expectation of symptom reduction triggered by diet, play a role. Recent research shows that treatment expectation plays an important role in the course of the disease and in the effectiveness of treatment approaches. For example, there are promising pain treatment options using open-label placebos (OLPs), which show that expectation alone, rather than the pharmacological substance of medication, can reduce pain experience. In our study protocol, we hypothesise that treatment expectation can be positively influenced by the given information regarding the placebos, resulting in improved treatment outcomes for pain and indigestions. In this trial, patients with FMS will undergo a food challenge and take an OLP (patients will be informed about the placebo), followed by a 3-week OLP treatment. The subjects will be randomised into four groups: (a) gluten-free porridge+neutral OLP instructions; (b) gluten-free porridge+positive OLP instructions; (c) gluten-containing porridge+neutral OLP instructions and (d) gluten-containing porridge+positive OLP instructions. Patients will be recruited via different institutions and support groups in Hamburg. The inclusion criteria are (a) diagnosed FMS, (b) absence of wheat allergy, coeliac disease or pain-related red flags and (c) being a minimum age of 18 years. The study requires 100 subjects to assess the primary outcomes: pain intensity and occurence of indigestion. Secondary outcomes are functional capacity, treatment expectation, and different pain-related and inflammation-related blood parameters. The measure time points will be before and after the food challenge and before and after the 3-week OLP treatment. Ethical approval was obtained in October 2021 from the Hamburg Medical Ethics Council. The results of the study will be disseminated through publications, presentations and conference meetings. German Clinical Trials Register (DRKS; DRKS00027130).


Lester R. Dragstedt 1893-1975. Chronic ulcerative colitis. A summary of evidence implicating Bacterium necrophorum as an etiologic agent.
Lester Dragstedt was born in Anaconda, Montana, the son of Swedish immigrant parents. His entire college and professional education took place at the University of Chicago, where he received a B.S. degree in 1915, a master's degree in physiology in 1916, a Ph.D. in physiology in 1920, and the M.D. degree (from Rush) in 1921. His first academic appointment was as a physiologist at the State University of Iowa. In 1925 Dragstedt was recruited by Dallas B. Phemister to help design the new University Hospital research facilities on the campus of the University of Chicago. Following completion of this responsibility Phemister appointed Dragstedt as Associate Professor of Surgery, stating, "I can teach surgery to a physiologist; I am interested in teaching physiology to surgeons." In 1947 Dragstedt succeeded Phemister as chairman, a post he occupied until his retirement in 1959. Dragstedt was regarded as a skilled clinician as well as a dexterous and artistic surgeon. But he was particularly recognized for his contributions as physiologist-surgeon in the treatment of diseases of the pancreas, parathyroids, and especially diseases of the stomach. In 1943, he performed a transthoracic vagotomy on a patient with a duodenal ulcer who refused to accept the standard operation, subtotal gastrectomy. A lesser known but classical work of Dragstedt and his coworkers is reproduced here for this series. Dragstedt was the originator of the skin-grafted ileostomy in the treatment of ulcerative colitis. The author describes a complete "take" of the split-thickness graft in four patients, although he observed that the "resulting ileostomy looked somewhat like a penis." One can only surmise about the psychologic disability that would be produced. The stoma could, however, be fitted with an appliance that would minimize the risk of abdominal wall digestion. When reading the article and understanding the experimental studies proposing the possible causative organism of ulcerative colitis, one is impressed by Dragstedt's creative thinking. Dragstedt's renown as a basic scientist was illustrated by his election to the National Academy of Sciences. Following his Chicago retirement he became again a full-time physiologist with appointments as research professor in both the department of surgery and the department of physiology at the University of Florida College of Medicine. Active until the end, he died at his summer home on Elk Lake, Michigan on July 16, 1975.


Cholera outbreak in Homa Bay County, Kenya, 2015.
Cholera is among the re-emerging diseases in Kenya. Beginning in December 2014, a persistent outbreak occurred involving 29 out of the 47 countries. Homa Bay County in Western Kenya was among the first counties to report cholera cases from January to April 2015. This case study is based on an outbreak investigation conducted by FELTP residents in Homa Bay County in February 2015. It simulates an outbreak investigation including laboratory confirmation, active case finding, descriptive epidemiology and implementation of control measures. This case study is designed for the training of basic level field epidemiology trainees or any other health care workers working in public health-related fields. It can be administered in 2-3 hours. Used as adjunct training material, the case study provides the trainees with competencies in investigating an outbreak in preparation for the actual real-life experience of such outbreaks.


Isolated vulval splitting--is this normal or pathological?
Vulval splitting may be seen in association with clinically apparent dermatological disease but occasionally occurs in patients presenting with dyspareunia only. These patients usually have normal-looking vulvas on examination, apart from splitting. They are usually diagnosed as vulval vestibulitis. We have biopsied several patients with isolated vulval splitting with surprising results. Between the months of October 2000 and April 2002, 310 new patients were seen in the vulval clinic at Hope Hospital, which is a tertiary referral centre. Among these were nine cases of isolated vulval splitting, eight of which had histological features of dermatological disease on vulval biopsies. There were three cases of lichen planus, three with chronic dermatitis and two with candidiasis.


Executive Function and Narrative Language Abilities in Emergent Bilingual Preschoolers: An Exploratory Study.
In light of the importance of preschool oral narrative skills as precursors to literacy, this exploratory study examined expressive language skills among emergent bilingual Latine preschoolers using a naturalistic personal narrative task. To understand the factors that support language use in the personal narrative context for this population, we examined the contribution of children's executive function (EF) skills to their narrative language abilities. Children completed two subtests from the Preschool Self-Regulation Assessment to measure EF and produced two personal narratives in response to conversational prompts. A series of linear regressions were used to evaluate the relation between children's EF skills and their narrative production ability, narrative organization, and expressive language skills derived from automated analyses of narrative samples. EF was found to predict children's ability to produce a personal narrative but not the language skills children demonstrated in these narratives. The current findings suggest that EF is implicated in emergent bilingual Latine children's narrative abilities. At the preschool age, the contribution of EF to narrative language production is apparent in the global task of producing a narrative, rather than in the organizational or linguistic features of the narrative. As such, supporting both EF and narrative skills might be an important means of facilitating preliteracy among bilingual children.


Primiparous women differ from multiparous women after early discharge regarding breastfeeding, anxiety, and insecurity: A prospective cohort study.
Breastfeeding and factors influencing breastfeeding are essential when considering the association between parity and neonatal and maternal morbidity risks when mothers are discharged within 24 hours after birth. However, there is a lack of studies examining the effect of parity and breastfeeding in a setting where all healthy mothers are recommended discharge four hours after birth. Therefore, this study examined the association between parity and the time for discharge, breastfeeding, and factors influencing breastfeeding. The study was designed as a prospective cohort study. Data were obtained from questionnaires at one and at six weeks after birth, and combined with registered data. All 147 included mothers were healthy, with an uncomplicated birth and a healthy newborn, discharged within 24 hours after birth. This study documented that primiparous women had a higher relative risk (RR=2.62; 95% CI: 1.35-5.10) of having doubts about infant feeding after discharge than multiparous women. Furthermore, 54% of primiparous women contacted the maternity ward after discharge compared to 27% of multiparous women. Twice as many primiparous than multiparous women felt anxious or depressed at one and at six weeks after birth. Finally, the study documented that 13% of primiparous women and 5% of multiparous women discharged within six hours after birth perceived the time before discharge to be too short. Primiparous women differ from multiparous women regarding breastfeeding, insecurity, and anxiety. Special attention towards primiparous women and a follow-up strategy that allows the mothers to contact the maternity ward after early discharge is recommended.


Self-Reported vs. Measured Height, Weight, and BMI in Young Adults.
Self-reported height and weight, if accurate, provide a simple and economical method to track changes in body weight over time. Literature suggests adults tend to under-report their own weight and that the gap between self-reported weight and actual weight increases with obesity. This study investigates the extent of discrepancy in self-reported height, weight, and subsequent Body Mass Index (BMI) versus actual measurements in young adults. Physically measured and self-reported height and weight were taken from 1562 students. Male students marginally overestimated height, while females were closer to target. Males, on average, closely self-reported weight. Self-reported anthropometrics remained statistically correlated to actual measures in both sexes. Categorical variables of calculated BMI from both self-reported and actual height and weight resulted in significant agreement for both sexes. Researcher measured BMI (via anthropometric height and weight) and sex were both found to have association with self-reported weight while only sex was related to height difference. Regression examining weight difference and BMI was significant, specifically with a negative slope indicating increased BMI led to increased underestimation of weight in both sexes. This study suggests self-reported anthropometric measurements in young adults can be used to calculate BMI for weight classification purposes. Further investigation is needed to better assess self-reported vs measured height and weight discrepancies across populations.


Serotonin Transporter Associated Protein Complexes Are Enriched in Synaptic Vesicle Proteins and Proteins Involved in Energy Metabolism and Ion Homeostasis.
The serotonin transporter (SERT) mediates Na+-dependent high-affinity serotonin uptake and plays a key role in regulating extracellular serotonin concentration in the brain and periphery. To gain novel insight into SERT regulation, we conducted a comprehensive proteomics screen to identify components of SERT-associated protein complexes in the brain by employing three independent approaches. In vivo SERT complexes were purified from rat brain using an immobilized high-affinity SERT ligand, amino-methyl citalopram. This approach was combined with GST pulldown and yeast two-hybrid screens using N- and C-terminal cytoplasmic transporter domains as bait. Potential SERT associated proteins detected by at least two of the interaction methods were subjected to gene ontology analysis resulting in the identification of functional protein clusters that are enriched in SERT complexes. Prominent clusters include synaptic vesicle proteins, as well as proteins involved in energy metabolism and ion homeostasis. Using subcellular fractionation and electron microscopy we provide further evidence that SERT is indeed associated with synaptic vesicle fractions, and colocalizes with small vesicular structures in axons and axon terminals. We also show that SERT is found in close proximity to mitochondrial membranes in both, hippocampal and neocortical regions. We propose a model of the SERT interactome, in which SERT is distributed between different subcellular compartments through dynamic interactions with site-specific protein complexes. Finally, our protein interaction data suggest novel hypotheses for the regulation of SERT activity and trafficking, which ultimately impact on serotonergic neurotransmission and serotonin dependent brain functions.


[The effect of Chinese drug therapy on the patients with male infertility. 1. Concomitant administration of ninjinto and hachimijiogan on patients with male infertility].
Ten patients (age range, 28 to 36 years with a mean of 32.3 years) with male infertility were orally given Ninjinto and Hachimijiogan concomitantly at a daily dose of 7.5 g each for 96 to 182 days (mean 116.8 days). Ten percent of these patients showed remarkable improvement in their volume of semen, 10% showed improvement and 80.0% showed no improvement. Thirty percent of these patients showed remarkable improvement in the number of sperm, 10.0% showed improvement, and 60.0% showed no improvement. Twenty percent of these patients showed remarkable improvement in their sperm mobility, 30.0% showed improvement and 50.0% showed no improvement. The fertility index was improved markedly in 60.0%, improved in 20.0% and not improved in 20.0%. The spouses of 2 patients became pregnant. Side effects were seen in only 30.0% (epigastralgia) of these patients. Laboratory examination of these patients revealed no significant change. These results suggested that concomitant administration of Ninjinto and Hachimijiogan is effective on patients with male infertility.


Strong philopatry derived from capture-recapture records does not lead to fine-scale genetic differentiation in lesser kestrels.
1. The integration of capture-recapture and molecular approaches can improve our understanding of the consequences of habitat fragmentation on population connectivity. Here we employed microsatellites to test dispersal hypotheses derived from intense and long-term ringing programmes of the lesser kestrel Falco naumanni in Western Europe. 2. Re-encounters of 1308 marked individuals in Spain have revealed that most first-time breeders settled within 10 km from their natal colony, with a negative association between dispersal and geographical distance. Although these findings would predict fine-scale spatial patterns of genetic differentiation, the genetic impact of rarely reported events concerning long-distance effective dispersal (> 100 km) is unknown. 3. First, we investigated a spatially structured and geographically isolated population located in north-eastern Spain, where capture-recapture records and genetic data could be appropriately compared over similar spatial and temporal scales. Spatial autocorrelation analyses (N = 174 nestlings from different broods) did not reveal either significant differences in average relatedness at any distance class nor decreased relatedness as a function of distance. At a broader spatial scale, Bayesian analysis of population structure (N = 432 nestlings) indicated panmixia across Western Europe. However, F(ST) comparisons between four geographically distinct populations indicated low but significant genetic differentiation. 4. Our genetic data would therefore challenge traditional assumptions associating philopatry with the emergence of fine-scale genetic structuring. This could be because even low levels of gene flow are enough to preclude the development of local genetic structure. Nevertheless, the analysis of a geographically isolated and small population from Southern France exemplifies a situation in which restricted dispersal has translated into weak but consistently significant genetic differentiation. 5. Relevant to conservation genetics and evolutionary biology, our results may lessen the genetic concerns derived from population fragmentation at relatively small geographical scales in species with apparently limited dispersal abilities, but raises concerns about increased genetic divergence in small and isolated demes.


[Medical treatment of the Raynaud phenomenon].
The medical treatment of Raynaud's phenomenon must be adapted to each particular case. Benign cases do not require drug therapy. Various substances seem able to relieve the most severe cases (calcium blockers, alpha-blockers). Prostaglandins perfusions and plasmaphoresis must be reserved for the most severe cases, with trophic disorders not improved with less aggressive treatments.


Midgut microbiota of the malaria mosquito vector Anopheles gambiae and interactions with Plasmodium falciparum infection.
The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.


[Validation of a Spanish version of the International Consultation on Incontinence Questionnaire Short-Form].
The International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) allows the assessment of urinary incontinence management results. To validate the ICIQ-SF in a Chilean population. An approved Spanish version of the ICIQ-SF was applied in two opportunities (separated by a mean of 44 days) to 52 women consulting for urinary incontinence in a public hospital and to 25 asymptomatic female workers of the same hospital. Content validity, internal consistency and construct validity of the ICIQ-SF were evaluated. The ages of surveyed women ranged from 21 to 80 years. Internal consistency measured using Cronbach alpha was 0.87. Intra observer agreement, measured using pondered Kappa, was 0.84. 0.86 and 0.8 for each of the three components of the questionnaire, respectively. This Spanish version of the ICIQ-SF meets the requirements to be used in the Chilean population.


[Malaria in Turkey and 14 years of clinical experience].
In this retrospective study, the epidemiologic and clinical characteristics of 105 adult malaria patients, who had been hospitalized between the period of 1992 and 2006 were evaluated. Nineteen percent of the patients were female, and the mean age was 28 +/- 10 years. Fifty percent of the patients acquired the infection in Southeastern Anatolia, while they were on military duty. The most common complaints were rigor (93%), fever (90%), sweating (90%), headache (76%), nausea (45%), and fatigue (38%). The most common physical examination findings were splenomegaly (86%) and hepatomegaly (62%). Anemia was detected in 23%, leukopenia in 47%, thrombocytopenia in 73%, two fold increase in ALT or AST enzyme levels in 32% of the patients. Plasmodium vivax was detected in 101 (96%) patients, whereas P. falciparum was detected in 4 patients (4%). Although the number of malaria cases in Turkey is declining in recent years, the febrile patients with a history of travel to the endemic regions should raise the suspicion of malaria.


Effects of lithium on calmodulin-stimulated adenylate cyclase activity in cortical membranes from rat brain.
The influence of lithium on calmodulin-stimulated adenylate cyclase activity has been studied in vitro and after chronic treatment. Chronic lithium treatment decreased calcium-calmodulin-stimulated adenylate cyclase activity in rat cortical membranes, while no effect was observed on GTP-stimulated activity. Lithium in vitro inhibited adenylate cyclase activity stimulated by isoprenaline, GTP or calcium-calmodulin. Calcium-calmodulin-stimulated activity was more sensitive to lithium (2 mM) than isoprenaline- and GTP-stimulated activities (5 mM) and activities by these agents combined. Lithium had no effect on the unstimulated enzyme activity. The inhibitory effect of lithium in vitro on calcium-calmodulin-stimulated adenylate cyclase activity was antagonized by magnesium. The inhibition induced by lithium in vitro on the GTP-stimulated adenylate cyclase activity was increased by substituting manganese for magnesium in the assay media. Furthermore, the manganese-stimulated activity was also reduced by lithium. The latter effect was not observed in calmodulin-depleted membranes, but the inhibitory effect of lithium could be restored by addition of exogenous calmodulin. The present results suggest that lithium might influence the interaction of calmodulin with the enzyme and/or interfere with the divalent cation site(s) on the adenylate cyclase system.


Newborn screening and prenatal diagnosis for Rett syndrome: implications for therapy.
Most girls with Rett syndrome develop normally prior to the appearance of the typical symptoms. A presymptomatic phase is also observed in many inborn errors of metabolism that are included in newborn screening programs. Diagnostic testing for mutations or large genomic rearrangements involving methyl-CpG binding protein 2 gene (MECP2) is highly sensitive and identifies mutations in up to 95% of female individuals with classic Rett syndrome. This has prompted some to ask whether MECP2 testing should be included in newborn and prenatal screening programs. We review current and evolving practices in these programs, emphasizing their relevance to Rett syndrome. The availability of a reliable test and the characteristic early latent phase, which creates a window of opportunity for early treatment, favor universal newborn screening for Rett syndrome. However, the high cost and the lack of an effective presymptomatic treatment make universal newborn screening for Rett syndrome impractical at present. In contrast, prenatal diagnosis should be offered to the parents of an affected child if the responsible mutation has been identified in the index case.


Minor and major health: a Nietzschean reading.
This paper aims to discuss the concept of health, understood as multiple and plural. We use Friedrich Nietzsche's philosophical thought as an analytical tool, allowing us to reach a typology involving minor and major health. While the first is normative and sustained by an ideal of healing, the second is an expanding strength, a condition constantly achieved. If minor health follows a preset life moralization script, major health relates to the expanded living being, which affirms its creative nature and transcends established rules. The notion of major health embraces the overcoming of imperative models rooted in biomedicine-based practices and approaches to health collective actions. Nevertheless, on the one hand, if this movement extends the co-participatory nature between staff and users of the health system, on the other hand, it lacks more radical actions to break with the moral nature of health-disease processes. Not refusing life's own vicissitudes, major health understands the need to incorporate pain and suffering involved in individuation movements.


Knowledge and Awareness of Colorectal Cancer among Undergraduate Students at King Abdulaziz University, Jeddah, Saudi Arabia: a Survey-Based Study.
This study explored the knowledge and awareness about colorectal cancer (CRC) among undergraduate students of one of the leading universities in Saudi Arabia, along with the mode of information access. The present cross-sectional study was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, among students of different faculties. The study questionnaire, containing 28 items, was adapted from surveys identified in the relevant literature. The CRC awareness questionnaire consisted of an awareness section (early CRC signs and symptoms, and risk factors) and a knowledge section. The data were analyzed using the SPSS version 21.0. A total of 525 undergraduate students participated in the study. The majority were females (63.0%) and approximately half (56.8%) were medical students. The majority of the students (82.3%) were aware of CRC, and 68% thought that CRC is a preventable disease. Regarding colorectal cancer screening tests, only one-third of students (33%) had actual knowledge, while the majority of the students (77.0%) thought that there are tests which help in early detection. Only 4% of the participants had a family history of CRC. The majority of the participants (84%) thought that CRC is a disease that can be cured. Almost 50-60% participants had good awareness level regarding risk factors, and signs and symptoms. Regarding knowledge, participant responses varied for family history (52%), age (59%), chronic infection of the colon (72%), obesity and lack of exercise (66%). More than one-third of the students had received information material regarding CRC from their curriculum followed by social media (20.4%), and nearly 40% from other sources such as TV, hospital and mass media. Female participants had significantly better awareness in a few questions regarding CRC awareness as compared to their male counterparts. There was a significant difference observed between medical and non-medical students (<0.001) in overall score of awareness and knowledge about CRC while no significant difference found in gender-wise comparison. Knowledge and awareness of students about CRC were not up to the mark. Medical students and female students had better knowledge in a few areas, but the overall situation is dismal.


Comparison of various sampling schemes and accumulation profiles in covariance spectroscopy with exponentially decaying 2D signals.
Two-dimensional covariance (COV2D) spectroscopy offers an alternative approach to 2D Fourier transformation (FT2D) to obtain homo-nuclear correlation NMR spectra. Considerable saving in experimental time, without loss of resolution, can be achieved by incorporating COV2D with: (i) uniform sampling with a t1 cut-off (CUO) or non-uniform sampling (NUS), and (ii) constant or Gaussian accumulation profiles. We find that covariance treatment, combined with the CUO sampling and Gaussian accumulation profile provides better gain in experimental time, with respect to that required with FT2D NMR. This is in contrast with the maximum entropy (MaxEnt) reconstruction for 2D spectra, which works better with the NUS scheme rather than with the CUO scheme. We further discuss the experimental conditions that define this optimum acquisition, and explain how these parameters can easily be optimized 'on the fly' according to the desired resolution, which is quite sample-dependent.


[Cardiogoniometry in coronary heart disease. A clinical study].
Maximal vectors of depolarization (QRS) and repolarization (ST/T), and the initial QRS-vector of CGM, were measured simultaneously with conventional ECG at rest and during exercise in a population of 85 patients with suspected coronary artery disease (CAD). Coronary angiography served as standard, luminal narrowing of at least 50% in a proximal segment of one or more major coronary arteries being taken to define CAD. CGM showed sensitivity of 0.89 and specificity of 0.64 (vs 0.76 and 0.18 for conventional stress ECG).


Can symptoms help in differential diagnosis between substance-induced vs independent psychosis in adults with a lifetime diagnosis of cocaine use disorder?
The main goal of this study it is explore the psychopathological differences between IPD and SIPD in a sample of 125 adults with a lifetime diagnosis of cocaine disorder recruited from treatment setting and through street contacts. A secondary analysis of six cross-sectional studies was conducted between 2000 and 2010. SIPD and IPD were diagnosed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). 38 subjects (30.4%) were diagnosed with lifetime IPD and 87 (69.6%) with lifetime SIPD. A binomial logistic regression analysis using SIPD as the reference group showed that only previous prison admissions (OR 2.59; 95% CI 1.05, 6.36) and visual hallucinations (OR 5.21; 95% CI 1.54, 17.65) remained significant variables in the group with lifetime SIPD. In the group with lifetime IPD, grandiose delusions (OR 0.19; 95% CI 0.06, 0.60) and disorganized speech (OR 0.16; 95% CI 0.04, 0.61) remained significant. Model predicts the diagnosis of lifetime SIPD with a sensitivity of 80.3% and a specificity of 78.2%. This clinical profile of lifetime SIPD could help distinguish between IPD and SIPD among adults with lifetime diagnosis of cocaine disorder.


Methoxyflurane revisited: tale of an anesthetic from cradle to grave.
Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.


Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel disease.
The human gut is one of the most complex ecosystems, composed of 1013-1014 microorganisms which play an important role in human health. In addition, some food products contain live bacteria which transit through our gastrointestinal tract and could exert beneficial effects on our health (known as probiotic effect). Among the numerous proposed health benefits attributed to commensal and probiotic bacteria, their capacity to interact with the host immune system is now well demonstrated. Currently, the use of recombinant lactic acid bacteria to deliver compounds of health interest is gaining importance as an extension of the probiotic concept. This review summarizes some of the recent findings and perspectives in the study of the crosstalk of both commensal and probiotic bacteria with the human host as well as the latest studies in recombinant commensal and probiotic bacteria. Our aim is to highlight the potential roles of recombinant bacteria in this ecosystem.


Evaluation of the performance of the reduced local lymph node assay for skin sensitization testing.
The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches.


On the Chemistry of Aqueous Ammonium Acetate Droplets during Native Electrospray Ionization Mass Spectrometry.
Ammonium acetate (NH4Ac) is a widely used solvent additive in native electrospray ionization (ESI) mass spectrometry. NH4Ac can undergo proton transfer to form ammonia and acetic acid (NH4+ + Ac- → NH3 + HAc). The volatility of these products ensures that electrosprayed ions are free of undesired adducts. NH4Ac dissolution in water yields pH 7, providing "physiological" conditions. However, NH4Ac is not a buffer at pH 7 because NH4+ and Ac- are not a conjugate acid/base pair (Konermann, L. J. Am. Soc. Mass Spectrom. 2017, 28, 1827-1835.). In native ESI, it is desirable that analytes experience physiological conditions not only in bulk solution but also while they reside in ESI droplets. Little is known about the internal milieu of NH4Ac-containing ESI droplets. The current work explored the acid/base chemistry of such droplets, starting from a pH 7 analyte solution. We used a two-pronged approach involving evaporation experiments on bulk solutions under ESI-mimicking conditions, as well as molecular dynamics simulations using a newly developed algorithm that allows for proton transfer. Our results reveal that during droplet formation at the tip of the Taylor cone, electrolytically generated protons get neutralized by Ac-, making NH4+ the net charge carriers in the weakly acidic nascent droplets. During the subsequent evaporation, the droplets lose water as well as NH3 and HAc that were generated by proton transfer. NH3 departs more quickly because of its greater volatility, causing the accumulation of HAc. Together with residual Ac-, these HAc molecules form an acetate buffer that stabilizes the average droplet pH at 5.4 ± 0.1, as governed by the Henderson-Hasselbalch equation. The remarkable success of native ESI investigations in the literature implies that this pH drop by ∼1.6 units relative to the initially neutral analyte solution can be tolerated by most biomolecular analytes on the short time scale of the ESI process.


The vocational continuum: how to make sense of vocational outcomes after group cognitive behavioural therapy for chronic pain sufferers.
Vocational outcomes following group CBT programmes for patients with chronic pain are scarcely reported within the literature, despite their importance as measures of function. This study reports vocational, physical and psychological outcomes following a group CBT programme for patients suffering chronic pain. The study aimed to examine the vocational situation of chronic pain patients who completed a group CBT programme, using a scale known as the vocational continuum. The scale was developed to measure changes in RTW intention and work status, in an effort to reconceptualise vocational outcomes for this population with respect to the RTW process. A group of patients referred to a hospital pain clinic that went on to complete a group CBT programme were retrospectively surveyed about their vocational status at various time points. Physical outcomes measured included the 12-min walk test, 2-min sit to stand test, 2-min stair climb test and timed 20-m walk test. Psychological outcomes measured included pain intensity, self-efficacy, psychological distress (depression, anxiety and stress), catastrophising and disability. Responses to vocational items including work status, hours of work, intention to RTW and barriers to RTW were incorporated into the vocational continuum. Two hundred and nine (58%) of the 360 patients who completed the group CBT programme between 1998 and 2005 completed the vocational survey. Ninety percent of participants reported that their chronic pain was a barrier to RTW or increasing hours of work pre-CBT. According to the vocational continuum, fifty per cent of the study population advanced toward working full-time (chi(2)(2, N = 163) = 28.87, P < 0.01) and this result was associated with a significant reduction in pain as a reported barrier to RTW or increasing participation in work post-CBT. Significant improvements were seen across all physical and psychological measures for study participants at 1, 6 and 12 month intervals post-CBT. The study demonstrates improvements across physical and psychological measures post-CBT, indicating that participants benefited from reduced levels of pain-related distress and disability. Although retrospective, the study also suggests improvements were made across vocational outcomes. By doing so, the study adds to scant literature reporting on vocational outcomes of group CBT programmes for patients with chronic pain and offers a new scale for measuring and interpreting vocational outcomes for this population.


Iodination-Group-Transfer Reactions to Generate Trisubstituted Iodoalkenes with Regio- and Stereochemical Control.
The regio- and stereodefined synthesis of trisubstituted alkenes remains a significant synthetic challenge. Herein, a method is developed for producing regio- and stereodefined trisubstituted iodoalkenes by diverting intermediates from an iodination-electrophilic-cyclization mechanism. Specifically, cyclized sulfonium ion-pair intermediates are diverted to alkenes by ring-opening with nucleophilic iodide. Alternatively, scavenging of the iodide by AgOTf prevents ring-opening, enabling isolation of the sulfonium ion-pair intermediate. Isolation of the ion pair enables access to complementary reactivity, including ring-opening by alternative nucleophiles (i.e., amines), yielding trisubstituted acyclic alkenes and an example acyclic tetrasubstituted alkene. X-ray crystallographic determination of reaction intermediates and products confirms that the initial electrophilic-cyclization step sets the stereo- and regiochemistry of the product. The products serve as synthetic building blocks by readily participating in downstream functionalization reactions, including oxidation, palladium-catalyzed cross-coupling, and nucleophilic displacement.


[Natural killer (NK) activity of peripheral blood and regional lymph nodes in patients with genitourinary malignant tumors. 2. NK activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes].
We investigated natural killer (NK) activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes in order to examine the host's defence mechanisms against cancer. The materials were obtained from 26 patients with genitourinary cancer and 9 patients with benign diseases, who were used as controls. NK activity was measured by ATP-chemiluminescence (ATP) assay, a new method which is well correlated to the 51Cr-release assay, and T-lymphocyte subsets were stained with anti-Leu-2, -3, -4, -7, and -11 monoclonal antibody. The NK activity of regional lymph nodes was lower than that of the peripheral blood in all 35 cases, and the percentage of Leu 7+ and Leu 11+ cells was in agreement with that of the NK activity detected by ATP assay. In the peripheral blood, the percentage of Leu 3+ cells was lower in high stage patients than it was in low stage patients and controls, but in the regional lymph nodes it was paradoxically higher. The NK activity of regional lymph nodes against autologous tumor cells was low in 8 patients with bladder cancer. It appears from this study that the regional lymph nodes have no function as immunological barriers for metastasis and we therefore conclude that they should be dissected during surgery.


Does industry take the susceptible subpopulation of asthmatic individuals into consideration when setting derived no-effect levels?
Asthma, a chronic respiratory disease, can be aggravated by exposure to certain chemical irritants. The objectives were first to investigate the extent to which experimental observations on asthmatic subjects are taken into consideration in connection with the registration process under the EU REACH regulation, and second, to determine whether asthmatics are provided adequate protection by the derived no-effect levels (DNELs) for acute inhalation exposure. We identified substances for which experimental data on the pulmonary functions of asthmatics exposed to chemicals under controlled conditions are available. The effect concentrations were then compared with DNELs and other guideline and limit values. As of April 2015, only 2.6% of 269 classified irritants had available experimental data on asthmatics. Fourteen of the 22 identified substances with available data were fully registered under REACH and we retrieved 114 reliable studies related to these. Sixty-three of these studies, involving nine of the 14 substances, were cited by the REACH registrants. However, only 17 of the 114 studies, involving four substances, were regarded as key studies. Furthermore, many of the DNELs for acute inhalation were higher than estimated effect levels for asthmatics, i.e., lowest observed adverse effect concentrations or no-observed adverse effect concentrations, indicating low or no safety margin. We conclude that REACH registrants tend to disregard findings on asthmatics when deriving these DNELs. In addition, we found examples of DNELs, particularly among those derived for workers, which likely do not provide adequate protection for asthmatics. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.


Active demethylation of individual genes in intracytoplasmic sperm injection rabbit embryos.
Intracytoplasmic sperm injection (ICSI), as an assisted reproduction technique, has been widely used in animal and human. However, its possible effect on epigenetic changes has not been well studied. To investigate whether ICSI can induce aberrant DNA methylation changes in rabbit preimplantation embryos, we examined the methylation status of the SP-A promoter region and the satellite sequence Rsat IIE by bisulfite-sequencing technology. The SP-A promoter region was extensively demethylated before the first round of DNA replication commences, and the unmethylated status was maintained until morula when dynamic remethylation occurred. A similar but more moderate demethylation process was observed in satellite sequence Rsat IIE. These results are in contrast with the previous reports of no active demethylation in normal rabbit embryos, suggesting that the active demethylation we observed may be induced by ICSI.


Hazard communication: challenges in the pharmaceutical industry.
Several of the major regulations mandating hazard communication programs around the world are reviewed and their applicability to the pharmaceutical industry is discussed. Regulation distinctions that are key to compliance activities are highlighted.


[Role of individual genes in expression of phenotypic properties of the cold-adapted strain A/Leningrad/134/47/57 (H2N2)-a donor of attenuation of live influenza vaccine].
The influenza A/Leningrad/134/47/57 (H2N2) (A/Len/47) cold-adapted virus expresses the ability to reproduce at 25 degrees C (the ca phenotype) and inability to reproduce at 40 degrees C (the ts phenotype). It was attenuated for mice. Reassortants of this donor virus with the genes coding for the surface glycoproteins from the epidemic viruses, i.e. hemagglutinin (HA) and neuraminidase (NA), have been shown to be attenuated, immunogenic and genetically stable. We made attempts to reveal the influence of individual genes from the A/Len/47 ca virus on the expression of some phenotypic properties. Different "single-gene" reassortants were created and investigated using the influenza A/PR/8/34 (H1N1) virus as another parent with the opposite phenotypic properties, i.e. lack of ca+ and ts+ phenotypes and high virulence for mice. We managed to obtain "single-gene" reassortants with PB1, NA and NS genes at this stage of the work. None of them (probably including the M gene as well) could determine the ca or ts phenotypes, nor could the presence of the NA and NS genes from the strain A/Len/47 influence these properties. However, our findings show that the combined influence (synergism) of the PB1 and NS genes from the ca donors results in the ts phenotype of the reassortants. Significant role of the NS gene for attenuation of influenza viruses in mice has been revealed.


Enhanced Bacterial Growth by Polyelemental Glycerolate Particles.
While polyelemental alloys are shown to be promising for healthcare applications, their effectiveness in promoting bacterial growth remains unexplored. In the present work, we evaluated the interaction of polyelemental glycerolate particles (PGPs) with Escherichia coli (E. coli) bacteria. PGPs were synthesized using the solvothermal route, and nanoscale random distribution of metal cations in the glycerol matrix of PGPs was confirmed. We observed 7-fold growth of E. coli bacteria upon 4 h of interaction with quinary glycerolate (NiZnMnMgSr-Gly) particles in comparison to control E. coli bacteria. Nanoscale microscopic studies on bacteria interactions with PGPs showed the release of metal cations in the bacterium cytoplasm from PGPs. The electron microscopy imaging and chemical mapping indicated bacterial biofilm formation on PGPs without causing significant cell membrane damage. The data showed that the presence of glycerol in PGPs is effective in controlling the release of metal cations, thus preventing bacterial toxicity. The presence of multiple metal cations is expected to provide synergistic effects of nutrients needed for bacterial growth. The present work provides key microscopic insights of mechanisms by which PGPs enhance biofilm growth. This study opens the door for future applications of PGPs in areas where bacterial growth is essential including healthcare, clean energy, and the food industry.


How nursing students' reactions to rape victims are affected by a perceived act of carelessness.
This experiment focused on how reactions to a rape victim would be affected by a perceived act of carelessness. The subjects were 116 graduating baccalaureate nursing students, 31% of whom were registered nurses. All subjects read a vignette of a rape in which the victim was described as having driven to a drugstore on a legitimate errand. Subjects were randomly assigned to read one of four versions, in which the victim either locked or failed to lock her car door (carelessness manipulation) and in which the rape occurred at 10:00 P.M. or midnight. All subjects evaluated the victim on a series of 11-point rating scales, and the data were analyzed by means of 2 x 2 analyses of variance. As hypothesized, subjects in the unlocked condition (compared to those in the locked condition) liked and identified with the victim significantly less, and attributed significantly more carelessness and responsibility for the rape to her. There was no significant main effect for the time the rape occurred. Use of vignettes as an unobtrusive measure of attitude toward rape, and implications for nursing education and practice are discussed.


Early intra-aortic balloon pumping following perioperative myocardial injury improves hospital and mid-term prognosis.
We evaluated the impact of immediate intra-aortic balloon pumping (IABP) on hospital and mid-term outcome of coronary artery bypass graft (CABG) whenever perioperative acute complications developed. We compared clinical, biochemical, echocardiographic in-hospital results and two-year follow-up outcome of 30 low-risk (EuroSCORE<5) CABG (group A) who immediately received perioperative IABP when acute complications were suspected, to a contemporary, uncomplicated case-matched group (30 patients; Group B). Two in-hospital deaths were recorded in group A with no deaths in controls (P=0.492). Group A showed significantly higher lactate only at ICU arrival (P=0.001). Troponin I was always higher, but never reached values diagnostic for myocardial infarction (P<0.001). Worse left ventricular ejection fraction (P<0.001) and wall motion score index (P=0.008) were recorded at ICU arrival in group A, although an almost complete recovery was registered at discharge. Two-year actuarial survival was similar between the two groups (P=0.598). No differences were observed in freedom from acute myocardial infarction (P=0.503) and from overall cardiac complications (P=0.410). Early IABP should be established whenever cardiac complications are suspected, because of its beneficial impact on enzymatic leakage, myocardial recovery at echocardiography, hospital outcome, mid-term follow-up survival and freedom from cardiovascular events.


Lyotropic Chromonic Mesophases Derived from Metal-Organic Complexes.
Lyotropic chromonic (LC) mesophases have received a large amount of attention, owing to the semi-stable nature of the chromonics. In these systems, the balance between the ordering forces and the thermal motion is delicate. As such, temperature changes, concentration variations, alterations to the electric and magnetic fields, and the addition of additives to the chromonic systems can be sensitively monitored. Herein, we review the general characterization methods for lyotropic chromonic mesophases, including polarized optical microscopy (POM), multinuclear NMR spectroscopy, X-ray diffractometry, cryo-TEM, and rheology. In recent years, lyotropic chromonic mesophases that are derived from metal-organic complexes have become established and offer the possibility of introducing the rich functionalities of the metal complexes into these systems. The chromonic properties, aggregation behaviors, and influence factors on such systems are reviewed case-by-case. Finally, preliminary attempts to utilize these systems are reviewed, which have demonstrated their potential application in optical devices, biosensing, luminescent materials, etc.


FOLFOX-4 regimen with concomitant highly active antiretroviral therapy in metastatic colorectal cancer HIV-infected patients: a report of five cases and review of the literature.
Colorectal cancers are rare in developing countries, but are the second most frequent malignancy in the affluent world. Data on colorectal cancer in HIV-positive patients are limited. Up to now, there are no published data on treatment patterns, response to therapy, or survival in this setting. Oxaliplatin is an antineoplastic agent currently indicated, concomitantly to fluorouracil and leucovorin, for the treatment of advanced colorectal cancer. The FOLFOX-4 regimen (oxaliplatin 85 mg/m(2) as a two-hour infusion on day 1; leucovorin 200 mg/m(2) as a two-hour infusion on days 1 and 2, fluorouracil as a bolus infusion on days 1 and 2, followed by a fluorouracil 22-hour infusion 600 mg/m(2) for two consecutive days every two weeks), with concomitant highly active antiretroviral therapy (HAART) is feasible and active, while the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of the FOLFOX-4 regimen.


Risk factors for subclinical and clinical ketosis and association with production parameters in dairy cows in the Netherlands.
Ketosis is associated with many transition cow diseases and the subclinical form has been found to be a common condition in high-producing dairy cows. The objectives of this field study in the Netherlands were (1) to determine risk factors for subclinical ketosis [SCK; 1.2-2.9mmol of β-hydroxybutyrate (BHBA)/L of serum] and clinical ketosis (CK: ≥3.0mmol of BHBA/L of serum) at 7 to 14 d in milk and (2) to assess the association of SCK and CK with production parameters at the first dairy herd improvement (DHI) testing. Twenty-three dairies were enrolled by a local veterinary practice from 2009 to 2010, and 1,715 cows were screened for ketosis by measuring serum BHBA concentrations at 7 to 14 d in milk. Overall, 47.2% of cows had SCK and 11.6% had CK. Mixed generalized logit models with a random effect of herd were used to evaluate cow level factors associated with SCK and CK. The associations of SCK and CK with milk production parameters were tested using mixed linear models with a random effect of herd. Cows at a moderate (3.25-3.75) or fat (≥4) body condition score before calving were more likely to develop SCK and CK than thin (body condition score≤3.0) cows. The risk for developing SCK was higher in parity 2 and older cows compared with heifers, whereas for CK only, parity ≥3 cows had a higher risk. The quarter of the year in which a cow calved was associated with the risk for SCK and CK. For SCK quarter 1 (January-March) and quarter 2 (April-June), and for CK quarter 1, quarter 2, and quarter 3 (July-September) all increased the risk of development of the condition compared with quarter 4 (October-December). An increased yield of colostrum at first milking was associated with increasing risk for SCK and CK. Prolonged previous lactation length and dry period length were both associated with increased odds for SCK and CK. Subclinical ketosis and CK were associated with a higher milk yield, a higher milk fat percentage, and a lower milk protein percentage at first DHI test day. Overall the study reinforces previous findings that the major risk factors for both SCK and CK are increasing parity, overconditioning of animals prepartum, season of calving, and dry period length. In addition, previous lactation length and liters of colostrum have been identified as additional risk factors for the development of ketosis.


Selected contribution: cerebrovascular nos and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-alpha.
Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-alpha knockout (alphaERKO) mice were used to test whether estrogen acts via ER-alpha. Mice were ovariectomized, with or without estrogen replacement, and cerebral blood vessels were isolated 1 mo later. Estrogen increased levels of endothelial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mice but was ineffective in alphaERKO mice. Endothelium-denuded middle cerebral artery segments from all animals constricted when pressurized. In denuded arteries from alphaERKO but not wild-type mice, estrogen treatment enhanced constriction. In endothelium-intact, pressurized arteries from wild-type estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethacin were greater in arteries from wild-type estrogen-treated mice compared with arteries from untreated wild-type mice. In contrast, estrogen treatment of alphaERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-alpha regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effects of estrogen on cerebral artery reactivity.


Genetic susceptibility to diabetes and long-term improvement of insulin resistance and β cell function during weight loss: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
Diet interventions have shown effectiveness in improving diabetes risk factors; however, little is known about whether the effects of diet intervention are different according to genetic susceptibility. We examined interactions between weight-loss diets and the genetic risk score (GRS) for diabetes on 2-y changes in markers of insulin resistance and β cell function in a randomized controlled trial. Data from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial were analyzed. A GRS was calculated on the basis of 31 diabetes-associated variants in 744 overweight or obese nondiabetic adults (80% white Americans). We assessed the changes in insulin resistance and β cell function over the 2-y intervention. Dietary protein significantly interacted with the diabetes GRS on fasting insulin, glycated hemoglobin (HbA1c), the homeostasis model assessment of β cell function (HOMA-B), and the homeostasis model assessment of insulin resistance (HOMA-IR) at 2 y in white Americans (P-interaction = 0.02, 0.04, 0.01, and 0.05, respectively). The lower GRS was associated with a greater decrease in fasting insulin (P = 0.04), HbA1c (P = 0.0001), and HOMA-IR (P = 0.02), and a lesser increase in HOMA-B (P = 0.004) in participants consuming a low-protein diet. Participants with a higher GRS might have a greater reduction in fasting insulin when consuming a high-protein diet (P = 0.03). Our data suggest that individuals with a lower genetic risk of diabetes may benefit more from consuming a low-protein weight-loss diet in improving insulin resistance and β cell function, whereas a high-protein diet may be more beneficial for white patients with a higher genetic risk. This trial was registered at clinicaltrials.gov as NCT00072995.


The therapeutic implications of immunosuppressive tumor aerobic glycolysis.
In 2011, Hanahan and Weinberg added "Deregulating Cellular Energetics" and "Avoiding Immune Destruction" to the six previous hallmarks of cancer. Since this seminal paper, there has been a growing consensus that these new hallmarks are not mutually exclusive but rather interdependent. The following review summarizes how founding genetic events for tumorigenesis ultimately increase tumor cell glycolysis, which not only supports the metabolic demands of malignancy but also provides an immunoprotective niche, promoting malignant cell proliferation, maintenance and progression. The mechanisms by which altered metabolism contributes to immune impairment are multifactorial: (1) the metabolic demands of proliferating tumor cells and activated immune cells are similar, thus creating a situation where immune cells may be in competition for key nutrients; (2) the metabolic byproducts of aerobic glycolysis directly inhibit antitumor immunity while promoting a regulatory immune phenotype; and (3) the gene programs associated with the upregulation of glycolysis also result in the generation of immunosuppressive cytokines and metabolites. From this perspective, we shed light on important considerations for the development of new classes of agents targeting cancer metabolism. These types of therapies can impair tumor growth but also pose a significant risk of stifling antitumor immunity.


The future of communicable disease control: toward a new concept in public health law.
The exercise of compulsory public health powers for the common good of the community, though rooted in constitutional authority, involves a potentially massive infringement of individual liberty, autonomy, and privacy. Yet, public health statutes do not reflect modern conceptions in either science or law. Most are structurally obsolete and lack criteria for judicial oversight and impartial decision making. Guidelines for a model statute are proposed to protect both communal and personal interests.


Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2.
A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.


Design of 3-D Printed Concentric Tube Robots.
Concentric tube surgical robots are minimally invasive devices with the advantages of snake-like reconfigurability, long and thin form factor, and placement of actuation outside the patient's body. These robots can also be designed and manufactured to acquire targets in specific patients for treating specific diseases in a manner that minimizes invasiveness. We propose that concentric tube robots can be manufactured using 3-D printing technology on a patient- and procedure-specific basis. In this paper, we define the design requirements and manufacturing constraints for 3-D printed concentric tube robots and experimentally demonstrate the capabilities of these robots. While numerous 3-D printing technologies and materials can be used to create such robots, one successful example uses selective laser sintering to make an outer tube with a polyether block amide and uses stereolithography to make an inner tube with a polypropylene-like material. This enables a tube pair with precurvatures of 0.0775 and 0.0455 mm-1, which can withstand strains of 20% and 5.5% for the outer and inner tubes, respectively.


Sodium and potassium salt stimulation of taste receptor cells: an allosteric model.
Stimulation of taste receptors with sodium chloride, sodium acetate, sodium propionate, and the respective potassium salts gave concentration-response profiles, measured electrophysiologically, which are remarkably consistent with a two-state allosteric mechanism. The allosteric constant or equilibrium constant for the transition between the active and inactive receptor states is low, resulting in a condition in which small differences in ion affinities for the two states are sufficient to significantly alter the equilibrium. Receptor activators, such as sodium ion, displaced the equilibrium toward the active receptor state by virtue of a higher affinity for that state, whereas receptor inhibitors, such as acetate and propionate ions, displaced the equilibrium in the opposite direction as a result of a higher affinity for the inactive state. The low allosteric constant increased about 10-fold after treatment with the protein modification reagent dimethyl(2-hydroxy-5-nitrobenzyl)sulfonium bromide, resulting in a marked reduction in the response to sodium chloride and sodium propionate without a significant change in ion affinities. In order to fully resolve the potassium response characteristics, it was necessary to consider both a potassium activation site and a potassium inhibition site. Analysis of the response from sodium chloride/potassium chloride mixtures showed that sodium ion is competitive with potassium binding at the activation site but not the inhibition site. With potassium propionate as the stimulus, the effect of both a receptor activator and a receptor inhibitor was quantitatively consistent with depression of the response below a water baseline level at low stimulus concentrations. Estimation of active and inactive state dissociation constants for each anion and cation permitted accurate prediction of the response magnitude for a range of cation ratios in sodium chloride/potassium chloride mixtures and anion ratios in sodium chloride/sodium propionate mixtures. The association of salty taste with receptor activators and bitter taste with receptor inhibitors may be relevant to the generation of these taste qualities.


Applying of Decision Tree Analysis to Risk Factors Associated with Pressure Ulcers in Long-Term Care Facilities.
The purpose of this study was to use decision tree analysis to explore the factors associated with pressure ulcers (PUs) among elderly people admitted to Korean long-term care facilities. The data were extracted from the 2014 National Inpatient Sample (NIS)-data of Health Insurance Review and Assessment Service (HIRA). A MapReduce-based program was implemented to join and filter 5 tables of the NIS. The outcome predicted by the decision tree model was the prevalence of PUs as defined by the Korean Standard Classification of Disease-7 (KCD-7; code L89*). Using R 3.3.1, a decision tree was generated with the finalized 15,856 cases and 830 variables. The decision tree displayed 15 subgroups with 8 variables showing 0.804 accuracy, 0.820 sensitivity, and 0.787 specificity. The most significant primary predictor of PUs was length of stay less than 0.5 day. Other predictors were the presence of an infectious wound dressing, followed by having diagnoses numbering less than 3.5 and the presence of a simple dressing. Among diagnoses, "injuries to the hip and thigh" was the top predictor ranking 5th overall. Total hospital cost exceeding 2,200,000 Korean won (US $2,000) rounded out the top 7. These results support previous studies that showed length of stay, comorbidity, and total hospital cost were associated with PUs. Moreover, wound dressings were commonly used to treat PUs. They also show that machine learning, such as a decision tree, could effectively predict PUs using big data.


Metabolic and inflammatory profiles, gut microbiota and lifestyle factors in overweight and normal weight young thai adults.
Obesity among young adults, especially those living in developing countries is increasing. A high body mass index (BMI) is one of the major causes of several diseases worldwide, constituting an important risk factor for non-communicable diseases (NCDs). Investigations describing the relationship between BMI, clinical and gut microbiota characteristics and lifestyle factors of overweight young adults, especially from Southeast Asian countries are limited. Metabolic and inflammatory biomarkers, fecal microbiota profiles and lifestyle factors were compared between overweight Thai young adults (n = 30, mean age 33 ± 9.48) and those with normal weight (n = 30, mean age 27 ±7.50). This study was registered with the Thai Clinical Trials Registry (TCTR20220204007). Health status including body composition, fasting glucose and insulin, lipid profiles, liver and kidney function, inflammatory biomarkers, blood pressure and fecal microbiota using 16S rRNA gene sequencing data was determined. Dietary intake was assessed using a 3-day dietary record and a food frequency questionnaire (FFQ), with physical activity levels compared using the international physical activity questionnaire (IPAQ). The overweight group had significantly higher BMI, waist-hip ratio, body fat mass, % body fat, skeletal mass, triglyceride level, C-reactive protein, insulin and blood pressure, with lower levels of high-density lipoprotein cholesterol (HDL-C) and blood urea nitrogen compared to the normal weight group. Significant differences in fecal microbiota composition at the family and genus levels were observed between the two groups. In our clinical setting, we also observed that unhealthy diets with high consumption of food rich in fat and sugar, processed meat and alcohol, and physical inactivity were associated with an increased prevalence of overweight in Thai young adults. Results provided the big picture of health and lifestyle characteristics of overweight young Thai people. Young adults should be encouraged to engage in health-promoting activities that maintain healthy bodyweight.


High affinity streptococcal binding to human fibronectin requires specific recognition of sequential F1 modules.
Fibronectin (Fn) binding by the Streptococcus pyogenes protein SfbI has been shown to trigger integrin-dependent internalization of this pathogen by human epithelial and endothelial cells. Here, using nuclear magnetic resonance spectroscopy and isothermal titration calorimetry in a dissection approach, the basis for the specificity and high affinity of the interaction between the N-terminal domain of Fn and SfbI is revealed. Each of the five Fn type 1 modules is directly involved in the interaction and is recognized by short consecutive motifs within the repeat region of SfbI. Crucially, these motifs must be combined in the correct order to form a high affinity ligand for the N-terminal domain of Fn.


Insight about the biochemical composition, postharvest processing, therapeutic potential of Indian gooseberry (amla), and its utilization in development of functional foods-A comprehensive review.
Indian gooseberry/Amla (Emblica officinalis Gaertn. syn. Phyllanthus emblica L) has an amazing nutritional profile and is a reservoir of biologically active compounds which have potential health benefits and are regarded as a remedy for lethal diseases. The unique features of amla, conferred by their bioactive components, have extended future prospects about their usage for useful effects on human nutrition and health globally. With the rapidly growing popularity of this unique therapeutic fruit, it is important to have comprehensive knowledge of this fruit. The current review article presents the nutritional profile, bioactive components, antioxidant and antimicrobial properties, and postharvest processing of amla fruit. Moreover, studies related to therapeutic properties of amla and its utilization in development of functional foods have been presented in this review. E. officinalis is a promising source of bioactive compounds which showed varied potential in the management of a number of human ailments which has been proven through various studies. Therefore, amla should be taken in the regular diet, thereby utilizing its potential health benefits. PRACTICAL APPLICATIONS: Amla (Indian gooseberry), as source of natural bioactive compounds, has a great potential application in improving the status of human nutrition and health. The utilization of amla extract has various biological effects, like antimicrobial, antioxidant, gastroprotective, anticancer, hepatoprotective, cardioprotective, radioprotective, anti-inflammatory, antidiabetic, neuroprotective, and immunomodulatory effect, owing to its bioactive components. The use of amla extract has recently increased in food, pharmaceutical, and cosmetic products to replace synthetic antioxidants which have inherent harmful health effects. The review report will provide information on bioactive components, therapeutic properties, utilization of amla in the development of future functional foods, and postharvest processing of amla, which will provide critical information to researchers all over the world.


Diet, anthropometry and breast cancer: integration of experimental and epidemiologic approaches.
The interrelation ships of dietary fat and energy, growth rates and anthropometry, and breast carcinogenesis have been examined by a diverse array of approaches throughout the last 50 y as new investigative tools have been developed by laboratory scientists and epidemiologists. A consensus among investigators has not emerged, however, and dietary recommendations for breast cancer prevention have not been clearly formulated or effectively communicated to the public. Indeed, the gap between those investigators utilizing laboratory-based approaches and those using epidemiologic models has expanded in recent years. Cancer epidemiologists have become increasingly skeptical that results derived form laboratory animal models of breast carcinogenesis and in vitro systems are directly applicable to human breast cancer risk. Concurrently, laboratory scientists have questioned the ability of epidemiological tools to accurately measure dietary intake and relevant biomarkers and to account for a diverse array of potentially confounding environmental and genetic factors characteristic of human populations under study. These polarized views are reinforced by a failure of investigators using diverse approaches to interact, integrate their skills and resources, develop novel hypotheses, and propose solutions using both laboratory and epidemiologic techniques. Therefore, the objectives of this symposium are to summarize experimental and epidemiologic knowledge, foster communication and collaboration, and attempt to identify appropriate studies to bridge the gaps in our knowledge concerning dietary lipid and energy, anthropometrics, and breast cancer risk.


Evaluation of a monoclonal antibody-based immunoassay for detecting type B Clostridium botulinum toxin produced in pure culture and an inoculated model cured meat system.
A monoclonal antibody-based amplified ELISA method for detecting Clostridium botulinum type B toxin was evaluated for its ability to detect the toxin in the supernatant fluid of pure cultures and after growth from Cl. botulinum spores inoculated into pork slurries. Slurries containing NaCl (1.5-4.5% w/v) and polyphosphate (0.3% w/v) were either unheated or heated 80 degrees C/5 min followed by 70 degrees C/2 h before incubation at 15 degrees, 20 degrees or 27 degrees C. Presence of specific toxin was confirmed by mouse bioassay and results were compared with those of the amplified ELISA method. A total of 48 strains, consisting of 38 Cl. botulinum and 10 Cl. sporogenes (putrefactive anaerobes), and 140 slurry samples were tested. Cultures of eight out of nine strains of type B Cl botulinum and 73 of 101 slurry samples containing type B toxin were positive by ELISA; the remaining 28 slurry samples contained type B toxin at levels below or close to the detection limit (20 LD50/ml) of the type B ELISA. No false-positive reactions occurred with Cl. botulinum types A, C, D, E or F, or with the 10 strains of Cl. sporogenes. Toxin produced by one strain of Cl. botulinum type B (NCTC 3807) was not detected by this single monoclonal antibody-based amplified ELISA. With a mixture of two monoclonal antibodies, however, the toxin from NCTC 3807 could be detected without reducing the sensitivity of the ELISA.


The Validity of Estimated Dietary Amino Acid and Protein Values via the Amino Acid Composition Table 2015.
The amino acid composition table (AACT) plays a pivotal role in examining the association between dietary amino acid intake and physical conditions. The updated version, AACT 2015, has been markedly expanded; however, most additions are not based on analytical values. The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) recommend that protein contents be calculated as the sum of amino acid residues (PROTCAA). However, due to the lack of a validated AACT, protein content calculated as reference nitrogen multiplied by a nitrogen to protein conversion factor (PROTRN) is still commonly used. In this study, validity of the estimated dietary amino acid values via the AACT 2015 was examined by comparing differences between the estimated and analytical values, for 14 consecutive days' meals provided in an elder care facility. There were no major differences between the analytical and estimated values over the 14 d; however, noticeable daily differences sometimes emerged. These results indicate that the AACT 2015 may contain accidental errors, but allows the estimation of habitual amino acid intake. In the near future, PROTCAA will become the international standard. It will be necessary to convert PROTRN values to PROTCAA to refer to past reports and data; we have determined a correction factor (0.896) for this conversion.


[A Case of ECA-MCA Double Anastomoses for Hemorrhagic Type of Twig-Like MCA].
Herein, we describe the case of a superficial temporal artery(STA)- and occipital artery (OA)-middle cerebral artery (MCA) double anastomoses that we performed to treat a hemorrhagic twig-like MCA. A 55-year-old man presented to our hospital for investigation of an incidentally identified left MCA occlusion. Left cerebral angiography revealed a twig-like MCA. The (123)I-IMP-single photon emission computed tomography( SPECT) demonstrated no reduction in the cerebral blood flow (CBF), so the patient was initially observed with no treatment. Three months later, he was readmitted with a disturbance of consciousness. The cranial computed tomography revealed a subcortical hemorrhage in the left frontotemporal region and a subdural hematoma. The hematoma was removed via emergency craniotomy. The abnormal vessels were identified and resected, but the parietal branch of the STA was damaged during the skin incision. The histological examination did not reveal the marked fibrous thickening of the intima or wavy internal elastic lamina typically seen with Moyamoya disease. Six months after the initial surgery, a STA-MCA bypass surgery was planned to prevent a future hemorrhage by reducing the hemodynamic overload of the twig-like MCA and improving the cerebral ischemia in the MCA territory that was detected on the preoperative SPECT. However, the parietal branch of the left STA had been injured during the first operation, so we performed a double anastomoses to the MCA using the frontal branch of the STA and the OA. The patient's postoperative course was uneventful and he was discharged 2 weeks after surgery. The follow-up study performed 1 year postoperatively demonstrated no evidence of cerebral infarction and revealed an improvement in the resting CBF and vascular reactivity in the left cerebral hemisphere. No subsequent cerebrovascular events have occurred in this patient during the 7 years since the double anastomoses surgery. Direct bypass for flow conversion from the internal carotid artery to the external carotid artery can be an indispensable treatment for patients with a hemorrhagic twig-like MCA.