Early results of a low-profile stent-graft for thoracic endovascular aortic repair.
To assess outcomes of a low-profile thoracic stent-graft in the treatment of thoracic aortic pathologies. A retrospective analysis of all consecutive patients with aortic thoracic pathologies treated with the RelayPro device in two university hospitals between October 2018 and July 2019. 23 patients (65% men; mean age 63.4 ± 15 years) were treated. Pathologies included aortic dissections (n = 10), 5 residual type A (22%) and 5 type B (22%), 6 degenerative aortic aneurysms (26%), 4 penetrating aortic ulcers (17%), and aortic erosion, intramural hematoma and aortic rupture (n = 1 and 4% in each case). Two cases (9%) were emergent and two urgent. Proximal landing was achieved in zones 0 (4%), 1 (4%), 2 (43%), and 3 (26%). Five grafts were frozen elephant trunk extensions. Technical success was 100% with accurate device deployment in the intended landing zone of the aortic arch in all 23 patients and with no Ia/III endoleaks and three (13%) type II endoleaks. Apposition was adequate in 96%. Two patients had post-implantation syndromes (one fever, one leukocytosis). Mean follow-up was 11.6 ± 3.7 months (range, 2-16) with no other complications, secondary interventions or conversions to open surgery. There was no 30-day mortality and no aortic-related mortality; all-cause mortality was 4% during follow-up. A 3-4 French reduced profile in the current generation of stent-grafts facilitates TEVAR particularly in patients with smaller vessels access. Early safety and effectiveness outcomes are favorable, even in endpoints such as deployment accuracy and apposition which may be surrogates for longer-term clinical success and durability.


Limonoids from the stems of Toona ciliata var. henryi (Meliaceae).
Ten limonoids, toonacilianins A-J, and two norlimonoids, toonacilianins K and L, together with seven known compounds were isolated from the stems of Toona ciliata var. henryi (Meliaceae). Their structures were elucidated by spectroscopic analysis. Two compounds showed strong cytotoxic activities.


The cost of Mycobacterium avium complex lung disease in Canada, France, Germany, and the United Kingdom: a nationally representative observational study.
Management of nontuberculous mycobacterial lung disease (NTMLD) consists of a long-term multi-drug antibiotic regimen, yet many patients do not achieve culture conversion. We estimated the NTMLD-related direct medical costs in Canada, France, Germany, and the United Kingdom (UK) among refractory patients who were infected with Mycobacterium avium complex (MAC), without concomitant cystic fibrosis, tuberculosis, or HIV. We conducted a retrospective observational physician survey of nationally representative samples. The survey captured anonymized information about patients' treatment histories for NTMLD-related health care resource utilization over a 24-month period. We summarized NTMLD-related resource use and estimated the total economic burden, from each country's health care payer perspective. In total, 59 physicians provided data on 157 patients. The average person time observed during the 24-month period was 1.7 years (SD: 0.4); 17% of patients died by the end of the study period. The major components of NTMLD-related direct medical costs among refractory patients were hospitalizations (varying from 29% of total annual costs in the UK to 69% in France), outpatient visits (8% in Canada to 51% in the UK), and outpatient testing such as post-diagnostic sputum testing, bronchial wash/lavage, spirometry, biopsies, imaging, and electrocardiograms (5% in France to 35% in Canada). In this patient cohort, the average direct medical costs per person-year, in local currencies, were approximately $16,200 (Canada), €11,600 (Germany), €17,900 (France) and £9,700 (UK). Based on this study's findings, we conclude that managing patients with refractory NTMLD caused by MAC is associated with a substantial economic burden.


LNA Inhibitor in microRNA miR-23b as a Potential Anti-proliferative Option in Human Hepatocellular Carcinoma.
Dysregulation of microRNAs (miRNAs) has been shown to be involved in the pathogenesis and progression of many malignancies. Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related deaths. Recent data suggest that microRNA-23b (miR-23b) is significantly high in different types of cancer, specifically human hepatocellular carcinoma. Locked nucleic acid (LNA)-modified oligonucleotides have recently been suggested as a novel approach for targeting miRNAs as antisense-based gene silencing. The aim of this study was to explore the functional role of LNA-anti-miR-23b in a HepG2 (hepatocarcinoma) cell line. HepG2 cells were transfected with LNA-anti-miR-23b for 24, 48, and 72 h. Quantitative real-time reverse transcriptase-PCR (qRT-PCR) was performed to assess miR-23b expression by LNA-anti-miR-23b. The viability of the cells was evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. LNA-anti-miR-23b was successfully transfected into human HepG2 cells and suppressed the miR-23b. LNA-anti-miR-23b reduced the invasive behaviors of HepG2 cells after 24 h, compared to untreated cells and scrambled LNA-transfected cells, and this effect was more pronounced after 72 h. Our findings suggest that inhibition of miR-23b could be used as a novel approach in inhibition of HCC proliferation.


Metal-reinforced glass ionomers: their flexural and bond strengths to tooth substrates.
This study compared the flexural strengths and bond strengths to dentin and enamel of two brands of silver-reinforced glass ionomers with their respective unfilled glass-ionomer cements for luting. The results led to the following conclusions. 1. No significant differences in bond strengths to tooth substrates were recorded between silver-reinforced and unfilled glass ionomers. 2. Although the mean bond-strength values of enamel were higher than those of dentin, no statistically significant differences were observed. 3. No significant differences in bond strengths to tooth substrates were observed between the two brands of glass ionomers studied. 4. No differences in flexural strengths were recorded between the silver-reinforced glass ionomer and glass ionomer of a similar brand for luting. 5. Ketac-Silver and Ketac-Cem cements had significantly higher flexural strength than Fuji II Lumi Alloy and Fuji I cements.


The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs. Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus. The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection.


Recognition of partially-folded mitochondrial malate dehydrogenase by GroEL. Steady and time-dependent emission anisotropy measurements.
The binding of partially-folded mitochondrial malate dehydrogenase (mMDH) to GroEL was assessed by steady and nanosecond emission spectroscopy. Partially-folded intermediates of mMDH show significant residual secondary structure when examined by CD spectroscopy in the far UV. They bind the extrinsic fluorescent probe ANS and the protein-ANS complexes display a rotational correlation time of 19 ns. Similar rotational correlation time (phi = 18.6 ns) was determined for partially-folded species tagged with anthraniloyl. GroEL recognizes partially-folded species with a K(D) approximately 60 nM. The rotational correlation time of the complex, i.e., GroEL-mMDH-ANT, approaches a value of 280 ns in the absence of ATP. Reactivation of mMDH-ANT by addition of GroEL and ATP brings about a significant decrease in the observed rotational correlation time. The results indicate that partially-folded malate dehydrogenase is rigidly trapped by GroEL in the absence of ATP, whereas addition of ATP facilitates reactivation and release of folded conformations endowed with catalytic activity.


A Practical Guide to the HIrisPlex System: Simultaneous Prediction of Eye and Hair Color from DNA.
The HIrisPlex system, which consists of two parts, allows the simultaneous prediction of eye and hair color from DNA, e.g., samples extracted from crime scene evidence. The first part is a highly sensitive multiplex genotyping assay consisting of 24 DNA markers using SNaPshot™ chemistry, for analysis on all Capillary Electrophoresis machines. The second part consists of statistical models that respectively establish eye and hair color prediction probabilities from complete and incomplete genotype profiles using parameters generated from large genotype and phenotype databases. This combined prediction tool constitutes the online system freely available to users. Here we provide a practical guide on how to use the HIrisPlex system for forensic and other DNA applications.


Adsorption of vanadium (V) ions from the aqueous solutions on different biomass-derived biochars.
The paper presents the results of the studies on the vanadium (V) ions removal from the aqueous solutions in the adsorption process on biochars from different biomass types (cow manure BC1, wet distiller grains BC2, spent mushroom substrates BC3). The adsorbents were characterized by means of the SEM-EDS, FTIR, XRD and XPS techniques. The influence of adsorbent type and basic process parameters, such as pH and metal ion concentration in aqueous phase, adsorbent dose and time of contact of phases on the efficiency of V(V) was determined. Based on the obtained results, the mechanism and kinetics of the adsorption processes occurring on the biochar originating from the wet distiller grains as adsorbents with the greatest affinity for the V(V) ions were characterized, using isotherm models of Langmuir, Freundlich, Temkin and Dubinin-Radushkevich and pseudo-first-order, pseudo-second-order as well as intraparticle diffusion kinetic models. Under the constant process conditions (pH = 3.0; m = 0.5 g; c0 = 50 mg/L) the order of V(V) ions removal from aqueous solutions was as follows: BC2 > BC1 = BC3. The biochar BC2 exhibited the maximum sorption capacity of 1.61 mg V(V)/g. The experimental kinetic data show the adsorption course according to the pseudo-second order model.


Identification of genetic interactions with priB links the PriA/PriB DNA replication restart pathway to double-strand DNA break repair in Escherichia coli.
Collisions between DNA replication complexes (replisomes) and impediments such as damaged DNA or proteins tightly bound to the chromosome lead to premature dissociation of replisomes at least once per cell cycle in Escherichia coli. Left unrepaired, these events produce incompletely replicated chromosomes that cannot be properly partitioned into daughter cells. DNA replication restart, the process that reloads replisomes at prematurely terminated sites, is therefore essential in E. coli and other bacteria. Three replication restart pathways have been identified in E. coli: PriA/PriB, PriA/PriC, and PriC/Rep. A limited number of genetic interactions between replication restart and other genome maintenance pathways have been defined, but a systematic study placing replication restart reactions in a broader cellular context has not been performed. We have utilized transposon-insertion sequencing to identify new genetic interactions between DNA replication restart pathways and other cellular systems. Known genetic interactors with the priB replication restart gene (uniquely involved in the PriA/PriB pathway) were confirmed and several novel priB interactions were discovered. Targeted genetic and imaging-based experiments with priB and its genetic partners revealed significant double-strand DNA break accumulation in strains with mutations in dam, rep, rdgC, lexA, or polA. Modulating the activity of the RecA recombinase partially suppressed the detrimental effects of rdgC or lexA mutations in ΔpriB cells. Taken together, our results highlight roles for several genes in double-strand DNA break homeostasis and define a genetic network that facilitates DNA repair/processing upstream of PriA/PriB-mediated DNA replication restart in E. coli.


Endemic asthma inhaler abuse among antisocial adolescents.
Approximately 40 million prescriptions were dispensed in the U.S. for asthma inhalers in 2006. Although the pervasive distribution of asthma inhalers warrants greater attention to possible misuse of these products, few investigations have examined asthma inhaler misuse. The purpose of this study was to describe the prevalence, correlates and consequences of asthma inhaler misuse among antisocial youth. A cross-sectional survey with face-to-face interviews assessing substance use, psychiatric symptoms, and antisocial behaviors among adolescents (N=723) in residential treatment. More than 26% (N=193) of youth were diagnosed with asthma; 91.2% of asthmatic youth had received a prescription for an inhaler. Of the 373 youth who had used a prescribed or non-prescribed asthma inhaler, 23.6% (N=88) reported using an inhaler to get high (i.e., were inhaler misusers). Asthma inhaler misusers had an earlier onset of antisocial conduct, significantly greater levels of current psychiatric distress and lifetime suicidality, higher rates of lifetime substance use problems and volatile solvent abuse, and significantly higher levels of temperamental impulsivity and fearlessness than did inhaler non-users or users. Caucasian racial status, current level of psychiatric distress, and lifetime volatile solvent abuse significantly distinguished lifetime asthma inhaler users and misusers in multivariate logistic regression analyses. Asthma inhaler misusers were significantly more likely to report euphoria, memory problems, slurred speech, blurred vision, confusion, dizziness, and a variety of other acute reactions to asthma inhaler use than were asthma inhaler users. Asthma inhaler misuse for the purposes of getting high was prevalent among antisocial youth, co-occurred with other psychiatric and substance use problems, and was associated with adverse consequences.


New debt recovery service provider.
Laura Carleton, member services officer, announces BVA's link with a new provider of debt recovery services.


Autologous bone marrow transplantation for non-Hodgkin's lymphoma resulting in long-term remission of coincidental Crohn's disease.
Crohn's disease usually runs a chronic relapsing and remitting course, characterized by a repeated need for immunosuppressive drug therapy or often surgery. and is considered to be incurable by standard treatment. We report a case of successful long-term disease control of Crohn's disease following autologous bone marrow transplantation. This case provides further support for the concept that some forms of severe immune-mediated diseases may be amenable to treatment by high-dose therapy with autologous stem cell support.


Studies on immunomodulatory properties of isoniazid. Influence of isoniazid on responsiveness of peripheral blood mononuclear cells to interleukin-2.
Peripheral blood mononuclear cells which were "resting" i.e. interleukin-2-receptor-negative were stimulated to proliferate by interleukin-2 in vitro. It was found that isoniazid at concentration of 10(-5)-10(-6) M increased the peak proliferation of "resting" cells but had no influence on the kinetics of proliferation. The mechanism of this effect of isoniazid remains unclear.


Two mucosal-parenteral schedules to coadminister a multiantigenic formulation against HIV-1 in Balb/c mice.
Previous studies showed that simultaneous immunization through the nasal (IN) and subcutaneous (SC) route of a multiantigenic formulation induced a Th1 anti-HIV humoral and cellular immune responses. The formulation was comprised of a recombinant protein of HIV-1 (named CR3; Cellular Response number 3) and the surface and nucleocapsid antigens of hepatitis B virus. This study asks whether four times simultaneous administration through the IN and SC routes (SC+IN) of the multiantigenic formulation induces a similar systemic and mucosal immune responses than two sequential IN priming and two SC boosting (2IN&2SC) inoculations in mice. To answer this question, we tested the same total dose of each antigen per animal in both schedules of inoculation. We found that SC+IN and 2IN&2SC coadministration induced comparable levels of CR3(HIV)-specific IFN-γ-secreting cells and CD8+ cells proliferation in the systemic compartment of animals. Consistent with these findings, a similar Th1 profile considering anti-CR3 IgG1:IGg2a ratio was observed. Additionally, the level of IgG antibodies and the frequency of seroconverting animals in vagina were not different. However, in the case of IgA antibodies the same parameters were significantly higher in the SC+IN group. We also found important level of HBsAg-specific antibodies in serum and vaginal washes.


Bond graph models for plant biosystems.
Computable dynamic models for plant biosystems permit the study of effects of environmental variables on plant growth and productivity. Using bond graphs, a comprehensive phenomenological model of a plant biosystem may be developed and used in computer simulations. Elements of a model studied in this papaer include a gas diffusion network between the atmosphere and leaf cytoplasm, intracellular chemistry, and the translocation networks of the phloem. Bond graphs are shown to provide a conceptual basis for the development of biological subsystem and system models and lead to computable representations.


Urinary bladder hypersensitivity and dysfunction in female mice following early life and adult stress.
Early adverse events have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. Despite high clinical relevance and reports of stress-related symptom exacerbation, animal models investigating the contribution of early life stress to female urological pain are lacking. We examined the impact of neonatal maternal separation (NMS) on bladder sensitivity and visceral neuroimmune status both prior-to, and following, water avoidance stress (WAS) in adult female mice. The visceromotor response to urinary bladder distension was increased at baseline and 8d post-WAS in NMS mice, while colorectal sensitivity was transiently increased 1d post-WAS only in naïve mice. Bladder micturition rate and output, but not fecal output, were also significantly increased following WAS in NMS mice. Changes in gene expression involved in regulating the stress response system were observed at baseline and following WAS in NMS mice, and WAS reduced serum corticosterone levels. Cytokine and growth factor mRNA levels in the bladder, and to a lesser extent in the colon, were significantly impacted by NMS and WAS. Peripheral mRNA levels of stress-responsive receptors were differentially influenced by early life and adult stress in bladder, but not colon, of naïve and NMS mice. Histological evidence of mast cell degranulation was increased in NMS bladder, while protein levels of protease activated receptor 2 (PAR2) and transient receptor potential ankyrin 1 (TRPA1) were increased by WAS. Together, this study provides new insight into mechanisms contributing to stress associated symptom onset or exacerbation in patients exposed to early life stress.


TCM therapies combined with chemotherapy for preventing recurrence and metastasis in postoperative II to IIIA NSCLC: A protocol for a systematic review and meta-analysis.
Traditional Chinese Medicine (TCM) therapies have been combined with chemotherapy for preventing Recurrence and metastasis in postoperative II to IIIA non-small-cell lung cancer (NSCLC) and the associated better disease-free survival (DFS), but its effects remain elusive. The purpose of this review is to assess the efficacy of TCM therapies as a treatment for postoperative II to IIIA NSCLC. Seventh databases will be searched for relevant studies from inception to the present date. We will include randomized controlled trials assessing TCM therapies combined with chemotherapy for preventing Recurrence and metastasis in postoperative II to IIIA NSCLC. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. The protocol for this systematic review has been registered on PROSPERO under the number CRD42019116594.


Face-to-face Information and Emotional Support from Trained Nurses Reduce Pain During Screening Mammography: Results from a Randomized Controlled Trial.
Pain and discomfort during breast examination can affect a woman's adherence to breast cancer-screening programs. The aim of this study was to determine whether a nursing intervention protocol that provides verbal information and support to women could reduce pain during mammography. A randomized controlled trial of 436 Spanish women aged 50-69 who attended a breast-screening program was performed. The experimental group received a customized nursing intervention that provided face-to-face information and emotional support during the examination. Pain and anxiety were measured using a visual analogue scale and the State-Trait Anxiety Inventory, respectively. Data regarding several potential confounders were also collected. The adjusted means of pain level in the study group were obtained from multiple linear regressions, and the adjusted odds ratios (OR) and 95% confidence intervals (CI) were obtained via logistic regression. After the intervention, the level of pain was significantly lower (p = .03) in the experimental group (0.98 ± 2.28) compared with the group treated with normal care (1.48 ± 2.29). Consequently, the probability of feeling pain during mammography was lower among women in the experimental group (OR = 0.44; 95% CI: 0.24-0.81). The intervention was more effective among women with the highest anxiety levels (OR = 0.33; 95% CI: 0.11-0.98), who did not expect pain (OR = 0.28; 95% CI: 0.08-0.97), and who did not fear the outcome of the mammography (OR = 0.18; 95% CI: 0.04-0.85). Providing verbal information, as well as supporting the women during the test, is a simple and achievable intervention for nurses and can help to reduce pain during screening mammography.


The effects of imipramine, mianserin and trazodone on the chronotropic, inotropic and coronary vascular responses in the isolated perfused rat heart.
1. The cardiovascular effects of the tricyclic antidepressant imipramine and two second generation antidepressants mianserin, a tetracyclic, and trazodone, a triazolopyridine derivative, were investigated in the isolated perfused rat heart. 2. Imipramine caused cardiac slowing and a negative inotropic effect at 2.5 microM after 30 min of perfusion. Conversely mianserin and trazodone had no effect on heart rate at 5 microM with inotropic state remaining above control values after 30 min of perfusion. 3. Varying effects on coronary flow, which appear to correlate well with the documented receptor actions of each drug, were demonstrated. Imipramine caused a decrease in coronary flow at 1.25 and 2.5 microM, followed by an increase at 10 microM. Mianserin decreased coronary flow at all concentrations between 1 and 20 microM. Trazodone elicited a marked elevation in coronary flow over the dose range of 2.5 to 250 microM. 4. The results in this model suggest that although the second generation agents appear to cause less cardiodepression all three agents elicit quantitatively different coronary vascular responses.


Infantile spasms: a proposal for a staged evaluation.
The purpose of this study was to determine whether a staged, algorithmic evaluation of infantile spasms could be developed to minimize patient discomfort, treatment delay, and overall costs. A retrospective chart review of patients diagnosed with infantile spasms at the authors' institution during a 10-year period was performed, with 29 patients identified; 28 charts were reviewed. By history and physical examination, 21 were classified as symptomatic and seven as cryptogenic. Of the 21 symptomatic patients, 13 had a known etiology at presentation; with further testing the specific etiology was determined in two more. Two in the cryptogenic group were reclassified on the basis of neuroimaging findings. Evaluations included neuroimaging (27, 15 abnormal), cerebrospinal fluid studies (nine, all normal), comprehensive metabolic studies (17, all normal), chromosomal analysis (11, two abnormal), and ophthalmologic evaluation (27, six abnormal). The average cost of the studies per patient was $5,076 at the authors' institution. Etiologic yield was increased by 20% with neuroimaging. The other investigations either confirmed a known etiology or were noncontributory. On the basis of these findings, the authors propose an algorithm for a more focused evaluation of infantile spasms. Using the algorithm, the authors suggest directly proceeding to therapy in patients with specific etiologies determined by history and examination. Further evaluation should start with neuroimaging. Subsequent evaluations should be on the basis of those results. The authors estimate a potential 60-90% reduction in total costs if this algorithm is applied.


[Large mycotic aneurysm of the common iliac artery in a child 15 months old (author's transl)].
The authors report an aneurysm of the common iliac artery in a 15 month old boy with Fallot's tetralogy. A persistent fever and sacciform type aneurysm emphasized infectious origin although any arterial catheterism. Aneurysm has been resected and the artery was termino-terminal repaired.


Deaths and injuries caused by land mines in Mozambique.
Land mines in Mozambique are still causing death and injuries years after the initial dispute. Since 1980, 3400 people have had an amputation because of land mine injuries. However, there are no direct estimates of the number of deaths or casualties which are not treated in hospitals. In March, 1994, a medical team assembled by Physicians for Human Rights (PHR) conducted household surveys in the province of Manica and in the sub-district of Metuchira, province of Sofala. The object was to assess the frequency and severity of injuries and mortality caused by land mines in the civilian population. We found ratios of 8.1 and 16.7 casualties per 1000 living people in Manica and Metuchira, respectively. The prevalence of amputees was 3.2 per 1000 in Manica, and 2.3 in Metuchira. These figures are several folds higher than suggested by hospital data. The case fatality rate was 48%. Most of the victims were civilians (68%) and were injured by antipersonnel mines (81%). 16% of victims were women, and 7% were under 15 years of age. Our results suggest that the impact of land mines is substantially higher than originally thought.


Triceps skinfold thickness and body mass index and the risk of gestational diabetes mellitus: Evidence from a multigenerational cohort study.
Pre-pregnancy obesity is a well-recognized risk factor for gestational diabetes mellitus (GDM). There is a continuity of obesity from childhood to adolescence and then adulthood. However, it is unknown whether early childhood obesity predicts GDM. We investigated the prospective association of childhood triceps skinfold thickness and body mass index (BMI) with GDM risk among women from the Mater-University of Queensland Study of Pregnancy (MUSP), a multigenerational cohort study. A multiple logistic regression model was applied to estimate the odds of experiencing GDM by childhood skinfold thickness and BMI. Out of 552 women in the study for whom data were available on triceps skinfold thickness and BMI at average age 5 (range 3-7) years old, 52 (9.42%) developed GDM by average age 30 (range 28-33) years. We found that the risk of developing GDM was greater among women who had greater skinfold thickness but not greater BMI at age 5 years. Women who were classified as overweight or obese based on skinfold thickness at age 5 years had an increased odds ratio of GDM compared to women who had normal skinfold thickness. This association remained significant after adjustment for the potential confounders (OR 2.74; 95% confidence interval=1.28-5.86). The risk of developing GDM was associated with higher skinfold thickness at age 5 years.


Kinetic analysis of electron flux in cytochrome P450 reductases reveals differences in rate-determining steps in plant and mammalian enzymes.
Herein, we compare the kinetic properties of CPR from Arabidopsis thaliana (ATR2), with CPR from Artemisia annua (aaCPR) and human CPR (hCPR). While all three CPR forms elicit comparable rates for cytochrome c(3+) turnover, NADPH reduction of the FAD cofactor is ∼50-fold faster in aaCPR and ATR2 compared to hCPR, with a kobs of ∼500 s(-1) (6 °C). Stopped-flow analysis of the isolated FAD-domains reveals that NADP(+)-FADH2 charge-transfer complex formation is also significantly faster in the plant enzymes, but the rate of its decay is comparable for all three proteins. In hCPR, transfer of a hydride ion from NADPH to FAD is tightly coupled to subsequent FAD to FMN electron transfer, indicating that the former catalytic event is slow relative to the latter. In contrast, interflavin electron transfer is slower than NADPH hydride transfer in aaCPR and ATR2, occurring with an observed rate constant of ∼50 s(-1). Finally, the transfer of electrons from FMN to cytochrome c(3+) is rapid (>10(3) s(-1)) in all three enzymes and does not limit catalytic turnover. In combination, the data reveal differences in rate-determining steps between plant CPR and their mammalian equivalent in mediating the flux of reducing equivalents from NADPH to external electron acceptors.


Lorazepam.
The nurse administering any BZD--especially lorazepam--to a neonate must be knowledgeable about the drug's effects and risks and must remember that BZDs do not provide analgesia. The sedative effects of lorazepam will increase with concomitant use of opioids. The nurse must be alert for adverse reactions (Table 1). Close monitoring of the neonate's respiratory effort and blood pressure is important. Because of the various reported cases of myoclonus in neonates after lorazepam administration, close observation for seizure activity is imperative. Although lorazepam use may be beneficial in specific instances, administration should be approached with caution in the neonate (especially in the preterm neonate) and other agents considered.


Precise application of sentinel lymph node biopsy in patients with ductal carcinoma in situ: A systematic review and meta-analysis of real-world data.
Although ductal carcinoma in situ (DCIS) seldom involves lymph nodes, some patients may upstage to invasive disease, thus requiring a second surgery for sentinel lymph node (SLN) biopsy (SLNB). However, the indications of SLNB remain inconclusive and clinical trials are rarely available. Our aim is to systematically review the real-world data to evaluate whether SLNB is precisely applied in patients with a high risk of upstaging from DCIS to invasive carcinoma. PubMed, EMBASE, and Cochrane library databases were searched. Prospective and retrospective cohort studies that evaluated the pathological outcomes of SLNB and the upstaging rate in women with DCIS were included. The primary outcomes were the upstaging and SLN-positive rates of patients initially diagnosed as having DCIS. We analyzed factors, namely biopsy methods, clinical presentations, histological patterns, and hormone receptor status, that potentially indicate nodal involvement risk. We retrieved 43 prospective and 69 retrospective studies including 44,001 patients. The pooled estimates of upstaging and SLN-positive rates were 25.8% (95% confidence interval [CI]: 0.230-0.286) and 4.9% (95% CI: 0.042-0.055), respectively. In subgroup analysis, the upstaging rate was significantly higher in patients with estrogen receptor-negative status, palpable mass, tumor size >2 cm on imaging, and high-nuclear grade and those who received a preoperative diagnosis through core needle biopsy. The upstaging and SLN-positive rates of DCIS were 25.8% and 4.9%, respectively. By selecting patients with high risk DCIS, surgeons may increase the precision of and reduce the excess and incomplete treatment rates of SLNB.


Serum TNF-α, GTH and MDA of high-fat diet-induced obesity and obesity resistant rats.
Mechanism of high fat diet-induced obesity is analyzed and serum tumor necrosis factor, malondialdehyde and glutathione levels of obesity resistant rats are effectively analyzed. 120 male SD rats were grouped into obesity group and control group, each group with 60 rats. Obese rats were fed with high fat diet, while control rats were fed with ordinary fodder. After six months of feeding, growth degree of two groups of rats is observed , and the rats are divided into obesity group and obesity resistant group based on extent of growth. Then glutathione, tumor necrosis factor-α and MDA content in bat serum are detected with enzyme-linked immunosorbent assay. The content of tumor necrosis factor α in obese rats and obesity resistant rats is far higher than that in control group (P < 0.05), there exists no statistical significance (P > 0.05) in tumor necrosis factor α in obesity group and obesity resistant group, glutathione level of obesity group rats and obesity resistant group rats is significantly increased (P < 0.05) compared with that of control group, and also serum MDA level of the two groups has statistical significance compared with that of normal control group (P < 0.05). Among rats fed with high fat diet, in comparison with weight of obesity resistant rats and control group rats, there is no statistically significant difference, (P > 0.05). However, high fat diet will impact mechanisms in vivo in rats, which then induces oxidative stress response and inflammatory response in rats.


Deleterious effects of hyperbaric oxygen treatment on mortality and pathological changes in nitrogen-dioxide-poisoned dogs.
Nitrogen dioxide poisoning was experimentally produced in dogs. PO2, PCO2 and pH were measured in poisoned animals and during treatment with hyperbaric oxygen (OHP) lung lesions in both groups were evaluated. It is concluded that OHP has a deleterious effect both in terms of mortality and pathological changes.


Application of Non-invasive Micro-test Technology (NMT) in environmental fields: A comprehensive review.
Non-invasive Micro-test Technology (NMT) is a selective microelectrode technique which can detect the flux rates and three-dimensional motion directions of ions or molecules into and out of living organisms in situ without damaging the sample. It has the advantages of maintaining sample integrity, high temporal and spatial resolution, and being able to measure multiple sites simultaneously. In this paper we provide a comprehensive review on the development of NMT in recent years. Its principles, characteristics, and the differences with other microelectrode techniques are introduced. We discuss the applications of NMT in the field of phytoremediation, plant resistance, water quality monitoring, and toxicity mechanisms of heavy metals on organisms. Furthermore, the challenges and future prospects of NMT in the environmental field are presented.


Regional pancreatectomy and transverse colectomy with mesenteric vascular reconstruction for inflammatory pseudotumour of the head of pancreas and mesenteric root.
Inflammatory myofibroblastic pseudotumour is a rare pancreatic lesion. A 32-year-old woman with such a tumour was treated by a radical operation comprising proximal pancreatic-duodenectomy (Whipple Procedure) and transverse colectomy with resection and reconstruction of the superior mesenteric artery and vein. She remains well 6 years later. The importance of aggressive surgical clearance rather than chemotherapy is highlighted in the management of patients with these unusual tumours.


Interaction of granulocyte proteases with inhibitors in pulmonary diseases.
The elastase-antielastase hypothesis of lung tissue destruction has focused our interest on the two main inhibitors of granulocyte elastase in the lung, alpha 1-antitrypsin dominating blood, interstitial tissue and alveolar fluid lining and antileukoprotease dominating the respiratory tract mucosa. Antileukoprotease as well as elastase and alpha 1-antitrypsin show increased serum levels during bronchitis and bronchopneumonia, alpha 1-antitrypsin because it is an acute phase reactant, elastase and antileukoprotease because of influx from the inflamed tissues. Elastase is identified in the bronchial expectorates, mainly in complex with antileukoprotease, but often also in a free, active form. The granulocyte elastase in serum from these patients is, however, only found in complex with alpha 1-antitrypsin. The increased amounts of antileukoprotease in serum are always in a free and largely active form. The explanation for the absence of elastase-antileukoprotease complexes in serum is offered by some of our recent results. The elastase-antileukoprotease complexes are rapidly dissociated when mixed with serum in vitro, although the equilibrium dissociation constant Ki of the complex is 1.2 X 10(-11) M. Furthermore, in a pure in vitro system, alpha 1-antitrypsin is able to dissociate a leukocyte elastase-antileukoprotease complex with the rate constant of 1.3 X 10(-4) X S-1. A small part of the antileukoprotease released from the elastase-antileukoprotease complex on mixture with serum is recovered bound by elastase-alpha 2-macroglobulin complexes. Antileukoprotease inhibits the enzymatic activity of elastase-alpha 2-macroglobulin complex relatively slowly. 1:1 elastase-alpha 2-macroglobulin complexes are, however, inhibited more readily than 2:1 saturated complexes.


[The acute puerperal inversion of uterus (inversio uteri puerperalis) (author's transl)].
Four cases of acute inversio uteri are discussed. Most important for the success of manual reposition and a postoperative process without complications is an instant therapy using beta-stimulators.


Alar retraction: etiology, treatment, and prevention.
The effect of different rhinoplasty maneuvers on alar retraction remains to be elucidated. To determine the etiology and treatment of alar retraction based on a series of specific rhinoplasty maneuvers. Retrospective review of a single surgeon's rhinoplasty digital photo database, examining preoperative alar retraction from January 1, 2002, to December 31, 2005, in 520 patients. Patients with more than 1 mm of alar retraction on preoperative photographs were identified. Postoperative photographs were examined to determine the effect of specific rhinoplasty maneuvers on the position of the alar margin; these maneuvers included cephalic trim, cephalic positioning of the lower lateral cartilage, composite grafts, alar rim grafts, alar batten grafts, and overlay of the lower lateral cartilage. Tertiary care academic health center. Forty-five patients with alar retraction met inclusion criteria, resulting in 63 nasal halves with alar retraction. Intraoperative findings, postoperative results. Forty-seven percent of the patients (n = 21) had prior surgery; 47% also had cephalically positioned lower lateral cartilages. Among patients with less than 4 mm of cartilage width at the outset, 46% of those who received supportive grafts achieved target correction vs only 7% for patients who did not undergo supportive cartilage grafting. In patients who underwent more than 4 mm of cephalic trim, those who received supportive grafts achieved 46% of target correction vs 11% among those who did not. Ninety-five percent of composite grafts, 69% of alar strut grafts, 47% of alar rim grafts, 43% of vertical lobule division, and 12% of alar batten grafts achieved their target correction values. Alar retraction is a highly complex problem. It can be seen de novo and is associated with cephalically positioned lower lateral cartilages. Structurally supportive grafting-including composite grafts, alar strut grafts, alar rim grafts, vertical lobule division, and alar batten grafts-can improve alar retraction. 4.


Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction.
Cyclosporine nephrotoxicity remains a major side effect in solid organ transplantation, and can be exacerbated by concomitant administration of sirolimus. Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates. We hypothesized that the Pgp activity level may affect cyclosporine cytotoxicity by interfering with the ability of Pgp to remove cyclosporine from within tubular cells, and that an interaction between cyclosporine and sirolimus on Pgp function may explain the enhancement of cyclosporine nephrotoxicity by sirolimus. Cyclosporine cytotoxicity was evaluated in primary cultures of normal human renal epithelial cells (HRECs) by cell viability and cytotoxicity assays. Verapamil, quinine, PSC833, and PGP-4008 were used as Pgp inhibitors. Rhodamine-123 (R-123), a fluorescent substrate of Pgp, was used to assess Pgp-mediated transport. Cellular cyclosporine concentration was measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Pgp expression and function were confirmed in HRECs and cyclosporine and sirolimus were shown to be Pgp inhibitors in this model. Verapamil-induced inhibition of Pgp led to a significant increase in cellular concentration of cyclosporine (P<0.05). Cyclosporine exerted a concentration-dependent cytotoxic effect on HRECs that was significantly increased by inhibition of Pgp activity. Sirolimus exerted an inhibitory effect on R-123 efflux in HRECs and increased cellular cyclosporine concentrations in a dose-dependent manner. These data demonstrate that Pgp plays a critical role in protecting renal epithelial cells from cyclosporine toxicity. The inhibitory effect of sirolimus on Pgp-mediated efflux and the cellular concentration of cyclosporine could explain the exacerbation of cyclosporine nephrotoxicity observed clinically.


Evidence that selective collateral elimination during postnatal development results in a restriction in the distribution of locus coeruleus neurons which project to the spinal cord in rats.
Experiments utilizing retrogradely transported fluorescent tracers in rats reveal that coeruleospinal cells are present throughout the locus coeruleus just after birth, but are confined to its ventral portion by the end of the fourth postnatal week. This change in distribution is not brought about by cell death, since neurons retrogradely labeled through their spinal axon following an injection of tracer shortly after birth are still present in the dorsal locus coeruleus even if the animal is not killed until the end of the fourth postnatal week. Thus the dorsal coeruleospinal neurons in newborn rats do not die but rather lose their spinal collateral.


Accuracy of identification of grating contrast by human observers: Bayesian models of V1 contrast processing show correspondence between discrimination and identification performance.
This paper presents the results of a contrast identification study, where accuracy in identification is quantified as mutual information between stimulus contrast and observer's response. The stimulus was a set of 2-8 gratings, spanning the range of visible contrasts. Gratings from the set were presented individually for 500 ms, and the observer had to respond by giving the number label corresponding to the contrast of the grating presented. Mutual information increased with set size up to a maximum of around 2.35 bits, i.e., only 5 clearly identifiable contrasts. Set sizes greater than 5 showed a plateau or decline in performance. These data were well fit by Bayesian models of V1 contrast coding, with the parameters obtained by fitting the contrast discrimination results of Chirimuuta and Tolhurst [Chirimuuta, M., & Tolhurst, D. J. (2005). Does a Bayesian model of V1 contrast coding offer a neurophysiological account of human contrast discrimination? Vision Research].


Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation.
Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.


The histamine H4 receptor as a new therapeutic target for inflammation.
Following the sequencing of the human genome, data-mining efforts have revealed the existence of a new histamine receptor that is expressed at high levels in mast cells and leukocytes. The histamine H(4) receptor has a distinct pharmacological profile and the first compounds that act selectively on the H(4) receptor have been developed. Initial experiments in vivo with H(4) receptor antagonists indicate a role for the H(4) receptor in inflammatory conditions.


Structure Elucidation of the spiro-Polyketide Svalbardine B from the Arctic Fungal Endophyte Poaceicola sp. E1PB with Support from Extensive ESI-MSn Interpretation.
Svalbardines A and B (1 and 2) and annularin K (3) were isolated from cultures of Poaceicola sp. E1PB, an endophyte isolated from the petals of Papaver dahlianum from Svalbard, Norway. Svalbardine A (1) is a pyrano[3,2-c]chromen-4-one, a new analogue of citromycetin. Svalbardine B (2) displays an unprecedented carbon skeleton based on a 5'-benzyl-spiro[chroman-3,7'-isochromene]-4,8'-dione core. Annularin K (3) is a hydroxylated derivative of annularin D. The structure of these new polyketides, along with those of known compounds 4-6, was established by spectrometric analysis, including extensive ESI-CID-MSn processing in the case of svalbardine B (2).


Author Correction: Global diversity and biogeography of bacterial communities in wastewater treatment plants.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma.
Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. We retrospectively reviewed 113 BTC patients who underwent curative-intent surgery and had available tumor sequencing data. Disease-free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS. Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04-0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51-5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups. Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.


Treatment of neural anosmia by topical application of basic fibroblast growth factor-gelatin hydrogel in the nasal cavity: an experimental study in mice.
A new treatment of neural anosmia. To investigate the effects of basic fibroblast growth factor (bFGF)-gelatin hydrogel on recovery of neural anosmia in mice. Anosmia was induced by intraperitoneal injection of 3-methylindole, 200 mg/kg. One week later, the animals underwent 1 of the following 3 procedures bilaterally: (1) group A: single-shot intranasal drip infusion of phosphate-buffered saline, (2) group B: single-shot intranasal drip infusion of bFGF, and (3) group C: placement of bFGF-gelatin hydrogel in the nasal cavity. The olfactory function of the animal was evaluated by the odor-detection test (ODT) 2 and 4 weeks later. Following the testing, the animal was killed, the thickness of the olfactory epithelium was measured, and the number of olfactory marker protein (OMP)-positive cells was counted. Research installation. Mice. The placement of bFGF-gelatin hydrogel in the nasal cavity. An ODT, thickness of olfactory epithelium, the number of OMP-positive cells The ODT proved that neural anosmia recovered in group C but not in groups A and B. Histologically, olfactory epithelium became thicker and the number of OMP-positive cells increased in group C, while such functional and histologic recovery was poor in groups A and B. These findings suggested that placement of bFGF-gelatin hydrogel in the nasal cavity was an efficient way to facilitate recovery of neural anosmia. As a gelatin hydrogel degrades slowly in the body, bFGF is gradually released around the site of the lesion; thus, it constantly exerts its effects on neural regeneration.


Embryonic cell culture in zebrafish.
Zebrafish embryonic cell cultures have many useful properties that make them complementary to intact embryos for a wide range of studies. Embryonic cell cultures allow for maintenance of transient cell populations, control of chemical and mechanical cues received by cells, and facile chemical screening. Zebrafish cells can be cultured in either heterogeneous or homogeneous cultures from a wide range of developmental time points. Here we describe two methods with particular applicability to chemical screening: a method for the culture of blastomeres for directed differentiation toward the myogenic lineage and a method for the culture of neural crest cells in heterogeneous cultures from early somitogenesis embryos.


Status shields and pharmacy work: Differences among workers by role and context.
Status and workplace context directly affect employee experiences at work. This study looks at an understudied essential health professional group: pharmacy workers. Using survey data from 298 pharmacy workers in the United States we test how status, status shields, and work context relate to perceptions of one's work. Specifically, we investigate how pharmacy roles (i.e., pharmacy technicians, pharmacists, and PharmD students) and pharmacy context (i.e., independent community, retail chain, and hospital care) affect feelings about work. Following research on status shields at work and the job characteristics model, we pose hypotheses about meaning in work, impact at work, as well as job satisfaction, and intent to quit. This study uses a conceptualization of status shields as both part of the pharmacy hierarchy and associated with work contexts. Further, testing the assumptions of the job characteristics model using varied work roles and contexts offers additional evidence the model's value. We offer implications for health and organizational social science across disciplines, as well as practical implications for scholars and practitioners.


Deep Natural Image Reconstruction from Human Brain Activity Based on Conditional Progressively Growing Generative Adversarial Networks.
Brain decoding based on functional magnetic resonance imaging has recently enabled the identification of visual perception and mental states. However, due to the limitations of sample size and the lack of an effective reconstruction model, accurate reconstruction of natural images is still a major challenge. The current, rapid development of deep learning models provides the possibility of overcoming these obstacles. Here, we propose a deep learning-based framework that includes a latent feature extractor, a latent feature decoder, and a natural image generator, to achieve the accurate reconstruction of natural images from brain activity. The latent feature extractor is used to extract the latent features of natural images. The latent feature decoder predicts the latent features of natural images based on the response signals from the higher visual cortex. The natural image generator is applied to generate reconstructed images from the predicted latent features of natural images and the response signals from the visual cortex. Quantitative and qualitative evaluations were conducted with test images. The results showed that the reconstructed image achieved comparable, accurate reproduction of the presented image in both high-level semantic category information and low-level pixel information. The framework we propose shows promise for decoding the brain activity.


Anti-Oxidative Effect of Cassia auriculata on Streptozotocin Induced Diabetic Rats.
The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited.


Description and biology of Trichopria painteri n.sp. (Hymenoptera: Diapriidae), a solitary parasitoid of Stomoxys calcitrans (Diptera: Muscidae) from Harare, Zimbabwe.
Taxonomic description and life history are given of Trichopria painteri n.sp. (Hymenoptera: Diapriidae), a solitary endoparasitoid that emerged from Stomoxys calcitrans (L.) (Diptera: Muscidae) pupae collected at an agricultural installation near Harare, Zimbabwe, Africa. Although its low level of parasitism. high immature mortality and short adult life span would require augmentative releases of T.painteri, this parasitoid could reduce isolated field populations of S.calcitrans to an acceptable level within several weeks.


[Efficacy of lumbopelvic stabilization exercises in patients with lumbalgia].
Low back pain is one of the main causes of work disability in Mexico, conservative treatment includes performing exercises. To assess the effects of lower back pain with a controlled exercise program to improve flexibility and strength in the core or center of the body. We included 18 people, 12 women and six men between 24 and 70 years of age, with low back pain, with a score of 2 to 10 using the visual analogue scale (VAS), with or without referred pain in the lower limb. Participants were advised to refrain from taking medications, alcohol and intense physical activities during the treatment period. The participants carried out 12 sessions of 10 exercises in 3 sets of 10 repetitions, 3 times per week, evaluating: weight, distance toes, anterior rectum strength, abdominal diameter, initial and final Oswestry index. The results were analyzed with the Wilcoxon test, showing a decrease not only in pain (p 0.01), but an improvement in weight, flexibility and perception of disability due to the Oswestry scale (p 0.01) showing that the series of exercises proposed is an alternative to the management of low back pain. It is recommended the presence of a therapist who accompanies and corrects the postures so that the exercises are performed well, as well as giving value to the degree of disability caused by pain in the daily performance of the people who present it.


Quality assessment of orthopedic surgery referral request letters from primary care consultation: Evaluation of a Spanish healthcare area.
One of the most requested referrals for specialist consultations from primary care (PC) is orthopedic surgery (OS). The purpose of this work was to analyze the number, characteristics, and quality of PC referral request letters in a Spanish healthcare area to their OS reference department. The referral rates for 10 years were collected, and a total of 6,225 referral letters issued during the first half of 2019 were analyzed in detail. Gender, age, patient provenance, as well as priority and other process descriptors (type of pathology, suspected diagnosis, exploratory signs, imaging tests) were assessed. A scoring system was developed to evaluate the quality of the referral to an OS consultation: Quality evaluation in OS (QEOS) model. The rate of referral to OS is rising. The mean age of the referred patient was 53 years and 59.3% were women. Degenerative pathologies justified most referral requests (65.7%), most of which related to the spine (24.2%) or the knee (23.2%). In the QEOS analysis of the referral request letters, we noted that only 36.5% described some physical exploration, 32.9% image tool request, 25.8% indicated the pharmacological treatment, and 11.2% subsequent physiotherapy, resulting in a poor average quality of PC to OS patient referral. There is a growing demand for patient referral from PC to OS, however, the number, content, and quality of referral request letters varies greatly. The QEOS tool can be the germ of a simple evaluation system that would help in the improvement of the process of continuous care.


The significance of 3D power Doppler in prenatal diagnosis and the evaluation of the anatomical structure of vein of Galen aneurysmatic malformation: case report.
Prenatal diagnosis of vein of Galen aneurysmatic malformation (VGAM) is made with the use of color Doppler, while in B-mode it is seen as a centrally placed supratentorial cystic structure. 3D-power Doppler (3D-PD) is a method that enables precise visualization of the vascular anatomy of this complex malformation. In our case, VGAM was detected in the 33rd week of gestation with power Doppler, and the use of 3D-PD enabled better visualization of the angioarchitecture and detection of feeding and drainage vessels of aneurysmatic widening. The diagnosis was confirmed postnatally with the use of MRI. A prenatal study of the angioarchitecture could have prognostic significance as well as being important in the therapeutic approach during the postnatal period.


Managing a Renal Transplant Programme During the COVID-19 Pandemic: Practical Experience from a Singapore Transplant Centre.
Coronavirus Disease 2019 (COVID-19) has significantly affected the way healthcare is delivered in Singapore. Healthcare services such as renal transplantation had to rapidly adjust and meet the needs to (1) protect patients and staff, (2) ramp up, conserve or redeploy resources while (3) ensuring that critical services remained operational. This paper aims to describe the experience of the renal transplant programme at the Singapore General Hospital (SGH) in responding to the risks and constraints posed by the pandemic. This is a review and summary of the SGH renal transplant programme's policy and protocols that were either modified or developed in response to the COVID-19 Pandemic. A multi-pronged approach was adopted to respond to the challenges of COVID-19. These included ensuring business continuity by splitting the transplant team into different locations, adopting video and tele-consults to minimise potential patient exposure to COVID-19, streamlining work processes using electronic forms, ensuring safe paths for patients who needed to come to hospital, ring-fencing and testing new inpatients at risk for COVID-19, enhancing precautionary measures for transplant surgery, ensuring a stable supply chain of immunosuppression, and sustaining patient and staff education programmes via video conferencing. Though the COVID-19 pandemic has reduced access to kidney transplantation, opportunities arose to adopt telemedicine into mainstream transplant practice as well as use electronic platforms to streamline work processes. Screening protocols were established to ensure that transplantation could be performed safely, while webinars reached out to empower patients to take precautions against COVID-19.


Surgery and Radiotherapy for Symptomatic Spinal Metastases Is More Cost Effective Than Radiotherapy Alone: A Cost Utility Analysis in a U.K. Spinal Center.
Surgery for symptomatic spinal metastases is effective at prolonging ambulation and life, but it can appear costly at first glance. We have studied the difference between the cost of surgery and reimbursement received, and the cost-effectiveness of surgery in a U.K. tertiary referral spinal center. A cost-versus-reimbursement and cost-utility analysis was performed in a prospective cohort of patients admitted for surgical treatment of spinal metastases. Outcome measures were health-related quality of life using the EuroQol EQ-5D-3L, Frankel score, quality-adjusted life years (QALYs), and treatment and reimbursement costs. One hundred thirty consecutive patients were prospectively recruited, of whom 92 had information available for cost and reimbursement comparison, and 100 had information to complete cost-utility analysis. Median cost of hospital treatment per patient was £20,752; median reimbursement received was £18,291, with a median shortfall of £1,967. Surgery in addition to radiotherapy over a lifetime horizon was both more effective and less costly than radiotherapy alone, and therefore was found to be cost-effective. Our results demonstrate that reimbursement to hospitals for surgical management of symptomatic spinal metastases in the United Kingdom is broadly in line with costs, and that there was an overall saving as a result of community care costs being mitigated by patients walking for longer, which is within the expected National Health Service threshold. Surgery for metastatic spinal tumors is effective and a good value for the money.


Association of SLC11A1 (NRAMP1) polymorphisms with pulmonary Mycobacterium avium complex infection.
Although genetic variants in SLC11A1 (NRAMP1) have been associated with mycobacterial diseases, these findings have not been extensively validated in pulmonary Mycobacterium avium complex (MAC) infection. This study investigated the genomic structure of SLC11A1 and its association with MAC infection. Nineteen polymorphic loci were genotyped in European descendents and the Japanese population. Linkage disequilibrium (LD) structures and frequencies of major haplotypes differed between these 2 populations. Tag single nucleotide polymorphisms (SNPs) were chosen from the data set, and 6 polymorphic sites were genotyped in 122 pulmonary MAC cases and 211 controls from Japan. We observed that the T allele of rs2279014 in the 3' untranslated region was associated with protection from MAC disease when comparing allele frequencies with an odds ratio of 0.582 (95% confidence interval 0.379-0.894, p = 0.013). The frequencies of haplotypes constructed with the above 6 variants did not differ between cases and controls. Allele-specific expression imbalance of SLC11A1 mRNA was evaluated in peripheral blood cells from heterozygous individuals, but no difference was observed among haplotypes. Although the significance was modest, rs2279014 is in strong LD with nearby SNPs and further studies are required for conclusive validation.


Implementation of non-invasive brain physiological monitoring concepts.
The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.


Plasma protein-facilitated coupled exchange of phosphatidylcholine and cholesteryl ester in the absence of cholesterol esterification.
A protein(s) which catalyzes the exchange of phosphatidylcholine and cholesteryl ester between plasma lipoproteins has been purified 10,000-fold from lipoprotein-free human plasma. The apparent molecular weight of the protein of the active fraction, designated lipid transfer complex (LTC), is approximately 61,000; when electrophoresed in 6 M urea, 0.1% sodium dodecyl sulfate on a 3-20% polyacrylamide gradient, the protein appears as a doublet of molecular weights 58,000 and 63,000. The active material is a glycoprotein which binds to concanavalin A. Human LTC is a lipid-protein complex with phospholipid, cholesterol, cholesteryl ester, and glyceride comprising 7% of the total mass. A similar glycoprotein (or glycoproteins) exists in rat plasma, although the fold-purification thus far achieved is low: about 500-fold. Moreover, the rat preparation enhances exchange of phosphatidylcholine, but does not appreciably enhance exchange of cholesteryl ester. Partially purified LTC (less than or equal to 3500-fold) exists in a complex with lecithin: cholesterol acyltransferase. Active lecithin: cholesterol acyltransferase is not, however, required for exchange of phosphatidylcholine or cholesteryl ester facilitated by human LTC. The rates of exchange of phosphatidylcholine and cholesteryl ester facilitated by human LTC are equal. Coupled lipid exchange occurs at all stages of LTC purification, at values of pH between 5 and 10, and at ionic strengths as great as 0.9. Moreover, phosphatidylcholine and cholesteryl ester are exchanged with 1:1 stoichiometry in the presence of thiol group reagents such as 5,5'-dithiobis-(2-nitrobenzoic acid). Both lipid exchange activities are relatively resistant to elevated temperatures. Coupled exchange of phospholipid and neutral lipid is not dictated by the nature of the lipoprotein donor and acceptor substrates: bovine liver phospholipid exchange protein catalyzes exchange of phosphatidylcholine but not cholesteryl ester between low and high density lipoproteins under conditions identical with those in which human LTC facilitates exchange of both lipids.


Fire-scarred fossil tree from the Late Triassic shows a pre-fire drought signal.
Exploring features of wood anatomy associated with fire scars found on fossil tree trunks is likely to increase our knowledge of the environmental and ecological processes that occurred in ancient forests and of the role of fire as an evolutionary force. In Petrified Forest National Park, Arizona, where Late Triassic fossil trees are exposed, we found 13 examples of fossil logs with external features resembling modern fire scars. One specimen with the unambiguous external features of a fire scar was collected for analysis of its fossilized wood. A light-colored band composed of compressed and distorted tracheids was associated with the scarring event. Cell lumen diameter and cell wall thickness in the pre-scarring fossilized wood show a response similar to that described in modern trees experiencing drought conditions. Tracheids in the post-scarring wood are initially smaller, and then become larger than average following a recovery period, as is often observed in modern conifers following fire. The responses in external morphology and wood anatomy to drought and fire were similar to those of some modern trees and support the view that some forests may have experienced conditions favoring the evolution of fire-adapted traits for more than 200 million years.


Hyperthermia increases HSP production in human PDMCs by stimulating ROS formation, p38 MAPK and Akt signaling, and increasing HSF1 activity.
Human placenta-derived multipotent cells (hPDMCs) are isolated from a source uncomplicated by ethical issues and are ideal for therapeutic applications because of their capacity for multilineage differentiation and proven immunosuppressive properties. It is known that heat shock preconditioning induces the upregulation of heat shock proteins (HSPs), which enhance survival and engraftment of embryonic stem cells (ESCs) during transplantation in live animal models, although whether heat shock preconditioning has the same effects in hPDMCs is unclear. The hPDMCs were isolated from placenta of healthy donors. The cells were treated with heat shock (43 °C, 15 min), followed by evaluation of cell viability. Furthermore, the HSPs expression was assessed by Western blot, qPCR. The reactive oxygen species (ROS) production and signal pathway activation were determined by flow cytometry and Western blot, respectively. The regulatory pathways involved in HSPs expression were examined by pretreatment with chemical inhibitors, and siRNAs of MAPK, Akt, and heat shock factor 1 (HSF1), followed by determination of HSPs expression. This study demonstrates that heat shock treatment induced ROS generation and HPSs expression in hPDMCs. Heat shock stimulation also increased p38 MAPK and Akt phosphorylation. These effects were reduced by inhibitors of ROS, p38 MAPK and Akt. Moreover, we found that heat shock treatment enhanced nuclear translocation of the HSF1 in hPDMCs, representing activation of HSF1. Pretreatment of hPDMCs with ROS scavengers, SB203580 and Akt inhibitors also reduced the translocation of HSF1 induced by heat shock. Our data indicate that heat shock acts via ROS to activate p38 MAPK and Akt signaling, which subsequently activates HSF1, leading to HSP activation and contributing to the protective role of hPDMCs.


Nanoparticle agglomerates of fluticasone propionate in combination with albuterol sulfate as dry powder aerosols.
Particle engineering strategies remain at the forefront of aerosol research for localized treatment of lung diseases and represent an alternative for systemic drug therapy. With the hastily growing popularity and complexity of inhalation therapy, there is a rising demand for tailor-made inhalable drug particles capable of affording the most proficient delivery to the lungs and the most advantageous therapeutic outcomes. To address this formulation demand, nanoparticle agglomeration was used to develop aerosols of the asthma therapeutics, fluticasone or albuterol. In addition, a combination aerosol was formed by drying agglomerates of fluticasone nanoparticles in the presence of albuterol in solution. Powders of the single drug nanoparticle agglomerates or of the combined therapeutics possessed desirable aerodynamic properties for inhalation. Powders were efficiently aerosolized (∼75% deposition determined by cascade impaction) with high fine particle fraction and rapid dissolution. Nanoparticle agglomeration offers a unique approach to obtain high performance aerosols from combinations of asthma therapeutics.


Adjustment of traumatic femur shortening assisted by an intramedullar skeletal kinetic distractor: a case report.
Distal comminuted femoral fractures with joint involvement are highly challenging for the surgeon. We present a potential therapeutic concept that aims especially at the treatment of posttraumatic leg length discrepancy. This case report describes a polytraumatized 19-year-old German woman. Among other injuries she had a third grade open distal comminuted femoral fracture with a long distance metaphyseal osseous defect. As a primary care procedure an external fixation was applied at first. On day 13, an open reconstruction of her distal femur and the articular surface was performed by screw osteosynthesis, shortening and intramedullary nailing. Due to delayed osseous consolidation an autologous cancellous bone grafting was performed twice. In addition to the second cancellous bone graft an allogeneic cortical bone graft was implemented. A 6.5cm posttraumatic leg length shortening after osseous consolidation was the result. The entire leg length shortening was successfully treated 16 months after her accident with the help of an intramedullar skeletal kinetic distractor. With the help of the current case report of a patient with polytrauma and a third grade open distal comminuted femoral fracture with joint involvement and a long distance osseous defect, we present a potential therapeutic concept that aims especially at the treatment of posttraumatic leg length discrepancy.


Dipole moment changes and voltage dependent membrane capacity of squid axon.
Changes in the membrane capacity of squid axons during hyper- and depolarizations are measured between --160 and +40 mV. After corrections for the series resistance and fringe effect, we found that the membrane capacity increased from 0.68 to 1.2 muF/cm2 with depolarization. It was further observed that tetrodotoxin the external medium eliminated the change in membrane capacity without affecting the conductivity. The voltage-dependent membrane conductivity is, in turn, greatley reduced by the internal cesium ion. These observations clearly indicate that the voltage-dependent membrane capacity and conductivity are closely related to ionic channels. Particularly, the increase in membrane capacity with depolarizations may be due to sodium channels. The change in the dipole moment associated with sodium sites was determined using values of alpham and betam at various depolarizations. We found, based on voltage clamp measurements, that the increase in the dipole moment of the sodium site between --40 and --5 mV is 1230 Debye units (D.U.) and 930 D.U. between --5 and +60mV, indicating that the depolarization of sodium channels may consist of two different steps.


Expression of plectin in muscle fibers with cytoarchitectural abnormalities.
Plectin is a protein belonging to the cytoskeletal anchoring system, concentrated at sites of mechanical stress in different cell types. In normal skeletal muscle, plectin is located at level of Z-discs, sarcolemma, post-synaptic membrane, and intermyofibrillar network. We investigated plectin immunocytochemistry in lobulated fibers, fibers with tubular aggregates, target fibers, central core disease and centronuclear myopathy. Thirty to forty percent of lobulated fibers had patchy increase of plectin immunoreactivity at sarcolemmal level with focal subsarcolemmal increases. Tubular aggregates revealed a low binding for plectin. Ten percent of central cores exhibited faint focal increase of plectin immunoreactivity. Target formations had a normal plectin pattern. In centronuclear myopathy, plectin immunoreactivity was increased around the centrally located nuclei in 8-12% of the fibers, at the sarcolemma of 50% of type 2 fibers, and at the membrane of small vacuoles located peripherally around the central nuclei. We postulate that plectin may play a role in the subsarcolemmal aggregation of mitochondria in the lobulated fibers, and in the central position of nuclei as well as in shape formation, positioning and moving of the vacuoles in centronuclear myopathy.


Lactogens protect rodent and human beta cells against glucolipotoxicity-induced cell death through Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling.
A leading cause of type 2 diabetes is a reduction in functional beta cell mass partly due to increased beta cell death, triggered by stressors such as glucolipotoxicity (GLT). This study evaluates the hypothesis that lactogens can protect beta cells against GLT and examines the mechanism behind the pro-survival effect. The effect of exogenous treatment or endogenous expression of lactogens on GLT-induced beta cell death was examined in INS-1 cells, and in rodent and human islets. The mechanism behind the pro-survival effect of lactogens was determined using an inhibitor, siRNAs, a dominant negative (DN) mutant, and Cre-lox-mediated gene deletion analysis. Lactogens significantly protect INS-1 and primary rodent beta cells against GLT-induced cell death. The pro-survival effect of lactogens in rodent beta cells is mediated through activation of the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling pathway. Lactogen-induced increase in the anti-apoptotic B cell lymphoma-extra large (BCLXL) protein is required to mediate its pro-survival effects in both INS-1 cells and primary rodent beta cells. Most importantly, lactogens significantly protect human beta cells against GLT-induced cell death, and their pro-survival effect is also mediated through the JAK2/STAT5 pathway. These studies, together with previous work, clearly demonstrate the pro-survival nature of lactogens and identify the JAK2/STAT5 pathway as an important mediator of this effect in both rodent and human beta cells. Future studies will determine the effectiveness of this peptide in vivo in the pathophysiology of type 2 diabetes.


A therapeutic index that predicts the individual effects of prednisone in patients with cirrhosis.
Our aim was to construct an index that accurately predicts the degree of benefit or harm that prednisone therapy holds for patients with liver cirrhosis. The admission and survival data of 488 patients with cirrhosis who participated in a controlled clinical trial of prednisone in a dosage of 10-15 mg daily (251 patients) versus placebo (237 patients) and who were observed for up to 12 yr were analyzed using Cox's multiple regression model. Four variables each provided significant therapeutic information: antinuclear factor (p = 0.02) and large piecemeal necroses (p = 0.02) were associated with a beneficial effect, whereas ascites (p = 0.0004) and large regenerative nodules (p = 0.0007) were associated with a harmful effect of prednisone. From these four variables a therapeutic index was constructed. For a given patient the therapeutic index is a measure of how big the effect will be if prednisone is given. The gain in survival time obtained by administering prednisone according to the therapeutic index was estimated to be 349 yr, mainly confined to 217 patients with a significant positive (121) or negative (96) therapeutic index. The therapeutic index may prove useful for the optimal administration of prednisone treatment in new patients with cirrhosis.


[Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)].
First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.


Simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design.
The negative control design can be used to provide evidence for whether a prenatal exposure-outcome association occurs by in utero mechanisms. Assortative mating has been suggested to influence results from negative control designs, although how and why has not yet been adequately explained. We aimed to explain why mutual adjustment of maternal and paternal exposure in regression models can account for assortative mating. We used directed acyclic graphs to show how bias can occur when modeling maternal and paternal effects separately. We empirically tested our claims using a simulation study. We investigated how increasing assortative mating influences the bias of effect estimates obtained from models that do and do not use a mutual adjustment strategy. In models without mutual adjustment, increasing assortative mating led to increased bias in effect estimates. The maternal and paternal effect estimates were biased by each other, making the difference between them smaller than the true difference. Mutually adjusted models did not suffer from such bias. Mutual adjustment for maternal and paternal exposure prevents bias from assortative mating influencing the conclusions of a negative control design. We further discuss issues that mutual adjustment may not be able to resolve.


The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model.
Voltage-gated sodium channels (VGSC) have been linked to inherited forms of epilepsy. The expression and biophysical properties of VGSC in the hippocampal neuronal culture model have not been clarified. In order to evaluate mechanisms of epileptogenesis that are related to VGSC, we examined the expression and function of VGSC in the hippocampal neuronal culture model in vitro and spontaneously epileptic rats (SER) in vivo. Our data showed that the peak amplitude of transient, rapidly-inactivating Na(+) current (I(Na,T)) in model neurons was significantly increased compared with control neurons, and the activation curve was shifted to the negative potentials in model neurons in whole cell recording by patch-clamp. In addition, channel activity of persistent, non-inactivating Na(+) current (I(Na,P)) was obviously increased in the hippocampal neuronal culture model as judged by single-channel patch-clamp recording. Furthermore, VGSC subtypes Na(V)1.1, Na(V)1.2 and Na(V)1.3 were up-regulated at the protein expression level in model neurons and SER as assessed by Western blotting. Four subtypes of VGSC proteins in SER were clearly present throughout the hippocampus, including CA1, CA3 and dentate gyrus regions, and neurons expressing VGSC immunoreactivity were also detected in hippocampal neuronal culture model by immunofluorescence. These findings suggested that the up-regulation of voltage-gated sodium channels subtypes in neurons coincided with an increased sodium current in the hippocampal neuronal culture model, providing a possible explanation for the observed seizure discharge and enhanced excitability in epilepsy.


Probable hereditary multiple system atrophy-autonomic (MSA-A) in a family in the United States.
Multiple system atrophy-autonomic (MSA-A) is a typically spontaneous neurological disorder. The disease, distinguished by a "hot cross bun" sign on MRI, causes a series of autonomic dysfunctions including orthostatic hypotension and genitourinary and gastrointestinal problems. We present an 84 year-old woman with MSA-A symptoms who was positive for a "hot cross bun" sign. Genetic testing was used to rule out other possible ataxias. Importantly, the patient's two sisters also presented with similar symptoms indicating a possible autosomal dominant linkage. To our knowledge, this is the first report of hereditary MSA-A in the USA.


The outside-in approach to the modified endoscopic Lothrop procedure.
Drilling in modified endoscopic Lothrop procedure (MELP) is traditionally described as commencing from the frontal recess (FR). This is challenging when the FR is involved by tumor, inflammatory disease, or scarring. The outside-in MELP, where the limits of the sinusotomy are first defined and the FR is addressed last, is described. Case-control study. Patients undergoing MELP, using the standard or outside-in approach, for inflammatory disease or endoscopic skull base surgery were assessed. Data were collected on demographics, disease characteristics, and FR involvement. Operative time was calculated from intraoperative video recording. Time points recorded were times to frontal sinus and recess connected for outside-in MELP and completion of Lothrop cavity for both groups. Perioperative complications (infection, skin breach or contusion, surgical emphysema, orbital bleeding, cerebrospinal fluid leak, and intracranial complications) were recorded. Thirty patients (67% female) with a mean age ± standard deviation of 56.0 ± 10.8 years underwent MELP (24 outside-in, six standard). Time for Lothrop completion was shorter for outside-in MELP (30.60 ± 14.10 minutes vs. 69.66 ± 64.52 minutes, P = .002). Among outside-in MELP, mean time to frontal sinus floor discovery was 8.41 ± 6.29 minutes, to recess connected 26.50 ± 12.45 minutes, and were similar regardless of pathology. The time for Lothrop cavity completion was shorter for tumor cases (24.63 ± 6.49 minutes) than for chronic rhinosinusitis without polyps (35.87 ± 20.18 minutes) and chronic rhinosinusitis with polyps (34.62 ± 11.56 minutes) (P = .05). One patient had skin edema. No other complications were recorded. The outside-in MELP is technically feasible and safe. Its advantage is a wide approach to the frontal sinus with development of the Lothrop cavity en route resulting in short predictable operative times. Defining the limits of the dissection early provides a robust and efficient approach.


A collision-free gallop-based triboelectric-piezoelectric hybrid nanogenerator.
Energy harvesting technologies that convert fluid energy into usable electrical energy are of great significance, especially in long-distance pipeline systems. Here, in order to avoid the collision of conventional galloping triboelectric nanogenerators (GTENGs), and cause material damage or noise, a freestanding gallop-based triboelectric-piezoelectric hybrid nanogenerator (HG P-TENG) is proposed to reduce material wear and improve the reliability of GTENG. Two piezoelectric sheets are attached to the cantilever beam. The root-mean-square (RMS) and peak output power of the HG P-TENG are 68.9 μW and 1.27 mW, respectively. To improve the harvesting efficiency, the fixed copper electrodes are segmented, and experiments indicate that this way of segmenting electrodes can improve the energy harvesting efficiency. Finer electrodes can effectively increase the charging rate of capacitors. A self-powered thermohygrometer and light-emitting diodes (LEDs) are demonstrated in the wind tunnel. It demonstrates that the proposed hybrid nanogenerator will exhibit great potential in pipeline systems.


Urethral circular smooth muscle in young and old women.
The purpose of this study was to determine whether thickness, fiber count, and density of urethral circular smooth muscle (CSM) differ in young and old women. Mid urethral hemiaxial sections from female cadavers aged 20-39 years (n = 12) and 70-89 years (n = 16) were stained for smooth muscle alpha actin. The CSM was studied at 0 degrees (pubic bone side) and 180 degrees (vaginal side) and in between at 45, 90, and 135 degrees. CSM layer width was measured; fibers were counted; density was calculated (fiber count/layer width). Density of urethral CSM was 25%-50% higher in specimens aged 20-39 years, compared with those aged 70-89 years. Differences were observed at 0, 135, and 180 degrees. In the younger group, higher fiber counts were observed at 135 and 180 degrees, and the CSM layer was thinner but not significantly so. The density of CSM was lower among older women, which may account for age-related decline in urethral closure pressure.


Silicone oil in the anterior chamber.
A total of 42 cases (42 eyes) with silicone oil in the anterior chamber after pars plana vitrectomy (PPV) and after silicone oil injection into the vitreous cavity (SIV) were analyzed. The main complications caused by silicone oil were corneal endothelial cell damage and secondary glaucoma. Specular microscopy showed decreased cell density, apparent pleomorphism of endothelial cells, and increased corneal thickness. In some cases, edematous and necrotic endothelial cells were found. The characteristic optical artifacts resulting from silicone oil coming into contact with the endothelium, such as a bright reflex, reversed pattern of illumination, and interference fringes, were also observed. There was a definite correlation between elevated intraocular pressure (IOP) and the presence of silicone oil in the anterior chamber; the IOP dropped significantly on removal of the oil. The treatment and prevention of conditions involving silicone oil in the anterior chamber are briefly discussed.


Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P<.05). However, dantrolene, whether alone (0 of 10 and 1 of 13) or combined with 8-CPT (0 of 10 and 0 of 13) did not increase VT incidence relative to those observed in untreated hearts (P>.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV.


Liver retransplantation for hepatitis C virus recurrence: a survey of liver transplant programs in the United States.
Hepatitis C virus (HCV)-related liver failure is the leading indication for liver transplantation (LT). The number requiring re-LT is expected to grow as patients live long enough to develop graft failure and recurrent disease. Numerous factors have been identified as influencing survival after re-LT. To gain insight into how transplant centers are dealing with this issue and whether published prognostic factors are being used, we conducted a survey of liver transplant centers across the US in late 2003. Surveys consisting of 6 multiple-choice questions were sent to all 96 adult transplant medical directors in the U.S. Fifty-five (57%) surveys were returned. Of these respondents, 95% would offer re-LT for allograft failure caused by recurrent HCV. A little more than half believed age >60 years and development of allograft cirrhosis after <2 years should exclude a patient from re-LT. However, less than half thought international normalized ratio (INR), Model for End-Stage Liver Disease (MELD), and bilirubin were important factors. After initial LT, 40% of the respondents do not have a protocol for managing HCV recurrence, and 33% responded that they treat only those who develop severe recurrence. In contrast, for re-LT, 67% preemptively treat HCV recurrence. Compared to 5 years ago, 75% believe practice patterns have changed in respect to retransplanting patients with HCV: Most were less likely to offer re-LT because of associated poor long-term survival in these patients. As of late 2003, nearly all surveyed transplant medical directors in the U.S. would offer re-LT to recurrent HCV. Perceived practice patterns for re-LT are at variance with published outcome data.


Medial temporal lobe atrophy in vascular dementia: visual temporal lobe rating scale.
Medial temporal lobe atrophy (MTA) as assessed by magnetic resonance imaging (MRI) can be measured in several ways. First of all, visual rating scale is a quick and easy measurement. MTA is a sensitive marker for Alzheimer's disease (AD), but not specific. It has been documented in other dementias including vascular dementia (VD). This study is to evaluate the degree of MTA in VD patients using a standardized visual rating scale and to suggest the importance of the possible role of MTA in VD. Twenty-five VD, 33 AD and 27 non-demented patients underwent a coronal three-dimensional magnetization prepared rapid gradient echo brain MRI sequence. MTA was rated visually using a 5-point rating scale from 0 (no atrophy) to 4 (severe atrophy). The mean summed MTA score was 5.39 in AD, 2.16 in VD and 0.56 in non-demented patients. Most of the VD patients (80%) showed MTA. They were greater in bilateral sides compared with the non-demented group, but milder than in AD. Additionally, MTA of left side score was significantly associated with age. Medial temporal lobe volumes measured visually are smaller in size in patients with VD, although not to the same extent as in AD. This suggests that MTA in VD patients may be associated with pre-existing AD.