Graphene-ferromagnet interfaces: hybridization, magnetization and charge transfer.
Electronic and magnetic properties of graphene-ferromagnet interfaces are investigated using first-principles electronic structure methods in which a single layer graphene is adsorbed on Ni(111) and Co(111) surfaces. Due to the symmetry matching and orbital overlap, the hybridization between graphene pπ and Ni (or Co) d(z(2)) states is very strong. This pd hybridization, which is both spin and k dependent, greatly affects the electronic and magnetic properties of the interface, resulting in a significantly reduced (by about 20% for Ni and 10% for Co) local magnetic moment of the top ferromagnetic layer at the interface and an induced spin polarization on the graphene layer. The calculated induced magnetic moment on the graphene layer agrees well with a recent experiment. In addition, a substantial charge transfer across the graphene-ferromagnet interfaces is observed. We also investigate the effects of thickness of the ferromagnet slab on the calculated electronic and magnetic properties of the interface. The strength of the pd hybridization and the thickness-dependent interfacial properties may be exploited to design structures with desirable magnetic and transport properties for spintronic applications.


Roles of Female and Male Genotype in Post-Mating Responses in Drosophila melanogaster.
Mating induces a multitude of changes in female behavior, physiology, and gene expression. Interactions between female and male genotype lead to variation in post-mating phenotypes and reproductive success. So far, few female molecules responsible for these interactions have been identified. Here, we used Drosophila melanogaster from 5 geographically dispersed populations to investigate such female × male genotypic interactions at the female transcriptomic and phenotypic levels. Females from each line were singly-mated to males from the same 5 lines, for a total of 25 combinations. Reproductive output and refractoriness to re-mating were assayed in females from the 25 mating combinations. Female × male genotypic interactions resulted in significant differences in these post-mating phenotypes. To assess whether female × male genotypic interactions affect the female post-mating transcriptome, next-generation RNA sequencing was performed on virgin and mated females at 5 to 6 h post-mating. Seventy-seven genes showed strong variation in mating-induced expression changes in a female × male genotype-dependent manner. These genes were enriched for immune response and odorant-binding functions, and for expression exclusively in the head. Strikingly, variation in post-mating transcript levels of a gene encoding a spermathecal endopeptidase was correlated with short-term egg production. The transcriptional variation found in specific functional classes of genes might be a read-out of female × male compatibility at a molecular level. Understanding the roles these genes play in the female post-mating response will be crucial to better understand the evolution of post-mating responses and related conflicts between the sexes.


Robust internal elastic lamina fenestration in skeletal muscle arteries.
Holes within the internal elastic lamina (IEL) of blood vessels are sites of fenestration allowing for passage of diffusible vasoactive substances and interface of endothelial cell membrane projections with underlying vascular smooth muscle. Endothelial projections are sites of dynamic Ca(2+) events leading to endothelium dependent hyperpolarization (EDH)-mediated relaxations and the activity of these events increase as vessel diameter decreases. We tested the hypothesis that IEL fenestration is greater in distal vs. proximal arteries in skeletal muscle, and is unlike other vascular beds (mesentery). We also determined ion channel protein composition within the endothelium of intramuscular and non-intramuscular skeletal muscle arteries. Popliteal arteries, subsequent gastrocnemius feed arteries, and first and second order intramuscular arterioles from rat hindlimb were isolated, cut longitudinally, fixed, and imaged using confocal microscopy. Quantitative analysis revealed a significantly larger total fenestration area in second and first order arterioles vs. feed and popliteal arteries (58% and 16% vs. 5% and 3%; N = 10 images/artery), due to a noticeably greater average size of holes (9.5 and 3.9 µm(2) vs 1.5 and 1.9 µm(2)). Next, we investigated via immunolabeling procedures whether proteins involved in EDH often embedded in endothelial cell projections were disparate between arterial segments. Specific proteins involved in EDH, such as inositol trisphosphate receptors, small and intermediate conductance Ca(2+)-activated K(+) channels, and the canonical (C) transient receptor potential (TRP) channel TRPC3 were present in both popliteal and first order intramuscular arterioles. However due to larger IEL fenestration in first order arterioles, a larger spanning area of EDH proteins is observed proximal to the smooth muscle cell plasma membrane. These observations highlight the robust area of fenestration within intramuscular arterioles and indicate that the anatomical architecture and endothelial cell hyperpolarizing apparatus for distinct vasodilatory signaling is potentially present.


[A case report of hepatectomy for liver metastasis of colon cancer after heavy particle radiotherapy].
A 51-year-old female patient was admitted to our hospital with a diagnosis of sigmoid colon cancer, and a sigmoidectomy and D3 lymphadenectomy was performed. The tumor was a moderately differentiated tubular adenocarcinoma (pT3N0M0, pStage II). No adjuvant therapy was administered. An abdominal computed tomography (CT) performed 11 months after the sigmoidectomy revealed a hepatic metastasis. The patient chose to undergo carbon ion radiotherapy (53.0 GyE/1 Fr). However, a second CT performed 10 months later indicated regrowth of the hepatic metastasis. A partial liver resection was performed, and severe deformity was observed in the irradiated region of the liver. The borderline between the tumor and surrounding tissue was not clearly discriminated. Histopathological examinations indicated increased numbers of fibrous cells in the irradiated region. To perform hepatic resection safely for liver metastasis of colorectal cancer following heavy particle radiotherapy, it is necessary to accurately determine the resection line before and during surgery. When feasible, resection of the whole irradiated area should be considered.


Large-vessel arteritis associated with chronic active Epstein-Barr virus infection.
This report describes an autopsy case of large-vessel arteritis associated with chronic active Epstein-Barr virus (EBV) infection in a 10-year-old Japanese girl. All of the 3 main coronary arteries, bilateral common carotid and subclavian arteries, abdominal aorta and its major branches, and bilateral common iliac arteries were involved, and all showed aneurysmal dilation of the lumens. Histopathologic examination revealed mesoarteritis characterized by moth-eaten-appearing destruction of the medial elastic laminae, with T lymphocyte infiltration around the vasa vasorum and severe intimal thickening. The EBV DNA genome was detected in the diseased aortic tissue by polymerase chain reaction, and in the infiltrating lymphocytes by in situ hybridization. The clinical symptoms and histopathologic manifestations of the arterial lesions in this patient were obviously different from those of Kawasaki disease and Takayasu arteritis, and the arteritis was considered to be associated with the EBV infection.


Sulfur single-wavelength anomalous diffraction crystal structure of a pheromone-binding protein from the honeybee Apis mellifera L.
Pheromone binding proteins (PBPs) are small helical proteins ( approximately 13-17 kDa) present in several sensory organs from moth and other insect species. They are involved in the transport of pheromones from the sensillar lymph to the olfactory receptors. We report here the crystal structure of a PBP (Amel-ASP1) originating from the honey-bee (Apis mellifera) antennae and expressed as recombinant protein in the yeast Pichia pastoris. Crystals of Amel-ASP1 were obtained at pH 5.5 using the nano-drops technique of crystallization with a novel optimization procedure, and the structure was solved initially with the single-wavelength anomalous diffraction technique using sulfur anomalous dispersion. The structure of Amel-ASP1 has been refined at 1.6-A resolution. Its fold is roughly similar to that of other PBP/odorant binding proteins, presenting six helices and three disulfide bridges. Contrary to the PBPs from Bombyx mori (Sandler, B. H., Nikonova, L., Leal, W. S., and Clardy, J. (2000) Chem. Biol. 7, 143-151) and Leucophea maderae (Lartigue, A., Gruez, A., Spinelli, S., Riviere, S., Brossut, R., Tegoni, M., and Cambillau, C. (2003) J. Biol. Chem. 278, 30213-30218), the extended C terminus folds into the protein and forms a wall of the internal hydrophobic cavity. Its backbone groups establish two hydrogen bonds with a serendipitous ligand, n-butyl-benzene-sulfonamide, an additive used in plastics. This mode of binding might, however, mimic that used by one of the pheromonal blend components and illustrates the binding versatility of PBPs.


Synergistic attraction of Aedes aegypti (L.) to binary blends of L-lactic acid and acetone, dichloromethane, or dimethyl disulfide.
Kairomones produced by humans provide female anthropophilic mosquitoes with vital cues used in host-seeking for a blood meal. These chemicals are emanated primarily by the skin and provide the mosquitoes a means to orient themselves to humans at a relatively close range. Chemical studies of these emanations have provided new ideas for the formulation of attractant blends. We report mosquito attraction responses for three binary blends and their separate components. The blends are comprised of L-lactic acid plus either acetone, dichloromethane, or dimethyl disulfide. At the emission rates used in our bioassays, these blends synergistically attract laboratory-reared female Aedes aegypti. Carbon dioxide is not a necessary component to yield high levels of attraction with these blends. It is postulated that at least one of these synergistic blends (L-lactic acid and acetone) produces mosquito attraction behavior similar to L-lactic acid and CO2.


Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission.
Neutrophil extracellular traps (NETs) have been visualized at the site of ANCA-associated vasculitis (AAV) lesions. Increased levels of NET remnants in the circulation have been reported in some AAV patients with active disease. The aim of the present study was to analyse NET remnants in a larger cohort of AAV patients with varying degrees of disease activity and to elucidate possible factors responsible for remnant variation. Levels of NET remnants in the circulation of healthy controls (HCs; n = 31) and AAV patients (n = 93) were determined with ELISA. NET remnants were then correlated with ANCA levels, spontaneous and induced cell death (NETosis/necrosis) in vitro, neutrophil count and corticosteroid therapy. Patients with active disease showed higher levels of circulating NET remnants compared with patients in remission (P = 0.026) and HCs (P = 0.006). From patients sampled during both remission and active disease, we found increased levels during active disease (P = 0.0010). In remission, ANCA-negative patients had higher levels of NET remnants than ANCA-positive patients and a negative correlation was observed between NET remnants and PR3-ANCA (rs = -0.287, P = 0.048). NET remnants correlated with neutrophil count in HCs (rs = 0.503, P = 0.014) but not in patients during remission. Neutrophils from patients showed enhanced spontaneous cell death (P = 0.043). We found increased levels of circulating NET remnants in patients with active AAV. Furthermore, AAV patients exhibited an increased propensity for spontaneous cell death. NET remnant levels seem to be positively related to disease activity and neutrophil count, but inversely related to ANCA at least during remission.


Arms race co-evolution of Magnaporthe oryzae AVR-Pik and rice Pik genes driven by their physical interactions.
Attack and counter-attack impose strong reciprocal selection on pathogens and hosts, leading to development of arms race evolutionary dynamics. Here we show that Magnaporthe oryzae avirulence gene AVR-Pik and the cognate rice resistance (R) gene Pik are highly variable, with multiple alleles in which DNA replacements cause amino acid changes. There is tight recognition specificity of the AVR-Pik alleles by the various Pik alleles. We found that AVR-Pik physically binds the N-terminal coiled-coil domain of Pik in a yeast two-hybrid assay as well as in an in planta co-immunoprecipitation assay. This binding specificity correlates with the recognition specificity between AVR and R genes. We propose that AVR-Pik and Pik are locked into arms race co-evolution driven by their direct physical interactions.


Relationship of etiology to treatment in congenital hypothyroidism.
We examined the patterns of TSH, T(4), and treatment schedules from diagnosis to 4 yr of age in 125 children (50 males anf 75 females) with congenital hypothyroidism (CH). Subjects were divided into 3 groups based on their thyroid scans: 1) athyreosis (n = 31), 2) dysgenesis (n = 54; 49 lingual and 5 hypoplastic), and 3) dyshormonogenesis (n = 40). Follow-up evaluation was carried out at 2-4 wk and 3, 6, 9, 12, 24, 36, and 48 months of age. Median gestational age, age at onset of therapy, and starting L-T(4) dose were similar in the three groups. In infants with athyreosis median screening TSH levels were higher (P < 0.02) and confirmatory T(4) levels were lower than in the other two groups (P < 0.01 vs. dysgenetic; P < 0.05 vs. dyshormonogenetic CH). During the first 6 months of therapy, mean TSH levels were highest in the athyrotic group, intermediate in the dysgenetic group, and lowest in the dyshormonogenetic group. In children with athyreosis, TSH levels normalized by 12 months of age. At 12 months dysgenetic patients had the highest TSH levels (P < 0.05). During the entire study period, TSH levels were lowest in patients with dyshormonogenesis (except at 48 months) and normalized earlier. Mean T(4) levels normalized by 2-4 weeks in all groups. At 3 and 6 months, the percentage of patients who required dose changes was highest in the athyrotic group, and at 12 months it was highest in the dysgenetic group. The athyrotic group received the highest dose of L-T(4), and dyshormonogenetic group received the lowest dose. We conclude that treatment and follow-up schedules for CH may differ in the three etiological categories based on the different hormonal patterns and responses to therapy. Children with athyreosis need close monitoring particularly early in life, whereas those with dysgenesis and dyshormonogenesis require more attention later in life.


Factors Associated with the Nutritional Status of Women with Non-Metastatic Breast Cancer in a Brazilian High Complexity Oncology Center.
Breast cancer poses a significant public health concern owing to its high prevalence and the risk of mortality associated with delayed diagnosis and treatment. The aim of this study was to assess the nutritional status of women with non-metastatic breast cancer and to identify factors associated with it. A cross-sectional observational study was conducted at a High Complexity Oncology Assistance Center in the southeast region of Brazil, with the aim of assessing the nutritional status in women undergoing treatment for stage I, II, or III breast cancer. Patients in palliative care or undergoing reconstructive surgery were excluded. Data collection took place between June 2022 and March 2023 and included questionnaires, physical examinations, laboratory tests, and anthropometric assessments. Nutritional status was assessed using measures such as BMI and skinfold thickness, while nutritional risk was assessed using the Nutritional Risk Screening (NRS-2002) tool. Significant associations were found between nutritional risk and educational level (p = 0.03) and BMI (p = 0.01). Binary logistic regression analysis revealed a significant association between educational level and nutritional risk, indicating that lower educational level was associated with higher odds of nutritional risk (OR = 4.59; 95% CI = 1.01-21.04; p = 0.049). In addition, regarding BMI, it was observed that a BMI above 20.5 kg/m2 was associated with a higher likelihood of nutritional risk (OR = 0.09; 95% CI = 0.01-0.89; p = 0.039). It is crucial to consider the nutritional status of breast cancer patients, alongside clinical factors, to offer comprehensive and personalized care. Gaining insight into the sociodemographic variables linked to nutritional risk can significantly contribute to our understanding of breast cancer. This knowledge, in turn, can aid in identifying effective strategies for public policy, health promotion, and prevention efforts aimed at tackling this condition.


Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis.
A simple gel technique is described for the detection of large, covalently closed, circular DNA molecules in eucaryotic cells. The procedure is based on the electrophoretic technique of Eckhardt (T. Eckhardt, Plasmid 1:584-588, 1978) for detecting bacterial plasmids and has been modified for the detection of circular and linear extrachromosomal herpesvirus genomes in mammalian cells. Gentle lysis of suspended cells in the well of an agarose gel followed by high-voltage electrophoresis allows separation of extrachromosomal DNA from the bulk of cellular DNA. Circular viral DNA from cells which carry the genomes of Epstein-Barr virus, Herpesvirus saimiri, and Herpesvirus ateles can be detected in these gels as sharp bands which comigrate with bacterial plasmid DNA of 208 kilobases. Epstein-Barr virus producer cell lines also show a sharp band of linear 160-kilobase DNA. The kinetics of the appearance of this linear band after induction of viral replication after temperature shift parallels the known kinetics of Epstein-Barr virus production in these cell lines. Hybridization of DNA after transfer to filters shows that the circular and linear DNA bands are virus specific and that as little as 0.25 Epstein-Barr virus genome per cell can be detected. The technique is simple, rapid, and sensitive and requires relatively low amounts of cells (0.5 X 10(6) to 2.5 X 10(6)).


Dual Electrochemical Treatments to Improve Properties of Ti6Al4V Alloy.
Surface treatments are considered as a good alternative to increase biocompatibility and the lifetime of Ti-based alloys used for implants in the human body. The present research reports the comparison of bare and modified Ti6Al4V substrates on hydrophilicity and corrosion resistance properties in body fluid environment at 37 °C. Several surface treatments were conducted separately to obtain either a porous oxide layer using nanostructuration (N) in ethylene glycol containing fluoride solution, or bulk oxide thin films through heat treatment at 450 °C for 3 h (HT), or electrochemical oxidation at 1 V for 3 h (EO), as well as combined treatments (N-HT and N-EO). In-situ X-ray diffraction and ex-situ transmission electron microscopy have shown that heat treatment gave first rise to the formation of a 30 nm thick amorphous layer which crystallized in rutile around 620 °C. Electrochemical oxidations gave rise to a 10 nm thick amorphous film on the top of the surface (EO) or below the amorphous nanotube layer (N-EO). Dual treated samples presented similar results with a more stable behavior for N-EO. Finally, for both corrosion and hydrophilicity points of view, the new combined treatment to get a total amorphous N-EO sample seems to be the best and even better than the partially crystallized N-HT sample.


Photonic band gap in isotropic hyperuniform disordered solids with low dielectric contrast.
We report the first experimental demonstration of a TE-polarization photonic band gap (PBG) in a 2D isotropic hyperuniform disordered solid (HUDS) made of dielectric media with a dielectric index contrast of 1.6:1, very low for PBG formation. The solid is composed of a connected network of dielectric walls enclosing air-filled cells. Direct comparison with photonic crystals and quasicrystals permitted us to investigate band-gap properties as a function of increasing rotational isotropy. We present results from numerical simulations proving that the PBG observed experimentally for HUDS at low index contrast has zero density of states. The PBG is associated with the energy difference between complementary resonant modes above and below the gap, with the field predominantly concentrated in the air or in the dielectric. The intrinsic isotropy of HUDS may offer unprecedented flexibilities and freedom in applications (i. e. defect architecture design) not limited by crystalline symmetries.


3,4-Dihydroxyphenylacetic acid is a predominant biologically-active catabolite of quercetin glycosides.
Since dietary flavonoid glycosides, including quercetin 4'-glucoside from onion, are poorly absorbed from the gastrointestinal tract, they are converted into smaller phenolic acids, which can be absorbed into the circulation. The purpose of this study was to compare the effects of the major phenolic acid catabolites of quercetin 4'-glucoside, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-hydroxyphenylacetic acid, 3,4-dihydroxybenzoic acid (protocatechuic acid) and hippuric acid, on the antioxidant activity and phase II cytoprotective enzyme induction in vitro. Both DOPAC and protocatechuic acid, having a catechol moiety, exhibited both DPPH radical scavenging and superoxide dismutase-like activities, whereas 3-hydroxyphenyl acetic acid and hippuric acid did not. DOPAC also more potently enhanced the gene expression of several phase II drug-metabolizing enzymes than the other phenolic acid catabolites. DOPAC significantly inhibited the hydrogen peroxide-induced cytotoxicity in hepatocytes with the enhancement of the total glutathione S-transferase activity. In conclusion, DOPAC may play a key role in the antioxidative potential of the colonic lumen after the ingestion of the quercetin glycoside-rich onion.


Task-sharing or public finance for the expansion of surgical access in rural Ethiopia: an extended cost-effectiveness analysis.
Despite a high burden of surgical disease, access to surgical services in low- and middle-income countries is often limited. In line with the World Health Organization's current focus on universal health coverage and equitable access to care, we examined how policies to expand access to surgery in rural Ethiopia would impact health, impoverishment and equity. An extended cost-effectiveness analysis was performed. Deterministic and stochastic models of surgery in rural Ethiopia were constructed, utilizing pooled estimates of costs and probabilities from national surveys and published literature. Model calibration and validation were performed against published estimates, with sensitivity analyses on model assumptions to check for robustness. Outcomes of interest were the number of deaths averted, the number of cases of poverty averted and the number of cases of catastrophic expenditure averted for each policy, divided across wealth quintiles. Health benefits, financial risk protection and equity appear to be in tension in the expansion of access to surgical care in rural Ethiopia. Health benefits from each of the examined policies accrued primarily to the poor. However, without travel vouchers, many policies also induced impoverishment in the poor while providing financial risk protection to the rich, calling into question the equitable distribution of benefits by these policies. Adding travel vouchers removed the impoverishing effects of a policy but decreased the health benefit that could be bought per dollar spent. These results were robust to sensitivity analyses.


MitoQ modulates oxidative stress and decreases inflammation following hemorrhage.
Oxidative stress associated with hemorrhagic shock and reperfusion (HSR) results in the production of superoxide radicals and other reactive oxygen species, leading to cell damage and multiple-organ dysfunction. We sought to determine if MitoQ, a mitochondria-targeted antioxidant, reduces morbidity in a rat model of HSR by limiting oxidative stress. HSR was achieved in male rats by arterial blood withdrawal to a mean arterial pressure of 25 ± 2 mm Hg for 1 hour before resuscitation. MitoQ (5 mg/kg), TPP (triphenylphosphonium, 5 mg/kg) or saline (0.9% vol./vol.) was administered intravenously 30 minutes before resuscitation, followed by an intraperitoneal administration (MitoQ, 20 mg/kg) immediately after resuscitation (n = 5 per group). Morbidity was assessed based on cumulative markers of animal distress (0-10 scale). Rats were sacrificed 2 hours after procedure completion, and liver tissue was collected and processed for histology or assayed for lipid peroxidation (thiobarbituric acid reactive substance [TBARS]) or endogenous antioxidant (catalase, glutathione peroxidase [GPx], and superoxide dismutase) activity. HSR significantly increased morbidity as well as TBARS and catalase activities versus sham. Conversely, no difference in GPx or superoxide dismutase activity was measured between sham, HSR, and TPP, MitoQ administration reduced morbidity versus HSR (5.8 ± 0.3 vs. 7.6 ± 0.3; p < 0.05), while TPP administration significantly reduced hepatic necrosis versus both HSR and HSR-MitoQ (1.2 ± 0.1 vs. 2.0 ± 0.2 vs. 1.9 ± 0.2; p < 0.05, n = 5). Analysis of oxidative stress demonstrated increased TBARS and GPx in HSR-MitoQ versus sham (12.0 ± 1.1 μM vs. 6.2 ± 0.5 μM and 37.9 ± 3.0 μmol/min/mL vs. 22.9 ± 2.7 μmol/min/mL, TBARS and GPx, respectively, n = 5; p < 0.05). Conversely, catalase activity in HSR-MitoQ was reduced versus HSR (1.96 ± 1.17 mol/min/mL vs. 2.58 ± 1.81 mol/min/mL; n = 5; p < 0.05). Finally, MitoQ treatment decreased tumor necrosis factor α (0.66 ± 0.07 pg/mL vs. 0.92 ± 0.08 pg/mL) and interleukin 6 (7.3 ± 0.8 pg/mL vs. 11 ± 0.9 pg/mL) versus HSR as did TPP alone (0.58 ± 0.05 pg/mL vs. 0.92 ± 0.08 pg/mL; 6.7 ± 0.6 pg/mL vs. 11 ± 0.9 pg/mL; n = 5; p < 0.05). Our data demonstrate that MitoQ treatment following hemorrhage significantly limits morbidity and decreases hepatic tumor necrosis factor α and interleukin 6. In addition, MitoQ differentially modulates oxidative stress and hepatic antioxidant activity.


Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing.
Antigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.


[Utility of Aspergillus-LFD: first experience in Chile].
The diagnosis of invasive aspergillosis remains a challenge. Detection of galactomannan in serum and bronchoalveolar lavage is a useful tool; however due to methodological and economic reasons, the test frequencies of galactomannan assays vary from daily to weekly, which constitute a risk to the patient. In this study, we aimed to evaluate and correlate the performance of the new kit Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast, economical and simple test; showed a good performance and excellent correlation with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an alternative to consider in the early diagnosis of invasive aspergillosis.


Assembling materials with DNA as the guide.
DNA's remarkable molecular recognition properties and structural features make it one of the most promising templates to pattern materials with nanoscale precision. The emerging field of DNA nanotechnology strips this molecule from any preconceived biological role and exploits its simple code to generate addressable nanostructures in one, two, and three dimensions. These structures have been used to precisely position proteins, nanoparticles, transition metals, and other functional components into deliberately designed patterns. They can also act as templates for the growth of nanowires, aid in the structural determination of proteins, and provide new platforms for genomics applications. The field of DNA nanotechnology is growing in a number of directions, carrying with it the promise to substantially affect materials science and biology.


Odontogenic sinusitis is a common cause of unilateral sinus disease with maxillary sinus opacification.
Unilateral sinus disease (USD) carries a broader differential diagnosis than bilateral sinus disease, including various inflammatory and neoplastic conditions. Odontogenic sinusitis (ODS) is a common cause of unilateral maxillary sinusitis, but few studies have examined its incidence among all USD etiologies. The main purposes of this prospective study were to determine the incidences of ODS and other etiologies causing USD with complete maxillary sinus opacification on computed tomography (CT), and to compare CT features of ODS and non-odontogenic USD patients. In addition, clinical features of the ODS cohort are described. A prospective case series of 134 patients with USD with complete maxillary sinus opacification on CT was conducted from August 2015 to November 2018. Based on nasal endoscopy, sinus CT, and dental examination and imaging, patients were categorized as having unilateral ODS or non-odontogenic USD. Patients with non-odontogenic USD were categorized as inflammatory or neoplastic. Demographic and clinical data were reported for ODS patients. Of the 134 patients, 45% had ODS, 36% had non-odontogenic inflammatory conditions, 17% had inverted papilloma, and 2% had malignancies. Of the 60 ODS cases, 86.7% were associated with middle meatal purulence on nasal endoscopy. On CT, 88.3% had extramaxillary sinus disease extension, and 65.5% of CT reports made no mention of dental pathology. ODS caused nearly 50% of all USD cases with maxillary sinus opacification on CT, and was the most common individual etiology. ODS was frequently associated with anterior ethmoid and frontal sinus disease on CT, and middle meatal purulence on nasal endoscopy.


Quantitative characterization of the energy circulation in helical beams by means of near-field diffraction.
We present a method to measure the skew angle of the wave-fronts in an optical vortex, which is directly related with the energy flux. It is based on the analysis of the evolution on propagation of the near-field diffraction pattern generated by a single-slit, consisting of two main lobes that shift in opposite directions depending on the vortex helicity. The transverse displacement of each lobe as a function of the propagation distance allows to quantify the energy circulation. Analytical, numerical and experimental results are compared, showing good agreement. We illustrate the method for the case of Bessel beams, although we also discuss other types of helical beams, such as Laguerre-Gauss and Mathieu beams.


Prevalence and clinical characteristics of psychotic versus nonpsychotic major depression in a general psychiatric outpatient clinic.
Psychotic major depression (PMD) is a severe mental disorder characterized by high levels of illness severity, chronicity, impairment, and treatment resistance. However, most past research on PMD has been conducted in inpatient hospital samples, and relatively little is known about PMD patients presenting for treatment in the community specifically. In this study, we examined the prevalence and clinical characteristics of PMD in a large sample (n=2,500) of treatment-seeking outpatients who were administered structured clinical interviews by trained diagnosticians. Of the patients diagnosed with major depression, 5.3% had psychotic features. PMD patients were more likely to be members of a racial/ethnic minority and to have lower educational attainment compared to those with nonpsychotic major depression. In addition, PMD patients were found to have greater current depression severity, suicidal ideation, and social and work impairment. These patients also were more likely to have histories of suicide attempts and psychiatric hospitalizations, to report an earlier age of illness onset, and to meet criteria for chronic depression. In terms of psychiatric comorbidity, PMD patients had higher rates of certain anxiety disorders as well as more somatoform and cluster A personality disorders. Results indicated that PMD was present in a relatively small percentage of treatment-seeking outpatients but was associated with disproportionately high levels of severity and impairment. Similarities and differences between the current findings and those from past research are discussed, including clinical implications for the identification and treatment of PMD in routine practice settings.


Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines.
The antiphospholipid (antibody) syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features, but primarily identified as thrombotic and/or obstetric related adverse events. APS is associated with the presence of antiphospholipid antibodies (aPL), including the so-called lupus anticoagulant (LA). These aPL are heterogeneous in nature, detected with varying sensitivity and specificity by a diverse range of laboratory tests. All these tests are unfortunately imperfect, suffer from poor assay reproducibility (inter-method and inter-laboratory) and a lack of standardisation and harmonisation. Clinicians and laboratory personnel may struggle to keep abreast of these factors, as well as the expanding range of available aPL tests, and consequent result interpretation. Therefore, APS remains a significant diagnostic challenge for many clinicians across a wide range of clinical specialities, due to these issues related to laboratory testing as well as the ever-expanding range of reported clinical manifestations. This review is primarily focussed on issues related to laboratory testing for APS in regards to the currently available assays, and summarises recent international consensus guidelines for aPL testing, both for the liquid phase functional LA assays and the solid phase assays (anticardiolipin and anti-beta-2-Glycoprotein-I).


Effect of Piezoelectric Technique on Auditory Function on Postoperative Day One in Septorhinoplasty Surgery.
To examine the effect of the piezoelectric application used increasingly for osteotomy and correction of nasal dorsum in septorhinoplasty surgeries on early auditory functions. Our study was conducted after the decision of 10840098-604.01.01-E.9057 taken from Istanbul Medipol University Clinical Research Local Ethics Committee. This study was designed to be prospective, randomized and controlled. Twenty patients between 18 and 50 years of age that piezoelectric technique was used in the study group and 10 patients in the same age range who underwent nasal surgery (endoscopic sinus surgery, septoplasty, lower concha radiofrequency and nasal valve surgery) for any reason in the control group were included in the study. Audiologic functions of the patients in both the groups were assessed by pure audio audiometry, tympanometry and distortion product otoacoustic emission test before the surgery and 24 hours after the surgery. The data obtained were statistically compared using the SPSS 22.0 program and P < 0.05 was considered significant. Twenty patients (5 males, 15 females) that piezoelectric (ultrasonics) technique was used during septorhinoplasty in the study group and 10 patients (5 males, 5 females) in the control group were included in the study. In the study and the control groups, preoperative and postoperative air/bone path thresholds at the right and left ears did not differ significantly (P > 0.05) at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hz. The results of distortion product otoacoustic emission results (signal/noise ratio) obtained postoperatively were not statistically significant (P > 0.05) with the results obtained preoperatively. The results of the study show that the piezoelectric technique used in septorhinoplasty does not cause a negative effect on auditory functions. This study is the first comparative study to investigate the effect of piezoelectric technique used in septorhinoplasty surgery on auditory functions. After further clinical studies performed with well-selected and large patient population, the piezoelectric techniques can be a preferred technique during septorhinoplasty operations.


Interpersonal Sensitivity Mediates the Effects of Childhood Maltreatment on the Evaluation of Life Events and Anxiety States in Adult Community Volunteers.
Childhood maltreatment has long-lasting psychological effects, which often manifest in adulthood. Previous studies have suggested that the effects of childhood maltreatment are not only direct but also indirect, being mediated by other factors. In this study, we hypothesized that the effects of childhood maltreatment on state anxiety in adulthood are mediated by interpersonal sensitivity and the evaluation of life events, and investigated this possibility by covariance structure analysis. Self-administered questionnaires (Child Abuse and Trauma Scale, State-Trait Anxiety Inventory Form Y, Life Experiences Survey, and Interpersonal Sensitivity Measure) were distributed to adult community volunteers in Japan, and 404 eligible responses were collected. A structural equation model was constructed to analyze the direct and indirect effects of childhood maltreatment on state anxiety, with interpersonal sensitivity and the evaluation of life events as potential mediators. Our model showed that childhood maltreatment increases state anxiety in adulthood both directly and indirectly via interpersonal sensitivity. In addition, interpersonal sensitivity mediated the effects of childhood maltreatment on the negative evaluation of life events, and the negative evaluation of life events mediated the effects of interpersonal sensitivity on anxiety symptoms. There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the results should be validated by a prospective study. The effects of childhood maltreatment on the state anxiety of adult volunteers are not only direct but are also mediated by interpersonal sensitivity. Our results suggest that assessing interpersonal sensitivity may help to determine optimal treatments for patients with anxiety who experienced maltreatment in childhood.


The mating sociometer: a regulatory mechanism for mating aspirations.
Two studies (Ns = 80 and 108) tested hypotheses derived from Kirkpatrick and Ellis's (2001) extension and application of sociometer theory to mating aspirations. Experiences of social rejection-acceptance by attractive opposite-sex confederates were experimentally manipulated, and the impact of these manipulations on self-esteem, mating aspirations, and friendship aspirations was assessed. Results indicated that social rejection-acceptance by members of the opposite sex altered mating aspirations; that the causal link between social rejection-acceptance and mating aspirations was mediated by changes in state self-esteem; and that the impact of social rejection-acceptance by members of opposite sex was specific to mating aspirations and did not generalize to levels of aspiration in approaching potential same-sex friendships. This research supports a conceptualization of a domain-specific mating sociometer, which functions to calibrate mating aspirations in response to experiences of romantic rejection and acceptance.


Surgical treatment outcome of subdural empyema: A clinical study.
A retrospective study of 28 patients identified with subdural empyema (SE) at the Department of Neurosurgery between the years 1995 and 2005 was carried out. SE occurred in all patients following bacterial meningitis. The six most frequently encountered clinical features included: (1) fever in 22 (79%) patients; (2) disturbed consciousness in 16 (57%) patients; (3) papilledema in 11 (39%) patients; (4) hemiparesis in 4 (14%) patients; (5) meningismus or meningeal signs in 4 (14%) patients, and (6) seizures in 3 (11%) patients. In the majority of cases, the most frequent causative pathogen of SE was Staphylococcus aureus. Surgery was performed on all patients, which included craniotomy in a group of 20 patients and burr hole drainage in a group of 8 patients. In conclusion, we believe that infants and young children should be carefully monitored following meningitis, in case of SE development, and that surgical intervention in patients presenting with meningitis may facilitate the development of SE. Furthermore, from a surgical point of view, our experience has led us to believe that craniotomy in comparison with burr hole surgery is the best surgical modality for management of SE as the recurrence rate of SE associated with burr hole surgery is high.


Personal attributions for melanoma risk in melanoma-affected patients and family members.
Personal attributions for cancer risk involve factors that individuals believe contribute to their risk for developing cancer. Understanding personal risk attributions for melanoma may dictate gene-environment melanoma risk communication strategies. We examined attributions for melanoma risk in a population-based sample of melanoma survivors, first degree family members, and family members who are also parents (N = 939). We conducted qualitative examination of open-ended risk attributions and logistic regression examining predictors (demographics, family member type, perceived risk) of the attributions reported (ultraviolet radiation [UVR] exposure, heredity/genetics, phenotype, personal melanoma history, miscellaneous). We found a predominance of risk attributions to UVR and heredity/genetics (80 and 45% of the sample, respectively). Those reporting higher education levels were more likely to endorse attributions to heredity/genetics, as well as to phenotype, than those of lower education levels. First-degree relatives and parent family members were more likely to endorse heredity/genetic attributions than melanoma survivors; melanoma survivors were more likely to endorse personal history of melanoma attributions compared to first-degree relatives and parent family members. These findings inform the development of risk communication interventions for melanoma families.


Long-term physical activity and risk of age-related cataract: a population-based prospective study of male and female cohorts.
To examine the association of total and specific types of physical activity, including walking or bicycling, exercising, work or occupational activity, home or housework, and leisure time inactivity with the risk of age-related cataract in women and men. Population-based prospective cohort study. A total of 52 660 participants (23 853 women and 28 807 men) 45 to 83 years of age from the Swedish Mammography Cohort and the Cohort of Swedish Men. Physical activity was assessed using a self-administered questionnaire at baseline. Cataract diagnosis and extraction were identified through linkage to registers. Incident age-related cataract diagnosis and cataract extraction. During a mean 12.1 years of follow-up (between January 1, 1998, and December 31, 2011; 634 631 person-years), 11 580 incident age-related cataract cases were identified. After adjusting for potential confounders, the highest quartile of total physical activity was statistically significantly associated with 13% decreased risk of cataract compared with the lowest (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.82-0.92). Walking or bicycling (>60 minutes/day vs. hardly ever; HR, 0.88; 95% CI, 0.82-0.95) and work or occupational activity (heavy manual labor vs. mostly sitting; HR, 0.84; 95% CI, 0.78-0.91) also were associated with decreased risk of cataract. Exercise training and home or housework were not associated with cataract risk. Leisure time inactivity was associated with increased risk of cataract (>6 vs. <1 hours/day; HR, 1.27; 95% CI, 1.07-1.50). The HR for high long-term total physical activity compared with low levels both at 30 years of age and at baseline was 0.76 (95% CI, 0.69-0.85). Our findings indicate that high total physical activity, especially in the long term, and such specific types of physical activity as walking or bicycling and work or occupational activity, may be associated with decreased risk of age-related cataract. Conversely, high inactivity levels may be associated with increased risk of cataract.


Visualization of multidrug resistance in vivo.
Various mechanisms are involved in multidrug resistance (MDR) for chemotherapeutic drugs, such as the drug efflux pumps, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP). In this review the mechanisms involved in MDR are described and results are reviewed with particular attention to the in vivo imaging of Pgp and MRP. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However, these methods do not yield information about the dynamic function of Pgp and MRP in vivo. For the study of Pgp- and MRP-mediated transport, single-photon emission tomography (SPET) and positron emission tomography (PET) are available. Technetium-99m sestamibi is a substrate for Pgp and MRP, and has been used in clinical studies for tumour imaging, and to visualize blockade of Pgp-mediated transport after modulation of the Pgp pump. Other 99mTc radiopharmaceuticals, such as 99mTc-tetrofosmin and several 99Tc-Q complexes, are also substrates for Pgp, but to date only results from in vitro and animal studies are available for these compounds. Several agents, including [11C]colchicine, [11C]verapamil and [11C]daunorubicin, have been evaluated for the quantification of Pgp-mediated transport with PET in vivo. The results suggest that radiolabelled colchicine, verapamil and daunorubicin are feasible substrates with which to image Pgp function in tumours. Uptake of [11C]colchicine and [11C]verapamil is relatively high in the chest area, reducing the value of both tracers for monitoring Pgp-mediated drug transport in tumours located in this region. In addition, it has to be borne in mind that only comparison of Pgp-mediated transport of radioalabelled substrates in the absence and in the presence of Pgp blockade gives quantitative information on Pgp-mediated pharmacokinetics. Leukotrienes are specific substrates for MRP. Therefore, N-[11C]acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively. Results obtained in MRP2 mutated GY/TR rats have demonstrated visualization of MRP-mediated transport. This tracer permits the study of MRP transport function abnormalities in vivo, e.g. in Dubin-Johnson patients, who are MRP2 gene deficient. Results obtained show the feasibility of using SPET and PET to study the functionality of MDR transporters in vivo.


Single species transport and self diffusion in wide single-walled carbon nanotubes.
We model and simulate gas flow through nanopores using a single-walled carbon nanotube model. Efficient protocols for the simulation of methane molecules in nanotubes are developed and validated for both the self-diffusivity, following a pulse perturbation, and for the transport diffusivity in an imposed concentration gradient. The former is found to be at least an order of magnitude lower than the latter, and to decline with increasing initial pressure, while the latter increases as the pressure gradient increases until it reaches an asymptotic value. Our previous analytic model, developed for single-file diffusion in narrow pores, is extended to wider pores for the case of single species transport. The model, which predicts the observed numerical results invokes four regimes of transport. The dominant transport is by ballistic motion near the wall in not too wide nanotubes when a pressure gradient or concentration is imposed; this mode is absent in the case of self-diffusion due to periodic boundary conditions. We also present results from systematic comparisons of flexible versus rigid tubes and explicit atom versus effective atomic potentials.


IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.
Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.


The genetic landscape of endometrial clear cell carcinomas.
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer that is generally associated with an aggressive clinical behaviour. Here, we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs), and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs. Eleven (34%), seven (22%) and six (19%) ECCs showed abnormal expression patterns for p53, ARID1A, and at least one DNA mismatch repair (MMR) protein, respectively. Targeted sequencing data were obtained from 30 of the 32 ECCs included in this study, and these revealed that two ECCs (7%) were ultramutated and harboured mutations affecting the exonuclease domain of POLE. In POLE wild-type ECCs, TP53 (46%), PIK3CA (36%), PPP2R1A (36%), FBXW7 (25%), ARID1A (21%), PIK3R1 (18%) and SPOP (18%) were the genes most commonly affected by mutations; 18% and 11% harboured CCNE1 and ERBB2 amplifications, respectively, and 11% showed DAXX homozygous deletions. ECCs less frequently harboured mutations affecting CTNNB1 and PTEN but more frequently harboured PPP2R1A and TP53 mutations than non-POLE endometrioid carcinomas from The Cancer Genome Atlas (TCGA). Compared to endometrial serous carcinomas (TCGA), ECCs less frequently harboured TP53 mutations. When a surrogate model for the molecular-based TCGA classification was used, all molecular subtypes previously identified in endometrial endometrioid and serous carcinomas were present in the ECCs studied, including POLE, MMR-deficient, copy-number high (serous-like)/p53 abnormal, and copy-number low (endometrioid)/p53 wild-type, which were significantly associated with disease-free survival in univariate analysis. These findings demonstrate that ECCs constitute a histologically and genetically heterogeneous group of tumours with varying outcomes. Furthermore, our data suggest that the classification of ECCs as being generally 'high-grade' or 'type II' tumours may not be warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


A randomised controlled trial of an intervention delivered by app instant messaging to increase the acceptability of effective contraception among young people in Tajikistan: study protocol.
Women in lower income countries experience unintended pregnancies at a higher rate compared with women in higher income countries. Unintended pregnancy is associated with numerous poorer health outcomes for both women and their children. In Tajikistan, an estimated 26% of married individuals aged 15-24 years have an unmet need for contraception. The strong cultural value placed on childbearing and oppositional attitudes towards contraception are major barriers to contraceptive uptake in the country.Mobile phone ownership is widespread in Tajikistan. The option of receiving reproductive health support on your personal phone may be an appealing alternative to attending a clinic, particularly for young people. The London School of Hygiene & Tropical Medicine and the Tajik Family Planning Association have partnered to develop and evaluate a contraceptive behavioural intervention delivered by mobile phone. The intervention was developed in 2015-2016 guided by behavioural science. It consists of short instant messages sent through an app over 4 months, contains information about contraception and behaviour change methods. This randomised controlled trial is designed to evaluate the effect of the intervention on self-reported acceptability of effective contraception at 4 months. 570 men and women aged 16-24 years will be allocated with a ratio of 1:1 to receive the intervention messages or the control messages about trial participation. The messages will be sent through the Tajik Family Planning Association's 'healthy lifestyles' app, which contains basic information about contraception. The trial was granted ethical approval by the London School of Hygiene & Tropical Medicine Interventions Research Ethics Committee on 16 May 2016 and by the Tajik National Scientific and Research Centre on Paediatrics and Child Surgery on 15 April 2016. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated to study stakeholders. Clinicaltrial.gov NCT02905513. 14 September 2016. WHO TRIAL REGISTRATION DATASET: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02905513.


Sound scattering by several zooplankton groups. II. Scattering models.
Mathematical scattering models are derived and compared with data from zooplankton from several gross anatomical groups--fluidlike, elastic shelled, and gas bearing. The models are based upon the acoustically inferred boundary conditions determined from laboratory backscattering data presented in part I of this series [Stanton et al., J. Acoust. Soc. Am. 103, 225-235 (1998)]. The models use a combination of ray theory, modal-series solution, and distorted wave Born approximation (DWBA). The formulations, which are inherently approximate, are designed to include only the dominant scattering mechanisms as determined from the experiments. The models for the fluidlike animals (euphausiids in this case) ranged from the simplest case involving two rays, which could qualitatively describe the structure of target strength versus frequency for single pings, to the most complex case involving a rough inhomogeneous asymmetrically tapered bent cylinder using the DWBA-based formulation which could predict echo levels over all angles of incidence (including the difficult region of end-on incidence). The model for the elastic shelled body (gastropods in this case) involved development of an analytical model which takes into account irregularities and discontinuities of the shell. The model for gas-bearing animals (siphonophores) is a hybrid model which is composed of the summation of the exact solution to the gas sphere and the approximate DWBA-based formulation for arbitrarily shaped fluidlike bodies. There is also a simplified ray-based model for the siphonophore. The models are applied to data involving single pings, ping-to-ping variability, and echoes averaged over many pings. There is reasonable qualitative agreement between the predictions and single ping data, and reasonable quantitative agreement between the predictions and variability and averages of echo data.


Dexmedetomidine dose-dependently enhances local anesthetic action of lidocaine.
The combination of α2-adrenoceptor agonists, such as dexmedetomidine (DEX) and clonidine, with local anesthetics has been found to extend the duration of peripheral nerve blocks, probably owing to the resultant local vasoconstriction in the peripheral nerves. However, because the clear elucidation of the effect of DEX requires examination of the local anesthetic effect with DEX alone and the combination of various concentrations of DEX with local anesthetics, we evaluated the local anesthetic effect of various concentrations of DEX alone and with a local anesthetic. The present study assessed the tail-flick (TF) latencies after injection of the appropriate drug in male Sprague-Dawley rats, using an epidural model that allowed constant pain stimulation intensity, dispersion of the anesthetic, and a precise injection site and dose. Lidocaine alone, lidocaine with 2.5-ppm DEX, lidocaine with 5.0-ppm DEX, lidocaine with 7.5-ppm DEX, and DEX alone were administered at the predetermined dose. The TF latency changes over time were compared using repeated measures analysis of variance (ANOVA). Comparisons among the groups were analyzed using ANOVA followed by a post hoc Dunnett's multiple comparison test or Tukey's multiple comparison test. The addition of DEX to lidocaine increased the TF latency and dose-dependently prolonged its duration as follows: 0-ppm DEX, 20 minutes; 2.5-ppm, 40 minutes; 5.0-ppm, 40 minutes; and 7.5-ppm, 50 minutes. DEX alone did not change the TF latency. Our results have demonstrated that DEX dose-dependently enhances the local anesthetic action of lidocaine in a rat TF model.


Validity and reliability of the Baecke questionnaire for the evaluation of habitual physical activity among people living with HIV/AIDS.
This study evaluates the validity and reliability of the Baecke questionnaire on habitual physical activity when applied to a population of HIV/AIDS subjects. Validity was determined by comparing measurements for 30 subjects of peak oxygen uptake, peak workload, and energy expenditure with scores for occupational physical activity (OPA), physical exercise in leisure (PEL), leisure and locomotion activities (LLA), and total score (TS). Reliability was determined by testing and retesting 29 subjects at intervals of 15-30 days. Validity was evaluated with the Pearson correlation and reliability analyses were done using the intraclass correlation, paired Student t-test, and Bland-Altman methods. Peak VO2 and peak workload had significant correlation with PEL (r = 0.41; r = 0.43; respectively). Energy expenditure had a significant correlation with OPA (r = 0.64). The intraclass coefficients were 0.70 or more for OPA, PEL and TS. There was no difference in OPA, PEL, LLA and TS between the two evaluations. The Bland-Altman methods showed that there was good agreement between the measurements for all habitual physical activities scores. Results show that the Baecke questionnaire is valid for the evaluation of habitual physical activity among people living with HIV/AIDS.


Brazilian version of the European Cross-Cultural Neuropsychological Test Battery (CNTB-BR): diagnostic accuracy across schooling levels.
To translate, establish the diagnostic accuracy, and standardize the Brazilian Portuguese version of the European Cross-Cultural Neuropsychological Test Battery (CNTB) considering schooling level. We first completed an English-Brazilian Portuguese translation and back-translation of the CNTB. A total of 135 subjects aged over 60 years - 65 cognitively healthy (mean 72.83, SD = 7.71; mean education 9.42, SD = 7.69; illiterate = 25.8%) and 70 with Alzheimer's disease (AD) (mean 78.87, SD = 7.09; mean education 7.62, SD = 5.13; illiterate = 10%) - completed an interview and were screened for depression. The receiver operating characteristic (ROC) analysis was used to verify the accuracy of each CNTB test to separate AD from healthy controls in participants with low levels of education (≤ 4 years of schooling) and high levels of education (≥ 8 years of schooling). The optimal cutoff score was determined for each test. The Recall of Pictures Test (RPT)-delayed recall and the Enhanced Cued Recall (ECR) had the highest power to separate AD from controls. The tests with the least impact from schooling were the Rowland Universal Dementia Assessment Scale (RUDAS), supermarket fluency, RPT naming, delayed recall and recognition, and ECR. The Brazilian Portuguese version of the CNTB was well comprehended by the participants. The cognitive tests that best discriminated patients with AD from controls in lower and higher schooling participants were RPT delayed recall and ECR, both of which evaluate memory.


A narrative analysis of clerkship reflections: Medical student identity development in a changing world.
Medical students' written reflections on their clinical experiences can be a useful tool for processing complex aspects of development as physicians. To create educational programs that scaffold adaptive professional identity development, it is essential to understand how medical students develop as professionals and process the dynamic sociocultural experiences of the current moment. To explore the developing professional consciousness of medical students through clerkship reflections. Narrative analysis of written reflections are produced by clerkship students, who were asked to tell a story that resonated with the physician's relationship with patient, self and colleagues. Two independent readers applied inductive labels to generate a homogenous codebook, which was used to generate themes that were then used to construct a conceptual model. Four themes were identified in the data that describe relationships between medical students' developing professional identities and the norms of their future professional and personal communities. These included: medical students as outsiders, conflict between the student identifying with the patient versus the healthcare team, medical students' own value judgements and, finally, the changing societal mores as they relate to social and racial injustice. The conceptual model for this experience depicts the medical student as pulled between patients and the social context on one side and the professional context of the medical centre on the other. Students long to move towards identification with the healthcare team, but reject the extremes of medical culture that they view on conflict with social and racial justice. Medical students in clinical training identify strongly with both patients and the medical team. Rather than viewing professional identity development as a longitudinal journey from one extreme to another, students have the power to call attention to entrenched problems within medical culture and increase empathy for patients by retaining their strong identification with the important issues of this time.


Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection.
Hepatitis C virus (HCV) persistence in the host results from inefficiencies of innate and adaptive immune responses. Most studies addressing the role of innate immunity concentrated on peripheral blood (PB) natural killer (NK) cells, whereas only limited information is available on intrahepatic (IH) NK cells. We therefore examined phenotypic and functional features of IH and PB NK cells in paired liver biopsy and venous blood samples from 70 patients with chronic HCV infection and 26 control persons subjected to cholecystectomy for gallstones as controls. Ex vivo isolated IH NK cells from HCV-infected patients displayed unique phenotypic features, including increased expression of NKp46-activating receptor in the face of reduced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cluster of differentiation (CD) 107a expression, which resulted in impaired degranulation compared with controls. To gain insights into the effect of HCV on NK cells, we exposed peripheral blood mononuclear cells (PBMCs) from patients and healthy donors to cell-culture-derived HCV (HCVcc) and measured NK cell degranulation, TRAIL, and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression. Exposure of PBMCs to HCVcc significantly boosted NK degranulation, pERK1/2, and TRAIL expression in healthy donors, but not in patients with chronic HCV infection, a defect that was completely reversed by interferon-alpha. Purified NK cells showed a minimal, though significant, increase in degranulation and TRAIL expression, both in patients and controls, after exposure to HCVcc. These findings indicate dysfunctional IH NK cell cytotoxicity associated with TRAIL down-regulation in chronic HCV infection, which may contribute to virus persistence. PB NK cell impairment upon exposure to HCVcc suggests the existence of an accessory cell-dependent NK cell lytic defect in chronic HCV infection predominantly involving the TRAIL pathway.


A Report of 2 Cases of Brainstem Hemorrhage After Suboccipital Craniectomy for Chiari Decompression.
Decompression surgery for Chiari malformation is known to have very low procedure-related complications. There has been no report of post-Chiari malformation decompression surgery development of brainstem hemorrhage. We report 2 post-Chiari decompression surgery brainstem hemorrhage cases with 2-yr follow-up. Two cases were reviewed in which patients underwent uncomplicated suboccipital craniectomy with expansive autologous pericranium duraplasty for Chiari decompression. Postoperatively, both patients awoke with hemibody sensory and motor deficits. Immediate postoperative magnetic resonance imaging revealed a small hemorrhage within the dorsal medulla in both cases. Follow-up imaging shows resolution along with near complete clinical recovery of deficits. These cases demonstrate a rare postdecompression surgery-related complication in Chiari malformation. We hypothesize that these hemorrhages may occur from the rapid drainage of cerebrospinal fluid resulting in a loss of positive pressure, allowing a low-pressure hemorrhage to occur. Given that these hemorrhages are of low pressure, recovery is excellent.


An Online Structural Plasticity Rule for Generating Better Reservoirs.
In this letter, we propose a novel neuro-inspired low-resolution online unsupervised learning rule to train the reservoir or liquid of liquid state machines. The liquid is a sparsely interconnected huge recurrent network of spiking neurons. The proposed learning rule is inspired from structural plasticity and trains the liquid through formating and eliminating synaptic connections. Hence, the learning involves rewiring of the reservoir connections similar to structural plasticity observed in biological neural networks. The network connections can be stored as a connection matrix and updated in memory by using address event representation (AER) protocols, which are generally employed in neuromorphic systems. On investigating the pairwise separation property, we find that trained liquids provide 1.36 0.18 times more interclass separation while retaining similar intraclass separation as compared to random liquids. Moreover, analysis of the linear separation property reveals that trained liquids are 2.05 0.27 times better than random liquids. Furthermore, we show that our liquids are able to retain the generalization ability and generality of random liquids. A memory analysis shows that trained liquids have 83.67 5.79 ms longer fading memory than random liquids, which have shown 92.8 5.03 ms fading memory for a particular type of spike train inputs. We also throw some light on the dynamics of the evolution of recurrent connections within the liquid. Moreover, compared to separation-driven synaptic modification', a recently proposed algorithm for iteratively refining reservoirs, our learning rule provides 9.30%, 15.21%, and 12.52% more liquid separations and 2.8%, 9.1%, and 7.9% better classification accuracies for 4, 8, and 12 class pattern recognition tasks, respectively.


Salutogenic Education? Movement and Whole Child Health in a Waldorf (Steiner) School.
Waldorf education, an independent alternative to public schooling, aims to produce holistically healthy graduates in a formulation that rejects the conventional distinction between education and health. Also striving to bridge that divide, this article characterizes the pedagogically salutogenic techniques Waldorf teachers use in pre-kindergarten (pre-K) and lower grade classes and explicates the ethnomedical understandings underlying them. Waldorf teachers position children as budding participants in a unified field of spiritual and other forces, prioritizing whole-child activities that keep these forces healthfully motile. Their work entails a critique not only of mainstream public schooling's ostensibly pathogenic "head-to-head" focus, but also of the biomedical approach to pediatric health. My analysis of this conjoined critique takes into account the cultural, structural, and existential realities within which Waldorf education's salutary pedagogy is daily framed and fabricated. Further, it explores the implications for anthropology of attending to movement as a key feature of healthful human experience.


The correlation between upper extremity musculoskeletal symptoms and joint kinematics, playing habits and hand span during playing among piano students.
We aimed to investigate the correlations between Upper Extremity Musculoskeletal Symptoms (MSD) and joint kinematics while playing the piano, as well as correlations between MSD and psychosocial, professional and personal habits, and bio-demographic risk factors of piano students. This cross-sectional study included 15 piano students. The research tools included 3D motion capture, anthropometric measurements, and questionnaires for obtaining data about MSD, psychological, and personal factors. The piano students recruited for this study experienced a variety of MSD during the past 12 months, with a particularly high prevalence of neck pain (80%). Extreme wrist extension and/or elbow flexion while playing the piano also correlated with MSD. Additionally, this study identified correlations between MSD and hand span (r = -.69, p≤.004) and number of playing hours per week (r = .58, p≤.024). Anthropometric factors and playing patterns should be considered together with well-known MSD risk factors, like extreme and repetitive movements. However, considering each joint singularly might not be sufficient to prevent the development of MSD when instructing the piano player; accordingly, joint synchronization should also be considered.


Biological variation of serum lipids and lipoproteins in patients with clinically well controlled non insulin dependent diabetes mellitus.
To investigate how the visit-to-visit variation in serum lipids measurements affects the decision making concerning treatment according to the National Cholesterol Education Program (NCEP) guidelines in patients with clinically well controlled non-insulin-dependent diabetes mellitus (NIDDM) we have measured the biological variation (CVb) in serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in 26 patients with NIDDM. We found the CVb as follows: TC, 5.1%; TG, 17.0%; HDL-C 4.4% and LDL-C, 8.3%. Confidence intervals (95%) were determined with total intra-individual variance values around the NCEP cut-off points to evaluate how well one, two and three lipid measurements provided reliable risk classification. A single TC measurements < 177 mg/dL or > 263 mg/dL allowed confident classification as "desirable" or "high risk" respectively. For LDL-C, one measurement was accurate only at below 106.3 mg/dL or above 183.7 mg/dL. The average of three measurements contracted these limits to < 186.7 mg/dL and > 253.3 mg/dL for TC, and < 116.3 mg/dL and > 173.7 mg/dL for LDL-C. For HDL-C also, multiple measurements improved risk assignment in a similar fashion. There were no values which allowed assignment to the "borderline high" category with one TC measurement and with one and two LDL-C measurements. The mean of three TC and three LDL-C measurements allowed assignment to the "borderline high" category, if between 213.3 and 226.7 mg/dL for TC, 143.7 and 146.3 mg/dL for LDL-C. Seven patients (26.9%) in this risk group based on the mean of two LDL-C estimates could be placed into a different category when the mean of three estimates was taken, even though the first two LDL-C test results did not differ by more than 30 mg/dL. Our results suggest that repeated lipid measurement is important especially for the "borderline-high" risk group because big variations existed in some patients, and further that TC is the most reliable quantity.


Aminoglycosides for life-threatening infections: a plea for an individualized approach using intensive therapeutic drug monitoring.
Aminoglycosides are potent antibiotics with a renewed interest due to the increase in multidrug resistant infections. Their use in life-threatening infections ‑ in combination with other antibiotics ‑ has been debated due to the lack of clear outcome benefits. However, based on recent pharmacokinetic-pharmacodynamic studies, conventional dosing may be inefficient in a considerable number of patients, which could preclude the efficiency of this potent drug class. Toxicity on the other hand remains a concern, with nephrotoxicity as the most relevant negative effect in the critically ill. Short term, intensively monitored treatment strategies - with monitoring both peak and trough levels - may increase efficacy as well as reduce toxicity in the critically ill patient.


Influence of oestrogen receptor alpha and beta on the immune system in aged female mice.
Oestrogen has a dichotomous effect on the immune system. T and B lymphopoiesis in thymus and bone marrow is suppressed, whereas antibody production is stimulated by oestrogen. In this study the importance of the oestrogen receptors (ER) ER-alpha and ER-beta in the aged immune system was investigated in 18 months old-wild type (WT), ER-alpha (ERKO), ER-beta (BERKO) and double ER-alpha and ER-beta (DERKO) knock-out mice, and compared with 4 months old WT mice. Cell phenotypes in bone marrow, spleen and thymus, and the frequency of immunoglobulin (Ig) spot forming cells (SFC) were determined. We show here that the 17-beta-oestradiol (E2)-induced downregulation of B lymphopoietic cells in bone marrow of young ovariectomized mice can be mediated through both ER-alpha and ER-beta. However, only ER-alpha is required for the age-related increased frequency of immunoglobulin M (IgM) SFC in the bone marrow, as well as for the increased production of interleukin-10 (IL-10) from cultured splenocytes in aged mice. Furthermore, increased age in WT mice resulted in lower levels of both pro- and pre-B cells but increased frequency of IgM SFC in the bone marrow, as well as increased frequency of both IgM and IgA SFC in the spleen. Results from this study provide valuable information regarding the specific functions of ER-alpha and ER-beta in the aged immune system.


Identification and partial characterization of six members of the kinesin superfamily in Drosophila.
Recent evidence has suggested that the principal polypeptide component of the microtubule motor protein kinesin may be a member of an extended superfamily of related motor proteins. To gain insight into how large the kinesin superfamily might be and to begin determining the potential functions in which various superfamily members might participate, we identified and partially characterized six additional members of the Drosophila kinesin superfamily. Genes encoding these proteins were identified by using the polymerase chain reaction with degenerate primers corresponding to highly conserved regions of the kinesin heavy-chain motor domain. Partial sequencing of the six genes revealed that they encode proteins that are 40-60% identical to the motor domain of the kinesin heavy-chain sequence. The cytogenetic locations as well as the developmental and tissue-specific expression patterns have been determined. The data suggest that each of these six kinesin-like proteins may have functions in a wide variety of cell types and tissues.


Incidence of delayed and missed diagnoses in whole-body multidetector CT in patients with multiple injuries after trauma.
Whole-body CT (WBCT) is the imaging modality of choice during the initial diagnostic work-up of multiple injured patients in order to identify serious injuries and initiate adequate treatment immediately. However, delayed diagnosed or even missed injuries have been reported frequently ranging from 1.3% to 47%. To highlight commonly missed lesions in WBCT of patients with multiple injuries. A total of 375 patients (age 42.8 ± 17.9 years, ISS 26.6 ± 17.0) with a WBCT (head to symphysis) were included. The final CT report was compared with clinical and operation reports. Discrepant findings were recorded and grouped as relevant and non-relevant to further treatment. In both groups, an experienced trauma radiologist read the CT images retrospectively, whether these lesions were missed or truly not detectable. In 336 patients (89.6%), all injuries in the regions examined were diagnosed correctly in the final reports of the initial CT. Forty-eight patients (12.8%) had injuries in regions of the body that were not included in the CT. Fourteen patients (3.7%) had injuries that did not require further treatment. Twenty-five patients (6.7%) had injuries that required further treatment. With secondary interpretation, 85.4% of all missed lesions could be diagnosed in retrospect from the primary CT data-set. Small pancreatic and bowel contusions were identified as truly non-detectable. In multiple traumas, only a few missed injuries in initial WBCT reading are clinically relevant. However, as the vast majority of these injuries are detectable, the radiologist has to be alert for commonly missed findings to avoid a delayed diagnosis.


Genetic testing in clinical practice.
The availability of genetic testing for neurologic conditions is increasing rapidly. Although several cases are discussed that present the different challenges confronting today's neurologist in using genetic testing, the focus of this article is on concepts and questions that neurologists can use to help make genetic testing decisions. Genetic testing is one of the most rapidly changing aspects of clinical medicine and will continue to evolve with the availability of whole-genome sequencing in the near future.


Disseminating quality improvement: study protocol for a large cluster-randomized trial.
Dissemination is a critical facet of implementing quality improvement in organizations. As a field, addiction treatment has produced effective interventions but disseminated them slowly and reached only a fraction of people needing treatment. This study investigates four methods of disseminating quality improvement (QI) to addiction treatment programs in the U.S. It is, to our knowledge, the largest study of organizational change ever conducted in healthcare. The trial seeks to determine the most cost-effective method of disseminating quality improvement in addiction treatment. The study is evaluating the costs and effectiveness of different QI approaches by randomizing 201 addiction-treatment programs to four interventions. Each intervention used a web-based learning kit plus monthly phone calls, coaching, face-to-face meetings, or the combination of all three. Effectiveness is defined as reducing waiting time (days between first contact and treatment), increasing program admissions, and increasing continuation in treatment. Opportunity costs will be estimated for the resources associated with providing the services. The study has three primary outcomes: waiting time, annual program admissions, and continuation in treatment. Secondary outcomes include: voluntary employee turnover, treatment completion, and operating margin. We are also seeking to understand the role of mediators, moderators, and other factors related to an organization's success in making changes. We are fitting a mixed-effect regression model to each program's average monthly waiting time and continuation rates (based on aggregated client records), including terms to isolate state and intervention effects. Admissions to treatment are aggregated to a yearly level to compensate for seasonality. We will order the interventions by cost to compare them pair-wise to the lowest cost intervention (monthly phone calls). All randomized sites with outcome data will be included in the analysis, following the intent-to-treat principle. Organizational covariates in the analysis include program size, management score, and state. The study offers seven recommendations for conducting a large-scale cluster-randomized trial: provide valuable services, have aims that are clear and important, seek powerful allies, understand the recruiting challenge, cultivate commitment, address turnover, and encourage rigor and flexibility. ClinicalTrials. govNCT00934141.


Bergmann's rule is a "just-so" story of human body size.
Carl Bergmann was an astute naturalist and physiologist. His ideas about animal size and shape were important advances in the pre-Darwinian nineteenth century. Bergmann's rule claims that that in cold climates, large body mass increases the ratio of volume-to-surface area and provides for maximum metabolic heat retention in mammals and birds. Conversely, in warmer temperatures, smaller body mass increases surface area relative to volume and allows for greater heat loss. For humans, we now know that body size and shape are regulated more by social-economic-political-emotional (SEPE) factors as well as nutrition-infection interactions. Temperature has virtually no effect. Bergmann's rule is a "just-so" story and should be relegated to teaching and scholarship about the history of science. That "rule" is no longer acceptable science and has nothing to tell us about physiological anthropology.


A small-molecule E2F inhibitor blocks growth in a melanoma culture model.
HLM006474 was identified using a computer-based virtual screen and the known crystal structure of the DNA-bound E2F4/DP2 heterodimer. Treatment of multiple cell lines with HLM006474 resulted in the loss of intracellular E2F4 DNA-binding activity as measured by electrophoretic mobility shift assay within hours. Overnight exposure to HLM006474 resulted in down-regulation of total E2F4 protein as well as known E2F targets. The effects of HLM006474 treatment on different cell lines varied but included a reduction in cell proliferation and an increase in apoptosis. HLM006474 induced apoptosis in a manner distinct from cisplatin and doxorubicin. E2F4-null mouse embryonic fibroblasts were less sensitive than wild-type counterparts to the apoptosis-inducing activity of the compound, revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture, and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system. Together, these results suggest that interference with E2F activity using small molecules may have clinical application in cancer therapy.


An Adaptive Actuation Mechanism for Anthropomorphic Robot Hands.
This paper presents an adaptive actuation mechanism that can be employed for the development of anthropomorphic, dexterous robot hands. The tendon-driven actuation mechanism achieves both flexion/extension and adduction/abduction on the finger's metacarpophalangeal joint using two actuators. Moment arm pulleys are employed to drive the tendon laterally and achieve a simultaneous execution of abduction and flexion motion. Particular emphasis has been given to the modeling and analysis of the actuation mechanism. More specifically, the analysis determines specific values for the design parameters for desired abduction angles. Also, a model for spatial motion is provided that relates the actuation modes with the finger motions. A static balance analysis is performed for the computation of the tendon force at each joint. A model is employed for the computation of the stiffness of the rotational flexure joints. The proposed mechanism has been designed and fabricated with the hybrid deposition manufacturing technique. The efficiency of the mechanism has been validated with experiments that include the assessment of the role of friction, the computation of the reachable workspace, the assessment of the force exertion capabilities, the demonstration of the feasible motions, and the evaluation of the grasping and manipulation capabilities. An anthropomorphic robot hand equipped with the proposed actuation mechanism was also fabricated to evaluate its performance. The proposed mechanism facilitates the collaboration of actuators to increase the exerted forces, improving hand dexterity and allowing the execution of dexterous manipulation tasks.


Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma.
Berberine (BBR) is a natural isoquinoline alkaloid with proven antiangiogenic and anticancer activities. We recently demonstrated that BBR and its synthetic derivative 13-(4-chlorophenylethyl)berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells. In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase of senescence associated β-galactosidase and p16 expression, and reduced expression of heparanase were observed in tumors from NAX014-treated mice than in tumors from control animals. Finally, NAX014 treatment decreased the level of perforine and granzyme mRNA in mammary tumors. Berberine did not show any statistically significant modulation in comparison with control mice. The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene. The antitumor efficacy of NAX014 is mainly related to its effect on tumor vascular network and on induction of tumor cell senescence.


Vascularized ulnar periosteal pedicled flap for forearm reconstruction: Anatomical study and a case report.
Through an anatomical review, the aim of this study is to define the ulnar periosteal branches of the posterior interosseous vessels (PIV). In addition, we report the clinical utility of a vascularized ulnar periosteal pedicled flap (VUPPF), supplied by the investigated PIV, in a complex case of radial nonunion. Ten upper limbs latex colored from fresh human cadavers were used. Branches of the PIV were dissected under 2.5× loupe magnification, noting the periosteal, muscular, and cutaneous branches arising distal to the interosseous recurrent artery. The VUPPF was measured in length (cm) and width (cm). The PIV provided a mean 12.8 periosteal branches to the ulna distributed along the most distal 15 cm, with a mean distance between branches of 1 cm, allowing for the design of a VUPPF which measured a mean 12 cm in length and 1.7 cm in width. We used a VUPPF of 7.8 cm in length and 2 cm in width to treat extensive nonvascularized bone graft nonunion with a defect of 2 cm of the left radius in a 6-year-old girl, secondary to previous Ewing's Sarcoma reconstruction. Successfully consolidation was achieved 6-months after surgery. The patient did not present postoperative complications. At 2-years of follow-up after surgery, active supination was 80° and pronation 0° (due an incomplete interosseous ossification); grip strength was 80% that of the opposite hand. The patient had resumed all her daily activities. VUPPF may be considered a valuable and reliable surgical option for forearm reconstruction in complex clinical scenarios.


[Effect of laser therapy in diabetic retinopathy on the hemodynamics of retinal vessels].
Changes in retinal hemodynamics are a factor of major influence in diabetic retinopathy. With the aid of videoangiography, the changes in retinal circulation times before and after therapeutic laser coagulation were examined in a prospective study. A marked diminution of all circulation times was observed after laser coagulation procedures: the arterial circulation time decreased from 1.02 s to 0.74 s average, the early venous circulation time from 5.18 s to 3.50 s average, and the late venous circulation time from 9.07 s to 8.16 s. Laser coagulation has a more significant influence on the capillary circulation of the retina than on the venous phase. In diabetic retinopathy, the improvement in pathologic hemodynamic situations in the retina may be a very important mechanism of action in laser coagulation therapy.


The specificity of social rank in eating disorder versus depressive symptoms.
It has been proposed that an evolutionary approach to understanding rank and social status may contribute to our understanding of eating disorder symptoms. The present study sought to explore the degree to which rank might be related to eating pathology independently of its known association with depression. A non-clinical sample of 74 women completed rank-relevant measures of social defeat, entrapment, submissive behavior and social comparison as well as measures of depressive and eating disorder symptoms. Independently of depressive symptoms, submissive behavior and an unfavorable social comparison predicted eating pathology while social defeat and internal entrapment predicted depressive symptoms. There appears to be a specific role for social rank in relation to eating pathology. However, further research is required to determine precisely what this role is and the degree to which it relates to risk or recovery.


Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.
Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the b-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.


Quantitative microbial community analysis of three different sulfidic mine tailing dumps generating acid mine drainage.
The microbial communities of three different sulfidic and acidic mine waste tailing dumps located in Botswana, Germany, and Sweden were quantitatively analyzed using quantitative real-time PCR (Q-PCR), fluorescence in situ hybridization (FISH), catalyzed reporter deposition-FISH (CARD-FISH), Sybr green II direct counting, and the most probable number (MPN) cultivation technique. Depth profiles of cell numbers showed that the compositions of the microbial communities are greatly different at the three sites and also strongly varied between zones of oxidized and unoxidized tailings. Maximum cell numbers of up to 10(9) cells g(-1) dry weight were determined in the pyrite or pyrrhotite oxidation zones, whereas cell numbers in unoxidized tailings were significantly lower. Bacteria dominated over Archaea and Eukarya at all tailing sites. The acidophilic Fe(II)- and/or sulfur-oxidizing Acidithiobacillus spp. dominated over the acidophilic Fe(II)-oxidizing Leptospirillum spp. among the Bacteria at two sites. The two genera were equally abundant at the third site. The acidophilic Fe(II)- and sulfur-oxidizing Sulfobacillus spp. were generally less abundant. The acidophilic Fe(III)-reducing Acidiphilium spp. could be found at only one site. The neutrophilic Fe(III)-reducing Geobacteraceae as well as the dsrA gene of sulfate reducers were quantifiable at all three sites. FISH analysis provided reliable data only for tailing zones with high microbial activity, whereas CARD-FISH, Q-PCR, Sybr green II staining, and MPN were suitable methods for a quantitative microbial community analysis of tailings in general.


Molecular cloning, developmental expression, promoter analysis and functional characterization of the mouse CNBP gene.
Striking conservation in various organisms suggests that cellular nucleic acid-binding protein (CNBP) plays a fundamental biological role across different species. However, the regulated expression and physiological properties of the CNBP gene are unknown. In this study, we report the molecular cloning, promoter characterization, developmental expression and functional analysis of the mouse CNBP gene. The gene contains five exons and is localized to chromosome 6 in the region corresponding to band 6 D1-D2. Primer extension assay indicates that the transcription start site is located 230 bp upstream of the initiator Met codon. Our promoter analysis indicates that strong transcription enhancer and silencer regions lie within the 1.6 kb proximal region of the promoter and the upstream -3.0 to -1.6 kb region, respectively. The promoter activity is 10 fold higher in embryonic carcinoma cells than that in fibroblast, as determined by CAT assay. Consistent with its function as a transcription factor, CNBP protein is located in the nucleus of cells. During mouse embryogenesis, CNBP is expressed in the anterior region of the early embryo and in the limb, tail and craniofacial region. Overexpression of CNBP strongly stimulates cell proliferation and increases c-myc promoter activity. Our finds suggest that CNBP may play an important role in cell proliferation and tissue patterning during anterior-posterior axis, craniofacial and limb development by targeting c-Myc.


Intraperitoneal Administration of Ethanol as a Means of Euthanasia for Neonatal Mice (Mus musculus).
The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of ethanol as "acceptable with conditions," and recent work confirmed that this method is appropriate for euthanizing adult mice, but neonatal mice have not been tested. To explore this method in neonatal mice, mouse pups (C57BL/6 and CD1, 162 total) were injected with 100% ethanol, a pentobarbital-phenytoin combination, or saline at 7, 14, 21, 28, or 35 d of age. Electrocardiograms, respiratory rates, and times to loss of righting reflex and death were recorded. Time to death (TTD) differed significantly between ethanol and pentobarbital-phenytoin at 7, 14, and 21 d and between ethanol groups at 7, 14, and 21 d compared with 35 d. The average TTD (± 1 SD) for ethanol-injected mice were: 7 d, 70.3 ± 39.8 min; 14 d, 51.7 ± 30.5 min; 21 d, 32.3 ± 20.8 min, 28 d, 14.0 ± 15.2; and 35 d, 4.9 ± 1.4. Mean TTD in pentobarbital-phenytoin-injected mice were: 7 d, 2.8 ± 0.4 min; 14 d, 2.9 ± 0.5 min; 21 d, 3.9 ± 1.2 min; 28 d, 3.9 ± 0.7 min; and 35 d, 4.4 ± 0.5. Although TTD did not differ between ethanol and pentobarbital-phenytoin at 28 d of age, the TTD in 3 of 12 mice was longer than 15 min after ethanol administration at this age. Therefore, ethanol should not be used as a method of euthanasia for mice younger than 35 d, because the criteria for humane euthanasia were met only in mice 35 d or older.


Time and financial analysis of an academic general internal medicine unit.
A detailed time and financial analysis of an academic general internal medicine unit was used to examine financial, educational, and research issues. The residents' outpatient service possessed the greatest patient visit and revenue capacity, but revenue recovery was limited by low productivity and collection rate. Outpatient revenue production could be improved but would still be less than current inpatient revenues. Full financial self-sufficiency would require improvements in several aspects of revenue production and would severely limit faculty time for teaching, personal study, and research. Indirect financial contributions to the medical center through hospitalizations and referrals dwarfed direct revenues. Several strategies for academic general internal medicine units to achieve financial and academic survival are possible, each with its own set of trade-offs. Because local circumstances differ, strategies and outcomes are likely to vary among units.