Complete Genome Sequence of Sedimenticola thiotaurini Strain SIP-G1, a Polyphosphate- and Polyhydroxyalkanoate-Accumulating Sulfur-Oxidizing Gammaproteobacterium Isolated from Salt Marsh Sediments.
We report the closed genome sequence of Sedimenticola thiotaurini strain SIP-G1 and an unnamed plasmid obtained through PacBio sequencing with 100% consensus concordance. The genome contained several distinctive features not found in other published Sedimenticola genomes, including a complete nitrogen fixation pathway, a complete ethanolamine degradation pathway, and an alkane-1-monooxygenase.


Qualitative block design performance in epilepsy patients.
Broken configuration errors on the WAIS-R Block Design subtest have been associated with right hemisphere brain damage. This study examined whether pre-surgical epilepsy patients with seizure foci restricted to the right hemisphere would break configuration more frequently than those with left hemisphere foci. Subjects included 38 patients with unilateral right or left hemisphere epilepsy of frontal or temporal lobe origin. The left and right hemisphere groups did not differ significantly in demographic or disease variables, IQ, or Block Design standard scores. Right hemisphere patients made more broken configurations than did those with left hemisphere foci. In the right hemisphere group, more broken configurations were associated with a lower Block Design Scaled Score and Full Scale IQ. These results suggest that the observation of broken configurations in the Block Design can assist in corroborating the seizure focus and highlight the importance of qualitative Block Design analysis.


The potential economic burden of Zika in the continental United States.
As the Zika virus epidemic continues to spread internationally, countries such as the United States must determine how much to invest in prevention, control, and response. Fundamental to these decisions is quantifying the potential economic burden of Zika under different scenarios. To inform such decision making, our team developed a computational model to forecast the potential economic burden of Zika across six states in the US (Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas) which are at greatest risk of Zika emergence, under a wide range of attack rates, scenarios and circumstances. In order to accommodate a wide range of possibilities, different scenarios explored the effects of varying the attack rate from 0.01% to 10%. Across the six states, an attack rate of 0.01% is estimated to cost $183.4 million to society ($117.1 million in direct medical costs and $66.3 million in productivity losses), 0.025% would result in $198.6 million ($119.4 million and $79.2 million), 0.10% would result in $274.6 million ($130.8 million and $143.8 million) and 1% would result in $1.2 billion ($268.0 million and $919.2 million). Our model and study show how direct medical costs, Medicaid costs, productivity losses, and total costs to society may vary with different attack rates across the six states and the circumstances at which they may exceed certain thresholds (e.g., Zika prevention and control funding allocations that are being debated by the US government). A Zika attack rate of 0.3% across the six states at greatest risk of Zika infection, would result in total costs that exceed $0.5 billion, an attack rate of 1% would exceed $1 billion, and an attack rate of 2% would exceed $2 billion.


Social Media and Web Presence for Patients and Professionals: Evolving Trends and Implications for Practice.
The use of social media has become very instinctive to many. It has become part of a daily routine. Enhanced communication, liberated expressions of self, becoming updated with all the trends and news, and marketing promotion are only some of the reasons why most people use social media. Health care providers including physicians should take advantage of these platforms for professional purposes. Social media extends far beyond the famous platforms such as Facebook, Twitter, Pinterest, and Instagram, used mostly for social connections. There are sites dedicated to serve professionals, for example, LinkedIn, or even physician-specific forums such as Sermo. The physical medicine and rehabilitation community has a forum (Phyzforum) created by the American Academy of Physical Medicine and Rehabilitation to share questions, comments, and ideas. Moreover, there are broadcast media (Podcast) and blogging sites (WordPress) used by many physiatrists. Surveys show that physicians actively use an average of 2-4 hours of professional-leaning networking sites per week; for example, 44% of physicians use Sermo and 42% use LinkedIn. The participation also extends to more popular sites, with 40%, 25%, and 20% physician participation in YouTube, Blogging, and Twitter, respectively. There are numerous guidelines available for medical practitioners pertaining to professional use of social media. Strategies such as timing of postings and posting content as well as methods to maintain your online reputation are discussed. Various benefits and potential pitfalls with regards to social media use are also analyzed, including how to engage followers and addressing negative comments and reviews.


[Comparative characteristics of efficacy of operations in ulcerous pyloroduodenal stenosis].
1107 patients with ulcerous pyloroduodenal stenosis (UPDS) were operated since 1968 to 2000. Duodenal ulcers caused stenosis in 1053 (95%) patients, gastric ulcers of types II and III--in 54 (5%). Various stomach resections were performed in 287 (92%) patients organ-saving operations--in 795 (71.8%) patients Longterm outcomes were studied in 797 (71.9%) patients, 491 (61.6%) of them were examined in hospital and 306 (38.4%) responded to questionnaires. Mean follow-up was 17 +/- 8.4 years. Early postoperative complications were in 138 (12.5%) patients, after resections--in 20.5%, after organ-saving operations--in 9.3%. General lethality after UPDS surgery was 0.6%, after organ-saving operations--0.2%, after resections--1.3%. Pathologic syndromes were seen in 31% patients. Recurrence of ulcer after organ-saving operations was revealed in 11% in remote terms. Demping-syndrome was in 22.9% patients. Most often it was revealed after 2/3 stomach resection by Bilrot-II in Gofmeister--Finsterer (G--F) modification, less often--after SPV with duodenoplasty. The only operation preventing reflux-gastritis was economic stomach resection with Roux anastomosis and trunk vagotomy (TV + Er Roux). Good and excellent results by Visick scale were achieved in 85% patients with UPDS. Evaluation by D. Johnston scale demonstrated best results after SPV in duodenoplasty (238 points) and TV + ER Roux (272 points), the worst results--after B-1 (773 points) and B-II G--F (1124 points). Optimal results like healthy quality of life was seen after TV + ER Roux and SPV with duodenoplasty.


Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy.
An international Clinical Outcomes Group consisting of clinicians, scientists, patient advocacy groups, and industries identified a need for a scale to measure motor performance of the upper limb. We report the steps leading to the development of the Performance of the Upper Limb (PUL), a tool specifically designed for assessing upper limb function in ambulant and non-ambulant patients with Duchenne muscular dystrophy (DMD). The development of the PUL followed a number of steps, from the systematic review and a preliminary study exploring the suitability of the existing measures, to the application of a pilot version in a multicentric setting, with Rasch analysis of the preliminary results, leading to a revised pro forma. The PUL was specifically designed for DMD, with a conceptual framework reflecting the progression of weakness and natural history of functional decline in DMD. Modern psychometric methods were used to create a scale with robust internal reliability, validity, and hierarchical scalability; males with DMD and their families were involved iteratively throughout the process of the clinician-reported outcome assessment tool development to establish clinical meaningfulness and relevance of individual PUL items to activities of daily living. The module was developed using innovative approaches and will be useful for designing clinical trials.


Ovarian cancer suspicion, urgent referral and time to diagnosis in Danish general practice: a population-based study.
Ovarian cancer (OC) survival rates are lower in Denmark than in countries with similar health care. Prolonged time to diagnosis could be a contributing factor. The Danish cancer patient pathway (CPP) for OC was introduced in 2009. It provides GPs with fast access to diagnostic work-up. To investigate cancer suspicion and pathway use among GPs and to explore the association between these factors and the diagnostic intervals (DIs). We conducted a national population-based cohort study using questionnaires and national registers. Of the 313 women with participating GPs, 91% presented with symptoms within 1 year of diagnosis, 61% presented vague non-specific symptoms and 62% were diagnosed with late-stage disease. Cancer was suspected in 39%, and 36% were referred to a CPP. Comorbidity [prevalence ratio (PR): 0.53, 95% confidence interval (CI): 0.29-0.98] and no cancer suspicion (PR: 0.35, 95% CI: 0.20-0.60) were associated with no referral to a CPP. The median DI was 36 days. Long DIs were associated with no cancer suspicion (median DI: 59 versus 20 days) and no referral to a CPP (median DI: 42 versus 23 days). Nine in ten patients attended general practice with symptoms before diagnosis. Two-thirds initially presented with vague non-specific symptoms were less likely to be referred to a CPP and had longer DIs than women suspected of cancer. These findings underline the importance of supplementing the CPP with additional accelerated diagnostic routes.


CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae.
The yeast Saccharomyces cerevisiae contains two functional homologues of the ras oncogene family, RAS1 and RAS2. These genes are required for growth, and all evidence indicates that this essential function is the activation of adenylate cyclase. In contrast, ras in mammalian cells does not appear to influence adenylate cyclase activity. To clarify the relation between ras function in yeast and in higher eukaryotes, and the role played by yeast RAS in growth control, it is necessary to identify functions acting upstream of RAS in the adenylate cyclase pathway. The evidence presented here indicates that CDC25, identified by conditional cell cycle arrest mutations, encodes such an upstream function.


Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey.
Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the US population. Stored serum samples from the National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999-2004 were available for 12,482 individuals of age ⩾50 years (2331 'blacks', 2475 Hispanics, 7051 'whites' and 625 'others') on which agarose-gel electrophoresis, serum protein immunofixation, serum-free light-chain assay and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the United States, respectively (P=0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the United States was found, which has etiologic implications.


Various taxo- and ecogroups of bacteria as index organisms for the enteric contamination of bottled waters: their significance and enumeration.
Bottled "still" waters may present bacterial and viral risks, particularly for compromised consumers and when stored for some length of time in opened containers. Therefore, bottling has to be supervised carefully and any sanitary deficiencies discovered, corrected immediately. When plants are thus controlled by a preventive system, bacteriological examination of samples will be warranted, whereas this is senseless, for mathematical reasons, in non-supervised bottling plants. A direct search for enteric pathogens is discouraged. Instead, detection of the entire Enterobacteriaceae group, P. aeruginosa and Lancefield group D streptococci, is advocated. Deficiencies of customarily used methods of detection of the coli-aerogenes group of bacteria are outlined. The need for resuscitation of cells of bacterial groups used as index organisms, debilitated by storage in bottled waters, before their inoculation into currently employed selective media is demonstrated.


The diagnostic performance of micro-RNA and metabolites in lung cancer: A meta-analysis.
The diagnosis of lung cancer is based on the microscopic exam of tissue or liquid. During the recent decade, many biomarkers have been pointed to have a potential diagnostic role. These biomarkers may be assessed in blood, pleural effusion or sputum and they could avoid biopsies or other risky procedures. The authors aimed to assess the diagnostic performances of biomarkers focusing on micro-RNA and metabolites. This meta-analysis was conducted under the PRISMA guidelines during a nine-year-period (2013-2022). the Meta-Disc software 5.4 (free version) was used. Q test and I2 statistics were carried out to explore the heterogeneity among studies. Meta-regression was performed in case of significant heterogeneity. Publication bias was assessed using the funnel plot test and the Egger's test (free version JASP). According to our inclusion criteria, 165 studies from 79 articles were included. The pooled SEN, SPE and dOR accounted, respectively, for 0.76, 0.79 and 13.927. The AUC was estimated to 0.859 suggesting a good diagnostic accuracy. The heterogeneity in the pooled SEN and SPE was statistically significant. The meta-regression analysis focusing on the technique used, the sample, the number of biomarkers, the biomarker subtype, the tumor stage and the ethnicity revealed the biomarker number (p = 0.009) and the tumor stage (p = 0.0241) as potential sources of heterogeneity. Even if this meta-analysis highlighted the potential diagnostic utility of biomarkers, more prospective studies should be performed, especially to assess the biomarkers' diagnostic potential in early-stage lung cancers.


Solution Structure, Self-Assembly, and Membrane Interactions of the Matrix Protein from Newcastle Disease Virus at Neutral and Acidic pH.
Newcastle disease virus (NDV) is an enveloped paramyxovirus. The matrix protein of the virus (M-NDV) has an innate propensity to produce virus-like particles budding from the plasma membrane of the expressing cell without recruiting other viral proteins. The virus predominantly infects the host cell via fusion with the host plasma membrane or, alternatively, can use receptor-mediated endocytic pathways. The question arises as to what are the mechanisms supporting such diversity, especially concerning the assembling and membrane binding properties of the virus protein scaffold under both neutral and acidic pH conditions. Here, we suggest a novel method of M-NDV isolation in physiological ionic strength and employ a combination of small-angle X-ray scattering, atomic force microscopy with complementary structural techniques, and membrane interaction measurements to characterize the solution behavior/structure of the protein as well as its binding to lipid membranes at pH 4.0 and pH 7.0. We demonstrate that the minimal structural unit of the protein in solution is a dimer that spontaneously assembles in a neutral milieu into hollow helical oligomers by repeating the protein tetramers. Acidic pH conditions decrease the protein oligomerization state to the individual dimers, tetramers, and octamers without changing the density of the protein layer and lipid membrane affinity, thus indicating that the endocytic pathway is a possible facilitator of NDV entry into a host cell through enhanced scaffold disintegration.IMPORTANCE The matrix protein of the Newcastle disease virus (NDV) is one of the most abundant viral proteins that regulates the formation of progeny virions. NDV is an avian pathogen that impacts the economics of bird husbandry due to its resulting morbidity and high mortality rates. Moreover, it belongs to the Avulavirus subfamily of the Paramyxoviridae family of Mononegavirales that include dangerous representatives such as respiratory syncytial virus, human parainfluenza virus, and measles virus. Here, we investigate the solution structure and membrane binding properties of this protein at both acidic and neutral pH to distinguish between possible virus entry pathways and propose a mechanism of assembly of the viral matrix scaffold. This work is fundamental for understanding the mechanisms of viral entry as well as to inform subsequent proposals for the possible use of the virus as an adequate template for future drug or vaccine delivery.


Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.
Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.


In situ probing of Xylella fastidiosa in honeydew of a xylem sap-feeding insect using 16S rRNA-targeted fluorescent oligonucleotides.
Xylella fastidiosa is a plant pathogen that threatens a US$ 4.6 billion worldwide wine and citrus industry. Monitoring its presence and distribution in plants and vectors is crucial for designing control strategies, as well as for understanding its ecological role and fate. We developed two fluorescent oligonucleotide probes complementary to different regions of the 16S rRNA gene of X. fastidiosa. The specificity of the newly designed probes S-S-X.fas-0067-a-A-18 and S-S-X.fas-1439-a-A-18 was demonstrated using fluorescence in situ hybridization (FISH) for 12 Xylella isolates, 15 closely related microorganisms and three plant endophytes. These probes were used to detect and quantify X. fastidiosa in plant sap (average value of 2.9 +/- 0.3 x 10(6) cells ml(-1)) from three different citrus orchards. In a second experiment, cells were quantified in honeydew (2.2 +/- 0.2 x 10(4) cells ml(-1)) collected from the insect vector Bucephalogonia xanthophis during the acquisition access period on an infected plant. The number of pathogen cells retained or digested by the insect is 10,000 times greater than the estimated minimum value to ensure an efficient transmission. Polymerase chain reaction (PCR) amplification using specific primers with plant sap and honeydew samples, followed by sequencing, confirmed the presence of the plant pathogen. This is the first demonstration of FISH being used for environmental samples, such as plant sap and insect honeydew, to estimate the abundance of a plant pathogen during infection.


Compact gradual bends for channel plasmon polaritons.
We report the design, fabrication and characterization of compact gradual bends for channel plasmon polaritons (CPPs) being excited at telecom wavelengths. We obtain high-quality near-field optical images of CPP modes propagating along a bent V-groove in gold, which indicate good CPP mode confinement in the groove and efficient guiding around the compact S-bend connecting two 5-mum-offset grooves over a distance of 5 mum. Using averaged cross sections of the CPP intensity distributions before and after the S-bend, the total bend loss is evaluated and found to be close to 2.3 dB for the wavelengths in the range of 1430-1640 nm.


Reverse phase liquid chromatographic determination of vitamins D2 and D3 in milk.
A single column reverse phase high pressure liquid chromatographic method is described for the determination of vitamins D2 and D3 in fluid milk. Resolution of vitamin D2 from D3 is helpful for use as an internal standard. The method involves overnight saponification at room temperature, extraction of unsaponifiables, precipitation of cholesterol, and aluminum oxide column cleanup. Sample extracts were chromatographed under isocratic conditions on a 10 micron Vydac reverse phase column using acetonitrile-methanol (90 + 10) as the mobile phase. In addition, a MicroPak MCH-5 reverse phase column with acetonitrile as the mobile phase was used with an automatic system for one product type. Thirty samples each of homogenized (3.8% fat), low fat (2.0% fat), and skim (less than or equal to 0.5% fat) milk spiked with 200, 400, and 600 IU vitamin D/qt were analyzed. Coefficient of variation (CV) and percent recovery for each product type and each spike level of vitamins D2 and D3 were calculated from 10 replicate analyses. Vitamin D2 recoveries for all product types at the 3 fortification levels varied from 85.2 to 99.7%; vitamin D3 recoveries varied from 85.9 to 98.8%. The minimum detectable quantity of vitamin D in milk was 15 IU/qt.


Zea diploperennis (Gramineae): A New Teosinte from Mexico.
A perennial teosinte or "wild maize" endemic to the Cerro de San Miguel, Sierra de Manantlan, Jalisco, Mexico differs from Zea perennis by dimorphic rhizomes, robust habit, and a larger number of longer, laxer tassel branches. The fact that it is a diploid (2n = 20) has taxonomic and agronomic significance. The seeds are used locally for food.


Iron Deficiency and Iron Excess Differently Affect Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Piglets.
Both iron deficiency and overload may adversely affect neurodevelopment. The study assessed how changes in early-life iron status affect iron homeostasis and cytoarchitecture of hippocampal neurons in a piglet model. On postnatal day (PD) 1, 30 Hampshire × Yorkshire crossbreed piglets (n = 15/sex) were stratified by sex and litter and randomly assigned to experimental groups receiving low (L-Fe), adequate (A-Fe), or high (H-Fe) levels of iron supplement during the pre- (PD1-21) and postweaning periods (PD22-35). Pigs in the L-Fe, A-Fe, and H-Fe groups orally received 0, 1, and 30 mg Fe · kg weight-1 · d-1 preweaning and were fed a diet containing 30, 125, and 1000 mg Fe/kg postweaning, respectively. Heme indexes were analyzed weekly, and gene and protein expressions of iron regulatory proteins in duodenal mucosa, liver, and hippocampus were analyzed through qRT-PCR and western blot, respectively, on PD35. Hippocampal neurons stained using the Golgi-Cox method were traced and their dendritic arbors reconstructed in 3-D using Neurolucida. Dendritic complexity was quantified using Sholl and branch order analyses. Pigs in the L-Fe group developed iron deficiency anemia (hemoglobin = 8.2 g/dL, hematocrit = 20.1%) on PD35 and became stunted during week 5 with lower final body weight than H-Fe group pigs (6.6 compared with 9.6 kg, P < 0.05). In comparison with A-Fe, H-Fe increased hippocampal ferritin expression by 38% and L-Fe decreased its expression by 52% (P < 0.05), suggesting altered hippocampal iron stores. Pigs in the H-Fe group had greater dendritic complexity in CA1/3 pyramidal neurons than L-Fe group pigs as shown by more dendritic intersections with Sholl rings (P ≤ 0.04) and a greater number of dendrites (P ≤ 0.016). In piglets, the developing hippocampus is susceptible to perturbations by dietary iron, with deficiency and overload differentially affecting dendritic arborization.


Evolution and mechanics of long jaws in butterflyfishes (family Chaetodontidae).
We analyzed the functional morphology and evolution of the long jaws found in several butterflyfishes. We used a conservative reanalysis of an existing morphological dataset to generate a phylogeny that guided our selection of seven short- and long-jawed taxa in which to investigate the functional anatomy of the head and jaws: Chaetodon xanthurus, Prognathodes falcifer (formerly Chaetodon falcifer), Chelmon rostratus, Heniochus acuminatus, Johnrandallia nigrirostris, Forcipiger flavissimus, and F. longirostris. We used manipulations of fresh, preserved, and cleared and stained specimens to develop mechanical diagrams of how the jaws might be protruded or depressed. Species differed based on the number of joints within the suspensorium. We used high-speed video analysis of five of the seven species (C. xanthurus, Chel. rostratus, H. acuminatus, F. flavissimus, and F. longirostris) to test our predictions based on the mechanical diagrams: two suspensorial joints should facilitate purely anteriorly directed protrusion of the lower jaw, one joint should allow less anterior protrusion and result in more depression of the lower jaw, and no joints in the suspensorium should constrain the lower jaw to simple ventral rotation around the jaw joint, as seen in generalized perciform fishes. We found that the longest-jawed species, F. longirostris, was able to protrude its jaws in a predominantly anterior direction and further than any other species. This was achieved with little input from cranial elevation, the principal input for other known lower jaw protruders, and is hypothesized to be facilitated by separate modifications to the sternohyoideus mechanism and to the adductor arcus palatini muscle. In F. longirostris the adductor arcus palatini muscle has fibers oriented anteroposteriorly rather than medial-laterally, as seen in most other perciforms and in the other butterflyfish studied. These fibers are oriented such that they could rotate the ventral portion of the quadrate anteriorly, thus projecting the lower jaw anteriorly. The intermediate species lack modification of the adductor arcus palatini and do not protrude their jaws as far (in the case of F. flavissimus) or in a purely anterior fashion (in the case of Chel. rostratus). The short-jawed species both exhibit only ventral rotation of the lower jaw, despite the fact that H. acuminatus is closely related to Forcipiger.


Upper Limb Movement Execution Classification using Electroencephalography for Brain Computer Interface.
An accurate classification of upper limb movements using electroencephalogram (EEG) signals is gaining significant importance in recent years due to the prevalence of brain-computer interfaces. The upper limbs in the human body are crucial since different skeletal segments combine to make a range of motions that helps us in our trivial daily tasks. Decoding EEG-based upper limb movements can be of great help to people with spinal cord injury (SCI) or other neuro-muscular diseases such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and periodic paralysis. This can manifest in a loss of sensory and motor function, which could make a person reliant on others to provide care in day-to-day activities. We can detect and classify upper limb movement activities, whether they be executed or imagined using an EEG-based brain-computer interface (BCI). Toward this goal, we focus our attention on decoding movement execution (ME) of the upper limb in this study. For this purpose, we utilize a publicly available EEG dataset that contains EEG signal recordings from fifteen subjects acquired using a 61-channel EEG device. We propose a method to classify four ME classes for different subjects using spectrograms of the EEG data through pre-trained deep learning (DL) models. Our proposed method of using EEG spectrograms for the classification of ME has shown significant results, where the highest average classification accuracy (for four ME classes) obtained is 87.36%, with one subject achieving the best classification accuracy of 97.03%.Clinical relevance- This research shows that movement execution of upper limbs is classified with significant accuracy by employing a spectrogram of the EEG signals and a pre-trained deep learning model which is fine-tuned for the downstream task.


Innate Root Exudates Contributed to Contrasting Coping Strategies in Response to Ralstonia solanacearum in Resistant and Susceptible Tomato Cultivars.
Tomato cultivars with contrasting resistance to pathogens regulate root exudates differentially in response to Ralstonia solanacearum attacks. However, strategies using innate root exudates against infection remain unknown. This study analyzed the innate root exudates of two tomato cultivars and their functions in regulating R. solanacearum infection. The innate root exudates differed between the two cultivars. Astaxanthin released from resistant plants inhibited colonization by R. solanacearum but promoted motility, while neferine released from susceptible plants suppressed motility and colonization. The secretion of astaxanthin in resistant tomatoes promoted the growth of biocontrol fungi in soil and reduced the abundance of pathogenic fungi. Neferine secreted by the susceptible cultivar inhibited the relative abundance of the bacterial-biocontrol-related Bacillus genus, indirectly reducing the soil's immune capacity. This study revealed contrasting strategies using root exudates in resistant and susceptible tomato cultivars to cope with R. solanacearum infection, providing a basis for breeding disease-resistant cultivars.


Association between body mass index and mental health among Scottish adult population: a cross-sectional study of 37,272 participants.
The evidence is conflicting as to whether body mass index (BMI) is associated with mental health and, if so, to what extent it varies by sex and age. We studied mental health across the full spectrum of BMI among the general population, and conducted subgroup analyses by sex and age. We undertook a cross-sectional study of a representative sample of the Scottish adult population. The Scottish Health Survey provided data on mental health, measured by the General Health Questionnaire-12 (GHQ), BMI, demographic and life-style information. Good mental health was defined as a GHQ score <4, and poor mental health as a GHQ score ⩾4. Logistic regression models were applied. Of the 37 272 participants, 5739 (15.4%) had poor mental health. Overall, overweight participants had better mental health than the normal-weight group [adjusted odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87-0.99, p = 0.049], and individuals who were underweight, class II or class III obese had poorer mental health (class III obese group: adjusted OR 1.26, 95% CI 1.05-1.51, p = 0.013). There were significant interactions of BMI with sex (p = 0.013) and with age (p < 0.001). Being overweight was associated with significantly better mental health in middle-aged men only. In contrast, being underweight at all ages or obese at a young age was associated with significantly poorer mental health in women only. The adverse associations between adiposity and mental health are specific to women. Underweight women and young women who are obese have poorer mental health. In contrast, middle-aged overweight men have better mental health.


Home treatment for acute psychiatric illness.
To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. Electoral ward of Sparkbrook, Birmingham. 99 Patients aged 16-65 with severe acute psychiatric illness. 65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service.


Comparison of lipid content and fatty acid composition and their distribution within seeds of 5 small grain species.
Barley, oats, rice, sorghum, and wheat, each with two genotypes, were sequentially abraded by an electric seed scarifier. The pearling fines (PF) and pearled kernels (PK) at each cycle were analyzed for lipid (mostly nonpolar) content and fatty acid (FA) composition. The oil content in whole or dehulled grains ranged from 2.18% of a wheat variety to 6.38% of an oat line. Compared with barley and wheat, rice, oat, and sorghum had higher relative % of C18:1 (31.60 to 36.64 compared with 12.15 to 15.61) and lower % of C18:2 (35.69 to 45.44 compared with 50.79 to 61.50). The relationship between oil content in PF and the cumulative level of surface removal essentially describes the distribution pattern of oil content within a seed. Barley, rice, and sorghum had a similar distribution pattern, characterized by a rapid rate of decreasing for the first few outer layers and then by gradual decrease to a flat value toward the inner core. In contrast, distribution within oats was characterized by a gradual reduction in oil content across the seed. The distribution of oil within wheat fell between the former 2 types. For all 10 grains, from seed surface to inner core, C16:0 and C18:0 increased, C18:1 and C18:3 decreased, and C18:2 changed slightly, providing a new reason for improved oxidative stability for pearled kernels. The differences in the changing intensity of FA composition among grain species correspond to those in oil distribution within a seed, while varietal difference in distribution patterns of content and FA composition of lipids within a species was insignificant. This study was the first to document fatty acid distribution across a grain seed. Results provide 2 major reasons for improved oxidative stability of pearled grains: reduced oil content and shift of fatty acids toward more saturated and less unsaturated composition.


Prognostic values of transketolase family genes in ovarian cancer.
Transketolase genes are key rate-limiting enzymes in the non-oxidative part of the pentose phosphate pathway, which is an important metabolic pathway in ribose-5-phosphate production. Three human transketolase genes have been identified: Transketolase (TKT), transketolase-like gene 1 (TKTL1) and transketolase-like gene 2 (TKTL2). Transketolase genes serve crucial roles in the tumorigenesis, metastasis and outcome of multiple types of cancer. However, the expression levels and prognostic values of transketolase family genes in patients with ovarian cancer remain unclear. The purpose of the study was to analyze the expression level and prognostic significance of transketolase family genes in ovarian cancer. In the present study, the mRNA expression levels of three transketolase genes in ovarian cancer and normal ovarian tissue were compared by Oncomine. The prognostic values of these genes were systemically assessed using the Kaplan-Meier plotter database. In addition, the associations between the mRNA levels of these transketolase genes and the clinicopathological characteristics of patients with ovarian cancer, such as histological subtype, clinical stage, grade, tumor protein p53 (TP53) mutation status and chemotherapy history were studied. The prognostic roles of transketolase genes were also evaluated in a validation dataset. The results demonstrated that TKT and TKTL1 expression in ovarian cancer tissues was elevated compared with that in normal ovarian tissues. In addition, high mRNA expression of the three transketolase genes was identified to be associated with poorer progression-free survival (PFS) in patients with serous ovarian cancer, especially in patients at an advanced stage. TKTL2 was significantly associated with poor overall survival in all patients with ovarian cancer. Additionally, transketolase family genes served a role in predicting PFS in patients with ovarian cancer treated with platinum and/or taxol. High expression of the three transketolase genes was associated with unfavorable PFS in patients with TP53-mutated ovarian cancer, but not in patients with TP53 wild-type ovarian cancer. These results suggested that transketolase family genes may serve important roles in the prognosis of patients with ovarian cancer.


Biological evaluation of surface-modified magnetic nanoparticles as a platform for colon cancer cell theranostics.
Magnetic nanoparticles offer multiple possibilities for biomedical applications. Besides their physico-chemical properties, nanoparticle-cellular interactions are determinant for biological safety. In this work, magnetic nanoparticles were synthesized by one-shot precipitation or two-step reaction and coated with biocompatible polymers, such as poly(l-lysine) and poly(N,N-dimethylacrylamide-co-acrylic acid), and carbohydrates, like l-ascorbic acid, d-galactose, d-mannose, and sucrose. The resulting magnetic nanoparticles were characterized by dynamic light scattering, FT-Raman spectroscopy, transmission electron microscopy, SQUID magnetometry, and Mössbauer spectroscopy. Ability of the nanoparticles to be used in theranostic applications was also evaluated, showing that coating with biocompatible polymers increased the heating efficiency. Nanoparticles synthesized by one-shot precipitation were 50% larger (∼13nm) than those obtained by a two-step reaction (∼8nm). Magnetic nanoparticles at concentrations up to 500μgmL-1 were non-cytotoxic to L929 fibroblasts. Particles synthesized by one-shot precipitation had little effect on viability, cell cycle and apoptosis of the three human colon cancer cell lines used: Caco-2, HT-29, and SW-480. At the same concentration (500μgmL-1), magnetic particles prepared by a two-step reaction reduced colon cancer cell viability by 20%, affecting cell cycle and inducing cell apoptosis. Uptake of surface-coated magnetic nanoparticles by colon cancer cells was dependent on particle synthesis, surface coating and incubation time.


Emerging technologies for rapid identification of bloodstream pathogens.
Technologies for rapid microbial identification are poised to revolutionize clinical microbiology and enable informed decision making for patients with life-threatening bloodstream infections. Species identification of microorganisms in positive blood cultures can be performed in minutes using commercial fluorescence in situ hybridization tests or mass spectroscopy. Microorganisms in positive blood cultures can also be identified within 1-2.5 hours using automated polymerase chain reaction-based systems that can also detect selected antibiotic resistance markers, such as methicillin resistance. When combined with antibiotic stewardship programs, these approaches improve clinical outcomes and reduce healthcare expenditures. Tests for direct detection in whole blood samples are highly desirable because of their potential to identify bloodstream pathogens without waiting 1-2 days for blood cultures to become positive. However, results for pathogen detection in whole blood do not overlap with those of conventional blood culture techniques and we are still learning how best to use these approaches.


Hybridization of β-Adrenergic Agonists and Antagonists Confers G Protein Bias.
Starting from the β-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no β-arrestin-2 recruitment at both β1- and β2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and β-arrestin recruitment of the hybrid ( S)-22, the full agonist epinephrine, and the β2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.


Possibility of blood and hepatitis B contamination through aerosols generated during debonding procedures.
The primary purpose of this study was to investigate the presence of blood or blood elements in aerosols generated during the debonding procedures. The presence of three hepatitis B carriers in the study group led us to investigate the possibility of hepatitis B virus (HBV) contamination through aerosols, which was the secondary purpose of the study. The study group consisted of 26 patients who had a mean age of 16 +/- 2 years. Collection of aerosol samples was done using a saliva ejector that fit on the handle of the high-speed dental instrument and was attached to a mobile evacuator. A second evacuator was used to remove and collect excess fluid accumulated in the patient's mouth. The guaiac method was used to investigate the presence of occult blood in aerosol and in excess fluid samples. Serum, excess fluid, and aerosol samples of three hepatitis B carriers were tested by enzyme-linked immunosorbent assay for detecting hepatitis B surface antigen (HBsAg) and by polymerase chain reaction for detecting HBV-deoxyribonucleic acid (DNA). Blood was found in all the aerosols and in excess fluid samples. HBsAg was detected in excess fluid samples of the two hepatitis B carriers, whereas HBV-DNA was detected in only one of the excess fluid samples. HBsAg and HBV-DNA were detected in aerosol sample of only one hepatitis B carrier. The results of this study showed that aerosols generated during the debonding procedure should always be considered as potential hazards to health.


COX5A as a potential biomarker for disease activity and organ damage in lupus.
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with limited therapeutic targets or clinical outcome predictors. This study aimed to gain more insights into the underlying immunological pathways and prognostic biomarkers of SLE. Integrated analyses of RNA-seq data from 64 SLE and 62 healthy controls, examining 27 immune cell types to explore the key pathways and driver genes in SLE pathogenesis. Single-cell RNA sequencing data from the skin and kidney were used to determine the association of COX5A expression with organ damage. The associations of COX5A with SLE phenotypes were further evaluated in two independent cohorts, and receiver operating characteristic (ROC) curves were constructed to assess the value of COX5A as a biomarker for disease activity and organ damage in SLE. We found that oxidative phosphorylation (OXPHOS) is the most significantly altered metabolic pathway in SLE, especially in effector T cells. Notably, we identified an OXPHOS-related enzyme, COX5A, whose expression was significantly higher in effector T cells than in naïve T cells and showed associations with disease activity, organ damage, and steroid treatment of SLE. Furthermore, ROC curves showed that COX5A is a robust biomarker for disease activity, kidney involvement, and new-onset skin lesions, with the area under the curve (AUC) values of 0.880, 0.801, and 0.805, respectively. Our results identified the OXPHOS signature as a prominent feature in SLE T cells, and COX5A as a potential candidate biomarker for disease activity and organ damage in SLE.


Crossover trial of an audience response system application for smartphone in undergraduate medical students.
This article was migrated. The article was marked as recommended. Objectives: Audience response systems (ARS) using dedicated devices have been shown to enhance interactivity, leading to an increase in knowledge acquisition. ARS applications for smartphones are easier to use, but the benefits of these applications might be negated by deleterious effects of smartphone usage on concentration. We investigated whether an ARS smartphone application (Socrative TM) is feasible and increases student satisfaction and knowledge acquisition. Methods: We performed a crossover study in the setting of a hematology course for second-year medical students. Two hundred and forty nine students were included in the study and analyzed for their access to the ARS application through a smartphone. The same interactive lectures were proposed by the same teachers. The first group (n=119) was asked to answer questions with the ARS application during the first 3 lectures, and without the application during the last 3 lectures; and conversely for the second group (n=130). The analysis of the final results was restricted to 146 students having attended to at least 5 of the 6 lectures and having a smartphone enabling the use of the ARS application. Student opinion was measured through questions based on a Likert scale, and knowledge acquisition was measured at short and long-term through multiple choice questions assessing either the first three lectures or the last three lectures. Results: Most of the students (86%) had a smartphone enabling the use of the application. They were satisfied by the use of the application (93%), and found that it increased both interactivity (92%) and concentration (68%). There was no difference in knowledge scores at short or long term. Conclusion: The use of an ARS application for smartphone is feasible and increases the satisfaction of the students, their concentration and the interactivity of the lectures. However, this does not translate into a measurable increase in knowledge acquisition.


Indirect Costs and Family Burden of Pediatric Crohn's Disease in the United States.
Crohn's disease (CD) negatively impacts patient quality of life and results in greater healthcare utilization. For pediatric CD patients, the burden also extends to their caregivers. We aimed to estimate work loss and productivity costs among caregivers of pediatric CD patients. Data were from Truven MarketScan databases (2000-2012). Patients were <18 years old with ≥2 ICD-9 CD diagnostic codes. Controls were those without CD or ulcerative colitis and were matched to patients by age, Charlson Comorbidity Index, index year, and insurance plan category. Continuous enrollment was required ≥6 months before and ≥12 months after index, defined as the patient's first CD diagnosis date. Outcomes included hours of work loss and associated productivity costs of caregivers 1-year postindex. Work loss and productivity costs were compared between caregivers of patients and controls. Adjustments for unbalanced baseline factors were made using a generalized linear regression model. Each cohort included 200 study participants and their caregivers. Unadjusted annual hours of work loss after first diagnosis were 214.4 ± 171.5 and 169.6 ± 157.5 for caregivers of CD patients and controls, respectively (P = 0.007). Annual productivity costs were 27.2% ($1122) higher for caregivers of CD patients than controls, estimated at $5243 and $4,121, respectively (P = 0.004). Adjusted cost analyses yielded similar findings. Over the course of a patient's childhood, accumulated productivity losses were $24,118 for CD patients and $18,957 for control caregivers. Caregivers of pediatric CD patients have significantly higher loss in productivity costs compared with controls.


Uncertainty representation using fuzzy measures.
We introduce the fuzzy measure and discuss its use as a unifying structure for modeling knowledge about an uncertain variable. We show that a large class of well-established types of uncertainty representations can be modeled within this framework. A view of the Dempster-Shafer (D-S) belief structure as an uncertainty representation corresponding to a set of possible fuzzy measures is discussed. A methodology for generating this set of fuzzy measures from a belief structure is described. A measure of entropy associated with a fuzzy measure is introduced and its manifestation for different fuzzy measures is described. The problem of uncertain decision making for the case in which the uncertainty represented by a fuzzy measure is considered. The Choquet integral is introduced as providing a generalization of the expected value to this environment.


Characterization of trisiloxane surfactants from agrochemical adjuvants and pollinator-related matrices using liquid chromatography coupled to mass spectrometry.
Trisiloxane surfactants (TSSs) have been associated with honeybee learning impairment and the ongoing global bee decline. A liquid chromatography-mass spectrometry strategy for the identification of TSSs from agrochemical adjuvants and pollinator-related matrices is introduced here. The strategy incorporates chromatographic retention behavior, isotope ratio, reference to a compiled database of accurate masses, and TSS hydrolysis when necessary. Using this analytical strategy, three TSSs (x = 0, R = H, m = 1, 2, or 3) were identified for the first time from almond flowers of a commercial orchard. The three major purified TSS components in popularly used spray tank adjuvants were identified as TSS (x = 0, m = 0, R = H, CH3, or C(O)CH3) and their structures confirmed by nuclear magnetic resonance spectroscopy. These monitoring tools allow the assessment of the agricultural residues and potential risks of major TSS contaminants to important nontarget species such as honeybee and other essential pollinators.


Olfactory perceptual decision-making is biased by motivational state.
Growing evidence suggests that internal factors influence how we perceive the world. However, it remains unclear whether and how motivational states, such as hunger and satiety, regulate perceptual decision-making in the olfactory domain. Here, we developed a novel behavioral task involving mixtures of food and nonfood odors (i.e., cinnamon bun and cedar; pizza and pine) to assess olfactory perceptual decision-making in humans. Participants completed the task before and after eating a meal that matched one of the food odors, allowing us to compare perception of meal-matched and non-matched odors across fasted and sated states. We found that participants were less likely to perceive meal-matched, but not non-matched, odors as food dominant in the sated state. Moreover, functional magnetic resonance imaging (fMRI) data revealed neural changes that paralleled these behavioral effects. Namely, odor-evoked fMRI responses in olfactory/limbic brain regions were altered after the meal, such that neural patterns for meal-matched odor pairs were less discriminable and less food-like than their non-matched counterparts. Our findings demonstrate that olfactory perceptual decision-making is biased by motivational state in an odor-specific manner and highlight a potential brain mechanism underlying this adaptive behavior.


Treating Polymicrobial Infections in Chronic Diabetic Wounds.
This review provides a comprehensive summary of issues associated with treating polyclonal bacterial biofilms in chronic diabetic wounds. We use this as a foundation and discuss the alternatives to conventional antibiotics and the emerging need for suitable drug delivery systems. In recent years, extraordinary advances have been made in the field of nanoparticle synthesis and packaging. However, these systems have not been incorporated into the clinic for treatments other than for cancer or severe genetic diseases. We present a unifying perspective on how the field is evolving and the need for an early amalgamation of engineering principles and a biological understanding of underlying phenomena in order to develop a therapy that is translatable to the clinic in a shorter time.


Comparison of Wound Complications After Immediate, Delayed, and Secondary Breast Reconstruction Procedures.
Few data are available concerning surgical site infection (SSI) and noninfectious wound complications (NIWCs) after delayed (DR) and secondary reconstruction (SR) compared with immediate reconstruction (IR) procedures in the breast. To compare the incidence of SSI and NIWCs after implant and autologous IR, DR, and SR breast procedures after mastectomy. This retrospective cohort study included women aged 18 to 64 years undergoing mastectomy from January 1, 2004, through December 31, 2011. Data were abstracted from a commercial insurer claims database in 12 states and analyzed from January 1, 2015, through February 7, 2017. Reconstruction within 7 days of mastectomy was considered immediate. Reconstruction more than 7 days after mastectomy was considered delayed if the mastectomy did not include IR or secondary if the mastectomy included IR. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for SSI and NIWCs. Mastectomy was performed in 17 293 women (mean [SD] age, 50.4 [8.5] years); 61.4% of women had IR or DR. Among patients undergoing implant reconstruction, the incidence of SSI was 8.9% (685 of 7655 women) for IR, 5.7% (21 of 369) for DR, and 3.2% (167 of 5150) for SR. Similar results were found for NIWCs. In contrast, the incidence of SSI was similar after autologous IR (9.8% [177 of 1799]), DR (13.9% [19 of 137]), and SR (11.6% [11 of 95]) procedures. Compared with women without an SSI after implant IR, women with an SSI after implant IR were significantly more likely to have another SSI (47 of 412 [11.4%] vs 131 of 4791 [2.7%]) and an NIWC (24 of 412 [5.8%] vs 120 of 4791 [2.5%]) after SR. The incidence of SSI (24 of 379 [6.3%] vs 152 of 5286 [2.9%]) and NIWC (22 of 379 [5.8%] vs 129 of 5286 [2.4%]) after implant SR was higher in women who had received adjuvant radiotherapy. Wound complications after IR were associated with significantly more breast surgical procedures (mean of 1.92 procedures [range, 0-9] after implant IR and 1.11 [range, 0-6] after autologous IR) compared with women who did not have a complication (mean of 1.37 procedures [range, 0-8] after implant IR and 0.87 [range, 0-6] after autologous IR). The incidence of SSI and NIWCs was slightly higher for implant IR compared with delayed or secondary implant reconstruction. Women who had an SSI or NIWC after implant IR had a higher risk for subsequent complications after SR and more breast operations. The risk for complications should be carefully balanced with the psychosocial and technical benefits of IR. Select high-risk patients may benefit from consideration of delayed rather than immediate implant reconstruction to decrease breast complications after mastectomy.


KRAS Controls Pancreatic Cancer Cell Lipid Metabolism and Invasive Potential through the Lipase HSL.
Oncogene-induced metabolic reprogramming is a hallmark of pancreatic cancer (PDAC), yet the metabolic drivers of metastasis are unclear. In PDAC, obesity and excess fatty acids accelerate tumor growth and increase metastasis. Here, we report that excess lipids, stored in organelles called lipid droplets (LD), are a key resource to fuel the energy-intensive process of metastasis. The oncogene KRAS controlled the storage and utilization of LD through regulation of hormone-sensitive lipase (HSL), which was downregulated in human PDAC. Disruption of the KRAS-HSL axis reduced lipid storage, reprogrammed tumor cell metabolism, and inhibited invasive migration in vitro and metastasis in vivo. Finally, microscopy-based metabolic analysis revealed that migratory cells selectively utilize oxidative metabolism during the process of migration to metabolize stored lipids and fuel invasive migration. Taken together, these results reveal a mechanism that can be targeted to attenuate PDAC metastasis. SIGNIFICANCE: KRAS-dependent regulation of HSL biases cells towards lipid storage for subsequent utilization during invasion of pancreatic cancer cells, representing a potential target for therapeutic intervention.See related commentary by Man et al., p. 4886.


Phospholipases during membrane dynamics in malaria parasites.
Plasmodium parasites, the causative agents of malaria, display a well-regulated lipid metabolism required to ensure their survival in the human host as well as in the mosquito vector. The fine-tuning of lipid metabolic pathways is particularly important for the parasites during the rapid erythrocytic infection cycles, and thus enzymes involved in lipid metabolic processes represent prime targets for malaria chemotherapeutics. While plasmodial enzymes involved in lipid synthesis and acquisition have been studied in the past, to date not much is known about the roles of phospholipases for proliferation and transmission of the malaria parasite. These phospholipid-hydrolyzing esterases are crucial for membrane dynamics during host cell infection and egress by the parasite as well as for replication and cell signaling, and thus they are considered important virulence factors. In this review, we provide a comprehensive bioinformatic analysis of plasmodial phospholipases identified to date. We further summarize previous findings on the lipid metabolism of Plasmodium, highlight the roles of phospholipases during parasite life-cycle progression, and discuss the plasmodial phospholipases as potential targets for malaria therapy.


Future treatments in systemic sclerosis.
Systemic sclerosis (SSc) is an autoimmune disorder with clinical manifestations resulting from immune activation, fibrosis development and damage of small blood vessels. Although there have been no established treatments for SSc, lots of new treatments targeting organ and pathogenesis are in the process of development. Transforming growth factor (TGF)-beta is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF-beta, blockade of ligand by the pan-isoform-specific antibody, soluble TGF-beta receptors and a recombinant latency associated peptide, as well as inhibitors for ALK5 and Smad3 are the potential strategies to abolish the pathological activation of TGF-beta signaling in SSc fibroblasts. Besides TGF-beta, connective tissue growth factor (CTGF)/CCN2, platelet-derived growth factor (PDGF) and endothelin-1 are the candidates for the new therapeutic targets. As for immune dysfunction in SSc, i.v. immunoglobulin infusion, stem cell transplantation and B-cell depletion are potential new therapies under or awaiting a randomized, double-blind, placebo-controlled trial, although their efficacies are still controversial. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and inhibitors for serotonin signaling are the new therapeutic targets for Raynaud's phenomenon, digital ulceration and pulmonary arterial hypertension in SSc. Imatinib mesylate may be a novel new therapy for fibrosis and vasculopathy in SSc because it reverses the expression levels of Fli1, which is a transcription factor downregulated in SSc through an epigenetic mechanism and is likely to be involved in the development of fibrosis and vasculopathy in this disease. Potential therapeutic targets other than those described above are also reviewed.


[Complicated postbulbar duodenal ulcers: the characteristics of the diagnosis and of the surgical procedure and management].
The paper reports on the authors' experience used on 164 patients with complicated postbulbar ulcers (12% of the duodenal ulcers) with hemorrhage (52 cases), perforation (9 cases), duodenal stenosis (13 cases), stenosis and penetration (36 cases) and pancreatic-biliary penetrations (36 cases). The frequency of hemorrhagic complication was of 31%. As the hemorrhage due to postbulbar ulcer is favoured by vascular fistula, the severe character of the hemorrhage and the frequency of the recurrence, mainly the cataclysmic one, impose the radical surgery as early as possible. The following were used: large Reichel-Polya's gastrectomy (26 cases with 7 deaths) Péan's gastro-duodenectomy (12 cases), Péan's hemigastrectomy+vagotomy (4 cases), gastrectomy for exclusion with hemostasis in situ and ligature of gastroduodenal artery (8 cases, of which 1 with vagotomy and 2 deaths) and pyloroplasty with vagotomy and hemostasis (2 cases). The postsurgical mortality was of 17%. In 9 cases with perforation: Reichel-Polya's gastrectomy in 5 patients (1 death), Péan's gastrectomy in 2 cases, excision pyloroplasty and suture of the perforation in one case, respectively, were used. In the postbulbar ulcers penetrating into the pancreas or into the hepatic pedicle associated with stenosis (36 cases) the following were performed: Reichel-Polya's gastrectomy (7 cases), Péan's gastrectomy (7 cases of which 2 with vagotomy) gastrectomy for exclusion of ulcer in 19 cases, of which 5 with vagotomy, Péan's hemigastrectomy+vagotomy (3 cases). The 36 cases of ulcers penetrating into pancreas were solved as follows: gastrectomy for exclusion (16 cases of which 5 with vagotomy), Reichel-Polya's gastrectomy (10 cases of which 1 with vagotomy), Péan's gastrectomy (10 cases of which 2 with vagotomy). In 13 patients with stenosed ulcers, Reichel's-Polya's gastric resection (10 cases), Péan's gastrectomy, gastrectomy for exclusion and gastrojejunostomy (in one case each) were performed. The conclusions may be drawn that the postbulbar ulcers are complicated ulcers that require differentiated surgical treatment, as early as possible, for diminishing the postsurgical morbidity and mortality (7.5% mortality).


Exploring the Experiences and Perceptions of Adults With Spinal Cord Injury or Disease Aged 50 Years or Older on Participation in Sports.
Sports are physical activities that provide physical, psychological, and social benefits for individuals with spinal cord injury/disease (SCI/D). However, most sports research has been completed on individuals with SCI/D who are aged >50 years, even though the majority of people with SCI/D are aged >50 years. Despite substantial evidence supporting sports for older adults not living with a disability, there is currently no research examining the impact of sports for adults with SCI/D aged ≥50 years. To explore the perceptions and experiences of individuals with SCI/D aged 50 years or older who participate in sports in the community. Fifteen adults with SCI/D aged ≥50 years who participated in community-based sports were interviewed. Interviews were audio-recorded and transcribed verbatim. Conventional content analysis was applied to the data. The overarching theme identified was that sports are fun and adaptable physical activities that have the potential to optimize physical, psychological, and social health in all people with SCI/D, regardless of age. Within this overarching theme, six categories surfaced: (1) importance of participating in sports later in life, (2) prioritizing health over performance, (3) uncertainties about participating in sports later in life, (4) reflections on participating in sports later in life, (5) beliefs on alternative sports involvement, and (6) advice for other aging adults with SCI/D considering sports. Sports are perceived to provide physical, psychological, and social benefits for individuals with SCI/D aged 50 years or older. Findings will inform the development of future adaptive sports programs for older individuals with SCI/D.


Spectroscopic evaluation of the surface quality of apple.
Different spectroscopic techniques based on infrared and Raman were used to evaluate the natural wax and related surface quality of apple fruit. Transmission near-infrared (NIR) spectroscopy was applied to solutions of single wax components and extracted apple wax. Fourier transform infrared (FTIR) spectroscopy was used for transmission measurements of wax films on NaCl crystals, diffuse reflectance spectroscopy (DRIFTS) was used to analyze wax powders, and FT-Raman spectroscopy was explored to examine intact wax layers on whole fruit. The natural wax layers of apple fruit from a maximum of three different cultivars (Jonagold, Jonagored, and Elshof) from three picking dates (early, commercial, and late), three controlled atmosphere storage durations (0, 4, and 8 months), and three shelf life periods (0, 1, and 2 weeks) within each storage duration were examined. Canonical discriminant analysis was carried out on the first derivative NIR and FTIR spectra to describe the information contained in the spectra. Discrimination between cultivars and between storage duration based on wax layer properties was achieved with reasonable accuracy from both of the techniques. Information contained in the spectra of apples from different picking dates and shelf life periods was not significant. Differences between cultivars and storage periods in this analysis mostly related to differences in the number of aliphatic chains (e.g., alkanes and esters) and the presence of alpha-farnesene. No satisfactory results were obtained by means of Raman spectroscopy and DRIFTS.


[Current aspects of surgical treatment of gastro-esophageal reflux disease].
Gastroesophageal reflux disease (GERD) is characterized by abnormal reflux of gastric content into the esophagus, pharynx, respiratory tract and oral cavity. In recent years, there has been a significant increase of the incidence of this disease, that significantly aggravates quality of life of the population. The 'gold standard' for treating GERD is anti-secretory therapy with proton pump inhibitors (PPIs). However, up to 40% of patients are unresponsive to PPIs even after dose adjustment. Advantages and disadvantages of modern surgical approaches for this pathology are reviewed. Laparoscopic fundoplication including Nissen (360°), Toupet (270°) and Dor procedures (180°) is the most common anti-reflux operation. In addition, new alternative surgical options are also discussed. For example, these are minimally invasive methods such as LINX reflux control system, electrical stimulation of the lower esophageal sphincter and transoral incisionless fundoplication (TIF). These methods are less aggressive and have less side effects. A comparative assessment of modern methods of surgical treatment of GERD is made.


Research on history of medicine in China in the last five years.
Since 1999, progress has been made, to varying degrees, in numerous areas of medical history research in China including history of TCM, history of western medicine, history of integrated Chinese and western medicine, history of traditional medicine of Chinese minorities, history of medicine of foreign countries, history of medical exchanges between China and other countries, and history of comparative medical history. Among others, the number of articles on history of diseases, history of specific medical disciplines, modern medical history, medical biographies, medical works, contemporary medical history, and history of medical culture has increased dramatically. In the field of history of diseases, the papers deal with diseases in gynecology and obstetrics, plague, lanhousha (scarlet fever), and nephritis; articles in the field of specific disciplines deal with history of acu-moxibustion, history of prescription-forms, and history of gynecology, endoscopic surgery, and evidence-based medicine. There are even distinguished papers appeared in these aspects. In the aspect of modern medical history, there are papers dealing with the developement of TCM, the introduction of western medicine into China, with some specific researches in these fields. Medical biographies include Tan Yun-xian, Quan Shao-qing, Du Chong-ming etc. Papers on medical works deal with the ancient unearthed literature lost yet spread and extant abroad, medical classics, canons on material medica, cold-pathogenic diseases, and formularies. While papers on history of medical culture discuss basically the influence of Confucianism, Taoism, Buddhism and I-discipline on Chinese medicine. During these five years, 300 original articles have been published in The Chinese journal of Medical History, with another 200 papers published in other Chinese journals. Forty monographs have been published and important ones are A General History of Chinese Medicine, Modern history of TCM, The Historical Development of Acupuncture, A General History of Tiberan Medicine. For the coming years, the stress points should be laid on the research on history of diseases, history of specific medical disciplines, and some specific academic topics. In addition, the weak points in the research fields of theoretical problems in studies of medical history, history of traditional medicine of Chinese minorities, medical history of communication between China and foreign countries, comparative study on medical history, and the study on history of medical also be strengthened continually. In the five years since 1999, progress has been made, more or less, in the research works in medical history in China, including history of TCM, history of western medicine, history of integrated Chinese and western medicine, history of traditional medicine of Chinese minorities, history of medicine of foreign countries, history of medical exchanges between China and other countries, and history of comparative medical history. And the number of articles on history of diseases, history of specific medical disciplines, modern medical history, medical biographies, medical works, contemporary medical history and history of medical culture has increased dramatically. The research work in ancient medical history is still progressing forcefully.


Protected area characteristics that help waterbirds respond to climate warming.
Protected area networks help species respond to climate warming. However, the contribution of a site's environmental and conservation-relevant characteristics to these responses is not well understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites) changed in response to increases in temperature over 25 years in 26 European countries. We measured community reshuffling based on abundance time series collected under the International Waterbird Census relative to N2K sites' conservation targets, funding, designation period, and management plan status. Waterbird community composition in sites explicitly designated to protect them and with management plans changed more quickly in response to climate warming than in other N2K sites. Temporal community changes were not affected by the designation period despite greater exposure to temperature increase inside late-designated N2K sites. Sites funded under the LIFE program had lower climate-driven community changes than sites that did not received LIFE funding. Our findings imply that efficient conservation policy that helps waterbird communities respond to climate warming is associated with sites specifically managed for waterbirds.


HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages.
Viruses often interfere with the DNA damage response to better replicate in their hosts. The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) protein has been reported to modulate the activity of the DNA repair structure-specific endonuclease subunit (SLX4) complex and to promote cell cycle arrest. Vpr also interferes with the base-excision repair pathway by antagonizing the uracil DNA glycosylase (Ung2) enzyme. Using an unbiased quantitative proteomic screen, we report that Vpr down-regulates helicase-like transcription factor (HLTF), a DNA translocase involved in the repair of damaged replication forks. Vpr subverts the DDB1-cullin4-associated-factor 1 (DCAF1) adaptor of the Cul4A ubiquitin ligase to trigger proteasomal degradation of HLTF. This event takes place rapidly after Vpr delivery to cells, before and independently of Vpr-mediated G2 arrest. HLTF is degraded in lymphocytic cells and macrophages infected with Vpr-expressing HIV-1. Our results reveal a previously unidentified strategy for HIV-1 to antagonize DNA repair in host cells.


Helper lipid structure influences protein adsorption and delivery of lipid nanoparticles to spleen and liver.
Nucleic acids, such as messenger RNAs, antisense oligonucleotides, and short interfering RNAs, hold great promise for treating previously 'undruggable' diseases. However, there are numerous biological barriers that hinder nucleic acid delivery to target cells and tissues. While lipid nanoparticles (LNPs) have been developed to protect nucleic acids from degradation and mediate their intracellular delivery, it is challenging to predict how alterations in LNP formulation parameters influence delivery to different organs. In this study, we utilized high-throughput in vivo screening to probe for structure-function relationships of intravenously administered LNPs along with quartz crystal microbalance with dissipation monitoring (QCM-D) to measure the binding affinity of LNPs to apolipoprotein E (ApoE), a protein implicated in the clearance and uptake of lipoproteins by the liver. High-throughput in vivo screening of a library consisting of 96 LNPs identified several formulations containing the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) that preferentially accumulated in the liver, while identical LNPs that substituted DOPE with the helper lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) preferentially accumulated in the spleen. Using QCM-D, it was found that one DOPE-containing LNP formulation (LNP 42) had stronger interactions with ApoE than an identical LNP formulation that substituted DOPE with DSPC (LNP 90). In order to further validate our findings, we formulated LNP 42 and LNP 90 to encapsulate Cy3-siRNA or mRNA encoding for firefly luciferase. The DSPC-containing LNP (LNP 90) was found to increase delivery to the spleen for both siRNA (two-fold) and mRNA (five-fold). In terms of liver delivery, the DOPE-containing LNP (LNP 42) enhanced mRNA delivery to the liver by two-fold and improved liver transfection by three-fold. Understanding the role of the helper lipid in LNP biodistribution and ApoE adsorption may aid in the future design of LNPs for nucleic acid therapeutics.


Surface hydrophobization of pulp fibers in paper sheets via gas phase reactions.
Hydrophobization of cellulosic materials and particularly paper products is a commonly used procedure to render papers more resistant to water and moisture. Here, we explore the hydrophobization of unsized paper sheets via the gas phase. We employed three different compounds, namely palmitoyl chloride (PCl), trifluoroacetic anhydride/acetic anhydride (TFAA/Ac2O)) and hexamethyldisilazane (HMDS) which were vaporized and allowed to react with the paper sheets via the gas phase. All routes yielded hydrophobic papers with static water contact angles far above 90° and indicated the formation of covalent bonds. The PCl and TFAA approach negatively impacted the mechanical and optical properties of the paper leading to a decrease in tensile strength and yellowing of the sheets. The HMDS modified papers did not exhibit any differences regarding relevant paper technological parameters (mechanical properties, optical properties, porosity) compared to the non-modified sheets. XPS studies revealed that the HMDS modified samples have a rather low silicon content, pointing at the formation of submonolayers of trimethylsilyl groups on the fiber surfaces in the paper network. This was further investigated by penetration dynamic analysis using ultrasonication, which revealed that the whole fiber network has been homogeneously modified with the silyl groups and not only the very outer surface as for the PCl and the TFAA modified papers. This procedure yields a possibility to study the influence of hydrophobicity on paper sheets and their network properties without changing structural and mechanical paper parameters.


Effect of decabrominated diphenyl ether exposure on spatial learning and memory, the expression and phosphorylation of hippocampal glutamate receptor subunits in adult Sprague-Dawley rats.
Previous studies have reported the potential developmental neurobehavioral effects of decabrominated diphenyl ethers (BDE 209) on developing animals, but the effects on adult animals are rare or controversial and the mechanism is not fully understood. In the present study, male adult Sprague-Dawley rats performed poor spatial learning and memory in Morris water maze after exposure to BDE 209 by gavage for 30 days. The expression of hippocampal glutamate receptor subunits NR1, NR2B and GluR1, the phosphorylation of NR2B subunit at Ser1301 (p-NR2B Ser1303) and GluR1 subunit at Ser831 (p-GluR1 Ser831) were all decreased, and the phosphorylation ratio of NR2B revealed an increasing trend after BDE 209 exposure. The present study provided evidence that BDE 209 could induce spatial learning and memory deficits in adult rats, and further explored the potential mechanism.


Effect of the polar head structure of polyene macrolide antifungal antibiotics on the mode of permeabilization of ergosterol- and cholesterol-containing lipidic vesicles studied by 31P-NMR.
Natural polyene macrolide antibiotics and their N-acyl and methyl ester derivatives, which differ mainly in their electric net charge, were compared for their ability to increase the ionic permeability of large unilamella vesicles, using the proton-cation exchange method and 31P-NMR spectroscopy. The zwitterionic (amphotericin B, vacidin A) and negatively charged (N-N'-diacetyl vacidin) compounds induced permeability according to an all-or-none process on both cholesterol- and ergosterol-containing membranes. The same mechanism of permeability induction is obtained only on ergosterol-containing vesicles for positively charged antibiotics (perimycin A, vacidin A methyl ester, amphotericin B methyl ester). A different type of action is observed for the latter group of ionophores in cholesterol-containing vesicles. In this case, a progressive proton efflux occurs in which all of the vesicle population is involved. This qualitative difference in the kinetics of ionic fluxes induced by antibiotics without a free carboxyl group in cholesterol-containing as compared to ergosterol-containing membranes was ascribed to differences in polyene-sterol interactions as well as in the life time of the ionic path formed. This difference may provide a basis for the improvement of selective toxicity of this group of antifungal agents by rational modifications.


Activity assessment of microalgal-bacterial consortia based on respirometric tests.
Respirometric techniques are useful tools to evaluate bacterial activities in activated sludge processes due to their fast execution and the possibility to obtain several kinetic parameters from a single test. Using such techniques in microalgae-bacteria consortia treating wastewater could allow a better understanding of mutual interactions between the microbial populations as a function of environmental parameters. This work aims at developing and testing a novel experimental respirometric protocol to determine oxygen uptake rates and oxygen production rates by a microalgae-bacteria consortium. The defined protocol is characterized by alternating light/dark regimes and by dosing substrates/inhibitors to selectively activate/inactivate microalgal and bacterial metabolisms. The protocol was then applied on microalgal and bacterial consortia, which were grown on the liquid fraction of black water from biogas plants fed on agricultural and municipal waste sludge. Results elucidate the presence and activity of microalgae and nitrifying bacteria in the tested systems, suggesting that the respirometric tests could be included into monitoring procedures of photobioreactors/algal ponds.


Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells.
Trefoil peptides (TFFs) are now considered as scatter factors, proinvasive and angiogenic agents acting through cyclooxygenase-2 (COX-2)- and thromboxane A2 receptor (TXA2-R)-dependent signaling pathways. As expression and activation levels of the epidermal growth factor receptor (EGFR) predict the metastatic potential of human colorectal cancers, the purpose of this study was to establish whether the EGF receptor tyrosine kinase (EGFR-TK) contributes to cellular invasion induced by TFFs in kidney and colonic cancer cells. Both the dominant negative form of the EGFR (HER-CD533) and the EGFR-TK inhibitor ZD1839 (Iressa) abrogated cellular invasion induced by pS2, spasmolytic polypeptide (SP) and the src oncogene, but not by ITF and the TXA2-R. Similarly, EGFR-TK inhibition by ZD1839 reversed the invasive phenotype promoted by the constitutively activated form of the EGFR (EGFRvIII) and the EGFR agonists transforming growth factor alpha (TGFalpha), amphiregulin and EGF. We also provide evidence that TFFs, EGFRvIII, and TGFalpha trigger common proinvasive pathways using the PI3'-kinase and Rho/Rho- kinase cascades. These findings identify the EGFR-TK as a key signaling element for pS2- and SP-mediated cellular invasion. It is concluded that although pS2, SP and ITF belong to the same family of inflammation- and cancer-associated regulatory peptides, they do not control identical signaling networks.


Surgical strategies for anomalous origin of coronary artery from pulmonary artery in adults.
Limited data are available regarding the surgical strategies for an anomalous origin of the coronary artery from the pulmonary artery (ACAPA) in adulthood. We reviewed our surgical experience with ACAPA in adults. From January 1960 to July 2011, 10 adults (30% men), aged 18 to 78 years (median, 43), underwent surgical repair of ACAPA. Anomalous left (ALCAPA) was present in 7, anomalous right (ARCAPA) in 2, and anomalous left anterior descending artery in 1. Most (90%) were symptomatic, with 7 (70%) having ischemic changes on a preoperative at rest or stress electrocardiogram. One patient had undergone previous ligation of ALCAPA in childhood. The mean left ventricular ejection fraction was 56% ± 10%, with mild dysfunction in 4. Of the 10 patients, 7 underwent repair by coronary artery button transfer to the aorta, with 2 requiring an interposition saphenous vein graft. In 3 patients, coronary transfer was not possible, and coronary artery bypass grafting with closure of the ACAPA was performed. The mean follow-up was 8.6 years (maximum, 37). Two late deaths occurred from noncardiac causes. One patient with ALCAPA who underwent direct reimplantation subsequently required coronary artery bypass grafting for left main stenosis, likely secondary to tension. At the last follow-up visit, all patients were in New York Heart Association class I or II. The postoperative left ventricular ejection fraction was similar at 53% ± 9%; No significant improvement was seen in those with below normal ejection fraction. Establishment of a dual coronary artery system with coronary transfer is preferred, even if an interposition graft is required. Coronary artery bypass grafting with closure of ACAPA should be reserved for when coronary transfer is not feasible. Surgical correction of ACAPA should be considered before the onset of left ventricular dysfunction.


[Clinical and experimental study of clofelin pharmacodynamics].
Hemodynamic mechanisms of clophelin hypotensive effect were studied in 122 patients with arterial hypertension. In most cases, antihypertensive clophelin therapy did not affect the nature or magnitude of orthostatic and stress-induced hemodynamic shifts. The fact that the fall in perfusion BP was not accompanied with a resting, orthostatic or stress-induced impairment of renal function was a particularly valuable aspect of clophelin treatment. Experimental studies demonstrated that clophelin hypotensive effect was partly due to limited Ca2+ entrance through the slow calcium channels in the cell membrane as well as limited potassium withdrawal during excitation. Single and repeated clophelin administration (0.03-1 mg/kg daily) was shown to depress reproductive capacity in rats of both sexes, due to suppressed blood levels of pituitary gonadotrophin as well as altered gonadal sensitivity to gonadotrophin effects.


The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection.
To assess the impact of immediate vs. deferred antiretroviral therapy (ART) on CD4 recovery among individuals early in HIV infection. Using serologic markers of early infection together with self-reported dates of infection and HIV diagnosis, ART-naive participants who were randomized to immediate vs. deferred ART in the Strategic Timing of Antiretroviral Treatment trial were classified into subgroups of duration of HIV infection at baseline. CD4 cell count recovery over follow-up according to duration of HIV infection was investigated. Three subgroups were defined: first, infected 6 months or less (n = 373); second, infected 6-24 months (n = 2634); and third, infected 24 months or longer (n = 1605). Follow-up CD4, CD8, and CD4 : CD8 ratio for the immediate and deferred ART groups were compared by subgroup using linear models. For the deferred ART group, decline to CD4 less than 350 cells/μl or AIDS according to infection duration was compared using time-to-event methods. Follow-up CD4 cell count differences (immediate minus deferred) were greater for those recently infected (+231 cells/μl) compared with the two other subgroups (202 and 171 cells/μl; P < 0.001). CD4 : CD8 ratio treatment differences varied significantly (P < 0.001) according to duration of infection. In the deferred ART group, decline to CD4 less than 350 cells/μl or AIDS was greater among those recently infected (16.1 vs. 13.2 and 10.5 per 100 person years for those infected 6-24 and ≥24 months; P = 0.002). In this randomized comparison of immediate vs. deferred ART, the CD4 cell count difference was greatest for those recently infected with HIV, emphasizing the importance of immediate ART initiation.


The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington's disease: an exploratory study.
There is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntington's disease (HD). Efforts to attenuate disease-related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity, depression, quality of life and some aspects of cognition in individuals with HD. This exploratory study aimed to evaluate, for the first time, whether multidisciplinary rehabilitation can slow further deterioration of disease-related brain changes and related cognitive deficits in individuals with manifest HD. Fifteen participants who manifest HD undertook a multidisciplinary rehabilitation intervention spanning 9 months. The intervention consisted of once-weekly supervised clinical exercise, thrice-weekly self-directed home based exercise and fortnightly occupational therapy. Participants were assessed using MR imaging and validated cognitive measures at baseline and after 9 months. Participants displayed significantly increased gray matter volume in the right caudate and bilaterally in the dorsolateral prefrontal cortex after 9 months of multidisciplinary rehabilitation. Volumetric increases in gray matter were accompanied by significant improvements in verbal learning and memory (Hopkins Verbal Learning-Test). A significant association was found between gray matter volume increases in the dorsolateral prefrontal cortex and performance on verbal learning and memory. This study provides preliminary evidence that multidisciplinary rehabilitation positively impacts on gray matter changes and cognitive functions relating to verbal learning and memory in individuals with manifest HD. Larger controlled trials are required to confirm these preliminary findings.


Unconditional probability of dying and age-specific mortality rate because of major non-communicable diseases in India: Time trends from 2001 to 2013.
Unconditional probability of dying because of four major non-communicable diseases (NCDs) between 30 and 70 years of age is the selected global indicator to measure the impact of NCD prevention and control programs. To calculate the unconditional probability of dying and age-specific mortality rate because of major NCDs in India from 2001 to 2013. This study used multiple data sources that are available in the public domain-Census 2001 and 2011, Sample Registration System, causes of death reports in 2001-03, 2004-06, and 2010-13. Unconditional probability of dying between ages 30 and 70 years during 2001, 2006, and 2013 was calculated by the formula suggested by the World Health Organization. Line graphs were used to depict time trends in age-specific mortality rates over the years in four major NCDs (cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases). The age-specific mortality rate because of four NCDs showed a decrease of 51 deaths per 100,000 population from 2001 to 2013. Of the four NCDs, age-specific mortality rate was highest in cardiovascular diseases (238.2/100,000 population) and least in diabetes mellitus (21.9/100,000 population); it was 76.3 and 58.2/100,000 population for cancer and chronic respiratory diseases, respectively. The probability of dying was very less and was almost the same from 30 to 44 years of life and increased steeply after that till 70 years of life; and it was more in males (24%) compared with females (17.4%). Although India has shown a decreasing trend in premature mortality because of NCDs in the past decade, the rate of decrease is not on par to achieve the global "25 × 25" target.


The effects of methylphenidate and maturation on exploratory activity in rats.
Treatment of attention-deficit hyperactivity disorder with stimulants such as methylphenidate reduces motor activity and improves performance of tasks requiring attention, learning, and memory. The present study reports the patterns of behavioral activity of rats of different ages, and the effect of methylphenidate on the behavioral activity. The behavioral activity of Wistar male rats was measured on the nine hole-board apparatus. In experiment I, the behavioral activity of rats from three age groups (4, 8 and 12 weeks old) were measured in terms of the activity time, specific exploratory behavior, diverse exploratory behavior and defecation number. The rats were re-exposed to the hole-board again every two weeks until they 14 weeks old. The younger rats showed higher activity level compared to the older rats. The activity level decreased as the rats grew older. The younger rats also showed more diverse exploratory behavior, but less specific exploratory behavior compared with the older rats. These suggested that the younger rats may be more hyperactive in nature, and less prone to focus on the specific targets. In experiment II, the methylphenidate (4 mg/kg, i.p.) injected rats showed higher activity level than the controls across the three age groups. The exploratory behavioral patterns were not significantly different among the three age groups. This suggests that the methylphenidate injection raises the motor activity level without affecting the exploratory tendency of rats.


A comparative study of the prevalence of domestic violence in women requesting a termination of pregnancy and those attending the antenatal clinic.
To compare the prevalence of domestic violence (DV) in women requesting antenatal care (ANC) and termination of pregnancy (TOP) in North East England. This was a cross-sectional comparative prevalence study using self-administered questionnaires, with women selected as opportunistic samples over a concurrent period. The participants were screened anonymously and confidentially in the ANC and TOP clinics. Pregnant women in the first trimester requesting a TOP or ANC. The participants were screened for a history of DV using a modified version of the Abuse Assessment Screening tool. Prevalence of DV between ANC and TOP populations, and any differences in the characteristics of the women, such as age, level of education, or marital status. We aimed to determine the reasons for requesting a TOP. There were 507 respondents, with 233 attending ANC and 274 requesting a TOP. Of the ANC population, 219 completed the questionnaire. In the TOP population, all the questionnaires were fully or partially completed. Women requesting a TOP were six times as likely to suffer physical abuse in the current relationship (5.8 versus 0.9%; χ(2) = 10.2 (2); P < 0.05), and were five times as likely to suffer emotional abuse (9.9 versus 1.8%; χ(2) = 13.6 (2); P < 0.0001), than those attending ANC. Of the 274 women requesting a TOP, only ten mentioned DV as a contributing factor. There is a higher prevalence of DV in the TOP population than in the ANC population, but very few women stated that DV influenced their request for a TOP.


Transformation model estimation of survival under dependent truncation and independent censoring.
Truncation is a mechanism that permits observation of selected subjects from a source population; subjects are excluded if their event times are not contained within subject-specific intervals. Standard survival analysis methods for estimation of the distribution of the event time require quasi-independence of failure and truncation. When quasi-independence does not hold, alternative estimation procedures are required; currently, there is a copula model approach that makes strong modeling assumptions, and a transformation model approach that does not allow for right censoring. We extend the transformation model approach to accommodate right censoring. We propose a regression diagnostic for assessment of model fit. We evaluate the proposed transformation model in simulations and apply it to the National Alzheimer's Coordinating Centers autopsy cohort study, and an AIDS incubation study. Our methods are publicly available in an R package, tranSurv.


Non-monotonic effect of additive particle size on the glass transition in polymers.
Effect of small additive molecules on the structural relaxation of polymer melts is investigated via molecular dynamics simulations. At a constant external pressure and a fixed number concentration of added molecules, the variation of the particle diameter leads to a non-monotonic change of the relaxation dynamics of the polymer melt. For non-entangled chains, this effect is rationalized in terms of an enhanced added-particle-dynamics which competes with a weaker coupling strength upon decreasing the particle size. Interestingly, cooling simulations reveal a non-monotonic effect on the glass transition temperature also for entangled chains, where the effect of additives on polymer dynamics is more intricate. This observation underlines the importance of monomer-scale packing effects on the glass transition in polymers. In view of this fact, size-adaptive thermosensitive core-shell colloids would be a promising candidate route to explore this phenomenon experimentally.


[The structural dynamics of the afferent flow in the action on the receptor field of a low-intensity stimulant].
The pattern of changes in afferent flow from a uniform isolated receptor field (3-5 mechanoreceptor units) under the effect of unspecific external stimulus of low intensity, was studied. A diverse dynamics of the afferent flow was observed: the firing rate, relative distribution of discharges in time, the amplitude and the form of spikes, are altered. The changes occur simultaneously, as a rule, which renders the idea of afferent flow's structure rather uncertain. The growth in amplitude and the change in the form of discharges seem to be based on a synchronizing of receptor units excitation. The latter can serve as a premise for actualization of the mechanism of sensory information compression by means of involvement of parallel afferent fibres in the excitation.