Hospital-based trauma quality improvement initiatives: first step toward improving trauma outcomes in the developing world.
Injuries remain a leading cause of death in the developing world. Whereas new investments are welcome, quality improvement (QI) at the currently available trauma care facilities is essential. The objective of this study was to determine the effect and long-term sustainability of trauma QI initiatives on in-hospital mortality and complications at a large tertiary hospital in a developing country. In 2002, a specialized trauma team was formed (members trained using advanced trauma life support), and a western style trauma program established including a registry and quality assurance program. Patients from 1998 onward were entered in to this registry, enabling a preimplementation and postimplementation study. Adults (>15 years) with blunt or penetrating trauma were analyzed. The main outcomes of interest were (1) in-hospital mortality and (2) occurrence of any complication. Multiple logistic regression was performed to assess the impact of formalized trauma care on outcomes, controlling for covariates reaching significance in the bivariate analyses. A total of 1,227 patient records were analyzed. Patient demographics and injury characteristics are described in Table 1. Overall in-hospital mortality rate was 6.4%, and the complication rate was 11.1%. On multivariate analysis, patients admitted during the trauma service years were 4.9 times less likely to die (95% confidence interval, 1.77-13.57) and 2.60 times (odds ratio; 95% confidence interval, 1.29-5.21) less likely to have a complication compared with those treated in the pretrauma service years. Despite significant delays in hospital transit and lack of prehospital trauma care, hospital level implementation of trauma QI program greatly decreases mortality and complication rates in the developing world. Care management study, level IV.


Replacement of glycoprotein B gene sequences in herpes simplex virus type 1 strain ANG by corresponding sequences of the strain KOS causes changes of plaque morphology and neuropathogenicity.
DNA sequences encoding glycoprotein B (gB) derived from herpes simplex virus type 1 (HSV-1) strain KOS321 were transferred to HSV-1 ANG. In cotransfection experiments the cloned HSV-1 KOS BamHI G fragment served as donor, and genomic DNA of two ANG variants as recipients. One of these variants, HSV-1 ANG path, expresses gC and the other, C18, was a spontaneous gC-negative mutant. Both ANG strains are of the syncytial (syn) phenotype whereas HSV-1 KOS321 is non-syncytial (syn+). Recombinants were identified by means of a monoclonal antibody which selectively recognizes gBKOS. Among the HSV-1 ANG path/gBKOS recombinants, the majority displayed an altered plaque morphology, i.e. they were of the syn+ phenotype. In contrast all of the C18/gBKOS recombinants were of the syn phenotype. The possibility that the mutant C18 carries a syn mutation not present in the parental strain could be excluded. Marker transfer experiments involving subfragments of the gB gene mapped the syn mutation of HSV-1 ANG path to a locus within the gene that has been previously termed syn 3. Subclones of HSV-1 ANG path were established either directly or after intermittent transfection or cotransfection with the KOS BamHI G fragment. The pathogenicity in mice of these clones was compared. The data obtained indicated that at high frequency, the BamHI G fragment confers apathogenicity.


Randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a single oral dose of vanoxerine for the conversion of subjects with recent onset atrial fibrillation or flutter to normal sinus rhythm: RESTORE SR.
Vanoxerine is an oral, 1,4-dialkylpiperazine derivative antiarrhythmic drug being evaluated for pharmacological cardioversion of atrial fibrillation (AF). The purpose of this study was to evaluate the safety and efficacy of vanoxerine for the restoration of sinus rhythm in subjects with recent onset AF or atrial flutter (AFL). RESTORE SR (randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a single oral dose of vanoxerine for the conversion of subjects with recent onset atrial fibrillation or flutter to normal sinus rhythm) was a prospective, multinational, randomized, double-blind, placebo-controlled trial that randomized subjects to a single oral dose of vanoxerine 400 mg or placebo (2:1 allocation). A total of 41 subjects were randomized in the study (placebo [n = 15] and vanoxerine [n = 26]). The study was terminated prematurely because of safety concerns. Overall, 61% (23 of 38) of the treated cohort had a history of AF/AFL and 66% (27 of 41) had structural heart disease (SHD). The primary efficacy end point-conversion to sinus rhythm through 24 hours-occurred in 20% (3 of 15) in the placebo arm vs 69% (18 of 26) in the vanoxerine arm (P = .0024). The mean length of stay was 4.2 ± 2.9 days in the placebo arm vs 4.7 ± 3.2 days in the vanoxerine arm (P = .6561). The primary safety end point (all-cause death, ventricular fibrillation/tachycardia requiring intervention, or torsades de pointes) occurred in no patient in the placebo arm vs 11.5% (3 of 26) in the vanoxerine arm. All 3 patients had torsades de pointes and underlying SHD. Vanoxerine is an oral, mixed ion channel blocker with IKr, INa, and L-type calcium channel activity. While oral therapy with 400 mg of vanoxerine appears effective for the termination of recent onset AF/AFL, its use was associated with a significant risk of ventricular proarrhythmia in patients with SHD.


Distinct subunit functions and cell cycle regulated phosphorylation of 20S APC/cyclosome required for anaphase in fission yeast.
We show here that the fission yeast gene products Cut9 and Nuc2 are the subunits of the 20S complex, the putative APC (anaphase promoting complex)/cyclosome which contains ubiquitin ligase activity required for cyclin and Cut2 destruction. The assembly of Cut9 into the 20S complex requires functional Nuc2, and vice versa. The size of fission yeast APC/cyclosome is similar to that of higher eukaryotes, but differs greatly from that (36S) of budding yeast. The 20S complex is present in cells arrested at different stages of the cell cycle, and becomes slightly heavier in mitosis than interphase. Cut9 in the 20S complex is hyperphosphorylated specifically at the time of metaphase. The truncated forms of Cut9 block entry into mitosis, however. The 20S assembly impaired in the cut9 mutant can be restored by elevating the level of a novel gene product Hcnl, similar to budding yeast Cdc26. Furthermore, deletion of protein kinase PKA (Pkal) suppresses the phenotype of the cut9 mutation and reduces phosphorylation of Cut9. In contrast, PP1 (Dis2) phosphatase mutation shows the reverse effect on the phenotype of cut9. The Cut9 subunit is likely to be a target for regulating APC/ cyclosome function through protein-protein interactions and phosphorylation.


Can the use of antibiotics interfere with the success of dental osseointegrated implants in diabetic patients?
The present review aims to discuss the last 10 years published data on the topic of the use of osseointegrated implants in diabetic subjects, particularly regarding the influence of antibiotics administration in the perioperative period. In the last decades, oral rehabilitation significantly has evolved particularly with the use of osseointegrated implants. Increased life expectation of population is reflecting in a greater number of diabetic patients who might require dental osseointegrated implants rehabilitation. Diabetes was considered for a long time as a contraindication for oral implant placement. In this context, the use of antibiotics is still a controversial factor when we correlate it to implant success rate. Although 228 articles were initially selected for evaluation of proposed criteria, only 16 articles were considered valid. Among the 16 selected articles, only six articles represented clinical research that discussed the influence of the antibiotic in the success of osseointegration of dental implants in diabetic subjects. Five were retrospective studies and one a prospective research. Data favors the use of antibiotics without significant side effects but clinical investigations of the need of prophylaxis antibiotic or therapeutic antibiotics are still scarce. The lack of adequate methodology is one of the main problems of the current articles. It is important to emphasize that studies should present detailed methodology in order to allow reproducibility. Permanent tooth loss is a pathological condition that affects millions of people worldwide. The possibility of successful treatment of edentulous areas through osseointegrated implants in those systemic compromised patients is a matter of scientific discussion. Although antimicrobial agents must be used rationally and carefully to avoid development of bacterial resistance, more studies are needed in order to support evidence regarding the influence of antibiotics in the success of dental implant surgery in diabetic patients.


Economic estimation of Bitcoin mining's climate damages demonstrates closer resemblance to digital crude than digital gold.
This paper provides economic estimates of the energy-related climate damages of mining Bitcoin (BTC), the dominant proof-of-work cryptocurrency. We provide three sustainability criteria for signaling when the climate damages may be unsustainable. BTC mining fails all three. We find that for 2016-2021: (i) per coin climate damages from BTC were increasing, rather than decreasing with industry maturation; (ii) during certain time periods, BTC climate damages exceed the price of each coin created; (iii) on average, each $1 in BTC market value created was responsible for $0.35 in global climate damages, which as a share of market value is in the range between beef production and crude oil burned as gasoline, and an order-of-magnitude higher than wind and solar power. Taken together, these results represent a set of sustainability red flags. While proponents have offered BTC as representing "digital gold," from a climate damages perspective it operates more like "digital crude".


Evolution of genetic abnormalities in hepatocellular carcinomas demonstrated by DNA fingerprinting.
Hepatocellular carcinomas (HCC) often contain subpopulations of cells showing heterogeneous differentiation within each tumour. The majority of HCCs first appear as well-differentiated lesions and proliferate with gradual dedifferentiation. The present study was designed to investigate the clonal diversity which is seen with progression in neoplasms. The degree of genomic heterogeneity of HCC nodules was assessed using the arbitrarily primed-polymerase chain reaction technique. Two or more sectors of 31 HCC nodules were needle-microdissected and amplified with two different arbitrary primers in appropriate conditions. In every HCC less than 6 mm in diameter (n=18, range 3-6 mm, mean diameter 4.7 mm), all sectors of each of these lesions had the same DNA fingerprint. All HCC nodules greater than 6 mm diameter (n=13, range 7-30 mm, mean diameter 15.4 mm) showed distinct DNA fingerprints in each sector sampled (p< 0. 05, compared with size less than 6 mm in diameter). When synchronous HCCs were present, no two tumour nodules had the same DNA fingerprint. These results suggest that a process of clonal evolution occurs in expanding HCC, with neoplasms more than 6 mm in diameter developing as multiple clones. The advent of laser capture microdissection technology makes such analysis much more rapid and easily applied. Studies of clonality in HCCs, including borderline cases, are made possible by the combination of these novel techniques.


Bak and Bax function to limit adenovirus replication through apoptosis induction.
Adenovirus infection and expression of E1A induces both proliferation and apoptosis, the latter of which is blocked by the adenovirus Bcl-2 homologue E1B 19K. The mechanism of apoptosis induction and the role that it plays in productive infection are not known. Unlike apoptosis mediated by death receptors, infection with proapoptotic E1B 19K mutant viruses did not induce cleavage of Bid but nonetheless induced changes in Bak and Bax conformation, Bak-Bax interaction, caspase 9 and 3 activation, and apoptosis. In wild-type-adenovirus-infected cells, in which E1B 19K inhibits apoptosis, E1B 19K was bound to Bak, precluding Bak-Bax interaction and changes in Bax conformation. Infection with E1B 19K mutant viruses induced apoptosis in wild-type and Bax- or Bak-deficient baby mouse kidney cells but not in those deficient for both Bax and Bak. Furthermore, Bax and Bak deficiency dramatically increased E1A expression and virus replication. Thus, Bax- and Bak-mediated apoptosis severely limits adenoviral replication, demonstrating that Bax and Bak function as an antiviral response at the cellular level.


Computational analysis of the effect of [Tea][Ms] and [Tea][H2PO4] ionic liquids on the structure and stability of Aβ(17-42) amyloid fibrils.
Experimental studies have reported the possibility of affecting the growth/dissolution of amyloid fibres by the addition of organic salts of the room-temperature ionic-liquid family, raising the tantalizing prospect of controlling these processes under physiological conditions. The effect of [Tea][Ms] and [Tea][H2PO4] at various concentrations on the structure and stability of a simple model of Aβ42 fibrils has been investigated by computational means. Free energy computations show that both [Tea][Ms] and [Tea][H2PO4] decrease the stability of fibrils with respect to isolated peptides in solution, and the effect is significantly stronger for [Tea][Ms]. The secondary structure of fibrils is not much affected, but single peptides in solution show a marked decrease in their β-strand character and an increase in α-propensity, again especially for [Tea][Ms]. These observations, consistent with the experimental picture, can be traced to two primary effects, i.e., the difference in the ionicity of the [Tea][Ms] and [Tea][H2PO4] water solutions and the remarkable affinity of peptides for [Ms]- anions, due to the multiplicity of H-bonds.


Dynamic coupling of excitatory and inhibitory responses in the medial nucleus of the trapezoid body.
The neuronal representation of acoustic amplitude modulations is an important prerequisite for understanding the processing of natural sounds. We investigated this representation in the medial nucleus of the trapezoid body (MNTB) of the Mongolian gerbil using sinusoidal amplitude modulations (SAM). Depending on the SAM's carrier frequency (f(C)) MNTB cells either increase or decrease their discharge rates, indicating underlying excitatory and inhibitory/suppressive mechanisms. As natural sounds typically are composed of multiple spectral components we investigated how stimuli containing two spectral components are represented in the MNTB, especially when they have opposing effects on the discharge rate. Three conditions were compared: SAM stimuli (1) with rate-increasing f(C), (2) with rate-increasing f(C) and an additional unmodulated rate-decreasing pure tone, and (3) with rate-decreasing f(C) and an unmodulated, rate-increasing pure tone. We found that responses under all three conditions showed comparable strength of phase-locking. Adding a rate-decreasing tone to a rate-increasing SAM increased phase-locking for modulation frequencies (f(AM)) of < or = 600 Hz. A comparison of two possible coding strategies--phase-locking vs. envelope reproduction--indicates that both strategies are realized to different degrees depending on the f(AM). We measured latencies for following modulations in rate-increasing and rate-decreasing SAMs using a modified reverse correlation approach. Although latencies varied between 2.5 and 5 ms between cells, a decrease in rate consistently followed an increase in rate with a delay of about 0.2 ms in each cell. These results suggest a temporally precise representation of rate-increasing and rate-decreasing stimuli at the level of the MNTB during dynamic stimulation.


Vector control in developed countries: With special reference to the establishment of semi-independent services in the state of California.
The recent rapid growth of California's population, leading to competition for space between residential, industrial and agricultural interests, the development of its water resources and increasing water pollution provide the basic ingredients of its present vector problems. Within the past half-century, the original mosquito habitats provided by nature have gradually given place to even more numerous and productive habitats of man-made character. At the same time, emphasis in mosquito control has shifted from physical to chemical, with the more recent extension to biological approaches as well. The growing domestic fly problem, continuing despite the virtual disappearance of the horse, is attributable to an increasing amount of organic by-products, stemming from growing communities, expanding industries and changing agriculture. The programme for the control of disease vectors and pest insects and animals directs its major effort to the following broad areas: (1) water management (including land preparation), (2) solid organic wastes management (emphasizing utilization), (3) community management (including design, layout, and storage practices of buildings and grounds), and (4) recreational area management (related to wildlife management). It is apparent that vector control can often employ economics as an ally in securing its objectives. Effective organization of the environment to produce maximum economic benefits to industry, agriculture, and the community results generally in conditions unfavourable to the survival of vector and noxious animal species. Hence, vector prevention or suppression is preferable to control as a programme objective.


African Swine Fever in Mongolia: Course of the Epidemic and Applied Control Measures.
African swine fever (ASF) is spreading rapidly in Asia and was confirmed in Mongolia on 10 January 2019. Following the outbreak confirmation, a state emergency committee was established with representation from municipal authorities and other relevant authorities including the General Authority for Veterinary Services, National Emergency Management Agency, General Agency for Specialized Inspection, and the Ministry of Environment and Tourism. The committee provided recommendations and coordinated closely with the State Central Veterinary Laboratory to ensure quick outbreak investigation and response. In addition to outbreak investigations, sampling took place at farms and food premises and suggests a link between the outbreaks and swill feeding practices among backyard pig farmers. Upon government request, the Food and Agriculture Organization of the United Nations (FAO) deployed an expert team to assist in identifying risk factors for the disease spread and provide recommendations as how to improve disease prevention and response. Following the control measures from the involved agencies, the epidemic was successfully controlled and declared over on 11 April 2019. In total, the epidemic affected 83 pig farming households and led to a total of 2862 dead or culled pigs in eleven districts of seven provinces in Mongolia.


Understanding the mechanisms of anaphylaxis.
The present review considers recent reports that identify the roles of key intermediate signaling components and mediators during and after mast cell activation and degranulation leading to anaphylaxis. Mechanisms of anaphylaxis are becoming better understood as the interaction of several regulatory systems in the mast cell activation and degranulation signaling cascade. Multiple tyrosine kinases, activated after immunoglobulin E binding to the high-affinity receptors for immunoglobulin E (FcepsilonRI), exert both positive and negative regulation on the signaling cascade, which may vary with genetic background or mutations in signaling proteins. Calcium influx, the essential, proximal intracellular event leading to mast cell degranulation, is controlled also by both negative and positive regulation through calcium channels. Sphingosine-1-phosphate is emerging as a newly realized mediator of anaphylaxis, acting as a signaling component within the mast cell and as a circulating mediator. Anaphylaxis is a systemic reaction involving multiple organ systems, but it is believed that it may be influenced by cellular events in mast cells and basophils resulting in the release of mediators. Therefore, understanding the mechanisms of mast cell activation and degranulation is critical to understanding the mechanisms of anaphylaxis. Recent reports have identified important regulatory components of the signaling cascade and, consequently, potential targets for therapeutic intervention.


Modulating plant hormones by enzyme action: the GH3 family of acyl acid amido synthetases.
Plants respond to developmental cues and environmental stresses by controlling both the level and activity of various hormones. One mechanism of modulating hormone action involves amino acid conjugation. In plants, the GH3 family of enzymes conjugates various amino acids to jasmonates, auxins, and benzoates. The effect of conjugation can lead to activation, inactivation, or degradation of these molecules. Although the acyl acid and amino acid specificities of a few GH3 enzymes have been examined qualitatively, further in-depth analysis of the structure and function of these proteins is needed to reveal the molecular basis for how GH3 proteins modulate plant hormone action.


Heterotopic ossification after total elbow arthroplasty: a systematic review.
Heterotopic ossification (HO) is a known complication that can arise after total elbow arthroplasty (TEA). In most cases, it is asymptomatic; however, in some patients, it can limit range of motion and lead to poor outcomes. The objective of this review was to assess and report the incidence, risk factors, prophylaxis, and management of HO after TEA. A systematic search was conducted using MEDLINE, Embase, and PubMed to retrieve all relevant studies evaluating the occurrence of HO after TEA. The search was performed in duplicate, and a quality assessment of all included studies was performed. A total of 1907 studies were retrieved, of which 45 were included involving 2256 TEA patients. HO was radiographically present in 10% of patients and was symptomatic in 3%. Fewer than 1% of patients went on to undergo surgical excision of HO, with outcomes after surgery reported as good or excellent as assessed by range of motion and the Mayo Elbow Performance Score. HO appears more likely to develop in patients undergoing TEA because of ankylosis, primary osteoarthritis, and distal humeral fractures. Surgical intervention is more likely to be required in patients in whom HO develops after TEA performed for ankylosis and post-traumatic osteoarthritis. HO is an uncommon complication after TEA, with most patients in whom HO develops being asymptomatic and requiring no surgical management. Routine HO prophylaxis for TEA is not supported by the literature. The effectiveness of prophylaxis in high-risk patients is uncertain, and future studies are required to clarify its usefulness.


Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a chronic bile duct inflammation strongly connected to ulcerative colitis (UC). PSC is associated with an increased risk of colon cancer, but the link between the intestinal and the bile duct inflammation is still unknown. Also, the involvement of intestinal immune cells in the pathogenesis of PSC remains to be determined. The eosinophil granulocyte is one of the immune cells implicated in the inflammatory process of ulcerative colitis. This study was performed to determine how the accumulation and activation of intestinal eosinophils may differ between UC with and without concomitant PSC, and how this may be influenced by the cytokine/chemokine profile of the intestinal compartment. Eosinophils from peripheral blood and multiple parts of the colon were analyzed by flow cytometry. The intestinal level of inflammatory mediators was assessed using a multiplex proximity extension assay and a quantitative immunoassay. We found that colonic eosinophils were more abundant in both UC and PSC-UC compared with controls, but that their expression of activation markers was significantly increased in UC only. The colonic level of pro-inflammatory cytokines was increased in active UC but not in PSC-UC. In conclusion, we show for the first time that eosinophil activation phenotype discriminates between UC and PSC-UC, and that this may depend on the local cytokine profile of the colonic mucosa.


Hidden genomic evolution in a morphospecies-The landscape of rapidly evolving genes in Tetrahymena.
A morphospecies is defined as a taxonomic species based wholly on morphology, but often morphospecies consist of clusters of cryptic species that can be identified genetically or molecularly. The nature of the evolutionary novelty that accompanies speciation in a morphospecies is an intriguing question. Morphospecies are particularly common among ciliates, a group of unicellular eukaryotes that separates 2 kinds of nuclei-the silenced germline nucleus (micronucleus [MIC]) and the actively expressed somatic nucleus (macronucleus [MAC])-within a common cytoplasm. Because of their very similar morphologies, members of the Tetrahymena genus are considered a morphospecies. We explored the hidden genomic evolution within this genus by performing a comprehensive comparative analysis of the somatic genomes of 10 species and the germline genomes of 2 species of Tetrahymena. These species show high genetic divergence; phylogenomic analysis suggests that the genus originated about 300 million years ago (Mya). Seven universal protein domains are preferentially included among the species-specific (i.e., the youngest) Tetrahymena genes. In particular, leucine-rich repeat (LRR) genes make the largest contribution to the high level of genome divergence of the 10 species. LRR genes can be sorted into 3 different age groups. Parallel evolutionary trajectories have independently occurred among LRR genes in the different Tetrahymena species. Thousands of young LRR genes contain tandem arrays of exactly 90-bp exons. The introns separating these exons show a unique, extreme phase 2 bias, suggesting a clonal origin and successive expansions of 90-bp-exon LRR genes. Identifying LRR gene age groups allowed us to document a Tetrahymena intron length cycle. The youngest 90-bp exon LRR genes in T. thermophila are concentrated in pericentromeric and subtelomeric regions of the 5 micronuclear chromosomes, suggesting that these regions act as genome innovation centers. Copies of a Tetrahymena Long interspersed element (LINE)-like retrotransposon are very frequently found physically adjacent to 90-bp exon/intron repeat units of the youngest LRR genes. We propose that Tetrahymena species have used a massive exon-shuffling mechanism, involving unequal crossing over possibly in concert with retrotransposition, to create the unique 90-bp exon array LRR genes.


[The relevance of junctional rhythm during neurocardiogenic reaction provoked by tilt testing].
During neurocardiogenic reaction provoked by tilt testing (TT), different arrhythmias such as sinus bradycardia, sinus arrest, atrioventricular block or junctional rhythm or beats (JR) may occur. The characteristics of the JR during neurocardiogenic reaction have not yet been systematically assessed. It is not known whether the presence of JR during neurocardiogenic reaction is related to clinical characteristics of syncopal patients or the outcome of TT. To assess whether clinical outcome of TT and clinical data are related to the presence of JR during TT. The study group consisted of 532 patients aged 43.3 ± 18.2 years with positive TT, divided into four groups on the basis of the presence of JR and/or a ventricular pause (VP) during neurocardiogenic reaction: group VP(-)/JR(+) - JR present and VP absent, group VP(+)/JR(+) - both JR and VP present, group VP(+)/JR(-) - JR absent and VP present, and group VP(-)/JR(-) - both JR and VP absent. The control group consisted of 53 patients with no history of syncope or presyncope, including 46 patients with negative TT and seven patients with false positive TT. Total loss of consciousness during TT occurred in group VP(-)/JR(+) less frequently than in groups VP(+)/JR(+) and VP(+)/JR(-), and more frequently than in group VP(-)/JR(-) (80% vs 96% vs 94% vs 62%; p 〈 0.05 for both comparisons). Group VP(-)/JR(+) was significantly younger than group VP(-)/JR(-) (37.3 ± 16.3 years vs 45.8 ± 18.9 years; p 〈 0.05) and had a lower number of syncopal events than group VP(+)/JR(+) and VP(+)/JR(-) (median [IQ]: 2.5 (1-6) vs 4 (2-12) and 4 (2-10), respectively; p 〈 0.05) and lower rate of traumatic injuries than group VP(+)/JR(+) and VP(+)/JR(-) (22% vs 45% and 39%, respectively; p 〈 0.05). Logistic regression analysis revealed that the presence of JR was associated with younger age, male gender, history of blood-instrumentation-injection phobia and higher number of syncopal spells in medical history. The ROC curve analysis revealed that a junctional rate of no more than 49 bpm was related to the total loss of consciousness during TT (p 〈 0.05). 1. JR frequently occurs during positive TT and in no subjects with negative TT. 2. Among patients with JR, two groups may be chosen on the basis of a VP occurrence, and these groups differ in respect to clinical characteristics and TT outcome. 3. Relatively rapid JR without VP is related to consciousness preservation during neurocardiogenic reaction at TT and fewer syncopal spells as well as syncope associated with injury in the past. 4. In patients with JR and VP, the JR is slower, of shorter duration, and more frequently single or pairs of junctional beats occur, which indicates high parasympathetic activity, whereas relatively rapid and stable JR may be the symptom of simultaneously increased sympathetic and parasympathetic activity.


[The mechanogenic reactions of the vessels during pulsatile flow: the theoretical predictions].
The basic ideas relating to mathematical modelling of blood flow in arteriolar and capillary microvessels of a skeletal muscle are briefly reviewed together with some qualitative results of the simulation. The emphasis is made on approaches used to describe the microvascular bed taking into account its structure, arterial vessels tonus, and myogenic regulatory reactions.


Evaluating the success of an inpatient PA and NP program through trends in ED consults.
We investigated the effect of an inpatient physician associate/assistant (PA) and NP program on consult volume, length of stay (LOS), and ED returns. A retrospective observational study of 4,118 orthopedic ED consults was conducted from January 2017 to March 2022. Univariate statistics were used to evaluate outcomes between cohorts and multivariate regression to evaluate the odds of an LOS of less than 24 hours. After implementation of the PA and NP program, surgeon consults steadily declined and orthopedic consults increased markedly. Statistically significant differences were found in LOS of less than 24 hours and ED arrival-to-discharge time. Adjusting for case mix, patients were 47% more likely to be discharged within 24 hours. Survey results noted that more than 80% of surgeons felt on-call workload, disruptions to clinic and surgical schedules decreased, and quality of care increased. Implementation of an inpatient PA and NP program reduced orthopedic surgeon consults and hospital LOS while improving surgeon satisfaction with on-call workload, schedule disruptions, and quality of care.


Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement.
We evaluated a simplified version of a previously developed QRS scoring system for estimating infarct size using observations of Q- and R-wave durations and R/Q and R/S amplitude ratios in the standard 12-lead ECG. Groups of subjects with a minimal likelihood of having myocardial infarcts and minimal likelihood of having common noninfarction sources of QRS modification were studied to establish the specificity of each of the 37 criteria. Only two criteria required modification to achieve 95% specificity. These 37 criteria form the basis of a 29-point QRS scoring system. A 98% specificity was achieved when a score of more than 2 points was required to identify a myocardial infarct. Fifty patients were studied to determine the intra- and interobserver agreement with this scoring system. Each criterion achieved at least 91% intra- and interobserver agreement. These impressive levels of specificity and observer agreement must be matched by high sensitivity of the scoring system and a good correlation between the point score and infarct size in patients with proven infarcts if the point score is to be useful for detecting and sizing infarcts. Sensitivity and correlation between point score and infarct size are evaluated in later studies in this series. The standard ECG is inexpensive and can be obtained repetitively and noninvasively; its QRS complex may be an important means of estimating the size, presence and location of myocardial infarcts.


Structural Properties of Defects in Glassy Liquids.
At zero temperature a disordered solid corresponds to a local minimum in the energy landscape. As the temperature is raised or the system is driven with a mechanical load, the system explores different minima via dynamical events in which particles rearrange their relative positions. We have shown recently that the dynamics of particle rearrangements are strongly correlated with a structural quantity associated with each particle, "softness", which we can identify using supervised machine learning. Particles of a given softness have a well-defined energy scale that governs local rearrangements; because of this property, softness greatly simplifies our understanding of glassy dynamics. Here we investigate the correlation of softness with other commonly used structural quantities, such as coordination number and local potential energy. We show that although softness strongly correlates with these properties, its predictive power for rearrangement dynamics is much higher. We introduce a useful metric for quantifying the quality of structural quantities as predictors of dynamics. We hope that, in the future, authors introducing new structural measures of dynamics will compare their proposals quantitatively to softness using this metric. We also show how softness correlations give insight into rearrangements. Finally, we explore the physical meaning of softness using unsupervised dimensionality reduction and reduced curve-fitting models, and show that softness can be recast in a form that is amenable to analytical treatment.


Dayglow photometry: a new approach.
A unique photometer capable of measuring line intensities of <0.1% of the bright background continuum (5 x 10(6)/A) has been developed and successfully commissioned for the measurement of daytime OI 630.0-nm emission from the thermosphere. The photometer employs a low resolution (10(4)) Fabry-Perot etalon, temperature tuned narrowband (3-A) interference filter, radial chopper, and up/down counting system. The optimum choice of the photometer parameters and a unique method of eliminating the background enabled us to overcome the limitations of the earlier attempts to make measurements on such phenomena as dayglow and has opened up a wide range of uses. However, at present, it is being discussed only in the context of dayglow measurements.


Prospective associations of maternal choline status with offspring body composition in the first 5 years of life in two large mother-offspring cohorts: the Southampton Women's Survey cohort and the Growing Up in Singapore Towards healthy Outcomes cohort.
Choline status has been positively associated with weight and fat mass in animal and human studies. As evidence examining maternal circulating choline concentrations and offspring body composition in human infants/children is lacking, we investigated this in two cohorts. Maternal choline concentrations were measured in the UK Southampton Women's Survey (SWS; serum, n = 985, 11 weeks' gestation) and Singapore Growing Up Towards healthy Outcomes (GUSTO); n = 955, 26-28 weeks' gestation) mother-offspring cohorts. Offspring anthropometry was measured at birth and up to age 5 years. Body fat mass was determined using dual-energy x-ray absorptiometry at birth and age 4 years for SWS; and using air-displacement plethysmography at birth and age 5 years for GUSTO. Linear-regression analyses were performed, adjusting for confounders. In SWS, higher maternal choline concentrations were associated with higher neonatal total body fat mass {β = 0.60 standard deviation [SD]/5 µmol/L maternal choline [95% confidence interval (CI) 0.04-1.16]} and higher subscapular skinfold thickness [β = 0.55 mm/5 µmol/L (95% CI, 0.12-1.00)] at birth. In GUSTO, higher maternal choline concentrations were associated with higher neonatal body mass index-for-age z-score [β = 0.31 SD/5 µmol/L (0.10-0.51)] and higher triceps [β = 0.38 mm/5 µmol/L (95% CI, 0.11-0.65)] and subscapular skinfold thicknesses [β = 0.26 mm/5 µmol/L (95% CI, 0.01-0.50)] at birth. No consistent trends were observed between maternal choline and offspring gain in body mass index, skinfold thicknesses, abdominal circumference, weight, length/height and adiposity measures in later infancy and early childhood. Our study provides evidence that maternal circulating choline concentrations during pregnancy are positively associated with offspring BMI, skinfold thicknesses and adiposity at birth, but not with growth and adiposity through infancy and early childhood to the age of 5 years.


A multimedia guide to spinal cord injury: empowerment through self instruction.
The Spinal Cord Injury (SCI) Project is developing a series of instructional modules on SCI that will be distributed via CD-ROM for patient and family education. The modules are based on an instructional program and patient manual distributed by the Paralyzed Veterans of America. The program includes topics ranging from the anatomy and physiology of spinal cord injuries to legal rights established under the Americans With Disabilities Act. The SCI project expands on the instructional manual by combining digital multimedia techniques with motivational features such as games and personal guides. The user selects a personal guide from among a selection of individuals with spinal cord injuries to guide them through tutorials that include accounts of personal experiences. The guides appear in small video windows at various points throughout the tutorials and give personal insight into the topic at hand. The user can also query the other guides to hear their views on a topic. The user interface incorporates 'seamless access' features, which enable persons with a wide range of disabilities to use the program. Innovative features of these modules are the use of personal instructional guides, motivational games and activities, incorporation of alternative input or access strategies, and the use of high quality, low cost, multimedia production strategies.


Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.
Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.


Various difunctionalizations of acrylamide: an efficient approach to synthesize oxindoles.
Various difunctionalizations of acrylamide can not only provide a simple approach to form a wide scope of functionalized oxindoles, but can also be applied and generated easily. This review concludes different difunctionalizations of acrylamide to synthesize oxindoles based on the mechanistic aspects. The goal is to encourage further mechanistic studies hopefully leading to an in-depth understanding of this strategy.


[Interconnection in activity of lipid peroxidation reactions and functional status of the liver in patients with chronic hepatitis of viral etiology].
There was a study of lipid peroxidation activity, ceruloplasmin level, bile acids content, and the liver detoxifying function state in 37 patients with chronic hepatitis types B and C of viral etiology. Changes of the indices under study were most apparent in patients with HCV. It was revealed that the degree of impairment of detoxifying and bile-producing functions of the liver are closely interrelated to the activity of the inflammatory reaction and lipid peroxidation processes. The increasing ceruloplasmin level in this category of patients hampers the reduction of the activity of lipid peroxidation processes, which is apparently related not only to the direct cytotoxic viral effect but also to the negative effect of superoxide ions on the cell membrane. Along with this, in cases of viral lesions of hepatocytes there are changes in the synthesis and conjugation of bile acids leading to the derangement of their correlation, their increased aggregate content and accumulation in tissues, which can also enhance the intensity of destruction of liver tissues and is an extra factor contributing to the intensification of lipid peroxidation processes.


Increased use of Twitter at a medical conference: a report and a review of the educational opportunities.
Most consider Twitter as a tool purely for social networking. However, it has been used extensively as a tool for online discussion at nonmedical and medical conferences, and the academic benefits of this tool have been reported. Most anesthetists still have yet to adopt this new educational tool. There is only one previously published report of the use of Twitter by anesthetists at an anesthetic conference. This paper extends that work. We report the uptake and growth in the use of Twitter, a microblogging tool, at an anesthetic conference and review the potential use of Twitter as an educational tool for anesthetists. A unique Twitter hashtag (#WSM12) was created and promoted by the organizers of the Winter Scientific Meeting held by The Association of Anaesthetists of Great Britain and Ireland (AAGBI) in London in January 2012. Twitter activity was compared with Twitter activity previously reported for the AAGBI Annual Conference (September 2011 in Edinburgh). All tweets posted were categorized according to the person making the tweet and the purpose for which they were being used. The categories were determined from a literature review. A total of 227 tweets were posted under the #WSM12 hashtag representing a 530% increase over the previously reported anesthetic conference. Sixteen people joined the Twitter stream by using this hashtag (300% increase). Excellent agreement (κ = 0.924) was seen in the classification of tweets across the 11 categories. Delegates primarily tweeted to create and disseminate notes and learning points (55%), describe which session was attended, undertake discussions, encourage speakers, and for social reasons. In addition, the conference organizers, trade exhibitors, speakers, and anesthetists who did not attend the conference all contributed to the Twitter stream. The combined total number of followers of those who actively tweeted represented a potential audience of 3603 people. This report demonstrates an increase in uptake and growth in the use of Twitter at an anesthetic conference and the review illustrates the opportunities and benefits for medical education in the future.


Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study.
The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. They were developed four years apart. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24-55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy. From our results and the review of the literature we conclude that: (1) patients with disseminated SCLC that respond to CT should be given RC to decrease chest relapses. (2) A dose of 3000 rad in two weeks seems to be enough to produce a low percentage of chest relapse in disseminated SCLC, as survival of these patients is short and many will die prior to developing chest relapse. However, according to the literature, 4000-4800 rad is probably a more effective dose. (3) More studies and guidelines are needed to outline proper boundaries of radiotherapy fields, to decrease chances of peripheral chest relapses. (4) Median survival might not be a good parameter to evaluate the impact of RC in disseminated SCLC. The study of long-term survivors seems to be more important.


Using an oral health-related quality of life measure in three cultural settings.
To assess the application of the Oral Impacts on Daily Performances (OIDP) index for use in three different language and cultural settings; To develop a Spanish and Afrikaans version of the OIDP for use in the USA and South Africa and to assess its reliability and validity in three counties: UK, USA and South Africa. Co-ordinated pilot studies using the OIDP questionnaire and clinical examination using WHO criteria in the three countries using cross-sectional convenience samples of children. Two populations in each country: relatively well-off and more socially disadvantaged in three age groups 40 years+, 15-16 and 11-12 year-olds. 525 volunteers participated in the study; 154 in Texas, 177 in Bristol and 194 in Cape Town, the majority being females. The prevalence of oral impacts on daily performances varied between the three sites, with the sample in Bristol showing lower prevalence of 28.8% reporting at least one oral impact in the past six months. Difficulty eating was a common impact in all three sites, reported by 22.7% of the Texas sample, 18.6% of the Bristol sample and 33.0% of the Cape Town sample. Criterion and construct validity: the OIDP performed consistently well in all three sites. The combined dental caries status of the two lower age groups (12- and 16-year-olds) varied by site: Texas had the highest overall mean DMFT of 4.31, then Bristol with 3.07 and Cape Town the lowest at 2.89. The OIDP index had excellent psychometric properties in the Cape Town and Texas samples and had an overall good performance in the Bristol sample. Potentially the index can be used for oral health needs assessment and planning services. Further studies using larger samples might provide information relevant to the revision of existing oral health care systems.


A retrospective study of risk factors for poor outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infection in surgical patients.
Since its isolation, Methicillin-resistant Staphlococcus aureus (MRSA) has become a major cause of hospital acquired infection (HAI), adverse patient outcome and overall resource utilisation. It is endemic in Scotland and widespread in Western hospitals. MRSA has been the subject of widespread media interest--a manifestation of concerns about sterile surgical techniques and hospital cleanliness. This study aimed to investigate patient outcome of MRSA infections over the last decade at a major orthopaedic trauma centre. The objective was to establish the association of variables, such as patient age and inpatient residence, against patient outcome, in order to quantify significant relationships; facilitating the evaluation of management strategies with an aim to improving patient outcomes and targeting high-risk procedures. This is a retrospective study of the rates and outcomes of MRSA infection in orthopaedic trauma at the Royal Infirmary of Edinburgh. Data was collated using SPSS 14.0 for Windows(R). Shapiro-Wilkes testing was performed to investigate the normality of continuous data sets (e.g: age). Data was analysed using both Chi-Squared and Fisher's exact tests (in cases of expected values under 5) This study found significant associations between adverse patient outcome (persistent deep infection, osteomyelitis, the necessity for revision surgery, amputation and mortality) and the following patient variables: Length of inpatient stay, immuno-compromise, pre-admission residence in an institutional setting (such as a residential nursing home) and the number of antibiotics used in patient care. Despite 63% of all infections sampled resulting from proximal femoral fractures, no association between patient outcome and site of infection or diagnosis was found. Somewhat surprisingly, the relationship between age and outcome of infection was not proved to be significant, contradicting previous studies suggesting a statistical association. Antibiotic prophylaxis, previously identified as a factor in reducing overall incidence of MRSA infection, was not found to be significantly associated with outcome. Early identification of high-risk patients as identified by this study could lead to more judicious use of therapeutic antibiotics and reductions in adverse outcome, as well as socioeconomic cost. These results could assist in more accurate risk stratification based on evidence based evaluation of the significance of the risk factors investigated.


Recommendations on prevention of infections in patients with T-cell lymphomas: a narrative review and synthesis.
T/Natural killer (NK) cell lymphomas (TCL) represent a heterogenous subgroup of non-Hodgkin lymphoma, associated with poorer prognosis and higher treatment toxicity. A cohesive synthesis of infection outcomes among TCL patients is lacking. International guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for TCL patients. This systematic narrative review highlights infection outcomes in TCL patients treated with conventional, and novel therapies. Recommendations for infection screening, antimicrobial prophylaxis and vaccination strategies are outined.


Multidimensional Sleep Health Problems Across Middle and Older Adulthood Predict Early Mortality.
Having multiple sleep problems is common in adulthood. Yet, most studies have assessed single sleep variables at one timepoint, potentially misinterpreting health consequences of co-occurring sleep problems that may change over time. We investigated the relationship between multidimensional sleep health across adulthood and mortality. Participants from the Midlife in the United States Study reported sleep characteristics in 2004-2006 (MIDUS-2; M2) and in 2013-2016 (MIDUS-3; M3). We calculated a composite score of sleep health problems across five dimensions: Regularity, Satisfaction, Alertness, Efficiency, and Duration (higher=more problems). Two separate models for baseline sleep health (n=5,140; median follow-up time=15.3 years) and change in sleep health (n=2,991; median follow-up time=6.4 years) to mortality were conducted. Cox regression models controlled for sociodemographics and key health risk factors (body mass index, smoking, depressive symptoms, diabetes, hypertension). On average, 88% of the sample reported having one or more sleep health problems at M2. Each additional sleep health problem at M2 was associated with 12% greater risk of all-cause mortality (hazard ratio [HR]=1.12, 95% confidence interval [CI]=1.04-1.21), but not heart disease related mortality (HR=1.14, 95% CI=0.99-1.31). An increase in sleep health problems from M2 to M3 was associated with 27% greater risk of all-cause mortality (HR=1.27, 95% CI=1.005-1.59), and 153% greater risk of heart disease mortality (HR=2.53, 95% CI=1.37-4.68). More sleep health problems may increase the risk of early mortality. Sleep health in middle and older adulthood is a vital sign that can be assessed at medical check-ups to identify those at greater risk.


Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer's Disease.
Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer's disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration. To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort. A total of 255 participants (55% female; mean age = 66.2 years, range = 42.5-86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels. Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status. These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer's disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition.


Mechanisms underlying the influence of skin properties on a single cavitation bubble in low-frequency sonophoresis.
As a safe and effective method for systemic transdermal drug delivery (TDD), sonophoresis has drawn much attention from researchers. Despite numerous studies confirming cavitation as the main reason for sonophoresis, the effect skin has on cavitation bubble dynamics remains elusive due to the difficulty of experimental challenges. For a start, we reveal how single cavitation bubble (SCB) dynamics are affected by skin properties, including elasticity, hydrophilicity and texture. We use polydimethylsiloxane (PDMS) to simulate human skin and record the temporary evolution of SCBs with synchronous ultrafast photography. The influences of skin properties on SCBs are concluded: 1) SCBs collapse later near walls with better elasticities and generate microjets with higher speed; 2) SCBs collapse later near hydrophilic walls with slower microjets; and 3) the existence of a texture structure on walls also delays the time of bubble collapse near them and slows the velocities of microjets (v) during collapses.


Influence of publicly available online wait time data on emergency department choice in patients with noncritical complaints.
Increased emergency department (ED) wait times lead to more patients who leave without being seen and decreased patient satisfaction. Many EDs post estimated wait times either online or in the ED to guide patient expectations. The objectives of this study were to assess patients' awareness of online wait time data and to investigate patients' willingness to use this information when choosing between two academic EDs in London, Ontario. A prospective study was conducted over a 2-month period in a tertiary ED with online available wait times. Patients over 18 years of age assigned a Canadian Triage and Acuity Scale (CTAS) score of 3, 4, or 5 were approached by trained research assistants to complete a 15-item paper-based questionnaire. Multivariable logistic regression models were used to determine factors independently associated with the outcomes. A total of 1,211 patients completed the survey. Of these, 109 (9%) were aware that ED wait time information was available on the Internet; 544 (45%) reported that they would use the available data to make a decision on which ED to visit, and 536 (44%) indicated that they were more likely to go to the ED with a shorter wait time. Age, gender, household income, education, and Internet access were not associated with awareness of online ED wait times. Participants less than 40 years of age were more likely to use online wait time information. There is low awareness of the availability of ED wait time data published online in the study locaton. Future research may include the delivery of a public awareness strategy for ED wait time data and a re-evaluation of ED use and patient satisfaction following this.


Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells.
High-density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake, and this selective uptake route forms an important step in reverse cholesterol transport. Recent data from Acton, Rigotti, Landschulz, Xu, Hobbs and Krieger [(1996) Science 271, 518-520] provide evidence that scavenger receptor B (SR-B1) can mediate selective uptake of HDL-CE. In order to identify if selective uptake of HDL-CE by rat liver parenchymal cells can be mediated by a protein with scavenger receptor properties we performed competition experiments in vivo with substrates for scavenger receptors. Addition of either low-density lipoprotein (LDL), acetylated LDL (AcLDL) or oxidized LDL (OxLDL) only marginally (<10%) decreased the association of HDL particles to parenchymal cells as measured by 125I-labelled HDL. HDL-CE association was inhibited by AcLDL by 35%, while addition of OxLDL did inhibit HDL-CE association by 80%, thereby completely blocking the selective uptake of HDL-CE. Studies with HDL labelled with a fluorescent cholesteryl-ester analogue confirmed that OxLDL mediated complete inhibition of HDL-CE selective uptake by rat liver parenchymal cells. The inhibition of HDL-CE selective uptake by OxLDL was insensitive to the additional presence of polyinosinic acid (poly I), indicating that the inhibitory effect did not involve a poly I-sensitive site. Anionic phospholipid liposomes inhibited HDL-CE association by 40%, while neutral liposomes were ineffective. The inhibition of the selective uptake of HDL-CE in liver parenchymal cells by modified LDL, in particular OxLDL and anionic phospholipids suggests that, in liver, the SR-B1 is responsible for the efficient uptake of HDL-CE.


Paroxysmal nocturnal hemoglobinuria: Review of the patient experience and treatment landscape.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder caused by complement-mediated hemolysis and thrombosis through the alternative pathway. The most common symptom of PNH is fatigue due to chronic anemia, which can negatively impact quality of life (QoL) and affect overall well-being. The currently approved therapies for PNH significantly limit intravascular hemolysis (IVH) and reduce the risk of thrombosis; however, they are associated with an infusion schedule that can become burdensome, and not all patients experience complete disease control. Several new complement inhibitors are in development that address the need for convenient routes of administration and aim to provide better disease control. With the variety of new treatment options on the horizon, hematologic markers as well as QoL concerns, patient opinion, and lifestyle factors should be considered to choose the optimal PNH treatment for each specific patient.


Phylogenetic analysis of West Nile virus, Nuevo Leon State, Mexico.
West Nile virus RNA was detected in brain tissue from a horse that died in June 2003 in Nuevo Leon State, Mexico. Nucleotide sequencing and phylogenetic analysis of the premembrane and envelope genes showed that the virus was most closely related to West Nile virus isolates collected in Texas in 2002.


Inhibition of phosphatidylinositol 3-kinase/Akt signaling attenuates hypoxia-induced pulmonary artery remodeling and suppresses CREB depletion in arterial smooth muscle cells.
Hypoxia-induced pulmonary hypertension is characterized by progressive remodeling of the pulmonary artery (PA) system and loss of the transcription factor, cAMP response element binding protein (CREB) in PA smooth muscle cells (SMCs). Previous in vitro studies suggested that platelet-derived growth factor, a mitogen produced in the hypoxic arterial wall, elicits loss of CREB in medial SMCs via the PI3K/Akt pathway. These events trigger switching of SMCs from a quiescent, contractile phenotype to a proliferative, migratory, dedifferentiated, and synthetic phenotype, which contributes to PA thickening. Here, we investigated whether inhibition of PI3K or Akt could attenuate arterial remodeling in the lung and prevent CREB loss in PA medial SMCs in rats subjected to chronic hypoxia. Inhibition of either enzyme-blunted hypoxia-induced PA remodeling and SMC CREB depletion and diminished SMC proliferation and collagen deposition. Inhibition of Akt, but not PI3K, suppressed muscularization of distal arterioles and blunted right ventricular hypertrophy. Interestingly, mean PA pressure was elevated equally by hypoxia in untreated and inhibitor-treated groups but was normalized acutely by the Rho kinase inhibitor, Fasudil. We conclude that PI3K and Akt inhibitors can attenuate hypoxia-induced PA remodeling and SMC CREB depletion but fail to block the development of pulmonary hypertension because of their inability to repress Rho kinase-mediated vasoconstriction.


Morphologic analysis of pulmonary neuroendocrine tumors.
Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis. Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes. The mean nuclear area was 0.318±0.101 µm(2) in typical carcinoid tumors, 0.326±0.119 µm(2) in atypical carcinoid tumors, 0.314±0.107 µm(2) in small cell carcinomas, and 0.446±0.145 µm(2) in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001). Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.


Perception of apparent motion in the common toad.
A simple and inexpensive apparatus makes possible the feeding of nonliving objects to the toad. The device is used to demonstrate the perception of apparent or "induced" motion. Two methods are successful: (i) toad and food moving together at a constatnt velocity in a stationary environment; (ii) toad and food stationary with the environment moving. The phenomena are similar to those found in human beings.


RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice.
Osteoclasts (OCs) function to reabsorb bone and are responsible for the bone loss associated with inflammatory arthritis and osteoporosis. OC numbers are elevated in most disorders of accelerated bone destruction, reflecting altered rates of precursor differentiation and apoptosis. Both of these processes are regulated by the JNK family of MAP kinases. In this study, we have demonstrated that the NF-kappaB subunit RelA/p65 inhibits JNK-mediated apoptosis during a critical period of commitment to the OC phenotype in response to the cytokine RANKL. This RelA/p65-mediated arrest of cell death led to enhanced OC differentiation. Hence, Rela-/- OC precursors displayed prolonged JNK activation in response to RANKL, and this was accompanied by an increase in cell death that prevented efficient differentiation. Although complete blockade of JNK activity inhibits osteoclastogenesis, both short-term blockade in RelA-deficient cultures and suppression of the downstream mediator, Bid rescued apoptosis and differentiation. These antiapoptotic effects were RelA specific, as overexpression of RelA, but not RelB, blocked apoptosis and rescued differentiation in Rela-/- precursors. Thus, RelA blocks a RANKL-induced, apoptotic JNK-Bid pathway, thereby promoting OC differentiation. Consistent with this, mice lacking RelA/p65 in the hematopoietic compartment were shown to have a deficient osteoclastogenic response to RANKL and were protected from arthritis-induced osteolysis.


Role of bilateral staged hip arthroplasty in Hip-spine syndrome: A case report.
Hip-spine syndrome is a frequent finding in patients presenting with symptoms both at the level of the hip and spine. Patient previously operated of lumbar laminectomy for supposed spinal stenosis presenting with persistent pain and disability. Clinical examination and imaging showed severe bilateral hip osteoarthritis. Full body standing and sitting biplanar radiographs showed an associated severe sagittal malalignment. 3D motion analysis and health-related quality of life (HRQOL) questionnaires showed a severe functional impact. He was operated of a staged bilateral total hip arthroplasty using the direct anterior approach. Spinopelvic and sagittal alignment parameters, as well as 3D motion analysis and HRQOL scores showed significant improvement after the first, then the second total hip arthroplasty. Comprehensive functional diagnostic testing, including full body standing and seated radiographs, 3D gait analysis and HRQOL questionnaires may provide important information for future management.


Immunolocalization of multiple Galpha subunits in mammalian spermatozoa and additional evidence for Galphas.
Like somatic cells, mammalian spermatozoa appear to contain several different heterotrimeric G protein alpha-subunits that could mediate specialized cell responses. However, the precise Galpha subunits present, their subcellular location and their possible roles are still incompletely defined. In this study, using commercially available specific antibodies, we have shown by immunoblotting that Galpha(s) is present in human and mouse sperm lysates. Immunolocalization using intact spermatozoa from both species revealed this protein to be in the acrosomal cap region and the flagellum, particularly the principal piece. Treatment of permeabilized mouse spermatozoa with cholera toxin led to enhanced ADP-ribosylation of a protein the same size as Galpha(s), as well as an increase in cAMP, providing further proof for Galpha(s). Evidence for the presence and distinct localizations of Galpha(i2), Galpha(i3), Galpha(o), Galpha(q/11), and Galpha(olf) was also obtained. Of particular interest was Galpha(i2) which, like Galpha(s), was present in the acrosomal cap region and flagellum, the same regions where stimulatory and inhibitory adenosine receptors are localized. These observations are consistent with our hypothesis that G proteins mediate adenosine receptor modulation of adenylyl cyclase, with consequent alterations in cAMP production, apparently crucial for the spermatozoon's acquisition and maintenance of fertilizing ability.


[Epistaxis following skull trauma].
Epistaxis is a common problem, which is usually benign in nature. In some cases, however, epistaxis is a symptom of a severe underlying condition. A 20-year-old male was treated conservatively following head injury with craniofacial and base-of-skull fractures. Recurrent episodes of epistaxis occurred some weeks after treatment. Further investigation showed an extradural dissecting aneurysm of the left internal carotid artery (ICA), projecting into the sphenoid sinus. The aneurysm was treated endovascularly by placing a coil in the aneurism and a stent in the artery. On the basis of this case study we describe the diagnostics and treatment of patients with posttraumatic posterior epistaxis. In cases if delayed epistaxis following head injury the physician should be alert for the possibility of trauma to the ICA. This is a potentially life-threatening situation that requires prompt treatment.


Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors.
Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in long-term childhood cancer survivors at their first visit to a specialized outpatient clinic. Estimated GFR; percentages of patients with albuminuria, hypomagnesemia, and hypophosphatemia; and BP were assessed in 1442 survivors ≥5 years after diagnosis. Multivariable logistic regression analyses were used to estimate effect of chemotherapy, nephrectomy, and radiation therapy on the different outcomes. At a median age of 19.3 years (interquartile range, 15.6-24.5 years), 28.1% of all survivors had at least one renal adverse effect or elevated BP. The median time since cancer diagnosis was 12.1 years (interquartile range, 7.8-17.5 years). High BP and albuminuria were most prevalent, at 14.8% and 14.5%, respectively. Sixty-two survivors (4.5%) had an estimated GFR <90 ml/min per 1.73 m(2). Survivors who had undergone nephrectomy had the highest risk for diminished renal function (odds ratio, 8.6; 95% confidence interval [CI], 3.4-21.4). Combined radiation therapy and nephrectomy increased the odds of having elevated BP (odds ratio, 4.92; 95% CI, 2.63-9.19), as did male sex, higher body mass index, and longer time since cancer treatment. Almost 30% of survivors had renal adverse effects or high BP. Therefore, monitoring of renal function in high-risk groups and BP in all survivors may help clinicians detect health problems at an early stage and initiate timely therapy to prevent additional damage.


Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years.
A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment. We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years. By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (+/-SD) scores on the Number of Different Words test, a measure of word diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14 vs. 101+/-13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior. In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years.


Effect of interceptive extraction of deciduous canine on palatally displaced maxillary canine: a prospective randomized controlled study.
To evaluate the effect of the extraction of deciduous canines on palatally displaced canines (PDCs), to analyze the impact of the age of the patient on this interceptive treatment, and to assess the outcome of one-sided extraction of a maxillary primary canine on the midline of the maxilla. This study included 48 PDCs in 24 consecutive patients with bilateral PDCs. The mean age of the patients at diagnosis was 11.6 years (standard deviation 1.2 years). After randomization, one deciduous canine of each patient was assigned to extraction, and the contralateral side served as control. The patients were then followed at 6-month intervals for 18 months with panoramic and intraoral occlusal radiographs. The rates of successful eruption of the PDCs at extraction and control sites were 67% and 42%, respectively, at 18 months. The difference between the sites was statistically significant, and the effect was significantly more pronounced in the younger participants. A significant decrease in arch perimeter occurred at extraction sites compared to control sites during the observation period. No midline shift toward the extraction side was observed in any patient. The extraction of the deciduous canine is an effective measure in PDC cases, but it must be done in younger patients in combination with early diagnosis, at the age of 10-11 years. Maintenance of the perimeter of the upper arch is an important step during the observation period, and a palatal arch as a space-holding device is recommended.


Characterization of an NF-kappaB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells.
Micro RNAs (miRNAs) represent a family of small ribonucleic acids (RNAs) that are post-transcriptional regulators of messenger RNA (mRNA) complexity. Brain cells maintain distinct populations of miRNAs that support physiologically normal patterns of expression, however, certain miRNA abundances are significantly altered in neurodegenerative disorders such as Alzheimer's disease (AD). Here we provide evidence in human neural (HN) cells of an aluminum-sulfate- and reactive oxygen species (ROS)-mediated up-regulation of an NF-kappaB-sensitive miRNA-146a that down-regulates the expression of complement factor H (CFH), an important repressor of inflammation. This NF-kappaB-miRNA-146a-CFH signaling circuit is known to be similarly affected by Abeta42 peptides and in AD brain. These aluminum-sulfate-inducible events were not observed in parallel experiments using iron-, magnesium-, or zinc-sulfate-stressed HN cells. An NF-kappaB-containing miRNA-146a-promoter-luciferase reporter construct transfected into HN cells showed significant up-regulation of miRNA-146a after aluminum-sulfate treatment that corresponded to decreased CFH gene expression. These data suggest that (1) as in AD brain, NF-kappaB-sensitive, miRNA-146a-mediated, modulation of CFH gene expression may contribute to inflammatory responses in aluminum-stressed HN cells, and (2) underscores the potential of nanomolar aluminum to drive genotoxic mechanisms characteristic of neurodegenerative disease processes.


[Treatment of infertile women with epimestrol (author's transl)].
155 patients have been treated with epimestrol during 593 menstrual cycles in a daily dosage of 5, 10 or 2.5 mg from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 patients with secondary amenorrhoea, anovulatory cycles, ovulatory oligomenorrhoea, corpus luteum insufficiency, and normal cycles received epimestrol after an average period of 2.4 years of involuntary infertility. The pregnancy rate was 21% (n = 30), the spontaneous abortion rate 13% (n = 4). Twelve further patients not seeking pregnancy were treated with epimestrol because of secondary amenorrhoea and (or) anovulatory bleeding. The results were as follows: 1) In eugonadotropic secondary amenorrhoea 8 out of 12 patients ovulated, 5 out of 10 patients wanting children became pregnant. No patient with hypogonadotropism ovulated. 2) Out of 25 patients with anovulatory cycles or bleeding 13 ovulated and 4 became pregnant. 3) 17 out of 68 oligomenorrhoeic patients became pregnant. 4) In 12 out of 24 patients with corpus luteum insufficiency the hyperthermic phase improved and four patients became pregnant. 5) In 12 patients without anomalous cycles these remained unchanged and there were no pregnancies. 6) No side effects could be observed.


Salmonella enterica Serovar Enteritidis Liver Abscess after Blunt Abdominal Trauma.
Salmonella enterica serovar Enteritidis is among the most reported serotypes of Salmonella species worldwide, but is rarely reported as the causative agent of a liver abscess. We present a patient with an abdominal blunt trauma. An initial abdominal computed tomography scan revealed a rupture of the right kidney and of the liver. Two days later, his physical state deteriorated and a new computed tomography scan was obtained. An extremely large 8-centimetre liver abscess was verified. Due to the unsatisfying response to antibiotic therapy and percutaneous drainage, we operated on the patient. An appendectomy, cholecystectomy and bisegmental liver resection were performed. An intraoperative swab from the abscess was positive for Salmonella enterica serovar Enteritidis. The patient was given intravenous ciprofloxacine. The post-operative course was complicated by a Coagulase-negative Staphylococcus infection of the wound, which improved with antibiotic therapy. Blunt abdominal trauma may initiate an unpredictable course of the disease in chronic Salmonella carriers.


Triacylglycerol synthesis in goat mammary gland. The effect of ATP, Mg2+ and glycerol 3-phosphate on the esterification of fatty acids synthesized de novo.
Goat mammary-gland microsomal fraction by itself induces synthesis of medium-chain-length fatty acids by goat mammary fatty acid synthetase and incorporates short- and medium-chain fatty acids into triacylglycerol. Addition of ATP in the absence or presence of Mg2+ totally inhibits triacylglycerol synthesis from short- and medium-chain fatty acids, and severely inhibits synthesis de novo of medium-chain fatty acids. The inhibition by ATP of fatty acid synthesis and triacylglycerol synthesis de novo can be relieved by glycerol 3-phosphate. The effect of ATP could not be mimicked by the non-hydrolysable ATP analogue, adenosine 5'-[beta,gamma-methylene]triphosphate and could not be shown to be caused by inhibition of the diacylglycerol acyltransferase by a phosphorylation reaction. Possible explanations for the mechanism of the inhibition by ATP are discussed, and a hypothetical model for its action is outlined.


Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital-based cohort study.
To examine the burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa (HS). Information on HS and ten systemic comorbidities was obtained by interview and clinical examination, including blood pressure, body mass index (BMI) and blood samples, in a cohort of consecutive HS outpatients. A total of 302 patients were included. About 86.6% had at least one comorbidity. The mean number of comorbidities per patient was 2.1. One or more cardiovascular comorbidities were observed in 76.5% with evidence of substantial unawareness and undertreatment; 48.4% had hypertension, 9.3% had diabetes, 57.7% had dyslipidaemia and 36.7% were obese. About 6.6% had inflammatory bowel disease, 6.3% had arthritis, 29.5% had a psychiatric diagnosis, 5.6% had psoriasis, 7.9% had obstructive lung disease, and 6.6% had polycystic ovary syndrome. These comorbidities occurred at different time points in relation to the onset of HS with evidence of shared as well as differential risk factors. Age (per year), HR = 0.87 (0.79-0.96), P < 0.006, age of onset of HS (per year), HR = 1.26 (1.14-1.40), P < 0.001, male sex, HR = 2.51 (0.88-7.16), P = 0.086, Hurley stage III (vs. Hurley I + II), HR = 3.46 (1.25-9.58), P = 0.017, BMI (per unit), HR = 1.12 (1.04-1.20), P = 0.002, and blood glucose (per unit), HR = 1.27 (1.16-1.39), P < 0.001 were significant predictors for onset of diabetes. There is a substantial burden, unawareness and undertreatment of several systemic comorbidities in patients with HS. Comorbidities occur at different time points in relation to the onset of HS. This should lead to higher awareness among treating specialists.


Pseudotumor cerebri syndrome in childhood: incidence, clinical profile and risk factors in a national prospective population-based cohort study.
To investigate the epidemiology, clinical profile and risk factors of pseudotumor cerebri syndrome (PTCS) in children aged 1-16 years. A national prospective population-based cohort study over 25 months. Newly diagnosed PTCS cases notified via British Paediatric Surveillance Unit were ascertained using classical diagnostic criteria and categorised according to 2013 revised diagnostic criteria. We derived national age, sex and weight-specific annual incidence rates and assessed effects of sex and weight categories. We identified 185 PTCS cases of which 166 also fulfilled revised diagnostic criteria. The national annual incidence (95% CI) of PTCS in children aged 1-16 years was 0.71 (0.57 to 0.87) per 100 000 population increasing with age and weight to 4.18 and 10.7 per 100 000 in obese boys and girls aged 12-15 years, respectively. Incidence rates under 7 years were similar in both sexes. From 7 years onwards, the incidence in girls was double that in boys, but only in overweight (including obese) children. In children aged 12-15 years, an estimated 82% of the incidence of PTCS was attributable to obesity. Two subgroups of PTCS were apparent: 168 (91%) cases aged from 7 years frequently presented on medication and with headache and were predominantly female and obese. The remaining 17 (9%) cases under 7 years often lacked these risk factors and commonly presented with paralytic squint. This uniquely large population-based study of childhood PTCS will inform the design of future intervention studies. It suggests that weight reduction is central to the prevention of PTCS.


Coupling of aerobic glycolysis and Na+-K+-ATPase in renal cell line MDCK.
The relation between the activity of the Na+-K+-ATPase and the metabolic source of ATP was investigated in suspensions of MDCK cells. The pump activity of Na+-K+-ATPase was estimated from the initial rate of ouabain-sensitive K+ uptake into K+-depleted cells. Uptake was initiated by the reintroduction of K+ to the medium in which the cells were suspended. The metabolic source of ATP was varied by changing the substrates supplied to the suspension. Cells respiring on glutamine produced ATP from oxidative metabolism alone, whereas cells incubated with glucose and glutamine produced ATP via glycolysis and oxidative phosphorylation. Over a wide range of extracellular K+ concentrations, the initial rate of K+ uptake was faster in cells incubated with glucose and glutamine when compared with cells incubated with glutamine alone. Kinetic analysis together with ouabain-binding data demonstrated that this increase in K+ uptake was due to an increase in maximal velocity (Vmax) at a constant number of Na+-K+-ATPase transport sites. In addition, steady-state studies revealed that the addition of glucose to K+-depleted cells respiring on glutamine alone resulted in a net ouabain-sensitive influx of K+. These data demonstrate that in MDCK cells the maximal capacity for transport via the Na+-K+-ATPase is greater when ATP is produced from both glycolysis and oxidative phosphorylation than when ATP is produced from oxidative phosphorylation alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Light-activatable prodrugs based on hyaluronic acid biomaterials.
Photosensitive in situ cross-linked hyaluronan (HA) hydrogels are prepared by modular chemoselective assembly from the biopolymer precursors and novel heterobifunctional linkers with middle photo-labile ortho-nitrobenzyl group and orthogonally reactive terminals. Starting from the thiol-modified HA and a linker with activated disulfide and hydrazide terminals, a photo-degradable HA hydrogel was prepared by the hydrazone cross-linking reaction. Moreover, a light-triggered drug-releasing hydrogel prodrug was constructed by an orthogonal conjugation of dopamine (DA) via a photo-labile linker to HA dually modified with thiol and hydrazide groups (hy-HA-SH) and a subsequent cross-linking with aldehyde-derivatized HA (HA-al). On-demand release of DA from the hydrogel was achieved upon exposure of the hydrogel to UV light whereas 11-fold less release of the drug was observed in the absence of light. The mechanical properties of the hydrogels, photodegradation kinetics, photorelease of the model drugs were studied by rheology, spectrophotometry, chromatography, and mass spectrometry. For the first time, integration of photolabile components into an actual polysaccharide of extracellular matrix was implemented for the light-controlled release of drug molecules.


Subpectoral implantation of the vagus nerve stimulator.
To report the technique of subpectoral (SP) implantation of the vagus nerve stimulator (VNS) generator. We retrospectively reviewed and compared demographics and complications from patients receiving either subcutaneous (SQ; n = 107) or SP (n = 138) VNS implants, performed by one surgeon (WKD) between 1999 and 2003. Selection of implant location was made during the preoperative surgeon-patient consultation on the basis of surgeon recommendation and patient preference. The standard VNS generator implantation is performed within a SQ pocket in the left infraclavicular region of the chest. We have modified this technique by placing the generator into a deeper pocket SP, beneath the pectoralis major muscle, while tunneling the electrodes SQ in the usual fashion. The SP group was substantially younger (median age 19 yr) compared with the SQ group (median age 29 yr). At an average follow-up of 52 months for SQ implants and 28.4 months for SP implants, there were 2.9% infections per patient in the SQ group and 2.5% infections per patient in the SP group. There were three cases of excessive generator mobility in the SQ group; no cases occurred in the SP group. The SP implantation technique provides an attractive alternative to SQ VNS implantation. With increased soft tissue coverage, we provide improved cosmesis, increased wound durability to tampering and trauma, and a comparable infection rate with the SQ group.


Entirely intracanalicular meningioma: contrast-enhanced MR findings in a rare entity.
We report an unusual case of an entirely intracanalicular meningioma in a 51-year-old woman. Contrast-enhanced MR images showed an enhancing lesion filling the lateral portion of the left internal auditory canal. Our findings suggest that meningiomas should be considered in the differential diagnosis of entirely intracanalicular masses.


R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family: Clinical, Genetic, and Neuropathological Study.
The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. To investigate a large family with late-onset AD (LOAD), in which R47H cosegregated with 75% of cases. This study includes genetic and pathologic studies of families with LOAD from 1985 to 2014. A total of 131 families with LOAD (751 individuals) were included from the University of Washington Alzheimer Disease Research Center. To identify LOAD genes/risk factors in the LOAD123 family with 21 affected members and 12 autopsies, we sequenced 4 exomes. Candidate variants were tested for cosegregation with the disease. TREM2 R47H was genotyped in an additional 130 families with LOAD. We performed clinical and neuropathological assessments of patients with and without R47H and evaluated the variant's effect on brain pathology, cellular morphology, and expression of microglial markers. We assessed the effect of TREM2 genotype on age at onset and disease duration. We compared Braak and Consortium to Establish a Registry for Alzheimer's Disease scores, presence of α-synuclein and TAR DNA-binding protein 43 aggregates, and additional vascular or Parkinson pathology in TREM2 R47H carriers vs noncarriers. Microglial activation was assessed by quantitative immunohistochemistry and morphometry. Twelve of 16 patients with AD in the LOAD123 family carried R47H. Eleven patients with dementia had apolipoprotein E 4 (ApoE4) and R47H genotypes. We also found a rare missense variant, D353N, in a nominated AD risk gene, unc-5 homolog C (UNC5C), in 5 affected individuals in the LOAD123 family. R47H carriers demonstrated a shortened disease duration (mean [SD], 6.7 [2.8] vs 11.1 [6.6] years; 2-tailed t test; P = .04) and more frequent α-synucleinopathy. The panmicroglial marker ionized calcium-binding adapter molecule 1 was decreased in all AD cases and the decrease was most pronounced in R47H carriers (mean [SD], in the hilus: 0.114 [0.13] for R47H_AD vs 0.574 [0.26] for control individuals; 2-tailed t test; P = .005 and vs 0.465 [0.32] for AD; P = .02; in frontal cortex gray matter: 0.006 [0.004] for R47H_AD vs 0.016 [0.01] for AD; P = .04 and vs 0.033 [0.013] for control individuals; P < .001). Major histocompatibility complex class II, a marker of microglial activation, was increased in all patients with AD (AD: 2.5, R47H_AD: 2.7, and control: 1.0; P < .01). Our results demonstrate a complex genetic landscape of LOAD, even in a single pedigree with an apparent autosomal dominant pattern of inheritance. ApoE4, TREM2 R47H, and rare variants in other genes, such as UNC5C D353N, are likely responsible for the notable occurrence of AD in this family. Our findings support the role of the TREM2 receptor in microglial clearance of aggregation-prone proteins that is compromised in R47H carriers and may accelerate the course of disease.


Synthesis of High-Molecular-Weight Multifunctional Glycerol Polyhydroxyurethanes PHUs.
Glycerol carbonate acrylate is a 5-membered cyclic carbonate synthesized from glycerol that is used as a chemical coupling agent and has proven highly suitable for use in the synthesis of multifunctional polyhydroxyurethanes (PHUs). The multifunctionality of the structure of PHUs is determined by the density of the carbon-amine groups generated by the Aza-Michael reaction and that of the urethane groups and adjacent primary and secondary hydroxyl groups generated by aminolysis. Glycerol carbonate acrylate is polymerized with polyfunctional mono-, di-, tri, and tetra-amines, by type-AB polyaddition, either in bulk or in solution, through stepwise or one-pot reaction strategies in the absence of added catalysts. These approaches result in the generation of linear, interchain, and crosslinked structures, through the polyaddition of linear and branched amines to the ethylene and cyclic carbonate sites of glycerol carbonate acrylate. The resulting collection of organic molecules gives rise to polyethylene amino ester PHUs with a high molar mass, exceeding 20,000 g·mol(-1), with uniform dispersity.


Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study.
Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 109/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628.


Umbelliferone aminoalkyl derivatives as inhibitors of human oxidosqualene-lanosterol cyclase.
Human and murine lanosterol synthases (EC 184.108.40.206) were studied as targets of a series of umbelliferone aminoalkyl derivatives previously tested as inhibitors of oxidosqualene cyclases from other eukaryotes. Tests were carried out on cell cultures of human keratinocytes and mouse 3T3 fibroblasts incubated with radiolabeled acetate, and on homogenates prepared from yeast cells expressing human lanosterol synthase, incubated with radiolabeled oxidosqualene. In cell cultures of both human keratinocytes and mouse 3T3 fibroblasts, the observed inhibition of cholesterol biosynthesis was selective for oxidosqualene cyclase. The most active compounds bear an allylmethylamino chain in position-7 of the coumarin ring. The inhibition was critically dependent on the position and length of the inhibitor side chain, as well as on the type of aminoalkyl group inserted at the end of the same chain. Molecular docking analyses, carried out to clarify details of inhibitors/enzyme interactions, proved useful to explain the observed differences in inhibitory activities.


In vivo evaluation of the presence of bone marrow in cortical porosity in postmenopausal osteopenic women.
This is the first observational study examining cortical porosity in vivo in postmenopausal osteopenic women and to incorporate data from two different imaging modalities to further examine the nature of cortical porosity. The goal of this study was to combine high-resolution peripheral computed tomography (HR-pQCT) images, which contain high spatial resolution information of the cortical structure, and magnetic resonance (MR) images, which allow the visualization of soft tissues such as bone marrow, to observe the amount of cortical porosity that contains bone marrow in postmenopausal osteopenic women. The radius of 49 and the tibia of 51 postmenopausal osteopenic women (age 56 +/- 3.7) were scanned using both HR-pQCT and MR imaging. A normalized mutual information registration algorithm was used to obtain a three-dimensional rigid transform which aligned the MR image to the HR-pQCT image. The aligned images allowed for the visualization of bone marrow in cortical pores. From the HR-pQCT image, the percent cortical porosity, the number of cortical pores, and the size of each cortical pore was determined. By overlaying the aligned MR and HR-pQCT images, the percent of cortical pores containing marrow, the number of cortical pores containing marrow, and the size of each cortical pore containing marrow were measured. While the amount of cortical porosity did not vary greatly between subjects, the type of cortical pore, containing marrow vs. not containing marrow, varied highly between subjects. The results suggest that cortical pore spaces contain components of varying composition, and that there may be more than one mechanism for the development of cortical porosity.