Lamellar phases containing vanadium oxide: synthesis, characterization and application of the adsorption of phenol from aqueous solutions.
Lamellar phases of the general formula [CnH(2n+1)N(CH3)3]VO3 (n = 14, 16, 18) have been prepared by an ion-exchange/precipitation reaction of alkyltrimethylammonium surfactants and NaVO3 in an aqueous medium at room temperature. The phases were characterized by powder X-ray diffraction, transmission electron microscopy, infrared spectroscopy, thermogravimetric analysis and differential scanning calorimetry. The data support a proposed crystal structure model in which single arrays of the one-dimensional chains of oligomers {(VO3)n}(n-) that may be generated from the starting material NaVO3 fragmented by the hydration during the dissolution into water and the surfactants layers alternate. The alkyl chains of the surfactants in these materials are arranged as monolayers or deeply penetrate into the interlayer region with a tilt angle of 37 degrees. The phenol adsorption in aqueous solution on a representative lamellar phase was investigated. The data being fitted to Langmuir Isotherms and a maximum adsorption capacity calculated from the Langmuir equation to be 178.6 mg of phenol/g for [C16H33N(CH3)3]VO3 have been obtained. The effect of pH on the adsorption and desorption of phenol has also been studied. Acetone solution of 20% is the best eluent for desorption of phenol from the loaded adsorbent with a desorption efficiency of 90.8%.


The adaptation in various languages of standardized periodontal terminology to recent acquisitions.
Before nomenclatorial translation can be begun, an approved definition of the term concerned is required, as is a systematic classification of related designations. Existing sources are bi- or multi-lingual dictionaries and glossaries but relatively few of these cover oral biology and dentistry in adequate detail. Much of the terminology developed for specialized fields of medicine is applicable to dentistry in general and periodontology in particular but the proliferation of new terms in English/American cannot always be matched appropriately in other languages. Examples of a uniform periodontal terminology in English, French and German--prepared for the impending revision of the FDI Dental Lexicon--are tabulated.


Emergent criticality in complex turing B-type atomic switch networks.
Recent advances in the neuromorphic operation of atomic switches as individual synapse-like devices demonstrate the ability to process information with both short-term and long-term memorization in a single two terminal junction. Here it is shown that atomic switches can be self-assembled within a highly interconnected network of silver nanowires similar in structure to Turing's "B-Type unorganized machine", originally proposed as a randomly connected network of NAND logic gates. In these experimental embodiments,complex networks of coupled atomic switches exhibit emergent criticality similar in nature to previously reported electrical activity of biological brains and neuron assemblies. Rapid fluctuations in electrical conductance display metastability and power law scaling of temporal correlation lengths that are attributed to dynamic reorganization of the interconnected electro-ionic network resulting from induced non-equilibrium thermodynamic instabilities. These collective properties indicate a potential utility for realtime,multi-input processing of distributed sensory data through reservoir computation. We propose these highly coupled, nonlinear electronic networks as an implementable hardware-based platform toward the creation of physically intelligent machines.


Relapsing polychondritis with isolated tracheal involvement and airway-only symptoms.
Relapsing polychondritis (RP) is a rare autoimmune disorder, characterized by the inflammation of cartilaginous structures and proteoglycan-rich tissues. Due to its rarity and the notoriously variable presentations, the diagnosis of RP could be challenging. We report an unusual case of RP with isolated tracheal involvement and very non-specific symptoms of exertional dyspnoea and dry cough. The initial chest radiograph showed long-segment narrowing of the trachea, and the computed tomography of the chest revealed thickened cartilaginous walls of the trachea, while the posterior membranous portion was spared. The tracheal narrowing was readily observed under bronchoscopy. The patient was treated with oral prednisolone. Although the subsequent course was transiently complicated by an episode of severe Pneumocystis jirovecii pneumonia with acute respiratory distress syndrome, the patient overall responded well to systemic corticosteroid therapy. No new symptoms developed during a two-year follow-up.


Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms.
Enhanced tolerance of biofilm-associated bacteria to antibiotic treatments is likely due to a combination of factors, including changes in cell physiology as bacteria adapt to biofilm growth and the inherent physiological heterogeneity of biofilm bacteria. In this study, a transcriptomics approach was used to identify genes differentially expressed during biofilm growth of Pseudomonas aeruginosa. These genes were tested for statistically significant overlap, with independently compiled gene lists corresponding to stress responses and other putative antibiotic-protective mechanisms. Among the gene groups tested were those associated with biofilm response to tobramycin or ciprofloxacin, drug efflux pumps, acyl homoserine lactone quorum sensing, osmotic shock, heat shock, hypoxia stress, and stationary-phase growth. Regulons associated with Anr-mediated hypoxia stress, RpoS-regulated stationary-phase growth, and osmotic stress were significantly enriched in the set of genes induced in the biofilm. Mutant strains deficient in rpoS, relA and spoT, or anr were cultured in biofilms and challenged with ciprofloxacin and tobramycin. When challenged with ciprofloxacin, the mutant strain biofilms had 2.4- to 2.9-log reductions in viable cells compared to a 0.9-log reduction of the wild-type strain. Interestingly, none of the mutants exhibited a statistically significant alteration in tobramycin susceptibility compared to that with the wild-type biofilm. These results are consistent with a model in which multiple genes controlled by overlapping starvation or stress responses contribute to the protection of a P. aeruginosa biofilm from ciprofloxacin. A distinct and as yet undiscovered mechanism protects the biofilm bacteria from tobramycin.


Cutoffs and Characteristics of Abnormal Bowel Dilatation in Pediatric Short Bowel Syndrome.
Although excessive intestinal dilatation associates with worsened outcomes in pediatric short bowel syndrome (SBS), little is known about the natural history and definition of pathological dilatation. We addressed fore-, mid-, and hind-gut dilatation in children with SBS, who had not undergone autologous intestinal reconstructive (AIR) surgery, in relation to controls. SBS children without history of AIR surgery (n = 59) and age-matched controls without any disclosed intestinal pathology (n = 140) were included. Maximum diameter of duodenum, small bowel (SB), and colon were measured in each intestinal contrast series during 2002 to 2020 and expressed as diameter ratio (DR) to L5 vertebrae height. Predictive ability of DR for weaning off parenteral nutrition (PN) was analyzed with Cox proportional hazards regression models using multiple cutoffs. Duodenum (DDR), SB (SBDR), and colon (CDR) DR were 53%, 183%, and 23% higher in SBS patients compared to controls ( P < 0.01 for all). The maximal DDR and SBDR measured during follow-up is associated with current PN dependence and young age. DDR correlated with SBDR ( r = 0.586, P < 0.01). Patients with maximal DDR less than 1.5, which was also the 99th percentile for controls, were 2.5-fold more likely to wean off PN ( P = 0.005), whereas SBDR and CDR were not predictive for PN duration. All segments of remaining bowel, especially SB, dilate above normal levels in children with SBS. In SBS children without AIR surgery, PN dependence and young age is associated with duodenal and small intestinal dilatation, while duodenal dilatation also predicted prolonged PN.


Reduction of spasticity with repetitive transcranial magnetic stimulation in patients with spinal cord injury.
Spasticity with increased tone and spasms is frequent in patients after spinal cord injury (SCI). Damage to descending corticospinal pathways that normally exert spinal segmental control is thought to play an important causal role in spasticity. The authors examined whether the modulation of excitability of the primary motor cortex with high-frequency repetitive transcranial magnetic stimulation (rTMS) could modify lower limb spasticity in patients with incomplete SCI. Patients were assessed by the Modified Ashworth Scale, Visual Analogue Scale, and the Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET) and neurophysiologically with measures of corticospinal and segmental excitability by the H(max)/M(max), T reflex, and withdrawal reflex. Fifteen patients received 5 days of daily sessions of active (n = 14) or sham (n = 7) rTMS to the leg motor area (20 trains of 40 pulses at 20 Hz and an intensity of 90% of resting motor threshold for the biceps brachii muscle). A significant clinical improvement in lower limb spasticity was observed in patients following active rTMS but not after sham stimulation.This improvement lasted for at least 1 week following the intervention. Neurophysiological studies did not change. High-frequency rTMS over the leg motor area can improve aspects of spasticity in patients with incomplete SCI.


Structural basis for (p)ppGpp-mediated inhibition of the GTPase RbgA.
Efficient adaptation to environmental changes is pivotal for all bacterial cells. Almost all bacterial species depend on the conserved stringent response system to prompt timely transcriptional and metabolic responses according to stress conditions and nutrient depletion. The stringent response relies on the stress-dependent synthesis of the second messenger nucleotides and alarmones (p)ppGpp, which pleiotropically target and reprogram processes that consume cellular resources, such as ribosome biogenesis. Here we show that (p)ppGpp acts on the ribosome biogenesis GTPase A (RbgA) of Gram-positive bacteria. Using X-ray crystallography, hydrogen-deuterium exchange MS (HDX-MS) and kinetic analysis, we demonstrate that the alarmones (p)ppGpp bind to RbgA in a manner similar to that of binding by GDP and GTP and thereby act as competitive inhibitors. Our structural analysis of Staphylococcus aureus RbgA bound to ppGpp and pppGpp at 1.8 and 1.65 Å resolution, respectively, suggested that the alarmones (p)ppGpp prevent the active GTPase conformation of RbgA by sterically blocking the association of its G2 motif via their 3'-pyrophosphate moieties. Taken together, our structural and biochemical characterization of RbgA in the context of the alarmone-mediated stringent response reveals how (p)ppGpp affects the function of RbgA and reprograms this GTPase to arrest the ribosomal large subunit.


A microarray analysis of gene expression in the free-living stages of the parasitic nematode Strongyloides ratti.
The nematode Strongyloides ratti has two adult phases in its lifecycle: one obligate, female and parasitic and one facultative, dioecious and free-living. The molecular control of the development of this free-living generation remains to be elucidated. We have constructed an S. ratti cDNA microarray and used it to interrogate changes in gene expression during the free-living phase of the S. ratti life-cycle. We have found very extensive differences in gene expression between first-stage larvae (L1) passed in faeces and infective L3s preparing to infect hosts. In L1 stages there was comparatively greater expression of genes involved in growth. We have also compared gene expression in L2 stages destined to develop directly into infective L3s with those destined to develop indirectly into free-living adults. This revealed relatively small differences in gene expression. We find little evidence for the conservation of transcription profiles between S. ratti and S. stercoralis or C. elegans. This is the first multi-gene study of gene expression in S. ratti. This has shown that robust data can be generated, with consistent measures of expression within computationally determined clusters and contigs. We find inconsistencies between EST representation data and microarray hybridization data in the identification of genes with stage-specific expression and highly expressed genes. Many of the genes whose expression is significantly different between L1 and iL3s stages are unknown beyond alignments to predicted genes. This highlights the forthcoming challenge in actually determining the role of these genes in the life of S. ratti.


An Impressive Result: AIR.
Results of endothelial photography indicate the occasional disregard for implant-corneal touch that may occur during many intraocular maneuvers. The use of air reduces this risk and undoubtedly can give the physician an impressive result.


[CAPSULE ENDOSCOPY: THE HISTORY AND PROSPECTS FOR DEVELOPMENT].
The review is focused on recent publications concerning examination of patients with gastroenterological pathology and the use of capsule endoscopy for diagnostics ofsmall bowel diseases. It is shown that radiological methods and enteroscopy are second line diagnostic tools while capsule endoscopy becomes the method ofchoice for the detection of latent gastrointestinal bleeding, tumours, Crohn's disease, and other enteropathies. The advantages of capsule enteroscopy include high effectiveness, atraumaticity, low frequency of complications and possibility to conduct studies without anesthesia. Much attention is given to indications and contraindicationsfor capsule endoscopy and methods of patient preparationfor this procedure.


Rectovaginal fistula with anal atresia in 5 dogs.
Five dogs with rectovaginal fistula and atresia ani that had been treated by surgical correction of the malformations were studied retrospectively. Ages at presentation varied from 1 to 3 months and weight from 350 g to 7.5 kg. The histories included voiding of feces through the vulva, with or without tenesmus, usually observed after weaning. Atresia ani, presence of feces in the vaginal canal, abdominal distention, and discomfort on abdominal palpation were observed during clinical examination. Also, 3 dogs had partial tail agenesis. In all dogs, the rectovaginal fistula was isolated and transected, the vulvar and rectal defects were closed separately, and the atresia ani was repaired. Normal defecation was restored, but 1 dog had fecal incontinence that subsequently resolved. One dog died 2.5 months postoperatively, and follow-up was done on the others for periods ranging from 1.6 year to 7.7 years. Surgical correction in dogs with rectovaginal fistula and atresia ani may result in a favorable outcome, if it is done early.


A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys. Part 1: Clinical and radiological findings.
The authors have developed a method to induce chronic cerebral vasospasm after subarachnoid hemorrhage (SAH) in monkeys. With microsurgical techniques, 33 monkeys had a frontotemporal craniectomy and unilateral opening of the subarachnoid cisterns. Cerebrospinal fluid was drained and a fresh hematoma, obtained from an average of 7 ml of autologous blood, was carefully placed against the major arteries of the anterior circulation on one side. The 30 monkeys studied for 7 to 14 days after the SAH were allocated randomly to two treatment groups of 15: one group received placebo and the other nimodipine, 1 mg/kg every 8 hours. Indices monitored before and after SAH included neurological status, cerebral blood flow, computerized tomography, and angiographic vessel caliber. In the placebo group, delayed ischemic neurological deficit developed in one monkey 4 days after clot placement and was present at sacrifice on Day 14. No such deficit occurred in the nimodipine group. The effect of nimodipine on vessel caliber at this dosage was equivocal. Significant vasospasm (31% to 100% reduction in vessel caliber) developed in 87% (26 of 30) of the animals. Overall, vasospasm was slightly more common in the placebo group: in this group, on Days 7 and 14, the incidence of vasospasm was significantly higher (p less than 0.05) than in the nimodipine group. However, the average percentage reduction in vessel caliber of the maximally constricted vessel in each monkey was not significantly different between the two groups.


Retrospective cohort study exploring whether an association exists between spatial distribution of cystoid spaces in cystoid macular oedema secondary to retinitis pigmentosa and response to treatment with carbonic anhydrase inhibitors.
Carbonic anhydrase inhibitors (CAIs) are frequently used as an initial step to treat retinitis pigmentosa-associated cystoid macular oedema (RP-CMO). Interestingly, it has been postulated that CAIs might reduce outer nuclear layer (ONL) fluid more effectively than inner nuclear layer (INL) fluid due to better access to retinal pigment epithelium basolateral membrane than neurosensory retina. This retrospective cohort study explores if an association between spatial distribution of cystoid spaces in RP-CMO and CAI response exists. Two independent graders reviewed pretreatment and post-treatment optical coherence tomography (OCT) images of 25 patients (43 eyes) initiated on topical and/or oral CAIs between January 2013 and December 2014. Documentation included the presence/absence of fluid (and layer(s) involved), external limiting membrane, epiretinal membrane (ERM), vitreomacular adhesion/traction, lamellar/full-thickness macular hole and central macular thickness (CMT)/volume. INL fluid was found in all study eyes. All 13 'responders' (at least 11% reduction of CMT after treatment) demonstrated pretreatment ONL fluid. In seven patients (four responders and three non-responders), complete clearance of ONL fluid was achieved despite persistence of INL fluid. ERM presence was similar in responders and non-responders. In this study, INL fluid was found to be the most common spatial distribution of RP-CMO. However, patients who were classed as a 'responder' to CAI treatment all demonstrated coexisting ONL fluid on their pretreatment OCT scans. This may be explained by CAIs having better access to retinal pigment epithelium basolateral membrane than neurosensory retina. Our study also suggests a minimal impact on response to CAIs by ERM.


Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis.
Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs during development, wound healing and cancer and involves stages that orchestrate a network of cooperative interactions. Peptide growth factors and extracellular matrix (ECM) components are two major groups of angiogenesis mediators. Among the different ECM proteins, collagens have been well-associated with in vivo angiogenesis. Using human umbilical vein endothelial cells (HUVEC) grown in 3-D collagen gels we show that: (1) HUVEC do not survive well in 3-D collagen gels due to rapid induction of apoptosis. (2) VEGF, a potent in vivo angiogenic factor, fails to induce tube formation. (3) PMA was effective in inducing tube formation and survival in HUVEC dispersed in 3-D collagen gels, activating MAP kinase, phosphoinositide 3-OH kinase (PI-3-kinase) and Akt/PKB (protein kinase B) pathways. (4) VEGF was effective in preventing PMA-induced tube-like structure regression after PMA-withdrawal by (5) activating the mitogen activated protein kinase (MAPK), rather than the Akt/PKB, signaling pathway.


Prevalence and Spectrum of Pathogenic Germline Variants in Japanese Patients With Early-Onset Colorectal, Breast, and Prostate Cancer.
We investigated the prevalence and spectrum of pathogenic germline variants in patients with early-onset colorectal cancer (CRC), breast cancer (BC), and prostate cancer (PCA) in the Japanese population. We also identified pathogenic variants in other cancer risk genes, giving consideration to future multigene testing panels for this population. We performed whole-genome sequencing for 1,037 Japanese individuals, including patients with early-onset CRC (n = 196), BC (n = 237), and PCA (n = 215) and controls (n = 389). We screened for pathogenic variants, including single nucleotide variants and copy number variants, among well-established first-tier cancer genes for each cancer type and examined an expended second-tier panel including cancer-predisposing genes from the Cancer Gene Census. Proportions of patients with germline pathogenic variants differed by cancer subgroup, with the highest in BC (14.8%), followed by CRC (9.2%), and PCA (3.7%). In contrast, 2 of 389 control subjects (0.5%) carried a germline pathogenic variant. In comparison with controls, the proportion of patients with pathogenic variants in the second-tier panel was increased significantly for PCA (3.7% to 11.6%, P = 2.96 × 10-4), but not for CRC or BC, after multitesting adjustment. In patients with PCA, DNA repair pathway genes in the extended panel often contained pathogenic variants (P = .011). Our analyses support the clinical usefulness of established cancer gene panels in the Japanese population for 3 major cancer types. Additional genes, especially those involved in DNA repair, might be considered for developing multipanel testing in Japanese patients with early-onset PCA.


Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex.
There is an extensive literature describing how stress disturbs cognitive processing and can exacerbate psychiatric disorders. There is, however, an insufficient understanding of the molecular mechanisms involved in stress effects on brain and behavior. Rats were given spatial memory training in a hippocampus-dependent water maze task. We investigated how a fear-provoking experience (predator exposure) would affect their spatial memory and neural cell adhesion molecule (NCAM) levels in the hippocampus, prefrontal cortex (PFC), amygdala, and cerebellum. Whereas the control (nonstress) group exhibited excellent memory for the hidden platform location in the water maze, the cat-exposed (stress) group exhibited a profound impairment of memory and a marked suppression of levels of the NCAM-180 isoform in the hippocampus. Predator stress produced a more global reduction of NCAM levels in the PFC but had no effect on NCAM levels in the amygdala and cerebellum. This work provides a novel perspective into dynamic and structure-specific changes in the molecular events involved in learning, memory, and stress. The selective suppression of NCAM-180 in the hippocampus and the more general suppression of NCAM in the PFC provide insight into the mechanisms underlying the great sensitivity of these two structures to be disturbed by stress.


Record based study of snake bite cases admitted at Shri Vasantrao Naik Government Medical College & Hospital, Yavatmal (Maharashtra).
The present hospital record based cross-sectional study was undertaken with the objectives of finding out the epidemiological profile of snake bite cases admitted in Shri V. N. Govt. Medical College and hospital during the period of 1998-2002. The data was collected from the filled case papers of snake bite cases, through medical record section under the department of PSM and analyzed manually. The outcome of snake bite treatment was noted and defined. Proportional case rate of snake bite cases varied from 6.8 per 1000 admissions in 1998 to 6.0 per 1000 in 2002. Snake bite cases were seen among Males (69.4%), 97.4% of cases were agricultural workers and labourers. The cases seen during the period of June to Aug (35.5%) followed by Septeber to November (33.5%). About 78.7% of the victims either got relived or cured with a experienced mortality 4.3%.


Chaotic genetic structure and past demographic expansion of the invasive gastropod Tritia neritea in its native range, the Mediterranean Sea.
To better predict population evolution of invasive species in introduced areas it is critical to identify and understand the mechanisms driving genetic diversity and structure in their native range. Here, we combined analyses of the mitochondrial COI gene and 11 microsatellite markers to investigate both past demographic history and contemporaneous genetic structure in the native area of the gastropod Tritia neritea, using Bayesian skyline plots (BSP), multivariate analyses and Bayesian clustering. The BSP framework revealed population expansions, dated after the last glacial maximum. The haplotype network revealed a strong geographic clustering. Multivariate analyses and Bayesian clustering highlighted the strong genetic structure at all scales, between the Black Sea and the Adriatic Sea, but also within basins. Within basins, a random pattern of genetic patchiness was observed, suggesting a superimposition of processes involving natural biological effects (no larval phase and thus limited larval dispersal) and putative anthropogenic transport of specimens. Contrary to the introduced area, no isolation-by-distance patterns were recovered in the Mediterranean or the Black Seas, highlighting different mechanisms at play on both native and introduced areas, triggering unknown consequences for species' evolutionary trajectories. These results of Tritia neritea populations on its native range highlight a mixture of ancient and recent processes, with the effects of paleoclimates and life history traits likely tangled with the effects of human-mediated dispersal.


Voltage equilibration for reactive atomistic simulations of electrochemical processes.
We introduce electrochemical dynamics with implicit degrees of freedom (EChemDID), a model to describe electrochemical driving force in reactive molecular dynamics simulations. The method describes the equilibration of external electrochemical potentials (voltage) within metallic structures and their effect on the self-consistent partial atomic charges used in reactive molecular dynamics. An additional variable assigned to each atom denotes the local potential in its vicinity and we use fictitious, but computationally convenient, dynamics to describe its equilibration within connected metallic structures on-the-fly during the molecular dynamics simulation. This local electrostatic potential is used to dynamically modify the atomic electronegativities used to compute partial atomic changes via charge equilibration. Validation tests show that the method provides an accurate description of the electric fields generated by the applied voltage and the driving force for electrochemical reactions. We demonstrate EChemDID via simulations of the operation of electrochemical metallization cells. The simulations predict the switching of the device between a high-resistance to a low-resistance state as a conductive metallic bridge is formed and resistive currents that can be compared with experimental measurements. In addition to applications in nanoelectronics, EChemDID could be useful to model electrochemical energy conversion devices.


NSAIDs, antihypertensive agents and loss of blood pressure control.
It is common for patients seen by primary care physicians to be taking both nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents. If blood pressure control diminishes in these patients, the physician must evaluate the potential interaction between the two classes of medication. Although the increase in blood pressure secondary to NSAID use may be only 5 to 10 mm Hg, this increase may be enough to justify a change in medication. For this reason, it is important to evaluate the interaction between the two types of drugs and determine its clinical significance in specific patients.


Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode.
Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16-65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood.


Significance of sludge and thickened wall in ultrasound evaluation of the gallbladder.
Ultrasonography is reliable in detecting the presence of cholelithiasis. Isolated findings of a thickened gallbladder wall or intraluminal sludge (echogenic bile), or both, are regarded as less reliable in the diagnosis of primary gallbladder pathologic factors and are often thought to be indicators of some other pathologic or physiologic process. A retrospective analysis of 72 patients with isolated findings of sludge or thickened wall was performed. Thickened wall remains a non-specific finding. The presence of sludge on ultrasound, when coupled with normal liver function and amylase test results and right upper quadrant pain, correlated with a significant incidence of intrinsic pathologic findings of the gallbladder.


Tobacco use and tobacco control.
Smoking begins when tobacco is readily available and others smoke. It easily becomes something more than experimentation, as the symptoms of nicotine dependence can develop rapidly. The social and environmental cues to smoke, the personal perceptions of smoking and the physiological effects of nicotine create strong links that are difficult to break. Programmes should be put in place to help people to stop smoking, but these programmes cannot reach their potential for success if the wider social and environmental factors are not also changed through strengthened anti-tobacco social values and tobacco control legislation, as exemplified in the WHO Framework Convention on Tobacco Control.


Reduction in baseline corticosterone secretion correlates with climate warming and drying across wild lizard populations.
Climate change should lead to massive loss of biodiversity in most taxa, but the detailed physiological mechanisms underlying population extinction remain largely elusive so far. In vertebrates, baseline levels of hormones such as glucocorticoids (GCs) may be indicators of population state as their secretion to chronic stress can impair survival and reproduction. However, the relationship between GC secretion, climate change and population extinction risk remains unclear. In this study, we investigated whether levels of baseline corticosterone (the main GCs in reptiles) correlate with environmental conditions and associated extinction risk across wild populations of the common lizard Zootoca vivipara. First, we performed a cross-sectional comparison of baseline corticosterone levels along an altitudinal gradient among 14 populations. Then, we used a longitudinal study in eight populations to examine the changes in corticosterone levels following the exposure to a heatwave period. Unexpectedly, baseline corticosterone decreased with increasing thermal conditions at rest in females and was not correlated with extinction risk. In addition, baseline corticosterone levels decreased after exposure to an extreme heatwave period. This seasonal corticosterone decrease was more pronounced in populations without access to standing water. We suggest that low basal secretion of corticosterone may entail downregulating activity levels and limit exposure to adverse climatic conditions, especially to reduce water loss. These new insights suggest that rapid population decline might be preceded by a downregulation of the corticosterone secretion.


Purification and some properties of the 45 kDa diphenylene iodonium-binding flavoprotein of neutrophil NADPH oxidase.
The 45 kDa diphenylene iodonium-binding flavoprotein of the human neutrophil superoxide-generating oxidase has been purified by affinity chromatography. The polypeptide was eluted from Blue Memsep or 2',5'-ADP-agarose columns with either NADP or low concentrations of the specific inhibitor diphenylene iodonium. The purified protein was shown to bind FAD at a ratio of 1.09 mol of FAD/mol of protein. The reconstituted flavoprotein had a fluorescence spectrum similar, but not identical, to that of free FAD. It had an isoelectric point of approx. 4.0. The reconstituted flavoprotein displayed no diaphorase activity towards a range of artificial electron acceptors. Polyclonal antibodies raised against the pure protein inhibited superoxide generation by solubilized oxidase in a dose-dependent manner, and inhibited superoxide generation when incubated with either cytosol or membrane fractions in a reconstituted system. These antibodies precipitated the 45 kDa polypeptide together with a haem-containing 23 kDa protein thought to be the small subunit of cytochrome b-245. Antibodies raised against cytochrome P-450 reductase also precipitated these two polypeptides. These results are consistent with the 45 kDa polypeptide being the flavoprotein of the neutrophil superoxide-generating oxidase.


Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure.
Despite increasing prevalence and incidence of heart failure (HF), therapeutic options remain limited. In early stages of HF, sudden cardiac death (SCD) from ventricular arrhythmias claims many lives. Reactive oxygen species (ROS) have been implicated in both arrhythmias and contractile dysfunction. However, little is known about how ROS in specific subcellular compartments contribute to HF or SCD pathophysiology. The role of ROS in chronic proteome remodeling has not been explored. We will test the hypothesis that elevated mitochondrial ROS (mROS) is a principal source of oxidative stress in HF and in vivo reduction of mROS mitigates SCD. Using a unique guinea pig model of nonischemic HF that recapitulates important features of human HF, including prolonged QT interval and high incidence of spontaneous arrhythmic SCD, compartment-specific ROS sensors revealed increased mROS in resting and contracting left ventricular myocytes in failing hearts. Importantly, the mitochondrially targeted antioxidant (MitoTEMPO) normalized global cellular ROS. Further, in vivo MitoTEMPO treatment of HF animals prevented and reversed HF, eliminated SCD by decreasing dispersion of repolarization and ventricular arrhythmias, suppressed chronic HF-induced remodeling of the expression proteome, and prevented specific phosphoproteome alterations. Pathway analysis of mROS-sensitive networks indicated that increased mROS in HF disrupts the normal coupling between cytosolic signals and nuclear gene programs driving mitochondrial function, antioxidant enzymes, Ca2+ handling, and action potential repolarization, suggesting new targets for therapeutic intervention. mROS drive both acute emergent events, such as electrical instability responsible for SCD, and those that mediate chronic HF remodeling, characterized by suppression or altered phosphorylation of metabolic, antioxidant, and ion transport protein networks. In vivo reduction of mROS prevents and reverses electrical instability, SCD, and HF. Our findings support the feasibility of targeting the mitochondria as a potential new therapy for HF and SCD while identifying new mROS-sensitive protein modifications.


Exploring the utility of measures of critical thinking dispositions and professional behavior development in an audiology education program.
Discussions about professional behaviors are growing increasingly prevalent across health professions, especially as a central component to education programs. A strong critical thinking disposition, paired with critical consciousness, may provide future health professionals with a foundation for solving challenging practice problems through the application of sound technical skill and scientific knowledge without sacrificing sensitive, empathic, client-centered practice. In this article, we describe an approach to monitoring student development of critical thinking dispositions and key professional behaviors as a way to inform faculty members' and clinical supervisors' support of students and ongoing curriculum development. We designed this exploratory study to describe the trajectory of change for a cohort of audiology students' critical thinking dispositions (measured by the California Critical Thinking Disposition Inventory: [CCTDI]) and professional behaviors (using the Comprehensive Professional Behaviors Development Log-Audiology [CPBDL-A]) in an audiology program. Implications for the CCTDI and CPBDL-A in audiology entry-to-practice curricula and professional development will be discussed. This exploratory study involved a cohort of audiology students, studied over a two-year period, using a one-group repeated measures design. Eighteen audiology students (two male and 16 female), began the study. At the third and final data collection point, 15 students completed the CCTDI, and nine students completed the CPBDL-A. The CCTDI and CPBDL-A were each completed at three time points: at the beginning, at the middle, and near the end of the audiology education program. Data are presented descriptively in box plots to examine the trends of development for each critical thinking disposition dimension and each key professional behavior as well as for an overall critical thinking disposition score. For the CCTDI, there was a general downward trend from time point 1 to time point 2 and a general upward trend from time point 2 to time point 3. Students demonstrated upward trends from the initial to final time point for their self-assessed development of professional behaviors as indicated on the CPBDL-A. The CCTDI and CPBDL-A can be used by audiology education programs as mechanisms for inspiring, fostering, and monitoring the development of critical thinking dispositions and key professional behaviors in students. Feedback and mentoring about dispositions and behaviors in conjunction with completion of these measures is recommended for inspiring and fostering these key professional attributes.


A structural remedy toward bright dipolar fluorophores in aqueous media.
The donor-acceptor (D-A) type dipolar fluorophores, an important class of luminescent dyes with two-photon absorption behaviour, generally emit strongly in organic solvents but poorly in aqueous media. To understand and enhance the poor emission behaviour of dipolar dyes in aqueous media, we undertake a rational approach that includes a systematic structure variation of the donor, amino substituent of acedan, an important two-photon dye. We identify several factors that influence the emission behaviour of the dipolar dyes in aqueous media through computational and photophysical studies on new acedan derivatives. As a result, we can make acedan dyes emit bright fluorescence under one- and two-photon excitation in aqueous media by suppressing the liable factors for poor emission: 1,3-allylic strain, rotational freedom, and hydrogen bonding with water. We also validate that these findings can be generally extended to other dipolar fluorophores, as demonstrated for naphthalimide, coumarin and (4-nitro-2,1,3-benzoxadiazol-7-yl)amine (NBD) dyes. The new acedan and naphthalimide dyes thus allow us to obtain much brighter two-photon fluorescent images in cells and tissues than in their conventional forms. As an application of these findings, a thiol probe is synthesized based on a new naphthalimide dye, which shows greatly enhanced fluorescence from the widely used N,N-dimethyl analogue. The results disclosed here provide essential guidelines for the development of efficient dipolar dyes and fluorescence probes for studying biological systems, particularly by two-photon microscopy.


Antiviral Activity of Essential Oils Against Hepatitis A Virus in Soft Fruits.
Berries have repeatedly been associated with outbreaks of hepatitis A virus (HAV) infection. The fruits are usually minimally processed in the food industry due to their delicate nature. While washing treatments partially remove enteric viruses, the commonly used chemical additives produce toxic by-products. A valid alternative to preserve the food safety of these products could be the use of essential oils (EOs). EOs exert antimicrobial activity and do not interfere with the nutritional characteristics of food products. We investigated the efficacy of four essential oils, lemon (Citrus limon), sweet orange (Citrus sinensis), grapefruit (Citrus paradisi), and rosemary cineole (Rosmarinus officinalis chemotype 1.8 cineole) in reducing viral loads of HAV in soft fruits. Mixed fruit berries were inoculated with 106.74 TCID50/ml of HAV, and treated with four different EOs (0.5% lemon, 0.1% sweet orange and grapefruit, and 0.05% rosemary) for 1 h at room temperature. Virus infectivity was then assessed by titration assays for its ability to grow on cell cultures. A statistically significant reduction in HAV titer on the fruit surface was observed after treating the berries with EOs of lemon (2.84 log TCID50/ml), grapefruit (2.89 log TCID50/ml), and rosemary cineole (2.94 log TCID50/ml). Rosemary cineole was the most effective EO in reducing viral titer on berries, followed by grapefruit EO. These results improve our knowledge about the antiviral activity of these EOs and highlight their potential use in fresh produce sanitation.


Study of the pathogenesis of paralytic ileus in animal models of experimentally induced postoperative and septic ileus.
Paralytic ileus is defined as an inhibition of propulsive intestinal motility. Postoperative ileus is the most common type, however, also during sepsis and critical illness paralytic ileus is a common finding. The pathogenesis of paralytic ileus is still debated. It is believed to result from the activation of inhibitory neural reflex pathways and activation of inflammatory processes. It is generally accepted that postoperative ileus results from the activation of an inhibitory neural reflex pathway. In our rat model we showed that different degrees of nociceptive stimulation activate different reflex pathways: laparatomy activates an adrenergic inhibitory reflex pathway, whereas manipulation results in additional activation of inhibitory NANC neurons releasing NO and VIP as neurotransmitters. We also demonstrated that blockade of the afferent limb of the reflex pathway by peripheral kappa-opioid agonists or by non-steroidal anti-inflammatory drugs ameliorated postoperative ileus. However, the use of prokinetics lead to disappointing results. In the murine septic model we demonstrated an important role for activation of inducible NO synthase in the endotoxin-induced delay in gastric emptying and small intestinal transit. We hypothesise that activation of the residential macrophages in the gut wall leads to the production of iNOS and other inflammatory mediators. These mediators will attract more inflammatory cells and influence smooth muscle contractility. Next, we provide evidence that production of iNOS results in the activation of guanylyl cyclase leading to the production of cGMP and smooth muscle relaxation. However, a parallel mechanism of action for NO via oxidative stress needs further investigation.


Default-name and tasting nudges increase salsify soup choice without increasing overall soup choice.
Nudging is a popular behavior change technique but the conditions for its effectiveness have not been researched extensively. The current study aimed to test whether the effectiveness of nudging is limited to certain characteristics of the nudged product by focusing on a specific product (salsify soup) within a broader category (soups). Two parallel studies were conducted in two sandwich restaurants in a university setting at which a default-name nudge ("suggestion of the chef") and a tasting nudge were implemented aimed at increasing the choice for salsify soup using a non-randomized study design during 10 and 12 measurement days. The beta-regression model showed that the default-name nudge increased the proportion of customers that choose the salsify soup during intervention days compared to non-intervention days, p < .001, OR: 1.70. The tasting nudge also increased the proportion of customers that choose the salsify soup from baseline to intervention, p < .001, OR: 6.17 and from baseline to post-intervention, p < .01, OR: 1.87, and decreased from intervention to post-intervention, p < .001, OR: 0.30. Both nudges did not increase the choice for the overall category of soups. The results show that certain types of nudges are able to increase specific products of a category without increasing overall choice of a category in contrast to previous findings.


Circulating levels of angiotensin I measured by radioimmunoassay in hypertensive subjects.
The development of a uniquely sensitive and specific antiserum to AI has led to the establishment of a radioimmunoassay capable of detecting 7.5 pg of AI per milliliter of plasma. Due to its sensitivity this assay permits the measurement of circulating levels of AI, obviating many of the controversial aspects of previously described AI assays which all required either an incubation step at 37 degrees C to allow renin to catalyze the formation of sufficient AI or an extraction procedure to concentrate sufficient peptide to make quantification feasible. Since the sensitivity of this assay also depends upon the availability of very pure trace, a method is described for preparing monoiodinated 125I-AI of specific activity greater than 1000 microCi/microgram. To demonstrate the versatility and sensitivity of this assay, changes in circulating AI levels in response to physiologic stimuli were measured. Blood samples were obtained from 88 subjects from the inferior vena cava below the renal veins in both the supine and upright positions. Values ranged from 12 to 1990 pg/ml of plasma. Eighty-five of the 88 displayed a rise in the AI level during an upright tilt, the mean for the group increasing from 220 to 385 pg/ml of plasma. Three subjects had samples drawn simultaneously from the inferior vena cava and a peripheral artery and/or vein. The amounts of AI in all three sampling locations were essentially the same. Seventeen patients with essential hypertension underwent an infusion of 1.5 L of normal saline, and circulating AI levels were determined before and 120 and 150 min after the start of the infusion. All 17 experienced suppression of their AI levels, the mean for the group at 0, 120 and 150 min being 177, 55, and 50 pg/ml of plasma, respectively. Circulating AI correlated well (r = 0.87009) with plasma renin activity in 226 samples from the renal veins and inferior vena cava from individuals with hypertension of various etiologies.


Submesoscale currents in the ocean.
This article is a perspective on the recently discovered realm of submesoscale currents in the ocean. They are intermediate-scale flow structures in the form of density fronts and filaments, topographic wakes and persistent coherent vortices at the surface and throughout the interior. They are created from mesoscale eddies and strong currents, and they provide a dynamical conduit for energy transfer towards microscale dissipation and diapycnal mixing. Consideration is given to their generation mechanisms, instabilities, life cycles, disruption of approximately diagnostic force balance (e.g. geostrophy), turbulent cascades, internal-wave interactions, and transport and dispersion of materials. At a fundamental level, more questions remain than answers, implicating a programme for further research.


[Dorsal dislocation of the proximal interphalangeal joints of the finger. Results after static and functional treatment].
In a follow-up examination of 30 patients who had sustained dorsal dislocations of the PIP joint, the results of two conservative therapy regimens, either immobilisation or early motion were investigated. In Group A, 15 patients were treated by closed reduction and immobilisation with a forearm cast for four weeks. Nine patients showed normal range of motion, whereas a limitation of extension of ten degrees and more was seen in six cases. All PIP joints were stable. Nine patients were satisfied. Three patients complained of a limitation of extension, two of a limitation of extension and pain and one of swelling. In Group B, 15 patients were treated by dorsal block splinting of the PIP joint following reposition. The finger was released in extension with daily active exercise of the PIP joint. Only two of 15 patients showed limitation of extension, whereas 13 cases showed normal range of motion. Instability of one collateral ligament was seen in two cases. Palmar instability did not occur. Eleven patients were satisfied. One patient complained of instability, pain and lack of extension, one of pain in combination with instability, one of pain and one of swelling of the joint.


Dietary methionine intake and neural tube defects in Mexican-American women.
Nutrients other than maternal folic acid are also thought to play a role in preventing neural tube defects (NTDs). Evidence suggests that methionine interacts with folic acid and vitamin B(12) in the methylation of contractile proteins involved in closing the neural folds. The role of dietary intake of methionine in NTD risk has not been specifically studied among Mexican Americans, a population with one of the highest prevalences of NTDs in the United States. We conducted a case-control study of 184 Mexican American women with NTD-affected pregnancies (case women) and 225 women with normal offspring (control women) who resided along the Texas-Mexico border. The average daily intakes of methionine were calculated from periconceptional food frequency questionnaire data. Women were categorized according to quartiles of daily methionine intake, based on the control mothers' distribution, and the risk for an NTD-affected pregnancy was calculated using the lowest quartile of intake as the referent. With adjustment for income, body mass index, hyperinsulinemia, and diarrhea, the odds ratios for increasing quartile of methionine intake were: 0.95 (95% confidence interval [CI], 0.48,1.90), 0.92 (95% CI, 0.46,1.84), and 0.66 (95% CI, 0.30,1.45). Some evidence of interaction between dietary methionine and serum vitamin B(12) was noted particularly at higher levels of both components. This study was limited by a small sample size but examined this association in an exclusively Hispanic population. Results were suggestive of a potential protective effect for NTDs with increasing maternal dietary methionine intake.


Pharmacokinetics and metabolism of 3'-azido-2',3'-dideoxy-5-methylcytidine in rhesus monkeys.
3'-Azido-2',3'-dideoxy-5-methylcytidine (AzddMeC, CS-92), a nucleoside analog with structural similarities to both 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), has been shown to be a potent and selective inhibitor of human immunodeficiency virus type 1 in vitro. The pharmacokinetics of AzddMeC were characterized following intravenous and oral administration of 60 mg/kg of the compound to male rhesus monkeys. AZT was found to be a major metabolite of AzddMeC in monkeys. AzddMeC concentrations in serum declined rapidly in a biexponential fashion with the terminal half-life ranging from 0.5 to 1.3 hr. Total clearance of AzddMeC was 2.00 +/- 0.41 liters/hr/kg (mean +/- SD) with the fraction of AzddMeC metabolized to AZT of 0.32 +/- 0.05. Renal excretion of unchanged nucleoside and metabolic deamination yielding AZT were the primary routes of AzddMeC clearance. No glucuronide metabolite of AzddMeC was detected in urine samples, although, AZT-glucuronide was found in urine. The volume of the central compartment of AzddMeC was 0.53 +/- 0.28 liters/kg, the volume of the tissue compartment was 0.37 +/- 0.29 liters/kg, and the steady-state volume of distribution was 0.90 +/- 0.55 liters/kg. Volume of distribution values indicate that AzddMeC distributes extravascularly. The first-order oral absorption rate constant was 0.53 +/- 0.56 hr-1, and oral bioavailability was 26 +/- 13%. Thus, the rate of absorption of AzddMeC after oral administration was variable, and oral bioavailability was incomplete.


A horizon scan of future threats and opportunities for pollinators and pollination.
Background. Pollinators, which provide the agriculturally and ecologically essential service of pollination, are under threat at a global scale. Habitat loss and homogenisation, pesticides, parasites and pathogens, invasive species, and climate change have been identified as past and current threats to pollinators. Actions to mitigate these threats, e.g., agri-environment schemes and pesticide-use moratoriums, exist, but have largely been applied post-hoc. However, future sustainability of pollinators and the service they provide requires anticipation of potential threats and opportunities before they occur, enabling timely implementation of policy and practice to prevent, rather than mitigate, further pollinator declines. Methods.Using a horizon scanning approach we identified issues that are likely to impact pollinators, either positively or negatively, over the coming three decades. Results.Our analysis highlights six high priority, and nine secondary issues. High priorities are: (1) corporate control of global agriculture, (2) novel systemic pesticides, (3) novel RNA viruses, (4) the development of new managed pollinators, (5) more frequent heatwaves and drought under climate change, and (6) the potential positive impact of reduced chemical use on pollinators in non-agricultural settings. Discussion. While current pollinator management approaches are largely driven by mitigating past impacts, we present opportunities for pre-emptive practice, legislation, and policy to sustainably manage pollinators for future generations.


Age-related difference in melodic pitch perception is probably mediated by temporal processing: empirical and computational evidence.
This study was designed to examine whether age-related differences in melodic pitch perception may be mediated by temporal processing. Temporal models of pitch suggest that performance will decline as the lowest component of a complex tone increases in frequency, regardless of age. In addition, if there are age-related deficits in temporal processing in older adults, this group may have reduced performance relative to younger adults even in the most favorable conditions. Six younger adults and 10 older adults with clinically normal audiograms up to 8 kHz were tested in a melodic pitch perception task. In each trial, two consecutive four-note melodies were presented to the listener. Melodies were identical with the exception of one note in the second melody that was shifted in pitch. The listener was required to identify which note was shifted. All notes consisted of eight successive harmonic components, with the average lowest component manipulated to be the 4th, 8th, or 12th component of the harmonic series, with lower components being absent. Age-related differences in melodic pitch perception were only apparent when stimulus parameters favored temporal processing of pitch. Furthermore, modeling a loss of periodicity coding yielded an outcome consistent with the observed behavioral results. Although younger adults generally outperformed older adults, about one-quarter of the older adults performed at levels that were equivalent to those of younger adults. The only follow-up tests that were able to differentiate these exceptional older adults were tests that would be sensitive to temporal processing: fundamental frequency difference limens and 500 Hz pure-tone difference limens. In contrast, otoacoustic emissions and high-frequency pure-tone thresholds, which are more commonly associated with spectral processing deficits, were not able to differentiate older exceptional adults from older typical adults. Age-related declines in temporal processing contribute to deficits in melodic pitch perception. However, some exceptional older adults with normal audiograms preserve excellent temporal processing and continue to perform at levels that are typical of younger adults.


Rapid diagnosis of bacterial meningitis by real-time PCR and fluorescence in situ hybridization.
Real-time PCR and fluorescence in situ hybridization (FISH) were evaluated as rapid methods for the diagnosis of bacterial meningitis and compared to standard diagnostic procedures. For PCR, a LightCycler approach was chosen, implementing eubacterial and specific PCR assays for the most relevant bacteria. For FISH, a similar probe set containing eubacterial and specific probes was composed of published and newly designed probes. Both methods were evaluated by use of cerebrospinal fluid (CSF) samples from patients with suspected bacterial meningitis. For all microscopy- and culture-positive samples (n = 28), the eubacterial PCR was positive. In addition, all identifiable pathogens were detected with specific PCR assays, according to an algorithm based on the Gram stain. The FISH method detected the pathogen in 13 of 18 positive samples. While the FISH method remained negative for all microscopy- and culture-negative samples (n = 113), the eubacterial PCR was positive for five of these samples. Sequencing of the amplicon revealed the presence of Neisseria meningitidis, Streptococcus agalactiae, and Haemophilus influenzae in three of these five samples. In addition, samples with discordant results by culture and microscopy were successfully investigated by PCR (10 samples) and FISH (5 samples). In conclusion, PCR is a highly sensitive tool for rapid diagnosis of bacterial meningitis. FISH is less sensitive but is useful for the identification of CSF samples showing bacteria in the Gram stain. Based on our results, an approach for laboratory diagnosis of meningitis including PCR and FISH is discussed.


Signatures of altered long noncoding RNAs and messenger RNAs expression in the early acute phase of spinal cord injury.
Spinal cord injury (SCI) is a highly severe disease and it can lead to the destruction of the motor and sensory function resulting in temporary or permanent disability. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt that play a critical role in central nervous system (CNS) injury. However, the exact roles of lncRNAs and messenger RNAs (mRNAs) in the early acute phase of SCI remain to be elucidated. We examined the expression of mRNAs and lncRNAs in a rat model at 2 days after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. Subsequently, a comprehensive bioinformatics analysis was also performed to clarify the interaction between DE mRNAs. A total of 3,193 DE lncRNAs and 4,308 DE mRNAs were identified between the injured group and control group. Classification, length distribution, and chromosomal distribution of the dysregulated lncRNAs were also performed. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. A protein-protein interaction (PPI) network indicated that IL6, TOP2A, CDK1, POLE, CCNB1, TNF, CCNA2, CDC20, ITGAM, and MYC were the top 10 core genes. The subnetworks from the PPI network were identified to further elucidate the most significant functional modules of the DE mRNAs. These data may provide novel insights into the molecular mechanism of the early acute phase of SCI. The identification of lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for SCI.


Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas.
To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). Patients, predominantly men, with their CSSCs' immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort's objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival. Median age of all patients was 79 years. The primary cohort's ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; P = .02). Responders' W15 total FACT-G score had improved (P = .025) compared with nonresponders. First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.


Validating and optimizing mismatch tolerance of Doppler backscattering measurements with the beam model (invited).
We use the beam model of Doppler backscattering (DBS), which was previously derived from beam tracing and the reciprocity theorem, to shed light on mismatch attenuation. This attenuation of the backscattered signal occurs when the wavevector of the probe beam's electric field is not in the plane perpendicular to the magnetic field. Correcting for this effect is important for determining the amplitude of the actual density fluctuations. Previous preliminary comparisons between the model and Mega-Ampere Spherical Tokamak (MAST) plasmas were promising. In this work, we quantitatively account for this effect on DIII-D, a conventional tokamak. We compare the predicted and measured mismatch attenuation in various DIII-D, MAST, and MAST-U plasmas, showing that the beam model is applicable in a wide variety of situations. Finally, we performed a preliminary parameter sweep and found that the mismatch tolerance can be improved by optimizing the probe beam's width and curvature at launch. This is potentially a design consideration for new DBS systems.


International web survey shows high prevalence of symptomatic testosterone deficiency in men.
Though the clinical significance of testosterone deficiency is becoming increasingly apparent, its prevalence in the general population remains unrecognised. A large web-based survey was undertaken over 3 years to study the scale of this missed diagnosis. An online questionnaire giving the symptoms characterising testosterone deficiency syndrome (Aging Male Symptoms-AMS-scale) was set up on three web sites, together with questions about possible contributory factors. Of over 10,000 men, mainly from the UK and USA, who responded, 80% had moderate or severe scores likely to benefit from testosterone replacement therapy (TRT). The average age was 52, but with many in their 40s when the diagnosis of 'late onset hypogonadism' is not generally considered. Other possible contributory factors to the high testosterone deficiency scores reported were obesity (29%), alcohol (17.3%), testicular problems such as mumps orchitis (11.4%), prostate problems (5.6%), urinary infection (5.2%) and diabetes 5.7%. In this self-selected large international sample of men, there was a very high prevalence of scores which if clinically relevant would warrant a therapeutic trial of testosterone treatment. This study suggests that there are large numbers of men in the community whose testosterone deficiency is neither being diagnosed nor treated.


Pesticides and breast cancer risk: a comparison between developed and developing countries.
A large number of studies in Europe and US find little or no association between pesticides and breast cancer, adding to the increasingly dominant view that pesticides are not causally related to breast cancer. We investigated whether there are any differences in the levels of pesticides like dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB), hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) and their effect for the development of breast cancer between developed and developing countries. A pubmed search for literature on pesticides, organochlorines, organophosphates and breast cancer risk from 1990 through 2009 was carried out. The level of pesticide exposure is higher in developing world than the developed world. DDT is found to be positively associated with breast cancer risk. Results for other pesticides are equivocal. There is a dearth of studies in developing countries, which cannot be made up for generalizing the results from developed countries to the developing and third world. More studies are needed in the developing and third world countries, investigating the relation between pesticides and breast cancer risk as the sheer amount of pesticides being relentlessly used in these countries due to lack of proper government regulations.


Streak formation in flow over biomimetic fish scale arrays.
The surface topology of the scale pattern from the European sea bass (Dicentrarchus labrax) was measured using a digital microscope and geometrically reconstructed using computer assisted design modelling. Numerical flow simulations and experiments with a physical model of the surface pattern in a flow channel mimic the flow over the fish surface with a laminar boundary layer. The scale array produces regular rows of alternating, streamwise low-speed and high-speed streaks inside the boundary layer close to the surface, with maximum velocity difference of approximately 9%. Low velocity streaks are formed in the central region of the scales whereas the high velocity streaks originated in the overlapping region between the scales. Thus, those flow patterns are linked to the arrangement and the size of the overlapping scales within the array. Because of the velocity streaks, total drag reduction is observed when the scale height is small relative to the boundary layer thickness, i.e. less than 10%. Flow simulations were compared with surface oil-flow visualisations on the physical model of the biomimetic surface placed in a flow channel. The results show an excellent agreement in the size and arrangement of the streaky structures. The existence of streaks is also shown on sea bass and common carp (Cyprinus carpio) by surface flow visualisation. From comparisons with recent literature on micro-roughness effects on laminar boundary layer flows, it is hypothesised that the fish scales could delay transition, which would further reduce the drag.


Specific T-cell response to a Pneumocystis carinii surface glycoprotein (gp120) after immunization and natural infection.
T cells have been shown to be important in recovery from Pneumocystis carinii pneumonitis, although no specific antigen of P. carinii has been defined as containing T-cell epitopes. P. carinii has an abundant mannosylated surface glycoprotein of approximately 120 kDa (gp120) which induces a prominent host antibody response in experimental animals after exposure to P. carinii in the environment or after recovery from P. carinii pneumonitis. P. carinii gp120 was purified from infected lungs by lectin affinity chromatography. Standard in vitro lymphocyte stimulation assays using purified gp120 and control normal lung preparations were performed on isolated T cells obtained from BALB/c mice after immunization with P. carinii-infected crude lung homogenates or lectin-purified gp120. Lymphocytes from reconstituted severe combined immunodeficient mice which had recovered from naturally acquired P. carinii pneumonitis were also tested. A specific T-cell response was elicited by gp120 after immunization with P. carinii gp120 and after recovery from P. carinii pneumonitis. In addition, the mice developed a strong antibody response to gp120 as ascertained by Western blot (immunoblot). These data suggest that gp120 may be important in the recognition of P. carinii by T cells.


Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts aqueous extract mitigates cisplatin-induced nephrotoxicity via attenuation of inflammation, and DNA damage.
Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their O- and C-glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.


Human carboxylesterase-2 hydrolyzes the prodrug of gemcitabine (LY2334737) and confers prodrug sensitivity to cancer cells.
The oral prodrug of gemcitabine LY2334737 is cleaved systemically to gemcitabine; the mechanism responsible for hydrolysis is unknown. LY2334737 cytotoxicity was tested in the NCI-60 panel; mining of microarray expression data identified carboxylesterase (CES) as a top hydrolase candidate. Studies examined whether CES is responsible for hydrolysis and whether cellular CES expression confers prodrug sensitivity. Human recombinant CES isozymes were assayed for LY2334737 hydrolysis. Stable CES-overexpressing HCT-116 transfectants and a SK-OV-3 knockdown were prepared. Cell lines were tested for drug sensitivity and CES expression by quantitative real time-PCR (qRT-PCR), Western blotting, and immunohistochemical staining. Bystander cytotoxicity studies were conducted with GFP-tagged PC-3 cells as the reporter cell line. Therapeutic response of the HCT-116 transfectants was evaluated in xenografts. Of 3 human CES isozymes tested, only CES2 hydrolyzed LY2334737. Five cell lines that express CES2 responded to LY2334737 treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. The drug response of CES2-transfected HCT-116 cells correlated with CES2 expression level. Bystander studies showed statistically greater PC-3-GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants. Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001). CES2 is responsible for the slow hydrolysis of LY2334737. Because intact prodrug circulates at high plasma levels after oral LY2334737 administration, improved response rates may be observed by tailoring LY2334737 treatment to patients with CES2 tumor expression.


Dysnatremia and mortality: do sweat the small stuff...
Marked dysnatremia is associated with increased mortality in patients admitted to intensive care. However, new evidence suggests that even mild deviations from normal and simple variability of sodium values may also be significant. Should these findings prompt clinicians to re-evaluate the approach to fluid management in this setting? Sodium disorders, on one hand, are known to result from overzealous administration or restriction of free water or sodium ions. However, they are also associated with a range of co-morbidities and drug treatments that alter water loss and sodium handling in the nephron independently of prescribed fluid regimens. Moreover, powerful neuroendocrine and inflammatory responses to surgery, trauma and other acute illness may induce or intensify such changes, altering the response to administered fluids. These observations suggest that both patient and treatment variables contribute, but the extent to which sodium disturbances are preventable and whether prevention improves outcome are unknown. Dysnatremia certainly reflects underlying systemic disorders, but how important is fluid management as a cause, and does it contribute independently to poorer outcomes through osmotic or other mechanisms? Although total fluid volume and doses of potassium and glucose are regularly adjusted in critically ill patients, sodium is usually delivered at standard concentrations as long as serum values lie within an acceptable range. It may be prudent to pay closer attention to these values, especially when abnormal, when fluctuating or when an adverse trend is present. More frequent measurements of sodium in blood, urine and drainage fluids, and appropriate adjustment of the sodium content of prescribed fluids, may be indicated. Until more light can be shed on the pathophysiology of dysnatremia in the critically ill, we should assume that better control of plasma sodium levels may yield better outcomes.


A role for photoreceptor outer segments in the induction of deprivation myopia.
An ultrastructural examination of the outer retina and choroid of hatchling chicks reared for periods of 1, 2 or 4 weeks with opaque occluders (MD) covering one eye, was instigated to elucidate the mechanism of deprivation myopia. Refractive myopia (approximately 20 D), retinal and choroidal thinning were induced in all deprived eyes. Electron microscopy showed significant changes in the MD eyes compared to normals. Cone inner segments were markedly thicker and outer segment lamellae more damaged. The rod outer segments were elongated and thicker than normal, such that their distal tips either directly apposed the basal lamina of the retinal pigment epithelium, or indented the cell nuclei. We hypothesize that this "rod-push" mechanism leads to thinning of the choroid in deprived eyes, and may directly contribute to axial myopia.


Penile dorsal vein arterialization in managing venogenic impotence.
Several surgical techniques have been applied for the treatment of venoocclusive dysfunction sufficient enough to create erectile dysfunction; however, long-term success rates have been dismal. Twenty-six patients (mean age, 41 years) with documented venogenic erectile dysfunction by dynamic pharmacocavernosometry and cavernosography, who had normal pelvic arteriograms, underwent deep dorsal vein arterialization. All patients preoperatively were nonresponders to injected intracavernosal vasoactive agents. These patients have been followed up for 18-52 months (mean, 37 months). Overall success rates show that eight patients (31%) are able to have unaided satisfactory intercourse and nine patients (35%) have become responders to intracavernosal vasoactive injection therapy. Postoperative complications were minimal, and no patient developed hypervascularization of the glans. Deep dorsal vein arterialization remains a viable treatment option for the properly selected, motivated, young patient who does not wish to pursue other treatment options for his venoocclusive dysfunction.


The proprotein convertase subtilisin/kexin type 9 (PCSK9) active site and cleavage sequence differentially regulate protein secretion from proteolysis.
Biologic-based strategies to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) show promise as anti-hypercholesterolemic and, therefore, anti-atherosclerotic therapies. Despite substantial effort, no small molecule strategy to inhibit PCSK9 has demonstrated feasibility. In this study we interrogated the chemistry of the PCSK9 active site and its adjacent residues to identify a foothold with which to drug the PCSK9 processing pathway and ultimately disrupt the interaction with the LDL receptor. Here, we develop a system in which we amplify the readout of PCSK9 proteolysis with a highly specific substrate in cells, showing that the PCSK9 catalytic domain is capable of proteolysis in trans. We use this system to show that the substrate specificity for PCSK9 proteolysis is distinct from the specificity for PCSK9 secretion, demonstrating that PCSK9 processing occurs in two separate sequential steps: that of proteolysis followed by secretion. We show that specific residues in the protease recognition sequence can differentially modulate the effects on proteolysis and secretion. Additionally, we demonstrate that the clinically described, dominant negative Q152H mutation restricts proteolysis and secretion independently. Our results suggest that the PCSK9 active site and its adjacent residues serve as an allosteric modulator of protein secretion independent of its role in proteolysis, revealing a new strategy for intracellular PCSK9 inhibition.


Targeting Insulin Receptor in Breast Cancer Using Small Engineered Protein Scaffolds.
Insulin receptor (InsR) and the type I insulin-like growth factor (IGF1R) are homologous receptors necessary for signal transduction by their cognate ligands insulin, IGF-I and IGF-II. IGF1R mAbs, intended to inhibit malignant phenotypic signaling, failed to show benefit in patients with endocrine-resistant tumors in phase III clinical trials. Our previous work showed that in tamoxifen-resistant cells, IGF1R expression was lacking, but InsR inhibition effectively blocked growth. In endocrine-sensitive breast cancer cells, insulin was not growth stimulatory, likely due to the presence of hybrid InsR/IGF1R, which has high affinity for IGF-I, but not insulin. Combination inhibition of InsR and IGF1R showed complete suppression of the system in endocrine-sensitive breast cancer cells. To develop InsR-binding agents, we employed a small protein scaffold, T7 phage gene 2 protein (Gp2) with the long-term goal of creating effective InsR inhibitors and diagnostics. Using yeast display and directed evolution, we identified three Gp2 variants (Gp2 #1, #5, and #10) with low nanomolar affinity and specific binding to cell surface InsR. These Gp2 variants inhibited insulin-mediated monolayer proliferation in both endocrine-sensitive and resistant breast cancer, but did not downregulate InsR expression. Gp2 #5 and Gp2 #10 disrupted InsR function by inhibiting ligand-induced receptor activation. In contrast, Gp2 #1 did not block InsR phosphorylation. Notably, Gp2 #1 binding was enhanced by pretreatment of cells with insulin, suggesting a unique receptor-ligand-binding mode. These Gp2 variants are the first nonimmunoglobulin protein scaffolds to target insulin receptor and present compelling opportunity for modulation of InsR signaling. Mol Cancer Ther; 16(7); 1324-34. ©2017 AACR.


Antibiotic Susceptibility Patterns of Mycobacterium tuberculosis Isolates from Guizhou Province of China Against 13 Antituberculosis Drugs.
A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected isolates were used to determine antibiotic susceptibility patterns against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin, capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57 new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5% of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR-TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug-resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR-TB, which is higher than the average numbers in China (about 8%) and in the world (9.6%). This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes.


Patterns of care for hypertension among hospitalized patients.
In a sample of 19,210 adult inpatients discharged from Maryland community hospitals in 1978, 1 in 4 had either an elevated diastolic blood pressure greater than or equal to 100 mmm Hg (3,338) or a diagnosis of hypertension (1,233). Among the patients with elevated blood pressure, hypertension was disgnosed in 44 percent, and 48 percent received advice concerning followup care. Likewise, of the patients with diagnosed hypertension, 72 percent were treated in the hospital, and 70 percent received advice concerning followup care. Age, race, and sex differences were significant. White male were least likely to have hypertension diagnosed, to be treated for it, or to receive instruction about it. The survey results were used to the Maryland State Department of Health and Mental Hygiene to formulate a statewide high blood pressure coordination plan and to construct modules for the education of professional in high blood pressure treatment and control. A followup survey is planned to evaluate the effect of these efforts.


Bypassing bacterial infection in phage display by sequencing DNA released from phage particles.
Phage display relies on a bacterial infection step in which the phage particles are replicated to perform multiple affinity selection rounds and to enable the identification of isolated clones by DNA sequencing. While this process is efficient for wild-type phage, the bacterial infection rate of phage with mutant or chemically modified coat proteins can be low. For example, a phage mutant with a disulfide-free p3 coat protein, used for the selection of bicyclic peptides, has a more than 100-fold reduced infection rate compared to the wild-type. A potential strategy for bypassing the bacterial infection step is to directly sequence DNA extracted from phage particles after a single round of phage panning using high-throughput sequencing. In this work, we have quantified the fraction of phage clones that can be identified by directly sequencing DNA from phage particles. The results show that the DNA of essentially all of the phage particles can be 'decoded', and that the sequence coverage for mutants equals that of amplified DNA extracted from cells infected with wild-type phage. This procedure is particularly attractive for selections with phage that have a compromised infection capacity, and it may allow phage display to be performed with particles that are not infective at all.


Sprouty is a negative regulator of transforming growth factor β-induced epithelial-to-mesenchymal transition and cataract.
Fibrosis affects an extensive range of organs and is increasingly acknowledged as a major component of many chronic disorders. It is now well accepted that the elevated expression of certain inflammatory cell-derived cytokines, especially transforming growth factor β (TGFβ), is involved in the epithelial-to-mesenchymal transition (EMT) leading to the pathogenesis of a diverse range of fibrotic diseases. In lens, aberrant TGFβ signaling has been shown to induce EMT leading to cataract formation. Sproutys (Sprys) are negative feedback regulators of receptor tyrosine kinase (RTK)-signaling pathways in many vertebrate systems, and in this study we showed that they are important in the murine lens for promoting the lens epithelial cell phenotype. Conditional deletion of Spry1 and Spry2 specifically from the lens leads to an aberrant increase in RTK-mediated extracellular signal-regulated kinase 1/2 phosphorylation and, surprisingly, elevated TGFβ-related signaling in lens epithelial cells, leading to an EMT and subsequent cataract formation. Conversely, increased Spry overexpression in lens cells can suppress not only TGFβ-induced signaling, but also the accompanying EMT and cataract formation. On the basis of these findings, we propose that a better understanding of the relationship between Spry and TGFβ signaling will not only elucidate the etiology of lens pathology, but will also lead to the development of treatments for other fibrotic-related diseases associated with TGFβ-induced EMT.


Is osteitis pubis associated with the use of bone anchors in urinary continence operations?
We studied 130 patients who underwent either a vaginal needle suspension procedure or a pubofascial sling procedure with Mitek titanium bone anchors to determine the association of osteitis pubis with bone anchoring in these procedures. Fifteen patients complained of postoperative suprapubic pain; five cases were due to wound infections and another five were associated with tying the suspension sutures too tightly. We suggest the use of the term 'periostitis pubis' to describe the remaining five patients who suffered suprapubic pain. We found no radiological evidence of osteitis pubis in any patients.


An Investigation of Electrospun Clerodendrum phlomidis Leaves Extract Infused Polycaprolactone Nanofiber for In Vitro Biological Application.
The in vitro antibacterial, anticancer, and antioxidant activities of a few plant extracts were widely known for decades, and they were used for application in the conventional way. Specifically, electrospun nanofibrous mats have recently exhibited great antibacterial, anticancer, and antioxidant activities. The herbal extracts infused into these formations are expected to have a more efficient and integrated effect on in vitro biological applications. The purpose of this study is to develop polycaprolactone- (PCL-) based nanofiber mats that are infused with a traditional plant extract using Clerodendrum phlomidis leaves to improve the synthesized nanofibers' antibacterial, anticancer, and antioxidant efficacy. This study examined the morphology, thermal properties, mechanical properties, structure, and in vitro drug release studies of electrospun nanofibers. Antibacterial, anticancer, and antioxidant activities of the electrospun nanofibrous mats were also studied. The HRTEM and FESEM pictures of PCL and PCL-CPM nanofibers provide that smooth, defect-free, and homogeneous nanofibers were found to be 602.08 ± 75 nm and 414.15 ± 82 nm for PCL and PCL-CPM nanofibers, respectively. The presence of Clerodendrum phlomidis extract in the electrospun nanofibers was approved by UV-visible and FTIR spectroscopy. The incorporation of Clerodendrum phlomidis extract to nanofiber mats resulted in substantial antibacterial activity against bacterial cells. PCL-CPM mats exposed to oral cancer (HSC-3) and renal cell carcinoma (ACHN) cell lines displayed promising anticancer activity with less than 50% survival rate after 24 h of incubation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay performed on PCL-CPM nanofibers revealed the antioxidant scavenging activity with maximum inhibition of 34% suggesting the role of the secondary metabolites release from scaffold. As a result, the findings of this study revealed that Clerodendrum phlomidis extract encapsulating PCL electrospun nanofibers has a high potential for usage as a biobased antibacterial, anticancer, and antioxidant agent.


Wave action modifies the effects of consumer diversity and warming on algal assemblages.
To understand the consequences of biodiversity loss, it is necessary to test how biodiversity-ecosystem functioning relationships may vary with predicted environmental change. In particular, our understanding will be advanced by studies addressing the interactive effects of multiple stressors on the role of biodiversity across trophic levels. Predicted increases in wave disturbance and ocean warming, together with climate-driven range shifts of key consumer species, are likely to have profound impacts on the dynamics of coastal marine communities. We tested whether wave action and temperature modified the effects of gastropod grazer diversity (Patella vulgata, Littorina littorea, and Gibbula umbilicalis) on algal assemblages in experimental rock pools. The presence or absence of L. littorea appeared to drive changes in microalgal and macroalgal biomass and macroalgal assemblage structure. Macroalgal biomass also decreased with increasing grazer species richness, but only when wave action was enhanced. Further, independently of grazer diversity, wave action and temperature had interactive effects on macroalgal assemblage structure. Warming also led to a reversal of grazer-macroalgal interaction strengths from negative to positive, but only when there was no wave action. Our results show that hydrodynamic disturbance can exacerbate the effects of changing consumer diversity, and may also disrupt the influence of other environmental stressors on key consumer-resource interactions. These findings suggest that the combined effects of anticipated abiotic and biotic change on the functioning of coastal marine ecosystems, although difficult to predict, may be substantial.


On the methodology of nematode extraction from field samples: baermann funnel modifications.
Routine quantitative nematode extraction for pest management purposes remains a problem. There is need for more knowledge of the parameters limiting efficiency of the various available methods. Sedimentation rates for several species of nematodes have been confirmed as slow and highly variable and therefore not suitable for quantitative separation of nematodes. Funnel losses with clean and unpitted glassware, whether closed or open stemmed, with or without misting, are negligible so long as misting periods are neither inadequate nor excessive; i.e., approximately a 1.5-min water spray period in a 10-min cycle. Tissue paper used to retain soil, sievings, or other substrate in the funnel extraction can greatly inhibit the passage of nematodes depending upon the tissue properties and the nematode species.


The clinical and genetical features of 124 children with Familial Mediterranean fever: experience of a single tertiary center.
The aim of the present study was to evaluate the clinical features of childhood-onset Familial Mediterranean fever (FMF) patients and to assess the phenotype-genotype correlation. The study included patients with childhood-onset FMF that followed up over a period of 18 years in the Division of Pediatric Allergy and Immunology clinic. Twelve MEFV mutations were investigated in all patients. The patients were classified into four groups according to mutations: 1, M694V homozygote; 2, M694V heterozygote; 3, compound heterozygote for M694V; and 4, other-other gene mutation group. The following parameters were evaluated: gender, age of onset, age at diagnosis, time interval between disease onset and diagnosis, fever, abdominal pain, chest pain, arthralgia, arthritis, myalgia, vomiting, diarrhea, constipation, headache, erysipela-like erythema, protracted febrile myalgia, splenomegaly, hepatomegaly, consanguinity, number of attacks before and after treatment, severity score, response to colchicine treatment. Of the 124 patients included in the study, 105 had at least one MEFV gene mutation. M694V homozygosity was the most common mutation, followed by M694V heterozygotes and M694V-M680I compound heterozygotes. Severity score was found significantly higher in patients with M694V homozygote and compound heterozygote for M694V compared with other groups. The data supported the findings in literature that FMF patients with M694V homozygote and compound heterozygote for M694V gene mutations experience a more severe clinical course.


[Systematized complex vascular malformations].
Various types of systematized vascular syndromes are described, either in the head or in the limbs. The Sturge-Weber syndrome includes a facial portwine stain, ocular anomalies, and a pial vascular malformation. Complex combined vascular malformations with limb overgrowth need careful investigations to clearly define the vascular component and the management.


Hypothesis on the evolution of cavitary lesions in nontuberculous mycobacterial pulmonary infection: thin-section CT and histopathologic correlation.
The objectives of our study were to evaluate the thin-section CT findings of the cavitary form of nontuberculous mycobacterial pulmonary infection and correlate these imaging findings with the histopathologic findings concerning the development of bronchiectasis and of centrilobular nodules and cavitary lesions. We retrospectively reviewed thin-section CT scans (2.5-mm collimation, both axial and coronal reformation images) of 24 cases (male-female ratio, 13:11; mean age, 61 years; age range, 43-82 years) of the cavitary form of culture-proven Mycobacterium avium-intracellulare complex pulmonary infection including two cases with lobectomy specimens. Any changes in CT findings detected on the follow-up CT scans that were available for seven patients (follow-up interval, 6-24 months; mean, 12 months) were also assessed. Thin-section CT findings were bronchiectasis (24/24 patients, 100%), a patent bronchus running into a cavitary lesion (the "feeding bronchus" appearance) (18/24, 75%), nodules less than 10 mm (17/24, 71%), centrilobular nodules (17/24, 71%), nodules of 10-30 mm (13/24, 54%), peribronchial nodules (8/24, 33%), lobular consolidation (6/24, 25%), bronchial wall thickening (4/24, 17%), and consolidation (2/24, 8%). Two lobectomy specimens showed large cavitary consolidations with the feeding bronchus appearance on pathologic specimens. In two patients, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance on follow-up CT, which represented inflamed focal cystic bronchiectasis. In the cavitary form of M. avium-intracellulare complex pulmonary infection, the feeding bronchus appearance is another very frequent thin-section CT finding. This appearance may suggest that peribronchial nodules of M. avium-intracellulare complex infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions.


Evaluation of HER2/neu oncoprotein in serum & tissue samples of women with breast cancer.
The proto-oncogene HER2/neu has been extensively studied in breast cancer patients. Serum levels of HER2/neu by ELISA in breast cancer patients were compared with tissue HER2/neu expression and with other clinicopathological parameters with the aim to investigate whether the serum assay could replace the established tests (IHC/FISH) for HER-2 status. Blood and Tru-cut biopsy samples were collected for determining HER2/neu status in 64 breast cancer patients. The tissue specimens were processed routinely and immunohistochemistry (IHC) for HER2/ER/PR (oestrogen/progesterone receptors) performed. Fluorescence in-situ hybridization (FISH) was performed on all HER2/neu 2 positive cases. Sixty age matched healthy females and females with benign breast disease were taken as controls for ELISA. Of the 64 breast cancer cases, 25 (39.1%) had elevated serum HER2/neu levels accompanied with increased tissue expression of HER2/neu receptors. On IHC, HER2/neu score was 3+ in 24 (37.5%) cases, 2+ in three (4.6%), 1+ in 18 (28.1%); while 19 cases (29.7%) showed no HER2/neu expression. o0 f the three 2+ cases on IHC, two showed amplification on FISH. Twenty one (32.8%) patients were ER positive and 17 (26.6%) were PR positive. There was a significant correlation (P<0.001) of serum HER2 concentration with tumour size, lymph node involvement, stage of disease and histological grade. Serum HER2/neu levels showed a negative correlation with ER status (P=0.047) but no correlation with PR status. The results suggest that elevated serum HER2 level was associated with a clinicopathological aggressive phenotype of breast carcinoma and was related to tissue HER2 overexpression. Therefore, serum HER2 may be useful for monitoring the course of the disease and response to treatment.