Effects of combined oral doxycycline and topical cyclosporine treatment on ocular signs, symptoms, and tear film parameters in rosacea patients.
This study reports the effects of combined use of oral doxycycline and topical cyclosporine on ocular signs, symptoms, and tear film parameters in rosacea patients. Fifty-four right eyes of 54 patients were included in this study. All patients underwent full ophthalmologic examination-including best corrected visual acuity measurement, slit-lamp anterior segment and fundus examination, tear film break-up time, and Schirmer test-before treatment and six months post-treatment. Patients were divided into two treatment groups. The first group was treated with oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. The second group received topical 0.05% cyclosporine emulsion drops twice daily for six months in addition to the oral doxycycline treatment regimen. All patients received preservati ve-free artificial tear drops, warm compress, eyelash cleaning, and topical corticosteroid drops three times daily for one month. A significant improvement in ocular signs and symptoms was recorded for all patients in groups 1 and 2 after treatment. There was not a significant difference in terms of itching, burning, meibomian gland inspissation, corneal neovascularization, and conjunctival hyperemia score changes between groups 1 and 2. The increases in Schirmer test and break-up time scores were significantly higher in group 2 than in group 1. Our results support the finding that topical cyclosporine in addition to the standard regimen improves tear function, as shown by Schirmer test and break-up time scores, in ocular rosacea patients.


Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy.
Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation (≥19% CD8(+)CD38(+)HLA-DR(+) T cells) or inflammation (hsCRP ≥2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Among 72 participants randomized to rosuvastatin and 75 to placebo, there were no significant differences in the relative changes in BMD (p > 0.29) or in fat (p ≥ 0.19). A trend toward increased LBM (p = 0.059) was seen in the rosuvastatin arm without differences in creatinine kinase or self-reported physical activity (p ≥ 0.10). In a multivariable regression model, rosuvastatin was associated with a significant positive effect on LBM after adjusting for age, sex, race, smoking status, and detectable HIV-1 viral load. Higher baseline sCD163 correlated with increases in LBM from weeks 0 to 96 (p = 0.023); greater changes in total and leg lean mass were seen among statin users with higher compared to lower baseline IP-10 levels (LBM 1.8 vs. -0.3%; p = 0.028 and leg lean mass 2.9 vs. -1.7%; p = 0.012). Rosuvastatin is associated with an absence of toxicity on BMD and a potential benefit on LBM over 96 weeks of therapy. The preservation of LBM in the rosuvastatin arm over the 2 years of the study is of major clinical relevance in delaying loss of muscle mass with aging.


Childbearing in Malawi, Africa.
Malawi is a small, landlocked country in South Eastern Africa that faces many challenges in providing health care to childbearing women. Through a partnership between the faculty of the University of Pennsylvania, School of Nursing, faculty of the Kamuzu College of Nursing in Malawi, and the Malawi Ministry of Health and Population, an ongoing collaboration has led to research and demonstration projects designed to improve the health of women and children in Malawi. To underscore the cultural context within which childbearing occurs, care of the childbearing family in Malawi is described, as is research that has documented some of the similarities and differences between childbearing in Malawi and the United States.


Signalling pathways in endometrial cancer.
Carcinogenesis is a multistage process, during which the activity of signalling pathways responsible for cell cycle regulation and division is disrupted which leads to inhibition of apoptosis and enhanced proliferation. Improper activation of Wnt/β-catenin and PI3K. Akt pathways play essential role in endometrial cancers (EC), mainly type I. Mutations in APC, axin or CTNBB1 may lead to β-catenin overactivation leading to excessive gene expression. PTEN inactivation, mutations in the PIK3CA or Akt result in increased transmission in the PI3K/Akt pathway, apoptosis inhibition, intensive cell division, mTOR excitation. In non-endometrioid cancers, key mutations include suppressor gene TP53 responsible for repairing damaged DNA or apoptosis initiation. Irregularities in gene P16, encoding a protein forming the p16-cyclinD/CDK-pRb have also been described. Understanding the complex relations between specific proteins taking part in signal transduction of the abovementioned pathways is key to research on drugs used in targeted therapy.


Selective arterial embolization in the treatment of arterial priapism.
Arterial or 'high-flow' priapism is a rare complication of penile or perineal trauma. The case is reported of a patient with a more than 2-week history of priapism who was successfully treated by selective arterial embolization, with maintenance of potency.


Molecular characterization of Trypanosoma cruzi SAP proteins with host-cell lysosome exocytosis-inducing activity required for parasite invasion.
To invade target cells, Trypanosoma cruzi metacyclic forms engage distinct sets of surface and secreted molecules that interact with host components. Serine-, alanine-, and proline-rich proteins (SAP) comprise a multigene family constituted of molecules with a high serine, alanine and proline residue content. SAP proteins have a central domain (SAP-CD) responsible for interaction with and invasion of mammalian cells by metacyclic forms. Using a 513 bp sequence from SAP-CD in blastn analysis, we identified 39 full-length SAP genes in the genome of T. cruzi. Although most of these genes were mapped in the T. cruzi in silico chromosome TcChr41, several SAP sequences were spread out across the genome. The level of SAP transcripts was twice as high in metacyclic forms as in epimastigotes. Monoclonal (MAb-SAP) and polyclonal (anti-SAP) antibodies produced against the recombinant protein SAP-CD were used to investigate the expression and localization of SAP proteins. MAb-SAP reacted with a 55 kDa SAP protein released by epimastigotes and metacyclic forms and with distinct sets of SAP variants expressed in amastigotes and tissue culture-derived trypomastigotes (TCTs). Anti-SAP antibodies reacted with components located in the anterior region of epimastigotes and between the nucleus and the kinetoplast in metacyclic trypomastigotes. In contrast, anti-SAP recognized surface components of amastigotes and TCTs, suggesting that SAP proteins are directed to different cellular compartments. Ten SAP peptides were identified by mass spectrometry in vesicle and soluble-protein fractions obtained from parasite conditioned medium. Using overlapping sequences from SAP-CD, we identified a 54-aa peptide (SAP-CE) that was able to induce host-cell lysosome exocytosis and inhibit parasite internalization by 52%. This study provides novel information about the genomic organization, expression and cellular localization of SAP proteins and proposes a triggering role for extracellular SAP proteins in host-cell lysosome exocytosis during metacyclic internalization.


High-frequency ventilation in newborn lambs after intra-uterine creation of diaphragmatic hernia.
Infants with congenital diaphragmatic hernia (CDH) die, because their lungs are hypoplastic and their pulmonary vascular resistance remains elevated after birth. In human newborns, it is difficult to appreciate the benefit of new therapeutic approaches, because the pathological findings are not uniform, the disease is rare and the clinical criteria for poor prognosis with conventional therapy are uncertain. To study the benefit of high-frequency ventilation (HFV) the use of Tolazoline in CDH, we created a diaphragmatic defect in sheep fetuses at 0.6 gestation and studied full-term newborns after a caesarian section. A sternotomy was performed to place catheters and flow probes on the aorta and pulmonary artery and to clamp the ductus arteriosus and the left pulmonary artery. Twins were used as control, and the CDH lambs were either ventilated with conventional ventilation (CV) or HFV. 23 ewes were operated upon with a 22% abortion rate and 31 newborn lambs (10 controls and 21 CDH) were studied. A complete gasometric and hemodynamic study was performed in 23 lambs (7 controls, 8 CDH with CV and 8 CDH with HFV). Clinical and pathological findings of the lambs with CDH were very similar to severe CDH in humans with bilateral lung hypoplasia, severe respiratory distress, high pulmonary vascular resistance and severe hypoxemia. HFV dramatically improved CO2 elimination, allowed less aggressive ventilation, and was associated with higher flows and lower systemic and pulmonary vascular resistance. However, HFV did not improve oxygenation leaving the newborn with severe hypoxemia associated with massive intrapulmonary foramen ovale shunting from right to left.


Efficacy and safety of a combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 as a submucosal injection solution for endoscopic resection: pilot study on a swine model.
Endoscopic resection techniques require use of submucosal injection. The aim of this study was to assess a new solution that combines hyaluronic acid, chondroitin sulfate, and poloxamer 407 for submucosal injection. A total of 48 gastric submucosal cushions were created in fresh porcine stomachs using gelafundin (n = 16) or the new solution diluted at 50 % (n = 16), or 80 % (n = 16). The duration of mucosal elevation was measured. In an in vivo model, 10 gastric submucosal cushions were created by injecting 2 mL of the new solution at 80 % and the animal was euthanized 30 minutes after the last injection. Submucosal cushions with the new solution at 80 % and 50 % concentration lasted longer than with gelafundin (23.13 ± 15.57, 13.1 ± 6.6, 3.94 ± 1.53 minutes, respectively; P = 0.000). In the in vivo study, no damage or necrosis was observed in the mucosa or muscularis propria. The combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 produces a long-lasting submucosal cushion and does not seem to induce acute damage in the tissue making it suitable for submucosal injection.


Bond insertion, complexation, and penetration pathways of vapor-deposited aluminum atoms with HO- and CH(3)O-terminated organic monolayers.
The interaction of vapor-deposited Al atoms with self-assembled monolayers (SAMs) of HS-(CH(2))(16)-X (X = -OH and -OCH(3)) chemisorbed at polycrystalline Au[111] surfaces was studied using time-of-flight secondary-ion mass spectrometry, X-ray photoelectron spectroscopy, and infrared reflectance spectroscopy. Whereas quantum chemical theory calculations show that Al insertion into the C-C, C-H, C-O, and O-H bonds is favorable energetically, it is observed that deposited Al inserts only with the OH SAM to form an -O-Al-H product. This reaction appears to cease prior to complete -OH consumption, and is followed by formation of a few overlayers of a nonmetallic type of phase and finally deposition of a metallic film. In contrast, for the OCH(3) SAM, the deposited Al atoms partition along two parallel paths: nucleation and growth of an overlayer metal film, and penetration through the OCH(3) SAM to the monolayer/Au interface region. By considering a previous observation that a CH(3) terminal group favors penetration as the dominant initial process, and using theory calculations of Al-molecule interaction energies, we suggest that the competition between the penetration and overlayer film nucleation channels is regulated by small differences in the Al-SAM terminal group interaction energies. These results demonstrate the highly subtle effects of surface structure and composition on the nucleation and growth of metal films on organic surfaces and point to a new perspective on organometallic and metal-solvent interactions.


The ultrastructure of the organic phase associated with the inorganic substance in calcified tissues.
An organic phase is closely associated with the mineral substance is all calcified matrices, where it can be demonstrated as crystal-bound proteins by biochemical methods and as crystal ghosts by electron microscopy. Interest in crystal ghosts derives chiefly from the observation that they have the same shape, arrangement, and orientation as inorganic crystallites, which suggests they may have a role in their formation. Histochemically, crystal ghosts of epiphyseal cartilage react with colloidal iron (pH 2.0), acidic phosphotungstic acid, ruthenium red, and a number of cations including calcium, barium, magnesium, lanthanum, strontium, and terbium chloride. Their reactivity is removed by methylation and only incompletely restored by saponification. Moreover, the crystal ghosts located at the periphery of the calcified areas contain vic-glycol groups, as shown by their reactivity with periodic acid-silver nitrate and periodic acid-thiosemicarbazide-osmium. All these reactions show that the crystal ghosts of epiphyseal cartilage contain acidic, probably sulfate groups and, at least initially, vic-glycol groups. Their reactivity decreases as the calcification process is completed. Although the available data are not sufficient to allow a full understanding of the nature and function of these structures, they seem to play an important role in calcification. The hypothesis is presented that crystal ghosts are preformed in calcifying matrices and are activated by the unmasking of the reactive groups in their polymeric molecule; the unmasked groups then link up with inorganic ions in such a way to form organic-inorganic structures the inorganic ions of which are arranged in an apatitelike configuration and the filamentlike shape of which is the same as that of the polymeric molecule.


Contribution of dietary lipid change to falling serum cholesterol levels between 1980 to 1982 and 1985 to 1987 in an urban population. The Minnesota Heart Survey.
We assessed dietary intake and serum total cholesterol trends during the 1980s, in the Minneapolis-St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to 74 years old participated in independent, cross-sectional, population-based surveys of risk factors for cardiovascular disease in 1980 to 1982 (n = 1611) and 1985 to 1987 (n = 2231). Age-adjusted total energy intake was similar in 1980 to 1982 and 1985 to 1987: 2528 kcal (10.6 MJ) versus 2574 kcal (10.8 MJ) for men and 1683 kcal (7.1 MJ) versus 1689 kcal (7.1 MJ) for women. However, significant changes were observed in macronutrient intake. The percent of energy from total fat intake decreased from 39.3 to 38.1% in men and 38.9 to 36.6% in women (both P < 0.01). The composition of fat consumed changed, such that the Keys score, an index of dietary fat and cholesterol, decreased by 3.3 units in both sexes (both P < 0.01). The predicted changes in serum total cholesterol (Keys score) were generally consistent with observed declines of 5.4 mg/dL (0.1 mmol/L) in men and 5.8 mg/dL (0.15 mmol/L) in women during this time period. These data suggest that members of this community are on average modifying their fat consumption and that these dietary changes are resulting in more favorable serum total cholesterol levels.


Clinical presentation of childhood soft tissue sarcomas: a systematic review and meta-analysis.
Time to diagnosis (TTD) of childhood soft tissue sarcoma (STS) is significantly associated with survival. This review aims to identify pre-diagnostic symptoms/signs to inform earlier diagnosis interventions. Medline, Embase, Cochrane and Web-of-Science were searched between January 2010 and February 2021 for studies including children (<18 years) diagnosed with STS, with no language restrictions. Pooled proportions of symptoms/signs were calculated and subanalysed by tumour location and age. Fifty-nine eligible studies were identified, totalling 2462 cases. The most frequent symptoms were lump/swelling (38%, 95% CI 27% to 51%), pain (6%, 95% CI 3% to 10%), cutaneous changes (4%, 95% CI 0 to 9%), localised eye swelling (3%, 95% CI 0 to 7%), cranial nerve deficits (2%, 95% CI 0 to 5%) and constitutional symptoms (2%, 95% CI 0 to 5%).Symptoms varied by location and age. Localised eye swelling (20%, 95% CI 3% to 45%), cranial nerve deficits (14%, 95% CI 4% to 28%) and impaired visual function (6%, 95% CI 0 to 17%) were frequent in head and neck tumours. For abdomen/pelvic tumours, urinary symptoms (24%, 95% CI 5% to 15%), abdominal distension/discomfort (22%, 95% CI 4% to 47%), genital lump/swelling (16%, 95% CI 1% to 42%), constitutional symptoms (9%, 95% CI 0%] to 23%), vaginal bleeding (7%, 95%C I 0 to 21%) and bowel habit changes (6%, 95% CI 0 to 17%) were frequent.In <5 years, consumptive coagulopathy (16%, 95% CI 0 to 48%), cutaneous changes (5%, 95% CI 0 to 40%), genital lump/swelling (4%, 95% CI 0 to 14%), reduced mobility (3%, 95% CI 0 to 11%), vaginal bleeding (2%, 95% CI 0 to 11%) and bleeding/bruising/petechiae (2%, 95% CI 0 to 20%) were frequent compared with lump/swelling, constitutional symptoms, pain and headaches which were frequent among >11 years. For STS, pre-diagnostic symptoms differ by age and location, highlighting the need to tailor early diagnosis interventions.


Posterior syphilitic uveitis: clinical characteristics, co-infection with HIV, response to treatment.
To describe the characteristics and clinical course of patients with active posterior syphilitic uveitis evaluated between 1991 and 2009. Retrospective chart review. Thirteen patients with active posterior syphilitic uveitis were identified at a single institution. All were men, and all with available data were men having sex with men (MSM). Ten of 12 (83%) with available data were HIV positive. Four (31%) had a history of syphilis. Clinical findings included infiltrative retinitis, necrotizing retinitis and optic neuritis. Two of 8 patients tested (25%) had a positive Venereal Disease Research Laboratory test in the cerebrospinal fluid. Treatments included intravenous penicillin, intramuscular penicillin and intramuscular ceftriaxone. All treated cases improved and, in some cases, inflammatory lesions completely resolved without scarring. In this series, syphilitic posterior uveitis presented only in men, and all with available data were MSM. The majority were concomitantly infected with HIV. Clinical presentations varied and all patients demonstrated either significant improvement or complete resolution of inflammation.


Increased Brain-Derived Neurotrophic Factor Levels in Cerebrospinal Fluid During the Acute Phase in TBI-Induced Mechanical Allodynia in the Rat Model.
The present study aimed to develop a rat model for mechanical allodynia after traumatic brain injury (TBI) and to investigate the expression of brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) using this model. A total of 180 rats were randomly allocated into three groups: a control group (group C), a sham-operated group (group S), and a controlled cortical impact induced TBI group (group T), 60 in each group. Von Frey test was performed to evaluate mechanical withdrawal thresholds. An enzyme-linked immunosorbent assay was performed to quantify BDNF level in CSF. The 50% withdrawal thresholds of group T were lower than those of group C and group S at all measuring points except for the preoperative period (P = 0.026, <0.001, and <0.001 for POD1, POD7, and POD14, respectively). The BDNF level of group T was higher than those of group C and group S at POD1 (P = 0.005). Upregulation of the BDNF expression in CSF was observed in rats who developed mechanical allodynia on the day after TBI. Based on our findings, to elucidate the relationship between TBI-induced neuropathic pain and BDNF expression in CSF, further research should be carried out through a multifaceted approach to a broad spectrum of pain behavior models.


Desferrioxamine treatment prevents chronic islet allograft damage.
BALB/cByJ islet allografts are acutely rejected when transplanted into allogeneic mice (CBA/J). Culture of the tissue for 7 days in 95% O2 before grafting is a suboptimal treatment for the reduction of immunogenicity in this strain combination. Approximately half the animals reject these transplants in a chronic fashion. Chronic islet rejection differs from acute rejection of uncultured allogeneic islets. During chronic rejection, beta cells within the transplanted tissue degranulate but remain intact when the animal returns to the diabetic condition. Acute islet rejection is characterized by the destruction of beta cells that remain heavily granulated as long as they remain intact. We examined the effect of the iron chelating agent, desferrioxamine, on chronic islet allograft damage. Desferrioxamine inhibited chronic islet allograft damage but did not influence the process of rejection of uncultured islet tissue. This effect of desferrioxamine could not be attributed to a direct immunosuppressive effect of this agent.


Nucleation at the contact line observed on nanotextured surfaces.
It has been conjectured that roughness plays a role in surface nucleation, the tendency for freezing to begin preferentially at the liquid-gas interface. Using high speed imaging, we sought evidence for freezing at the contact line on catalyst substrates with imposed characteristic length scales (texture). Length scales consistent with the critical nucleus size and with δ∼τ/σ, where τ is a relevant line tension and σ is the surface tension, range from nanometers to micrometers. It is found that nanoscale texture causes a shift in the nucleation of ice in supercooled water to the three-phase contact line, while microscale texture does not.


Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.
We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.


Antisocial personality disorder and TC treatment outcomes.
There is a belief that persons diagnosed with antisocial personality disorder (APD) do not respond well to treatment, but the existing research has not supported this hypothesis. This study examined the relationship of APD to therapeutic community (TC) treatment outcomes. A total of 275 men and women were randomly assigned to two TCs. It was hypothesized that clients diagnosed with APD via the Millon Clinical Multiaxial Inventory (MCMI-II) would have poorer treatment outcomes than those with no APD. The MCMI-II was used to diagnose APD because of its focus in underlying pathological personality traits, as opposed to strict behavioral criteria as used in the Diagnostic and Statistical Manual of Mental Disorders classifications for APD; this hypothesis was not supported. Logistic regression analyses indicated that an MCMI-II diagnosis of APD was unrelated to treatment outcomes. Treatment completion was the most important factor in reducing recent drug use and post-discharge arrests. The results indicate that persons diagnosed with APD, with histories of substantial drug abuse and criminality, can benefit from TC treatment with aftercare in the community or at the very least, do as well as those with no APD. In light of the high prevalence rates of APD in substance-abusing populations, future research should continue to explore the many issues surrounding the diagnosis of APD, as well as its relationship to treatment outcomes.


THE HISTORICAL PATTERN OF GENE FLOW AMONG MIGRATORY AND NONMIGRATORY POPULATIONS OF PRAIRIE WARBLERS (AVES: PARULINAE).
Within a group of interbreeding organisms, the balance of gene flow among populations and microevolutionary forces acting within populations is expected to result in clinal transitions in the phenotypes possessed by members of differentiated populations. Discontinuous variation between geographically adjacent populations suggests the presence of a significant barrier to gene flow. Here I present genetic evidence for restricted gene flow between migratory and nonmigratory populations of prairie warblers. The nonmigratory form of this species is restricted to coastal mangroves in Florida and is morphologically distinguishable from the typical, migratory form that occurs across the remainder of the eastern United States. Pairs of migratory populations exhibited little population subdivision (ΦST ⩽ 0.09), whereas pairs of migratory and nonmigratory populations are much more differentiated (ΦST = 0.27-0.42). A phylogenetic analysis of mitochondrial DNA haplotypes did not offer evidence of long-term isolation of migratory and nonmigratory populations. Together with the population genetic analysis, the phylogenetic relationship of haplotypes suggests that isolation between these forms must have arisen relatively recently in their history. Evidence for significant population structure is unexpected, given the geographic proximity of migratory and nonmigratory populations, the capacity for long-distance movements (e.g., migration) by prairie warblers, and several previous studies of population structure in North American birds. However, the findings are consistent with the geographic distribution of morphological and behavioral variation and demonstrate that significant boundaries between populations of vagile organisms may be relatively cryptic.


Displacement Patterns of the Maxilla During Parallel and Rotational Setback Movements: A Finite Element Analysis.
BACKGROUND The purpose of this analysis was to evaluate the displacement patterns of the maxilla under parallel and rotational setbacks using the finite element method (FEM). MATERIAL AND METHODS A three-dimensional (3D) finite element model of a hemimaxilla was constructed. Through a conventional Le Fort I osteotomy, 2 and 3 mm of posterior movement in a parallel and rotational manner were simulated and the displacement pattern of the maxilla in each movement type was evaluated. RESULTS Both parallel and rotational setbacks resulted in lateral and inferior displacement of the maxillary segment. The largest inferior displacement was 3.0 mm and the largest lateral displacement was 1.84 mm. All lateral displacements in the anterior region were found to be more than 1 mm. CONCLUSIONS The results of this study may provide insight into how the maxilla tends to move during total maxillary setback surgery.


Recent progress in water-splitting electrocatalysis mediated by 2D noble metal materials.
Two-dimensional (2D) nanostructures have enabled noble-metal-based nanomaterials to be promising electrocatalysts toward overall water splitting due to their inherent structural advantages, including a high specific surface active area, numerous low-coordinated atoms, and a high density of defects and edges. Moreover, it is also disclosed that the electronic effect and strain effect within 2D nanostructures also benefit the further promotion of the electrocatalytic performance. In this review, we have focused on the recent progress in the fabrication of advanced electrocatalysts based on 2D noble-metal-based nanomaterials toward water splitting electrocatalysis. First, fundamental descriptions about water-splitting mechanisms, some promising engineering strategies, and major challenges in electrochemical water splitting are given. Then, the structural merits of 2D nanostructures for water splitting electrocatalysis are also highlighted, including abundant surface active sites, lattice distortion, abundant surface defects, electronic effects, and strain effects. Additionally, some representative water-splitting electrocatalysts have been discussed in detail to highlight the superiorities of 2D noble-metal-based nanomaterials for electrochemical water splitting. Finally, the underlying challenges and future opportunities for the fabrication of more advanced electrocatalysts for water splitting are also highlighted. We hope that this review article provides guidance for the fabrication of more efficient electrocatalysts for boosting industrial hydrogen production via water splitting.


Kinetics of MgATP-dependent iron chelation from the Fe-protein of the Azotobacter vinelandii nitrogenase complex. Evidence for two states.
Chelation of Fe from the Fe-protein component (Av2) of Azotobacter vinelandii nitrogenase has been investigated. The chelation, which requires MgATP binding by Av2, is best described as a two-exponential process. The rates for the two phases differed by approximately 10-fold and increased as the concentration of MgATP was increased. The rates for both phases were 50% of maximum at approximately 1.5 mM MgATP. At MgATP concentrations greater than 100 microM, the more rapid phase represented approximately 25% of the total Fe chelated from Av2. However, below 100 microM MgATP, the proportion of the faster phase decreased until at 20 microM MgATP, only a single phase could be detected. The properties of Av2 were studied at various stages of Fe chelation. The partially chelated protein was isolated from the reaction by gel filtration and was subjected to a second MgATP-dependent Fe chelation. Material isolated after the completion of the first phase regained biphasic kinetics in subsequent chelation reactions. However, if MgATP was present during the isolation of Av2, then only a single phase was observed in the subsequent chelation studies. In addition, the enzymatic activity of Av2 decreased concomitantly with total Fe chelation. To account for these observations, a model is presented in which Av2 exists in two conformers. Fe chelation is proposed to occur from either conformer but only when two MgATP are bound. Both conformers bind MgATP with the same affinity but are distinguished by a 10-fold difference in chelation rate. The two conformers are in equilibrium and can interconvert only in the absence of MgATP. That is, MgATP binding prevents the conversion of the two conformational states.


Influence of fd gene 2-protein and the viral replication origin on the compatibility of pfd-plasmids.
Plasmids with the replication origin of bacteriophage fd, the pfd-plasmids, were investigated for compatibility in E. coli cells expressing fd gene 2-protein. This was measured by transformation of Ca-treated cells with and without a residing pfd-plasmid. When the two plasmids contained the complete intergenic region of bacteriophage fd, they were fully compatible in contrast to the situation in which at least one plasmid had a shortened origin for viral strand replication. This incompatibility effect was partially compensated for by a pfd-plasmid with a short origin and with the fd gene 2. The fd replication origin on a colEl plasmid did not affect compatibility in polA+ cells indicating its idling in the presence of the colEl origin. It can be concluded that a short replication origin requires high amounts of gene 2-protein in contrast to the long origin. Accumulation of replication intermediates severely interferes with host cell metabolism.


Prognostic significance of unintentional body weight loss in colon cancer patients.
The aim of the present study was to investigate whether unintentional body weight loss (BWL) provides additional clinical information in terms of tumor progression and prognosis in non-metastatic colon cancer. In the present study, a total of 2,406 consecutive colon cancer patients without metastasis were retrospectively enrolled. Unintentional BWL was defined as loss of >5% of body weight within the last 6-12 months, or defined subjectively upon fulfillment of at least two of the following: Evidence of change in clothing size and corroboration of the reported weight loss by family or friend. This category was recorded as present ('with') or absent ('without'). Logistic regression analysis was performed to determine the correlation between BWL and the tumor characteristics and post-operative outcomes of patients with colon cancer. The Cox regression model was used to determine the association of BWL with long-term survival of colon cancer patients. A significant association between BWL and tumor location [right vs. left: Odds ratio (OR)=1.62; P<0.001], tumor size (≥5 vs. <5 cm: OR=2.17; P<0.001), and tumor stage based on the tumor-nodes-metastasis system (T3-T4 vs. T1-T2: OR=2.02; P<0.001). Post-operative morbidity and mortality were not significantly influenced by BWL. Multivariate analysis revealed that BWL was significantly associated with overall survival [with vs. without BWL: Hazard ratio (HR)=1.178; P=0.036] and relapse-free survival (with vs. without BWL: HR=1.332; P=0.003). In conclusion, BWL in patients with colon cancer is not just a symptom, but it is also correlated with tumor location, size and depth, and is a prognostic factor for poor outcomes including overall survival and tumor relapse.


Segregation distortion causes large-scale differences between male and female genomes in hybrid ants.
Hybridization in isolated populations can lead either to hybrid breakdown and extinction or in some cases to speciation. The basis of hybrid breakdown lies in genetic incompatibilities between diverged genomes. In social Hymenoptera, the consequences of hybridization can differ from those in other animals because of haplodiploidy and sociality. Selection pressures differ between sexes because males are haploid and females are diploid. Furthermore, sociality and group living may allow survival of hybrid genotypes. We show that hybridization in Formica ants has resulted in a stable situation in which the males form two highly divergent gene pools whereas all the females are hybrids. This causes an exceptional situation with large-scale differences between male and female genomes. The genotype differences indicate strong transmission ratio distortion depending on offspring sex, whereby the mother transmits some alleles exclusively to her daughters and other alleles exclusively to her sons. The genetic differences between the sexes and the apparent lack of multilocus hybrid genotypes in males can be explained by recessive incompatibilities which cause the elimination of hybrid males because of their haploid genome. Alternatively, differentiation between sexes could be created by prezygotic segregation into male-forming and female-forming gametes in diploid females. Differentiation between sexes is stable and maintained throughout generations. The present study shows a unique outcome of hybridization and demonstrates that hybridization has the potential of generating evolutionary novelties in animals.


[Challenges to implement strategies for the primary and secondary prevention of cervical cancer in Mexico].
Mortality due to cervical cancer (CC) has decreased in developed countries given extensive screening and effective coverage. In developing countries mortality rates due to CC remain high. Since the mid-nineties there has been a decrease in mortality due to CC in Mexico, which can be attributed to the increase in coverage of the Papanicolaou (PAP) (beta -.195, IC95% -.274, -.117) and the decrease in the birth rate (beta -.407, IC95% -.632, -.182). The use of the PAP in conjunction with an HPV test within the early CC detection program would have a synergistic effect; HPV testing should be combined with the Pap test. Primary prevention of CC is possible with the HPV vaccine. This vaccine will be an additional tool for reducing CC-related morbidity and mortality, but will not replace screening and treatment. To adopt a prevention policy that includes an HPV vaccine we will need to: determine the burden of HPV-related disease; have sufficient epidemiological evidence and data about technical aspects of the vaccine; take into account the psyschosocial and ethical aspects of the vaccine and guarantee good organization of vaccine implementation.


Contracture Treatment With 5-FU.
We present a case of a 53-year-old female patient who was treated with 5-Fluorouracil (5-FU) after postsurgical contracture. A review of the literature regarding the use of 5-FU injections as a minimally invasive way to treat contracture was performed. We describe that the use of 5-FU injections is the preferred method for the effective treatment of contracture with minimal risk to the patient.


Subjective health complaints and quality of life in patients with irritable bowel syndrome following Giardia lamblia infection: a case control study.
Irritable bowel syndrome (IBS) is associated with unexplained medical symptoms, and the degree of somatic comorbidity may indicate whether the aetiology of IBS is predominantly psychological or biological in origin. The purpose of this study was to examine the comorbidity and quality of life of patients with IBS following infection with Giardia lamblia. Sixty-seven consecutive patients with persistent abdominal symptoms, initiated by an acute infection with G. lamblia, completed questionnaires for scoring of subjective health complaints (SHC) and quality of life (Short-form Nepean Dyspepsia Index (SF-NDI)). The scores were compared with corresponding scores in persons from the general population (n=70). Compared with controls, each of the two groups of patients, those with present (n=17) and those with cured (n=50) G. lamblia infection, had significantly higher scores (p<0.0001) on SHC. However, subscores on somatic comorbidity (musculoskeletal pain) were low and similar to those in the general population (OR 1.2 (0.51-2.73)). Quality of life was substantially impaired in the patients; sum scores 30.0+/-8.0 (mean+/-SD) and 31.7+/-9.3 in the patient groups and 13.5+/-6.8 in the general population (p<0.0001). Patients with post-giardiasis IBS suffer very little somatic comorbidity, suggesting that the aetiology of this form of postinfective IBS is predominantly biological in origin and may thus differ from the more common, non-postinfective forms of IBS. The combination of persisting abdominal symptoms and psychological distress might be a perpetuating factor contributing to low quality of life.


Flame synthesis of nanosized Cu-Ce-O, Ni-Ce-O, and Fe-Ce-O catalysts for the water-gas shift (WGS) reaction.
A flame synthesis method has been used to prepare nanosized, high-surface-area Cu-Ce-O, Ni-Ce-O, and Fe-Ce-O catalysts from aqueous solutions of metal acetate precursors. The particles were formed by vaporization of the precursors followed by reaction and then gas to particle conversion. The specific surface areas of the synthesized powders ranged from 127 to 163 m(2)/g. High-resolution transmission electron microscope imaging showed that the particle diameters for the ceria materials are in the range of 3-10 nm, and a thin layer of amorphous material was observed on the surface of the particles. The presence and surface enrichment of the transition-metal oxides (CuO, NiO, and Fe(2)O(3)) on the ceria particles were detected using X-ray photoelectron spectroscopy. Electron energy-loss spectroscopic studies suggest the formation of a core-shell structure in the as-prepared particles. Extended X-ray absorption fine structure studies suggest that the dopants in all M-Ce-O systems are almost isostructural with their oxide counterparts, indicating the doping materials form separate oxide phases (CuO, Fe(2)O(3), NiO) within the host matrix (CeO(2)). Etching results confirm that most of the transition-metal oxides are present on the surface of CeO(2), easily dissolved by nitric acid. The performance of the flame-synthesized catalysts was examined toward water-gas shift (WGS) activity for fuel processing applications. The WGS activity of metal ceria catalysts decreases in the order Cu-Ce-O > Ni-Ce-O > Fe-Ce-O > CeO(2) with a feed mixture having a hydrogen to carbon monoxide (H(2)/CO) ratio of 1. There was no methane formation for these catalysts under the tested conditions.


[Ambulatory venous thromboembolitic disease. Clinical, etiological and evolutive data].
Venous stasis in bedridden patients is recognized as one of the risk factors for venous thromboembolism but the phenomena is known to occur in ambulatory subjects and another cause must be involved. We investigated a series of consecutive ambulatory patients with venous thromboembolism in order to distinguish the particular clinical manifestations and possible aetiologies. We compared a retrospective series of 120 consecutive patients with deep vein thromboembolism of the lower limbs and 127 patients with the same disease who had been bedridden at onset. In addition to the physical examination, the aetiological work-up included echography (n = 14), abdominal computed tomography (n = 38) and/or haemostasis studies (n = 61). Mean follow up was 23 +/- 13 months (range 1-45 months). Family history of deep venous thromboembolism was found in 17 patients and recurrence was observed in 50 patients. Phlebitis was on the right in 52 cases, on the left in 47 and bilateral in 17. Proximal locations were more frequent (74%) and pulmonary embolism occurred in one-half of the patients (n = 58). A cause was identified in 61 cases (50.8%): cancer (n = 24, 17 known, 7 previously unknown), dyscrasia (n = 17, protein S or C deficiency (5), increased plasminogen activator inhibitor I (8), circulating anticoagulants (3), hypofibrinogen (1), idiopathic varicose veins (n = 7), pregnancy (n = 5), oral contraceptives (n = 4) and other causes (n = 4). No cause was identified in 59 patients. Pulmonary embolism led to death in 4 cases. Seven patients were lost to follow-up and anticoagulation therapy was taken by 79 (72%) then interrupted in the others 3 to 6 months later. Eighteen patients died, 14 due to the underlying disease, 2 from new cancers and 12 after recurrent thromboembolism. Ambulatory venous embolism is as frequent as embolism in bedridden patients and the cause can be observed in 50% of the cases.


Evaluating Complex Mixtures in the Zebrafish Embryo by Reconstituting Field Water Samples: A Metal Pollution Case Study.
Accurately assessing the toxicity of complex, environmentally relevant mixtures remains an important challenge in ecotoxicology. The goal was to identify biological effects after exposure to environmental water samples and to determine whether the observed effects could be explained by the waterborne metal mixture found in the samples. Zebrafish embryos were exposed to water samples of five different sites originating from two Flemish (Mol and Olen, Belgium) metal contaminated streams: "Scheppelijke Nete" (SN) and "Kneutersloop" (K), and a ditch (D), which is the contamination source of SN. Trace metal concentrations, and Na, K, Mg and Ca concentrations were measured using ICP-MS and were used to reconstitute site-specific water samples. We assessed whether the effects that were observed after exposure to environmental samples could be explained by metal mixture toxicity under standardized laboratory conditions. Exposure to "D" or "reconstituted D" water caused 100% mortality. SN and reconstituted SN water caused similar effects on hatching, swim bladder inflation, growth and swimming activity. A canonical discriminant analysis confirmed a high similarity between both exposure scenarios, indicating that the observed toxicity was indeed primarily caused by metals. The applied workflow could be a valuable approach to evaluate mixture toxicity that limits time and costs while maintaining biological relevance.


Morphogenesis of the secondary palate in normal and hydrocortisone-treated hamsters.
Fetal palate morphogenesis was studied in normal and hydrocortisone-treated hamsters. Formation of the normal palate was completed between day 12:00 and 13:00 of gestation, and during this period 8 distinct developmental stages were recognized. Following hydrocortisone administration the early stages, during which vertical-to-horizontal shelf reorientation occurs, appeared to be unaffected, but subsequent fusion between opposing shelves was inhibited. Both chronological age and fetal weight provided reliable criteria for stages of normal palatal development. Following hydrocortisone administration, however, fetal weight was a poorer indicator of stage of palate organogenesis than chronological age.


[Central and peripheral type small cell carcinoma of the lung--histologic, immunohistochemical, and clinical analyses].
In 17 cases of resected small cell carcinoma of the lung, there were 4 cases of central type and 13 cases of peripheral type. Histologic subtypes were classified into oat cell carcinoma (OAT), intermediate cell type (INT), and small cell carcinoma with large cell component (SC/LC). SC/LC was divided according to the criteria of Radice et al. Immunohistochemically, gastrin-releasing peptide (GRP) and neuron specific enolase (NSE) were used as markers for neuroendocrine cells, and keratin and secretory component (SC) were used as markers for epithelial and gland epithelial cells, respectively. Histologically, 4 cases of the central type were divided into 3 cases of INT and one case of SC/LC. Thirteen cases of the peripheral type were divided into 3 cases of OAT, 6 cases of INT, and 4 cases of SC/LC. SC/LC was more frequently seen in the peripheral type than in the central type. Immunohistochemically, there was no difference in the frequency of positive staining for GRP and NSE between the central and peripheral types, but positive staining for keratin and SC were more frequent in the peripheral type than in the central type. Three cases who survived more than 3 years were histologically divided into two cases of INT and one case of SC/LC. Immunohistochemically, these 3 cases showed positive staining for GRP or NSE, but also showed positive staining for keratin or SC. Our results showed that some of the peripheral type small cell carcinoma of the lung had histologic and immunohistochemical features which were different from those of typical small cell carcinoma. Long survival time after resection in some of the peripheral cases might be due to these features.


Influence of lipids on the interfacial disposition of respiratory syncytical virus matrix protein.
The propensity of a matrix protein from an enveloped virus of the Mononegavirales family to associate with lipids representative of the viral envelope has been determined using label-free methods, including tensiometry and Brewster angle microscopy on lipid films at the air-water interface and atomic force microscopy on monolayers transferred to OTS-treated silicon wafers. This has enabled factors that influence the disposition of the protein with respect to the lipid interface to be characterized. In the absence of sphingomyelin, respiratory syncytial virus matrix protein penetrates monolayers composed of mixtures of phosphocholines with phosphoethanolamines or cholesterol at the air-water interface. In ternary mixtures composed of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and cholesterol, the protein exhibits two separate behaviors: (1) peripheral association with the surface of sphingomyelin-rich domains and (2) penetration of sphingomyelin-poor domains. Prolonged incubation of the protein with mixtures of phosphocholines and phosphoethanolamines leads to the formation of helical protein assemblies of uniform diameter that demonstrate an inherent propensity of the protein to assemble into a filamentous form.


Monitoring of volume status after subarachnoid hemorrhage.
Hypovolemia is common after subarachnoid hemorrhage, and fluid imbalance negatively affects clinical outcome. Standard bedside volume measures fail to adequately assess fluid status after subarachnoid hemorrhage. An electronic literature search of original research studies evaluating fluid status after subarachnoid hemorrhage was conducted for English language articles published through October 2010. Sixteen articles were included in this review, with seven articles produced by two research groups. These studies highlight that fluid status is often affected and difficult to assess after subarachnoid hemorrhage. Both non-invasive and invasive monitors may be used to more accurately define volume status.


Cerebral lipiodol embolism during transcatheter arterial chemoembolization.
Cerebral lipiodol embolism (CLE) is a rare complication that may occur during chemoembolization. The authors present three cases of CLE during transcatheter arterial chemoembolization for hepatocellular carcinoma. Multiple small nonconfluent hyperintense intracerebral lesions were found on the diffusion-weighted and fluid-attenuated inversion recovery MRI. Clinical signs completely resolved and MRI lesions markedly improved on follow-up evaluation within a 3-week period.


Holocarboxylase Synthetase: A Moonlighting Transcriptional Coregulator of Gene Expression and a Cytosolic Regulator of Biotin Utilization.
The vitamin biotin is an essential nutrient for the metabolism and survival of all organisms owing to its function as a cofactor of enzymes collectively known as biotin-dependent carboxylases. These enzymes use covalently attached biotin as a vector to transfer a carboxyl group between donor and acceptor molecules during carboxylation reactions. In human cells, biotin-dependent carboxylases catalyze key reactions in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotin is attached to apocarboxylases by a biotin ligase: holocarboxylase synthetase (HCS) in mammalian cells and BirA in microbes. Despite their evolutionary distance, these proteins share structural and sequence similarities, underscoring their importance across all life forms. However, beyond its role in metabolism, HCS participates in the regulation of biotin utilization and acts as a nuclear transcriptional coregulator of gene expression. In this review, we discuss the function of HCS and biotin in metabolism and human disease, a putative role for the enzyme in histone biotinylation, and its participation as a nuclear factor in chromatin dynamics. We suggest that HCS be classified as a moonlighting protein, with two biotin-dependent cytosolic metabolic roles and a distinct biotin-independent nuclear coregulatory function.


[Effectiveness of complex containing antrale and tymohexine in the treatment of patients with chronic hepatitis].
The effectiveness of the combination of immunologically active tymohexine and antioxidant antrale was studied on 89 patients aged from 26 to 58 years with chronic viral or alcoholic hepatitis. The combination was found to have positive effect on the course of chronic hepatitis, immunological and biochemical indices. The following positive tendencies were observed: the rise in T-cell level, normalization of immunoregulatory index, decrease in activity of autoimmune, immune complex reactions, and lipid peroxidation, increase in activity of enzymes antioxidant system.


Neutrality point of graphene with coplanar charged impurities.
The ground state and the transport properties of graphene subject to the potential of in-plane charged impurities are studied. The screening of the impurity potential is shown to be nonlinear, producing a fractal structure of electron and hole puddles. Statistical properties of this density distribution as well as the charge compressibility of the system are calculated in the leading-log approximation. The conductivity depends logarithmically on alpha, the dimensionless strength of the Coulomb interaction. The theory is asymptotically exact when alpha is small, which is the case for graphene on a substrate with a high dielectric constant.


Physiology of the thermophilic acetogen Moorella thermoacetica.
Moorella thermoacetica (originally isolated as Clostridium thermoaceticum) has served as the primary acetogenic bacterium for the resolution of the acetyl coenzyme A (acetyl-CoA) or Wood-Ljungdahl pathway, a metabolic pathway that (i) autotrophically assimilates CO2 and (ii) is centrally important to the turnover of carbon in many habitats. The purpose of this article is to highlight the diverse physiological features of this model acetogen and to examine some of the consequences of its metabolic capabilities.


Factors impacting prognosis prediction in BCLC stage C and Child-Pugh class A hepatocellular carcinoma patients in prospective clinical trials of systemic therapy.
The purpose of this study was to determine the prognostic significance of clinical factors and staging systems for survival of hepatocellular carcinoma (HCC) patients who are candidates for therapeutic clinical trials. From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into six published phase II trials assessing various therapeutic regimens. Of these, 156 chemotherapy-naive patients with Child-Pugh class A and Barcelona Clinic Liver Cancer stage C disease were included in this analysis. Twenty-seven relevant clinical characteristics were analyzed to identify prognostic factors of survival. Beyond these prognosticators, the predictive ability of eight staging systems (the tumor-node-metastasis, Okuda, Cancer of the Liver Italian Program [CLIP], Chinese University Prognostic Index, Japanese Integrated Staging, Tokyo, National Taiwan University Risk Estimation, and Advanced Liver Cancer Prognostic System [ALCPS] score) were compared using the Akaike information criteria. The median overall survival time was 129 days (95% confidence interval, 111-147 days). Significant predictors of a shorter overall survival time were an Eastern Cooperative Oncology Group performance status score ≥2, the presence of symptoms, ascites, an aspartate transaminase level more than two times the upper limit of normal, and regional lymph node involvement. The ALCPS and CLIP scores were superior to the other systems for predicting survival. The prognosis of patients with advanced HCC who are candidates for therapeutic clinical trials is affected by several factors related to the patient, liver function, and the tumor. The ALCPS and CLIP scores appear to be superior to the other systems for predicting survival.


Allosteric modulation of human dopamine transporter activity under conditions promoting its dimerization.
The human dopamine (DA) transporter (hDAT) is a key regulator of neurotransmission and a target for antidepressants and addictive drugs. Despite the recent resolution of dDAT structures from Drosophila melanogaster, complete understanding of its mechanism of function and even information on its biological assembly is lacking. The resolved dDAT structures are monomeric, but growing evidence suggests that hDAT might function as a multimer, and its oligomerization may be relevant to addictive drug effects. Here, using structure-based computations, we examined the possible mechanisms of hDAT dimerization and its dynamics in a lipid bilayer. Using a combination of site-directed mutagenesis, DA-uptake, and cross-linking experiments that exploited the capacity of Cys-306 to form intermonomeric disulfide bridges in the presence of an oxidizing agent, we tested the effects of mutations at transmembrane segment (TM) 6 and 12 helices in HEK293 cells. The most probable structural model for hDAT dimer suggested by computations and experiments differed from the dimeric structure resolved for the bacterial homolog, LeuT, presumably because of a kink at TM12 preventing favorable monomer packing. Instead, TM2, TM6, and TM11 line the dimer interface. Molecular dynamics simulations of the dimeric hDAT indicated that the two subunits tend to undergo cooperative structural changes, both on local (extracellular gate opening/closure) and global (transition between outward-facing and inward-facing states) scales. These observations suggest that hDAT transport properties may be allosterically modulated under conditions promoting dimerization. Our study provides critical insights into approaches for examining the oligomerization of neurotransmitter transporters and sheds light on their drug modulation.


[The possible role of acetaldehyde in the brain damage caused by the chronic consumption of alcohol].
The purpose of this study is to collect and evaluate the experimental evidence suggesting that acetaldehyde, the first oxidative metabolite of ethyl alcohol (ethanol), plays a mediating role in the brain damage associated with the chronic consumption of this substance. Although the brain damage associated with the chronic consumption of ethanol is multifactorial and, possibly, dependent on the numerous actions of this substance on the central nervous system (CNS), there is data to suggest that the oxidative metabolism of ethanol and resulting substances are involved in the aetiology of such processes. Similarly, the generation of free radicals and the formation of adducts between the products of this metabolism and substrates contained in the CNS could be the main mediators in such pathological processes. This idea is supported by the fact that the adducts derived from the metabolism of ethanol are formed in the same areas of the brain as those which present structural and functional disorders in chronic consumers of alcohol. There are currently different experimental findings that appear to support the proposal that the substances resulting from the metabolism of ethanol can be important mediators in the brain damage associated with the chronic consumption of alcohol. Although more research is required, this theoretical proposal is very interesting, not just because of its relative novelty, but also because it is based on the same principles put forward to explain the toxic effects of alcohol consumption on organs and tissues.


The impact of automatic speech recognition technology on second language pronunciation and speaking skills of EFL learners: a mixed methods investigation.
This study employed an explanatory sequential design to examine the impact of utilizing automatic speech recognition technology (ASR) with peer correction on the improvement of second language (L2) pronunciation and speaking skills among English as a Foreign Language (EFL) learners. The aim was to assess whether this approach could be an effective tool for enhancing L2 pronunciation and speaking abilities in comparison to traditional teacher-led feedback and instruction. A total of 61 intermediate-level Chinese EFL learners were randomly assigned to either a control group (CG) or an experimental group (EG). The CG received conventional teacher-led feedback and instruction, while the EG used ASR technology with peer correction. Data collection involved read-aloud tasks, spontaneous conversations, and IELTS speaking tests to evaluate L2 pronunciation and speaking skills. Additionally, semi-structured interviews were conducted with a subset of the participants to explore their perceptions of the ASR technology and its impact on their language learning experience. The quantitative analysis of the collected data demonstrated that the EG outperformed the CG in all measures of L2 pronunciation, including accentedness and comprehensibility. Furthermore, the EG exhibited significant improvements in global speaking skill compared to the CG. The qualitative analysis of the interviews revealed that the majority of the participants in the EG found the ASR technology to be beneficial in enhancing their L2 pronunciation and speaking abilities. The results of this study suggest that the utilization of ASR technology with peer correction can be a potent approach in enhancing L2 pronunciation and speaking skills among EFL learners. The improved performance of the EG compared to the CG in pronunciation and speaking tasks demonstrates the potential of incorporating ASR technology into language learning environments. Additionally, the positive feedback from the participants in the EG underscores the value of using ASR technology as a supportive tool in language learning classrooms.


Optical Method to Quantify Mechanical Contraction and Calcium Transients of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
Differentiation of human pluripotent stem cells into cardiomyocytes (hPS-CMs) holds promise for myocardial regeneration therapies, drug discovery, and models of cardiac disease. Potential cardiotoxicities may affect hPS-CM mechanical contraction independent of calcium signaling. Herein, a method using an image capture system is described to measure hPS-CM contractility and intracellular calcium concurrently, with high spatial and temporal resolution. The image capture system rapidly alternates between brightfield and epifluorescent illumination of contracting cells. Mechanical contraction is quantified by a speckle tracking algorithm applied to brightfield image pairs, whereas calcium transients are measured by a fluorescent calcium reporter. This technique captured changes in contractile strain, calcium transients, and beat frequency of hPS-CMs over 21 days in culture, as well as acute responses to isoproterenol and Cytochalasin D. The technique described above can be applied without the need to alter the culture platform, allowing for determination of hPS-CM behavior over weeks in culture for drug discovery and myocardial regeneration applications.


Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b).
Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1(-/-) mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b.


[Treatment of bleeding from oesophageal varices in patients with cirrhosis].
This review summarizes the evidence of therapy for primary and secondary prevention of bleeding from oesophageal varices and treatment of acute bleeding. Continuing advances in the knowledge of portal hypertension have led to a reduction in primary and secondary bleeding episodes from oesophageal varices and a reduction in mortality from acute bleeding.


Organization of Microgels at the Air-Water Interface under Compression: Role of Electrostatics and Cross-Linking Density.
Poly(N-isopropylacrylamide) (pNIPAM) microgels are soft and deformable particles, which can adsorb at liquid interfaces. In the present paper, we study the two-dimensional organization of charged and quasi-neutral microgels with different cross-linking densities, under compression at the air-water interface and the transfer of the microgel monolayer onto a solid substrate at different surface pressures. At low cross-linking densities, the microgels form highly ordered hexagonal lattices on the solid substrate over large areas, with a unique lattice parameter that decreases continuously as the surface pressure increases. We thus prove that the microgel conformation evolves at the air-water interface. The microgels undergo a continuous transition from a highly flattened state at low surface coverage, where the maximal polymer segments are adsorbed at the interface, to entangled flattened microgels, and finally the thickening of the layer up to a dense hydrogel layer of compacted microgels. Moreover, two batches of microgels, with and without charges, are compared. The contribution of electrostatic interactions is assessed via changing the charge density of the microgels or modulating the Debye length. In both cases, electrostatics does not change the lattice parameter, meaning that, despite the microgel different swelling ratio, charges do not affect neither interactions between particles at the interface nor microgels adsorption. Conversely, the cross-linking density has a strong impact on microgel packing at the interface: increasing the cross-linking density strongly decreases the extent of microgel flattening and promotes the occurrence of coexisting hexagonally ordered domains with different lattice parameters.


[Correlation between sarcopenia and albuminuria in patients with type 2 diabetes].
To investigate the correlation between sarcopenia and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 360 T2DM patients (including 206 male and 154 female patients) hospitalized in our hospital between January, 2015 and December, 2018 were enrolled. According to their medical history and laboratory test results, the patients were divided into albuminuria group (n=122) and non-albuminuria group (n=238). The clinical and anthropological data were collected and skeletal muscle index (SMI), appendage lean mass, muscle index, total body fat, bone mineral capacity and bone mineral density were measured using dual-energy X-ray absorptiometry. Logistic regression was used to analyze the correlation of these body composition parameters with albuminuria or chronic kidney disease (CKD) in the diabetic patients. The disease course of T2DM, history of hypertension, age, systolic blood pressure, low density lipoprotein cholesterol, triglyceride, uric acid, waistline, Urinary albumin creatinine ratio, serum creatinine, and glomerular filtration rate differed significantly between the diabetic patients with albuminuria and those without albuminuria (P < 0.05). The prevalence rate of sarcopenia was significantly higher in patients with albuminuria (31.4% vs 13.1%, P < 0.01). Compared with those without albuminuria, the patients with albuminuria had significantly decreased SMI (t=-2.304, P=0.021) and body mass index (Z=- 5.534, P < 0.01) and significantly increased total body fat (Z=- 2.838, P=0.005). Multivariate logistic regression analysis showed that after adjustment for age, gender, total body fat, smoking history, drinking history, duration of diabetes, HbA1c, history of hypertension, systolic blood pressure, low density lipoprotein cholesterol, body mass index, and triglyceride, the patients with a decreased SMI had a significantly increased risk of albuminuria (P=0.011 and 0.010), but SMI was not correlated with the risk of CKD in patients with T2DM (P > 0.05). Sarcopenia is probably an independent risk factor for albuminuria in patients with T2DM.


Cavernous Sinus Swelling and Abducens Nerve Paresis Due to Intracranial Hypotension.
The most common neurological symptom of spontaneous intracranial hypotension (SIH) is abducens nerve paresis, and the precise pathophysiology is unclear. The accepted explanation is traction on the cranial nerves caused by the downward displacement of the cranial content. We herein report magnetic resonance imaging of SIH that can explain the mechanism underlying abducens nerve paresis. The cavernous sinuses were particularly thickened compared with the surrounding dura. This phenomenon can be explained by venous swelling, which can occur after leakage of cerebrospinal fluid in a closed cavity. This swelling pushes the abducens nerve up, which then causes abducens nerve paresis.


Content validation using Aiken methodology through expert judgment of the first Spanish version of the Eppendorf Schizophrenia Inventory (ESI) in Peru: A brief qualitative report.
The main objective of this study was the validation through the expert judgment of the first Spanish version of the Eppendorf Schizophrenia Inventory (ESI-Sp). A translation and cultural adaptation procedure as a first stage was carried out, which was evaluated by four psychiatrists with clinical experience. In a second stage, we recruited a group of clinical psychiatrists to evaluate the translated instrument by judging the items' clarity and relevance. Content validity was performed using the Aiken methodology (Aiken's V). For the first stage, we did not find any items that needed alteration during translation and adaptation. Concerning the raters' stage, 30 clinical psychiatrists (47.07±13.62 years) completed the rating of the ESI-Sp. Of them, the majority worked in an institute (10/30; 33.33%) and had "15 or more" years of experience (12/30; 40.00%). The null hypothesis was rejected for all items and demonstrated the content validity of each item. Similar results were found for the factors of the ESI. Finally, the total Aiken's V for the ESI did not include the values of the null hypothesis in the confidence intervals (V=0.78; CI95 [0.70; 0.85]), demonstrating content validity. ESI-Sp is a valid and representative instrument to determine subjective experiences in patients with a high risk of schizophrenia. The construct validation of the ESI-Sp is pending, which our research group will carry out after this first step.


Phocine distemper in harbor seals (Phoca vitulina) from Long Island, New York.
The first occurrence of phocine distemper (PD) disease in harbor seals (Phoca vitulina) from the United States is reported. Two seals stranded on Long Island, New York (USA) in February 1992 with clinical signs of respiratory distress, fever, and depression. Pneumonia and diffuse pulmonary congestion were the most significant post mortem findings. On histologic examination one seal had a diffuse broncho-interstitial pneumonia with formation of syncytia. The principal lesion in the second animal was nonsuppurative meningoencephalitis. Using immunoperoxidase staining, PD viral antigen was found in the cytoplasm of bronchiolar epithelium and cerebral cortex neurons. With a differential virus neutralization test, there were higher titers against phocine distemper virus (PDV) than against canine distemper virus. Thus, PDV is the most likely agent responsible for the observed lesions.


Antimicrobial activity of essential oils from Mediterranean aromatic plants against several foodborne and spoilage bacteria.
The antimicrobial activity of essential oils extracted from a variety of aromatic plants, often used in the Portuguese gastronomy was studied in vitro by the agar diffusion method. The essential oils of thyme, oregano, rosemary, verbena, basil, peppermint, pennyroyal and mint were tested against Gram-positive (Listeria monocytogenes, Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, and Staphylococcus epidermidis) and Gram-negative strains (Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa). For most essential oils examined, S. aureus, was the most susceptible bacteria, while P. aeruginosa showed, in general, least susceptibility. Among the eight essential oils evaluated, thyme, oregano and pennyroyal oils showed the greatest antimicrobial activity, followed by rosemary, peppermint and verbena, while basil and mint showed the weakest antimicrobial activity. Most of the essential oils considered in this study exhibited a significant inhibitory effect. Thyme oil showed a promising inhibitory activity even at low concentration, thus revealing its potential as a natural preservative in food products against several causal agents of foodborne diseases and food spoilage. In general, the results demonstrate that, besides flavoring the food, the use of aromatic herbs in gastronomy can also contribute to a bacteriostatic effect against pathogens.


[Chronic heart failure and depression].
Depression is a frequent comorbidity in chronic heart failure. It can be triggered by the experience of suffering from heart disease, but it can also play a causal role in accelerated development and poor prognosis of heart failure. The aim of this study was to investigate the interrelationships between heart failure and depression and the psychophysiological and behavioral mechanisms involved in this association. The effects of comorbid depression on quality of life in patients with heart failure were also examined and therapeutic options reviewed. A narrative review of the literature was undertaken. Several psychophysiological and behavioral mechanisms have been identified as mediators of the association between depression and heart failure and the adverse prognostic effects of this comorbidity. Comorbid depression leads to substantial reductions in health-related quality of life. These effects are only incompletely antagonized by exercise training and cognitive behavioral therapy. No specific effect of antidepressant medication has been demonstrated as yet in patients with heart failure. While current guidelines recommend the identification and treatment of depressive comorbidity in patients with heart failure, the available evidence provides no convincing rationale for specific treatment recommendations beyond the guideline-based treatment of heart failure itself, lifestyle interventions and patient-centered medical care. If available, psychotherapy should be offered, ideally cognitive behavioral therapy. For patients that do not improve sufficiently under outpatient treatment, the German health care system offers dedicated psychocardiological inpatient treatment programs.


Anopheles culicifacies: siblings species composition and its relationship to malaria incidence.
Entomological and epidemiological surveys in May, August and November 1985 and March 1986 were conducted in villages in Bulandshahr, a western district in Uttar Pradesh and in three eastern districts, Jaunpur, Ballia and Saran. In Bulandshahr, Anopheles culicifacies sibling species A and B were found, with a predominance of species A. Both Plasmodium vivax and P. falciparum were present and the malaria incidence remained high (SPR, 6-50%) indicating an active transmission. In contrast, in three eastern districts predominance of species B with an occasional occurrence of species A was observed. Malaria cases were almost absent in Ballia and Saran and in Jaunpur 10.3% slide positivity rate was observed in May but in later surveys cases were considerably lower (SPR, 0.5-2.9%) indicating the absence of indigenous transmission. In the eastern districts, malaria parasites are regularly brought in from endemic areas by the migrant labor population. Although An. culicifacies s.l. occurs in both the areas, the difference in malaria incidence appears to be due to the difference in the composition of the sibling species which is, the predominant presence of species A in the western district and its absence in eastern districts. This indicates that species A is responsible for active malaria transmission while species B is not.


Catalytic Intermolecular Dicarbofunctionalization of Styrenes with CO2 and Radical Precursors.
A redox-neutral intermolecular dicarbofunctionalization of styrenes with CO2 at atmospheric pressure and carbon-centered radicals is described. This mild protocol results in multiple C-C bond-forming reactions from simple precursors in the absence of stoichiometric reductants, thus exploiting a previously unrecognized opportunity that complements existing catalytic carboxylation events.


Antibacterial Effects of Quinazolin-4(3H)-One Functionalized-Conjugated Silver Nanoparticles.
Infections due to multi-drug resistant bacteria are on the rise and there is an urgent need to develop new antibacterials. In this regard, a series of six functionally diverse new quinazolinone compounds were synthesized by a facile one-pot reaction of benzoic acid derivatives, trimethoxymethane and aniline derivatives. Three compounds of 3-aryl-8-methylquinazolin-4(3H)-one, and 3-aryl-6,7-dimethoxyquinazolin4(3H)-one were prepared and tested against multi-drug resistant bacteria. Furthermore, we determined whether conjugation with silver nanoparticles improved the antibacterial efficacy of these quinazolinone derivatives. The newly synthesized compounds were characterized by ultraviolet visible spectrophotometry (UV-vis), Zetasizer analysis, Fourier transform infrared spectroscopic methods (FT-IR), and scanning electron microscopy (SEM). Using bactericidal evaluation, effects were determined against selected Gram-negative and Gram-positive bacteria. Furthermore, cytotoxicity of nanoconjugates on human cells were determined. The UV-vis spectrum of silver nanoparticles conjugated quinazolinone displayed surface plasmon resonance band in the range of 400-470 nm, and the size of nanoparticles was detected to be in the range of 100-250 nm by dynamic light scattering (DLS). FT-IR study confirmed the stabilization of silver nanoparticles by the presence of diverse functional arayl on each compound. SEM further revealed the construction of spherical nanoparticles. Among the quinazolinone derivative tested, two compounds (QNZ 4, QNZ 6) conjugated with silver nanoparticles showed enhanced antibacterial activity against Escherichia coli K1, Streptococcus pyogenes, Klebsiella pneumoniae, B. cereus and P. aeruginosa as compared to the compounds.


[Efficacy of SMC-electrophoresis of peat mud in primary chronic duodenitis].
Sinusoidal modulated current (SMC) electrophoresis of peat mud was used as monotherapy of primary chronic duodenitis in Uva sanatorium. A total of 65 patients with primary chronic duodenitis received SMC electrophoresis of peat mud diluted with distilled water. The effect was followed up with fibrogastroduodenoscopy and target biopsy of duodenal mucosa with further study of its morphological structure and element composition, acid-producing function of the stomach, hormonal profile, collagen metabolism. Positive changes were observed in clinical-endoscopic and morphological picture of the disease which is explained by favourable shifts in hormonal status and normalization of collagen metabolism in duodenal mucosa.


Recent Advances in Polymeric Nanocomposites of Metal-Organic Frameworks (MOFs).
Recently, metal-organic frameworks (MOFs) have garnered enormous attention from researchers owing to their superior physicochemical properties, which are of particular interest in various fields such as catalysis and the diverse areas of biomedicine. Despite their position in the utilization for various applications compared to other innovative nanocarriers such as dendrimers and mesoporous silica nanoparticles (MSNs), in terms of advantageous physicochemical attributes, as well as attractive textural properties, ease of characterization, and abundant surface chemistry for functionalization and other benefits, MOFs yet suffer from several issues such as poor degradability, which might lead to accumulation-induced biocompatibility risk. In addition, some of the MOFs suffer from a shortcoming of poor colloidal stability in the aqueous solution, hindering their applicability in diverse biomedical fields. To address these limitations, several advancements have been made to fabricate polymeric nanocomposites of MOFs for their utility in various biomedical fields. In this review, we aim to provide a brief emphasis on various organic polymers used for coating over MOFs to improve their physicochemical attributes considering a series of recently reported intriguing studies. Finally, we summarize with perspectives.


Prediction of Severe Cisplatin-Induced Neutropenia Using Serum Albumin Concentration-A Retrospective Study.
Cisplatin that is used in the treatment of gastric cancer not only has gastrointestinal side effects but also has a high serum protein-bound fraction. Reduction of serum albumin concentration may cause increase the risk of cisplatin- induced neutropenia. Hence, alteration of serum albumin concentration poses a major safety issue during anticancer therapy. For gastric cancer patients who received cisplatin plus S-1 therapy, we investigated the relationship between the serum albumin concentration before cisplatin administration in the treatment course during which the neutrophil count reached nadir and the neutrophil count fluctuation after cisplatin administration. In the grade 3-4 neutropenia and grade 0-2 neutropenia groups, the mean serum albumin concentration before cisplatin administration was 3.39±0.60 and 3.85±0.59 g/dL, respectively; in the former group were significantly lower than in the latter group(p=0.006). Lower serum albumin concentrations before cisplatin administration were significantly correlated with a decrease in neutrophil count after cisplatin administration(r=0.463, p<0.001). According to the receiver operating characteristic curve analysis, patients with serum albumin concentrations below 3.25 g/dL before cisplatin administration exhibited a significantly higher incidence of grade 3-4 neutropenia(odds ratio: 4.33). Decreased serum albumin levels were found to be strongly associated with the prediction of the development of severe neutropenia. Our findings emphasize serum albumin concentration needs to be evaluated before each administration of cisplatin.


[Current status and vaccine indication for hepatitis A virus infection in Korea].
One of the major cause of recent acute viral hepatitis in Korean adults is hepatitis A virus (HAV) infection. Most of hepatitis A cases are young adults in their twenties or thirties, and the severity of the disease is related to the age of patients. The seroprevalence of HAV among the adolescents and young adults in their teens and twenties is about 10%, which suggests that a growing number of young adults are susceptible to HAV infection. Development of more adult cases with severe presentation is expected in the near future, and some preliminary data suggest the incidence rate of hepatitis A in Korea might be higher than 20/100,000 population. This clinical features and the epidemiological shift of HAV urge to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults. More extensive evaluation on the nationwide epidemiology of HAV infection, cost-benefit analysis of HAV vaccination, and setting-up of guidelines for HAV vaccination are urgently warranted.


On the brain barrier system function and changes of cerebrospinal fluid concentrations of phenylalanine and tyrosine in human phenylketonuria.
In 6 patients with classic phenylketonuria (PKU) the plasma and cerebrospinal fluid (CSF) concentrations of phenylalanine and tyrosine were measured fluorimetrically. The results of the PKU group were compared with data obtained from 17 children without abnormal CSF parameters and free of metabolic or central nervous disorders, in whom a diagnostic lumbal puncture has been performed. The PKU patients showed statistically significant differences in comparison with the controls: plasma and CSF phenylalanine contents were markedly higher (on the average 6.4 and 4.6 times, respectively) in PKU patients. Plasma tyrosine was 1.8 times lower, but CSF tyrosine was about 2.2 times higher in comparison to the controls. In general, the plasma CSF-ratio ( PLR ) of phenylalanine did not change in PKU and could be found in the same range as in the normal controls. In contrast to this, the PLR of tyrosine was found to be significantly lower in PKU patients. The results are discussed with respect to an altered function of the brain barrier systems for the amino acid transport in PKU, and that increased CSF tyrosine contents in PKU may rather reflect disturbances of the intracellular metabolism of the brain cells than changes of the amino acid transport through the brain barrier produced by hyperphenylalaninemia.


High-speed high-resolution gas-phase Raman spectroscopy.
A new Raman spectrometer has been developed that can produce a complete high-resolution gas-phase vibrational spectrum during the time period of a single laser pulse. Conventional gas-phase Raman spectroscopy uses a single narrow-band laser to produce signals that are weak, requiring relatively long collection times. This spectrometer uses a degenerate OPO as a broad-band source that covers a continuous range of >3000 cm(-1). When a beam from this broad-band source is added to a narrow-band laser beam, the intensity of the Raman signal is amplified by the nonlinear optical effect. The resulting instrument can generate spectra with high-spectral (<1 cm(-1)), spatial (<0.05 mm2), and temporal resolution (<1 s).


Legitimacy of concerns about caffeine and energy drink consumption.
Whether caffeine and energy drink consumption presents a critical emerging health problem is not currently known. Available evidence suggests that energy drink consumption represents a change in the ways in which individuals in the United States consume caffeine but that the amount of caffeine consumed daily has not appreciably increased. In the present review, the question of whether Americans are sleep deprived (a potential reason for using caffeine) is briefly explored. Reported rates of daily caffeine consumption (based on beverage formulation) and data obtained from both civilian and military populations in the United States are examined, the efficacy of ingredients other than caffeine in energy drinks is discussed, and the safety and side effects of caffeine are addressed, including whether evidence supports the contention that excessive caffeine/energy drink consumption induces risky behavior. The available evidence suggests that the main legitimate concern regarding caffeine and energy drink use is the potential negative impact on sleep but that, otherwise, there is no cause for concern regarding caffeine use in the general population.


Context-dependent DNA methylation signatures in animal livestock.
DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.


Effect of Intensive Blood Pressure Reduction on Left Ventricular Mass, Structure, Function, and Fibrosis in the SPRINT-HEART.
In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =-2.7±0.5 g versus -2.3±0.7 g; P=0.368), ejection fraction, or native T1 (P=0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (-0.04±0.01 versus -0.01±0.01; P=0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.


A national longitudinal study of the psychological consequences of the September 11, 2001 terrorist attacks: reactions, impairment, and help-seeking.
This article examines the evolution of psychological and behavioral reactions following the September 2001 terrorist attacks in a nationally representative sample, and describes where people turned for support, information, and counseling. From November 9 to November 28, 2001, we resurveyed 395 (71%) of the original 560 adults 19 years or older within the United States who participated in our national random-digit-dialing telephone survey conducted on September 14 to September 16, 2001, about their terrorism-related psychological distress and behavior. Sixteen percent of adults had persistent distress, reporting one or more substantial distress symptoms in both September and November. Adults with persistent distress reported accomplishing less at work (65%); avoiding public gathering places (24%); and using alcohol, medications, or other drugs to relax, sleep, or feel better because of worries about terrorism (38%). Seventy-five percent talked with family and friends; however, 43% reported sometimes feeling unable to share their terrorism-related thoughts and feelings with others because it made others uncomfortable. Few reported receiving counseling or information about psychological distress from general medical providers (11%). These findings suggest that a significant number of adults across the country were continuing to experience terrorism-related distress and disruption of their daily lives approximately 2 months after September 11; many turned to family and friends for support, but at times many felt uncomfortable doing so, and few used clinicians as a source of information or support. Clinicians and policymakers should consider how the healthcare system and other community organizations might provide a coordinated community-wide response for individuals needing information and counseling following terrorist events.


Characterization of [3H]Met-enkephalin-Arg6-Phe7 binding to opioid receptors in frog brain membrane preparations.
A tritiated heptapeptide, [3H]Tyr-Gly-Gly-Phe-Met-Arg-Phe ([3H]Met-enkephalin-Arg6-Phe7), with high specific radioactivity has been synthesized in order to characterize its opioid binding activity to frog brain membrane fractions. The apparent KD value of the radioligand calculated from homologous displacement experiments was 3.4 nM, and the maximal number of specific binding sites was 630 fmol/mg of protein. The KD determined from equilibrium saturation binding studies was found to be 3.6 nM. However, the Hill coefficient was far below unity (nH = 0.43), which suggests the presence of a second, lower affinity binding site. The presence of this binding component is strengthened by the displacement experiments performed with levorphanol and some other ligands. It is assumed that the lower affinity site has no opiate character. The rank order of potency of the applied ligands in competing reversibly with [3H]Met-enkephalin-Arg6-Phe7 binding reflects a kappa 2- and/or delta-subtype specificity of the heptapeptide. Binding to a kappa 1 and/or mu site of opioid receptors is excluded, but the existence of a novel endogenous opiate receptor subtype for Met-enkephalin-Arg6-Phe7 in frogs cannot be ruled out. The [3H]-Met-enkephalin-Arg6-Phe7 binding was inhibited by both sodium ions and GppNHp, which suggests the opioid agonist character of the heptapeptide.


Retinoid modulation of insulin-like growth factor-binding proteins and inhibition of breast carcinoma proliferation.
Retinoids induce cellular differentiation and inhibit cellular proliferation. Proliferation of human breast carcinoma cells in vitro is markedly inhibited by these compounds. On the other hand, insulin-like growth factors (IGFs) and their receptors seem to be involved in the growth of certain breast carcinoma cells by autocrine or paracrine effects. Since the effects of both IGF-I and IGF-II may be modulated by specific binding proteins (IGF-BPs) we examined the possibility that one mechanism by which retinoic acid may inhibit cancer growth is by an alteration in these BPs, thereby blocking IGF's growth effect. Retinoic acid (RA; 1 microM) completely blocked the effect of IGF-I (50 ng/ml) on enhancing proliferation of MCF-7 cells in culture. This effect of RA was not associated with any significant change in specific IGF-I-binding sites on these cells. RA induced a 3-fold increase in IGF-binding activity in conditioned medium, measured using a polyethylene glycol-immunoglobulin precipitation assay and a charcoal absorption assay. This increase was associated with the appearance of 42- and 46-kDa IGF-BPs on ligand blotting. The effect of RA on these IGF-BPs was time and concentration dependent. In contrast, during some experiments the 27- and 36-kDa BPs actually decreased. These findings support the hypothesis that RA may inhibit the growth of certain breast carcinoma cells by increasing the secretion of certain IGF-BPs, which could directly modulate the growth effect of IGFs.


Deletion of p75NTR impairs regeneration of peripheral nerves in mice.
After peripheral nerve injury, p75NTR was upregulated in Schwann cells of the Wallerian degenerative nerves and in motor neurons but down-regulated in the injured sensory neurons. As p75NTR in neurons mediates signals of both neurotrophins and inhibitory factors, it is regarded as a therapeutic target for the treatment of neurodegeneration. However, its physiological function in the nerve regeneration is not fully understood. In the present study, we aimed to examine the role of p75NTR in the regeneration of peripheral nerves. In p75NTR knockout mice (exon III deletion), the sciatic nerves and facial nerves on one side were crushed and regenerating neurons in the facial nuclei and in the dorsal root ganglia were labelled by Fast Blue. The regenerating fibres in the sciatic nerve were also labelled by an anterograde tracer and by immunohistochemistry. The results showed that the axonal growth of injured axons in the sciatic nerve of p75NTR mutant mice was significantly retarded. The number of regenerated neurons in the dorsal root ganglia and in the facial nuclei in p75NTR mutant mice was significantly reduced. Immunohistochemical staining of regenerating axons also showed the reduction in nerve regeneration in p75NTR mutant mice. Our data suggest that p75NTR plays an important role in the regeneration of injured peripheral nerves.


Intraoperative fetal oxygen saturation during Caesarean section: general anaesthesia using sevoflurane with either 100% oxygen or 50% nitrous oxide in oxygen.
The study was designed to evaluate whether the administration of sevoflurane in 100% oxygen for anaesthesia during Caesarean section would improve fetal and neonatal oxygenation compared with the administration of sevoflurane with 50% nitrous oxide in oxygen. The randomized, single-blind controlled study examined 24 mothers, ASA I-II, at term undergoing Caesarean section who were allocated to receive sevoflurane in either 100% oxygen (n = 13) or 50% nitrous oxide in oxygen (n= 11). General anaesthesia was induced in both groups with thiopental 4-5 mg kg(-1) followed by succinylcholine 1.5 mg kg(-1) to facilitate tracheal intubation. Parturients received sevoflurane given either in 100% O2 or in a 50:50 nitrous oxide and oxygen mixture, using 0.5-1.0% progressive incremental dosing up to 1.5-2.0 MAC. Non-invasive fetal oxygen saturation was measured between induction to delivery, and umbilical artery and vein PaO2 were evaluated at birth. Intraoperative fetal oxygen saturation increased in all patients after maternal 100% oxygen administration (P < 0.01). Maternal hyperoxygenation significantly increased the umbilical vein and umbilical artery PaO2 and the umbilical artery SaO2 at birth (P < 0.0001). Maternal hyperoxygenation significantly improves fetal as well as neonatal oxygenation.


NMR studies of the interaction of bleomycin with (dC-dG)3.
The interaction of bleomycin A2 and Zn(II)-bleomycin A2 with the oligonucleotide (dC-dG)3 has been monitored by nuclear magnetic resonance spectroscopy. Binding of the drug to the oligonucleotide is indicated by an upfield shift of the bithiazole proton resonances consistent with partial intercalation of this group between base pairs. The effect of temperature and ionic strength on the binding of both free bleomycin and the Zn(II) complex has been studied. Consistent with earlier studies on polynucleotides, the rate of exchange between the free drug and the drug-oligonucleotide complex is rapid on the 1H NMR chemical shift time scale. Binding of the oligonucleotide induced changes in resonances assigned to protons in the metal-binding region of Zn(II)-bleomycin. Intermolecular nuclear Overhauser effect enhancements between bleomycin and the oligonucleotide have not been detected.