Antitumor properties of five-coordinate gold(III) complexes bearing substituted polypyridyl ligands.
In an on-going effort to discover metallotherapeutic alternatives to the chemotherapy drug cisplatin, neutral distorted square pyramidal gold(III) coordination complexes possessing 2,9-disubstituted-1,10-phenanthroline ligands {[((R)phen)AuCl3]; R = n-butyl, sec-butyl} have been previously synthesized and characterized. A structurally analogous gold(III) complex bearing a 6,6'-di-methylbipyridine ligand ([((methyl)bipy)AuCl3]) has been synthesized and fully characterized to probe the effect of differing aromatic character of the ligand on solution stability and tumor cell cytotoxicity. The two compounds [((sec-butyl)phen)AuCl3] and [((methyl)bipy)AuCl3]) were subsequently assessed for their stability against the biological reductant glutathione, and it was found that the [((sec-butyl)phen)AuCl3] complex exhibits slightly enhanced stability compared to the [((methyl)bipy)AuCl3] complex and significantly higher stability than previously reported square planar gold(III) complex ions. Furthermore, these complexes were tested for cytotoxic effects against existing lung and head and neck cancer cell lines in vitro. The [((sec-butyl)phen)AuCl3] complex was found to be more cytotoxic than cisplatin against five different tumor cell lines, whereas [((methyl)bipy)AuCl3] had more limited in vitro antitumor activity. Given that [((sec-butyl)phen)AuCl3] had significantly higher antitumor activity, it was tested against an in vivo tumor model. It was found that this complex did not significantly reduce the growth of xenograft tumors in mice and initial model binding studies with bovine serum albumin indicate that interactions with serum albumin proteins may be the cause for the limited in vivo activity of this potential metallotherapeutic.


Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress.
Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells. Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition. For this purpose, ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress. Resveratrol induced cell death at high concentrations (>20 μM), but not at low ones (0.1-20 μM). Pretreatment with 2.5 μM protected the cells from oxidative damage, whereas 50 μM intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells. Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies.


Sequestration of methylene blue dye using sodium alginate poly(acrylic acid)@ZnO hydrogel nanocomposite: Kinetic, Isotherm, and Thermodynamic Investigations.
In this study, a sodium alginate poly(acrylic acid) (SA-poly(AA)) hydrogel and sodium alginate poly(acrylic acid)/zinc oxide (SA-poly(AA)/ZnO) hydrogel nanocomposite (HNC) was synthesized by in situ free-radical polymerization for the sequestration of toxic methylene blue (MB) dye from aqueous solution. The structural properties were analyzed using FTIR, XRD, SEM, TEM, TGA, and DMA The swelling analysis revealed that SA-poly(AA)/ZnO HNC exhibited high water uptake capacity. The kinetics, isotherms, and thermodynamics of adsorption were examined, and results showed that equilibrium data fitted the Langmuir isotherm model, and the adsorption kinetics of MB followed pseudo-second-order model. The maximum adsorption capacity was found to be 1129 mg/g for the SA-poly(AA) hydrogel and 1529.6 mg/g for the SA-poly(AA)/ZnO HNC in 0.25 g/L MB solution at pH 6.0 within 40 min. Thermodynamic parameters for SA-poly(AA) hydrogel and SA-poly(AA)/ZnO HNC substantiated the exothermic and endothermic nature of the adsorption processes, respectively. Moreover, SA-poly(AA)/ZnO HNC presented outstanding reusability with relatively better adsorption efficiencies as compared to SA-poly(AA) hydrogel.


On the nature of Romanowsky--Giemsa staining and its significance for cytochemistry and histochemistry: an overall view.
The chances of Romanowsky---Giemsa (RG) staining becoming a reliable and useful histochemical procedure are reviewed, based on the now proven fact that RG staining requires two dyes only, namely, cationic Azure B and anionic Eosin Y. These two dyes differ from otherwise similar dye combinations in that they give, on distinct biological substrates, one additional colour, purple, which cannot be obtained by the use of either dye alone. The purple colour characterizes the Romanowsky--Giemsa effect (RGE), which is the essential feature of RG staining. Consideration is given to the physico-chemical and morphological implications of RGE. Of primary importance is the nature of the biological substrates where RGE occurs, and also of those where it has never been observed. The way substrates react to RG stains largely depends on the kind of pretreatment they have received; for instance, alcoholic fixation preserves RGE but formaldehyde may inhibit it. Physico-chemical factors are considered which, by altering either the biological substrates or the composition of the staining solutions, may modify the RG staining pattern. This review also serves as an introduction for a series of experimental papers that will follow and which are intended to consolidate the basis of RG staining, a method which holds much promise as a useful histochemical tool.


Regulation of EGF-induced phospholipase C-gamma1 translocation and activation by its SH2 and PH domains.
Translocation of phospholipase C-gamma1 is essential for its function in response to growth factors. However, in spite of recent progress, the phospholipase C-gamma1 translocation pattern and the molecular mechanism of the translocation are far from fully understood. Contradictory results were reported as to which domain, PH or SH2, controls the epidermal growth factor-induced translocation of phospholipase C-gamma1. In this communication, we studied epidermal growth factor-induced translocation of phospholipase C-gamma1 by using comprehensive approaches including biochemistry, indirect fluorescence and live fluorescence imaging. We provided original evidence demonstrating that: (i) endogenous phospholipase C-gamma1, similar to YFP-tagged phospholipase C-gamma1, translocated to endosomes following its initial translocation from cytosol to the plasma membrane in response to epidermal growth factor; (ii) phospholipase C-gamma1 remained phosphorylated in endosomes, but phospholipase C-gamma1 activity is not required for its translocation, which suggests a signaling role for phospholipase C-gamma1 in endosomes; (iii) the PH domain was not required for the initial translocation of phospholipase C-gamma1 from cytosol to the plasma membrane, but it stabilizes phospholipase C-gamma1 in the membrane at a later time; (iv) the function of the phospholipase C-gamma1 PH domain in stabilizing phospholipase C-gamma1 membrane association is very important in maintaining the activity of phospholipase C-gamma1; and (v) the role of the PH domain in phospholipase C-gamma1 membrane association and activation is dependent on PI3K activity. We conclude that the phospholipase C-gamma1 SH2 and PH domains coordinate to determine epidermal growth factor-induced translocation and activation of phospholipase C-gamma1.


Impact of lumbar fusion on spinopelvic sagittal alignment from standing to sitting position: which factor is associated with postoperative functional limitations due to lumbar stiffness?
To investigate the impact of lumbar fusion on spinopelvic sagittal alignment from standing to sitting position and the influencing factors of postoperative functional limitations due to lumbar stiffness. A total of 107 patients who undertook posterior lumbar interbody fusion were included. Patients were divided into two groups: Group A (lumbosacral fusion; n = 43) and Group B (floating fusion; n = 64). Spinopelvic parameters in standing and sitting position including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), fusion segment lordosis (FSL), upper residual lordosis (URL), lower residual lordosis (LRL), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), sagittal vertical axis (SVA) and T1 pelvic angle (TPA) were measured before and after lumbar fusion. The Lumbar Stiffness Disability Index (LSDI) was used to assess functional limitations due to lumbar stiffness. Accompanied by increased postoperative LSDI, the values of changes from standing to sitting (∆) were reduced in some parameters compared with the preoperative values. ∆PT and ∆SS significantly decreased in both two groups. In Group A, ∆LL significantly decreased with increased ∆URL. In Group B, ∆LL, ∆URL and ∆LRL showed no significant difference before and after surgery. Multiple linear regression analysis showed that age and ∆PT independently influenced the postoperative LSDI in Group A. After lumbar fusion, changes of lumbopelvic sagittal parameters from standing to sitting would be restricted. Adjacent segment lordosis could partially compensate for this restriction. For patients with lumbosacral fusion, postoperative functional limitations due to lumbar stiffness were related to age and the postoperative ∆PT from standing to sitting.


Thermal property evaluation of a 2.5D integration method with device level microchannel direct cooling for a high-power GaN HEMT device.
Gallium nitride high electron mobility transistor (GaN HEMT) devices have become critical components in the manufacturing of high-performance radio frequency (RF) or power electronic modules due to their superior characteristics, such as high electron saturation speeds and high power densities. However, the high heat characteristics of GaN HEMTs make device level cooling a critical problem to solve since performance degradation or even failure may occur under high temperatures. In this paper, we proposed a 2.5D integration method with device-level microchannel direct cooling for a high-power GaN HEMT device. To demonstrate this technological concept, a multigate GaN HEMT device featuring a gate length/width/source drain spacing of 0.5 μm/300 μm/6 μm that underwent in-house backside thinning and metallization was used as the test vehicle. A high-resistivity silicon (HR Si) interposer embedded with four-layer microchannels was designed, having widths/pitches of 30 μm/30 μm at the top microchannel. The high-power GaN HEMT device was soldered on a Si interposer embedded with open microchannels for heat dissipation. A pair of GSG Pad chips was soldered simultaneously to display the capacity for the heterogeneous integration of other chip types. Thermal property evaluation was conducted with experiments and simulations. The test results showed that the maximum surface temperature of the GaN HEMT device decreased to 93.8 °C when it experienced a heat dissipation density of 32 kW/cm2 in the gate finger area and an average heat dissipation density of 5 kW/cm2 was found in the active area with the DI water coolant at a flow rate of 3 mL/min. To our knowledge, among recently reported works, this finding was the best cooling capacity of heterogeneously integrated microchannels for GaN HEMT devices. In addition, this technology was scalable regarding the numbers of gate fingers or GaN HEMT devices.


A Randomised Controlled Study Comparing the Anterior Mandibular Labio-Lingual Neutral Zone Position in Edentulous Subjects With and Without Their Maxillary Denture In-Situ.
Opinion is divided as to whether the neutral zone impression to determine the labio-lingual position of mandibular complete dentures requires the maxillary denture to remain in-situ or not. Two such neutral zone impressions were recorded for each of the 12 participants of this randomised controlled study. The presence of the maxillary denture made no statistically significant mean difference in labio-lingual position of the mandibular neutralzone. Within the confines of this research protocol there was no evidence that the shift in the labio-linguial position of the anterior mandibular neutral zone was consistently affected by the presence of a maxillary appliance.


RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis.
It is known that mammalian rpS3 functions as a DNA repair endonuclease and ribosomal protein S3. It was also observed that several ribosomal proteins or DNA repair enzymes are related to apoptosis. We report here a third function of rpS3, induction of apoptosis. The localization of green fluorescent protein (GFP)-rpS3 is changed to the nuclear membrane when lymphocytic cells undergo rpS3-induced apoptosis. Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis. Deletion analysis reveals that the two functions of rpS3, DNA repair and apoptosis, use independent functional domains.


Network Protein Interaction in Parkinson's Disease and Periodontitis Interplay: A Preliminary Bioinformatic Analysis.
Recent studies supported a clinical association between Parkinson's disease (PD) and periodontitis. Hence, investigating possible interactions between proteins associated to these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins with variants strongly associated with PD and periodontitis. Genes of interest were collected via the Genome-Wide Association Studies (GWAS) database. Then, we conducted a protein interaction analysis, using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, with a highest confidence cutoff of 0.9 and sensitivity analysis with confidence cutoff of 0.7. Our protein network casts a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted, giving the limitations of this approach.


A Brazilian Portuguese version of the Revised Fibromyalgia Impact Questionnaire (FIQR): a validation study.
The Fibromyalgia Impact Questionnaire (FIQ) was specifically developed to assess disease severity and functional ability in fibromyalgia patients. In 2009, a revised version of the FIQ was published, the FIQR; this version achieved a better balance among different domains (function, overall impact, symptoms). Here, we present the validity and reliability of the Brazilian version of the Revised Fibromyalgia Impact Questionnaire (FIQR). Female fibromyalgia patients (n = 106) completed an online survey consisting of the Short Form 36 (SF-36) questionnaire, the original FIQ, and the Brazilian Portuguese FIQR, which was translated by a standard method. Validity was established with correlational analyses between the FIQR, FIQ, and SF-36 items. Three domains were established for the FIQR (function, overall impact, symptoms), and their contribution for the SF-36 subscales was also scrutinized. The Brazilian FIQR validation process showed that the questions performed in a very similar way to the original English FIQR. The new questions in the FIQR symptoms domain (memory, balance, tenderness, and environmental sensitivity) revealed a significant impact in fibromyalgia (FM) patients. The Brazilian Portuguese FIQR demonstrated excellent reliability, with a Cronbach's alpha of 0.96. There was a gain on weight of the function domain and a decrease of the symptom domain, leading to a better balance among domains. The FIQR predicted a great number of SF-36 subscales, showing good convergent validity. The Brazilian Portuguese version of the FIQR was validated and found to be a reliable, easy-to-use, and score FM-specific questionnaire that should prove useful in routine clinical practice and FM-related research.


Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review.
Progesterone (P), the natural hormone, binds to its specific receptors to induce specific progestational effects. In addition to this binding, P is able to interfere with the binding sites of other steroids. Therefore the natural hormone exhibits an anti-estrogenic activity, and anti-androgenic activity and also exerts anti-mineralocorticoid effects. For a long time progesterone could not be used in clinical applications because of a rapid liver inactivation after oral administration. An oral micronized preparation of progesterone is now available which produces adequate plasma and tissue levels of progesterone. The preparation reproduces the anti-estrogenic effect of the natural hormone on the endometrium at the dose of 200 mg daily. It also reproduces the anti-mineralocorticoid effect and has no androgenic action. No side effects have been reported as far as lipids profile, coagulation factors and blood pressure are concerned. Therefore oral micronized progesterone appears suitable for hormonal replacement therapy in various areas, essentially postmenopause therapy, premenstrual syndrome, correction of irregular cycles and pregnancy maintenance.


The effects of selenium supplementation on inflammatory markers in critically ill patients.
Low serum selenium (Se) levels have been shown in critical illness, which is associated with poor clinical outcomes and a higher mortality rate. Se plays an important role in inflammation and oxidative stress. Since the overproduction of inflammatory cytokines and increased oxidative stress is a major component of critical illnesses, its supplementation has been demonstrated to have promising effects on critically ill patients. This study aims to review the evidence regarding the effects of Se supplementation on inflammatory and oxidative markers in critically ill patients. The literature review highlights alterations of inflammatory markers, including procalcitonin, leukocyte count, albumin, prealbumin, C-reactive protein (CRP), inflammatory cytokines, and cholesterol following Se supplementation in critically ill patients. Besides, the antioxidant properties of Se due to its presence in the structure of several selenoenzymes have been reported. Low serum Se level have been shown in critical illness, which is associated with poor clinical outcome and higher mortality rate.Se plays an important role in inflammation and oxidative stress.Se supplementation can have promising effects by alterations of inflammatory markers and its antioxidant properties for critically ill patients.


Feasibility of tissue plasminogen activator formulated for pulmonary delivery.
This study was conducted to assess the feasibility of a pulmonary formulation of tissue plasminogen activator (tPA) for nebulization into the airway by measuring protein stability, biologic activity, particle size, and estimating human lung distribution. Formulations were derived by varying the surfactant and protein concentrations. Protein stability and recovery of each nebulized tPA formulation were assessed by ultraviolet spectroscopy. Formulations that met protein stability feasibility criteria were assessed for biologic and fibrinolytic activities. Biologic activity was determined by their ability to inhibit superoxide anion production by human neutrophils. Fibrinolytic activity was assessed by the cleavage of plasminogen to plasmin. Aerodynamic properties were assessed using a cascade impactor, and an estimation of human airway deposition was made via a human lung replica. Twenty-seven tPA formulations were initially assessed, 15 of which met protein stability criteria. Subsequently, three of these formulations maintained biologic and fibrinolytic activities. These formulations exhibited particle sizes of 2.4-3.1 microm, and had respirable doses > or =65%. A formulation of 1mg mL(-1) tPA and 0.1% Tween 80 exhibited a 45% deposition in the lower airways of a human lung replica. A suitable pulmonary tPA formulation was identified that, following nebulization, maintained protein stability as well as biologic and fibrinolytic activities, and resulted in an optimal respirable dose and human airway deposition. This formulation may be applicable in the treatment of lung diseases, such as acute respiratory distress syndrome by permitting targeted pulmonary delivery of a therapeutic protein to the lungs.


Pancreatic hyperenzymemia is associated with bacterial culture positivity, more severe and right-sided colitis.
Several studies reported pancreatic hyperenzymemia (PHE) related to acute colitis. However, there is no consensus on its clinical significance. This study was addressed to find the clinical significance of PHE in acute colitis. Pancreatic hyperenzymemia was defined as abnormal increase in serum concentrations of the pancreatic enzymes by three times of normal upper range without definite pancreatic symptoms and evidence of pancreatitis at abdominal CT imaging of pancreatic disease. And clinical and laboratory and biologic parameters of PHE group and normal pancreatic enzymemia (NPE) group were compared. A total of 1,069 patients admitted to hospitals due to acute colitis were analyzed. Of these patients, 2.99 % (32/1,069) showed PHE. PHE group showed more severe symptoms and had longer hospital stays than the NPE group (12.15 vs. 4.59 days; P < 0.001). Multivariable analysis showed that right-sided colitis (OR 2.846; 95 % CI 1.122-7.224; P = 0.028) and culture positivity (OR 3.346; 95 % CI 1.119-10.008; P = 0.031) are associated with PHE during acute colitis. Also, PHE group was more common when a microorganism could be identified in the cultures (28.1 vs. 7.0 %; P = 0.003), especially blood culture. Among patients with positive cultures, Salmonella spp. had a positive correlation with the right-sided colitis and PHE (amylase P = 0.002; lipase P = 0.029), Salmonella serovar typhimurium (group B) was especially related to increased serum lipase but not to increased serum amylase (lipase; P = 0.041: amylase; P = 0.485). Pancreatic hyperenzymemia is associated with right-sided colitis, bacterial culture positivity, and severe acute colitis.


Kaposi's sarcoma in rheumatoid arthritis.
Cutaneous Kaposi's sarcoma developed eight months after initiation of prednisone treatment in a 58-year-old man with systemic rheumatoid disease (rheumatoid arthritis, Felty's syndrome, rheumatoid vasculitis, and myositis). This patient did not have the acquired immune deficiency syndrome. Review of the literature suggests that the onset of his Kaposi's sarcoma may have been related to immunosuppressive therapy with corticosteroids.


Validation of Direct Analysis Real Time source/Time-of-Flight Mass Spectrometry for organophosphate quantitation on wafer surface.
Microelectronic wafers are exposed to airborne molecular contamination (AMC) during the fabrication process of microelectronic components. The organophosphate compounds belonging to the dopant group are one of the most harmful groups. Once adsorbed on the wafer surface these compounds hardly desorb and could diffuse in the bulk of the wafer and invert the wafer from p-type to n-type. The presence of these compounds on wafer surface could have electrical effect on the microelectronic components. For these reasons, it is of importance to control the amount of these compounds on the surface of the wafer. As a result, a fast quantitative and qualitative analytical method, nondestructive for the wafers, is needed to be able to adjust the process and avoid the loss of an important quantity of processed wafers due to the contamination by organophosphate compounds. Here we developed and validated an analytical method for the determination of organic compounds adsorbed on the surface of microelectronic wafers using the Direct Analysis in Real Time-Time of Flight-Mass Spectrometry (DART-ToF-MS) system. Specifically, the developed methodology concerns the organophosphate group.


Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy.
In an aqueous environment, polymorphic forms I-III of carbamazepine all convert to the dihydrate. This study investigated the conversion of each polymorphic form individually and of a mixture of forms III and I to the dihydrate. Two batches of form I with different crystal morphology were used. Samples were dispersed independently in water at 23+/-1 degrees C and recovered at various timepoints varying from 10 to 210 min. Scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy were used to characterize the initial polymorphic forms and the recovered samples after 210 min. Raman spectroscopy combined with partial least squares analysis was used to generate quantitative models of binary and ternary mixtures of the different polymorphic forms with the dihydrate. On the basis of these models the conversion kinetics of the polymorphic forms I-III were characterized. First-order kinetics with an unconverted portion were used to model the data (R2> or =0.95). The unconverted portions ranged from 16 to 51% after dispersion for 210 min. The conversion kinetics were similar between polymorphic forms with comparable crystal morphology, but differed significantly between batches of the same polymorph (form I) with different crystal morphology. Furthermore, the conversion of forms III and I in the aqueous suspension was not influenced by the presence of the other polymorph when dispersed together.


In vivo phosphorylation of titin and nebulin in frog skeletal muscle.
Titin and nebulin are two major protein components of the sarcomere matrix in striated muscles. Purified titin and nebulin from frog (Xenopus laevis) skeletal muscle are similar in size and in amino acid composition to their mammalian or avian counterparts. Both proteins contain substantial amounts of protein-bound phosphate: about 5 to 6 per titin subunit and 8 to 9 per nebulin subunit. Injection of radioactive inorganic phosphate into the dorsal lymph sacs of Xenopus laevis resulted in the significant incorporation of radioactivity into titin and nebulin within three days of incubation. Purified titin from in vivo labeled frog gastrocnemius muscle contains one mole of radioactive phosphoserine per mole of titin subunit. These data indicate that phosphorylation of frog titin and nebulin occurs in vivo.


[In vitro effect of tuftsin (L-prolyl-L-arginine) on the oxidative capacity of polymorphonuclear lymphocytes in small-for-gestational-age newborn infants].
Tuftsin has the function of activating cellular macrophages and polymorphonuclears (PMNs). This tetrapeptide is transported by the CH2 domain of the heavy chain between residues 289 and 292 of the gammaglobulin (IgG) molecule. The objective of this work is to determine the effect of synthetic tuftsin in its oxidative capacity of PMN cells of newborns of low birth weight for their gestational age having already been demonstrated that the phagocytic activity of these cells of macrophages and PMNs is diminished compared with the cells of newborns of normal birth weight according to gestational age. Results showed a stimulatory effect of the PMNs oxidative capacity with synthetic tuftsin by the increase of the nitrotetrazolium blue reduction, demonstrating that the low oxidative capacity of the cells of newborns of low birth weigh for gestational age does not correlate with an intrinsic cellular defect.


Sensitive procedures for measuring chloride fluxes mediated by the purified glycine receptor incorporated into phospholipid vesicles.
Two novel methods have been developed to directly measure chloride influx into purified glycine receptor-containing phospholipid vesicles. Using a method based on the fluorescence quenching of a chloride-sensitive probe entrapped into the vesicles, a chloride influx was detected which could be enhanced by glycine and completely abolished by the antagonist strychnine. In addition, by tracing the 36Cl- influx into the proteoliposomes, a stimulatory effect of both glycine and beta-alanine could be seen, which can be inhibited by strychnine and other glycine antagonists. These data, together with a previous report demonstrating ligand-mediated iodide fluxes in the same preparation (Biochemistry, 28 (1989) 6405-6409), clearly demonstrate the utility of the reconstituted receptor preparation to investigate some ion channel and pharmacological properties of the glycine receptor.


Lactatdehydrogenase (LDH) prior and post implantation of ATS heart valves.
Establishing guidelines towards an assessment of prostheses dysfunction using LDH as a marker is difficult as shown by [M. Suedkamp, A.J. Lercher, F. Mueller-Riemenschneider, K. LaRosee, P. Tossios, U. Mehlhorn, Hemolysis parameters of St Jude Medical hemodynamic valves in aortic position, Int. J. Cardiol (95) (2004) 89-93]. In response to their work we would like to add our data concerning ATS valves (AP) and say a word of caution in interpreting an increase of LDH values.


Golgi studies of the neurons in layer II of the dorsal horn of the medulla (trigeminal nucleus caudalis).
The translucent band which lies just beneath the spinal V tract at the lower end of the spinal trigeminal nucleus (nucleus caudalis) can be divided into three layers. These three layers are distinguished by textural differences in their neuropil and by the morphology and laminar distribution of the axons and dendrites of their neurons. Layer II contains four different kinds of interneurons. Stalked cells are named after their short, stalk-like branches. Their cell bodies are found in greatest numbers in the outer half of layer II. Their coneshaped dendritic arbors extend medially across layers II and III and sometimes extend into layer IV. Their axons form extensive, canopy-like arborizations in layer I. Stalked cells are considered to be excitatory interneurons receiving input on their dendritic spines from primary axonal endings in the layers II and III glomeruli and transferring it to the dendrites of the layer I projection neurons. Layer II contains three kinds of Golgi type II inteneurons, i.e, neurons whose axons branch repeatedly within the confimes of their dendritic arbors. Islet cells similar to those found in layer III (Gobel), '75a), are found in small clusters in layer II. Their dendrites and axons are largely confined in layer II. The dendrites of the arboreal cell burst, in tree-like fashion, into highly focal dendritic arbors confined largely in layer II while the extensive rostral and caudal dendritic arbors of the II-III border cell lie largely in layers II and III with a few branches extending into layer I. The axons of both of these interneurons arborize in layers II and III with a few collaterals extending into layer I. Islet cells, arboreal cells and II-III border cells are considered to be inhibitory interneurons. They are strategically situated to interrupt transmission between primary axonal endings in layers II and III and the layer I projection neurons by altering the output of the stalked cells.


Risk and protection: the discourse of confinement in contemporary mental health policy.
Confinement has regained respectability in the discourses of contemporary UK mental health policy. This development reflects concern about violent offences by people with mental health problems and is rooted in claims about the 'failure' of community care. Confinement is presented as a strategic response to the risks and dangers posed by particular fractions of the population of mental health service users. Using two key policy statements issued by the Department of Health and associated discussions in the health services management press, the confinement theme is explored and assessed. The paper notes its emergence as a consequence of the spatial impacts of deinstitutionalization and its specific origins in response to violent offences by people with mental health problems. The notion that the growing emphasis on confinement presages a return to the asylum is considered and rejected. Rather, the paper stresses the importance of discourses of protection, safety, risk and dangerousness in understanding the turn to confinement.


Displaying concerns within telephone triage conversations of callers with chest discomfort in out-of-hours primary care: A conversation analytic study.
In primary care out of hours service (OHS-PC), triage nurses ask questions to assign urgency level for medical assessment. A semi-automatic decision tool (the Netherlands Triage Standard, NTS) facilitates triage nurses with key questions, but does not leave much room for paying attention to callers' concerns. We wanted to understand how callers with chest pain formulate their concerns and are helped further during telephone triage. We conducted a conversation analytic study of 68 triage calls from callers with chest discomfort who contacted OHS-PC of which we selected 35 transcripts in which concerns were raised. We analyzed expressions of concerns and the corresponding triage nurse response. Due to the task-oriented nature of the NTS, callers' concerns were overlooked. For callers, however, discussing concerns was relevant, stressed by the finding that the majority of callers with chest discomfort expressed concerns. Interactional difficulties in concern-related discussions arised directly after expressed concerns if not handled adequately, or during the switch to the counseling phase. When callers display concerns during telephone triage, we recommend triage nurses to explore them briefly and then return to the sequence of tasks described in the NTS-assisted triage process.


Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search of a simple yet effective cryopreservation protocol.
To investigate whether solid-surface vitrification (SSV) is an effective cryopreservation strategy regarding the integrity and function of prepubertal mouse testicular tissue. Prospective experimental study. Academic research unit. Mice. Testicular tissue from 5- to 10-day-old GFP(+) mice was cryopreserved with the use of a conventional uncontrolled slow freezing (USF) technique and SSV before intratesticular grafting in busulfan-treated GFP(-) mice. Ultrastructural cryoinjury to spermatogonial stem cells (SSCs) and somatic cells was assessed by electron microscopy. Tubular structure was evaluated by histology, and graft survival and spermatogenic recovery by immunohistochemistry. The tubular morphology and the proportion of ultrastructural cryodamage were similar between vitrified and slow-frozen testicular fragments. Allografting of tissue after both USF and SSV resulted in a recovery of spermatogenesis similar to fresh samples. SSV resulted in success rates similar to USF in maintaining testicular cell ultrastructure, tubular morphology, and tissue function. These data provide further evidence that vitrification, being an inexpensive and simple technique, can be considered as an alternative for cryopreservation of prepubertal testicular tissue.


Possible constraints on adaptive variation in sex ratio at birth in humans and other primates.
There is general agreement that adaptive variation of sex ratio at birth has not been decisively demonstrated in primates (including human beings). So some workers have questioned whether it actually exists. Others have conjectured that it exists but is subject to as yet unidentified 'constraints' (factors opposing the modifying influences of selection in the phenotype). Meanwhile though most workers have called for research to reveal the proximate causes of sex ratio variation, few (if any) have directed studies toward that end. Here it is argued that hormonal action is responsible both for much adaptive and non-adaptive sex ratio variation, and for constraints on the adaptive variation. My hypothesis proposes that levels of steroid hormones (testosterone and oestrogen) of both parents around the time of conception are positively associated with offspring sex ratio (proportion male at birth) of mammals including man. Testosterone in men and oestrogen in women are also known to be positively associated with the health, attractiveness and fertility of individual human beings. However, high levels of testosterone in women are frequently associated with adverse medical conditions. It is suggested that for these reasons (and contrary to some adaptive theory) some classes of people (particularly women) in suboptimal health ("condition") produce excesses of sons. It seems that gonadal hormones are responsible for adaptive variation; and that maternal adrenal hormones are responsible for maladaptive variation. In evolutionary terms, gonadal hormones precede adrenal hormones.


The supernormal period of the cerebellar parallel fibers effects of [Ca2+]o and [K+]o.
The nonmyelinated parallel fibers (Pfs) of the cerebellar cortex exhibit a pronounced supernormal period following a single conditioning volley. In the present investigation a comparison is made between the effects of changes in extracellular calcium ([Ca2+]o) and potassium ([K+]o) on the supernormal period of the Pfs. [Ca2+]o was monitored directly using ion-sensitive microelectrodes while rat cerebellar Pfs were continuously superfused with solutions containing varying concentrations of K+ (5-30 mM) or Ca2+ (0-6 mM). Pf recovery properties were studied by monitoring control (unconditioned) and test (conditioned by a previous impulse) response latencies. [Ca2+]o did not affect the activity-dependent relative increase in Pf excitability observed following conditioning stimulation (i.e. the supernormal period) although both control and test Pf volley latencies were related to [Ca2+]o. Relatively small increases in superfusate K+ concentration elicited a decrease in the control Pf volley latency but had no effect on the test latency. This resulted in the reduction or obliteration of the latency shift elicited by a conditioning stimulus. Simultaneously decreasing [Ca2+]o and increasing [K+]o decreased control Pf volley latency further than when each ion was altered separately. The test Pf volley latency was unchanged. Therefore, under these conditions, there was no Pf volley latency change following conditioning stimulation. These results are consistent with the hypothesis that activity-dependent changes in extracellular ionic concentrations may, in part, be responsible for the supernormal period in cerebellar parallel fibers.


Determinants of adherence to medical regimens by hypertensive patients.
This study employed multivariate analyses and structural modeling procedures to examine a model for the determinants of adherence to medical regimens. Fifty adult hypertensive patients at a health maintenance organization completed questionnaires and participated in home interviews over a 10-week period. Knowledge of medical regimens, information communication between the patient and the medical professionals, satisfaction with health-care providers, health locus of control, social support, and treatment disruption to life-style were assessed. Adherence was assessed through self-report and behavioral (i.e., pill-count ratio, percentage of kept medical appointments) indices. Finally, repeated blood-pressure measurements were obtained. Structural modeling procedures revealed that greater expectancy for internal control over health and hypertension, greater knowledge of the treatment regimen, and stronger social support were significant determinants of adherence; in turn, higher levels of adherence facilitated blood-pressure reduction.


A nomogram-based diabetic sensorimotor polyneuropathy severity prediction using Michigan neuropathy screening instrumentations.
Diabetic Sensorimotor polyneuropathy (DSPN) is one of the major indelible complications in diabetic patients. Michigan neuropathy screening instrumentation (MNSI) is one of the most common screening techniques used for DSPN, however, it does not provide any direct severity grading system. For designing and modeling the DSPN severity grading systems for MNSI, 19 years of data from Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials were used. Different Machine learning-based feature ranking techniques were investigated to identify the important MNSI features associated with DSPN diagnosis. A multivariable logistic regression-based nomogram was generated and validated for DSPN severity grading using the best performing top-ranked MNSI features. Top-10 ranked features from MNSI features: Appearance of Feet (R), Ankle Reflexes (R), Vibration perception (L), Vibration perception (R), Appearance of Feet (L), 10-gm filament (L), Ankle Reflexes (L), 10-gm filament (R), Bed Cover Touch, and Ulceration (R) were identified as important features for identifying DSPN by Multi-Tree Extreme Gradient Boost model. The nomogram-based prediction model exhibited an accuracy of 97.95% and 98.84% for the EDIC test set and an independent test set, respectively. A DSPN severity score technique was generated for MNSI from the DSPN severity prediction model. DSPN patients were stratified into four severity levels: absent, mild, moderate, and severe using the cut-off values of 17.6, 19.1, 20.5 for the DSPN probability less than 50%, 75%-90%, and above 90%, respectively. The findings of this work provide a machine learning-based MNSI severity grading system which has the potential to be used as a secondary decision support system by health professionals in clinical applications and large clinical trials to identify high-risk DSPN patients.


Prognostic impact of germline BRCA1/2 pathogenic variants in breast cancer.
This study investigates the impact of different subtypes of pathogenic BRCA variants on the prognosis and on the survival of breast cancer (BC) patients. Associations between BRCA1/2 pathogenic variants (PVs) mutations, clinicopathological features, locoregional tumor reappearance, and survival data were analyzed. The Gray's test was used to test difference of the cumulative incidence of local relapse between missense/splicing and other mutations, taking into of competing events. The multivariate proportional hazard model was used to assess the independent association between type of mutation and local relapse, after adjustment for other prognostic factors and clinicopathological characteristics. Out of 482 patients, 285 presented 98 different BRCA1 PVs and 201 harbored 103 different BRCA2 PVs. Missense mutations were found in 46 BC patients (9.5%), splicing mutations in 42 (8.6%), deletions in 206 (42.4%), insertions in 73 (15%), indel mutations in 6 (1.2%), nonsense mutations in 86 (17.7%), and large rearrangements in 27 (5.6%). Kalbfleisch and Prentice cumulative incidence curves analysis showed a significantly lower locoregional recurrence incidence in the missense/splicing group (Gray-test P-value = 0.011). We found that the risk of local relapse was 58% less likely in women carrying missense/splicing variants than in those with other PV subtypes (HR 95% CI 0.42 [0.21-0.82]; P-value = 0.0108). No significant differences were observed in overall survival (OS) in all groups. Having been found to be associated with a lower risk of BC reappearance, germline BRCA1/2 PVs of the missense/splicing subtypes can be used as prognostic predictors and are likely to improve BC patients' management.


Polycyclic aromatic hydrocarbon dynamics in soils along proglacial chronosequences in the Alps.
Polycyclic aromatic hydrocarbons (PAHs) were studied in the soils of three proglacial areas in France (Noir and Chardon Glaciers) and Italy (Miage Glacier). PAH contents, PAH stocks and PAH contents normalized to the total organic carbon contents (PAHs/TOC ratio) were investigated along proglacial soil chronosequences to infer their evolutions with soil age (from 3 to 4200 years), where the PAH contamination was only related to long-range atmospheric transport. Evolutions of PAH and TOC contents, PAHs/TOC ratio and PAH stock were fitted with exponential and logarithmic relations. For the three proglacial areas, PAH contents increased rapidly during the first 150 years of soil development, ranged from 4 to 152 ng·g-1, and showed a strong relationship with total organic carbon (TOC) contents (r = 0.83, p < 0.05). The joint increase of PAH and TOC contents suggested that PAH accumulation in soils were not only driven by PAH inputs but also by the capacity of soils to store these contaminants. PAH contents in the oldest soils (from 1200 BCE and 2200 BCE) were similar than for soils from 1850 CE. The period 1850-2019 CE corresponded to a decrease in the PAHs/TOC ratio suggesting both a faster accumulation of TOC than PAHs and a dilution effect of PAHs already present in soils. For the oldest soils, the PAHs/TOC ratio appeared similar to those for soils from 1850 CE, with values ranging from 0.48 to 2.06 ng·mg-1, suggesting an equilibrium between both parameters for soils older than 170 years. Finally, PAH stocks ranged from 0.41 mg·m-2 to 6.80 mg·m-2 in the youngest and oldest soils, respectively. These results do not allow us to identify the same period of greatest emission as other studies (estimated ~1960), but they revealed changes in the capacity of soils to store these pollutants.


A left-handed alpha-helix containing both L- and D-amino acids: the solution structure of the antimicrobial lipodepsipeptide tolaasin.
The 18-amino acid cytolytic lipodepsipeptide tolaasin, produced in culture by virulent strains of Pseudomonas tolaasii, is the causal agent of the brown blotch disease of the cultivated mushroom. Tolaasin has a sequence of D-amino acids in its N-terminal region, then alternates L- and D-amino acids, and bears a C-terminal lactone macrocycle composed of 5-residues. The solution structure of tolaasin in sodium dodecyl sulfate was studied by 2D-NMR spectroscopy and molecular dynamics simulated annealing calculations. Tolaasin forms an amphipathic left-handed alpha-helix in the regionDPro2-DalloThr14 comprising the sequence of seven D-amino acids and the adjacent L-D-L-D-D-region. To the best of our knowledge, this is the first recognized example of a left-handed alpha-helix including both D- and L-amino acids. The lactone macrocycle adopts a "boat-like" conformation and is shifted from the helical axis as to form a "golf-club" overall conformation. These structural features will be of importance in understanding, and preventing, tolaasin's role in the bacterial colonization of the host plant, and its toxic action on cells. Furthermore, the observed antimicrobial activity together with the potential resistance to enzymatic degradation and the increased antigenicity (both due to the presence of L- and D-amino acids) strongly suggests for tolaasin a potential role as a template model for the design of new therapeutic antibacterial molecules.


The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis.
To systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients. PubMed, EMBASE and the Cochrane Library were searched up to March 1st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. EHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01). EHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.


Long-term survival with thorotrast cervical granuloma.
Thorium dioxide, a radioactive contrast material, was commonly used for cerebral angiography prior to recognition of its radiation hazard. Extravasation of the material into the extravascular tissue in the neck results in granuloma formation, thorotrastoma, long-term morbidity, and an increased incidence of benign and malignant tumors. We report our experience with the management of 2 patients who underwent cerebral angiography with thorotrast more than 25 years ago. Aggressive surgical excision of involved tissue is warranted to ameliorate symptoms and diminish the risk of malignancy.


Reduction of orthopaedic wound infections in 21 hospitals.
The German national nosocomial infections surveillance system (KISS) has been collecting surveillance data from hip and knee prosthesis operations since 1997. The purpose of this article is to investigate whether surveillance and feedback of surgical site infection (SSI) information to the physicians and nurses of participating hospitals lead to reduced SSI rates or not. Only information from hospitals previously participating for at least 3 years was used for the analysis. Monthly SSI rates were pooled over the 36-month period, beginning in each clinic's case with its first month of participation, the rates then being compared for 12-month periods. Relative risks were calculated for comparison of the SSI rates in the first and third years of participation. A multiple logistic regression analysis with stepwise variable selection was performed to identify significant risk factors, including the year of surveillance after starting surveillance activities. The overall SSI rates were 1.4% for hip prosthesis and 1.0% for knee prosthesis. Fourteen clinics participated in KISS for at least 3 years continuously with HIP prostheses and 21 with knee prostheses. It was possible to include a total of 15,457 hip and 9,011 knee procedures for this analysis. A comparison of data from the first and the third years show a significant SSI reduction with hip procedures, with a relative risk of 0.54 (CI95 0.38-0.77), and a trend towards reduced SSI rates for knee procedures. The multiple logistic regression analysis confirmed that the SSI rate for hip prosthesis was significantly lower in the third year than in the first year of surveillance (OR = 0.57; CI95 0.42-0.78), though for knee prosthesis the level of significance was not achieved. A reduction of SSIs following hip and knee prosthesis operations through the introduction of ongoing surveillance and the possibility of using benchmark data for comparison does seem to be possible in many institutions.


Green corolla segments in a wild Petunia species caused by a mutation in FBP2, a SEPALLATA-like MADS box gene.
A Petunia inflata isolate with a novel phenotype of a purple corolla limb with green corolla segments (GCS) was characterized. The GCS have stomata and trichomes on the adaxial side, and resemble calyx segments in epidermal morphology. The GCS phenotype was inherited in a recessive manner. In the GCS plant, a novel inhibitor/defective spm-like transposable element (dPifTp1) was inserted in the second intron of the Floral Binding Protein 2 (FBP2) gene. The sequence of the resulting transcript contained five silent mutations as compared the corresponding open reading frame of P. x hybrida FBP2 mRNA. The GCS phenotype co-segregated with an FBP2 fragment containing a dPifTp1 insertion. The transcript level of the FBP2 gene in GCS flowers was markedly lower than that in wild-type (WT) flowers, suggesting that partially inhibited FBP2 gene expression caused the morphogenesis of calyx-like tissue in the corolla segments of GCS flowers. Gene expression pattern analysis using a full-length Petunia floral cDNA microarray indicated that some photosynthesis-related genes were expressed at significantly higher levels in the GCS of GCS flowers, but the mRNA levels of most other genes in the GCS were similar to those in the WT corolla. Taken together, these data suggest that the partial loss of FBP2 expression does not shift global gene expression in the corolla segments of the GCS flower toward that of calyx, even though calyx-like morphogenesis was established in the corolla segments.


Hematocrit Response and Risk Factors for Significant Hematocrit Elevation with Implantable Testosterone Pellets.
We studied the incidence and risk factors for the development of erythrocytosis with implantable testosterone pellets. A multi-institutional retrospective database analysis was used to evaluate men treated with testosterone pellets between 2009 and 2014. Inclusion criteria consisted of adult, hypogonadal males who had a full complement of pretreatment and posttreatment surveillance studies. Pretreatment and posttreatment values were compared with Wilcoxon signed rank tests. Multiple linear regression was used to identify potential risk factors for significant hematocrit elevation. A total of 97 patients were included in the study. The average age of the cohort was 52 years (range 24 to 80). Mean hematocrit before and after pellet implantation was 43.9% and 46.1%, respectively, corresponding to an increase of 2.2% (CI 1.4-2.9, p <0.001). The average increase in testosterone was 145.3 ng/dl from an initial mean of 278.9 ng/dl (CI 105.7-184.9, p <0.001). Multiple linear regression demonstrated that pretreatment hematocrit was inversely related to the expected change in hematocrit. Pretreatment comorbidity status (ie the presence of hypertension, hyperlipidemia, obesity or diabetes) was not associated with a significant increase in posttreatment hematocrit. Although the data demonstrate a statistically significant increase in hematocrit, an increment of 2.2% is unlikely to translate into clinical relevance. Thus, for this cohort of patients implantable testosterone pellets appear safe in terms of the risk of polycythemia. Pretreatment hematocrit may serve as a predictor of a significant hematocrit increase after the initiation of therapy.


An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients.
To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients. Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after "endometrial scratching." Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle. University hopsital. Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age. None. Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change >|0.5| were selected as the threshold for differentially expressed genes. Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including HSD11B2, that catalyzes the conversion of cortisol into cortisone. Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity. The study was registered in the Dutch trial registry (www.trialregister.nl), registration number NL5193/NTR5342, available at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6687. The date of registration is July 31, 2015. The first enrollment is on January 1, 2016.


A case report demonstrating that follicle maturing drugs may create an adverse uterine environment even when not used for controlled ovarian hyperstimulation.
To evaluate whether follicle maturing drugs used in lower dosages for luteal phase defects rather than controlled ovarian hyperstimulation may have an adverse effect on successful implantation. Unique case report. A 40-year-old woman who failed to conceive after six years of follicle maturing drugs with or without progesterone supplementation and four years of in vitro fertilization with embryo transfer (92 embryos transferred in 10 cycles) successfully conceived with the first cycle after the exclusive use of vaginal progesterone in the luteal phase. This case provides convincing evidence that for some women follicle maturing drugs, even when used in lower dosages, can adversely affect the uterine environment.


Mechanistic Insight into the Internalization, Distribution, and Autophagy Process of Manganese Nanoparticles in Capsicum annuum L.: Evidence from Orthogonal Microscopic Analysis.
Orthogonal techniques were used to track manganese nanoparticles (MnNPs) in Capsicum annuum L. leaf tissue and cell compartments and subsequently to explain the mechanism of uptake, translocation, and cellular interaction. C. annuum L was cultivated and foliarly exposed to MnNPs (100 mg/L, 50 mL/per leaf) before analysis by using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) as well as dark-field hyperspectral and two-photon microscopy. We visualized the internalization of MnNP aggregates from the leaf surface and observed particle accumulation in the leaf cuticle and epidermis as well as spongy mesophyll and guard cells. These techniques enabled a description of how MnNPs cross different plant tissues as well as selectively accumulate and translocate in specific cells. We also imaged abundant fluorescent vesicles and vacuoles containing MnNPs, indicating likely induction of autophagy processes in C. annuum L., which is the bio-response upon storing or transforming the particles. These findings highlight the importance of utilizing orthogonal techniques to characterize nanoscale material fate and distribution with complex biological matrices and demonstrate that such an approach offers a significant mechanistic understanding that can inform both risk assessment and efforts aimed at applying nanotechnology to agriculture.


Insight into illness in late-life schizophrenia: a function of illness severity and premorbid intellectual function.
Impaired insight into illness is a common but poorly understood phenomenon in schizophrenia. Several studies in midlife adults with schizophrenia have reported an association between impaired insight and illness severity, executive dysfunction, premorbid intellectual function, and to a lesser degree attention. Aging is associated with a decline in attention and executive function. Thus, the relationship between cognition and insight is expected to differ between younger and older adults with schizophrenia. This study assessed this relationship among 50 patients with schizophrenia 60 years and older. Insight was explained by illness severity (16.2% of the variance) and premorbid intellectual function (23.9% of the variance), but not by attention or executive function. Our findings suggest that the predictors of insight in schizophrenia differ early and later in life. In particular, insight's association with attention and executive function observed in younger patients is attenuated by age-related changes in cognition. In contrast, premorbid intellectual function continues to be a strong predictor of insight in late life, which highlights the need to better understand and enhance cognitive function early in the course of schizophrenia.


Echocardiographic visualization of coronary artery anatomy in the adult.
In the light of technologic advances and the development of new imaging planes, the feasibility of two-dimensional echocardiographic visualization of coronary artery anatomy was reevaluated in the adult. Thirty-five subjects were studied using an ultrasonograph equipped with a 3.5 and 5.0 MHz annular array transducer, digital processing and cine loop review. There were 18 normal subjects and 17 patients with heart disease, including 9 patients with valvular, 5 patients with coronary, 2 patients with congenital and 1 patient with cardiomyopathic disease. The mean age was 47 +/- 18 years (range 17 to 79). Modifications of standard parasternal and apical views permitted high quality images of portions of each of the major epicardial vessels adequate for assessment of luminal diameter. The left main coronary artery was seen in 30 (86%) of the 35 subjects and its bifurcation was seen in 15. The left anterior descending coronary artery was seen in 30 subjects (mean length 3.9 +/- 2.3 cm, maximal length 7.5), the left circumflex artery in 11 (1.1 +/- 1.0, maximal 3.0) and the right coronary artery in 32 (5.6 +/- 2.6, maximal 12). Proximal and mid portions of the left anterior descending artery were seen in 23 and 11 subjects, respectively. The average proximal length visualized was 4.2 cm, and the average luminal diameter visualized was 4.9 mm. The average length of the mid left anterior descending coronary artery seen was 1.9 cm and the average luminal diameter seen was 4.6 mm. The proximal right coronary artery was seen in 17 subjects (average visualized length 2.7 cm and average diameter 3.1 mm).(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic diversity and gene differentiation among ten species of Zingiberaceae from Eastern India.
In the present study, genetic fingerprints of ten species of Zingiberaceae from eastern India were developed using PCR-based markers. 19 RAPD (Rapid Amplified polymorphic DNA), 8 ISSR (Inter Simple Sequence Repeats) and 8 SSR (Simple Sequence Repeats) primers were used to elucidate genetic diversity important for utilization, management and conservation. These primers produced 789 loci, out of which 773 loci were polymorphic (including 220 unique loci) and 16 monomorphic loci. Highest number of bands amplified (263) in Curcuma caesia whereas lowest (209) in Zingiber cassumunar. Though all the markers discriminated the species effectively, analysis of combined data of all markers resulted in better distinction of individual species. Highest number of loci was amplified with SSR primers with resolving power in a range of 17.4-39. Dendrogram based on three molecular data using unweighted pair group method with arithmetic mean classified all the species into two clusters. Mantle matrix correspondence test revealed high matrix correlation in all the cases. Correlation values for RAPD, ISSR and SSR were 0.797, 0.84 and 0.8, respectively, with combined data. In both the genera wild and cultivated species were completely separated from each other at genomic level. It also revealed distinct genetic identity between species of Curcuma and Zingiber. High genetic diversity documented in the present study provides a baseline data for optimization of conservation and breeding programme of the studied zingiberacious species.


[COVID-19: risks of psychological trauma for patients in intensive care or for their families].
For serious cases of COVID-19, with severe respiratory failure due to damage to the lungs by SARS-CoV-2, hospitalisation in intensive care with intubation is often essential. What psychotraumatic risks does this episode present for these patients? Are these sudden, complex treatments, sometimes with fatal outcomes and frequently reported in the media, also a factor in the appearance of psychological trauma for families? These questions are the subject of this clinical reflection.


Predatory - prey relationships in subtropical zooplankton: water mite against cladocerans in an Argentine lake.
In a small lake in northern Argentina pelagic water mite Piona sp. had the maximum of population density in January following with a five-day delay after the peak of zooplankton dominant - Daphnia laevis. The mite density was highly predicted by the previous variations of Daphnia density during 4 months of observation (December-March). Daphnia density was a negative delayed function of the predator density but only in December-January when Piona was abundant. During that period Daphnia death rate, d was also correlated with the mite density (r 2=0.80, P<0.005). In laboratory experiments water mites killed 1-7 Daphnia · predator-1 · hour-1 in a broad range of prey density. Another zooplankton component, Diaphanosoma birgei, was consumed at the same rates. The mite hardly consumed any copepods. In the pelagium during 24 hours the mite was more associated with Daphnia, than with Diaphanosoma, probably, because of the coincidence in photoreactions with Daphnia. Piona contribution to the death rates of its prey estimated by using the data on functional and numerical responses as well as by means of Edmondson-Paloheimo model, could reach 53% for Daphnia and 40% for Diaphanosoma. A computer experiment on the reconstruction of prey dynamics after subtraction of predator influence showed that the mite could have caused a depression in Daphnia numbers observed in the lake, but the declines in Diaphanosoma population were caused by other factors. After the "removal" of mite pressure model Daphnia population increased its average density 10-fold. Experiments on Piona feeding revealed a strong effect of interference among predators. This was eliminated by putting one mite per experimental vessel, which led to a 20-fold increase in predation rate. The effect explains the low feeding rates of Piona obtained by the previous authors who ignored the possibility of interference.


Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues.
The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as sustained activation of liver fibrogenesis and wound healing response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular and tissue process responsible for driving the excess accumulation of extracellular matrix (ECM) components (i.e., liver fibrosis) sustained by an eterogeneous population of hepatic myofibroblasts (MFs). The process of liver fibrogenesis recognizes a number of common and etiology-independent mechanisms and events but it is also significantly influenced by the specific etiology, as also reflected by peculiar morphological patterns of liver fibrosis development. In this review we will analyze the most relevant established and/or emerging pathophysiological issues underlying CLD progression with a focus on the role of critical hepatic cell populations, mechanisms and signaling pathways involved, as they represent potential therapeutic targets, to finally analyze selected and relevant clinical issues.


The origin and evolution of a distinct mechanism of transcription initiation in yeasts.
The molecular process of transcription by RNA Polymerase II is highly conserved among eukaryotes ("classic model"). A distinct way of locating transcription start sites (TSSs) has been identified in a budding yeast Saccharomyces cerevisiae ("scanning model"). Herein, we applied genomic approaches to elucidate the origin of the scanning model and its underlying genetic mechanisms. We first identified TSSs at single-nucleotide resolution for 12 yeast species using the nAnT-iCAGE technique, which significantly improved the annotations of these genomes by providing accurate 5' boundaries for protein-coding genes. We then inferred the initiation mechanism of each species based on its TSS maps and genome sequences. We discovered that the scanning model likely originated after the split of Yarrowia lipolytica and the other budding yeasts. Species that use the scanning model showed an adenine-rich region immediately upstream of the TSS that might facilitate TSS selection. Both initiation mechanisms share a strong preference for pyrimidine-purine dinucleotides surrounding the TSS. Our results suggest that the purine is required to accurately recruit the first nucleotide, thereby increasing the chances of a messenger RNA of being capped during mRNA maturation, which is critical for efficient translation initiation during protein biosynthesis. Based on our findings, we propose a model for TSS selection in the scanning-model species, as well as a model for the stepwise process responsible for the origin and evolution of the scanning model.


Varus malposition relates to functional outcomes following open reduction and internal fixation for proximal humeral fractures: A retrospective comparative cohort study with minimum 2 years follow-up.
The aim of this study was to evaluate functional outcomes in patients with varus malposition following open reduction and internal fixation of displaced proximal humeral fractures. Data of 685 patients with a mean age of 67±15.8 years (67% female), that were treated by open reduction and internal fixation for a displaced proximal humeral fracture at a level 1 trauma center, were analyzed. On standardized x-ray imaging, the degree of varus displacement was measured over a minimum of two years follow-up and patients were divided into three groups. Group A: anatomic or <10° of varus or valgus malposition, group B: 10-20° of varus malposition and group C: >20° varus malposition, while anatomic head-shaft-angle was defined 135° The groups were compared with regards to functional outcomes by means of the Constant Score (CS). In 565 patients with anatomic to minor <10° varus or valgus malposition (Group A), the mean CS was 72.5 ± 18.8 points. The %CS to the uninjured side was 87.2 ± 24.1 and the age and gender normalized nCS was 84.7 ± 21.7. In comparison, in group B (10-20° varus) the mean CS was 64.7 ± 16.9, the mean %CS was 84.5 ± 18.3 and the mean nCS was 76.2 ± 20.6. In group C (>20° varus) the mean CS was 54.1 ± 19.5, the mean was %CS: 72.3 ± 26.4 and the mean nCS was 64.8 ± 23.8 (p = 0.02, p = 0.03, p = 0.01). Overall, the CS, %CS and nCS correlated significantly with the degree of varus position (Pearson correlation, r = 0.23, r = 0.21, r = 0.25). Varus malposition is related to inferior functional outcomes compared to anatomic healing in patients treated by open reduction and internal fixation for proximal humeral fractures. The data supports suggestions to prevent varus malposition in open reduction and internal fixation. In severe >20° of varus malposition, revision surgery should be considered.


Overview of randomized trials in laparoscopic inguinal hernia repair.
There are more than 20 randomized trials that compare laparoscopic with open hernia repair. Results of these show a longer operating time, less postoperative pain, a faster return to normal activity, and increased costs for laparoscopic over open hernia repair. Recurrence rates are lower for laparoscopic compared with open nonmesh repairs.


Spatial congruence of neuronavigated transcranial magnetic stimulation and functional neuroimaging.
Transcranial magnetic stimulation (TMS) is progressively gaining relevance as a tool in cognitive neuroscience and clinical research. However, most studies in this field do not consider individual anatomy. Neuronavigational devices allow to guide the coil to a specific cortical area, predetermined by functional magnetic resonance imaging (fMRI). Therefore, it is crucial to know whether the area of a certain function as identified by fMRI corresponds to the area where the TMS should be placed in order to influence this function. We investigated the spatial relation between the cortical area activated by a motor task in fMRI and the area of magnetically evoked motor potentials (MEP) in 8 subjects, using a spacing of 5x5 mm. A neuronavigational system was adapted for coil positioning and for the registration of the stimulation coordinates. A spatial divergence of the centers of gravity from fMRI and MEP was found with a mean distance of about 10 mm, with the MEP centers being, by a mean derivation of 7.5 mm, consistently anterior to the center of fMRI activation. However, regarding MEP areas and fMRI activities, a large overlap was found for stimulation intensities of both 110 and 120% motor threshold. The combination of fMRI and neuronavigated TMS is useful for non-invasive investigation of individual cortical functions predetermined by fMRI. Whereas both are spatially by and large congruent, discrepencies in the exact spatial relation between MEP and fMRI areas should be considered and further studied.


PA-MSHA induces inflamed tumor microenvironment and sensitizes tumor to anti-PD-1 therapy.
A low response rate to immune checkpoint inhibitor (ICI) therapy has impeded its clinical use. As reported previously, an inflamed tumor microenvironment (TME) was directly correlated with patients' response to immune checkpoint blockade (ICB). Thus, restoring the cytotoxic effect of immune cells in the TME is a promising way to improve the efficacy of ICB and overcome primary resistance to immunotherapy. The effect of Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) in facilitating T cell activation was determined in vitro and in vivo. Subsets of immune cells were analyzed by flow cytometry. Proteomics was carried out to comprehensively analyze the discriminated cellular kinases and transcription factors. The combinational efficacy of PA-MSHA and αPD-1 therapy was studied in vivo. In this study we demonstrated that PA-MSHA, which is a clinically used immune adjuvant, effectively induced the anti-tumor immune response and suppressed the growth of non-small cell lung cancer (NSCLC) cells. PA-MSHA showed great potential to sensitize refractory "cold" tumors to immunotherapy. It effectively enhanced macrophage M1 polarization and induced T cell activation. In vivo, in combination with αPD-1, PA-MSHA suppressed tumor growth and prolonged the survival time of allograft model mice. These results indicate that PA-MSHA is a potent agent to stimulate immune cells infiltration into the TME and consequently induces inflammation in tumors. The combination of PA-MSHA with αPD-1 is a potential strategy to enhance the clinical response rate to ICI therapy.


Occupational stress and alcohol use: a study of two nationwide samples of operational police and ambulance, personnel in Norway.
Police and ambulance personnel are widely believed to have a high prevalence of excessive alcohol consumption. However, the empirical basis for this assumption is scant or nonexistent. We assessed the association of alcohol use with burnout and job stressors, with drinking to cope and neuroticism as two possible moderating factors in two occupations, the police and ambulance services. We undertook a comprehensive nationwide questionnaire survey of police (n = 2,372) and ambulance (n = 1,096) personnel in operational duty. The questionnaire encompassed the Alcohol Use Disorders Identification Test (AUDIT), the Maslach Burnout Inventory, the Job Stress Survey, and the Basic Character Inventory. With a modified AUDIT score of 6 or more, the prevalence for men was 17.7% (police personnel) versus 16.6% (ambulance personnel). The prevalence for women was 9.1% versus 7.4%, respectively. Personnel who were male, were younger, and had higher levels of neuroticism reported higher levels of alcohol-related problems. Drinking to cope was most strongly associated with higher levels of alcohol-related problems (standardized beta = .29, p < .001) and was found to moderate the effect of depersonalization (e.g., cynical and distant attitude toward one's work and the people with whom one works) and gender. In general, the present study does not support the notion of a strong relationship between occupational stress and alcohol use in these emergency service occupations. However, drinking to cope may be a risk factor for alcohol-related problems, particularly among male personnel and those experiencing higher levels of depersonalization.


Effect of modulating endogenous prolactin secretion on testosterone production in the adult male bonnet monkey (Macaca radiata).
Adult male bonnet monkeys maintained under regulated light: dark conditions exhibit a nycthemeral surge of testosterone. The present study attempts to determine the effect of administration of drugs that modulate prolactin levels like ergobromocriptine (EBC) and chlorpromazine (CPZ) on testosterone production. The injection of EBC, a known inhibitor of prolactin secretion, could abolish nocturnal testosterone surge irrespective of the drug being given at 8.00 or 17.00 h. Testosterone surge could likewise be inhibited by treating animals with CPZ, a potent stimulator of prolactin secretion. This suggests that alteration in endogenous prolactin level from the normal effects nycthemeral surges of testosterone. The in vivo responsiveness of the testes of monkeys injected either CPZ oder EBC to exogenous LH or LHRH stimulation was tested. While LH could completely override the CPZ induced inhibition in testosterone production it could only partially reverse the EBC effect.


Epigenome rewiring in human pluripotent stem cells.
The epigenome plays a crucial role in modulating the activity of regulatory elements, thereby orchestrating diverse transcriptional programs during embryonic development. Human (h)PSC stepwise differentiation provides an excellent platform for capturing dynamic epigenomic events during lineage transition in human development. Here we discuss how recent technological advances, from epigenomic mapping to targeted perturbation, are providing a more comprehensive appreciation of remodeling of the chromatin landscape during human development with implications for aberrant rewiring in disease. We predict that the continuous innovation of hPSC differentiation methods, epigenome mapping, and CRISPR (clustered regularly interspaced short palindromic repeats) perturbation technologies will allow researchers to build toward not only a comprehensive understanding of the epigenomic mechanisms governing development, but also a highly flexible way to model diseases with opportunities for translation.


Olfactory conditioning experiments in a food-searching passerine bird in semi-natural conditions.
Because passerine birds have a very small relative olfactory bulb size, they have been considered to have weak olfactory capacities for decades. Recent investigations however suggest that breeding female blue tits (Parus caeruleus) are sensitive to lavender odour in the reproductive context of building and maintaining the nest. Here, we present results of an olfactory conditioning experiment in blue tits held in semi-natural conditions during the breeding season. We show that captive male blue tits, trained to associate lavender odour with a food reward, are more attracted to an empty feeder box emitting lavender odour than an odourless empty feeder box. Females did not distinguish significantly between empty feeders with and without lavender odour during the test phase, although they responded positively at the end of the training phase. These results suggest that male blue tits can use olfaction in a context not related to nest building. Additional experiments will be required to better understand the observed sex differences in response to the experimental set up, and in what context free-ranging individuals use olfaction.


Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions.
The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.


Toward functioning and usable brain-computer interfaces (BCIs): a literature review.
The aim of this paper is to provide an exhaustive review of the literature about brain-computer interfaces (BCIs) that could be used with these paralysed patients. The electroencephalography (EEG) is the best candidate for the continuous use in the environment of patients' houses, due to its portability and ease of use. For this reason, the present paper will focus on this kind of BCI. Moreover, it is our aim to focus more on the patients, regarding their active role in the modulation of the brain activity. This leads to a differentiation between studies that use an active regulation and studies that use a non-active regulation. Relevant articles in the BCIs field were selected using MEDLINE and PsycINFO. Research through data banks produced 980 results, which were reduced to 127 after exclusion criteria selection. These references were divided in four categories, based on the use of active or non-active regulation, and on the event related potential used. In most of the examined works, the focus was on the development of systems and algorithms able to recognise and classify brain events. Although this kind of research is fundamental, a user-centred point of view was rarely adopted. [Box: see text].


Biochemical and functional properties of recombinant human sickle hemoglobin expressed in yeast.
Previous studies had indicated that recombinant and natural human sickle hemoglobin had similar chemical properties (Martin de Llano, J. J., Schneewind, O., Stetler, G., and Manning, J. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 918-922). In the present study, additional biochemical and physiological characterization of some primary through quaternary structural features of recombinant sickle hemoglobin are described. The molecular weight of the purified recombinant sickle hemoglobin was identical to natural sickle hemoglobin as determined by mass spectrometry, thus excluding extensive post-translational modification in the yeast system. Carboxypeptidases A and B together catalyzed the release of COOH-terminal amino acids at the same rate for recombinant and natural hemoglobin S, consistent with identity in their primary and secondary structures in this region of the molecule. The tryptic peptide maps of natural and recombinant hemoglobins were practically indistinguishable, indicating the same internal protein sequences for recombinant and natural hemoglobins. As a probe of the secondary structure of recombinant sickle Hb, the reactivity of the SH group of Cys-93(beta) was investigated for the glutathione sickle hemoglobin adduct, which has significant anti-gelling and anti-sickling properties. The position of glutathione at Cys-93(beta) was established by direct mass spectrometric analysis of enzyme digests; reduction of this derivative to the unmodified chains was also observed by mass spectrometry and by isoelectric focusing. The oxygen equilibrium curves of recombinant and natural sickle hemoglobin at high protein concentration were superimposable with identical Hill coefficients of 3.3. The response of recombinant sickle hemoglobin to chloride with respect to a lowered oxygen affinity was identical to that of natural sickle hemoglobin. The gelation properties of recombinant and natural sickle hemoglobins were identical at the high hemoglobin concentrations that occur in the red cell. Therefore, the yeast expression system synthesizes a completely functional recombinant sickle hemoglobin with the same biochemical and physiological properties as natural sickle hemoglobin with respect to features characteristic of its primary through quaternary structures.


Shoulder MR Arthrography: Comparative Evaluation of Three Different Contrast Injection Techniques Using an Anterior Approach.
MR arthrography (MRA) is commonly used in the assessment of shoulder internal derangements. Correct intra-articular contrast injection is required for this modality. Anterior injections under fluoroscopic, ultrasound-guidance, or without image-guidance have been described in the literature. However, no simultaneous comparison has been performed between the three techniques. To compare the accuracy and performance of fluoroscopy (FL)-guided, ultrasound (US)-guided and non-image-guided intra-articular contrast injection via an anterior approach for performing shoulder MRA. Prospective. Two-hundred and ten patients (180 men and 30 women; mean age, 33 ± 12 years; range 20-60 years) with clinically suspected shoulder pathology. 1.5T/fat-suppressed T1 -weighted, T2 -weighted, and 3D-gradient-echo images. Patients underwent shoulder MRA after anterior intra-articular contrast injection under FL- or US-guidance or without image-guidance. Patients were randomized among the three techniques with each group comprising 70. The techniques were compared according to the accuracy of intra-articular needle placement, attempts success rate, pain during and 24 hours after injection, procedure times, contrast extravasation rate, joint distension, and MRA diagnostic efficacy. Pain was assessed by the visual analog scale (VAS) pain-score. Pearson's chi-squared and Kruskal-Wallis tests. FL- and US-guided injections (100% accuracy) were significantly more accurate than non-image-guided (85.7% accuracy) (P < 0.05). US-guidance was the least painful, with statistical differences between image-guided and non-image-guided techniques regarding the first attempt success rate (95.7% and 92.8% for FL- and US-guided vs. 78.6% for blinded), VAS-score 24 hours-post-procedure (1.7 ± 1.7, and 1.5 ± 1.4 vs. 2.2 ± 1.4), procedure time (11.9 ± 1.6, and 7.4 ± 1.7 vs. 4.3 ± 0.76 minutes), and contrast extravasation rate (5.7%, and 8.6% vs. 30%) (all P < 0.05). Procedure time was also significantly different between FL and US-guidance (P < 0.05). Imaging-guided injections are more accurate and tolerable than non-image-guided and should be considered to confirm intra-articular needle position, hence adequate capsular distension and good diagnostic quality of shoulder MRA. US guidance is a less painful, rapid, and safe alternative to the FL approach. Evidence Level: 2 Technical Efficacy Stage: 5. J. MAGN. RESON. IMAGING 2021;53:481-490.


Review on chromatographic and specific detection methodologies for unravelling the complexity of MOAH in foods.
Contamination of foods with mineral oil hydrocarbons, particularly mineral oil aromatic hydrocarbons (MOAH), can potentially pose a health hazard to consumers. However, identifying toxic substances among the many thousands of compounds comprising mineral oils in food samples is a difficult analytical challenge. According to the European Food Safety Authority, there is a lack of concentration and structural data about mineral oil hydrocarbons in foods, and therefore it is not clear to what extent consumers in Europe might be exposed to toxic levels of MOAH. The current gold standard method for determination of mineral oil hydrocarbons is online high-performance liquid chromatography (LC)-gas chromatography (GC) with flame ionization detection, which quantifies total saturated/aromatic content, but gives no qualitative information. The objective of this review is to explore the future prospects in mineral oil hydrocarbon determination and MOAH characterization in foods. To that end, peer reviewed literature was explored, particularly from the viewpoint of a methodology for detailed characterization of the MOAH fraction that can aid toxicological assessment. The literature clearly shows that there is much to be gained from the orthogonality power of multidimensional chromatographic separations and mass spectrometric (MS) detection. Comprehensive two-dimensional GC coupled to MS, preceded by pre-fractionations of MOAH by LC is suggested to be the most promising approach for further research. In addition, the strengths and weaknesses of a number of other, alternative approaches, both for qualitative and quantitative analysis, are discussed.


Acquisition of nonmaternal Enterobacteriaceae by infants delivered in hospitals.
To determine whether Escherichia coli strains that colonize the intestinal tract of newborn infants in hospitals are of maternal origin or come from the environment, plasmid profiles of E. coli strains isolated from the stools of infants were compared with those from the stools of their mothers. Twenty-nine mother-infant pairs were studied in three different hospitals. In only 4 of 29 pairs, plasmid profiles of E. coli or other Enterobacteriaceae were shared by infant and mother; vertical transmission seemed to be uncommon, unlike findings in previous reports. In one hospital, 8 of 10 infant fecal E. coli strains shared a single plasmid profile, strongly suggesting nosocomial acquisition. In another, 7 of 9 neonate strains also shared a unique profile, and additionally carried K1 capsular antigen, a known virulence factor. Two other infants from the latter nursery acquired a urinary tract infection with E. coli K1 carrying the same plasmid profile. This study indicates that nosocomial acquisition of hospital strains of E. coli by neonates may be common in some hospitals and that the clinical implications are potentially serious.


What will you want tomorrow? Children-But not adults- mis-predict another person's future desires.
Young children have difficulty predicting a future physiological state that conflicts with their current state. This finding is explained by the fact that children are biased by their current state (e.g., thirsty and desiring water) and thus have difficulty imagining themselves in a different state (e.g., not thirsty and desiring pretzels) "tomorrow," for example. Another potential explanation that we explore here is that young children have difficulty understanding how physiological states, like thirst, fluctuate over time. We asked 3-, 4- and 5-year-olds (Experiment 1) and adults (Experiment 2) to predict what a thirsty Experimenter-who preferred crisps to water-would want ("water" or "crisps") "right now" and "tomorrow." Only adults correctly predicted someone else's future desires when this person's future and current desires conflicted. In contrast, both adults and children in the control groups (in which the Experimenter was not thirsty) had no difficulty predicting that the Experimenter would want crisps "right now" and "tomorrow." Our findings suggest that children's difficulty predicting future desires cannot solely be attributed to their being biased by their current state since the children in our study were, themselves, not thirsty. We discuss our results in the context of children's difficulty understanding fluctuations in physiological states.


Semi-supervised method for image texture classification of pituitary tumors via CycleGAN and optimized feature extraction.
Accurately determining the softness level of pituitary tumors preoperatively by using their image textures can provide a basis for surgical options and prognosis. Existing methods for this problem require manual intervention, which could hinder the efficiency and accuracy considerably. We present an automatic method for diagnosing the texture of pituitary tumors using unbalanced sequence image data. Firstly, for the small sample problem in our pituitary tumor MRI image dataset where T1 and T2 sequence data are unbalanced (due to data missing) and under-sampled, our method uses a CycleGAN (Cycle-Consistent Adversarial Networks) model for domain conversion to obtain fully sampled MRI spatial sequence. Then, it uses a DenseNet (Densely Connected Convolutional Networks)-ResNet(Deep Residual Networks) based Autoencoder framework to optimize the feature extraction process for pituitary tumor image data. Finally, to take advantage of sequence data, it uses a CRNN (Convolutional Recurrent Neural Network) model to classify pituitary tumors based on their predicted softness levels. Experiments show that our method is the best in terms of efficiency and accuracy (91.78%) compared to other methods. We propose a semi-supervised method for grading pituitary tumor texture. This method can accurately determine the softness level of pituitary tumors, which provides convenience for surgical selection and prognosis, and improves the diagnostic efficiency of pituitary tumors.


[Minutes of the Working Group on Gynecopathology and Breast Pathology, 24 May 2018 : 102nd Annual Congress of the German Society of Pathology].


Possible progenesis in Neophasis anarrhichae (Nicoll, 1909) Bray, 1987 in the White Sea.
Neophasis anarrhichae (Nicoll, 1909) Bray, 1987, unlike the majority of acanthocolpid digeneans, has an abbreviated two-host life cycle. The reproduction of rediae, development of cercariae, and their transformation into unencysted metacercariae occur within the only intermediate host, the whelk Buccinum undatum. Normally, the metacercariae develop into sexual adults (maritae) and egg production starts when the infected whelk is eaten by a wolffish Anarhichas lupus. In the White Sea, we have found three cases of infection of B. undatum by progenetic metacercariae of N. anarrichae. These metacercariae had a fully developed and functioning hermaphroditic reproductive system, and eggs were found in their uterus. Most eggs observed in the histological sections were abortive, but some contained embryos at early stages of development. The progenetic metacercariae were similar in their morphometric characteristics to the sexual adults from the wolffish, the main differences being the size of the ovary and eggs. In order to confirm progenesis, and thus a facultative one-host life cycle in N. anarrichae, we need to prove that the eggs from metacercariae are viable.


ICER induced by hyperglycemia represses the expression of genes essential for insulin exocytosis.
The GTPases Rab3a and Rab27a and their effectors Granuphilin/Slp4 and Noc2 are essential regulators of neuroendocrine secretion. Chronic exposure of pancreatic beta-cells to supraphysiological glucose levels decreased selectively the expression of these proteins. This glucotoxic effect was mimicked by cAMP-raising agents and blocked by PKA inhibitors. We demonstrate that the transcriptional repressor ICER, which is induced in a PKA-dependent manner by chronic hyperglycemia and cAMP-raising agents, is responsible for the decline of the four genes. ICER overexpression diminished the level of Granuphilin, Noc2, Rab3a and Rab27a by binding to cAMP responsive elements located in the promoters of these genes and inhibited exocytosis of beta-cells in response to secretagogues. Moreover, the loss in the expression of the genes of the secretory machinery caused by glucose and cAMP-raising agents was prevented by an antisense construct that reduces ICER levels. We propose that induction of inappropriate ICER levels lead to defects in the secretory process of pancreatic beta-cells possibly contributing, in conjunction with other known deleterious effects of hyperglycemia, to defective insulin release in type 2 diabetes.