Feasibility of bioelectrical impedance analysis in persons with severe intellectual and visual disabilities.
Body composition measurements provide important information about physical fitness and nutritional status. People with severe intellectual and visual disabilities (SIVD) have an increased risk for altered body composition. Bioelectrical impedance analysis (BIA) has been evidenced as a reliable and non-invasive method to asses body composition in healthy persons and various patient populations; however, currently, there is no feasible method available to determine body composition in people with SIVD. In this study, therefore, we aimed to assess the feasibility of BIA measurements in persons with SIVD. In 33 participants with SIVD and Gross Motor Functioning Classification System (GMFCS) Scale I, II, III, or IV, two BIA measurements were sequentially performed employing Resistance and Reactance in Ohm and fat-free mass (FFM) in kg as outcome variables, utilizing the Bodystat(®) QuadScan 4000. Feasibility was considered sufficient if ≥ 80% of the first measurement was performed successfully. Agreement between two repeated measurements was determined by using the paired t-test and Intraclass Correlation Coefficient (ICC; two way random, absolute agreement). Bland-Altman analyses were utilized to determine limits of agreement (LOAs) and systematic error. Agreement was considered acceptable if LOAs were <10% of the mean of the first measurement. The first BIA measurements were completed successfully in 88% of the participants. The paired t-test demonstrated no significant differences in Resistance, Reactance, and FFM between BIA Measurements 1 and 2 (P=0.140, 0.091, and 0.866). ICC was 0.965 (95% CI: 0.922-0.984) for Resistance; 0.858 (95% CI: 0.705-0.934) for Reactance; and 0.992 (95% CI: 0.982-0.996) for FFM. LOAs expressed as a percentage of the mean of Measurement 1 were 6.1% for Resistance, 17.6% for Reactance, and 3.8% for FFM. The results of this study suggest that BIA measurements seem to be feasible in persons with SIVD. Although these results require confirmation in a more extensive sample of persons with SIVD, the findings of this study are an important first step in the assessment of applicability of BIA measurements for non-invasive monitoring of physical fitness and nutritional status of persons with SIVD.


Cloning of a Thiobacillus ferrooxidans plasmid in Escherichia coli.
Three separate plasmids of 6, 7, 16, and greater than 23 kilobases were purified from a single clone of Thiobacillus ferrooxidans ATCC 33020 grown in the presence of uranium. The 6.7-kilobase plasmid (pTf1) was cloned separately into the HindIII or BamHI site of Escherichia coli plasmid pBR322. Restriction maps of the recombinant plasmids, termed pTf100 and pTf110, respectively, were constructed, creating potential cloning vehicles for exchanging genetic information between E. coli and T. ferrooxidans. Evidence from restriction enzyme analysis and Southern blot DNA-DNA hybridization indicates that the three native plasmids share little sequence homology.


Human Papilloma Virus Vaccination Among Adolescents in a Community Clinic Before and After Intervention.
Human Papilloma Virus (HPV) is the most common sexually transmitted disease with over 14 million infections in 2008. Certain HPV types have been identified in up to 70% of cases of cervical and anal cancers. Despite being safe and effective, HPV vaccination rates remain low. Vaccination and demographic data was collected pre-and post-intervention. Among 13 thru 17-year-old cohort females were significantly more likely to be fully vaccinated. Assessment also found that patients insured by Medicaid were significantly more likely to be fully vaccinated than patients insured privately. Post-intervention vaccination rate is similar to baseline rates. There was non-significant improvement in HPV vaccination coverage after intervention. Male and privately insured patients of Creighton's Pediatric Clinic have lower HPV vaccination coverage than their counterparts. More direct efforts are needed in vaccination process and policy in the clinic to improve immunization against HPV among children and adolescents.


Characteristics of abstinent substance abusers who first sought treatment in adolescence.
A survey was given to 141 male and female substance abusers who had eleven or more months of continuous abstinence and first sought treatment in adolescence in an attempt to add to the limited knowledge of known variables associated with successful adolescent response to clinical and community-based treatment. Results were used to create a composite of successfully abstinent adolescents. Generally, parental alcoholism and most drug use patterns were not related to the number of relapses or length of sobriety. Most of the respondents entered twelve-step programs via treatment. The only two variables that were significantly correlated with the dependent measures of more relapses and less overall sobriety were getting high for the first time at a younger age and polydrug abuse. There were about five times more adoptees represented in this sample than would be statistically expected. Implications for adolescent substance abuse diagnosis and prognosis are discussed.


Adsorption Behavior of Arabinogalactan-Proteins (AGPs) from Acacia senegal Gum at a Solid-Liquid Interface.
Adsorption of five different hyperbranched arabinogalactan-protein (AGP) fractions from Acacia senegal gum was thoroughly studied at the solid-liquid interface using a quartz crystal microbalance with dissipation monitoring (QCM-D), surface plasmon resonance (SPR), and atomic force microscopy (AFM). The impact of the protein/sugar ratio, molecular weight, and aggregation state on the adsorption capacity was investigated by studying AGP fractions with different structural and biochemical features. Adsorption on a solid surface would be primarily driven by the protein moiety of the AGPs through hydrophobic forces and electrostatic interactions. Increasing ionic strength allows the decrease in electrostatic repulsions and, therefore, the formation of high-coverage films with aggregates on the surface. However, the maximum adsorption capacity was not reached by fractions with a higher protein content but by a fraction that contains an average protein quantity and presents a high content of high-molecular-weight AGPs. The results of this thorough study highlighted that the AGP surface adsorption process would depend not only on the protein moiety and high-molecular-weight AGP content but also on other parameters such as the structural accessibility of proteins, the molecular weight distribution, and the AGP flexibility, allowing structural rearrangements on the surface and spreading to form a viscoelastic film.


Progress on norovirus vaccine research: public health considerations and future directions.
Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis (AGE) cases globally, and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. A norovirus vaccine should target high-risk populations, including the young and the elderly, and protect them against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development.


The twisted ion-permeation pathway of a resting voltage-sensing domain.
Proteins containing voltage-sensing domains (VSDs) translate changes in membrane potential into changes in ion permeability or enzymatic activity. In channels, voltage change triggers a switch in conformation of the VSD, which drives gating in a separate pore domain, or, in channels lacking a pore domain, directly gates an ion pathway within the VSD. Neither mechanism is well understood. In the Shaker potassium channel, mutation of the first arginine residue of the S4 helix to a smaller uncharged residue makes the VSD permeable to ions ('omega current') in the resting conformation ('S4 down'). Here we perform a structure-guided perturbation analysis of the omega conductance to map its VSD permeation pathway. We find that there are four omega pores per channel, which is consistent with one conduction path per VSD. Permeating ions from the extracellular medium enter the VSD at its peripheral junction with the pore domain, and then plunge into the core of the VSD in a curved conduction pathway. Our results provide a model of the resting conformation of the VSD.


Inhibition of calcitonin secretion by exogenous calcitonin in the rat.
The effect of synthetic salmon calcitonin (CT) on calcium- and pentagastrin-stimulated plasma CT was investigated in male Sprague-Dawley rats. Plasma samples were obtained before and 3 and 6 min after calcium (1 mg/100 g BW, iv) or pentagastrin (5 micrograms/100 g BW, iv) infusion. Although salmon CT at the dose of 0.4 MRC U/100 g BW administered 15 min before either the calcium or pentagastrin infusion did not influence circulating endogenous CT levels, salmon CT in doses of 4 and 20 U/100 g BW administered 15 min before the injection of secretogogues significantly reduced the response of CT to either calcium or pentagastrin without significantly changing plasma calcium levels from those of control animals. Salmon CT (20 U/100 g BW) given 5 min before pentagastrin infusion again significantly suppressed the response of plasma CT to this stimulus. Similarly, salmon CT administered chronically in a dose of 2 U/100 g BW for 28 days significantly reduced the response of CT to the calcium infusion. These data suggest that in the rat, at least pharmacological dosage of CT modulates the production and/or secretion of glandular CT itself.


Effect of sample handling and storage time on the stability of total CO2 in equine plasma.
The stability of total CO2 concentration (ctCO2) in plasma is influenced by storage temperature and handling during sample processing. Conflicting information exists regarding the stability of ctCO2 in equine plasma over time, and the effect of centrifugation on the measured value for plasma ctCO2 is unclear. To determine plasma ctCO2 stability over 5 days when equine blood is collected into Vacutainer tubes, centrifuged within 30 min of collection, and stored at 4 degrees C; and to determine whether a delay in centrifugation increases the rate at which plasma ctCO2 decreases over time. Blood was collected from 6 adult horses into 3 ml plastic Vacutainer tubes and randomly assigned to be centrifuged immediately, or after, storage. Plasma ctCO2 was measured in triplicate at 0, 24, 48, 72 and 96 h after collection using a NOVA-4 analyser Data were analysed using multivariable linear regression, with P < 0.05 being defined as significant. Plasma ctCO2 decreased linearly over time during storage at 4 degrees C. The measured value for ctCO2 decreased at a faster rate (-0.28 mmol/l/day; P < 0.0001) when centrifugation was delayed, compared with immediate centrifugation (-0.10 mmol/l/day). There was a significant effect of sequence of sample analysis on the ctCO2 value when measured in triplicate: the second and third measurements were 0.31 and 0.41 mmol/l lower than the first measurement, respectively. Blood samples collected from horses into Vacutainer tubes should be centrifuged immediately after collection and analysed as soon as possible to ensure accurate values for plasma ctCO2. Failure to centrifuge, or excessive delay in measuring ctCO2 after centrifugation, produces values significantly lower than the true value.


Silver staining of the supernumerary chromosome in the cat-eye syndrome.
A case of the Cat-eye syndrome (CES) with 47,YX, + mar is presented. Silver staining method revealed the marker chromosome to be bisatellited. This abnormal chromosome is interpreted as the product of a Robertsonian translocation between the short arm and satellites of chromosome 22 and short arm of another D-group chromosome, probably No. 13.


CLAST: CUDA implemented large-scale alignment search tool.
Metagenomics is a powerful methodology to study microbial communities, but it is highly dependent on nucleotide sequence similarity searching against sequence databases. Metagenomic analyses with next-generation sequencing technologies produce enormous numbers of reads from microbial communities, and many reads are derived from microbes whose genomes have not yet been sequenced, limiting the usefulness of existing sequence similarity search tools. Therefore, there is a clear need for a sequence similarity search tool that can rapidly detect weak similarity in large datasets. We developed a tool, which we named CLAST (CUDA implemented large-scale alignment search tool), that enables analyses of millions of reads and thousands of reference genome sequences, and runs on NVIDIA Fermi architecture graphics processing units. CLAST has four main advantages over existing alignment tools. First, CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT. Second, CLAST executes global alignment as the default (local alignment is also an option), enabling CLAST to assign reads to taxonomic and functional groups based on evolutionarily distant nucleotide sequences with high accuracy. Third, CLAST does not need a preprocessed sequence database like Burrows-Wheeler Transform-based tools, and this enables CLAST to incorporate large, frequently updated sequence databases. Fourth, CLAST requires <2 GB of main memory, making it possible to run CLAST on a standard desktop computer or server node. CLAST achieved very high speed (similar to the Burrows-Wheeler Transform-based Bowtie 2 for long reads) and sensitivity (equal to BLAST, BLAT, and FR-HIT) without the need for extensive database preprocessing or a specialized computing platform. Our results demonstrate that CLAST has the potential to be one of the most powerful and realistic approaches to analyze the massive amount of sequence data from next-generation sequencing technologies.


[Update on current care guidelines: antimicrobials in acute dentistry].
In most cases, acute oral infections originate from the dentition. The use of antimicrobials is secondary to appropriate dental care and does not allow postponing the elimination of the infection source. Medically compromised patients are more susceptible to odontogenic infection complications and antimicrobials have a more important role in their treatment. In the treatment of dental abscesses, a pre-operative 2 g single-dose of amoxicillin is recommended for all patients. An additional five to seven-day course of penicillin V or amoxicillin, in combination with metronidazole or clavulanic acid, should be considered, especially in the treatment of medically compromised patients.


Occurrence and Prediction of Flare After Tapering of Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis.
Patients with axial spondyloarthritis (axSpA) in clinical remission tapered tumor necrosis factor inhibitor (TNFi) therapy according to a clinical guideline. Over a 2-year follow-up period, we aimed to investigate flare frequency, dose at which flare occurred, type of flare, and predictors thereof. Patients in clinical remission (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 40, physician global score < 40, and without disease activity the previous year) tapered TNFi to two-thirds the standard dose at baseline, half at week 16, one-third at week 32, and discontinued at week 48. Flares were defined as BASDAI flare (BASDAI ≥ 40 and change ≥ 20 since inclusion), and/or clinical flare (development of inflammatory back pain, musculoskeletal or extraarticular manifestations, and/or Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 0.9), and/or magnetic resonance imaging (MRI) flare (≥ 2 new or worsened inflammatory lesions). Of 108 patients, 106 (99%) flared before 2-year follow-up: 29 patients (27%) at two-thirds standard dose, 21 (20%) at half dose, 29 (27%) at one-third dose, and 27 (25%) after discontinuation. Regarding type of flare, 105 (99%) had clinical flares, 25 (24%) had BASDAI flares, and 23 (29% of patients with MRI at flare available) had MRI flares. Forty-one patients (41%) fulfilled the Assessment of SpondyloArthritis international Society (ASAS) definition of clinically important worsening (≥ 0.9 increase since baseline). Higher baseline physician global score was an independent predictor of flare after tapering to two-thirds (OR 1.19, 95% CI 1.04-1.41, P = 0.01). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare. Almost all (99%) patients with axSpA in clinical remission experienced flare during tapering to discontinuation, but in over half of these patients, flare did not occur before receiving one-third dose or less. Higher physician global score was an independent predictor of flare.


An evaluation of the experiences of young people in Patient and Public Involvement for palliative care research.
The active involvement of patients and the public in the design and conduct of research (Patient and Public Involvement) is important to add relevance and context. There are particular considerations for involving children and young people in research in potentially sensitive and emotional subject areas such as palliative care. To evaluate the experiences of young people of Patient and Public Involvement for a paediatric palliative care research study. Anonymous written feedback was collected from group members about their experiences of Patient and Public Involvement in a paediatric palliative care research study. An inductive thematic analysis of the feedback was conducted using NVivo. Young people aged 12-22 years who were members of existing advisory groups at a children's hospital, hospice and the clinical research network in the West Midlands, UK. Feedback was provided by 30 young people at three meetings, held between December 2016 and February 2017. Three themes emerged: (1) Involvement: Young people have a desire to be involved in palliative care research, and recognise the importance of the subject area.(2) Impact: Researchers should demonstrate the impact of the involvement work on the research, by regularly providing feedback. (3) Learning: Opportunities to learn both about the topic and about research more widely were valued. Young people want to be involved in palliative care research, and recognise its importance. A continuous relationship with the researcher throughout the study, with clear demonstration of the impact that their input has on the research plans, are important.


PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in mouse HSC.
Increased expression of PDGF-beta receptors is a landmark of hepatic stellate cell activation and transdifferentiation into myofibroblasts. However, the molecular mechanisms that regulate the fate of the receptor are lacking. Recent studies suggested that N-acetylcysteine enhances the extracellular degradation of PDGF-beta receptor by cathepsin B, thus suggesting that the absence of PDGF-beta receptors in quiescent cells is due to an active process of elimination and not to a lack of expression. In this communication we investigated further molecular mechanisms involved in PDGF-beta receptor elimination and reappearance after incubation with PDGF-BB. We showed that in culture-activated hepatic stellate cells there is no internal protein pool of receptor, that the protein is maximally phosphorylated by 5 min and completely degraded after 1 h by a lysosomal-dependent mechanism. Inhibition of receptor autophosphorylation by tyrphostin 1296 prevented its degradation, but several proteasomal inhibitors had no effect. We also showed that receptor reappearance is time and dose dependent, being more delayed in cells treated with 50 ng/ml (48 h) compared with 10 ng/ml (24 h).


Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort.
Atazanavir (ATV) not boosted by ritonavir (uATV) has been frequently used in the past for switching combination antiretroviral therapy (cART). However, the clinical outcomes and predictors of such strategy are unknown. An observational study was carried out on the Italian MASTER, selecting HIV infected patients on cART switching to an uATV-containing regimen. Baseline was set as the last visit before uATV initiation. In the primary analysis, a composite clinical end-point was defined as the first occurring of any condition among: liver, cardiovascular, kidney, diabetes, non AIDS related cancer or death events. Incidence of AIDS events and incidence of composite clinical end-point were estimated. Kaplan-Meier and multivariable Cox regression analysis were used to assess predictors of the composite clinical end-point. 436 patients were observed. The majority of patients were males (61.5%) and Italians (85.3%), mean age was 42.7 years (IQR: 37.7-42), the most frequent route of transmission was heterosexual intercourse (47%), followed by injection drug use (25%) and homosexual contact (24%); the rate of HCV-Ab positivity was 16.3%. Patients were observed for a median time of 882 days (IQR: 252-1,769) under uATV. We recorded 93 clinical events (3 cardiovascular events, 20 kidney diseases, 33 liver diseases, 9 non AIDS related cancers, 21 diabetes, 7 AIDS events), and 19 deaths, accounting for an incidence of 3.7 (composite) events per 100 PYFU. At multivariable analysis, factors associated with the composite clinical end-point were intravenous drug use as risk factor for HIV acquisition vs. heterosexual intercourses [HR: 2.608, 95% CI 1.31-5.19, p = 0.0063], HIV RNA per Log10 copies/ml higher [HR: 1.612, 95% CI 1.278-2.034, p < 0.0001], number of switches in the nucleoside/nucleotide (NRTI) backbone of cART (performed to compose the uATV regimen under study or occurred in the past) per each more [HR: 1.085, 95% CI 1.025-1.15, p = 0.0051], Fib-4 score per unit higher [HR: 1.03, 95% CI 1.018-1.043, p < 0.0001] and Neutrophil/lymphocytes ratio (NLR inflammation score) per Log10 higher [HR: 1.319, 95% CI 1.047-1.662, p = 0.0188]. Intravenous drug users with high HIV RNA, high Fib-4 levels and more heavily exposed to antiretroviral drugs appeared to be more at risk of clinical events. Interestingly, high levels of inflammation measured through NLR, were also associated with clinical events. So, these patients should be monitored more strictly.


Development of pigmented scales on rat skin: relation to age, sex, strain, and hormonal effect.
Development of brownish scales on the skin was examined in seven inbred strains of laboratory rats, Rattus norvegicus (F344, WM, WF, LOU, BUF, ACI, and LEJ rats) up to 104 weeks old. Pigmented scales appeared mainly on the dorsum of the body but also on the perineum and the tail. The distribution of the scales changed with age and showed sex and strain differences. In males of all seven strains except F344, the scales on the dorsal region appeared at puberty then gradually developed and spread extensively in a strain-dependent pattern, until the rats were of adult age. The coloring gradually decreased with further aging. However, in F344 rats, the coloring did not spread after puberty, and in adult rats, it was partial and very weak. Among female rats, scales appeared only in LEJ rats when they were of adult and old age. Gonadectomy in WM and WF rats caused fading of the dorsal scales in males but slightly induced coloring in females. Androgen administration to the gonadectomized rats increased the pigmented scales in both sexes of both strains. In F344 rats, however, skin color was hardly changed by gonadectomy and/or the subsequent androgen administration in either sex. In F344 male rats, the testosterone concentration in serum was not significantly lower than that of WM and WF male rats. These results indicate that the development of brownish scales on rat skin is dependent on age, sex, strain, and androgen, and it is suggested that the ability producing the scales is genetically poor in the F344 strain.


[Usefulness of hepatic arterial infusion chemotherapy using lecithin-added lipiodol emulsion in hepatocellular carcinoma].
After implanting a reservoir in the hepatic artery, we performed intra-arterial chemotherapy with a smaller particle size lipiodol emulsion and examined its therapeutic effect. Subjects were 21 patients with advanced/recurrent hepatocellular carcinoma (HCC). Arterial infusion was performed once every 2 weeks on an outpatient basis using 2 mL lipiodol emulsion with lecithin added as a surface active agent and 10 mg doxorubicin hydrochloride. As of 6 months after the start of treatment, the response rate was 38.1%. Median survival was 17.0 months. Serious adverse events were not noted in any of the subjects;during the course of treatment, catheter occlusion was observed in 2 patients. This therapy allows fewer visits and provides a relatively substantial therapeutic effect while maintaining QOL, so it may serve as an effective treatment for highly advanced/multiple HCC not suited to other treatments.


[Design, synthesis and activity of N-acyl-thiochromenothiazol-2-amine as acetylcholinesterase inhibitors].
A series of novel N-acyl-thiochromenothiazol-2-amine derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase was investigated. N-Acyl-thiochromenothiazol-2-amines were prepared from thiophenol by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on AChE, and the compound 10a was the best in them. The IC50 of 10a to AChE is 7.92 μmol x L(-1), and the value is better than that of rivastigmine. N-Acyl-thiochromenothiazol-2-amine derivatives showed a certain bioactivity in vitro, which were worth further investigation.


Postconcussive Symptoms, PTSD, and Medical Disease Burden in Treatment-Seeking OEF/OIF/OND Veterans.
The most common psychological and cognitive sequelae associated with deployments to Afghanistan (Operation Enduring Freedom) and Iraq (Operation Iraqi Freedom) are mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). High rates of PTSD are often observed among Veterans with a history of mTBI, and persistent postconcussive symptoms commonly endorsed after mTBI are known to be associated with PTSD. Therefore, this study examined whether PTSD mediates relations between postconcussive symptoms and 2 indices of medical disease burden: 1) the number of disease categories positive for a diagnosis, or system disease burden, and 2) total number of physical diagnoses, or cumulative disease burden. Participants were 91 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans seeking treatment at a Veterans Affairs Medical Center who screened positive for mTBI and later attended a follow-up Polytrauma clinic evaluation for neuropsychiatric assessment. Medical records were reviewed for a history of mTBI, postconcussive symptoms, and physician diagnoses, which were used to derive system and cumulative disease burden variables. Mediation was tested using bootstrapping procedures. Participants provided written informed consent and all study procedures were approved by both the VA and university institutional review boards. Postconcussive symptoms (r = 0.53) and PTSD symptoms (r = 0.32) were both associated with cumulative disease burden. Only postconcussive symptoms were associated with system disease burden (r = 0.32). Results of our follow-up mediation analysis suggest that PTSD did not mediate relations between postconcussive symptoms and cumulative disease burden (bootstrap coefficient = -0.02, 95% confidence interval [-0.05 to 0.01]). These findings join an emerging body of literature suggesting that postconcussive symptoms have a direct impact on Veterans' health above and beyond the effects of PTSD. Strengths of this study include the use of objective, clinician-diagnosed medical conditions as an indicator of health, whereas limitations include the use of self-report measures to assess postconcussive and PTSD symptoms. This study underscores the need for more original research on the impact of mTBI on the long-term health and readjustment of returning Veterans. Furthermore, this study highlights the need for additional research on the psychosocial and pathophysiological mechanisms underlying the link between mTBI and poor health.


Mitomycin C in Filtering Surgery for Primary Congenital Glaucoma: A Comparison of Exposure Durations.
To compare the effect of two exposure durations of mitomycin C in combined angle and filtering surgery for primary congenital glaucoma. This was a prospective study conducted in the Department of Ophthalmology at Alexandria Main University Hospital, Alexandria, Egypt, on 75 eyes with primary congenital glaucoma that underwent combined trabeculotomy-trabeculectomy with intraoperative mitomycin C application for 1 minute (MMC 1) or 2 minutes (MMC 2) and were followed up for 24 months. Success rates were studied and complications noted. Success was defined by a composite primary end point of an intraocular pressure (IOP) of less than 16 mm Hg under general anesthesia, without any IOP-lowering medications and with no hypotony-related complications and/or lack of IOP-related progression of the disease as evidenced by worsening of the ocular biometric characteristics. The mean age of the study participants was 6.7 ± 4.1 months (range: 2 to 16 months; median: 6 months) in the MMC 1 group (35 eyes) and 7.7 ± 5.7 months (range: 1 to 32 months; median: 6.5 months) in the MMC 2 group (40 eyes). The initial surgery was successful in 32 (91.5%) and 31 (77.5%) eyes in the MMC 1 and MMC 2 groups, respectively. The mean IOP was 18.4 ± 5.1 and 18.1 ± 6.1 mm Hg preoperatively and 5.5 ± 3.5 and 4.8 ± 2.8 mm Hg at the end of follow-up in the MMC 1 and MMC 2 groups, respectively. There was no statistically significant difference in the clinical parameters between the two groups. Complications included cataracts in each group and hypotony optic disc edema in 3 eyes (7.5%) in the MMC 2 group. Both mitomycin C application durations were effective in combined trabeculotomy-trabeculectomy with mitomycin C for primary congenital glaucoma. The longer duration was not advantageous in disease control and there were no significant differences in complications. [J Pediatr Ophthalmol Strabismus. 2018;55(3):164-170.].


Hope from Abroad in the International Medical Travel of Yemeni Patients.
Studies of care-seeking behaviour have generally focused only on the medical facilities that are available within a country's national boundaries. However, a growing number of patients worldwide are pursuing medical services outside of their own countries. The burgeoning literature on 'medical tourism' tends to offer the perspectives of the treatment destinations, not the experiences of patients. This paper examines the international medical travel of patients from the capital-poor country of Yemen. Families in Yemen often sacrifice greatly to seek the advanced, trustworthy technological medicine that is unavailable locally. The paper draws on interviews conducted with 71 Yemeni medical travellers in India and Jordan, as well as a survey of 205 doctors in Yemen about their disclosure practices regarding terminally ill patients. While perhaps an attractive option in today's global world, the use of medical services abroad affects local perceptions: it perpetuates a lack of trust in local capabilities, invites criticism of the government for not providing care to its citizens and fosters the hope that a cure exists somewhere in the world.


Oropharyngeal aspiration of Burkholderia mallei and Burkholderia pseudomallei in BALB/c mice.
Burkholderia mallei and Burkholderia pseudomallei are potentially lethal pathogens categorized as biothreat agents due, in part, to their ability to be disseminated via aerosol. There are no protective vaccines against these pathogens and treatment options are limited and cumbersome. Since disease severity is greatest when these agents are inhaled, efforts to develop pre- or post-exposure prophylaxis focus largely on inhalation models of infection. Here, we demonstrate a non-invasive and technically simple method for affecting the inhalational challenge of BALB/c mice with B. pseudomallei and B. mallei. In this model, two investigators utilized common laboratory tools such as forceps and a micropipette to conduct and characterize an effective and reproducible inhalational challenge of BALB/c mice with B. mallei and B. pseudomallei. Challenge by oropharyngeal aspiration resulted in acute disease. Additionally, 50% endpoints for B. pseudomallei K96243 and B. mallei ATCC 23344 were nearly identical to published aerosol challenge methods. Furthermore, the pathogens disseminated to all major organs typically targeted by these agents where they proliferated. The pro-inflammatory cytokine production in the proximal and peripheral fluids demonstrated a rapid and robust immune response comparable to previously described murine and human studies. These observations demonstrate that OA is a viable alternative to aerosol exposure.


Herbicidal Spectrum, Absorption and Transportation, and Physiological Effect on Bidens pilosa of the Natural Alkaloid Berberine.
Berberine is a natural herbicidal alkaloid from Coptis chinensis Franch. Here we characterized its herbicidal spectrum and absorption and transportation in the plant, along with the possible mechanism. Berberine showed no effect on the germination of the 10 tested plants. The IC50 values of berberine on the primary root length and fresh weight of the 10 tested plants ranged from 2.91 to 9.79 mg L-1 and 5.76 to 35.07 mg L-1, respectively. Berberine showed a similar herbicidal effect on Bidens pilosa as the commercial naturally derived herbicide cinmethylin. HPLC and fluorescence analysis revealed that berberine was mainly absorbed by B. pilosa root and transported through vascular bundle acropetally. Enzyme activity studies, GC-MS analysis, and SEM and TEM observations indicated that berberine might first function on the cell membrane indicated by variation of the IUFA percent and then cause POD, PPO, and SOD activity changes and cellular structure deformity, which was eventually expressed as the decrease of cell adaptation ability and abnormal cell function and may even result in cell death. Environmental safety evaluation tests revealed that berberine was low in toxicity to Brachydanio rerio. These indicate that berberine has the potential to be a bioherbicide and/or a lead molecule for new herbicides.


Sevoflurane anesthesia following administration of atropine-guaifenesin-thiopental in spontaneous-breathing adult cattle.
The effect of sevoflurane-oxygen anesthesia at surgical depth on clinically important features was evaluated in spontaneously breathing cattle given atropine-guaifenesin-thiopental. The mean end-tidal sevoflurane concentrations ranged from 1.4 to 2.0% for 75 min maintenance. Recovery from anesthesia was extremely rapid and smooth. Heart rate increased and arterial pressure was higher during anesthesia, but respiratory rate did not change significantly. Arrhythmia was not observed. Minute ventilation was low due to decreased tidal volume during anesthesia, and changes in blood gases and pH showed mild respiratory acidosis. There were no marked changes in hematologic or serum biochemical values for 7 days postanesthesia. These findings suggest that sevoflurane is an effective inhalant anesthetic showing rapid recovery from anesthesia.


BPH/LUTS and ED: common pharmacological pathways for a common treatment.
This article reviews the current literature on common physiopathogenetic factors and pharmacological pathways of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men and their implications for diagnosis and treatment. A literature search was conducted to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: lower urinary tract symptoms, erectile dysfunction and phosphodiesterase type 5 inhibitors (and their abbreviations LUTS, ED and PDE5-Is). We identified manuscripts presenting: (i) The existence of several newly discovered common pathophysiological mechanisms of LUTS and ED indicating that PDE5-Is might represent an alternative to current treatments of men with LUTS (e.g., α1-adrenergic blockers and 5α-reductase inhibitors); (ii) Randomized controlled clinical trials have shown that treatment with PDE5-Is is associated with improvements in both LUTS and ED in men with significant problems in both areas. The presence of common pathophysiological mechanisms between LUTS and ED seems well recognized and needs further exploration. Further comparisons between different PDE5-Is would be useful to determine the most appropriate regimen and their efficacy to safety ratio.


A long-term outcome study of tardive dyskinesia in patients on antipsychotic medication.
We followed 28 patients with tardive dyskinesia (TD) (eight men and 20 women, mean age 55.1 years) for 11-12 years to elucidate the long-term outcome of TD. All the patients received their physicians' choice of therapy, mainly comprising antipsychotics. The severity of TD was assessed at 5 and 11-12 years after the baseline evaluation. TD did not disappear in any patient. The severity of TD was unchanged in 39.3%, and improved in 17.9% despite continuous treatment with low doses of antipsychotics (mean 221.4 mg chlorpromazine equivalent daily). TD fluctuated in 21.4% and worsened in only 21.4%. Outcome was not correlated with patient sex or age, duration of primary illness, dosage of antipsychotics, or changes in dosage. The initial severity of TD showed some relationship to outcome. The number of bodily areas affected by TD increased in some patients with unchanged TD severity.


Rock bottom is right.
I agree with the findings of your survey of NHS staff (analysis, 22 March). However, I thought the percentage who said morale was at rock bottom would have been higher.


Two families of repeated DNA sequences in Thiobacillus ferrooxidans.
The genome of Thiobacillus ferrooxidans ATCC 19859 is about 2.8 X 10(6) base pairs as determined by analysis of reassociation kinetics of sheared DNA. This is 70% of the size of the genome of Escherichia coli. About 6% of the genome of T. ferrooxidans consists of moderately repetitive DNA sequences that are repeated an average of 20 times per genome. Two distinct repeated sequences, designated family 1 and family 2, have been analyzed in more detail. Both families are approximately 1 kilobase in length and are repeated 20 to 30 times per genome. Preliminary evidence from restriction enzyme analysis, Southern blotting experiments, and thermal melting analysis indicates that members of both families are conserved and are interspersed with single-copy DNA. Six copies of one family are present on the 45-kilobase-pair plasmid of strain ATCC 19859.


Calcium-Mediated Biophysical Binding of Cryptosporidium parvum Oocysts to Surfaces Is Sensitive to Oocyst Age.
Cryptosporidium parvum causes potentially life-threatening gastrointestinal disease in humans and may not be effectively removed from drinking water via conventional methods. Prior research has shown that environmental biofilms immobilize oocysts from the water column, but the biophysical mechanisms driving this attraction are still under investigation. This study investigates the affinity of C. parvum oocysts to silanized surfaces. Surfaces were prepared with hydroxyl, amine, and carboxyl moieties. Binding forces between the oocysts and these engineered substrates were analyzed, with and without divalent ions, using atomic force microscopy. Binding forces were measured over several weeks to investigate the influence of age on adhesion. C. parvum oocysts bind most strongly to carboxylic acid functional groups, with rupture forces greater than that required to break noncovalent molecular bonds, regardless of oocyst age. This adhesion is shown to be due to divalent cation bridging mechanisms. In addition, the binding strength increases over a 5-week period as the oocysts age, followed by a decrease in the binding strength, which may be related to structural or biochemical changes in the outer wall-bound glycosylated proteins. This study sheds new light on the biochemical parameters that influence C. parvum oocyst binding to surfaces. Increased understanding of how age and water chemistry influence the binding strength of oocysts may inform future developments in environmental detection and drinking water treatment, such as with the development of oocyst-specific sensors that allow for more frequent tracking of oocysts in the environment.IMPORTANCE The mechanisms by which pathogens bind to surfaces are of interest to a wide variety of scientific communities, as these mechanisms drive infectivity, fate, and transport of the pathogenic organisms. This study begins to reveal the mechanism of direct binding of Cryptosporidium parvum to surfaces containing both carboxylic acid and amine moieties, in an attempt to understand how much of the binding ability is due to long-range electrostatic forces versus other mechanisms (specific or nonspecific) of bonding. In addition to improving the scientific understanding of fate and transport of oocysts, an expanded understanding of the binding mechanisms may aid in the development of new tools and sensors designed to detect and track oocysts in waterways. Furthermore, the methods used to examine binding in this study could be translated to other waterborne pathogens of interest.


The effect of the steroidal androgen receptor antagonist, Win 49,596, on the prostate and testis of beagle dogs.
The effect of the steroidal androgen receptor antagonist Win 49,596 on the prostate and testis was studied in beagle dogs and was compared to the effects of the nonsteroidal androgen receptor antagonist ICI 176,334 and the steroidal 5 alpha-reductase inhibitor MK-906. Win 49,596 was shown to bind to the androgen receptor from normal canine prostate with a Ki of 2.2 microM. After 16 weeks of treatment, prostate size, as estimated by transrectal ultrasonography, was unchanged in intact controls and was 26% of the initial size in castrate controls. Oral doses of Win 49,596 from 0.625-40 mg/kg.day for 16 weeks caused dose-dependent prostatic regression and a dose-related increase in both the incidence and severity of glandular atrophy of the prostate. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at 40 mg/kg.day on prostatic weight, total DNA, histomorphology, and secretory function were similar to those of castration, while the effects of Win 49,596 at 10 mg/kg.day were similar to those of ICI 176,334 at 0.25 mg/kg.day and MK-906 at 1.0 mg/kg.day. No effects on testicular weight, daily sperm production, or spermatogenesis were observed; however, mild Leydig cell hyperplasia was observed in two dogs treated with 40 mg/kg.day Win 49,596. In addition, at 10 and 40 mg/kg.day Win 49,596, moderate but variable increases in serum testosterone levels were observed. In summary, Win 49,596 caused regression of the hypertrophic canine prostate without effects on spermatogenesis and/or sexual function, supporting its possible use in the treatment of human benign prostatic hypertrophy/hyperplasia.


The urgent need for HIV and hepatitis prevention in drug treatment programs in Hungary.
We assess HIV and hepatitis testing and counseling in drug treatment programs in Hungary, a country with low rates of HIV but high rates of hepatitis C among injection drug users. The official context of drug treatment programs is described, and using key informants from representative drug treatment programs, the practice of HIV and hepatitis testing and counseling in such programs is assessed. Although HIV testing and counseling occurs, testing and counseling for hepatitis B and C are rare, especially in outpatient settings, and sexual risk in the drug use context is ineffectively addressed by treatment programs. Drug treatment centers are not adequately addressing the need to provide either HIV or hepatitis prevention services. There is an urgent need for preventing HIV and related infections among drug users by integrating HIV and hepatitis B and C prevention with drug treatment.


Deficiency of the insulin, glucose-mediated decrease in serum triglycerides in normolipidemic obese subjects.
The effects of a 6-h insulin, glucose infusion on lipid metabolism were compared in 29 normolipidemic obese and 20 control subjects. Alterations in serum triglycerides (TG), cholesterol, and high-density lipoprotein (HDL) cholesterol were similar within groups when either 40 or 120 mU/m2 per min of regular insulin were infused. Although changes in the HDL cholesterol responses to the insulin, glucose infusions were also similar in obese and control subjects, TG fell more in insulin, glucose-infused controls (35 +/- 4 mg/dl, means +/- s.e.m.) than obese subjects (23 +/- 3) (P less than 0.001). The rate and magnitude of the insulin, glucose-mediated fall in free fatty acids, however, were not different between the two groups. This diminished responsiveness of TG to an insulin, glucose infusion in normotriglyceridemic obese subjects is another manifestation of the insulin resistance of obesity.


Topoisomerases and tubulin inhibitors: a promising combination for cancer treatment.
Modern approaches to treatment of cancer seek to activate the internal suicide program in the malignant cells, and thereby effectively eliminate them without engaging most of other bodily systems. Many currently used cytostatics are known to induce apoptosis and efforts are being paid to develop new ones with better and more effective proapoptotic potential. Nevertheless, despite recent developments in this field, there are still numerous malignancies showing a varying degree of resistance to cell death due to the corrupted signaling pathways and genetic alterations, often in conjunction with expansive proliferation rate. It has been shown that topoisomerase inhibiting agents such as etoposide, camptothecin and others represent a powerful and dynamic group of cytostatic chemicals used in experimental and clinical conditions. So, it is a group of microtubule targeting poisons comprising classical colchicines on the one hand and new taxanes on the other hand. Since several members of both groups have been evidenced as apoptosis inducers operating via distinct mechanism, their combination should theoretically enhance the final therapeutic outcome. This minireview focuses on the possibilities of such a combinational approach with respect to possible benefits and hazards of this strategy.


[MCTD (mixed connective tissue disease)].
Mixed connective tissue disease (MCTD) was proposed by Sharp and others in 1972. MCTD is a unique disease in which the presence of nuclear RNP antibody is characteristic and the patient shows partial symptoms of SLE, PSS and or PM/DM. Among them, Raynaud's phenomenon and sausage like finger or swollen hand are the most common symptoms. Although patients with MCTD generally respond to small amount of corticosteroid and the prognosis is not so bad, some patients with MCTD especially those with pulmonary hypertension show high mortality.


Long term Suboxone™ emotional reactivity as measured by automatic detection in speech.
Addictions to illicit drugs are among the nation's most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states ("true ground emotionality") in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of "true" emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate "true ground" emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.


Overweight and at-risk for overweight among Hawai'i public school students entering kindergarten, 2002-2003.
Recent studies have pointed to an increasing problem of overweight and obesity in children in Hawai'i, but all of these studies have been conducted in specific communities or special population groups. No broad population-based studies have been conducted to document the extent of overweight in the general population of children in Hawai'i. To provide a population based estimate of overweight in Hawai'i's children, this study examined Student Health Records for 10, 199 children entering kindergarten in public schools during 2002-2003. Data on age, gender, height, and weight were used to calculate BMI (body mass index) scores. Because records for all students entering public school kindergarten were available for analysis, the data presented here represents the broadest estimates of overweight and at risk for overweight in Hawai'i's children published to date. The results illustrate that almost one-third of the children aged 4-6 years old entering Hawai'i public schools are either overweight or at risk for overweight. Rates are higher in rural school complexes than urban ones. Compared to a 1984 study that found 'no significant under or over nutrition' in Hawai'i's school children, our results suggest that almost one-third of children aged 4-6 entering Hawai'i public schools are either overweight or at risk for overweight. Physicians should be aware of this growing problem, and seek to implement practices to combat overweight among their pediatric patients and families.


Reactions of 1-alkyl-1,2-diphospholes with 1,3-dipoles: diphenyldiazomethane and nitrones.
The reaction of 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes (1-alkyl-1,2-diphospholes) (1) with diphenyldiazomethane proceeds at room temperature via unstable [3+2] cycloadducts to form bicyclic phosphiranes (2). However, 1-alkyl-1,2-diphospholes (1) react with N,alpha-diphenylnitrone or N-tert-butyl-alpha-phenylnitrone depending on the temperature to give either dimers of 1-alkyl-1-oxo-1,2-diphospholes (5) or 1-alkyl-1,7-dioxo-6-azo-1,7-diphospha-bicyclo[3.2.0]hept-2-enes (7) - phosphorus analogues of β-lactams.


Treatment of diabetic (neuropathic) foot ulcers with two-stage debridement and closure.
We reviewed 33 patients with 37 wounds treated between November of 1991 and December of 1995 in the Wound Care Center. A two-stage debridement and closure technique for neuropathic foot ulcers was performed. Patients selected included those with obvious osteomyelitis and those who had failed nonsurgical treatment. The approach included initial surgical excision of the ulcer with biopsy, bone resection with biopsy, and deep culture. The second-stage procedure 4 to 8 days later included debridement of the wound and delayed closure. Intravenous antibiotic treatment using a central line was given postoperatively in patients with documented osteomyelitis for at least 6 weeks and in patients with infected soft tissues only for about 4 weeks. All patients remained nonweightbearing for 4 weeks; this was felt necessary to prevent separation of the wound edges. Four wounds in four patients failed to heal, and two of these went on to amputation. Satisfactory healing occurred in 29 of 33 patients and in 33 of 37 wounds. The authors conclude that two-stage surgical debridement and closure is an acceptable treatment in selected nonhealing diabetic (neuropathic) foot ulcers.


Ionic liquids supported on metal-organic frameworks: remarkable adsorbents for adsorptive desulfurization.
Acidic ionic-liquids (IL) supported on metal-organic frameworks (MOFs) have been shown to be beneficial for adsorptive desulfurization. A remarkable improvement in the adsorption capacity (ca. 71%) was observed in for ILs supported on MIL-101 compared with virgin MIL-101. The improved adsorptive performance might be explained by the acid-base interactions between the acidic ionic liquid and basic benzothiophene (BT). Moreover, from this study, it can be suggested that porous MOFs, supported with ionic liquids, may introduce a new class of highly porous adsorbents for the efficient adsorption of various compounds.


Percutaneous drainage of thoracic collections.
Various infected and noninfected thoracic fluid collections may be diagnosed and treated by interventional radiologic techniques. The core procedure of ultrasound-guided thoracentesis has been expanded to allow catheter drainage of empyema, bronchopleural fistula, abscesses in the lung, mediastinum, pericardium, and infected tumors. Tailored use of guidance methods permits effective evacuation of most of these abscesses and noninfected collections. This paper details the authors' approach to each of these entities while highlighting the results and expected pitfalls of these techniques.


Synthesis, Crystal Structures, and Magnetic and Electrochemical Properties of Highly Phenyl Substituted Trinuclear 5,6,11,12,17,18-Hexaazatrinaphthylene (HATNPh6)-Bridged Titanium Complexes.
Trinuclear titanium complexes coordinated by one ligand with three coordination sites have shown properties of mixed valency and a high number of reversible redox steps. Herein we report on the hexaphenyl-substituted derivative (Cp2Ti)3(μ3-HATNPh6) (2). On reaction of 2 with the ferrocenium salt [Cp2Fe]BF4, the cationic complexes [(Cp2Ti)3(μ3-HATNPh6)] n+ ( n = 1-3; 3-5) become available in a selective way. Cyclic voltammograms show 10 reversible redox states of the trinuclear species 2 without decomposition. In order to classify the degree of electronic communication between the titanium centers, comproportionation constants Kc, IVCT bands in NIR spectra, and magnetic measurements were analyzed. These parameters show strong coupling effects between the titanium centers but no full delocalization. In addition, single-crystal X-ray analysis of the neutral complex 2 and its oxidation products (1+ (3), 2+ (4), and 3+ (5)) revealed the geometric structure of the molecule in the solid state. For the cationic species anion-π interactions between the electron-deficient central ring of the HATNPh6 ligand and BF4- counterions were found.


Contribution of oxidative stress and growth factor receptor transactivation in natriuretic peptide receptor C-mediated attenuation of hyperproliferation of vascular smooth muscle cells from SHR.
Earlier studies have shown the implication of growth factor receptor activation in angiotensin II (Ang II)-induced hyperproliferation of aortic VSMC as well as in hyperproliferation of VSMC from spontaneously hypertensive rats (SHR). We previously showed that NPR-C specific agonist C-ANP4-23 attenuates the hyperproliferation of VSMC from SHR through the inhibition of MAP kinase, Giα protein signaling and overexpression of cell cycle proteins. The aim of the present study was to investigate if C-ANP4-23- mediated attenuation of hyperproliferation of VSMC from SHR also involves growth factor receptor activation and upstream signaling molecules. For this study, C-ANP 4-23 (10 nmole/kg body weight) was injected intraperitoneally into 2 week-old prehypertensive SHR and Wistar Kyoto (WKY) rats twice per week for 6 weeks. The blood pressure in SHR was significantly attenuated by C-ANP4-23 treatment. In addition, C-ANP4-23 treatment also attenuated the hyperproliferation of VSMC from SHR as well as the enhanced phosphorylation of EGF-R, PDGF-R, IGF-R and c-Src. Furthermore, the enhanced levels of superoxide anion, NADPH oxidase activity, and enhanced expression of Nox4,Nox1,Nox2 and P47phox in SHR compared to WKY rats was also significantly attenuated by C-ANP4-23 treatment. In addition, N-acetyl cysteine (NAC), a scavenger of O2-, inhibitors of growth factor receptors and of c-Src, all inhibited the overexpression of cell cycle proteins cyclin D1 and cdk4 in VSMC from SHR. These results suggest that in vivo treatment of SHR with C-ANP4-23 inhibits the enhanced oxidative stress, c-Src and EGF-R, PDGF-R, IGF-R activation which through the inhibition of overexpression of cell cycle proteins result in the attenuation of hyperproliferation of VSMC.


Effect of pentosan polysulphate on endothelial regeneration.
Endothelium was removed from rabbit aortae using a balloon catheter and the endothelial outgrowth was measured. In the controls, after initial regrowth of approximately 4 weeks, endothelial regeneration stopped before cellular regrowth was complete. However, when treated with daily subcutaneous injections of pentosan polysulphate (PPS) (8 mg/kg/day), endothelium fully repopulated the denuded areas 16 weeks after beginning of the treatment. These results illustrate the possibility of using pentosan polysulphate in the prevention of atherogenesis, by enhancing endothelial regeneration.


Benefit adequacy among elderly Social Security retired-worker beneficiaries and the SSI federal benefit rate.
Both target effectiveness and administrative simplicity are desirable properties in the design of minimum benefit packages for public retirement programs. The federal benefit rate (FBR) of the Supplemental Security Income (SSI) program has been proposed by some analysts as a potentially attractive basis of establishing a new minimum benefit for Social Security on both of these grounds. This type of proposal is related to a broader array of minimum benefit proposals that would establish a Social Security benefit floor based on the poverty rate. In contrast to Social Security, the SSI program is means tested, including both an income and asset screen and also a categorical eligibility screen (the requirement to qualify as aged or disabled). The SSI FBR provides an inflation-adjusted, guaranteed income floor for aged and disabled people with low assets. The FBR has been perceived by proponents as a minimal measure of Social Security benefit adequacy because it represents a subpoverty income level for a family of one or two depending on marital status. For this same reason it has been seen as a target-effective tool of designing a minimum Social Security benefit. An FBR-based minimum benefit has also been viewed as administratively simple to implement; the benefit can be calculated from Social Security administrative records using a completely automated electronic process. Therefore-in contrast to the SSI program itself-an FBR-based minimum benefit would incur virtually no ongoing administrative costs, would not require a separate application for a means-tested program, and would avoid the perception of welfare stigma. While these ideas have been discussed in the literature and among policymakers in the United States over the years, and similar proposals have been considered or implemented in several foreign countries, there have been no previous analyses measuring the size of the potentially affected beneficiary population. Nor has there been any systematic assessment of the FBR as a measure of benefit adequacy or the tradeoffs between potential target effectiveness and administrative simplicity. Based on a series of simulations, we assess the FBR as a potential foundation for minimum Social Security benefits and we examine the tradeoffs between administrative simplicity and target effectiveness using microdata from the 1996 panel of the Survey of Income and Program Participation (SIPP). Our empirical analysis is limited to Social Security retired-worker beneficiaries aged 65 or older. We start with the assessment of the FBR as a measure of benefit adequacy. We are particularly concerned about two types of error: (1) incorrectly identifying some Social Security beneficiaries as "economically vulnerable," and (2) incorrectly identifying others as "not economically vulnerable." Operationally we measure economic vulnerability by two alternative standards. One of our measures considers beneficiaries with family income below the official poverty threshold as vulnerable. Our second measure is more restrictive; it uses a family income threshold equal to 75 percent of the official poverty threshold. We find that a substantial minority of retired workers have Social Security benefits below the FBR. The results also show that the FBR-based measure of Social Security benefit adequacy is very imprecise in terms of identifying economically vulnerable people. We estimate that the vast majority of beneficiaries with Social Security benefits below the FBR are not economically vulnerable. Conversely, an FBR-level Social Security benefit threshold fails to identify some beneficiaries who are economically vulnerable. Thus an FBR-level minimum benefit would be poorly targeted in terms of both types of errors we are concerned about. An FBR-level minimum benefit would provide minimum Social Security benefits to many people who are clearly not poor. Conversely, an FBR-level minimum benefit would not provide any income relief to some who are poor. The administrative simplicity behind these screening errors also results in additional program cost that may be perceived as substantial. We estimate that an FBR-level minimum benefit would increase aggregate program cost for retired workers aged 65 or older by roughly 2 percent. There are two fundamental reasons for these findings. First, the concept of an FBR-level minimum benefit looks at the individual or married couple in artificial isolation; however, the family is the main consumption unit in our society. The income of an unmarried partner or family members other than a married spouse is ignored. Second, individuals and couples may also have income from sources other than Social Security or SSI, which is also ignored by a simple FBR-based minimum benefit concept. The substantial empirical magnitude of measurement error arising from these conceptual simplifications naturally leads to the assessment of the tradeoff between target effectiveness and administrative simplicity. To facilitate this analysis, we simulate the potential effect of alternative screening methods designed to increase target effectiveness; while reducing program cost, such alternatives also may increase administrative complexity. For example, considering the combined Social Security benefit of a married couple (rather than looking at the husband and wife in isolation) might substantially increase target effectiveness with a relatively small increase in administrative complexity. Adding a family income screen might increase administrative complexity to a greater degree, but also would increase target effectiveness dramatically. The results also suggest that at some point adding new screens-such as a comprehensive asset test-may drastically increase administrative complexity with diminishing returns in terms of increased target effectiveness and reduced program cost. Whether a broad-based minimum benefit concept that is not tied to previous work experience is perceived by policymakers as desirable or not may depend on several factors not addressed in this article. However, to the extent that this type of minimum benefit design is regarded as potentially desirable, the tradeoffs between administrative simplicity and target effectiveness need to be considered.


Genome-Wide Identification and Characterization of Carboxypeptidase Genes in Silkworm (Bombyx mori).
The silkworm (Bombyx mori) is an economically-important insect that can secrete silk. Carboxypeptidases have been found in various metazoan species and play important roles in physiological and biochemical reactions. Here, we analyzed the silkworm genome database and characterized 48 carboxypeptidases, including 34 metal carboxypeptidases (BmMCP1-BmMCP34) and 14 serine carboxypeptidases (BmSCP1-BmSCP14), to better understand their diverse functions. Compared to other insects, our results indicated that carboxypeptidases from silkworm have more family members. These silkworm carboxypeptidases could be divided into four families: Peptidase_M2 carboxypeptidases, Peptidase_M14 carboxypeptidases, Peptidase_S10 carboxypeptidases and Peptidase_S28 carboxypeptidases. Microarray analysis showed that the carboxypeptidases had distinct expression patterns, whereas quantitative real-time PCR demonstrated that the expression level of 13 carboxypeptidases significantly decreased after starvation and restored after re-feeding. Overall, our study provides new insights into the functional and evolutionary features of silkworm carboxypeptidases.


Tissue harmonic imaging sonography of the axillary lymph nodes: evaluation of response to neoadjuvant chemotherapy in breast cancer patients.
In breast cancer patients, the number of surgically resected metastatic axillary lymph nodes has been considered to correlate with prognosis. Therefore, the lymph nodes' response to chemotherapy may provide a favorable prognosis by suggesting an appropriate regimen of post-operative chemotherapy. In the present study, we evaluated the therapeutic efficacy of neoadjuvant chemotherapy of the axillary lymph nodes of breast cancer patients, using tissue harmonic imaging ultrasonography. Thirty-three female patients with breast cancer >2 cm in the longest diameter were examined by tissue harmonic imaging both before and following neoadjuvant chemotherapy. Nodes were defined as metastasis positive or negative on the basis of Yang's criteria, at each ultrasonography examination. The ultrasonography findings were correlated with the histopathologic results of the surgically resected specimens. Patients with constantly positive nodes over two ultrasonography examinations had a higher pathological nodes positive rate (8/9, 88.9%) than those (3/10, 30.0%) whose lymph nodes shrunk from the first to second ultrasonography exam (p=0.02, Fisher's exact method). All patients with negative nodes at both ultrasonography examinations had negative pathological results. Thus, changes in consecutive tissue harmonic imaging findings may be used to accurately evaluate the response of axillary lymph nodes to neoadjuvant chemotherapy.


[What can be now expected of the determination of estrogen and progesterone receptors in the treatment of breast cancers].
Since the first published correlations around the years 1975 between estrogen and progesterone receptors and response to hormone therapy, numerous data have modified our insight on hormone dependency. For instance, it is now well established that tumors are not "receptor positive" or "receptor negative" but contain variable receptor quantities synthesized by a more or less important fraction of tumor cells. This allows to better understand events leading to partial response or to relapse. Receptor detection by classical assays gives no indications on receptor functionality, and data from molecular biology have shown that mutated receptors exist that have lost their property to induce genes, or that present new acquired properties. Nevertheless, these functional modifications are rare, and must not mask a reality: 75 to 80% of tumors with high receptor levels respond to hormone therapy, and the clinician must take this fact into account in three situations: for adjuvant therapy, for metastasis therapy, and for some special cases of difficult diagnosis.


Comparison of the efficacy of methotrexate and actinomycin D in the treatment of patients with stage I low risk gestational trophoblastic neoplasia (GTN).
Gestational trophoblastic neoplasia (GTN) refers to malignant lesions that arise from abnormal proliferation of placental trophoblast. Even in its metastatic forms GTN is curable with a cure rate of 90-100 %. Currently, methotrexate with or without folic acid, andactinomycin D is recommended for low risk GTN. The aim of this study is to compare the efficacy of methotrexate and actinomycin D as the first-line single chemotherapeutic agents for women with low-risk gestational trophoblastic neoplasia (LR-GTN). A total of 30 women with LR-GTN were randomized to receive a weekly pulsed dose of 40 mg/m (2) of methotrexate intramuscularly (n=15) or a pulsed intravenous bolus of 1.25 mg/m (2) of actinomycin D every 2 weeks (n=15). An additional cycle was administered as consolidation treatment following normalization of the serum level of beta-human chorionic gonadotropin (˂10 IU/L). Complete remission was achieved in 53.3% of patients in the methotrexate group and 86.7% in the actinomycin D group (p˂0.04). The mean number of treatment cycles needed to achieve response was lower in the actinomycin D group (4.3 vs. 6.5). The mean duration from beginning of treatment till achieving complete remission was 9.6 weeks for the Act group and 13 weeks for the MTX group. Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN but larger multicenter randomized controlled trials should be conducted to establish the most appropriate regimen for these patients.


Formal derivation of dissipative particle dynamics from first principles.
We show that the Markovian approximation assumed in current particle-based coarse-grained techniques, like dissipative particle dynamics, is unreliable in situations in which sound plays an important role. As an example we solve analytically and numerically the dynamics of coarse-grained harmonic systems by using first principle methods, showing the presence of long-lived memory kernels. This effect raises questions about the connection of these approaches at their current form to molecular dynamics.


Special Care Dentistry: attitudes of Specialists in Paediatric Dentistry practising in the UK to the creation of a new specialty.
This study was designed to examine the attitudes of Specialists in Paediatric Dentistry (SPDs) practising in the UK towards the creation of a specialty of Special Care Dentistry (SCD). Data were collected by postal questionnaire. Sample and methods. Two hundred and eleven dentists whose names were entered on the General Dental Council's Specialist List in Paediatric Dentistry, and who were resident and practising in the UK, were asked to complete a questionnaire consisting of both open and closed questions. Questionnaires were returned by 167 (79.2%) of the eligible SPDs. One hundred and sixty respondents (95.8%) expressed an opinion in relation to the creation of a specialty of SCD. One hundred and forty-three respondents (85.6%) stated that they supported such a proposal. However, slightly fewer (n = 149) respondents were prepared to indicate what they considered to be the remit of the proposed specialty. Ninety-two respondents (55.1%) considered that it should be restricted to the provision of specialist care for adults with 'special needs'; the remaining 57 respondents felt that it should provide specialist care across the entire age spectrum. Among SPDs, there is overwhelming support for the creation of a specialty of SCD, the majority view being that this should be dedicated to the provision of specialist care for adults with 'special needs'.


Integrating practice issues in managed care into the curriculum: a Delphi survey.
This project evolved from a partnership between an advanced practice nurse (APN) graduate program and a care management insurer. The purpose of this Delphi survey was to identify (a) role components germane to the practice of APNs in managed care and (b) topics reflecting these components in the curriculum. Data were gathered from two expert panels, clinician preceptors and faculty members. Each panel had 11 members: 11.3% and 100%, respectively, of the target populations of clinicians and faculty in the partnering agencies. There was considerable congruence between the panels on the survey. Case vignettes could be used as a vehicle for discussion of the broader issues of population approaches to specific problems. Faculty could partner with clinicians to develop cases for discussion of evidence-based practice. Faculty and clinicians could create preceptorships focused on business management, postgraduate fellowships within managed care systems, and regular opportunities to dialogue about curriculum and essential attributes of APN graduates.


Pentoxifyllin treatment of oligoasthenospermic men.
A randomised group of 90 men with idiopathic oligoasthenozoospermia was subjected to control study with pentoxifyllin. Pentoxifyllin was given to 51 men 1200 mg daily for 3 months. The other group of 39 infertile men was followed during the same period of time. Significant improvement was observed, in treated group, in percentage of motile sperms and normal shaped sperms after 3 months treatment. This study emphasizes that pentoxifyllin is a relatively good drug for restoring sperm motility and morphology in oligoasthenozoospermic men.


HBV-Specific CD8+ T-Cell Tolerance in the Liver.
Hepatitis B virus (HBV) remains a leading cause of liver-related morbidity and mortality through chronic hepatitis that may progress to liver cirrhosis and cancer. The central role played by HBV-specific CD8+ T cells in the clearance of acute HBV infection, and HBV-related liver injury is now well established. Vigorous, multifunctional CD8+ T cell responses are usually induced in most adult-onset HBV infections, while chronic hepatitis B (CHB) is characterized by quantitatively and qualitatively weak HBV-specific CD8+ T cell responses. The molecular basis of this dichotomy is poorly understood. Genomic analysis of dysfunctional HBV-specific CD8+ T cells in CHB patients and various mouse models suggest that multifaceted mechanisms including negative signaling and metabolic abnormalities cooperatively establish CD8+ T cell dysfunction. Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. A series of recent studies with mouse models of HBV infection suggest that genetic and epigenetic changes in dysfunctional CD8+ T cells are the manifestation of prolonged antigenic stimulation, as well as the absence of co-stimulatory or cytokine signaling. These new findings may provide potential new targets for immunotherapy aiming at invigorating HBV-specific CD8+ T cells, which hopefully cures CHB.


Diagnostics of plasma reactive species and induced chemistry of plasma treated foods.
Cold plasma is a promising technique that has been tested as a process technology for a range of food commodities, mainly to destroy microorganisms, but also aimed at toxin degradation, enzyme inactivation, residual pesticide degradation and functionalization of food properties. Plasma has already been employed by industry for food packaging material sterilization and surface modification. As most of the current literature on cold plasma in the field of food science is focused on microbial inactivation efficacy, the information about its chemical influences on food is sparse. To better understand the chemical interactions of with plasma, this review focuses on plasma chemistry diagnostics techniques available to characterize the plasma reactive species generated. Equally important is the detection of induced chemistry in the food and here we present approaches to analyze likely reactions with key food bio-molecules. Such analysis will support mechanistic insights involved in these complex chemical reactions (i.e., DNA, lipid and protein) along with potential physical modifications of the food structure. For successful adoption of plasma as a food processing aid it is critical to elucidate these interactions as they have an important role in demonstrating the technology's safety as a food processing technique along with understanding any effect on food nutrients.


In vitro approaches to lymphopoiesis, hemopoiesis, and oncogenesis.
Lymphopoiesis still remains a black box. Much remains to be learned about the identification of the cellular stages and the factors that regulate the rate of production of lymphocytes. Modifications of the Dexter system should assist with answers to these questions. Our work on PSF and that of other groups who have studied what is almost certainly the same factor under names such as hemopoietic growth factor, IL-3, BPA or multi-CSF suggests that this factor may provide an alternative means of generating cells for transplantation and replacement therapy. At present the only established sources of PSF are the activated T cell or tumors in which we think the gene has been anomalously activated, such as WEHI-3B; the long-term bone marrow culture system, however, seems to be defining a factor or influence that may be identical with, or is able to replace, the T cell factor. Finally, our experiments with the heterogeneous P cell lines and the initiation of oncogenesis by activation of the PSF gene raise some caveats about the use of cultured cells for human therapy. In the mouse system the production of immortalized factor-dependent lines appears to be more frequent in cells taken from long-term bone marrow cultures rather than normal bone marrow. Obviously, further information on the mechanism of immortalization and on the frequency and mechanism of activation of PSF genes in such lines will be of great importance in guiding the practical use of in vitro-derived cells and in the understanding of leukemogenesis.


Influence of nanopores of MCM-41 and SBA-15 confining (n-BuCp)2ZrCl2 on copolymerization of ethylene-alpha-olefin.
The effect of nanopore in mesoporous materials confining (n-BuCp),ZrCl2 and methylaluminoxane (MAO) on ethylene-1-hexene and ethylene-1-octene copolymerization was investigated on the basis of the copolymerization results, and the analysis of the supported catalyst and the copolymers. SBA-15 and MCM-41 together with amorphous silica were employed as supports, which are capable of confining (n-BuCp)2ZrCl2 and MAO in the nanopore. The copolymerization activities of MCM-41-supported (n-BuCp)2ZrCl2 were higher than those of SBA-15 and SiO2 although that its Zr content was quite lower than those of SBA-15 and SiO2. SBA-15 and MCM-41 showed a remarkable decrease in BET surface area after confining MAO and (n-BuCp)2ZrCl2 compared to SiO2, explaining an even adsorption of MAO and (n-BuCp)2ZrCl2 complexes on the nanopore surface. Temperature rising elution fractionation (TREF) results showed bimodal curves of MCM-41-supported (n-BuCp)2ZrCl2 at the C6/C2 and C8/C2 molar ratios of 0.6 and 0.5, respectively, which was attributed to the differences in ethylene and alpha-olefin concentrations along with the cylindrical nanopore of MCM-41 due to the narrow nanospace.


Conformational Equilibrium and Potential Energy Functions of the O-H Internal Rotation in the Axial and Equatorial Species of 1-Methylcyclohexanol.
The rotational spectra of four conformers (At, Ag, Et, Eg) of the tertiary alcohol 1-methylcyclohexanol were assigned by pulsed jet Fourier transform microwave spectroscopy. The transitions of two gauche conformers were split in two separated component lines, but it was not possible-from the available measured transitions-to accurately determine their vibrational ΔE0+0- ground-state splittings, respectively. In addition, the rotational spectra of the four OD deuterated isotopologues were measured and assigned. For the gauche species of this isotopologue we were able to determine the tunneling splittings, ΔE0+0-(Ag, OD) = 15.581(5) GHz and ΔE0+0-(Eg, OD) = 18.17(3) GHz, respectively. From these splittings the inversion barriers for Ag and Eg were determined, by using a flexible model, to be B2(Ag) = 356(10) and B2(Eg) = 320(10) cm(-1), respectively.


Chronic hepatitis B patients with high liver fibrosis levels should receive antiviral treatment.
The present study aimed to evaluate improvements in liver stiffness (LS) measured by transient elastography (TE) and associated factors in Chinese patients with chronic hepatitis B (CHB) treated with entecavir (ETV). A total of 190 consecutive CHB patients who received entecavir therapy and two LS measurements (LSMs) were enrolled in this retrospective study (average age, 47 years; 137 males [72.1%]), including 111 patients without liver cirrhosis (group 0) and 79 patients with liver cirrhosis (group 1). Each patient received LSM twice with an interval of six months. Normalized aspartate aminotransferase (AST) levels were accompanied by a significant reduction in LSM values (P<0.001) in each group. Multivariate analysis revealed that a higher initial LS value in groups 0 and 1, and a higher prothrombin time activity in group 1 was associated with a greater decline of the LS value. Higher initial quantitative hepatitis B surface antigen (qHBsAg) levels were correlated with a greater decline of the qHBsAg value in the two groups. In conclusion, LS values in CHB patients significantly improved after 24 weeks of entecavir therapy. The results suggested that higher LSM values at baseline contributed to a greater regression of LSM, and higher initial qHBsAg values could lead to greater qHBsAg reduction during ETV therapy. Extrapolating our results, we might be able to consider CHB patients who have higher initial LSM values or have higher levels of qHBsAg values when enrolled would have more benefit during ETV treatment.


Experiences of living without a sense of smell: Like "Being Behind Glass".
This study addresses the paucity of research concerning the subjective experiences of those affected by anosmia. In the study, we interviewed individuals(n = 11) recruited via the charity (Fifth Sense) and used Interpretative Phenomenological Analysis (IPA) to analyse the data. Findings revealed three main themes and seven sub themes. The main themes are Living with Anosmia; Remembrance of things old and new and Resilience. The study reveals the process of becoming aware of being anosmic and the relationships with others in this process including potentially unhelpful minimisations of the impact by professionals. In addition to a sense of isolation and insecurity, living with anosmia for some participants brought with it an identification of being 'anosmic' and feeling part of a community. This was in contrast to a general lack of public knowledge and understanding of anosmia. The findings of the study demonstrated the importance of smell to time, place and relationship and the recalling of smells as bringing a sense of connectivity to loved ones, of times past and also a sense of loss of ability. Participants also described the ways in which they coped and adapted to a life with anosmia and focused on positive aspects of life. These findings provide a rich qualitative account of the experience of anosmia. The findings point towards future research which could inform us about the lives of those who are anosmic and currently unaware and of those recently diagnosed, which will create a richer understanding of the experiences of anosmia.


Decreased Wnt4 expression inhibits thymoma development through downregulation of FoxN1.
The Wnt signaling pathway controls the development of thymic epithelial cells by regulating the expression of FoxN1. Thymoma is a type of malignant tumor arising from the thymic epithelial cells. To determine whether Wnt4 and FoxN1 are involved in the pathogenesis of thymoma, this study determined the mRNA and protein levels of Wnt4 and Foxn1 in thymoma, and analyzed the effect of thymoma cell apoptosis and tumor growth in nude mice after Wnt4 and FoxN1 downregulation. Wnt4 and FoxN1 mRNA and protein levels in thymoma tissues were analyzed by RT-qPCR and immunohistochemistry, respectively. Thymoma cells were cultured and transfected with siRNA targeting the Wnt4, JNK, and FoxN1 genes. Apoptosis of thymoma cells were analyzed after Wnt4 and FoxN1 downregulation. In addition, thymoma cells were inoculated into nude mice and tumor growth was analyzed. The rates of expression of Wnt4 and FoxN1 protein were 64.3% and 58.9%, while the levels of mRNA expression were 2.56±0.04 and 1.83±0.11, respectively. With increasing malignancy of thymoma, the rates of positivity for Wnt4 and FoxN1 mRNA and protein expression gradually increased. Upon interfering with Wnt4, JNK, and FoxN1 gene expression by using siRNA technology, the inhibition rates were 56.7%, 72.6%, and 63.2%, respectively. The expression of FoxN1 mRNA and protein was decreased after Wnt4 and JNK downregulation. After downregulation of Wnt4 and FoxN1 gene expression, the apoptosis rate of thymoma cells increased and the tumor volume decreased in nude mice. High expression of Wnt4 and FoxN1 may play an important role in the generation and development of thymoma. The FoxN1 gene produced a marked downstream effect through the regulation of Wnt4. Determining the positivity for both Wnt4 and FoxN1 can help us to evaluate the level of malignancy of thymoma.


Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study.
Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. This study involved six healthy purpose-bred Beagles (weight range 8.9-11.4 kg). Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs.


[Reserpine in the prevention of migraine and in the therapy of tension-vascular headache].
The results of many researches on migraine pathogenesis and our knowledge of the pharmacological action of reserpine led us to start using it in migraine prophylaxis ten years ago. For this purpose, standardized cycles of twenty administrations--heach dose being of 0.20 mg--were given intravenously; each cycle lasted a period of six to eight weeks. The positive data obtained on 300 patients suffering from severe migraine resulted statistically significant. Then, a double-blind clinical trial was carried out in Turin in agreement with a double-blind biochemical trial carried out in Copenhagen by Fog-Møller, Dalsgaard-Nielsen, Byrndum and Kemp Genefke. The results obtained have confirmed the efficacy of reserpine administered in appropriate doses and enabled the demonstration of its pharmacological mechanism. The results obtained also in "tension-vascular headache" with reserpine treatment were reviewed retrospectively and were highly significant.


Validation of spot urine in predicting 24-h sodium excretion at the individual level.
Background: Evidence for the effect of dietary sodium intake on the risk of cardiovascular disease has been controversial. One of the main explanations for the conflicting results lies in the great variability associated with measurement methods for sodium intake. Spot urine collection is a convenient method commonly used for sodium estimation, but its validity for predicting 24-h urinary sodium excretion at the individual level has not been well evaluated among the general population.Objective: The aim of this study was to evaluate the validity of the Kawasaki, the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT), and the Tanaka formulas in predicting 24-h urinary sodium excretion by using spot urine samples in Chinese adults.Design: We analyzed the relative and absolute differences and misclassification at the individual level from 3 commonly used methods for estimating sodium intake among 141 Chinese community residents.Results: The mean measured 24-h sodium excretion was 220.8 mmol/d. The median (95% CIs) differences between measured sodium and those estimated from the Kawasaki, INTERSALT, and Tanaka methods were 6.4 mmol/d (-17.5, 36.8 mmol/d), -67.3 mmol/d (-96.5, -46.9 mmol/d), and -42.9 mmol/d (-59.1, -24.8 mmol/d), respectively. The proportions of relative differences >40% with the Kawasaki, INTERSALT, and Tanaka methods were 31.2%, 41.1%, and 22.0%, respectively; and the absolute difference for the 3 methods was >51.3 mmol/d (3 g salt) in approximately half of the participants. The misclassification rate was 63.1% for the Kawasaki method, 78.7% for the INTERSALT method, and 66.0% for the Tanaka method at the individual level.Conclusion: The results from our study do not support the use of spot urine to estimate 24-h urinary sodium excretion at the individual level because of its poor performance with respect to misclassification. This trial was registered at www.chictr.org.cn as ChiCTR-IOR-16010278.


Efficacy of plasma exchange in children with severe hemophagocytic syndrome: a prospective randomized controlled trial.
To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS). A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis. Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05). Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.


Low frequency genetic variants in the μ-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine.
The μ-opioid receptor (MOR) binds exogenous and endogenous opioids and is known to mediate the rewarding effects of drugs of abuse. Numerous genetic studies have sought to identify common genetic variation in the gene encoding MOR (OPRM1) that affects risk for drug addiction. The purpose of this study was to examine the contribution of rare coding variants in OPRM1 to the risk for addiction. Rare and low frequency variants were selected using the National Heart Lung and Blood Institute - Exome Sequencing Project (NHLBI-ESP) database, which has screened the exomes of over 6500 individuals. Two SNPs (rs62638690 and rs17174794) were selected for genotyping in 1377 European American individuals addicted to heroin and/or cocaine. Two different SNPs (rs1799971 and rs17174801) were genotyped in 1238 African American individuals addicted to heroin and/or cocaine. Using the minor allele frequencies from the NHLBI-ESP dataset as a comparison group, case-control association analyses were performed. Results revealed an association between rs62638690 and cocaine and heroin addiction in European Americans (p=0.02; 95% C.I. 0.47 [0.24-0.92]). This study suggests a potential role for rare OPRM1 variants in addiction disorders and highlights an area worthy of future study.


Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules.
Recently we identified a molecular basis for differentiating benign and malignant follicular thyroid tumors. The purpose of these studies was to determine whether molecular analysis can be used to differentiate papillary thyroid carcinomas from benign thyroid nodules. Gene expression patterns of 14 papillary thyroid carcinomas and 21 benign tumors were analyzed by oligonucleotide array analysis. The carcinomas included seven classical papillary thyroid carcinomas (PTC) and seven follicular variant of PTC (FVPTC), and the benign tumors included 14 follicular adenomas and seven hyperplastic nodules. A hierarchical clustering analysis was performed to examine the groups for potential differences. The combined PTC and FVPTC groups had a distinct gene expression profile compared with the benign lesions. The sensitivity for a diagnosis of carcinoma was 93%, with a 100% specificity (one FVPTC clustered with the benign nodules). Cancer gene profiles contained both known (Met and galectin-3) and previously unidentified genes. Gene profiling is a reliable means of distinguishing PTC, FVPTC, and benign tumors of the thyroid. These gene profiles may provide insight into the pathogenesis of papillary thyroid carcinoma and may ultimately enhance the preoperative diagnosis of thyroid nodules on a molecular basis.


A combined genetic algorithm and finite element method for the determination of a practical elasto-electric set for 1-3 piezocomposite phases.
1-3 piezocomposites are widely used in ultrasonic transducers, particularly for imaging applications. The fabrication process is often based on the dice and fill method, leading to a periodic structure. This process can modify the initial properties of the two phases due to the machining of the piezoelectric bulk ceramic and setting of the polymer. A method is proposed to directly determine a practical set for 1-3 piezocomposite properties and all the elastic, dielectric and piezoelectric parameters of the two piezoelectric (11 constants) and inert phases (3 constants). This method is based on a fitting process of the electrical impedance as a function of frequency (one thickness and two lateral modes). For this purpose, a genetic algorithm coupled with a finite element method (GA/FEM) was used in an iterative process to deduce all these parameters. This method was first performed on a numerical phantom (Pz21/epoxy resin). Comparisons showed that the GA/FEM obtained a good set of the 14 parameters, and the accuracy of several parameters was discussed. Finally, the GA/FEM algorithm was applied to a fabricated 1-3 piezocomposite (dice and fill method). The results showed that the fabrication process introduced several changes in the properties of the two phases (in particular, the dielectric constants of the ceramic and one elastic constant of the polymer) compared to the initial commercial data, while keeping the identical thickness coupling factor at 64%.