Surveillance for Violent Deaths - National Violent Death Reporting System, 34 States, Four California Counties, the District of Columbia, and Puerto Rico, 2017.
In 2017, approximately 67,000 persons died of violence-related injuries in the United States. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 34 states, four California counties, the District of Columbia, and Puerto Rico in 2017. Results are reported by sex, age group, race/ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics. 2017. NVDRS collects data regarding violent deaths obtained from death certificates, coroner and medical examiner reports, and law enforcement reports. This report includes data collected for violent deaths that occurred in 2017. Data were collected from 34 states (Alaska, Arizona, Colorado, Connecticut, Delaware, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, West Virginia, and Wisconsin), four California counties (Los Angeles, Sacramento, Shasta, and Siskiyou), the District of Columbia, and Puerto Rico. NVDRS collates information for each death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. For 2017, NVDRS collected information on 45,141 fatal incidents involving 46,389 deaths that occurred in 34 states, four California counties, and the District of Columbia; in addition, information was collected on 961 fatal incidents involving 1,027 deaths in Puerto Rico. Data for Puerto Rico were analyzed separately. Of the 46,389 deaths in the 34 states, four California counties, and District of Columbia, the majority (63.5%) were suicides, followed by homicides (24.9%), deaths of undetermined intent (9.7%), legal intervention deaths (1.4%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm deaths (<1.0%). (The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision, and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Demographic patterns and circumstances varied by manner of death. The suicide rate was higher among males than among females and was highest among adults aged 45-64 years and ≥85 years and non-Hispanic American Indians/Alaska Natives and non-Hispanic Whites. The most common method of injury for suicide was a firearm among males and poisoning among females. Suicide was most often preceded by a mental health, intimate partner, or physical health problem or a recent or impending crisis during the previous or upcoming 2 weeks. The homicide rate was highest among persons aged 20-24 years and was higher among males than females. Non-Hispanic Black males had the highest homicide rate of any racial/ethnic group. The most common method of injury for homicide was a firearm. When the relationship between a homicide victim and a suspect was known, the suspect was most frequently an acquaintance or friend for male victims and a current or former intimate partner for female victims. Homicide most often was precipitated by an argument or conflict, occurred in conjunction with another crime, or, for female victims, was related to intimate partner violence. Among intimate partner violence-related homicides, the largest proportion occurred among adults aged 35-54 years, and the most common method of injury was a firearm. When the relationship between an intimate partner violence-related homicide victim and a suspect was known, most female victims were killed by a current or former intimate partner, whereas approximately half of male victims were killed by a suspect who was not their intimate partner. Almost all legal intervention deaths were among males, and the legal intervention death rate was highest among men aged 25-29 years. Non-Hispanic American Indian/Alaska Native males had the highest legal intervention death rate, followed by non-Hispanic Black males. A firearm was used in the majority of legal intervention deaths. When a specific type of crime was known to have precipitated a legal intervention death, the type of crime was most frequently assault/homicide. The most frequent circumstances for legal intervention deaths were reported use of a weapon by the victim in the incident and a mental health or substance use problem (other than alcohol use). Unintentional firearm deaths more frequently occurred among males, non-Hispanic Whites, and persons aged 15-24 years. These deaths most often occurred while the shooter was playing with a firearm and most frequently were precipitated by a person unintentionally pulling the trigger or mistakenly thinking the firearm was unloaded. The rate of death when the manner was of undetermined intent was highest among males, particularly among non-Hispanic Black and non-Hispanic American Indian/Alaska Native males, and persons aged 30-34 years. Poisoning was the most common method of injury in deaths of undetermined intent, and opioids were detected in nearly 80% of decedents tested for those substances. This report provides a detailed summary of data from NVDRS on violent deaths that occurred in 2017. The suicide rate was highest among non-Hispanic American Indian/Alaska Native and non-Hispanic White males, whereas the homicide rate was highest among non-Hispanic Black males. Intimate partner violence precipitated a large proportion of homicides for females. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary circumstances for multiple types of violent death. NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in developing, implementing, and evaluating programs and policies to reduce and prevent violent deaths. For example, South Carolina VDRS and Colorado VDRS are using their data to support suicide prevention programs through systems change and the Zero Suicide framework. North Carolina VDRS and Kentucky VDRS data were used to examine intimate partner violence-related deaths beyond homicides to inform prevention efforts. Findings from these studies suggest that intimate partner violence might also contribute to other manners of violent death, such as suicide, and preventing intimate partner violence might reduce the overall number of violent deaths. In 2019, NVDRS expanded data collection to include all 50 states, the District of Columbia, and Puerto Rico, providing more comprehensive and actionable violent death information for public health efforts to reduce violent deaths.


Understanding help-seeking in older people with urinary incontinence: an interview study.
The prevalence of urinary incontinence (UI) increases with age and can negatively affect quality of life. However, relatively few older people with UI seek treatment. The aim of this study was to explore the views of older people with UI on the process of seeking help. Older people with UI were recruited to the study from three continence services in the north of England: a geriatrician-led hospital outpatient clinic (n = 18), a community-based nurse-led service (n = 22) and a consultant gynaecologist-led service specialising in surgical treatment (n = 10). Participants took part in semi-structured interviews, which were transcribed and underwent thematic content analysis. Three main themes emerged: Being brushed aside, in which participants expressed the feeling that general practitioners did not prioritise or recognise their concerns; Putting up with it, in which participants delayed seeking help for their UI due to various reasons including embarrassment, the development of coping mechanisms, perceiving UI as a normal part of the ageing process, or being unaware that help was available; and Something has to be done, in which help-seeking was prompted by the recognition that their UI was a serious problem, whether as a result of experiencing UI in public, the remark of a relative, the belief that they had a serious illness or the detection of UI during comprehensive geriatric assessment. Greater awareness that UI is a treatable condition and not a normal part of ageing is needed in the population and among health professionals. Comprehensive geriatric assessment appeared an important trigger for referral and treatment in our participants. Screening questions by healthcare professionals could be a means to identify, assess and treat older people with UI.


The influence of seasonality on the content of goyazensolide and on anti-inflammatory and anti-hyperuricemic effects of the ethanolic extract of Lychnophora passerina (Brazilian arnica).
Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites. Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities. Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice. HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts. The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.


A historical and proteomic analysis of botulinum neurotoxin type/G.
Clostridium botulinum is the taxonomic designation for at least six diverse species that produce botulinum neurotoxins (BoNTs). There are seven known serotypes of BoNTs (/A through/G), all of which are potent toxins classified as category A bioterrorism agents. BoNT/G is the least studied of the seven serotypes. In an effort to further characterize the holotoxin and neurotoxin-associated proteins (NAPs), we conducted an in silico and proteomic analysis of commercial BoNT/G complex. We describe the relative quantification of the proteins present in the/G complex and confirm our ability to detect the toxin activity in vitro. In addition, we review previous literature to provide a complete description of the BoNT/G complex. An in-depth comparison of protein sequences indicated that BoNT/G shares the most sequence similarity with the/B serotype. A temperature-modified Endopep-MS activity assay was successful in the detection of BoNT/G activity. Gel electrophoresis and in gel digestions, followed by MS/MS analysis of/G complex, revealed the presence of four proteins in the complexes: neurotoxin (BoNT) and three NAPs--nontoxic-nonhemagglutinin (NTNH) and two hemagglutinins (HA70 and HA17). Rapid high-temperature in-solution tryptic digestions, coupled with MS/MS analysis, generated higher than previously reported sequence coverages for all proteins associated with the complex: BoNT 66%, NTNH 57%, HA70 91%, and HA17 99%. Label-free relative quantification determined that the complex contains 30% BoNT, 38% NTNH, 28% HA70, and 4% HA17 by weight comparison and 17% BoNT, 23% NTNH, 42% HA70, and 17% HA17 by molecular comparison. The in silico protein sequence comparisons established that the/G complex is phenetically related to the other six serotypes of C. botulinum. Proteomic analyses and Endopep-MS confirmed the presence of BoNT and NAPs, along with the activity of the commercial/G complex. The use of data-independent MS(E) data analysis, coupled to label-free quantification software, suggested that the weight ratio BoNT:NAPs is 1:3, whereas the molar ratio of BoNT:NTNH:HA70:HA17 is 1:1:2:1, within the BoNT/G progenitor toxin.


Stimulus-to-matching-stimulus interval influences N1, P2, and P3b in an equiprobable Go/NoGo task.
Previous research has shown that as the stimulus-to-matching-stimulus interval (including the target-to-target interval, TTI, and nontarget-to-nontarget interval, NNI) increases, the amplitude of the P300 ERP component increases systematically. Here, we extended previous P300 research and explored TTI and NNI effects on the various ERP components elicited in an auditory equiprobable Go/NoGo task. We also examined whether a similar mechanism was underpinning interval effects in early ERP components (e.g., N1). Thirty participants completed a specially-designed variable-ISI equiprobable task whilst their EEG activity was recorded. Component amplitudes were extracted using temporal PCA with unrestricted Varimax rotation. As expected, N1, P2, and P3b amplitudes increased as TTI and NNI increased, however, Processing Negativity (PN) and Slow Wave (SW) did not show the same systematic change with interval increments. To determine the origin of interval effects in sequential processing, a multiple regression analysis was conducted on each ERP component including stimulus type, interval, and all preceding components as predictors. These analyses showed that matching-stimulus interval predicted N1, P3b, and weakly predicted P2, but not PN or SW; SW was determined by P3b only. These results suggest that N1, P3b, and to some extent, P2, are affected by a similar temporal mechanism. However, the dissimilar pattern of results obtained for sequential ERP components indicates that matching-stimulus intervals are not affecting all aspects of stimulus processing. This argues against a global mechanism, such as a pathway-specific refractory effect, and suggests that stimulus processing is occurring in parallel pathways, some of which are not affected by temporal manipulations of matching-stimulus interval.


Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life.
Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.


Return of spinal reflex after spinal cord surgery for brachial plexus avulsion injury.
Motor but not sensory function has been described after spinal cord surgery in patients with brachial plexus avulsion injury. In the featured case, motor-related nerve roots as well as sensory spinal nerves distal to the dorsal root ganglion were reconnected to neurons in the ventral and dorsal horns of the spinal cord by implanting nerve grafts. Peripheral and sensory functions were assessed 10 years after an accident and subsequent spinal cord surgery. The biceps stretch reflex could be elicited, and electrophysiological testing demonstrated a Hoffman reflex, or Hreflex, in the biceps muscle when the musculocutaneous nerve was stimulated. Functional MR imaging demonstrated sensory motor cortex activities on active as well as passive elbow flexion. Quantitative sensory testing and contact heat evoked potential stimulation did not detect any cutaneous sensory function, however. To the best of the authors' knowledge, this case represents the first time that spinal cord surgery could restore not only motor function but also proprioception completing a spinal reflex arch.


Cross-sensitivity effect in temperature-compensated sensors based on highly birefringent fibers.
We analyzed the influence of the measurand-temperature cross-sensitivity effect on temperature stability in fiber-optic cross-spliced sensors that employ highly birefringent fibers. We show that the ratio of the measurand-temperature cross-sensitivity coefficient to the measurand first-order sensitivity determines the physical limit for temperature stability in cross-spliced sensors. Employing polarimetric as well as white-light interferometric methods, we experimentally determine a hydrostatic pressure-temperature cross-sensitivity coefficient in York bow-tie 800 fiber. From this we estimate the achievable limit for temperature stability of cross-spliced pressure sensors under environmental temperature changes.


Clinical characteristics and longitudinal changes of informal cost of Alzheimer's disease in the community.
Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n=170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4.


Sphingomyelinase D/ceramide 1-phosphate in cell survival and inflammation.
Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.


Patterns of naturally occurring restriction map variation, dopa decarboxylase activity variation and linkage disequilibrium in the Ddc gene region of Drosophila melanogaster.
Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (greater than or equal to 9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal adult DDC activities.


Mid-term coral-algal dynamics and conservation status of a Gorgona Island (Tropical Eastern Pacific) coral reef.
Colombian coral reefs, as other reefs worldwide, have deteriorated significantly during the last few decades due to both natural and anthropogenic disturbances. The National Monitoring System for Coral Reefs in Colombia (SIMAC) was established in 1998 to provide long-term data bases to assess the changes of Colombian coral reefs against perturbations and to identify the factors responsible for their decline or recovery. On the Pacific coast, data on coral and algal cover have been collected yearly during seven consecutive years (1998-2004) from 20 permanent transects in two sites at La Azufrada reef, Gorgona Island. Overall, coral cover was high (55.1%-65.7%) and algal cover low (28.8%-37.5%) and both exhibited significant changes among years, most notably on shallow areas. Differences between sites in both coral and algal cover were present since the study began and may be explained by differences in sedimentation stress derived from soil runoff. Differences between depths most likely stem from the effects of low tidal sub-aerial exposures. Particularly intense sub-aerial exposures occurred repeatedly during January-March, 2001 and accounted for a decrease in coral and an increase in algal cover on shallow depths observed later that year. Additionally, the shallow area on the Northern site seems to be negatively affected by the combined effect of sedimentation and low tidal exposure. However, a decrease in coral cover and an increase of algal cover since 2001 on deep areas at both sites remain unexplained. Comparisons with previous studies suggest that the reef at La Azufrada has been more resilient than other reefs in the Tropical Eastern Pacific (TEP), recovering pre-disturbance (1979) levels of coral cover within a 10 year period after the 1982-83 El Niño, which caused 85% mortality. Furthermore, the effects of the 1997-98 El Niño, indicated by the difference in overall live coral cover between 1998 and 1999, were minor (< 6% reduction). Despite recurrent natural disturbances, live coral cover in 2004 was as high as that existing before 1982 at La Azufrada, and one of the highest observed on healthy coral reefs in the TEP region.


Estimation of sensitivity, specificity and predictive values of two serologic tests for the detection of antibodies against Actinobacillus pleuropneumoniae serotype 2 in the absence of a reference test (gold standard).
Latent-class models were used to determine the sensitivity, specificity and predictive values of a polyclonal blocking enzyme-linked immunosorbent assay (ELISA) and a modified complement-fixation test (CFT) when there was no reference test. The tests were used for detection of antibodies against Actinobacillus pleuropneumoniae serotype 2 in a survey of respiratory diseases in Danish finishing pigs. The estimates were obtained by maximum-likelihood and also by a Bayesian method (implemented with Gibbs sampling). Possible dependence of diagnostic errors was investigated by comparing models where independence was assumed to models allowing for conditional dependence, given the true disease status. No strong evidence of conditional dependence in either test sensitivity or specificity was found. Assuming independence, maximum-likelihood estimates and 95% confidence intervals of the sensitivity and specificity of the ELISA were 100% and 92.8% (90.1-95.5%) and the corresponding values of the CFT were 90.6% (85.8-95.4%) and 98.6% (98.0-99.3%), respectively. Bayesian estimates and posterior 95% credible intervals of the sensitivity and specificity of the ELISA were 99.7% (98.7-100%) and 92.7% (89.9-95.3%) and of the CFT were 90.6% (86.0-95.3%) and 98.7% (98.0-99.3%). The sensitivity and specificity of a combined test, where the CFT is subsequently applied to the pig sera that test positive in the ELISA, were estimated at 90.2% (85.6-95.0%) and 99.9% (99.8-100%), respectively. The cost of the combined test was less than the cost of the use of the CFT alone, at prevalences <54%. Prevalences and predictive values and their 95% limits were estimated in six sub-samples of data. The estimates of sensitivity and specificity obtained in the present investigation generally validate those reported from other sources.


Analysis of resistance genes in pan-resistant Myroides odoratimimus clinical strain PR63039 using whole genome sequencing.
To clarify the antibiotic resistance mechanisms of Myroides odoratimimus, pan-resistant M. odoratimimus strain PR63039 was isolated and its genome sequenced and analyzed. Antimicrobial susceptibility testing was conducted using the Kirby-Bauer disk diffusion method, and the Phoenix-100 Automated Microbiology System with a NMIC/ID-4 panel including aminoglycosides, β-lactams, polypeptides, quinolones, sulfonamides, chloramphenicols, and tetracyclines. Single-molecule real-time whole genome sequencing was conducted using the PacBio RSII system, and genome annotation was performed using RAST and IMG ER. To characterize the genome features, a number of databases and software programs, including GC-Profile, CG viewer, the VFDB database, ISfinder, RADB, CARD, ResFinder, and PHAST, were used. M. odoratimimus isolate PR63039 was resistant to almost all antibiotics tested, suggesting pan-drug resistance. The genome consisted of a 4,366,950-bp chromosome and a 90,798-bp plasmid (p63039), which contained a large number of resistance genes and virulence factors. The distribution of the resistance genes was distinctive, and a resistance region, designated MY63039-RR, was identified. RAST analysis indicated that 108 of the annotated genes were potentially involved in virulence, disease, and defense, all of which could be associated with resistance and pathogenicity. Prophage analysis also identified two incomplete prophages in the genome of M. odoratimimus PR63039. Multiple antibiotic-resistance genes were identified, including those associated with resistance to tetracycline (tetX), macrolides (ereB, cfrA, lasE), sulfonamides (sul2, sul3), β-lactams (blaMUS-1, blaTUS-1, blaSFB-1, blaSLB-1, blaOXA-209, blaOXA-347), and chloramphenicol (cat). Further, the presence of 18 antibiotic efflux pump-encoding resistance genes, including acrB, acrD, acrF, adeB, adeG, adeJ, amrB, ceoB, cmeB, mdsB, mexB, mexD, mexF, mtrD, smeE, mdtF, macB, likely accounts for the observed quinolone resistance of strain PR63039. To the best of our knowledge, this is the first report of the presence of the blaSFB-1, blaSLB-1, blaOXA-209, blaOXA-347, and tetX resistance genes in M. odoratimimus.


Neurospecific translation control and the problem of potent danger of drugs and chemicals: a caution.
At present, chemicals are an integral part of the surrounding biosphere. A great number of new xenobiotics for industrial, pharmaceutical, agricultural, or mode-of-life daily use (perfumes, cosmetics, food additives, etc.) may play a role of a danger health hazards. These chemicals may be environmental pollutants and due to this circumstance they promote different ecological disorders including the several epidemic-like processes such as, for instance, Minamata disease (chronic alimentary poisoning with methyl mercury), etc. Also, these chemicals may be industrial hazards promoting the origin and development of various occupational diseases. Finally, the numerous side effects of multiple new drugs may serve as causes of a number of different health disorders. Briefly, we must agree that modern man exists in the world with such inalienable elements as the steadfast increase of chemical soiling of Earths biosphere. Naturally, human health protection in our "chemically soiled" world is very difficult by urgent task. As for the solving of this task, it may be reached only in the case of successful fundamental studies of mechanisms of toxic action of different classes of chemicals performed at different biological levels (systemic, organ/tissue, cellular and molecular levels of research). A separate and special population of modern health-hazardous chemicals is a group of agents which selectively suppress protein synthesis in mammalian cells and tissues due to the direct effect on the translation machinery elements or on the messenger RNA processing steps. The agents of this group ("translation blockers" or, the same but more broadly, "protein synthesis inhibitors" (PSI) usually are quite dangerous for human health since these substances inhibit the central molecular process of life, i.e., the synthesis of protein molecules. The small but important subclass of the PSI is represented by the agents with marked neurotropic properties, i.e., by the agents which are able to promote the effective inhibition of protein synthesis in the brain, while the same agents do not essentially influence the translation processes in the liver and all other organs of the animal (human) organism. The main aim of the present monograph is to review and analyze the data obtained recently in the course of biochemical research of several neurotropic PSI (methyl mercury, lithium salts). However, this is not the single aim of the book. Thus, besides this the present monograph deals with analysis of the general peculiarities of action of some non-neurotrophic inhibitors which are able, nevertheless, to direct a number of specific neurotrophic effects (Cordycepin, tRNA).(ABSTRACT TRUNCATED AT 400 WORDS)


Community acceptability and adoption of integrated community case management in Uganda.
Integrated community case management (iCCM) is a recommended strategy to curb child mortality. Drawing on diffusion of innovations (DOIs), the acceptability and adoption of iCCM were qualitatively explored. Data from focus group discussions and interviews with community members, community health workers (CHWs), and supervisors conducted in seven communities were analyzed using content analysis. Perceived relative advantage and compatibility of the program with sociocultural beliefs and healthcare expectations of the communities positively affected acceptability and adoption of iCCM. The degree of stringency, quality, and cost of access to healthcare were crucial to adoption. Failure of the health system to secure regular drug supplies, monetary support, and safe referrals globally hindered adoption. Individual CHW characteristics like undesired behavior, demotivation, and lack of reciprocated trust deterred adoption in some areas. Optimal functioning of iCCM programs will require community sensitization and targeted health systems strengthening to enhance observable program benefits like reduced child mortality.


Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer.
The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher's exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43-0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22-1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51-1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.


Aromaticity in transition structures.
Aromaticity is an essential concept in chemistry, employed to account for the unusual stability, reactivity, molecular structures, and other properties of many unsaturated organic compounds. This concept was later extended to inorganic molecules and to saturated systems with mobile electrons, as well as to transition structures, the focus of the present review. Although transition structures are inherently delocalized, not all exhibit aromaticity. We contrast here examples of pericyclic reaction transition structures (where aromaticity is significant) with those for illustrative pseudo-pericyclic reactions (where aromaticity is less or not important). Non-pericyclic reactions may also have aromatic transition structures. State-of-the-art computational methods to evaluate the aromaticity of transition structures are described briefly.


Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring: hurdles, achievements, and future outlook.
In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics-Moving into Regulation and Monitoring, held 21-23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada). The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets. Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data. The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach.


Multisensory integration sites identified by perception of spatial wavelet filtered visual speech gesture information.
Perception of speech is improved when presentation of the audio signal is accompanied by concordant visual speech gesture information. This enhancement is most prevalent when the audio signal is degraded. One potential means by which the brain affords perceptual enhancement is thought to be through the integration of concordant information from multiple sensory channels in a common site of convergence, multisensory integration (MSI) sites. Some studies have identified potential sites in the superior temporal gyrus/sulcus (STG/S) that are responsive to multisensory information from the auditory speech signal and visual speech movement. One limitation of these studies is that they do not control for activity resulting from attentional modulation cued by such things as visual information signaling the onsets and offsets of the acoustic speech signal, as well as activity resulting from MSI of properties of the auditory speech signal with aspects of gross visual motion that are not specific to place of articulation information. This fMRI experiment uses spatial wavelet bandpass filtered Japanese sentences presented with background multispeaker audio noise to discern brain activity reflecting MSI induced by auditory and visual correspondence of place of articulation information that controls for activity resulting from the above-mentioned factors. The experiment consists of a low-frequency (LF) filtered condition containing gross visual motion of the lips, jaw, and head without specific place of articulation information, a midfrequency (MF) filtered condition containing place of articulation information, and an unfiltered (UF) condition. Sites of MSI selectively induced by auditory and visual correspondence of place of articulation information were determined by the presence of activity for both the MF and UF conditions relative to the LF condition. Based on these criteria, sites of MSI were found predominantly in the left middle temporal gyrus (MTG), and the left STG/S (including the auditory cortex). By controlling for additional factors that could also induce greater activity resulting from visual motion information, this study identifies potential MSI sites that we believe are involved with improved speech perception intelligibility.


Computational design of a biologically active enzyme.
Rational design of enzymes is a stringent test of our understanding of protein chemistry and has numerous potential applications. Here, we present and experimentally validate the computational design of enzyme activity in proteins of known structure. We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity. The resulting designs contain 18 to 22 mutations, exhibit 10(5)- to 10(6)-fold rate enhancements over the uncatalyzed reaction, and are biologically active, in that they support the growth of Escherichia coli under gluconeogenic conditions. The inherent generality of the design method suggests that many enzymes can be designed by this approach.


Survey of 243 ART patients having made a final disposition decision about their surplus cryopreserved embryos: the crucial role of symbolic embryo representation.
In couples who have chosen and confirmed the fate of surplus frozen embryos, which factors influence their decision, with a special emphasis on their symbolic representation of the embryo(s)? Embryo representation and gamete donation use significantly influence the fate of surplus cryopreserved embryos. Previous studies report difficulties for couples to decide whether or not to continue storing their frozen embryo(s) and different factors have been already highlighted which influence their decision, including embryo conceptualization, information and support provided by the medical institution, quality of embryo(s) and life events. Little is known, however, about couples who definitely decided to stop their parental project and finalized the process of decision-making about the fate of their cryopreserved embryo(s). This prospective study was conducted over a period of 3 years (2007-2010) and included IVF/ICSI patients with surplus frozen embryos, who made a final embryo disposition decision. Among the 280 eligible IVF/ICSI patients, 247 agreed to participate in the study. According to the available options, 91 persons chose to 'stop cryopreservation', 77 chose donation to 'research' and 48 'embryo donation' to infertile couples. Furthermore, 31 participants who chose embryo donation for a parental project were refused by the center as not compatible with their mandatory medical conditions. Among them, 27 participants then selected donation to research as a new option and were included in a fourth group: 'donation to research after Refusal of Embryo Donation for parental project' or 'research-RED' (n = 27). Four participants chose 'stop cryopreservation', however, given the small number of subjects this latter group was not included in the analysis. In all, 243 participants who made a final choice concerning the fate of their cryopreserved embryos were included in this study. Participants were sent a letter of invitation to a semi-structured interview of 30 min with a psychologist. Interviews were conducted separately for each partner, including a questionnaire with a common part and a specific part, according to the chosen option, and allowing a quantitative evaluation. A multivariate logistic regression model was used to assess the link between their embryo representation and their decision about their embryos' fate. After adjustment for age, gender, gamete donation, number of children and the different embryo representations, a choice to 'stop cryopreservation' is more frequent if the embryo is represented as a child [odds ratio (OR) adjusted = 3.29, 95% confidence interval (CI) = 1.62-6.66], P = 0.0009. Representing the embryo as a project prompts patients to choose 'donation to research' [OR adjusted = 3.76, 95% CI = 1.56-9.06], P = 0.0032. Respondents are more likely to choose 'embryo donation' if they represent the embryo as a potential person [OR adjusted = 3.77, 95% CI = 1.45-9.80], P = 0.0064. Furthermore, patients who benefited from gamete donation are ∼10 times more likely to donate their embryos to another couple [OR adjusted = 10.62, 95% CI = 3.99-28.30], P < 0.0001. For more than half the participants (57%) the decision-making was easy, however, deciding to stop cryopreservation was significantly more difficult than choosing research or embryo donation (P < 0.0001). Socio-economic status, moral and religious affiliations are known to influence the choice of couples but analyzing these factors was not an aim of the present study. When couples definitely decide to stop their parental project, the embryo symbolic representation remains the main factor that influences the fate of their frozen embryo(s). Moreover, this representation can evolve when influenced by external events and information provided. In order to support patients who are making this difficult decision, it could be helpful to explore this symbolic representation early in the IVF/ICSI procedure, before surplus embryo freezing, as a new tool enhancing the accuracy of counseling. this study was supported by a grant from the 'Agence de la biomedicine (ABM)', the national regulatory ART agency, under the authority of the French Ministry of Health. The authors have no conflict of interest to declare.


Ecological regime shift drives declining growth rates of sea turtles throughout the West Atlantic.
Somatic growth is an integrated, individual-based response to environmental conditions, especially in ectotherms. Growth dynamics of large, mobile animals are particularly useful as bio-indicators of environmental change at regional scales. We assembled growth rate data from throughout the West Atlantic for green turtles, Chelonia mydas, which are long-lived, highly migratory, primarily herbivorous mega-consumers that may migrate over hundreds to thousands of kilometers. Our dataset, the largest ever compiled for sea turtles, has 9690 growth increments from 30 sites from Bermuda to Uruguay from 1973 to 2015. Using generalized additive mixed models, we evaluated covariates that could affect growth rates; body size, diet, and year have significant effects on growth. Growth increases in early years until 1999, then declines by 26% to 2015. The temporal (year) effect is of particular interest because two carnivorous species of sea turtles-hawksbills, Eretmochelys imbricata, and loggerheads, Caretta caretta-exhibited similar significant declines in growth rates starting in 1997 in the West Atlantic, based on previous studies. These synchronous declines in productivity among three sea turtle species across a trophic spectrum provide strong evidence that an ecological regime shift (ERS) in the Atlantic is driving growth dynamics. The ERS resulted from a synergy of the 1997/1998 El Niño Southern Oscillation (ENSO)-the strongest on record-combined with an unprecedented warming rate over the last two to three decades. Further support is provided by the strong correlations between annualized mean growth rates of green turtles and both sea surface temperatures (SST) in the West Atlantic for years of declining growth rates (r = -.94) and the Multivariate ENSO Index (MEI) for all years (r = .74). Granger-causality analysis also supports the latter finding. We discuss multiple stressors that could reinforce and prolong the effect of the ERS. This study demonstrates the importance of region-wide collaborations.


Astronomical Fourier spectrometer.
A high resolution near ir Fourier spectrometer with the same general design as previously described laboratory instruments has been built for astronomical observations at a coudé focus. Present spectral range is 0.8-3.5 microm with PbS and Ge detectors and maximum path difference 1 m. The servo system can accommodate various recording modes: stepping or continuous scan, path difference modulation, sky chopping. A real time computer is incorporated into the system, which has been set up at the Hale 500-cm telescope on Mount Palomar. Samples of the results are given.


Qualitative and quantitative assessment of adenosine triphosphate stress whole-heart dynamic myocardial perfusion imaging using 256-slice computed tomography.
The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA) using stress dynamic whole-heart computed tomography perfusion (CTP) imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF) for the estimation of the severity of coronary artery stenosis. Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min) stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation), and 9 of the 11 patients underwent coronary angiography (CAG). Stress dynamic CTP (whole-heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps) was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv). The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural). MBF (ml/100g/min) was measured by deconvolution. Differences in MBF (mean ± standard error) according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients), 11 coronary stenoses (> 50% reduction in diameter) were observed. In 353 myocardial segments, HPA was significantly related to MBF (P < 0.05; normal 295 ± 94; subendocardial 186 ± 67; and transmural 80 ± 53). Coronary territory analysis revealed a significant relationship between coronary stenosis severity and MBF (P < 0.05; non-significant stenosis [< 50%], 284 ± 97; moderate stenosis [50-70%], 184 ± 74; and severe stenosis [> 70%], 119 ± 69). The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease.


Evaluation of the WinROP system for identifying retinopathy of prematurity in Czech preterm infants.
Retinopathy of Prematurity (ROP) is a potentially serious condition that can afflict preterm infants. Timely and correct identification of individuals at risk of developing a serious form of ROP is therefore of paramount importance. WinROP is an online system for predicting ROP based on birth weight and weight increments. However, the results vary significantly for various populations. It has not been evaluated in the Czech population. This study evaluates the test characteristics (specificity, sensitivity, positive and negative predictive values) of the WinROP system in Czech preterm infants. Data on 445 prematurely born infants included in the ROP screening program at the University Hospital Ostrava, Czech Republic, were retrospectively entered into the WinROP system and the outcomes of the WinROP and regular screening were compared. All 24 infants who developed high-risk (Type 1 or Type 2) ROP were correctly identified by the system. The sensitivity and negative predictive values for this group were 100%. However, the specificity and positive predictive values were substantially lower, resulting in a large number of false positives. Extending the analysis to low risk ROP, the system did not provide such reliable results. The system is a valuable tool for identifying infants who are not likely to develop high-risk ROP and this could help to substantially reduce the number of preterm infants in need of regular ROP screening. It is not suitable for predicting the development of less serious forms of ROP which is however in accordance with the declared aims of the WinROP system.


Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation.
Galactooligosaccharides (GOS), prebiotic nondigestible oligosaccharides derived from lactose, have the potential for improving mineral balance and bone properties. This study examined the dose-response effect of GOS supplementation on calcium and magnesium absorption, mineral retention, bone properties, and gut microbiota in growing rats. Seventy-five 4-week-old male Sprague-Dawley rats were randomized into one of five treatment groups (n = 15/group) and fed a diet containing 0, 2, 4, 6, or 8% GOS by weight for 8 weeks. Dietary GOS significantly decreased cecal pH and increased cecal wall weight and content weight in a dose-dependent manner (p < 0.0001). Fingerprint patterns of the 16S rRNA gene PCR-DGGE from fecal DNA indicated the variance of bacterial community structure, which was primarily explained by GOS treatments (p = 0.0001). Quantitative PCR of the samples revealed an increase in the relative proportion of bifidobacteria with GOS (p = 0.0001). Net calcium absorption was increased in a dose-response manner (p < 0.01) with GOS supplementation. Dietary GOS also increased (p < 0.02) net magnesium absorption, femur ⁴⁵Ca uptake, calcium and magnesium retention, and femur and tibia breaking strength. Distal femur total and trabecular volumetric bone mineral density (vBMD) and area and proximal tibia vBMD increased (p < 0.02) with GOS supplementation. Trabecular-rich bones, that is, those that rapidly turn over, were most benefited. Regression modeling showed that GOS benefited calcium and magnesium utilization and vBMD through decreased cecal pH, increased cecal wall and content weight, and increased proportion of bifidobacteria.


A case-control study of male breast cancer.
A case-control study was conducted in Los Angeles County, CA, of 75 male breast cancer cases aged 20-74 yr at diagnosis to investigate the role of a number of suspected risk factors. The study involved both interviews and laboratory measurements. Factors under study included fertility and marital history, obesity, alcohol and cigarette consumption, use of drugs known or suspected of causing gynecomastia, family history of breast cancer, history of radiation exposure to the upper body, sex chromatin analysis, serum levels of prolactin, testosterone, estrone, estradiol and sex-hormone-binding globulin, as well as urinary levels of estrone, estradiol, and estriol. Two patients versus no controls tested positive for sex chromatin and were excluded from further analyses. The only statistically significant risk factor identified was greater weight of the cases at age 30; a man who weighed 80 or more kg at age 30 had twice the risk of breast cancer of a man weighing less than 60 kg at that age. Serum estrone levels were positively, and sex-hormone-binding globulin levels were negatively, related to body weight, and we interpret the greater weight of the cases as suggesting that the underlying risk factor is an increased exposure to bioavailable estrogen. None of the differences observed between cases and controls for either the serum or urinary hormone levels was, however, statistically significant and there did not appear to be any large absolute excess of estrogens or deficit of testosterone in the cases. This apparent contradiction may be explained by the fact that there was little difference in weight between the cases and controls at the time of sampling.


Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity.
The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)- DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.


Differences in Perceived Need for Medical, Therapeutic, and Family Support Services Among Children With ASD.
Identifying racial and ethnic differences in perceived need for treatment among families of children with autism spectrum disorder (ASD) will improve understanding of disparities in care seeking. We described racial and ethnic differences in perceived need for services that children with ASD and their families frequently use. We conducted bivariate analyses of racial and ethnic categories and perceived need for 6 common services used by children with ASD as found in the 2005 to 2006 (n = 2123) and the 2009 to 2010 (n = 3055) National Survey of Children With Special Health Care Needs data sets. Multivariate logistic regressions within concatenated data sets were conducted to examine associations between racial and ethnic category and perceived service needs while controlling for predisposing, enabling, and child factors. Compared with caregivers of white non-Hispanic children with ASD, caregivers of Hispanic children reported less need for prescription medications in adjusted multivariate analyses. Caregivers of black non-Hispanic children with ASD reported less need for prescription medications and for child and family mental health services than caregivers of white non-Hispanic children. Both English-speaking Hispanic caregivers and black non-Hispanic caregivers reported greater need for occupational, speech, and physical therapy than white non-Hispanic caregivers. No racial or ethnic differences were found in perceived need for specialty medical care or respite care. Caregivers of children with ASD from different racial and ethnic backgrounds may differentially perceive need for different types of care. Their perceptions may in turn affect how they prioritize and seek care, independent of their child's specific needs.


Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids.
The emergence of multiple axes is an essential element in the establishment of the mammalian body plan. This process takes place shortly after implantation of the embryo within the uterus and relies on the activity of gene regulatory networks that coordinate transcription in space and time. Whereas genetic approaches have revealed important aspects of these processes1, a mechanistic understanding is hampered by the poor experimental accessibility of early post-implantation stages. Here we show that small aggregates of mouse embryonic stem cells (ESCs), when stimulated to undergo gastrulation-like events and elongation in vitro, can organize a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimic embryonic spatial and temporal gene expression. The establishment of the three major body axes in these 'gastruloids'2,3 suggests that the mechanisms involved are interdependent. Specifically, gastruloids display the hallmarks of axial gene regulatory systems as exemplified by the implementation of collinear Hox transcriptional patterns along an extending antero-posterior axis. These results reveal an unanticipated self-organizing capacity of aggregated ESCs and suggest that gastruloids could be used as a complementary system to study early developmental events in the mammalian embryo.


Aggressive Behaviors in Alzheimer Disease and Mild Cognitive Impairment: Systematic Review and Meta-Analysis.
We aim to estimate the risk of perpetrating aggression in Alzheimer disease (AD) and mild cognitive impairment (MCI) by conducting a systematic review and meta-analysis of primary studies. A systematic search was conducted in six bibliographic databases according to a preregistered protocol. Studies that reported aggressive behaviors in individuals with AD and MCI compared with healthy individuals or those with other dementia etiologies were identified. Risks of aggressive behaviors were assessed using random effects models to calculate pooled odds ratios (ORs). Publication bias was examined. In total, 17 studies involving 6,399 individuals with AD and 2,582 with MCI were identified. Compared with healthy individuals, significantly increased risks of aggressive behaviors were found in AD (OR, 4.9, 95% CI, 1.8-13.2) but not in MCI (OR, 1.8, 95% CI, 0.7-4.3). When comparing AD with MCI, the risk in AD was higher (OR, 2.6, 95% CI, 1.7-4.0). We found no differences in risk of aggressive behaviors between AD and other dementia subtypes or between amnestic and nonamnestic MCI. Individuals with AD are at higher risk of manifesting aggressive behaviors than healthy individuals or those with MCI. Our findings not only underscore the necessity of treatment of aggressive behaviors in AD but also highlight the importance of preventing the transition from MCI to AD.


The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis.
Tumor development in the human colon is commonly accompanied by epigenetic changes, such as DNA methylation and chromatin modifications. These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor cells with enhanced survival potential. A recent high-throughput gene expression analysis conducted by our group identified numerous genes whose transcription was markedly diminished in colorectal tumors. One of these, the protein-tyrosine phosphatase receptor type R (PTPRR) gene, was dramatically downregulated from the earliest stages of cellular transformation. Here, we show that levels of both major PTPRR transcript variants are markedly decreased (compared with normal mucosal levels) in precancerous and cancerous colorectal tumors, as well in colorectal cancer cell lines. The expression of the PTPRR-1 isoform was inactivated in colorectal cancer cells as a result of de novo CpG island methylation and enrichment of transcription-repressive histone-tail marks, mainly H3K27me3. De novo methylation of the PTPRR-1 transcription start site was demonstrated in 29/36 (80%) colorectal adenomas, 42/44 (95%) colorectal adenocarcinomas, and 8/8 (100%) liver metastases associated with the latter tumors. Epigenetic downregulation of PTPRR seems to be an early alteration in colorectal cell transformation, which is maintained during the clonal selection associated with tumor progression. It may represent a preliminary step in the constitutive activation of the RAS/RAF/MAPK/ERK signalling, an effect that will later be consolidated by mutations in genes encoding key components of this pathway.


Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial.
Vitamin D may decrease depression symptoms through its beneficial effects on neurotransmitters, metabolic profiles, biomarkers of inflammation, and oxidative stress. This study was designed to assess whether vitamin D supplementation can reduce symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). This randomized, double-blind, placebo-controlled clinical trial was performed in 40 patients between 18 and 65 y of age with a diagnosis of MDD based on criteria from the Diagnostic and Statistical Manual of Mental Disorders. Patients were randomly assigned to receive either a single capsule of 50 kIU vitamin D/wk (n = 20) or placebo (n = 20) for 8 wk. Fasting blood samples were taken at baseline and postintervention to quantify relevant variables. The primary [Beck Depression Inventory (BDI), which examines depressive symptoms] and secondary (glucose homeostasis variables, lipid profiles, hs-CRP, and biomarkers of oxidative stress) outcomes were assessed. Baseline concentrations of mean serum 25-hydroxyvitamin D were significantly different between the 2 groups (9.2 ± 6.0 and 13.6 ± 7.9 μg/L in the placebo and control groups, respectively, P = 0.02). After 8 wk of intervention, changes in serum 25-hydroxyvitamin D concentrations were significantly greater in the vitamin D group (+20.4 μg/L) than in the placebo group (-0.9 μg/L, P < 0.001). A trend toward a greater decrease in the BDI was observed in the vitamin D group than in the placebo group (-8.0 and -3.3, respectively, P = 0.06). Changes in serum insulin (-3.6 compared with +2.9 μIU/mL, P = 0.02), estimated homeostasis model assessment of insulin resistance (-1.0 compared with +0.6, P = 0.01), estimated homeostasis model assessment of β cell function (-13.9 compared with +10.3, P = 0.03), plasma total antioxidant capacity (+63.1 compared with -23.4 mmol/L, P = 0.04), and glutathione (+170 compared with -213 μmol/L, P = 0.04) in the vitamin D group were significantly different from those in the placebo group. Overall, vitamin D supplementation of patients with MDD for 8 wk had beneficial effects on the BDI, indicators of glucose homeostasis, and oxidative stress. This trial was registered at www.irct.ir as IRCT201412065623N29.


Web-based mammography audit feedback.
Interpreting screening mammography accurately is challenging and requires ongoing education to maintain and improve interpretative skills. Recognizing this, many countries with organized breast screening programs have developed audit and feedback systems using national performance data to help radiologists assess and improve their skills. We developed and tested an interactive Website to provide screening and diagnostic mammography audit feedback with comparisons to national and regional benchmarks. Radiologists who participate in three Breast Cancer Surveillance Consortium registries in the United States were invited during 2009 and 2010 to use a Website that provides tabular and graphical displays of mammography audit reports with comparisons to national and regional performance measures. We collected data about the use and perceptions of the Website. Thirty-five of 111 invited radiologists used the Website from one to five times in a year. The most popular measure was sensitivity for both screening and diagnostic mammography, whereas a table with all measures was the most visited page. Of the 13 radiologists who completed the postuse survey, all found the Website easy to use and navigate, 11 found the benchmarks useful, and nine reported that they intended to improve a specific outcome measure that year. An interactive Website to provide customized mammography audit feedback reports to radiologists has the potential to be a powerful tool in improving interpretive performance. The conceptual framework of customized audit feedback reports can also be generalized to other imaging tests.


Regulation of B lymphocyte and macrophage development by graded expression of PU.1.
The ets family transcription factor PU.1 is required for the development of multiple lineages of the immune system. Using retroviral transduction of PU.1 complementary DNA into mutant hematopoietic progenitors, we demonstrate that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages. A low concentration of PU. 1 protein induces the B cell fate, whereas a high concentration promotes macrophage differentiation and blocks B cell development. Conversely, a transcriptionally weakened mutant protein preferentially induces B cell generation. Our results suggest that graded expression of a transcription factor can be used to specify distinct cell fates in the hematopoietic system.


The adaptation of a CTN-1 rabies virus strain to high-titered growth in chick embryo cells for vaccine development.
Rabies virus is the causative agent of rabies, a central nervous system disease that is almost invariably fatal. Currently vaccination is the most effective strategy for preventing rabies, and vaccines are most commonly produced from cultured cells. Although the vaccine strains employed in China include CTN, aG, PM and PV, there are no reports of strains that are adapted to primary chick embryo cells for use in human rabies prevention in China. Rabies virus strain CTN-1 V was adapted to chick embryo cells by serial passage to obtain the CTNCEC25 strain. A virus growth curve demonstrated that the CTNCEC25 strain achieved high titers in chick embryo cells and was nonpathogenic to adult mice by intracerebral inoculation. A comparison of the structural protein genes of the CTNCEC25 strain and the CTN-1 V strain identified eight amino acid changes in the mature M, G and L proteins. The immunogenicity of the CTNCEC25 strain increased with the adaptation process in chick embryo cells and conferred high protective efficacy. The inactivated vaccine induced high antibody responses and provided full protection from an intramuscular challenge in adult mice. This is the first description of a CTNCEC25 strain that was highly adapted to chick embryo cells, and both its in vitro and in vivo biological properties were characterized. Given the high immunogenicity and good propagation characteristics of the CTNCEC25 strain, it has excellent potential to be a candidate for development into a human rabies vaccine with high safety and quality characteristics for controlling rabies in China.


Twinfilin is an actin-filament-severing protein and promotes rapid turnover of actin structures in vivo.
Working in concert, multiple actin-binding proteins regulate the dynamic turnover of actin networks. Here, we define a novel function for the conserved actin-binding protein twinfilin, which until now was thought to function primarily as a monomer-sequestering protein. We show that purified budding yeast twinfilin (Twf1) binds to and severs actin filaments in vitro at pH below 6.0 in bulk kinetic and fluorescence microscopy assays. Further, we use total internal reflection fluorescence (TIRF) microscopy to demonstrate that Twf1 severs individual actin filaments in real time. It has been shown that capping protein directly binds to Twf1 and is required for Twf1 localization to cortical actin patches in vivo. We demonstrate that capping protein directly inhibits the severing activity of Twf1, the first biochemical function ascribed to this interaction. In addition, phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] inhibits Twf1 filament-severing activity. Consistent with these biochemical activities, a twf1Delta mutation causes reduced rates of cortical actin patch turnover in living cells. Together, our data suggest that twinfilin coordinates filament severing and monomer sequestering at sites of rapid actin turnover and is controlled by multiple regulatory inputs.


Graphene oxide size and oxidation degree govern its supramolecular interactions with siRNA.
Several studies have demonstrated the ability of graphene oxide (GO) to efficiently adsorb small-interfering RNA (siRNA) on its surface and to transport it into cells. However, studies on whether and how siRNA interacts with GO are still inconclusive. In this context, understanding the interaction between GO and siRNA is fundamental to design new efficient gene silencing tools. In this work, the interactions between GO and siRNA molecules were systematically investigated. We focused on how the GO size, oxygenated groups present on the surface and chemical functionalization affect the double helix siRNA structure, using gel electrophoresis, UV-Vis spectroscopy, fluorescence resonance energy transfer (FRET) and circular dichroism (CD). We found that the siRNA secondary structure was clearly altered by the interaction with GO flakes. In addition, we were able to correlate the double strand damage with the size and the oxygenated groups present on the GO sheets. Finally, we demonstrated that GO functionalized with low molecular weight polyethyleneimine (PEI, 800 Da) is able to protect siRNA from structural modifications. We believed that this research effort will improve our understanding of the behavior of GO/siRNA complexes, and thus facilitate the design of appropriate bio/nanointerfaces and new efficient gene silencing systems.


Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.
During cerebellar development, the main portion of the cerebellar plate neuroepithelium gives birth to Purkinje cells and interneurons, whereas the rhombic lip, the germinal zone at its dorsal edge, generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components cooperate to form the intricate cerebellar structure. Here, we found that a polarized cerebellar structure self-organizes in 3D human embryonic stem cell (ESC) culture. The self-organized neuroepithelium differentiates into electrophysiologically functional Purkinje cells. The addition of fibroblast growth factor 19 (FGF19) promotes spontaneous generation of dorsoventrally polarized neural-tube-like structures at the level of the cerebellum. Furthermore, addition of SDF1 and FGF19 promotes the generation of a continuous cerebellar plate neuroepithelium with rhombic-lip-like structure at one end and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human-ESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.


Towards a neuromorphic vestibular system.
The vestibular system plays a crucial role in the sense of balance and spatial orientation in mammals. It is a sensory system that detects both rotational and translational motion of the head, via its semicircular canals and otoliths respectively. In this work, we propose a real-time hardware model of an artificial vestibular system, implemented using a custom neuromorphic Very Large Scale Integration (VLSI) multi-neuron chip interfaced to a commercial Inertial Measurement Unit (IMU). The artificial vestibular system is realized with spiking neurons that reproduce the responses of biological hair cells present in the real semicircular canals and otholitic organs. We demonstrate the real-time performance of the hybrid analog-digital system and characterize its response properties, presenting measurements of a successful encoding of angular velocities as well as linear accelerations. As an application, we realized a novel implementation of a recurrent integrator network capable of keeping track of the current angular position. The experimental results provided validate the hardware implementation via comparisons with a detailed computational neuroscience model. In addition to being an ideal tool for developing bio-inspired robotic technologies, this work provides a basis for developing a complete low-power neuromorphic vestibular system which integrates the hardware model of the neural signal processing pathway described with custom bio-mimetic gyroscopic sensors, exploiting neuromorphic principles in both mechanical and electronic aspects.


Effectiveness of convalescent plasma therapy in severe COVID-19 patients.
Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.


[Quality of life and health: conceptual and methodological issues].
The quality of life (QL) concept has led to extensive scientific research and has been increasingly used by health care professionals treating a wide range of diseases. This paper addresses the historical use of the concept and specific issues linked to conceptual and methodological aspects of the QL construct within the health care context. Reviewing the literature, two aspects stand out: subjectivity and multidimensionality. In the methodological field, the construction and/or adaptation of QL measurement instruments appear as a significant trend. Theoretical and methodological efforts have helped clarify and improve the concept's adequacy. The QL construct is definitely interdisciplinary, encompassing contributions by different areas of knowledge and research, thereby improving its conceptual and methodological potential as a research instrument. Therefore, use of the concept can actually help improve both the quality and the integrated, multidimensional nature of health care from a perspective that views the latter as a basic citizen's right.


The classical and quantum dynamics of molecular spins on graphene.
Controlling the dynamics of spins on surfaces is pivotal to the design of spintronic and quantum computing devices. Proposed schemes involve the interaction of spins with graphene to enable surface-state spintronics and electrical spin manipulation. However, the influence of the graphene environment on the spin systems has yet to be unravelled. Here we explore the spin-graphene interaction by studying the classical and quantum dynamics of molecular magnets on graphene. Whereas the static spin response remains unaltered, the quantum spin dynamics and associated selection rules are profoundly modulated. The couplings to graphene phonons, to other spins, and to Dirac fermions are quantified using a newly developed model. Coupling to Dirac electrons introduces a dominant quantum relaxation channel that, by driving the spins over Villain's threshold, gives rise to fully coherent, resonant spin tunnelling. Our findings provide fundamental insight into the interaction between spins and graphene, establishing the basis for electrical spin manipulation in graphene nanodevices.


Mechanisms of methotrexate resistance in osteosarcoma.
High-dose methotrexate is a major component of current protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resistance include decreased transport through the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade osteosarcoma. RFC and DHFR mRNA expression were studied by semiquantitative reverse transcription-PCR. The RFC and DHFR genes were studied for deletions and amplification by Southern blot. Thirteen of 20 (65%) osteosarcoma samples were found to have decreased RFC expression at the time of initial biopsy. At definitive surgery and relapse, 10 of 22 (45%) were found to have decreased RFC expression. Seventeen of 26 (65%) samples with a poor response to chemotherapy had decreased RFC expression, whereas 5 of 14 (36%) samples with a good response had a decrease (P = 0.03). None of the samples had an RFC gene deletion. Two of 20 samples (10%) showed increased DHFR expression at initial biopsy. The frequency of increased DHFR expression was significantly higher in metastatic or recurrent tumors (62%, P = 0.014). None of the samples showed evidence of DHFR gene amplification. The high frequency of decreased RFC expression in the biopsy material suggests that impaired transport of methotrexate is a common mechanism of intrinsic resistance in osteosarcoma. Increased DHFR expression in the pulmonary metastases may be a mechanism of acquired methotrexate resistance or a difference between primary and metastatic lesions.


The Functional Mobility Scale (FMS).
We devised a new Functional Mobility Scale (FMS) to describe functional mobility in children with cerebral palsy, as an aid to communication between orthopaedic surgeons and health professionals. The unique feature of the FMS is the freedom to score functional mobility over three distinct distances, chosen to represent mobility in the home, at school and in the wider community. We examined the construct, content, and concurrent validity of the FMS in a cohort of 310 children with cerebral palsy by comparing the FMS to existing scales and to instrumented measures of physical function. We demonstrated the scale to be both valid and reliable in a consecutive population sample of 310 children with cerebral palsy seen in our tertiary referral center. The FMS was useful for discriminating between large groups of children with varying levels of disabilities and functional mobility and sensitive to detect change after operative intervention.


Intraosseous hemangioma of the rib mimicking an aggressive chest wall tumor.
Bone hemangiomas are extremely rare in the ribs, with only a handful of cases reported in the literature. A case of a rib hemangioma is presented in which the pre-resection diagnosis was an aggressive chest wall tumor. The plain film, CT, MRI and bone scan features of the lesion were reviewed with the pathological correlation. On imaging, the lesion was expansile and lytic, and it also had fine bony trabeculae. The lesion also demonstrated growth beyond a disrupted bony cortex, suggesting malignancy. This case report adds to the literature on this rare condition and discusses the issues in the diagnosis of chest wall tumors.


Distinct actions of akt1 on skeletal architecture and function.
Skeletal integrity is dependent on the coordinated actions of bone-forming osteoblasts and bone-resorbing osteoclasts, which recognize and respond to multiple environmental inputs. Here we have studied the roles in bone development and growth of Akt1 and Akt2, two closely related signaling proteins, by evaluating mice lacking either of these enzymes. Global deficiency of Akt1 but not Akt2 caused a reduction in whole body and femoral bone mineral density, in femoral cortical thickness and volume, and in trabecular thickness in both males and females when measured at 20-weeks of age, which was reflected in diminished femoral resistance to fracture. Haplo-deficiency of Akt1 in male mice also decreased femoral cortical and trabecular skeletal parameters, and reduced bone strength. Cell-based studies showed that genetic Akt1 deficiency diminished the rate of proliferation of osteoblast progenitors and impaired osteoclast differentiation in primary culture but that loss of Akt2 did not. Our results demonstrate differential effects of Akt1 and Akt2 on skeletal maturation and architecture through actions on both osteoblast and osteoclast precursors.


Can utility-weighted health-related quality-of-life estimates capture health effects of quality improvement for depression?
Utility methods that are responsive to changes in desirable outcomes are needed for cost-effectiveness (CE) analyses and to help in decisions about resource allocation. Evaluated is the responsiveness of different methods that assign utility weights to subsets of SF-36 items to average improvements in health resulting from quality improvement (QI) interventions for depression. A group level, randomized, control trial in 46 primary care clinics in six managed care organizations. Clinics were randomized to one of two QI interventions or usual care. One thousand one hundred thirty-six patients with current depressive symptoms and either 12-month, lifetime, or no depressive disorder identified through screening 27,332 consecutive patients. Utility weighted SF-12 or SF-36 measures, probable depression, and physical and mental health-related quality of life scores. Several utility-weighted measures showed increases in utility values for patients in one of the interventions, relative to usual care, that paralleled the improved health effects for depression and emotional well being. However, QALY gains were small. Directly elicited utility values showed a paradoxical result of lower utility during the first year of the study for intervention patients relative to controls. The results raise concerns about the use of direct single-item utility measures or utility measures derived from generic health status measures in effectiveness studies for depression. Choice of measure may lead to different conclusions about the benefit and CE of treatment. Utility measures that capture the mental health and non-health outcomes associated with treatment for depression are needed.


Minimal access spinal technologies (MAST) fusion procedures for the treatment of the degenerative lumbar spine (a part of multicentral prospective study). Case Report.
A prospective multicentral observational study of minimally invasive fusion to treat degenerative lumbar disorders, and to report outcomes of one or two level minimally invasive posterior lumbar interbody fusion (MLIF) for degenerative lumbar disorders in a multi-center 1-year prospective study. We prospectively studied a group of 32 patients, mostly female 24 (75% female), and 8 males (25%). They underwent minimally invasive transforaminal lumbar interbody fusion (mTLIF), 21 of them monosegmental and 11 bisegmental. Patients demographics, intra-operative data and complications were recorded. Time to first ambulation, time to study-defined recovery, surgical duration, blood loss, fluoroscopy time and adverse events were recorded. Visual analogue scale (VAS) of back and legs pain, Oswestry disability index (ODI) and health-related questionnaire (EQ-5D) were assessed preoperatively and at defined time points through 12 months postoperatively. Mean surgical duration, blood loss and intraoperative fluoroscopy time were 125 vs. 175 minutes, 150 vs. 170 ml, and 105 vs. 145 seconds in one- and two-level segments, respectively. Mean preoperative VAS back (6.5) and VAS leg (7.9) scores dropped significantly (p<0.0001) to 3.5 (2.6) and 2.6 (2.0) at discharge (6 weeks). At the end, this is the largest prospective multi-center observational study of MLIF to date, following routine local standard of practice and, MLIF demonstrated favourable clinical results with early and sustained improvement in patient reported outcomes and low major perioperative morbidity.


Teenage sexual attitudes and behaviour in China: a literature review.
China is the most populated of any country in the world. Social norms and values pertaining to love and marriage have changed considerably since the launch of its open-door policy and economic reforms of the 1980s. Attitudes to sex have become more open, while the negative consequences of early sexual intercourse have become issues of health and social concern. The aim of this study is to provide an overview of the teenage sexual attitudes and behaviour in contemporary China. A literature review was conducted between 2000 and 2010, using both English (Medline, CINAHL, PsycINFO, ASSIA) and Chinese language databases (China National Knowledge Infrastructure, Wanfang database). Thirty-six studies were included and reviewed. It was found that young people reported poor sexual knowledge, especially in relation to reproductive matters and sexually transmitted infections. The media, such as television, magazines and the Internet, were seen as their main sources of information on sex. Despite the frequently reported liberal attitudes to sexual behaviour, only a small number of young people had already lost their virginity or been involved in pregnancies. Young men were more likely than young women to report having had sex, while respondents at vocational high schools were less likely to remain virgins than those at common/key high schools. Although the prevalence of sexual intercourse among Chinese teenagers was still lower than that reported in studies conducted in most western countries, the findings do reflect some changes in sexual values and behaviour of young people within the country. They also suggest the need to develop more comprehensive sex education programmes in co-operation with young people, schools, health organisations, families and communities and to make sexual and reproductive health services accessible to teenagers and unmarried young people throughout China.


Cervical cancer cell supernatants induce a phenotypic switch from U937-derived macrophage-activated M1 state into M2-like suppressor phenotype with change in Toll-like receptor profile.
Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages.


Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?
Lyme disease has been reported to be associated with various psychiatric presentations. Borreliaburgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations. We report a case of a 41-year-old male with a past history of Bb infection who presents with psychosis. Later in the course of his hospitalization, he developed mood symptoms and was diagnosed with schizoaffective disorder, bipolar type. This case highlights the diagnosis and treatment of a patient with the unique presentation of schizoaffective disorder, bipolar type in the setting of previous Bb infection.


Characterization of the 3' exonuclease subunit DP1 of Methanococcus jannaschii replicative DNA polymerase D.
The B-subunits associated with the replicative DNA polymerases are conserved from Archaea to humans, whereas the corresponding catalytic subunits are not related. The latter belong to the B and D DNA polymerase families in eukaryotes and archaea, respectively. Sequence analysis places the B-subunits within the calcineurin-like phosphoesterase superfamily. Since residues implicated in metal binding and catalysis are well conserved in archaeal family D DNA polymerases, it has been hypothesized that the B-subunit could be responsible for the 3'-5' proofreading exonuclease activity of these enzymes. To test this hypothesis we expressed Methanococcus jannaschii DP1 (MjaDP1), the B-subunit of DNA polymerase D, in Escherichia coli, and demonstrate that MjaDP1 functions alone as a moderately active, thermostable, Mn2+-dependent 3'-5' exonuclease. The putative polymerase subunit DP2 is not required. The nuclease activity is strongly reduced by single amino acid mutations in the phosphoesterase domain indicating the requirement of this domain for the activity. MjaDP1 acts as a unidirectional, non-processive exonuclease preferring mispaired nucleotides and single-stranded DNA, suggesting that MjaDP1 functions as the proofreading exonuclease of archaeal family D DNA polymerase.


Genetic correlation between melanization and antibacterial immune responses in a natural population of the malaria vector Anopheles gambiae.
The immune system of invertebrates can mount different responses, including melanotic encapsulation and several antibacterial defense mechanisms. Variation of the efficacies of these responses is generally considered to be a product of the evolutionary pressure on each response due to infection by parasites. However, potential interactions and trade-offs among the different responses of the immune system could constrain the evolutionary potential of each response. In a natural population of the mosquito Anopheles gambiae, we measured the genetic association between the melanization response and an antibacterial response in two environmental qualities (well-fed and undernourished larvae). In both environments the two immune responses were positively genetically correlated: in full-sib families that were most likely to melanize a bead, injected bacteria were most likely to be cleared. Thus, our data do not support the idea of a trade-off among different outcomes of the invertebrate immune system, but rather that some families are overall immunologically superior to others.


Size determination by use of two-dimensional Mueller matrices backscattered by optically thick random media.
Here we are concerned with the systematic study of polarized light transport in thick, isotropic, homogeneous random media and of the associated inverse problem. An original spatial and intensity rescaling of the polarization transport allows one to account implicitly for the volume fraction. This parameter elimination permits a complete exploration, by means of Monte Carlo simulations of the dependence of polarized light transport on microscopic parameters. Analysis of the Mueller matrices obtained from the simulations show that additional correlations (with respect to scalar transport) are obtained between the microscopic parameters and the spatial distribution of specific elements of the Mueller matrix. As a consequence, using carefully chosen polarization states, one can determine an average particle size independently of the volume fraction of particles, with only the knowledge of the refractive-index ratio being required. This analysis is validated with experimental Mueller matrices obtained for emulsions of various size, concentration, and polydispersity.