Structure of the acetylcholine receptor and specificities of antibodies to it in myasthenia gravis.
Acetylcholine receptors in skeletal muscle and fish electric organs are intrinsic membrane proteins whose function is to bind acetylcholine released from the nerve ending and trigger the opening of a cation-specific channel in the postsynaptic membrane, thereby facilitating transmission of the nerve signal to the muscle. Investigations from several laboratories indicate that acetylcholine receptors from fish electric organs are composed of four homologous glycoprotein subunits of apparent relative molecular masses (Mr) approximating 40, 50, 57 and 64 x 10(3) designated, respectively, alpha, beta, gamma and delta. These subunits are present in receptor monomers in the mole ratio alpha 2 beta gamma delta. Receptor purified from skeletal muscle appears to have a similar structure. The alpha subunits are unknown. It is known that the cation channel regulated by acetylcholine binding is located within the receptor monomer. Experimental autoimmune myasthenia gravis (EAMG) is induced by immunizing animals with purified receptor. The mechanisms by which neuromuscular transmission is impaired in this model are very similar to those in myasthenia gravis (MG). Although there are many immunogenic determinants on receptors, and EAMG can be induced in rats by any of the denatured subunits, there is a main immunogenic region at which most of the antibodies to native receptors are directed. The main immunogenic region is a conformationally dependent part of the external surface of alpha subunits other than the acetylcholine-binding site or the attached carbohydrate. Antisera from MG patients are also directed primarily at this region. No correlation was detected between the specificities of antibodies to receptor in patients' sera and the severity of their weakness.


Implementation principles and strategies for Title XXI (State Children's Health Insurance Program). Academy of Pediatrics. Committee on Child Health Financing.
A major provision of the Balanced Budget Act of 1997 established the State Children's Health Insurance Program (Title XXI of the Social Security Act). This program is a historic milestone in the financing of health care for children. Not since the enactment of Medicaid has there been a greater investment in children's health care. Title XXI does not create universal coverage for all children, but this program does offer an unprecedented opportunity to expand insurance ot a large portion of uninsured children. Title XXI of the Social Security Act makes >$40 billion in federal grants available to states over the next 10 years to provide health insurance coverage, including Medicaid. However, states mus contribute a defined share of funds to obtain federal matching funds. The legislation gives great flexibility to states in designing and implementing their programs, and it is critical that they do this in a timely manner. If states fail to use all State Children's Health Insurance Program funds available, it is possible that future federal funding will be reduced. If this happens, a major opportunity to improve health insurance coverage of America's children will be diminished.


Study on interaction between a new fluorescent probe 2-methylbenzo[b][1,10]phenanthrolin-7(12H)-one and BSA.
A new fluorescence reagent, 2-methylbenzo[b][1,10]phenanthrolin-7(12H)-one (mBPO), synthesized in our laboratory was used as the probe for protein and its interaction with Bovine Serum Albumin (BSA) was investigated in detail in this paper. It was found that BSA had the ability to quench the fluorescence of mBPO at 411 nm (λ(ex) = 286 nm), and the quenched intensity of fluorescence was proportional to the concentration of BSA. Based on this fact, mBPO has been used as a fluorescence probe for the detection of BSA. Under the optimal conditions, the calibration graph is linear up to 0.5 mg L(-1) for BSA and the limit of detection (LOD) was 0.06 mg L(-1). The regression equation is y = 1048.8x + 7.2093 with R(2) = 0.9913. The mechanism for the interaction of mBPO with BSA was also studied, while the binding constant and the number of binding sites were calculated. According to the thermodynamics parameter, the binding mode between mBPO and BSA was deduced. The results suggested the interaction between mBPO and BSA to be hydrophobic force in nature. It also proved that the fluorescence quenching reaction was affected by the tryptophan residue of BSA. For there are two tryptophan (Trp) residues, in site 134 and site 212 of BSA, and mBPO maybe has interaction with them respectively.


The antioxidative effects of the isoflavan glabridin on endogenous constituents of LDL during its oxidation.
The effect of the consumption of glabridin, an isoflavan isolated from Glycyrrhiza glabra (licorice) root, on the susceptibility of low density lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E deficient (E[o] mice) and was compared with that of the known flavonoids, quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of human LDL was also investigated by determining the formation of lipid peroxides and oxysterols and the consumption of LDL-associated lipophilic antioxidants. Determination of the extent of LDL oxidation by measuring the formation of thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5 mM), revealed that glabridin or quercetin consumption resulted in a 53 and 54% reduction in copper ion induced oxidation, respectively, and a 95 and 83% reduction in AAPH induced LDL oxidation, respectively. No inhibition was obtained with consumption of catechin. About 80% of glabridin was found to bind to the LDL human particle. In the in vitro oxidation of LDL induced by AAPH (5 mM), glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM), while in oxidation induced by copper ions (10 microM), glabridin exhibited a pro-oxidant activity at concentrations lower than 20 microM, and a clear antioxidant activity at concentrations greater than 20 microM. Glabridin (30 microM) inhibited the formation of cholest-5-ene-3,7-diol (7-hydroxycholesterol), cholest-5-ene-3-ol-7-one (7-ketocholesterol) and cholestan-5,6-epoxy-3-ol (5,6-epoxycholesterol) after 6 h of AAPH induced LDL oxidation, by 55, 80 and 40%, respectively, and after 6 h of copper ion induced LDL oxidation, by 73, 94 and 52%, respectively. Glabridin also inhibited the consumption of beta-carotene and lycopene by 38 and 52%, respectively, after 0.5 h of LDL oxidation with AAPH, but failed to protect vitamin E. The in vivo and in vitro reduction of the susceptibility of LDL to oxidation obtained with glabridin, may be related to the absorption or binding of glabridin to the LDL particle and subsequent protection of LDL from oxidation by inhibiting the formation of lipid peroxides and oxysterols, and by protecting LDL associated carotenoids.


Reduced aromatase activity in granulosa cells of women with endometriosis undergoing assisted reproduction techniques.
The aim of the present study was to measure the in vitro aromatase activity in granulosa cells of women with endometriosis submitted to assisted reproduction techniques. A case-control study was conducted on eight patients with endometriosis and eight with other infertility causes submitted to in vitro fertilization or intracytoplasmic sperm injection. Granulosa cells were obtained from pre-ovulatory follicles during oocyte retrieval and cultured for 24 h in the presence or absence of testosterone (2 x 10(-6) and 2 x 10(-5) M), follicle-stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) (both at 50 ng/ml). Estradiol (radioimmunoassay) was measured in the obtained culture fluids. The basal production of estradiol and its production under testosterone addition to the culture (aromatase activity) were analyzed. Reduced aromatase activity was detected in cultured granulosa cells in endometriosis cases, compared with controls, when testosterone was added at the concentration at 2 x 10(-6) M (p = 0.0303). The basal production of estradiol was also reduced in endometriosis patients (p = 0.0390). The effect of addition of FSH and IGF-I did not differ between groups. In conclusion, the in vitro basal production of estradiol and aromatase activity in granulosa cells were reduced in women with endometriosis submitted to assisted reproduction techniques, compared with the control group.


Recent ice-sheet growth in the interior of Greenland.
A continuous data set of Greenland Ice Sheet altimeter height from European Remote Sensing satellites (ERS-1 and ERS-2), 1992 to 2003, has been analyzed. An increase of 6.4 +/- 0.2 centimeters per year (cm/year) is found in the vast interior areas above 1500 meters, in contrast to previous reports of high-elevation balance. Below 1500 meters, the elevation-change rate is -2.0 +/- 0.9 cm/year, in qualitative agreement with reported thinning in the ice-sheet margins. Averaged over the study area, the increase is 5.4 +/- 0.2 cm/year, or approximately 60 cm over 11 years, or approximately 54 cm when corrected for isostatic uplift. Winter elevation changes are shown to be linked to the North Atlantic Oscillation.


Stabilization of the 81-channel coherent beam combination using machine learning.
We develop a rapidly converging algorithm for stabilizing a large channel-count diffractive optical coherent beam combination. An 81-beam combiner is controlled by a novel, machine-learning based, iterative method to correct the optical phases, operating on an experimentally calibrated numerical model. A neural-network is trained to detect phase errors based on interference pattern recognition of uncombined beams adjacent to the combined one. Due to the non-uniqueness of solutions in the full space of possible phases, the network is trained within a limited phase perturbation/error range. This also reduces the number of samples needed for training. Simulations have proven that the network can converge in one step for small phase perturbations. When the trained neural-network is applied to a realistic case of 360 degree full range, an iterative scheme exploits random walking at the beginning, with the accuracy of prediction on phase feedback direction, to allow the neural-network to step into the training range for fast convergence. This neural-network-based iterative method of phase detection works tens of times faster than the commonly used stochastic parallel gradient descent approach (SPGD) using a single-detector and random dither when both are tested with random phase perturbations.


Combined effects of carbonic anhydrase inhibitor and adenosine A1 receptor antagonist on hemodynamic and tubular function in the kidney.
Carbonic anhydrase inhibitors (CAI) reduce proximal reabsorption, activating tubuloglomerular feedback (TGF) and reducing glomerular filtration rate (GFR). Adenosine A(1) receptors (A(1)R) mediate the TGF response and stimulate proximal reabsorption. Clearance and micropuncture studies were performed in Wistar rats to determine whether blockade of A(1)R (KW3902 0.3 mg/kg i.v.) would prevent CAI (benzolamide 5 mg/kg i.v.) from lowering GFR, whether CAI and KW3902 exert additive effects on sodium excretion, and to what extent such interactions depend on events in the glomerulus, proximal tubule, or distal nephron. KW3902 raised GFR and prevented CAI from lowering GFR. KW3902 and CAI caused additive diuresis and natriuresis. KW3902 and CAI increased lithium clearance, but their effects were redundant. CAI increased the dependence of proximal reabsorption on active chloride transport. KW3902, alone, did likewise, but to a lesser extent than CAI. Adding KW3902 to CAI lessened the shift toward active chloride transport. The data reveal that A(1)R mediate glomerular vascular resistance whether or not TGF is activated, that additive effects of CAI and KW3902 on salt excretion occur, in part, because KW3902 inhibits reabsorption downstream from the macula densa, and that KW3902 likely inhibits proximal reabsorption by interfering with apical sodium-hydrogen exchange.


[Animal experiments on direct drug effects on disseminated intravascular coagulation (DIC) in asphyxic shock].
In a total of 41 rabbit fetus it could be demonstrated in an asphyxia model to what extent disseminated intravascular coagulation may be influenced by directly applying drugs in the foetal circulation. Administration of heparin or streptokinase in the umbilical vessels led to a decrease of fibrin sediments in the areas of terminal coagulation, whereas an increase was caused by injecting noradrenalin or PAMBA.


PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site.
Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr(387) of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.


Liposuction of a pediatric giant superficial lipoma.
Liposuction can be considered a preferable alternative to conventional surgery in pediatric lipomas that are bigger than 4 cm. Liposuction of pediatric lipomas has not been found in the English-language literature. The case of a 5-year-old girl who had liposuction of a large lipoma extending from the lower cervical to the right lumbar region is reported with a review of the literature on the technique, follow-up, and outcome of the procedure.


Long-term results of total hip arthroplasty with the CementLess Spotorno (CLS) system.
This study presents the long-term results of the Cementless Spotorno (CLS) total hip arthroplasty system and an analysis of factors associated with clinical and radiographic outcome. We studied a series of 120 consecutive CLS arthroplasties in a young patient group (mean age at surgery: 55.9 ± 5.9 years). The Merle d'Aubigné-Postel score, polyethylene (PE) wear, and radiographic status were recorded during follow-up. Survival analyses, repeated-measures analysis of variance, and a nested case-control study were used for statistical evaluation. After a mean follow-up of 14.6 years (range 0.1-24.2 years, including revisions and lost to follow-up), 24 revisions had been performed, 16 of which for aseptic cup loosening. Kaplan-Meier survival analysis showed a 24-year survival of 72.8% (95% CI, 63.0%-82.6%) with revision for any reason as endpoint, and 80.1% (95% CI, 70.9%-89.3%) for revision for aseptic cup loosening. Mean final Merle d'Aubigné-Postel score was 16.1 points (range 7-18). Mean PE wear at final follow-up was 2.3 mm (range 0.6-6.8 mm). A higher rate of PE wear was associated with better clinical scores but also with revision for cup loosening. Factors associated with more PE wear were: younger age at surgery; 32 - mm head; longer follow-up; and steeper inclination angle. Beyond 10 years, the CLS stem is reliable, but the high revision rate for aseptic cup loosening is concerning, specifically with better performing (cementless) alternatives available.


Regulation of insulin secretion and reactive oxygen species production by free fatty acids in pancreatic islets.
Free fatty acids regulate insulin secretion through metabolic and intracellular signaling mechanisms such as induction of malonyl-CoA/long-chain CoA pathway, production of lipids, GPRs (G protein-coupled receptors) activation and the modulation of calcium currents. Fatty acids (FA) are also important inducers of ROS (reactive oxygen species) production in β-cells. Production of ROS for short periods is associated with an increase in GSIS (glucose-stimulated insulin secretion), but excessive or sustained production of ROS is negatively correlated with the insulin secretory process. Several mechanisms for FA modulation of ROS production by pancreatic β-cells have been proposed, such as the control of mitochondrial complexes and electron transport, induction of uncoupling proteins, NADPH oxidase activation, interaction with the renin-angiotensin system, and modulation of the antioxidant defense system. The major sites of superoxide production within mitochondria derive from complexes I and III. The amphiphilic nature of FA favors their incorporation into mitochondrial membranes, altering the membrane fluidity and facilitating the electron leak. The extra-mitochondrial ROS production induced by FA through the NADPH oxidase complex is also an important source of these species in β-cells.


A Case Report on Congenital Cytomegalovirus.
Cytomegalovirus (CMV) is the most common congenital infection worldwide and in the United States. The majority of healthy adults who acquire CMV infections have few symptoms and no long-term consequences, though this is not the case for certain groups, including neonates infected in utero. This infection can lead to permanent sequelae, including death. Despite this, congenital cytomegalovirus (cCMV) is not well known among women of childbearing age. Women are more informed about neural tube defects, fetal alcohol syndrome, Down syndrome, and toxoplasmosis than they are about cCMV, although these pose less threat to the newborn. This is a case of a newborn presenting with petechiae, thrombocytopenia, and direct hyperbilirubinemia due to cCMV infection. The initial diagnosis was congenital sepsis, not cCMV. This case report highlights the importance of including a TORCH (toxoplasmosis, others, such as syphilis, rubella, CMV, and herpes) panel when considering abnormal neonatal findings. Diagnosing cCMV is critical, especially because untreated infection can cause permanent sequelae, including death.


Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture.
Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features. The cultures are composed of CK18, desmoglein 3, and CK19-positive luminal cells and vimentin, p63, and CK14-positive myoepithelial cells, suggesting the maintenance of in vivo heterogeneity. In addition, the cultures contain subpopulations with different CD49f and EpCAM expression profiles. When grown in 3D conditions, cells self-organize into distinct structures that express either luminal or basal cell markers. Among these structures, CK8-positive cells enclosing a lumen are capable of differentiation into milk-producing cells in the presence of lactogenic stimulus. Furthermore, our short-term cultures retain the expression of ERα, as well as its ability to respond to estrogen stimulation. We have investigated conditionally reprogrammed normal epithelial cells in terms of cell type heterogeneity, cellular marker expression, and structural arrangement in two-dimensional (2D) and three-dimensional (3D) systems. The conditional reprogramming methodology allows generation of a heterogeneous culture from normal human mammary tissue in vitro. We believe that this cell culture model will provide a valuable tool to study mammary cell function and malignant transformation.


[Measurement of bone mineral content by single-photon absorptiometry in children].
Bone mineral content (BMC) was measured in 64 children (33 boys [aged 4-17] and 31 girls [aged 2-12]) having no signs of metabolic bone disease, at the distal third of their radius using single photon absorptiometry (SPA), to establish normative data. Relationships were studied between the obtained bone mineral content and the age, weight, as well as height of children. The obtained BMC values were compared with that of healthy Swedish and American children. Authors suggest the routine use of SPA in home children suffering from metabolic bone diseases.


Practice facilitators: a review of the literature.
Practice facilitators (PFs) are health care professionals who assist primary care clinicians in research and quality improvement projects. Although they have been used in Europe and Australia for more than 20 years, the concept is relatively new in the United States. The recent evolution of primary care practice-based research networks (PBRNs) has led to greater awareness and expansion of this concept. This study's objective was to review the literature on PFs and describe their origin, training, funding, roles, methods they use, and their impact on patient care outcomes in primary care. We searched four electronic databases from 1966 through the present, reviewing all articles pertaining to PFs in an effort to understand the history, training, financing, roles, methods, and impact of PFs. Since the early 1980s, PFs have worked with individual practices on relationship building, education, and quality improvement (QI), particularly in the area of prevention. A number of publications provide information on the roles of PFs in primary care and methods they use to enhance practices. Many prospective, uncontrolled studies and a few randomized, controlled trials have documented the effectiveness of PFs but usually in combination with other interventions. A number of primary care PBRNs in the United States have begun to use PFs as a way to bridge the gap between research and practice. Limited information has been published about the training and funding of PFs. The PF concept seems to be a useful practice enhancement approach in primary care.


Towards sustainable management of forest residues in the southern Apennine Mediterranean mountain forests: a scenario-based approach.
Managing forest residues according to the carbon content of the soil helps to minimize the ecological footprint of their removal. In Mediterranean mountain ecosystems, unsustainable harvesting of wood residues might contribute to land degradation, carbon, and nutrient depletion in forest soils. This study aimed to assess the amount of forest biomass residues that should be left on-site to minimize the depletion of soil fertility. We estimated the availability of biomass residues in the public forest land of the Basilicata region of Southern Italy by collecting stand-scale inventory attributes from forest management plans. Subsequently, we quantified the amount of forest biomass residue released by implementing a scenario-based approach. Approximately 5800 m3 year-1 of forest residues could be potentially available for bio-based industries at the regional scale within the next 10 years. Such residues mainly belong to broadleaved forest types, having a high variability in their soil organic stock (228.5-705.8 Mg C ha-1) and altitudinally spanning from 400 to 1500 m a.s.l. In these forests, the simulated scenarios displayed a wide range of average harvestable residues from 2.5 to 5.5 m3 ha-1, containing approximately 1.1 to 2.1 Mg ha-1 of organic carbon. Our study suggests that forest management plans are a useful source of information to estimate the available forest biomass residues consistently. In southern Mediterranean mountain forests, the management of forest residues according to soil carbon content helps to minimize the environmental impact and increase their sustainability.


Serogroup-level resolution of the "Super-7" Shiga toxin-producing Escherichia coli using nanopore single-molecule DNA sequencing.
DNA sequencing and other DNA-based methods are now broadly used for detection and identification of bacterial foodborne pathogens. For the identification of foodborne bacterial pathogens, taxonomic assignments must be made to the species or even subspecies level. Long-read DNA sequencing provides finer taxonomic resolution than short-read sequencing. Here, we demonstrate the potential of long-read shotgun sequencing obtained from the Oxford Nanopore Technologies (ONT) MinION single-molecule sequencer, in combination with the Basic Local Alignment Search Tool (BLAST) with custom sequence databases, for foodborne pathogen identification. A library of mixed DNA from strains of the "Super-7" Shiga toxin-producing Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, O145, and O157[:H7]) was sequenced using the ONT MinION resulting in 44,245 long-read sequences. The ONT MinION sequences were compared to a custom database composed of the E. coli O-antigen gene clusters. A vast majority of the sequence reads were from outside of the O-antigen cluster and did not align to any sequences in the O-antigen database. However, 58 sequences (0.13% of the total sequence reads) did align to a specific Super-7 O-antigen gene cluster, with each O-antigen cluster aligning to at least four sequence reads. BLAST analysis against a custom whole-genome database revealed that 5096 (11.5%) of the MinION sequence reads aligned to one and only one sequence in the database, of which 99.6% aligned to a sequence from a "Super-7" STEC. These results demonstrate the ability of the method to resolve STEC to the serogroup level and the potential general utility of the MinION for the detection and typing of foodborne pathogens.


[Exanthematic typhus epidemic in Chile (1932-1939)].
After the great epidemic of the exanthematic typhus of 1918-1919 in Chile, there was a gradual decrease in the number of cases , until it became endemic around 1926. Starting in 1932 and until 1939 a new epidemic outbreak occured that prompted researchers to its study supported by the new clinical and technological advances of this period. Subsequently, two important events occured: the erradication of the vector ( human louse) by means of effective insecticides and the discovery of an effective antibiotic treatment.


Disturbed sense of identity in borderline personality disorder.
Traditionally, personal identity is considered to be important for psychological health and adaptive functioning. Identity diffusion and other more severe forms of disturbance associated with personal identity are regarded as being essential parts of the borderline personality disorder. Moreover, disturbances in identity are seen as being part of the dynamic background for many of the symptoms and maladaptive behaviors found in borderline patients. It is argued, that the development of personal identity is intimately related to, and indeed dependent on, elements of modern culture, with significant cultural changes having affected the conditions under which human identity develops. Therefore, the identity diffusion seen in patients with borderline disorders must be understood in relation to not only the individual patient's personal history and inner structures but also contemporary late modern culture and social organization.


[The significance of determination of Lp(a) in health examinations].
Lp(a), an independent risk factor of thrombotic and arteriosclerotic diseases, was determined in subjects undergoing health examinations, and the significance of the determination of Lp(a) in such examinations was investigated by studying its relation wih other risk factors for arteriosclerosis, etc. The subjects were 838 individuals. Lp(a) was determined by latex immunoassay (LIA). The mean Lp(a) value for all of the subjects was 10.9 +/- 7.2 mg/dl. Both gender groups were compared by age, but no significant changes were observed. In a study of Lp(a) in accordance with complications, there was no significant difference between the DM group and the non-DM group. There was also no significant difference between the IHD group and the non-IHD group. In the hyperlipemia group, the value of Lp(a) tender to be higher than in the non-hyperlipemia group. In the abnormal ECG group, the Lp(a) value was significantly higher than in the normal ECG group. When the relation between Lp(a) and other factors was studied, there was positive correlation with TC, beta Lp and LDLC, and a significant negative correlation with TRG. There was significant negative correlation with GOT, GPT and TTT. When the incidence of disease was compared by cut-off value, the incidence of abnormal ECGs was significantly higher at Lp(a) values of 25 mgdl or higher. In this study, Lp(a) showed positive correlations with TC, beta Lp and LDLC, the atherogenic risk of Lp(a) was evident. Because of the significant incidence of abnormal ECGs at the Lp(a) cut-off value of 25 mg/dl or higher, the risk range for Lp(a) should probably be considered as 25 mg/dl or higher.(ABSTRACT TRUNCATED AT 250 WORDS)


Mirizzi syndrome: a new insight provided by a novel classification.
Mirizzi syndrome (MS) is an uncommon complication of cholelithiasis. The aim of this study is to evaluate our 15-year experience in this challenging entity and to propose a new classification for this disease. A retrospective study including patients diagnosed with Mirizzi syndrome and undergoing surgical procedures for Mirizzi syndrome between January 2000 and October 2015 was conducted. Data collected included clinical, surgical procedure, postoperative morbidity. Patients were evaluated according to the Csendes classification and the proposed system, in which patients were divided into three types and three subtypes. 28 patients were included for analysis. They accounted as the 0.5% of a total of 4853 cholecystectomies performed in the study period. There were 21 women and 7 men. Initial laparotomic approach was performed in 12 patients and in 16 patients laparoscopic procedures were attempted. The procedure was completed in only 6 patients, 5 presenting type I and 1 type II Mirizzi syndrome. Mean postoperative stay was 15±9 days. Postoperative morbidity rate was 28%. Postoperative mortality was none. Laparoscopic surgery for Mirizzi syndrome has been shown succesful only in early stages. A novel classification is proposed, based on the types of common bile duct injuries and in the presence cholecystoenteric fistula.


Gabapentin in the treatment of mental illness: the echo chamber of the case series.
Bipolar disorder is a common and debilitating psychiatric illness. Several antiepileptic drugs (AEDs) have been approved for the treatment of bipolar disorder. Gabapentin gained a large market share of AED use in the late 1990s in spite of a lack of randomized clinical trial (RCT) evidence and no labeled indication from the U.S. Food and Drug Administration for its use in psychiatric illness. This article describes the results of a literature review, the purpose of which was to examine the characteristics of studies conducted in humans concerning the efficacy of gabapentin in bipolar disorder. Publications relevant to this topic were identified based on a PUBMED search as well as an examination of references from a published systematic review and citations from relevant review articles. The search located 29 studies published between 1997 and 2007, with the greatest number of articles published in 1998 and 1999. Of these 29 publications, 15 involved uncontrolled case series, while 6 were single case reports. The sample size in the studies was generally small, and often we could not identify the funding source. Despite the generally weak study design in the identified publications, the authors of the articles often commented on the promising nature of gabapentin therapy for bipolar disorder. However, 4 small, randomized trials in heterogeneous populations demonstrated little if any evidence of such efficacy. Nine letters to the editor demonstrated a similar pattern. The large number of case series concerning gabapentin is striking. The number of reports and their distribution in many different journals created a type of "echo chamber" effect, through which the sheer number of publications and citations may give legitimacy to the practice of using gabapentin for bipolar disorder. Although the case series were generally of poor quality, their publication in peer-reviewed journals may have been partially responsible for the widespread use of an ineffective medication.


Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys.
Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4-6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Animals exposed to manganese sulfate at > or = 0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for > or = 15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. High-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (< or = 0.3 mg Mn/m3) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.


Effect of Dy3+ and Tb3+ Rare-Earth Cation Co-Substitution on the Structure, Magnetic, and Magnetostrictive Properties of Ni-Co-Ferrites.
The design and development of electromagnetic and magnetoelectric materials with enhanced properties and performance are desirable for numerous technologies, which are based on integrated electromagnetic materials and components. Nevertheless, engineering the crystalline materials with multi-complex chemistry and multiple cations is challenging. In this context, herein, we report on the effect of rare-earth (RE) cations, namely, Dy3+ and Tb3+, co-substituted into the Co-Ni-mixed ferrite materials for applications in stress/torque sensors. The RE-cations that co-substituted Co-Ni-ferrite materials with a composition of Ni0.8Co0.2Fe2-x(Dy1-yTby)xO4 (x = 0-0.1, y = 0.3; NCFDT) were prepared by the high-temperature solid-state chemical reaction method. The effect of variable composition (x) on the structure, morphology, chemical bonding, and magnetic properties of NCFDT materials is investigated in detail, and the structure-property optimization enabled realizing magnetostrictive NCFDT for sensor applications. X-ray diffraction analysis coupled with Rietveld refinement confirms the face-centered cubic crystal structure. Chemical bonding analysis made using Raman spectroscopic and Fourier transform infrared spectroscopic measurements validates the active modes corresponding to the spinel ferrite structure. The effect of Dy3+ and Tb3+ substitution is primarily seen in the grain size (range of 5-15 μm), as evident from the scanning electron microscopy patterns. Energy-dispersive spectroscopy confirms the presence of all constituent elements with expected composition and without any impurities. The magnetic property measurements indicate that the remnant magnetization (Mr) increases from 0.06 to 0.17 μB/f.u. with the rare-earth (Dy and Tb) substitution and has achieved the maximum squareness ratio (Mr/Ms) = 0.097 at x = 0.10. To validate their application potential in magneto-mechanical sensors, we have measured the magnetostriction coefficients (λ11 and λ12), which demonstrate high values of λ11 = -92 ppm (along the parallel direction) and λ12 = 66 ppm (along the perpendicular direction) for NCFDT with x = 0.05 at H = 7000 Oe. In addition, the maximum value of strain sensitivity is observed, particularly dλ11dH = -0.764 nm/A whereas dλ12dH = 0.361 nm/A. The correlation between strain sensitivity (dλ/dH) and susceptibility (dM/dH), as derived from magnetostriction and magnetization measurements, respectively, is established. The outcomes of this study indicate that Ni-Co-ferrites with Dy3+ and Tb3+ substitution are suitable for stress/torque sensors. These NCFDT ferrites may also be useful as a necessary constitutive phase for the manufacture of magnetoelectric composite materials, making them appropriate for magnetic field sensors and energy harvesting applications.


FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation.
Fat mass and obesity-associated protein (FTO) is a RNA demethylase, whether FTO regulates fat metabolism through its demethylation is unclear. The results of this study confirmed that N6-methyladenosine (m6 A) is associated with fat accumulation both in vivo and in vitro. The data showed that FTO down-regulated m6 A levels, decreased mitochondrial content, and increased triglyceride (TG) deposition. However, an FTO (R316A) mutant lacking demethylation activity could not regulate mitochondria and TG content, indicating that FTO affects mitochondrial content and fat metabolism by modulating m6 A levels in hepatocytes. In addition, the regulatory roles of cycloleucine (methylation inhibitor) and betaine (methyl donor) could regulate m6 A levels and fat deposition. This work clarified that the demethylation function of FTO plays an essential role in the fat metabolism of hepatocytes and links the epigenetic modification of RNA with fat deposition, thereby providing a new target (m6 A) for regulation of hepatic fat metabolism.


Intra-abdominal bleeding after rupture of hepatic cyst.
We have described the successful surgical management of intra-abdominal bleeding after rupture of a hepatic cyst. In cases of acute arterial hemorrhage, operation is the treatment of choice, whereas unruptured hepatic cysts seldom cause symptoms and rarely need treatment.


Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis.
Hypercalcemia may occur during the course of various granuloma-forming diseases. Herein we describe a patient who had symptomatic hypercalcemia as a prominent sign of Wegener's granulomatosis. We observed a direct correlation between the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] and both the serum and the urinary calcium levels. Administration of prednisone and cyclophosphamide led to a substantial decrease in the levels of calcium and serum 1,25(OH)2D, but the serum levels of 25-hydroxyvitamin D remained unchanged. Two months after admission of the patient, the levels of calcium and 1,25(OH)2D increased; after we increased the dose of cyclophosphamide, these levels decreased (the dose of corticosteroids was not changed). We suggest that the excessive synthesis of 1,25(OH)2D was inhibited by a direct or indirect action not only of prednisone but also of cyclophosphamide on the 1 alpha-hydroxylation of 25-hydroxyvitamin D in the activated macrophage of Wegener granulomas. Furthermore, in view of this case and two other recently reported cases, we believe that Wegener's granulomatosis must be definitively added to the list of granulomatous diseases that are responsible for 1,25(OH)2D-mediated hypercalcemia.


Renal rupture associated with a poorly differentiated follicular thyroid carcinoma metastasizing to the thigh muscle, lung and kidney.
A 76-year-old woman with a history of total thyroidectomy for a thyroid carcinoma at the age of 63 was admitted to our hospital for the treatment of a renal rupture induced by a tumor of about 3 cm in diameter. High levels of blood thyroglobulin (Tg>1,000 ng/ml) led us to suspect a recurrence of thyroid carcinoma. Strong accumulation in whole-body 123I and 201Tl scintigraphy scans after the nephrectomy revealed tumors in the right lung and left thigh muscle measuring 5 cm and 9 cm in diameter, respectively. The tumors of the kidney and thigh muscle were pathologically diagnosed as poorly differentiated follicular thyroid carcinoma, and the lung tumor was also suggested to be a metastasis of the thyroid carcinoma based on the scintigraphy findings. We report this rare case of follicular thyroid carcinoma associated with metastases to the thigh muscle and kidney leading to a rupture 13 years after a total thyroidectomy. Care should be taken to determine whether unknown tumors are thyroid carcinoma metastases.


[Evaluation of chromatographic performance of polymerized ionic liquid stationary phase for capillary gas chromatography].
The selectivity and thermal stability of ionic liquids as the stationary phases for capillary gas chromatography (CGC) have attracted much attention of researchers in recent years. In this study, 1-vinyl-3-benzyl imidazolium-bis(trifluoromethane-sulphonyl)imidate (VBIm-NTf2) was synthesized and polymerized (PVBIm-NTf2) in a CGC column. In comparison with VBIm-NTf2, PVBIm-NTf2 exhibits much better thermal stability and chromatographic selectivity, and achieves satisfactory resolution for Grob test mixture, alcohols mixture, esters mixture and aromatics mixture with narrow and symmetric peak shapes. The satisfactory resolution and selectivity of the polymerized column still remain after conditioned at 250 degrees C for 6 h. Additionally, the Abraham solvation parameters of PVBIm-NTf2 were determined and the interactions between the stationary phase and solutes were elucidated. The present work demonstrates that the polymerization is an effective way to improve the selectivity and thermal stability of common ionic liquids as CGC stationary phases.


Trajectories of BMI change impact glucose and insulin metabolism.
The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m2) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time.


New sacral neuromodulation lead for percutaneous implantation using local anesthesia: description and first experience.
In functional urology today chronic stimulation of the sacral nerves has become one of the most accepted methods of stimulation treatment. Many studies have described the advantage of test stimulation prior to implanting the definitive system to enable effective patient selection. We studied a method aimed at improving lead anchoring by developing a self-blocking electrode with a simple placement procedure, in the process creating a 2-stage approach to full percutaneous implantation that allows a long screening period during the first temporary stimulation stage. A new tined lead was specifically designed to allow minimally invasive percutaneous lead placement requiring no incision and no additional fascial anchoring. From September 2001 to November 2002, 15 consecutive patients (3 males and 12 females) 27 to 70 years old (mean age 49) underwent this procedure and were prospectively evaluated. No PNE test was performed. Following the first stage screening phase 12 patients were implanted with the implantable pulse generator (IPG), while 3 who did not respond positively to test stimulation (neurogenic voiding dysfunction, urge incontinence and neurogenic urge incontinence in 1 each) did not undergo IPG implantation and had the tined lead removed under local anesthesia. We did not observe any lead displacement during the screening period (average 38.8 days) or during followup of IPG implanted cases (average 11 months, range 5 to 19). Our results show that the new tined anchoring system is a reliable way to allow truly minimally invasive placement of the chronic lead.


Enhanced Copolymer Gel Modified by Dual Surfactants for Flexible Zinc-Air Batteries.
Zinc-air batteries using gels as carriers for electrolyte absorption have attracted extensive attention due to their flexibility, deformability, and high specific capacity. However, traditional mono-polymer gel electrolytes display poor mechanical properties and low ionic conductivity at wide-window temperatures. Here, the enhanced gel polymer (PAM-F/G) modified by dual surfactants is present by way of pluronic F127 and layered graphene oxide introduced into the polyacrylamide (PAM) matrix. The gel electrolyte procured by absorbing 6 M KOH exhibits improved mechanical characteristics, temperature adaptability, and a satisfactory ionic conductivity (276 mS cm-1). The results demonstrate that a flexible zinc-air battery assembled by PAM-F/G electrolyte outputs a high power density (155 mW cm-2) and can even operate reliably (>40 h) at -20 °C. These findings are available for promoting the research and popularization of flexible zinc-air batteries with high performance.


The relationship between acid reduction and rate of ulcer healing.
Using data from published clinical trials of acid inhibitory drugs it can be shown that a linear relationship exists between the rate of ulcer healing and the degree of acid inhibition. Since the data used to demonstrate this relationship are group averages of acid reduction and of healing rate, and since there are known to be great individual variations in sensitivity to acid inhibitory drugs as well as in healing rate, it seems likely that the individual relationship between pharmacologic acid inhibition and increase in rate of ulcer healing is different from that which comes out of meta-analysis. Future identification of individual healing curves may form basis for individualized medical treatment in duodenal ulcer diseases.


Melanoma of the anorectal region: the experience of the National Cancer Institute of Milano.
This study describes the experience of the National Cancer Institute of Milano in the treatment of anorectal melanoma over the last 32 years. The influence of different surgical approaches on local care and final outcome was investigated on 40 completely evaluable patients, followed for a median follow-up time of 75 months. The analysis was carried out by calculating and comparing overall survival, disease-free survival and cumulative incidence curves of disease recurrence. Thirty-one patients underwent radical surgery: nine abdominoperineal resections, four total rectal resections and coloendoanal anastomosis, and 18 local excisions. The remaining nine patients received palliative treatments. Median overall survival time for patients receiving non-radical treatments was poor: only 6 months. However, even when a radical surgery was undergone, the prognosis of patients with anal melanoma remains dismal. Local relapse incidence was 45.8% for the limited surgery group, but non-existent for the extended-surgery group (p = 0.007). However, the median disease-free survival time was 7 and 9 months for patients receiving limited or major surgery (p = 0.97). Overall survival was 17 months, irrespective of the adopted surgery. Prognosis of anal melanoma remains poor. Final outcome is not influenced by modality of surgery. A limited but radical excision can be considered whenever possible while a major demolitive surgery should be applied only for therapy of advanced or bulky lesions.


Self-Reported Visual Ability Versus Task Performance in Individuals With Ultra-Low Vision.
Visual functioning questionnaires are commonly used as patient-reported outcome measures to estimate visual ability. Performance measures, on the other hand, provide a direct measure of visual ability. For individuals with ultra-low vision (ULV; visual acuity (VA) <20/1600), the ultra-low vision visual functioning questionnaire (ULV-VFQ) and the Wilmer VRI-a virtual reality-based performance test-estimate self-reported and actual visual ability, respectively, for activities of daily living. But how well do self-reports from ULV-VFQ predict actual task performance in the Wilmer VRI? We administered a subset of 10 matching items from the ULV-VFQ and Wilmer VRI to 27 individuals with ULV. We estimated item measures (task difficulty) and person measures (visual ability) using Rasch analysis for ULV-VFQ and using latent variable signal detection theory for the Wilmer VRI. We then used regression analysis to compare person and item measure estimates from self-reports and task performance. Item and person measures were modestly correlated between the two instruments, with r2 = 0.47 (P = 0.02) and r2 = 0.36 (P = 0.001), demonstrating that self-reports are an imperfect predictor of task difficulty and performance. While self-reports impose a lower demand for equipment and personnel, actual task performance should be measured to assess visual ability in ULV. Visual performance measures should be the preferred outcome measure in clinical trials recruiting individuals with ULV. Virtual reality can be used to standardize tasks.


Surface-guided tomotherapy improves positioning and reduces treatment time: A retrospective analysis of 16 835 treatment fractions.
In this study, we have quantified the setup deviation and time gain when using fast surface scanning for daily setup/positioning with weekly megavoltage computed tomography (MVCT) and compared it to daily MVCT. A total of 16 835 treatment fractions were analyzed, treated, and positioned using our TomoTherapy HD (Accuray Inc., Madison, USA) installed with a Sentinel optical surface scanning system (C-RAD Positioning AB, Uppsala, Sweden). Patients were positioned using in-room lasers, surface scanning and MVCT for the first three fractions. For the remaining fractions, in-room laser was used for setup followed by daily surface scanning with MVCT once weekly. The three-dimensional (3D) setup correction for surface scanning was evaluated from the registration between MVCT and the planning CT. The setup correction vector for the in-room lasers was assessed from the surface scanning and the MVCT to planning CT registration. The imaging time was evaluated as the time from imaging start to beam-on. We analyzed 894 TomoTherapy treatment plans from 2012 to 2018. Of all the treatment fractions performed with surface scanning, 90 % of the residual errors were within 2.3 mm for CNS (N = 284), 2.9 mm for H&N (N = 254), 8.7 mm for thorax (N = 144) and 10.9 for abdomen (N = 134) patients. The difference in residual error between surface scanning and positioning with in-room lasers was significant (P < 0.005) for all sites. The imaging time was assessed as total imaging time per treatment plan, modality, and treatment site and found that surface scanning significantly reduced patient on-couch time compared to MVCT for all treatment sites (P < 0.005). The results indicate that daily surface scanning with weekly MVCT can be used with the current target margins for H&N, CNS, and thorax, with reduced imaging time.


C2'-F Stereoconfiguration As a Puckering Switch for Base Stacking at the Dinucleotide Level.
Fluorine configuration at C2' of the bis(2'-fluorothymidine) dinucleotide is demonstrated to drive intramolecular base stacking. 2'-β F-Configuration drastically reduces stacking compared to the 2'-α series. Hence, base stacking emerges as being tunable by the C2'-F stereoconfiguration through dramatic puckering variations scrutinized by NMR and natural bond orbital analysis. Accordingly, 2'-β F-isomer photoreactivity is significantly reduced compared to that of the 2'-α F-isomer.


Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension.
The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations. To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and β1 -adrenoreceptor (β1-ADR)) and response to Ramipril. We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed. One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and β1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response. Variable responses to Ramipril may be the result of genetic factors. Pre-prescription genotyping may help individualize treatment.


EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.
Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex.


Nonconfinement growth of edge-curved molecular crystals for self-focused microlasers.
Synthesis of single-crystalline micro/nanostructures with curved shapes is essential for developing extraordinary types of optoelectronic devices. Here, we use the strategy of liquid-phase nonconfinement growth to controllably synthesize edge-curved molecular microcrystals on a large scale. By varying the molecular substituents on linear organic conjugated molecules, it is found that the steric hindrance effect could minimize the intrinsic anisotropy of molecular stacking, allowing for the exposure of high-index crystal planes. The growth rate of high-index crystal planes can be further regulated by increasing the molecular supersaturation, which is conducive to the cogrowth of these crystal planes to form continuously curved-shape microcrystals. Assisted by nonrotationally symmetric geometry and optically smooth curvature, edge-curved microcrystals can support low-threshold lasing, and self-focusing directional emission. These results contribute to gaining an insightful understanding of the design and growth of functional molecular crystals and promoting the applications of organic active materials in integrated photonic devices and circuits.


Ecological Processes Shaping Bulk Soil and Rhizosphere Microbiome Assembly in a Long-Term Amazon Forest-to-Agriculture Conversion.
Forest-to-agriculture conversion has been identified as a major threat to soil biodiversity and soil processes resilience, although the consequences of long-term land use change to microbial community assembly and ecological processes have been often neglected. Here, we combined metagenomic approach with a large environmental dataset, to (i) identify the microbial assembly patterns and, (ii) to evaluate the ecological processes governing microbial assembly, in bulk soil and soybean rhizosphere, along a long-term forest-to-agriculture conversion chronosequence, in Eastern Amazon. We hypothesized that (i) microbial communities in bulk soil and rhizosphere have different assembly patterns and (ii) the weight of the four ecological processes governing assembly differs between bulk soil and rhizosphere and along the chronosequence in the same fraction. Community assembly in bulk soil fitted most the zero-sum multinomial (ZSM) neutral-based model, regardless of time. Low to intermediate dispersal was observed. Decreasing influence of abiotic factors was counterbalanced by increasing influence of biotic factors, as the chronosequence advanced. Undominated ecological processes of dispersal limitation and variable selection governing community assembly were observed in this soil fraction. For soybean rhizosphere, community assembly fitted most the lognormal niche-based model in all chronosequence areas. High dispersal and an increasing influence of abiotic factors coupled with a decreasing influence of biotic factors were found along the chronosequence. Thus, we found a dominant role of dispersal process governing microbial assembly with a secondary effect of homogeneous selection process, mainly driven by decreasing aluminum and increased cations saturation in soil solution, due to long-term no-till cropping. Together, our results indicate that long-term no-till lead community abundances in bulk soil to be in a transient and conditional state, while for soybean rhizosphere, community abundances reach a periodic and permanent distribution state. Dominant dispersal process in rhizosphere, coupled with homogeneous selection, brings evidences that soybean root system selects microbial taxa via trade-offs in order to keep functional resilience of soil processes.


Mechanism of the paradoxical, inhibitory effect of phenobarbital on hepatocarcinogenesis initiated in infant B6C3F1 mice with diethylnitrosamine.
Phenobarbital (PB), a classical rodent hepatopromoter, remarkably enhances hepatocarcinogenesis initiated by diethylnitrosamine (DEN) in adult B6C3F1 mice. However, it is also known to strongly inhibit liver tumor development in the B6C3F1 mice initiated with DEN in their infancy. The present study aimed to elucidate the unknown biological mechanisms for this paradoxical, inhibitory effect of PB on B6C3F1 mouse hepatocarcinogenesis. Male 12-day-old infant B6C3F1 mice were injected i.p. with DEN and, at 6 weeks of age, divided into PB-treated (PB+ group) and untreated (PB- group) animals. At 24 weeks, PB treatment was ceased for half of the PB+ animals (PB+/- group) and started for half of the PB- animals (PB-/+ group). Finally, all mice were sacrificed at 36 weeks and examined for the development of liver tumors. The mean multiplicity of gross tumors in the PB+ group was only one-fifteenth of that for the PB- group. PB-/+ animals developed fewer than half of the tumors found in PB- mice, indicating that the PB effect depends solely on the treatment duration, rather than the animal age. The effect was proven to be reversible, because the mean tumor multiplicity for the PB+/- group was seven times larger than that for the PB+ group. Stereological analysis revealed the mean volume of hepatocellular proliferative lesions in the PB- animals to be 7.7- and 4.1-fold the values for the PB+ and PB-/+ groups, respectively. The mean proliferating cell nuclear antigen-labeling indices for hepatocellular adenomas in PB+ and PB-/+ animals were also one-third of that for tumors in PB- animals, whereas no significant differences were observed with regard to the mean apoptotic index. In conclusion, the inhibitory effect of PB seemed to be primarily caused by the suppression of tumor cell proliferation. Irrespective of the group, most lesions observed were basophilic hepatocellular adenomas or foci, positive for Bcl-2 oncoprotein. They were thus distinct from the eosinophilic Bcl-2- lesions that predominate with PB promotion after the initiation of adult B6C3F1 mice. This age-dependent nature of initiation, together with the differential responses of Bcl-2+ and Bcl-2- lesions, may be responsible for the apparently contradictory outcomes of PB treatment in infant and adult B6C3F1 mice.


Inhalation and dietary exposure to PCBs in urban and rural cohorts via congener-specific measurements.
Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr(–1)) and children (12.0 (1.2) μg yr(–1)) than for rural mothers (2.4 (0.4) μg yr(–1)) and children (8.9 (0.3) μg yr(–1)). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children's inhalation exposure.


From subjects to relations: Bioethics and the articulation of postcolonial politics in the Cambodia Pre-Exposure Prophylaxis trial.
Controversies about global clinical trials, particularly HIV trials, tend to be framed in terms of ethics. In this article, I explore debates about ethics in the Cambodia Pre-Exposure Prophylaxis trial, which was designed to test the safety and efficacy of tenofovir as a prevention for HIV infection. Bringing together studies of public participation in science with studies of bioethics, I show how activists around the Cambodian Pre-Exposure Prophylaxis trial circulated and provoked debates about standards of research ethics, as opposed to research methodology. This postcolonial bioethics was configured through the circulation of and debate about ethics guidelines, and historically and culturally specific relations of vulnerability and responsibility between foreigners and Cambodians and between Cambodian leaders and Cambodian subjects. I argue that this shift in the object of ethical concern, from the experimental human subject to the relation between subjects and researchers, illustrates how a postcolonial field of articulation reformulates classical bioethics.


Response to Blomgren, Roy, Callister, and Merrill (2005).
The purpose of this letter is to register concerns about a study reported by M. Blomgren, N. Roy, T. Callister, and R. Merrill (2005), entitled "Intensive Stuttering Modification Therapy: A Multidimentional Assessment of Treatment Outcomes." Concerns include questions about the description of the treatment, the duration of treatment time, and the results of the treatment. The treatment program did not inherently lend itself to clear description (would not be easily replicable), the participants did not improve their speech fluency, and the treatment time was extensive. One must take caution in the interpretation of the results given the concerns noted.


Association of crown emergence angle and profile with dental plaque and inflammation at dental implants.
The shape of implant restorations is critical for function and aesthetics. It may also be important in peri-implant tissue health preservation. This study aimed to associate the restorative contour of a single crown with marginal dental plaque accumulation, tissue inflammation and probing depths. Subjects with a single screw-retained implant restoration were clinically examined. The presence of dental biofilm, tissue inflammation and probing pocket depths were the dependent variables. The emergence angle, profile and depth of the mucosal tunnel were measured on superimposed digital scans of the crown soft-tissue complex, the removed crown mounted on an analogue and the soft tissue. One hundred twenty two subjects (46.7% female, 68.9% never smokers, 77% with treated periodontitis and 52.5% participating in regular supportive peri-implant care) were examined. The emergence angles at the mucosal margin were 15.3 ± 9.4°, 12.7 ± 8.5°, 31.3 ± 11.8° and 19.2 ± 9.8° for the mesial, distal, vestibular and oral aspects of the crowns. The largest emergence profile angles were observed on the vestibular aspect (74.6% of cases), reaching a maximum of 61.7°, and profiles were convex in 59% of cases. Generalized estimating equations indicated that the site-specific platform-level emergence angle and profile and depth of the mucosal tunnel were significantly associated with the presence of detectable plaque accumulation (p < .01) and bleeding on probing (p < .02). Subtle variations in the shape of the restorative crown are associated with biofilm accumulation and mucosal inflammation. These findings are important for 3D implant planning/positioning and preservation of peri-implant tissue health.


Emergency blood transfusion services after the 2005 earthquake in Pakistan.
On 8 October 2005, an earthquake measuring 7.6 on the Richter Scale struck the Himalayan region of Kashmir and Hazara divisions, killing an estimated 73,000 people. Soon after, a situation and response analysis of the emergency blood transfusion services was carried out in the affected areas to ascertain specific needs and suggest appropriate measures to assist in the disaster plan. A semistructured questionnaire, complete with a checklist and participatory observation method, was used to collect data between 12 and 20 October 2005. Study sites were Abbotabad, Mansehra and Muzzafarabad in Pakistan, and interviewees were surgeons and blood bank personnel. Of the seven major hospitals in the area, 3 (43%) had a functional blood transfusion service. Although supply of voluntary blood was abundant, shortage of individual blood groups was noted at each centre. Quality assurance standards were either non-existent or inadequate. Only three blood banks had refrigerators, but with limited storage capacities. A complete breakdown of infrastructure coupled with frequent power failures posed a serious threat to safety of the blood. The continued aftershocks added to the problems. Although initial estimates of blood requirement were high, actual demand noted later was much lower. Timely establishment of blood banks in disaster areas, is a challenging task. Mobile blood banks can be advantageous in such situations. Organisation at a national level for blood transfusion services and development of a minimum standard of quality assurance in normal times should ensure safe emergency blood transfusion services when disaster strikes.


Midface: Clinical Anatomy and Regional Approaches with Injectable Fillers.
The clinical approach towards the midface is one of the most important interventions for practitioners when treating age-related changes of the face. Currently a plethora of procedures are used and presented. However, few of these approaches have been validated or passed review board assigned evaluations. Therefore, it is the aim of this work to establish a guideline manual for practitioners for a safe and effective mid-face treatment based on the most current concepts of facial anatomy. The latter is based on the 5-layered structural arrangement and its understanding is the key towards the favoured outcome and for minimizing complications.


[Severe late stage lesions of pulmonary histiocytosis X. Report of 3 transplantations].
The anatomical lesions of three subjects suffering from pulmonary histiocytosis X and treated with lung transplantation were studied in order to detail the changes occurring in late stages of the disease; the early stages are known on account of lung biopsies done with a diagnostic aim. All the subjects were, at the time of transplantation, in a precarious clinical state and were practically bed-bound as a result of their dyspnoea with a history of histiocytosis X which had been known for 9, 7 and 3 years respectively; one patient had a cardiopulmonary bypass and two unilateral lung transplant. The results of the histological study produced data which was slightly discordant from the communly held ideas; the de Langerhans cells persist in large numbers and after many years of the evolution of the disease, even though other elements of the granuloma have practically disappeared. Fibrosis is absent playing no role in the genesis of the respiratory failure. The lesions are destructive, leading to a disappearance of the alveolar capillary bed which is the source of the dyspnea. The honeycomb cavities to the destroyed lung are varied in nature: most correspond to the disappearance of the dividing walls of the alveoli or the pulmonary acinus, some others related to dilated terminal bronchioles and finally others to hollowed out granulomas which have become cavities. The peculiar characteristic of the lung allows for destructive cavities to be produced by the airflow, submitted to a process of auto-aggravation by the elastic forces and the tension of the pulmonary parenchyma.


A hospital-based study on etiology and prognosis of bacterial meningitis in adults.
Bacterial meningitis is a neurological emergency with high morbidity and mortality. We herein investigated clinical features, etiology, antimicrobial susceptibility profiles, and prognosis of bacterial meningitis in adults from a single tertiary center. We retrospectively reviewed medical records of patients with laboratory-confirmed bacterial meningitis from 2007 to 2016. Patients with recent neurosurgery, head trauma, or indwelling neurosurgical devices were classified as having healthcare-related meningitis. Causative microorganisms were identified by analyzing cerebrospinal fluid (CSF) and blood cultures, and antimicrobial susceptibility profiles were evaluated. We performed multiple logistic regression analysis to identify factors associated with unfavorable outcomes. We identified 161 cases (age, 55.9 ± 15.5 years; male, 50.9%), of which 43 had community-acquired and 118 had healthcare-related meningitis. CSF and blood culture positivity rates were 91.3% and 30.4%, respectively. In community-acquired meningitis patients, Klebsiella pneumoniae (25.6%) was the most common isolate, followed by Streptococcus pneumoniae (18.6%) and Listeria monocytogenes (11.6%). The susceptibility rates of K. pneumoniae to ceftriaxone, cefepime, and meropenem were 85.7%, 81.3%, and 100%, respectively. Among healthcare-related meningitis patients, the most common bacterial isolates were coagulase-negative staphylococci (28.0%), followed by Staphylococcus aureus (16.1%) and Enterobacter spp. (13.6%). Neurological complications occurred in 39.1% of the patients and the 3-month mortality rate was 14.8%. After adjusting for covariates, unfavorable outcome was significantly associated with old age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.06), neurological complications (OR 4.53, 95% CI 1.57-13.05), and initial Glasgow coma scale ≤ 8 (OR 19.71, 95% CI 4.35-89.40). Understanding bacterial pathogens and their antibiotic susceptibility may help optimize antimicrobial therapy in adult bacterial meningitis.


Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy.
Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer.


Topical Administration of Bevacizumab to Facilitate the Functional Filtering Bleb After Trabeculectomy in the Rabbit.
Purpose: To evaluate the effects of bevacizumab in 3 different application methods, subconjunctival injection (SCI), hyaluronic acid retardant (HAR), and eye drop (ED), on attenuating scar formation in the filtering bleb. Methods: Trabeculectomy (TRAB) was performed on New Zealand rabbits. TRAB rabbits were intervened with bevacizumab SCI, HAR, ED, or mitomycin C, respectively. Intraocular pressure (IOP) of 1, 7, 14, and 28 days after TRAB was recorded, and the bleb survival rate was analyzed. Bleb height, area, and vascularization were evaluated using anterior segment optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) at 7, 14 and 28 days after surgery. A histopathology examination of the bleb tissue was performed. The expression levels of vascular endothelial growth factor (VEGF)-A, interleukin (IL)-1α, tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA) were measured by Western blot. Results: Bevacizumab significantly reduced postoperative IOP and increased the survival of the filtering bleb, especially in the ED group. Less vascularization was shown in the SCI, HAR, and ED groups. Histopathological results showed the fewest levels of scarring and fibrosis in the ED group. The local VEGF-A, IL-1α, and TNF-α expression levels after bevacizumab ED were decreased, combined with suppression of TGF-β1 and α-SMA. Conclusions: Postoperative use of bevacizumab EDs was an effective application method for improving surgical outcomes after TRAB in rabbits. It might be effective in preventing scarring of the filtering bleb by antivascularization and anti-inflammation.


Solar cyclic variability can modulate winter Arctic climate.
This study investigates the role of the eleven-year solar cycle on the Arctic climate during 1979-2016. It reveals that during those years, when the winter solar sunspot number (SSN) falls below 1.35 standard deviations (or mean value), the Arctic warming extends from the lower troposphere to high up in the upper stratosphere and vice versa when SSN is above. The warming in the atmospheric column reflects an easterly zonal wind anomaly consistent with warm air and positive geopotential height anomalies for years with minimum SSN and vice versa for the maximum. Despite the inherent limitations of statistical techniques, three different methods - Compositing, Multiple Linear Regression and Correlation - all point to a similar modulating influence of the sun on winter Arctic climate via the pathway of Arctic Oscillation. Presenting schematics, it discusses the mechanisms of how solar cycle variability influences the Arctic climate involving the stratospheric route. Compositing also detects an opposite solar signature on Eurasian snow-cover, which is a cooling during Minimum years, while warming in maximum. It is hypothesized that the reduction of ice in the Arctic and a growth in Eurasia, in recent winters, may in part, be a result of the current weaker solar cycle.


[Bloch-Sulzberg syndrome in pathology].
The authors present some pathological findings in the skin and hair of the child affected by rather rare Bloch-Sulzberg syndrome manifested in incontinentia pigmenti, followed for 10 years. In this work are presented also some recent data about pathogenesis of the disease with X-chromosome dominant heredity, primary of neuroectodermal origincaused by mutation of nuclear factor kappa-B of essential modulator (NEMO) of the gene (chromosomal locus Xq28).


Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate radiotracers for imaging mutant IDH1 expression in tumors.
Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as potential probes for imaging mutant IDH1 expression in tumors with positron emission tomography (PET). Radioiodination of AGI-5198 was achieved using a tin precursor in 79 ± 6% yield (n = 9), and 18F-labeling was accomplished by the Ugi reaction in a decay-corrected radiochemical yield of 2.6 ± 1.6% (n = 5). The inhibitory potency of the analogous nonradioactive compounds against mutant IDH1 (IDH1-R132H) was determined in enzymatic assays. Cell uptake studies using radiolabeled AGI-5198 analogues revealed somewhat higher uptake in IDH1-mutated cells than that in wild-type IDH1 cells. The radiolabeled compounds displayed favorable tissue distribution characteristics in vivo, and good initial uptake in IDH1-mutated tumor xenografts; however, tumor uptake decreased with time. Radioiodinated AGI-5198 exhibited higher tumor-to-background ratios compared with 18F-labeled AGI-5198; unfortunately, similar results were observed in wild-type IDH1 tumor xenografts as well, indicating lack of selectivity for mutant IDH1 for this tracer. These results suggest that AGI-5198 analogues are not a promising platform for radiotracer development. Nonetheless, insights gained from this study may help in design and optimization of novel chemical scaffolds for developing radiotracers for imaging the mutant IDH1 enzyme.


Replica-Based Protein Structure Sampling Methods II: Advanced Hybrid Solvent TIGER2hs.
In many cases, native states of proteins may be predicted with sufficient accuracy by molecular dynamics simulations (MDSs) with modern force fields. Enhanced sampling methods based on MDS are applied for exploring the phase space of a protein sequence and to overcome barriers on rough conformational energy landscapes. The minimum free energy state is obtained with sampling algorithms providing sufficient convergence and accuracy. A reliable but computationally very expensive method is replica exchange molecular dynamics, with many modifications to this approach presented in the past. Recently, we demonstrated how our temperature intervals with global exchange of replicas hybrid (TIGER2h) solvent sampling algorithm made a good compromise between efficiency and accuracy. There, all states are sampled under full explicit solvent conditions with a freely chosen number of replicas, whereas an implicit solvent is used during the swap decisions. This hybrid method yielded a much better approximation to the agreement with calculations in an explicit solvent than fully implicit solvent simulations. Here, we present an extension of TIGER2h and add a few layers of explicit water molecules around the peptide for the energy calculations, whereas the dynamics in fully explicit water is maintained. We claim that these water layers better reproduce steric effects, the polarization of the solvent, and the resulting reaction field energy than typical implicit solvent models. By investigating the protein-solvent interactions across comprehensive thermodynamic state ensembles, we found a strong conformational dependence of this reaction field energy. All simulations were performed with nanoscale molecular dynamics on two peptides, the α-helical peptide (AAQAA)3 and the β-hairpin peptide HP7. A production-ready TIGER2hs implementation is supplied, approaching the accuracy of full explicit solvent sampling at a fraction of computational resources.


The TRbeta-selective agonist, GC-1, stimulates mitochondrial oxidative processes to a lesser extent than triiodothyronine.
Specific tissue responses to thyroid hormone are mediated by the hormone binding to two subtypes of nuclear receptors, TRalpha and TRbeta. We investigated the relationship between TRbeta activation and liver oxidative metabolism in hypothyroid rats treated with equimolar doses of triiodothyronine (T(3)) and GC-1, a TRbeta agonist. T(3) treatment produces increases in O(2) consumption and H(2)O(2) production higher than those elicited by GC-1. The greater effects of T(3) on oxidative processes are linked to the higher hormonal stimulation of the content of respiratory chain components including autoxidizable electron carriers as demonstrated by the measurement of activities of respiratory complexes and H(2)O(2) generation in the presence of respiratory inhibitors. It is conceivable that these differential effects are dependent on the inability of GC-1 to stimulate TRalpha receptors that are likely involved in the expression of some components of the respiratory chain. The greater increases in reactive oxygen species production and susceptibility to oxidants exhibited by mitochondria from T(3)-treated rats are consistent with their higher lipid and protein oxidative damage and lower resistance to Ca(2)(+) load. The T(3) and GC-1 effects on the expression levels of nuclear respiratory factor-1 and -2 and peroxisome proliferator-activated receptor-gamma coactivator-1alpha suggest the involvement of respiratory factors in the agonist-linked changes in mitochondrial respiratory capacities and H(2)O(2) production.


Plasma glucose response after intravenous injection of tolbutamide in insulin-treated type I and type II diabetic patients.
To estimate the residual beta-cell function, plasma glucose and C-peptide response to an intravenous injection of tolbutamide were observed in seven Type I (insulin dependent) and nine Type II (non-insulin dependent) diabetic patients on insulin therapy. Fasting plasma glucose in the patient was controlled below 11 mmol/l by conventional insulin therapy, and 1 g of tolbutamide was intravenously injected. In the serum C-peptide response following tolbutamide injection, seven of nine Type II diabetics showed the peak values of serum C-peptide more than 0.3 nmol/l from 20 min to 60 min after the load, and Type I diabetics gained the peak values less than 0.3 nmol/l except one patient. The decrease of plasma glucose within 60 min after tolbutamide injection was more than 20% of the basal level in eight of nine Type II diabetics, and in all of seven Type I diabetics the decrease did not exceed 15%. Both serum C-peptide and plasma glucose after tolbutamide load responded differently between Type I and Type II diabetics on insulin therapy, and it was thought that tolbutamide load-glucose response test may be a useful method to estimate the residual beta-cell function in the diabetics.


Highly Flexible Dielectric Films from Solution Processable Covalent Organic Frameworks.
Covalent organic frameworks (COFs) are known to be a promising class of materials for a wide range of applications, yet their poor solution processability limits their utility in many areas. Here we report a pore engineering method using hydrophilic side chains to improve the processability of hydrazone and β-ketoenamine-linked COFs and the production of flexible, crystalline films. Mechanical measurements of the free-standing COF films of COF-PEO-3 (hydrazone-linked) and TFP-PEO-3 (β-ketoenamine-linked), revealed a Young's modulus of 391.7 MPa and 1034.7 MPa, respectively. The solubility and excellent mechanical properties enabled the use of these COFs in dielectric devices. Specifically, the TFP-PEO-3 film-based dielectric capacitors display simultaneously high dielectric constant and breakdown strength, resulting in a discharged energy density of 11.22 J cm-3 . This work offers a general approach for producing solution processable COFs and mechanically flexible COF-based films, which hold great potential for use in energy storage and flexible electronics applications.


Curcumin and genistein: the combined effects on disease-associated CFTR mutants and their clinical implications.
Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect of genistein and curcumin on G551D-CFTR, which exhibits gating defects without abnormalities in protein synthesis or trafficking using the patch-clamp technique. We found that genistein and curcumin showed additive effects on their potentiation of G551D-CFTR in high concentration range and also, more importantly, showed a significant synergistic effect in their minimum concentration ranges. These results are consistent with the idea that multiple mechanisms are involved in the action of these CFTR potentiators. In this review, we revisit the pharmacology of genistein and curcumin on CFTR and also propose new pharmaceutical implications of combined use of these compounds in the development of drugs for CF pharmacotherapy.


Full optical SESAM characterization methods in the 1.9 to 3-µm wavelength regime.
Semiconductor saturable absorber mirrors (SESAMs) are widely used for modelocking of various ultrafast lasers. The growing interest for SESAM-modelocked lasers in the short-wave infrared and mid-infrared regime requires precise characterization of SESAM parameters. Here, we present two SESAM characterization setups for a wavelength range of 1.9 to 3 µm to precisely measure both nonlinear reflectivity and time-resolved recovery dynamics. For the nonlinear reflectivity measurement, a high accuracy (<0.04%) over a wide fluence range (0.1-1500 µJ/cm2) is achieved. Time-resolved pump-probe measurements have a resolution of about 100 fs and a scan range of up to 680 ps. Using the two setups, we have fully characterized three different GaSb-SESAMs at an operation wavelength of 2.05 µm fabricated in the FIRST lab at ETH Zurich. The results show excellent performance suitable for modelocking diode-pumped solid-state and semiconductor disk lasers. We have measured saturation fluences of around 4 µJ/cm2, modulation depths varying from 1% to 2.4%, low non-saturable losses (∼ 0.2%) and sufficiently fast recovery times (< 32 ps). The predicted influence of Auger recombination in the GaSb material system is also investigated.


Body dysmorphic disorder and its relationship to sexuality, impulsivity, and addiction.
This study sought to examine the prevalence of probable body dysmorphic disorder (BDD) in a university sample and its associated physical and mental health correlates. A 156-item anonymous online survey was distributed via email to a randomly chosen subset of 10,000 university students, at a large public university. The survey queried current use of alcohol and drugs, psychological and physical status, academic performance, sexual behaviors, and questionnaire-based measures of impulsivity and compulsivity. A total of 3,459 participants (59.1% female) completed the survey and were included in the analysis. The overall prevalence of BDD was 1.7% (n = 59). Compared to students without BDD, those with BDD were significantly more likely to endorse symptoms of compulsive sexual behavior, depression, PTSD, and anxiety. Questionnaire-based measures revealed higher levels of both compulsivity and impulsivity associated with BDD. BDD appears to be common in young adults, and is associated with specific mental health comorbidities, as well as both impulsive and compulsive traits. Clinicians should be aware of the presentation of BDD and screen for it in primary care and mental health settings.


A comparison of intramolecular rearrangements promoted by transposons Tn5 and Tn10.
The bacterial transposon Tn10 has previously been shown to move to other genomic sites by a conservative mechanism, whereby the transposon is excised by double-strand breaks and inserted between a pair of staggered nicks at the target. Other transposons, like Tn3, have been shown to transpose by a replicative mechanism that involves symmetrical nicking of the element and formation of the 'Shapiro intermediate', which can mature into either a cointegrate or a simple insert. The situation with respect to Tn5 is unclear; it was originally reported to use a conservative mechanism, but other evidence suggests that the mechanism might be replicative. In this paper, rearrangements of adjacent DNA promoted by Tn10 and Tn5 have been compared using positive selection for galactose-resistance to detect such rearrangements. Tn10 promoted the formation of adjacent deletions (that started from an inside end of Tn10), deletion/inversions and simple IS10 insertions, but no cointegrates. This behaviour is fully consistent with a conservative mechanism. In contrast, Tn5 was found to promote formation of adjacent deletions (that started mainly from an outside end of Tn5), IS50 insertions (that were frequently accompanied by inversions of adjacent DNA) and cointegrates. These characteristics seem compatible with a replicative, rather than a conservative, mode of transposition. Clearly, Tn5 and Tn10 exhibit some significant differences in their transposition. These results, and results of some previous experiments, have been interpreted to mean that Tn5 could use a replicative mechanism for its transposition.


Molecule-optimized basis sets and Hamiltonians for accelerated electronic structure calculations of atoms and molecules.
Molecule-optimized basis sets, based on approximate natural orbitals, are developed for accelerating the convergence of quantum calculations with strongly correlated (multireferenced) electrons. We use a low-cost approximate solution of the anti-Hermitian contracted Schrödinger equation (ACSE) for the one- and two-electron reduced density matrices (RDMs) to generate an approximate set of natural orbitals for strongly correlated quantum systems. The natural-orbital basis set is truncated to generate a molecule-optimized basis set whose rank matches that of a standard correlation-consistent basis set optimized for the atoms. We show that basis-set truncation by approximate natural orbitals can be viewed as a one-electron unitary transformation of the Hamiltonian operator and suggest an extension of approximate natural-orbital truncations through two-electron unitary transformations of the Hamiltonian operator, such as those employed in the solution of the ACSE. The molecule-optimized basis set from the ACSE improves the accuracy of the equivalent standard atom-optimized basis set at little additional computational cost. We illustrate the method with the potential energy curves of hydrogen fluoride and diatomic nitrogen. Relative to the hydrogen fluoride potential energy curve from the ACSE in a polarized triple-ζ basis set, the ACSE curve in a molecule-optimized basis set, equivalent in size to a polarized double-ζ basis, has a nonparallelity error of 0.0154 au, which is significantly better than the nonparallelity error of 0.0252 au from the polarized double-ζ basis set.


Pure squamous cell carcinoma of the breast presenting as a pyogenic abscess: a case report.
The field of oncology is studded with fascinating case reports of rarities, and management of breast cancer by the oncologist has, at times, resulted in the surfacing of such instances of rarities. Pure squamous cell carcinoma (SCC) of the breast is such an example of a rare and generally aggressive malignancy constituting < 0.1% of invasive breast cancers. To the best of our knowledge, until 2006, only 5 patients of primary SCC of the breast, which presented clinically as breast abscess, have been reported in medical literature. We report the sixth worldwide case of pure primary SCC of the breast presenting as an abscess. In this report, we highlight the fact that a benign lesion like breast abscess can harbor such a rare malignancy. Clinicians should be aware of that fact, and adequate investigations should be done to rule out that possibility. Extensive literature review has been done to discuss the clinical and radiologic features as well as management of this rare lesion.


Regulation of human breast epithelial stem cells.
Breast epithelial stem cells are thought to be the primary targets in the aetiology of breast cancer. As breast cancers are predominantly oestrogen and progesterone receptor-positive (ERalpha/PR+), we investigated the biology of ERalpha/PR+ cells and their relationship to stem cells in normal human breast epithelium. Several complementary approaches were used to characterize the stem-cell population and relate it to ERalpha/PR+ cells, including dual label colocalization on tissue sections, isolation of a Hoechst dye-effluxing 'side population' using flow cytometry, and examination of DNA label retention. The intermediate or suprabasal population suggested by others to be breast stem cells comprises ERalpha/PR+ cells that coexpress the putative stem-cell markers including cytokeratin 19. Human breast epithelial cells with Hoechst dye-effluxing 'side population' properties characteristic of mammary stem cells in mice were demonstrated by lack of expression of myoepithelial and luminal cell-specific antigens such as CALLA and MUC1 to be undifferentiated cells. Using DNA radiolabelling of human tissue implanted into athymic nude mice, a population of label-retaining putative stem cells (LRC) were shown to be enriched for cells expressing the putative stem-cell markers p21CIP1/WAF1 and Musashi-1, which, interestingly, were expressed in separate subpopulations of ERalpha/PR+ cells. Finally, expression patterns of Musashi-1 and Notch-1 in relation to ERalpha/PR+ and adjacent proliferating cells suggest that the evolutionarily conserved Delta/Notch signalling pathway regulates asymmetric division of the putative stem-cell population. The data suggest a model in which ERalpha/PR+ cells scattered through the epithelium are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells. ERalpha/PR+ breast cancers exhibit loss of the two key regulators of asymmetric cell division, Musashi-1 and Notch-1 and thus may arise from symmetric division of the ERalpha/PR+ stem cell.