Continual measurement of arterial dP/dtmax enables minimally invasive monitoring of left ventricular contractility in patients with acute heart failure.
Continuous, reliable evaluation of left ventricular (LV) contractile function in patients with advanced heart failure requiring intensive care remains challenging. Continual monitoring of dP/dtmax from the arterial line has recently become available in hemodynamic monitoring. However, the relationship between arterial dP/dtmax and LV dP/dtmax remains unclear. This study aimed to determine the relationship between arterial dP/dtmax and LV dP/dtmax assessed using echocardiography in patients with acute heart failure. Forty-eight patients (mean age 70.4 years [65% male]) with acute heart failure requiring intensive care and hemodynamic monitoring were recruited. Hemodynamic variables, including arterial dP/dtmax, were continually monitored using arterial line pressure waveform analysis. LV dP/dtmax was assessed using continuous-wave Doppler analysis of mitral regurgitation flow. Values from continual arterial dP/dtmax monitoring were significantly correlated with LV dP/dtmax assessed using echocardiography (r = 0.70 [95% confidence interval (CI) 0.51-0.82]; P < 0.0001). Linear regression analysis revealed that LV dP/dtmax = 1.25 × (arterial dP/dtmax) (P < 0.0001). Arterial dP/dtmax was also significantly correlated with stroke volume (SV) (r = 0.63; P < 0.0001) and cardiac output (CO) (r = 0.42; P = 0.0289). In contrast, arterial dP/dtmax was not correlated with SV variation, dynamic arterial elastance, heart rate, systemic vascular resistance (SVR), or mean arterial pressure. Markedly stronger agreement between arterial and LV dP/dtmax was observed in subgroups with higher SVR (N = 28; r = 0.91; P < 0.0001), lower CO (N = 26; r = 0.81; P < 0.0001), and lower SV (N = 25; r = 0.60; P = 0.0014). A weak correlation was observed in the subjects with lower SVR (N = 20; r = 0.61; P = 0.0004); in the subgroups with higher CO (N = 22) and higher SV (N = 23), no significant correlation was found. Our results suggest that in patients with acute heart failure requiring intensive care with an arterial line, continuous calculation of arterial dP/dtmax may be used for monitoring LV contractility, especially in those with higher SVR, lower CO, and lower SV, such as in patients experiencing cardiogenic shock. On the other hand, there was only a weak or no significant correlation in the subgroups with higher CO, higher SV, and lower SVR.


Pediatric neurosurgical disease.
The most common, primary referrals to a pediatric neurosurgeon's office are the evaluation and management of the child with a large head (to rule out hydrocephalus and other space occupying lesions) a mishappen head (to rule out various forms of craniosynostosis), or some form of congenital spinal abnormality (spinal dysraphism). The authors discuss the pathogenesis and clinical features of these disorders, provide a framework for diagnostic evaluation and referral, and discuss the various treatment options available for each.


Optimization of In-Continuity Spring-Mediated Intestinal Lengthening.
Spring-mediated intestinal lengthening has been studied in numerous animal models to effectively achieve up to a 3-fold increase in length. In this study we are interested in optimizing this method of spring lengthening. Juvenile mini-Yucatan pigs underwent laparotomy for spring implantation. Springs were secured by plicating the intestine around the springs. In one set of experiments, varying degrees of plication were compared to determine the necessary narrowing needed to confine the spring. In another set of experiments, dissolvable sutures were used for the plication to allow for spontaneous spring passage postoperatively. Intestinal segments were retrieved and evaluated for lengthening and histological changes. Pigs tolerated their diet advancement to a regular diet postoperatively. 10% plication resulted in a 1.3-fold increase in length, while 50% plication resulted in a 2.7-fold increase in length (p<0.05). At two months postoperatively, the majority of springs had safely passed out of the intestine. All lengthened intestine showed significant growth histologically. A 50% reduction in lumen diameter achieves optimal spring-mediated intestinal lengthening. Springs can safely pass out of the intestine, thus avoiding a second operation for spring removal. These results may be important in developing future therapies for short bowel syndrome. Level I experimental study.


Small optical magnetic-field sensor that uses rare-Earth iron garnet films based on the faraday effect.
Highly accurate optical magnetic-field probe sensors that use iron garnet films have been developed. New probe-type sensors were designed with a confocal optical system. A new garnet composition, Bi(0.98)Gd(0.92)La(0.03)Y(1.07)Fe(4.72)Ga(0.28)O(12), was found that shows high temperature stability for a sensitivity of less than 2.0% from -20 to +80 degrees C. The linearity error of the sensor output was within 1.0% for alternating magnetic fields from 0.3 to 42 mT. An optical current transformer that uses the proposed sensor has an ac linearity of 1.0% for input current up to nearly 300 A. The sensor realized high performance in actual use.


Vertical profile of photosynthetic light response within rice canopy.
Measured leaf photosynthetic light response (PLR) curves at different positions were fitted by non-rectangular hyperbola (NRH) equation to characterize vertical profile of parameters in NRH equation, namely maximum net photosynthetic rate Pnmax, initial quantum yield of assimilation φ, dark respiration rate Rd, and convexity of the curve k, at both jointing and heading stages within rice canopy. And leaf-position-specific and canopy average NRH equations were constructed respectively based on measured PLR curves at each specific leaf position and all measured PLR curves within rice canopy. The results showed that the Pnmax, φ, and Rd reached the maximum at the top second leaf and then decreased at jointing stage and decreased in downward leaves at heading stage. The k increased with lowering leaf position at both stages. The leaf-position-specific NRH equation performed well in estimating net photosynthetic rate Pn for all leaves at different positions and stages, while the canopy average NRH equation underestimated leaf Pn at upper canopy and overestimated Pn at lower canopy. The top fourth leaf was suitable for estimating photosynthetic parameters at canopy scale, as the Pnmax, φ, Rd, and k of the top fourth leaf were near to these parameters of rice canopy, and the canopy average NRH equation performed well in estimating leaf Pn for the top fourth leaf. The results will provide basic information for upscaling leaf photosynthesis to canopy scale.


The sequences of the S2 genome segments of reovirus serotype 3 and of the dsRNA-negative mutant ts447.
The most temperature-sensitive dsRNA-negative mutant of reovirus serotype 3 is ts447; the amount of dsRNA formed in cells infected with it at 39 degrees is less than 0.1% of that formed in cells with wt virus at 37 degrees. The genome segment in which this mutation is located is S2. We compare here the sequence of the S2 genome segment of wt reovirus serotype 3 with that of mutant ts447. The two sequences differ in three locations, at two of which there are C to U transitions, while at the third there is an A to G transition. All cause amino acid changes (Ala to Val, Ala to Val, and Asn to Asp, respectively). One mutation (at nucleotide position 581, which causes an Ala to Val change) causes the length of an alpha-helix to be significantly reduced and may be that which is responsible for the ts phenotype.


(E)-1-(4-Fluoro-2-hy-droxy-phen-yl)-3-(2,3,4-tri-meth-oxy-phen-yl)prop-2-en-1-one.
In the title mol-ecule, C18H17FO5, the conformation about the C=C bond of the central enone group is trans. The dihedral angle between the benzene rings is 13.08 (3)°. The hy-droxy group attached to the benzene ring is involved in an intra-molecular O-H⋯O hydrogen bond. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into chains along [001].


Symptomatic osteoma originated from lamina papyracea.
We describe a 74-year-old woman with osteoma of the lamina papyracea who only presented with 4-month history of an unspecific compression and pain in the medial canthal area of the left eye. The patient reported prompt relief from her pain after resection of the osteoma by endoscopic sinus surgery and she was free of pain clinically with no evidence of recurrence at 12 months followup. Also, we reviewed the literature relevant to the pathophysiology of the osteoma pain.


An evaluation of influenza, pneumococcal and herpes zoster vaccination coverage in Australian aged care residents, 2018 to 2022.
For older persons, vaccination mitigates the harmful impact of vaccine preventable infections. Our study objectives were to evaluate in the Victorian public sector residential aged care services (PSRACS) (1) the existence of local vaccination policies and admission assessment practices, (2) the current documented status of resident influenza, pneumococcal and herpes zoster vaccination uptake and (3) changes in documented resident vaccination uptake over time. Standardised data were annually reported by all PSRACS between 2018 and 2022. The influenza, pneumococcal and herpes zoster vaccination status of each resident was classified as vaccinated, declined, contraindicated or unknown. Annual trends in vaccination status were assessed using Spearman's correlation. In 2022, most PSRACS reported an influenza immunisation policy existed (87.1%) and new residents were assessed for their influenza vaccination status (97.2%); fewer PSRACS reported the same for pneumococcal disease (73.1% and 78.9%) and herpes zoster (69.3% and 75.6%). The median resident influenza, pneumococcal and herpes zoster (70-79 years old) vaccination uptake was 86.8%, 32.8% and 19.3% respectively. The median unknown status was 6.9%, 63.0% and 76.0% respectively. Statistical evidence of an increase in annual uptake was observed for the herpes zoster (all resident) surveillance module (rs = 0.900, p = 0.037). Our study showed local influenza vaccination policies and practices exist and influenza vaccination uptake was consistently high. Pneumococcal and herpes zoster vaccination uptake were lower. Quality improvement strategies that at least determine the status of those residents classified as unknown are required.


Controlled release of protein from gelatin/chitosan hydrogel containing platelet-rich fibrin encapsulated in chitosan nanoparticles for accelerated wound healing in an animal model.
The physiological healing process is disrupted in many cases using the current wound healing procedures, resulting in delayed wound healing. Hydrogel wound dressings provide a moist environment to enhance granulation tissue and epithelium formation in the wound area. However, exudate accumulation, bacterial proliferation, and reduced levels of growth factors are difficulties of hydrogel dressings. Here, we loaded platelet-rich fibrin-chitosan (CH-PRF) nanoparticles into the gelatin-chitosan hydrogel (Gel-CH/CH-PRF) by solvent mixing method. Our goal was to evaluate the characteristics of hydrogel dressings, sustained release of proteins from the hydrogel dressing containing PRF, and reduction in the risk of infection by the bacteria in the wound area. The Gel-CH/CH-PRF hydrogel showed excellent swelling behavior, good porosity, proper specific surface area, high absorption of wound exudates, and proper vapor permeability rate (2023 g/m 2.day), which provided requisite moisture without dehydration around the wound area. Thermal behavior and the protein release from the hydrogels were investigated using simultaneous thermal analysis and the Bradford test, respectively. Most importantly, an excellent ability to control the release of proteins from the hydrogel dressings was observed. The high antimicrobial activity of hydrogel was confirmed using Gram-positive and Gram-negative bacteria. Due to the presence of chitosan in the hydrogels, the lowest scavenging capacity-50 value (5.82 μgmL-1) and the highest DPPH radical scavenging activity (83 %) at a concentration 25 μgmL-1 for Gel-CH/CH-PRF hydrogel were observed. Also, the hydrogels revealed excellent cell viability and proliferation. The wound healing process was studied using an in vivo model of the full-thickness wound. The wound closure was significantly higher on Gel-CH/CH-PRF hydrogel compared to the control group, indicating the highest epidermis thickness, and enhancing the formation of new granulation tissue. Our findings demonstrated that Gel-CH/CH-PRF hydrogel can provide an ideal wound dressing for accelerated wound healing.


Rational use of paracetamol among out-patients in a Bhutanese district hospital bordering India: a cross-sectional study.
Paracetamol or acetaminophen is a weak analgesic commonly used worldwide and in Bhutan. It is available across all levels of Bhutan's health care system and for purchase without prescription. Little is known, however, about patterns of paracetamol use in Bhutan. This study aimed to assess what the Bhutanese population knows about the indications for use of paracetamol, safe use, and common patterns of usage (frequency, dosage). These questions were studied among Bhutanese living in Phuentsholing, a large commercial town at Bhutan-India border. Among 441 participants, most (72.1%) reported having used paracetamol in the past 1 year. The mean knowledge score was 57.6%; only 30 participants (6.8%) had what was characterized as "good knowledge." Level of knowledge was positively associated with level of education (p = 0.031). Less than half (41.3%) had a "good attitude" towards use of paracetamol. In practice, few (4.8%) knew the correct dose, including about one in ten who reported exceeding the recommended therapeutic dose. Most knew about side effects (61.2%) and possible allergic reactions (77.3%). Many participants (47.9%) acknowledged that the self-use of paracetamol may not reduce the number of hospital visits.


Water permeation drives tumor cell migration in confined microenvironments.
Cell migration is a critical process for diverse (patho)physiological phenomena. Intriguingly, cell migration through physically confined spaces can persist even when typical hallmarks of 2D planar migration, such as actin polymerization and myosin II-mediated contractility, are inhibited. Here, we present an integrated experimental and theoretical approach ("Osmotic Engine Model") and demonstrate that directed water permeation is a major mechanism of cell migration in confined microenvironments. Using microfluidic and imaging techniques along with mathematical modeling, we show that tumor cells confined in a narrow channel establish a polarized distribution of Na+/H+ pumps and aquaporins in the cell membrane, which creates a net inflow of water and ions at the cell leading edge and a net outflow of water and ions at the trailing edge, leading to net cell displacement. Collectively, this study presents an alternate mechanism of cell migration in confinement that depends on cell-volume regulation via water permeation.


Effects of quercetin and genistein on egg quality, lipid profiles, and immunity in laying hens.
After the peak laying stage, laying hens become susceptible to lipid accumulation and inflammatory reactions. The objective of this experiment was to examine the impact of quercetin and genistein on egg quality and lipid profiles in laying hens. A total of 240 Hy-Line Brown hens were randomly assigned to three dietary treatments. Each treatment had eight replicates, with ten hens in each replicate, and the hens were aged between 46 and 56 weeks. The test diets consisted of a corn-soybean meal-based basal diet, a basal diet supplemented with 300 mg kg-1 quercetin, and a basal diet supplemented with 300 mg kg-1 quercetin and 40 mg kg-1 genistein. Results showed that, separately, supplemental quercetin significantly improved egg quality (eggshell strength, albumen height, and Haugh unit, P < 0.05) and reduced the deposition of abdominal fat (P < 0.05). Our findings also showed that, separately or as a combination, supplemental quercetin and genistein significantly increased eggshell thickness (P < 0.05), decreased the levels of lipids in serum (low-density lipoprotein cholesterol, total cholesterol, total triglycerides, and non-esterified fatty acids, P < 0.05) and significantly increased serum immunoglobulins A and G (P < 0.05), and promoted the expression of splenic immune-related genes (IgA and IL-4, P < 0.05). This study confirmed that supplemental quercetin and genistein, either separately or in combination, can enhance eggshell thickness, lipid profiles, and immune function in aging hens. Moreover, both quercetin alone and quercetin + genistein exhibited similar abilities to lower lipid levels and improve immune function. © 2023 Society of Chemical Industry.


A conserved TN8TCCT motif in the octapeptide-encoding region of Pax genes which has the potential to direct cytosine methylation.
Our previous findings have shown that the developmental genes Pax7 and Pax3 are differentially methylated; the gene region that encodes the paired domain is hypomethylated, whereas the region that encodes the homeodomain is hypermethylated. For this reason, the known DNA sequence between the paired and homeoboxes was analysed for the presence of a conserved DNA motif to which a modifying protein could bind in order to direct the methylation or demethylation of surrounding gene sequences. The octapeptide-encoding region was found to contain several nucleotides that were highly conserved throughout the Pax gene family from phylogenetically distant species. The most conserved nucleotides are thought to comprise a motif TN8TCCT where N8=any combination of eight nucleotides. A conserved octapeptide-like-encoding sequence containing the TN8TCCT motif was also found in non-Pax genes of higher eukaryotes and in the non-coding strand of plants. Moreover, differential methylation seems to be associated with the presence of the TN8TCCT motif in p53 and the human oestrogen receptor genes. The presence of the TN8TCCT motif within an octapeptide-like-encoding sequence in human T-cell leukaemia virus type 1 might suggest that the putative recognition motif may have been introduced into various host genomes via some form of retroviral agent.


Suggested guidelines for the treatment of children with sickle cell anemia.
It is the purpose of this article to provide guidelines used in our sickle cell center for the treatment of several frequent medical complications that occur in children with sickle cell anemia.


Localisation of members of the vascular endothelial growth factor (VEGF) family and their receptors in human atherosclerotic arteries.
Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. The existence of single or multiple VEGF isoforms and receptors suggests that these proteins may have overlapping but distinct functions, which may be reflected in their cell expression and distribution. The localisation of VEGFs A-C and their receptors (VEGFRs 1-3, respectively) in 30 fresh human atherosclerotic arteries, 15 normal uterine arteries, and 15 saphenous veins using immunohistochemistry and western blotting. Saphenous veins showed no staining for VEGF-B or VEGFR-2. Smooth muscle cells (SMCs) showed the strongest staining for VEGF-A, VEGF-B, VEGFR-1, and VEGFR-2 in all specimens. Conversely, VEGFR-3 and VEGF-C were predominantly localised to the endothelial vasa vasorum in normal arteries, whereas medial SMCs showed the strongest staining in atherosclerotic arteries. Western blotting showed variations in VEGF protein localisation, with lower amounts of VEGF-B and VEGF-C in saphenous veins, compared with arterial tissue. Amounts of VEGF-C were lower than those of VEGF-A and VEGF-B in all specimens. This study provides direct evidence of the presence of VEGF proteins and receptors in human physiology and pathology, with variations in both the amounts of VEGF proteins expressed and their cellular distribution in normal arteries compared with atherosclerotic arteries. The presence of VEGFs A-C and their receptors in normal arterial tissue implies that VEGF functions may extend beyond endothelial cell proliferation. Reduced VEGFR-2 staining in atherosclerotic arteries may have implications for the atherosclerosis process and the development of vascular disease and its complications.


Cellular response to substrate rigidity is governed by either stress or strain.
Cells sense the rigidity of their substrate; however, little is known about the physical variables that determine their response to this rigidity. Here, we report traction stress measurements carried out using fibroblasts on polyacrylamide gels with Young's moduli ranging from 6 to 110 kPa. We prepared the substrates by employing a modified method that involves N-acryloyl-6-aminocaproic acid (ACA). ACA allows for covalent binding between proteins and elastomers and thus introduces a more stable immobilization of collagen onto the substrate when compared to the conventional method of using sulfo-succinimidyl-6-(4-azido-2-nitrophenyl-amino) hexanoate (sulfo-SANPAH). Cells remove extracellular matrix proteins off the surface of gels coated using sulfo-SANPAH, which corresponds to lower values of traction stress and substrate deformation compared to gels coated using ACA. On soft ACA gels (Young's modulus <20 kPa), cell-exerted substrate deformation remains constant, independent of the substrate Young's modulus. In contrast, on stiff substrates (Young's modulus >20 kPa), traction stress plateaus at a limiting value and the substrate deformation decreases with increasing substrate rigidity. Sustained substrate strain on soft substrates and sustained traction stress on stiff substrates suggest these may be factors governing cellular responses to substrate rigidity.


Determination of ROS-Induced Lipid Peroxidation by HPLC-Based Quantification of Hydroxy Polyunsaturated Fatty Acids.
Because they are highly unsaturated, plant lipids are sensitive to oxidation and constitute a primary target of reactive oxygen species. Therefore, quantification of lipid peroxidation provides a pertinent approach to evaluating oxidative stress in plants. Here, we describe a simple method to measure upstream products of the peroxidation of the major polyunsaturated fatty acids in plants, namely, linolenic acid (C18:3) and linoleic acid (C18:2). The method uses conventional HPLC with UV detection to measure hydroxy C18:3 and C18:2 after reduction of their respective hydroperoxides. The described experimental approach requires low amounts of plant material (a few hundred milligrams), monitors oxidation of both membrane and free fatty acids, and can discriminate between enzymatic and non-enzymatic lipid peroxidation.


Optimal scheduling in demand-side management based grid-connected microgrid system by hybrid optimization approach considering diverse wind profiles.
Demand side management (DSM) is one of the trending economic strategies which shifts the elastic demand to the off-peak hours from the peak hours so as to reduce the overall generation cost of the system. The work done in this paper can be categorized in three phases. In the first phase, various wind speed to power conversion mathematical models available in literature are analysed to find out the one with maximum level of wind penetration. For second phase, an economic DSM strategy is implemented to restructure the forecasted load demand model for various participation levels. In the final phase the cost-effective optimization of two microgrid distribution systems are percolated. As an optimization tool, novel hybrid CSAJAYA has been used to carry on the study. Different types of grid participating and pricing strategies along with valve point loading effect and wind energy uncertainty are considered to amplify the complexity and practicality of the study. The generation costs reduced from 3 to 5% when the forecasted demand was reformed with 20% DSM participation for both the test systems. A detailed comparison with the results from various optimization tools studied confirms the effectiveness of the proposed hybrid approach. The hybrid optimization tool presented in this paper performs better in terms of central tendencies, nonparametric statistical analysis, and algorithm execution time.


Predicting risk of postpartum haemorrhage: a systematic review.
Postpartum haemorrhage (PPH) causes substantial morbidity and mortality worldwide. A reliable prognostic tool for PPH has potential to aid prevention efforts. Systematically to identify and appraise prognostic modelling studies for prediction of PPH. MEDLINE, Embase, CINAHL and the Cochrane Library were searched using a combination of terms and synonyms including 'prediction tool', 'risk score' and 'postpartum haemorrhage'. Any observational or experimental study developing a prognostic model for women's risk of PPH. English language publications. Predesigned data extraction form to record: data source; participant criteria; outcome; candidate predictors; actual predictors; sample size; missing data; model development; model performance; model evaluation; interpretation. Of 2146 citations screened, 14 studies were eligible for inclusion. Studies addressed populations of women who experienced placenta praevia, placenta accreta spectrum, vaginal birth, caesarean birth (CS) and the general obstetric population. All studies were at high risk of bias due to low sample size, no internal validation, suboptimal or no external validation or no reporting or handling of missing data. Five studies raised applicability concerns. Three externally validated and three internally validated studies show potential for robust external validation. Of 14 prognostic models for PPH risk, three have some potential for clinical use: in CS, in placenta accreta spectrum disorders with MRI placental Evaluation and in placenta praevia. Future research requires robust internal and external validation of existing tools and development of a model for use in the general obstetric population. Current PPH prediction tools need external validation: one for CS, one for placenta praevia and one for placenta accreta. Tools are needed for labouring women.


Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.
Inhibition of BACE1 is being pursued as a therapeutic target to treat patients suffering from Alzheimer's disease because BACE1 is the sole β-secretase that generates β-amyloid peptide. Knowledge regarding other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. Neuregulin-1 (Nrg1) is a BACE1 substrate and BACE1 cleavage of Nrg1 is critical for signaling functions in myelination, remyelination, synaptic plasticity, normal psychiatric behaviors, and maintenance of muscle spindles. This review summarizes the most recent discoveries associated with BACE1-dependent Nrg1 signaling in these areas. This body of knowledge will help to provide guidance for preventing unwanted Nrg1-based side effects following BACE1 inhibition in humans. To initiate its signaling cascade, membrane anchored Neuregulin (Nrg), mainly type I and III β1 Nrg1 isoforms and Nrg3, requires ectodomain shedding. BACE1 is one of such indispensable sheddases to release the functional Nrg signaling fragment. The dependence of Nrg on the cleavage by BACE1 is best manifested by disrupting the critical role of Nrg in the control of axonal myelination, schizophrenic behaviors as well as the formation and maintenance of muscle spindles.


Role of the 5-HTTLPR and SNP Promoter Polymorphisms on Serotonin Transporter Gene Expression: a Closer Look at Genetic Architecture and In Vitro Functional Studies of Common and Uncommon Allelic Variants.
The serotonin (5-hydroxytriptamine (5-HT)) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats (VNTR) located in the promoter region of the human 5-HTT-encoding gene SLC6A4. This length polymorphism gives rise to different promoter variants, variously influencing SLC6A4 expression. Over the years, an extensive literature has investigated the relationships between these promoter variants and SLC6A4 gene expression, since these variants have been variously associated to complex neuropsychiatric conditions and traits. In this review, we detail the genetic architecture of the 5-HTTLPR allelic variants reported so far, with a closer look at the two single nucleotide polymorphisms (SNPs) rs25531 and rs25532 that lies in the VNTR and thus increase genetic variability of the SLC6A4 promoter. We summarize the hypothesized molecular mechanisms underlying this variation. We also provide an update on common and uncommon 5-HTTLPR allelic variants reviewing the available data on functional in vitro analysis of their regulatory effect on SLC6A4 gene transcription. Controversial findings are highlighted and critically discussed. A deeper knowledge of the "5-HTTLPR universe" will be useful to better understand the molecular basis of serotonin homeostasis and the pathological basis underlying serotonin-related neuropsychiatric conditions and traits.


In Vivo Microbial Antigen Discovery (InMAD) to identify diagnostic proteins and polysaccharides that are circulating during microbial infections.
Immunoassays employed at the point-of-care (POC) are often useful for diagnosing acute infections. Many of these assays rely on identification of microbial antigens that are secreted or shed during infection. However, determining which microbial antigens are best to target by immunoassay can be the most difficult aspect of developing a new diagnostic product. Here we describe a novel technique termed "In vivo Microbial Antigen Discovery" or "InMAD" for identification of microbial antigens that may be targeted for the diagnosis of infectious diseases.


Effect of individual or combined physical and chemical factors on the anaerobic biodegradation of linear alkylbenzene sulphonate.
The effect of six important factors on the anaerobic biodegradation of linear alkylbenzene sulphonate (LAS) was evaluated using a response surface methodology. The factors were: (i) co-substrate concentration (CC), (ii) contact time between LAS and microorganisms, (iii) temperature, (iv) hardness, (v) pH, and (vi) LAS source. The results showed that individually or combined, CC with chemical oxygen demand (COD) ≤50 mg L-1 was the factor that mostly favoured LAS biodegradation; whereas at COD >50 mg L-1, adsorption to sludge and solubilisation in the aqueous medium were favoured. Two-factor interactions promoted the highest percentages of biodegradation (45-52%), adsorption (43-45%), and solubilisation (18-25%). The three-factor interactions resulted in small percentage increases of up to 11%, 5%, and 13% for biodegradation, adsorption, and solubilisation, respectively, compared to those of two-factor interactions. The interactions of four, five, and six factors resulted in a non-significant effect on LAS biodegradation, adsorption, and solubilisation, with percentages close to those quantified for the two- and three-factor interactions. Concentrations of up to 30 mg LAS L-1 did not significantly affect the COD removal efficiency (74-88%) from the medium. These values are commonly obtained in full-scale anaerobic systems used to treat domestic sewage.


Response-monitoring dysfunction in aging and Alzheimer's disease: an event-related potential study.
Executive control is a broad-reaching function that includes response monitoring and is likely implemented in the frontal lobes. Age- and dementia-related changes in response-monitoring were assessed during a Picture-Name Verification Task, using response-synchronized event-related potential (ERP) markers of response monitoring: the centrally oriented error-related negativity (ERN); the smaller and more frontally-oriented correct-response negativity (CRN); and the positivity associated with errors (Pe), a marker of error awareness. These were recorded from 10 younger and 10 older healthy controls, as well as 12 Alzheimer's disease (AD) patients. Although the older and younger controls showed equivalent accuracy, error awareness (Pe), and relative ERN>CRN amplitude, aging was associated with slower behavioral responses and decreased ERN amplitude. Although dementia was associated with decreased accuracy, decreased ERN, and a loss of relative ERN>CRN amplitude, error awareness (Pe) remained somewhat intact in AD patients. In AD patients, CRN amplitude was affected by item certainty (assessed a week earlier), being larger to items that were idiosyncratically difficult for patients to name.


P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model.
P-glycoprotein is considered to be a major factor impeding effective drug therapy for many diseases of the central nervous system (CNS). Thus, efforts are being made to gain a better understanding of P-glycoprotein's role in drug distribution to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to validate and introduce a novel P-glycoprotein-deficient (ABCB1-1Delta) canine model for studying P-glycoprotein-mediated effects of drug distribution to brain tissue and CSF. CSF concentrations of drug are often used to correlate efficacy of CNS drug therapy as a surrogate for determining drug concentration in brain tissue. A secondary goal of this study was to investigate the validity of using CSF concentrations of P-glycoprotein substrates to predict brain tissue concentrations. Loperamide, an opioid that is excluded from the brain by P-glycoprotein, was used to confirm a P-glycoprotein-null phenotype in the dog model. ABCB1-1Delta dogs experienced CNS depression following loperamide administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In summary, we have validated a novel P-glycoprotein-deficient canine model and have used the model to investigate transport of the P-glycoprotein substrate (99m)Tc-sestamibi at the blood-brain barrier and blood-CSF barrier.


Activation and inhibition of lipoprotein lipase. Studies with artificial lipoproteins.
Human plasma very low density apolipoproteins C-I, C-II and C-III were recombined in vitro with triolein. The lipid-protein complexes were analyzed by ultracentrifugal flotation, agarose gel electrophoresis, immunoelectrophoresis and electron microscopy. Maximal protein/triolein ratios for apoprotein C-I, C-II, C-III-1 and C-III-2 were 50, 45, 95 and 55 microgram/mg, respectively. Electron micrographs exhibited spherical particles with diameters ranging from 200--2000 A comparable to native VLDL and chylomicrons. On agarose gel electrophoresis these complexes showed alpha-mobility. Kinetics of triolein hydrolysis by purified human plasma lipoprotein lipase were studied using these artificial lipoprotein substrates with different apoprotein/triolein ratios. The reaction followed the Michaelis-Menten equation. With increasing amounts of apo C-II, the apparent Km decreased from 0.60 to 0.11 mM. Incubation of the substrate with either rabbit anti-apo C-II gamma-globulins or digestion with trypsin prior to hydrolysis reversed this lowering effect on apparent Km. V was not altered significantly. Increasing amounts of apo C-I, apo C-III-1 or apo C-III-2 without apo C-II caused inhibition of triolein hydrolysis. In the presence of apo C-II, however, similar kinetic parameters were obtained as described above.


Novel Mutations in Serbian MEN1 Patients: Genotype-phenotype Correlation.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA) and pancreatic neuroendocrine tumor (pNET). Whether the underlying mutations in MEN1 gene predict clinical presentation of affected heterozygotes or not, is still a matter of a debate. Clinical and genetic analysis of 90 consecutive MEN1 patients was performed in a retrospective, single - center study. MEN1 mutation was found in 67 (74.4%) patients belonging to 31 different families. Twenty nine different heteozygous mutations were found, including 6 novel point mutations (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (OR=5.8, 95% CI 1.7 - 19.7%) and PHPT (OR=4.3, 95% CI 1.5 - 12.4%). Large number of novel mutations among MEN1 patients confirmed previously reported data. PNETs and PHPT were more frequent in patients with truncating mutations.


Retroviral rebound syndrome with fatal outcome after discontinuation of antiretroviral therapy.
We report the case of a patient with AIDS who developed retroviral rebound syndrome that led to death after antiretroviral therapy was stopped because of toxicity. Cases of retroviral rebound syndrome reported in the literature are briefly reviewed.


Electrochemical quantification of piperine in black pepper.
A simple, rapid method of the detection of piperine in black pepper is reported using a voltammetric sensor based on a glassy carbon (GC) electrode with analysis following a short one-step extraction using ethanol. The method is based on a novel potential sweep designed to maximise signal sizes and shown with context of the present analytical challenge to be essential for gathering data allowing the construction of a linear calibration curve for the analysis in the relevant range namely 0.25-5.0 mM.


GATA-4 upregulates glucose-dependent insulinotropic polypeptide expression in cells of pancreatic and intestinal lineage.
A thorough examination of glucose-dependent insulinotropic polypeptide (GIP) expression has been hampered by difficulty in isolating widely dispersed, GIP-producing enteroendocrine K-cells. To elucidate the molecular mechanisms governing the regulation of GIP expression, 14 intestinal and pancreatic cell lines were assessed for their suitability for studies examining GIP expression. Both STC-1 cells and the pancreatic cell line betaTC-3 were found to express GIP mRNA and secrete biologically active GIP. However, levels of GIP mRNA and bioactive peptide and the activity of transfected GIP reporter constructs were significantly lower in betaTC-3 than STC-1 cells. When betaTC-3 cells were analyzed for transcription factors known to be important for GIP expression, PDX-1 and ISL-1, but not GATA-4, were detected. Double staining for GIP-1 and GATA-4 in mouse duodenum demonstrated GATA-4 expression in intestinal K-cells. Exogenous expression of GATA-4 in betaTC-3 cells led to marked increases in both GIP transcription and secretion. Lastly suppression of GATA-4 via RNA interference, in GTC-1 cells, a subpopulation of STC-1 cells with high endogenous GIP expression resulted in a marked an attenuation of GIP promoter activity. Our data support the hypothesis that GATA-4 may function to augment or enhance GIP expression rather than act as an initiator of GIP transcription.


Parameterization of hyperpolarized (13)C-bicarbonate-dissolution dynamic nuclear polarization.
(13)C metabolic MRI using hyperpolarized (13)C-bicarbonate enables preclinical detection of pH. To improve signal-to-noise ratio, experimental procedures were refined, and the influence of pH, buffer capacity, temperature, and field strength were investigated. Bicarbonate preparation was investigated. Bicarbonate was prepared and applied in spectroscopy at 1, 3, 14 T using pure dissolution, culture medium, and MCF-7 cell spheroids. Healthy rats were imaged by spectral-spatial spiral acquisition for spatial and temporal bicarbonate distribution, pH mapping, and signal decay analysis. An optimized preparation technique for maximum solubility of 6 mol/L and polarization levels of 19-21% is presented; T1 and SNR dependency on field strength, buffer capacity, and pH was investigated. pH mapping in vivo is demonstrated. An optimized bicarbonate preparation and experimental procedure provided improved T1 and SNR values, allowing in vitro and in vivo applications.


Dynamic processes in conjunction with microbial response to unveil the attenuation mechanisms of tris (2-chloroethyl) phosphate (TCEP) in non-sanitary landfill soils.
Although the environmental and health risks of chlorinated organophosphate esters (OPEs-Cl) have drawn much attention, its environmental behaviors have been insufficiently characterized. As a notable sink of this emerging contaminant, non-sanitary landfills, which may decompose/accumulate OPEs-Cl, is of particular concern. In the present study, the dynamic processes of the typical OPEs-Cl, tris(2-chloroethyl) phosphate (TCEP), in non-sanitary landfill soils were analyzed under anaerobic condition, and the microbial taxa involved in these processes were explored. Our results showed that TCEP could be simultaneously reduced by abiotic and biotic processes, as it was reduced by 73.9% and 65.5% over the 120-day experiment in landfill humus and subsoil, respectively. Notably, the degradation of TCEP was significantly (p < 0.05) enhanced under the stress of a high TCEP concentration (10 μg g-1), while its ecological consequences were found insignificant regarding the microbial diversity and community structure and the typical soil redox processes, including Fe(III)/SO42- reduction and methanogenesis, in both soils. The microbial diversity of subsoil was significantly lower, and acetate was an important factor in changing microbial communities in landfill soils. The microbes in the family Nocardioidaceae and genus Pseudomonas might contribute to in the degradation of TCEP in landfill humus and subsoil, respectively. The metabolism related to sulfur and sulfate respiration were significantly (p < 0.05) correlated with TCEP reduction, and Desulfosporosinus were found as a potentially functional microbial taxon in TCEP degradation in both soils. The results could advance our understanding of the environmental behavior of OPEs-Cl in landfill-like complex environments.


Cardiac magnetic resonance imaging in small rodents using clinical 1.5 T and 3.0 T scanners.
Cardiac magnetic resonance (CMR) imaging can provide noninvasive, high resolution images of heart anatomy, viability, perfusion, and function. However, the adoption of clinical CMR imaging protocols for small rodents has been limited due to the small heart size and rapid heart rates. Therefore, most CMR studies in small rodents have been performed on non-clinical, high-field MR magnets. Because such high-field systems are not readily available at most institutions, the technical aspects that are needed to perform CMR on clinical 1.5 T and 3.0 T MR scanners are presented in this paper. Equipment requirements are presented, and a comprehensive description of the methods needed to complete a CMR exam including the animal preparation, imaging, and image analysis are discussed. In addition, the advanced applications of myocardial tagging and delayed-contrast-enhanced imaging are reviewed for the assessment of regional contractile function and myocardial viability, respectively.


UMB-3, a novel rabbit monoclonal antibody, for assessing μ-opioid receptor expression in mouse, rat and human formalin-fixed and paraffin-embedded tissues.
The immunohistochemical localization of the μ-opioid receptor (MOR, MOP) has been studied in detail in mouse and rat brain using a variety of polyclonal antibodies. However, biochemical analysis of the MOR signaling complex in vivo has been hampered by the lack of suitable monoclonal antibodies for efficient immunoprecipitation of the receptor protein from native sources. Moreover, previous immunohistochemical investigations were restricted to frozen sections from perfusion-fixed rodent brain, largely due to the limited availability of MOR antibodies that effectively stain paraffin-embedded tissues. Here, we extensively characterized the novel rabbit monoclonal anti-MOR antibody UMB-3 using transfected cells and MOR-deficient mice. UMB-3 was also subjected to a comparative immunohistochemical study of formalin-fixed, paraffin-embedded mouse and rat organ samples as well as human normal and neoplastic tissues. Specificity of UMB-3 was demonstrated by detection of a broad band migrating at M(r) 70,000-80,000 in immunoprecipitates from crude brain homogenates of MOR+/+ mice but not of MOR⁻/⁻ mice; cell surface staining of MOR-transfected cells; translocation of MOR receptor immunostaining after agonist exposure; distinct immunostaining of neuronal cell bodies and fibers in MOR-expressing brain regions; absence of staining in MOR-deficient mice; and abolition of tissue immunostaining by preadsorption of UMB-3 with its immunizing peptide. The rabbit monoclonal antibody UMB-3 is an excellent tool for immunoprecipitation of MOR from native sources as well as for immunohistochemical staining of MOR in paraffin-embedded tissue samples of rodent and human origin.


Diagnosis of tuberculosis among COVID-19 suspected cases in Ghana.
Tuberculosis (TB) and COVID-19 pandemics are both diseases of public health threat globally. Both diseases are caused by pathogens that infect mainly the respiratory system, and are involved in airborne transmission; they also share some clinical signs and symptoms. We, therefore, took advantage of collected sputum samples at the early stage of COVID-19 outbreak in Ghana to conduct differential diagnoses of long-standing endemic respiratory illness, particularly tuberculosis. Sputum samples collected through the enhanced national surveys from suspected COVID-19 patients and contact tracing cases were analyzed for TB. The sputum samples were processed using Cepheid's GeneXpert MTB/RIF assay in pools of 4 samples to determine the presence of Mycobacterium tuberculosis complex. Positive pools were then decoupled and analyzed individually. Details of positive TB samples were forwarded to the NTP for appropriate case management. Seven-hundred and seventy-four sputum samples were analyzed for Mycobacterium tuberculosis in both suspected COVID-19 cases (679/774, 87.7%) and their contacts (95/774, 12.3%). A total of 111 (14.3%) were diagnosed with SARS CoV-2 infection and six (0.8%) out of the 774 individuals tested positive for pulmonary tuberculosis: five (83.3%) males and one female (16.7%). Drug susceptibility analysis identified 1 (16.7%) rifampicin-resistant tuberculosis case. Out of the six TB positive cases, 2 (33.3%) tested positive for COVID-19 indicating a coinfection. Stratifying by demography, three out of the six (50%) were from the Ayawaso West District. All positive cases received appropriate treatment at the respective sub-district according to the national guidelines. Our findings highlight the need for differential diagnosis among COVID-19 suspected cases and regular active TB surveillance in TB endemic settings.


First-generation versus third-generation comprehensive geriatric assessment instruments in the acute hospital setting: a comparison of the Minimum Geriatric Screening Tools (MGST) and the interRAI Acute Care (interRAI AC).
Comparison of the first-generation Minimum Geriatric Screening Tools (MGST) and the third-generation interRAI Acute Care (interRAI AC). Based on a qualitative multiphase exchange of expert opinion, published evidence was critically analyzed and translated into a consensus. Both methods are intended for a multi-domain geriatric assessment in acute hospital settings, but each with a different scope and goal. MGST contains a collection of single-domain, internationally validated instruments. Assessment is usually triggered by care givers' clinical impression based on geriatric expertise. A limited selection of domains is usually assessed only once, by disciplines with domain-specific expertise. Clinical use results in improvement to screen geriatric problems. InterRAI AC, tailored for acute settings, intends to screen a large number of geriatric domains. Based on systematic observational data, risk domains are triggered and clinical guidelines are suggested. Multiple observation periods outline the evolution of patients' functioning over stay in comparison to the premorbid situation. The method is appropriate for application on geriatric and non-geriatric wards, filling geriatric knowledge gaps. The interRAI Suite contains a common set of standardized items across settings, facilitating data transfer in transitional care. The third-generation interRAI AC has advantages compared to the first-generation MGST. A cascade system is proposed to integrate both, complementary methods in practice. The systematic interRAI AC assessment detects risk domains. Subsequently, clinical protocols suggest components of the MGST as additional assessment. This cascade approach unites the strength of exhaustive assessment of the interRAI AC with domain-specific tools of the MGST.


Micropuncture studies on the renal handling of 2,4-diamino-6,7-dimethylpteridine.
The excretion of the diuretic substance DADMP (I,4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2 . 10(-4) cm . s-1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20--30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2 . 10(-13) mol . min-1 and 10(-9) mol . min-1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.


Saharan dust and associations between particulate matter and daily mortality in Rome, Italy.
Outbreaks of Saharan-Sahel dust over Euro-Mediterranean areas frequently induce exceedances of the Europen Union's 24-hr standard of 50 μg/m3 for particulate matter (PM) with aerodynamic diameter ≤ than 10 μm (PM10). We evaluated the effect of Saharan dust on the association between different PM fractions and daily mortality in Rome, Italy. In a study of 80,423 adult residents who died in Rome between 2001 and 2004, we performed a time-series analysis to explore the effects of PM2.5, PM2.5-10, and PM10 on natural, cardiac, cerebrovascular, and respiratory mortality. We defined Saharan dust days by combining light detection and ranging (LIDAR) observations and analyses from operational models. We tested a Saharan dust-PM interaction term to evaluate the hypothesis that the effects of PM, especially coarse PM (PM2.5-10), on mortality would be enhanced on dust days. Interquartile range increases in PM2.5-10 (10.8 μg/m3) and PM10 (19.8 μg/m3) were associated with increased mortality due to natural, cardiac, cerebrovascular, and respiratory causes, with estimated effects ranging from 2.64% to 12.65% [95% confidence interval (CI), 1.18-25.42%] for the association between PM2.5-10 and respiratory mortality (0- to 5-day lag). Associations of PM2.5-10 with cardiac mortality were stronger on Saharan dust days (9.73%; 95% CI, 4.25-15.49%) than on dust-free days (0.86%; 95% CI, -2.47% to 4.31%; p = 0.005). Saharan dust days also modified associations between PM10 and cardiac mortality (9.55% increase; 95% CI, 3.81-15.61%; vs. dust-free days: 2.09%; 95% CI, -0.76% to 5.02%; p = 0.02). We found evidence of effects of PM2.5-10 and PM10 on natural and cause-specific mortality, with stronger estimated effects on cardiac mortality during Saharan dust outbreaks. Toxicological and biological effects of particles from desert sources need to be further investigated and taken into account in air quality standards.


The completeness of cancer registration in follow-up studies--a cautionary note.
In Britain the National Health Service Central Registers (NHSCRs) provide the facility for a study population to be 'flagged', initiating a system of notification to investigators of deaths and cancers that occur in the population. This system of notification is an invaluable resource for epidemiological research. A comment on its efficiency is provided here by a comparison of the system with an independently ascertained series of breast cancers. Fifty verified breast cancer cases were identified during a study of a flagged cohort of British women taking hormone replacement therapy. At the time of analysis (May 1985), some 2.5 years after diagnosis of the most recent case, twenty-eight of the 50 cases had not been notified to the investigators by the NHSCRs. Of these, fourteen had not been registered. Eight had been duly registered, but had not yet been recorded at the NHSCRs. Five of the remaining six cases were in the process of being notified. The implications of these findings for cancer researchers are discussed. The potential for omission and delay between the diagnosis of cancers in a flagged population and their notification to the investigators must be taken into account, if underestimation of the true level of cancer risk is to be avoided.


Sclerostin small-molecule inhibitors promote osteogenesis by activating canonical Wnt and BMP pathways.
The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established. We computationally identified two FDA-approved drugs, as well as a single novel small-molecule drug, for their ability to disrupt the interaction between sclerostin and its receptor, LRP5/6. The drugs were tested in several in vitro biochemical assays using murine MC3T3 and MSCs, assessing their ability to (1) enhance canonical Wnt signaling, (2) promote the accumulation of the active (non-phosphorylated) form of β-catenin, and (3) enhance the intensity and signaling duration of BMP signaling. These drugs were then tested subcutaneously in rats as standalone osteoinductive agents on plain collagen sponges. Finally, the top drug candidates (called VA1 and C07) were tested in a rabbit posterolateral spine fusion model for their ability to achieve a successful fusion at 6 wk. We show that by controlling GSK3b phosphorylation our three small-molecule inhibitors (SMIs) simultaneously enhance canonical Wnt signaling and potentiate canonical BMP signaling intensity and duration. We also demonstrate that the SMIs produce dose-dependent ectopic mineralization in vivo in rats as well as significantly increase posterolateral spine fusion rates in rabbits in vivo, both as standalone osteogenic drugs and in combination with autologous iliac crest bone graft. Few if any osteogenic small molecules possess the osteoinductive potency of BMP itself - that is, the ability to form de novo ectopic bone as a standalone agent. Herein, we describe two such SMIs that have this unique ability and were shown to induce de novo bone in a stringent in vivo environment. These SMIs may have the potential to be used in novel, cost-effective bone graft substitutes for either achieving spinal fusion or in the healing of critical-sized fracture defects. This work was supported by a Veteran Affairs Career Development Award (IK2-BX003845).


Nephrogenic systemic fibrosis: center case review.
To retrospectively analyze nephrogenic systemic fibrosis (NSF) cases at our center, to determine prior gadolinium based contrast agent (GBCA) administration and to evaluate possible common risk factors for the development of NSF by reviewing laboratory data and concurrent medications. A total of four data bases (pathology, MRI, dialysis, and medical records) were cross-referenced for identification and evaluation of NSF patients. Medical history of NSF patients was assessed as for previous deep venous thrombosis (DVT), surgery, or infections. Laboratory data (creatinine, anion gap, calcium, phosphorus, and albumin) as well as concurrent medication were evaluated. Findings were compared to those of a control group of non-NSF dialysis patients. Between October 2003 and February 2007 a total of nine NSF cases were identified. All patients had undergone contrast-enhanced MRI prior to the diagnosis of NSF. Only one gadolinium chelate had been used at our MRI center (Omniscan, gadodiamide; GE Healthcare). Of nine patients, eight were receiving dialysis at the time of the MRI scan. During the same time 312 dialysis patients received gadodiamide. Thus, the prevalence of NSF within dialysis patients exposed to gadodiamide was 2.6%. NSF patients presented with a higher creatinine and anion gap than the control patients. Other laboratory values as well as medication did not show a significant difference. There were no patterns regarding previous history of DVT, surgery, or infection in the NSF group. Our findings are consistent with the previously reported association between gadodiamide exposure and NSF. All NSF patients had severe renal insufficiency with glomerular filtration rate (GFR) < 30 (highest GFR = 25 mL/minute) at the time of last gadodiamide administration, and on average had received 71 mL of gadodiamide over an average of 2.9 administrations.


Populations of the cattle tick (Boophilus microplus) on purebred Nellore, Ibage and Nellore X European crossbreds in the Brazilian savanna.
Studies on purebred Nellore cattle and their crosses with Fleckvieh, Chianina, Charolais and the Ibagé breed (5/8 Aberdeen Angus, 3/8 Nellore) during 39 months in the field gave mean daily counts for engorging female ticks of 3.3, 25.2, 22.2, 21.0 and 59.7 per animal respectively. Annual fluctuations were similar in all groups; with the exception of the purebred Nellore mean counts are at levels considered dangerous for the stability of enzootic tick fever.


Informed consent-It's more than a signature on a piece of paper.
Informed consent is an ethical concept that is codified in the law and is in daily practice at every health care institution. Three fundamental criteria are needed for clinical informed consent: the patient must be competent, adequately informed and not coerced. Physician-patient interaction is rooted in the ethical concept of beneficence, but over the 19th and 20th centuries, case law and societal changes brought respect for autonomy and with it--informed consent. This article briefly reviews the basics of informed consent, when is it required, how did informed consent evolve into what it is today and what can the surgeon do to truly achieve informed consent.


Gonad development and plasma steroid profiles by HRGC/HRMS during one reproductive cycle in reference and leachate-exposed female perch (Perca fluviatilis).
Endocrine processes were studied in reference female perch (Perca fluviatilis) from Lake Djursjön and in leachate-exposed females from Lake Molnbyggen during one reproductive cycle. A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) technique enabled the analysis of circulating sex steroids [progesterone (P), 17alpha-hydroxyprogesterone (17alpha-OHP), androstenedione (A), testosterone (T), estrone (E1), and 17beta-estradiol (E2)], the maturation-inducing hormone (MIH) 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P), and glucocorticoids [11-deoxycortisol (11-DC) and cortisol]. Body and organ measurements, ratio of sexually mature (SM) females, and frequencies of body lesions, were also recorded. High frequencies of body lesions and a low ratio of SM females were generally found in Molnbyggen. These females also had lower gonadosomatic index (GSI) and liver-somatic index (LSI) in the early stages of vitellogenesis, indicating either a delayed onset of oogenesis or an impaired vitellogenesis. Non-reproducing females from both lakes showed a similar LSI cycle as SM females. Increasing T and A levels in SM females from Djursjön coincided with the GSI peak at the time of spawning. These two androgens were on several occasions lower in SM females from Molnbyggen, possibly the result of a disrupted 17,20-lyase activity of the P450 17alpha enzyme because only minor effects were observed on circulating P and 17alpha-OHP levels. E2 and E1 levels increased during vitellogenesis in females from both lakes, with E1 levels more closely resembling the peaks of A and GSI. Peak levels of 17alpha,20beta-P at the time of spawning confirmed its function as the MIH in perch, while the simultaneous peak of 11-DC suggests that it also may be involved in final maturation of the oocytes.


Asthma management--a new dimension.
This report describes a consensus on current asthma management in the UK, indicates areas of clinical concern and provides a rationale for improved therapy.


Practical research-based guidance for motor imagery practice in neurorehabilitation.
The purpose of this appraisal is to offer guidance to clinicians on applying motor imagery in neurorehabilitation and provide guidance to support this process. We used evidence from a variety of fields as well as clinical experience with motor imagery to develop guidance for employing motor imagery during neurorehabilitation. Motor imagery is a relatively new intervention for neurorehabilitation supported by evidence from areas such as cognitive neuroscience and sports psychology. Motor imagery has become a very popular intervention modality for clinicians but there is insufficient information available on how to administer it in clinical practice and make deliberate decisions during its application. We provide evidence-based guidance for employing motor imagery in neurorehabilitation and use the principles of motor learning as the framework for clinical application.


Expression of erythropoietin and its receptor in the brain of late-gestation fetal sheep, and responses to asphyxia caused by umbilical cord occlusion.
Asphyxia and hypoxia are common threats faced by the fetus in utero. In late-gestation fetal sheep, asphyxia produced by umbilical cord occlusion (UCO) results in widespread lipid peroxidation and apoptosis. Adaptive mechanisms that might limit fetal brain damage include induction of the hemopoietic cytokine, erythropoietin (EPO). In unanesthetized fetal sheep, we investigated if 1 or 2 bouts of brief asphyxia (UCO for 10 min) induced EPO and EPO type I receptor (EPO-R) expressions, with the second UCO repeated 48 h after the first. Fetal brains were recovered 48 h after either sham, 1 x or 2 x UCO at 129-133 (term approximately 147) days of gestation and prepared for immunocytochemistry. In age-matched control brain, low levels of EPO and EPO-R proteins were present in oligodendrocytes (OLs), periventricular and cortical white matter (WM), with no EPO and very low EPO-R expression in neurons. After 1 x UCO, EPO and EPO-R expressions were increased in astrocytes (periventricular and cortical WM, striatum, corpus callosum), choroid plexus epithelial cells, scattered neurons in cortical layers IV-VI, hippocampal CA1 neurons, and in the molecular and granule layers of the cerebellum. After 2 x UCO, higher levels of EPO and EPO-R occurred in the periventricular and cortical WM, corpus callosum, hippocampal CA1, and in neurons of all cortical layers. Paradoxically, EPO and EPO-R were now lower in hippocampal CA1 neurons and cerebellar molecular and granule cell layers. Few OLs expressed EPO or EPO-R after 1 x or 2 x UCO. Thus, brief asphyxia induces EPO and EPO-R in fetal astrocytes, but only after repeated asphyxial insult in neurons. Whether this is a response to increased injury, or represents an adaptive response that limits further cell death and brain damage awaits further investigation.


A gene-based anti-angiogenesis therapy as a novel strategy for cancer treatment.
Angiogenesis-targeted therapy of cancer is considered a promising strategy for therapeutic management of cancer progression. Over the last two decades, a few anti-angiogenesis monoclonal antibodies (mAbs) blocking VEGF signaling have been developed and approved by the FDA. The most widely used anti-angiogenesis drug is bevacizumab which binds VEGFA and prevents its interaction with VEGF receptor leading to suppression of angiogenesis. Despite the remarkable success in development of angiogenesis inhibitory mAbs, their clinical application is limited by the high-cost of mAbs-based regimen which includes multiple doses of mAbs due to their short biological half-life. Antibody gene therapy is an alternative system of antibody production. In this study, we have developed a gene-based anti-VEGF mAb system which is expected to produce a high concentration of anti-VEGFA mAb upon a single administration in cancer patients. The full-length cDNA bevacizumab light and heavy chains joint with T2A sequence were cloned in pCDH lentivirus vector. The lentiviral particles expressing bevacizumab was produced in HEK-293T cells. Recombinant lentiviral particles containing bevacizumab (rLV-bev) efficiently transduced HEK-293cells and produced functional bevacizumab mAb. Bevacizumab expression in the transduced cell was assessed by qRT-PCR and western blot at both the mRNA and protein level, respectively. The functionality of the recombinant bevacizumab was confirmed using the tube formation assay in the co-culture system of endothelial cells and HT-29cells transduced with rLV-bev viral particles. Our results show that rLV-bev gene therapy can be useful for angiogenesis-targeted therapy of cancer.


Mentoring Medical Students Towards Oncology: Results from a Pilot Multi-institutional Mentorship Programme.
The mounting global cancer burden has generated an increasing demand for oncologists to join the workforce. Yet, students report limited oncology exposure in undergraduate medical curricula, while undergraduate oncology mentorships remain underutilised. We established an undergraduate oncology society-led mentorship programme aimed at medical students across several UK universities to increase medical student oncology exposure. We electronically recruited and paired oncologist mentors and medical student mentees and distributed a dedicated questionnaire (pre- and post-mentorship) to compare mentees' self-reported cancer specialty knowledge and oncology career motivation after undertaking a 6-week mentorship. We also determined students' interest across specialties and subspecialties and measured mentor availability via percentage programme uptake. Statistical analysis included univariate inferential tests on SPSS software. Twentynine (23.4%) of 124 oncology specialists agreed to become mentors. The mentorship was completed by 30 students across three medical schools: 16 (53.3%) Barts, 10 (33.3%) Birmingham, and 4 (13.3%) King's; 11 (36.7%) mentored by medical oncologists, 10 (33.3%) by clinical/radiation oncologists, and 9 (30%) by surgical oncologists. The mentorship generated a statically significant increase in students' knowledge of the multidisciplinary team and all oncology-related specialties including academia/research but not interest towards a career in oncology. Undergraduate oncology mentoring is an effective educational, networking and motivational tool for medical students. Student societies are a valuable asset in cultivating medical student oncology interest by connecting students to faculty and increasing mentor accessibility. Further research should focus on developing an optimal mentorship structure and evaluating long-term outcomes of such educational initiatives.


Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids.
Chlorination of drinking water yields hundreds of disinfection by-products (DBPs). Among the DBPs, four trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acid) are U.S. EPA regulated. We assessed the combined toxicity of these DBPs. F344 rats were treated with mixtures of the four THMs (THM4), the five HAAs (HAA5), or nine DBPs (DBP9; THM4+HAA5). Mixtures were administered in 10% Alkamuls(®) EL-620 daily by gavage on gestation days 6-20. Litters were examined postnatally. All three mixtures caused pregnancy loss at ≥ 613 μmol/kg/day. In surviving litters, resorption rates were increased in groups receiving HAA5 at 615 μmol/kg/day and DBP9 at 307 μmol/kg/day. HAA5 caused eye malformations (anophthalmia, microphthalmia) at ≥ 308 μmol/kg/day. Thus, both HAAs and THMs contributed to DBP9-induced pregnancy loss. The presence of THMs in the full mixture, however, appeared to reduce the incidence of HAA-induced eye defects.


Prolonged hypoxaemia following inhalation of hydrogen chloride vapour.
A patient is described who developed prolonged hypoxaemia and subsequent asthma after a single exposure to a high concentration of hydrogen chloride vapour (and a small amount of phosphorus trichloride).


In vitro effects of trans-4-hydroxy-2-alkenals on mouse liver cytochrome P-450.
Under in vitro conditions, trans-4-hydroxy-2-hexenal (t-4HH), trans-4-hydroxy-2-nonenal (t-4-HN) and trans-2-hexenal (t-2H) significantly reduced the levels of mouse liver microsomal cytochrome P-450. Incubation of trans-4-hydroxy-alkenals, under anaerobic conditions in the absence of an NADPH-generating system indicated that these compounds were converting cytochrome P-450 to cytochrome P-420. Prior activation by the mixed function oxidase system was not required for trans-4-hydroxy-alkenals to alter cytochrome P-450 concentrations. trans-4-Hydroxy-alkenals and non-hydroxylated alpha,beta-unsaturated aldehydes may be exerting their effects on cytochrome P-450 by binding to sulfhydryl groups in a similar manner as reported for sulfhydryl reagents such as p-chloromercuriphenylsulfonic acid and p-chloromercuribenzoate.


Consistent viral DNA quantification after prolonged storage at ambient temperature.
Long-term storage of biological specimens at low temperatures is costly and impractical in resource limited settings, where the disease burden of chronic viral infections is highest, and the need for research greatest. We examined the necessity of cold storage by comparing the quantity of HHV-8 DNA recovered from swab samples before and after 9-11 months of storage at temperatures of -20 °C, 4 °C and 37 °C. Quantitative levels of HHV-8 DNA remained consistent for laboratory or mucosal swab samples regardless of storage temperature. Freezer storage is determined to be not necessary for mucosal samples destined for HHV-8 DNA quantification.


Comparison of two mobilization techniques in management of chronic non-specific low back pain.
The aim of the study was to compare between the effects of Maitland's postero-anterior (PA glide) mobilization and Mulligan's sustained natural apophyseal glide (SNAG) on pain, mobility, muscle activation and functional disability in subjects with chronic, non-specific low back pain. The study was a two arm repeated measure design with random allocation of subjects (n = 33). Subjects in group 1 received Maitland's PA glide mobilization and those in group 2 received Mulligan's SNAG. Along with the respective mobilization technique, individualized exercises were common for subjects in both the groups. Subjects in both groups received treatment for 4 days a week for 4 weeks. The outcome measures were numeric pain rating scale (NPRS) scores, lumbar flexion and extension range of motion, erector spinae muscle activity and Oswestry low back pain disability questionnaire score. The outcome measure scores showed statistical significance in time effect on NPRS (p = 0.001); lumbar flexion and extension range of motion (p = 0.001); erector spinae muscle activity (0.001); Oswestry low back pain disability questionnaire score (p = 0.001); group effect on lumbar flexion (p = 0.03) and extension range of motion (p = 0.05); and interaction effect (time x group) on lumbar flexion (p = 0.003) and extension range of motion (p = 0.002); and, erector spinae muscle activity (p = 0.05) at the 3rd lumbar vertebral level. The addition of Maitland or Mulligan mobilization techniques of the spine does not show a difference in the improvement of symptoms associated with chronic non-specific low back pain.


Pulse methylprednisolone therapy in the treatment of immune globulin-resistant Kawasaki disease: case report and review of the literature.
A subgroup of patients with Kawasaki disease (KD) did not respond to intravenous immune globulin (IVIG) therapy. Corticosteroid therapy remains a controversial alternative in such cases. We report two young children with KD who failed to respond to three courses of IVIG therapy and subsequently received pulse methylprednisolone as an alternative. One had a satisfactory outcome but the other developed giant coronary aneurysms and had a myocardial infarction 2 months after onset of the illness. A review of relevant literature showed that the timing of initiation of pulse methylprednisolone therapy is important. It is suggested that pulse methylprednisolone therapy should be considered if there is no response to two standard doses of IVIG treatment.


Sleep disturbances in early alcohol recovery: Prevalence and associations with clinical characteristics and severity of alcohol consumption.
We aimed to assess the prevalence of sleep disturbance in early alcohol recovery and its association with psychiatric comorbidity, cravings, propensity and severity of alcohol consumption. The sample consisted of 18-80 year old patients (n = 303) receiving treatment for alcohol dependence. Sleep disturbance was measured using the Pittsburgh Sleep Quality Index (PSQI). Additional measures included PHQ-9, GAD-7 and Penn alcohol cravings scale (PACS), Inventory of Drug Taking Situations (IDTS) and alcohol consumption was measured utilizing the Time Line Follow Back (TLFB).Bivariate analyses evaluated the association between PSQI total score and other clinical characteristics. A multivariable model was computed for sleep disturbance with predictors entered into the model using automated stepwise selection. The sample was majority male (66%), White (93%) with a mean age of 42.2 ± 11.6 years. Baseline PSQI score was 10.2 ± 4.13 and most subjects (88%) reported sleep disturbance at baseline. Baseline sleep disturbance was associated with depressive symptoms (p < .0001), anxiety symptoms (p < .0001), craving (p < .0001), propensity to drink when experiencing unpleasant emotions (p < .0001), physical discomfort (p < .0001), loss of personal control (p = 0.03), conflict (p = 0.002), number of drinks consumed (p = 0.004), drinking days (p = 0.004) and hazardous drinking days (p = 0.03) in bivariate analyses. However, in the multivariable model, only PHQ-9 total score and IDTS physical discomfort subscale were associated with sleep disturbance. Sleep disruption is common in early alcohol recovery. Future studies should examine the prognostic and clinical implications of its association with current depressive symptoms and a propensity to drink while experiencing physical discomfort.


Prediction of corticosteroid responsiveness based on fibroblast-specific protein 1 (FSP1) in patients with IgA nephropathy.
Corticosteroids are frequently used to treat patients with active IgA nephropathy (IgAN); however, there have been few reports describing factors that are predictive of the response to corticosteroid treatment. The purpose of this study is to determine the extent to which fibroblast-specific protein 1-positive (FSP1(+)) cells are predictive of corticosteroid responsiveness in patients with IgAN. Fifty biopsy-proven IgAN patients who received corticosteroid therapy were enrolled and followed for 7.1 +/- 3.0 years. FSP1(+) cells were identified using an anti-FSP1 antibody. Twelve patients showed progression of renal impairment or no reduction of urinary protein (non-responders) after steroid therapy. In the remaining 38 patients, renal function was stable during follow-up, and their urinary protein declined to <1.0 g/day (responders). Serum creatinine, estimated GFR, severity of mesangial proliferation, percent glomerulosclerosis/total glomeruli, extent of interstitial damage and FSP1(+) cell number were all significantly higher in non-responders than in responders. Cox regression analysis using two covariates with every possible combination of factors indicated that FSP1(+) cell number was the strongest and most significant predictor of corticosteroid responsiveness. When IgAN patients had >32.6 FSP1(+) cells/HPF at diagnosis, they were the more likely to show steroid resistance. FSP1(+) cell number can serve as an excellent predictor of corticosteroid responsiveness in patients with IgAN.


Construction of antibody/insulin receptor chimera for growth induction of mammalian cells.
The insulin receptor (IR) is expressed ubiquitously in various tissues, where insulin exerts various biological effects on the target cells, such as cellular metabolic changes, cell proliferation and differentiation. Therefore, mimicry of insulin signaling would be a promising strategy to realize artificial control of such cellular fates. In this study, we constructed an antibody/insulin receptor chimera that enables to utilize any antigen as the ligand in principle. We constructed chimeric receptors consisting of anti-fluorescein single chain Fv (scFv), the extracellular D2 domain of erythropoietin receptor and the transmembrane/intracellular domains of IR (scFv-IR; S-IR). The function of S-IR was evaluated in terms of growth signal transduction in murine pro-B Ba/F3 cells and murine fibroblast NIH/3T3 cells. S-IR exerted IL-3-independent cell growth in Ba/F3 cells, while NIH/3T3 cells expressing S-IR acquired growth advantage over parental NIH/3T3 cells in a low-serum condition. S-IR induced phosphorylation of S-IR itself and key signaling molecules downstream of IR. Although antigen-independent activation was significantly observed, S-IR enabled specific amplification of the gene-transduced cells.


[Prevention of depression and anxiety in older people].
In older people, sub-threshold symptom levels of depression or anxiety are characterised by a high prevalence and an unfavourable prognosis. They are the best predictors of the onset of full-blown disorders. There is an urgent need to develop effective preventative strategies. To determine the effectiveness and feasibility of an indicated depression- and anxiety- prevention programme for older people. 170 individuals (75+) with sub-threshold symptom levels of depression or anxiety were randomized between a preventive intervention programme consisting of watchful waiting, bibliotherapy, problem-solving treatment, and re-referral to primary care to discuss medication, or usual care. The intervention halved the incidence of (DSM-IV) depressive and anxiety disorders. A stepped-care approach to the prevention of depression and anxiety in later life was successful in halving the incidence of depressive and anxiety disorders after one year, were cost-effective, and the favourable effects were sustained for up to 24 months.


The expression of CD2 in chronic HBV infection.
It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection.


Comparative Effectiveness of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in Older Nursing Home Residents After Myocardial Infarction: A Retrospective Cohort Study.
Evidence regarding differences in outcomes between angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) among older nursing home (NH) residents after acute myocardial infarction (AMI) is limited. The purpose of our study was to estimate the post-AMI effects of ARBs versus ACEIs on mortality, rehospitalization, and functional decline outcomes in this important population. This retrospective cohort study used national Medicare claims linked to Minimum Data Set assessments. The study population included individuals aged ≥ 65 years who resided in a US NH ≥ 30 days, were hospitalized for AMI between May 2007 and March 2010, and returned to the NH. We compared 90-day mortality, rehospitalization, and functional decline outcomes between ARB and ACEI users with inverse-probability-of-treatment-weighted binomial and multinomial logistic regression models. Of the 2765 NH residents, 270 (9.8%) used ARBs and 2495 (90.2%) used ACEIs. The mean age of ARB versus ACEI users was 82.3 versus 82.7 years, respectively. No marked differences existed between ARB and ACEI users for mortality [odds ratio (OR) 1.18; 95% confidence interval (CI) 0.78-1.79], rehospitalization (OR 1.22; 95% CI 0.90-1.65), or functional decline (OR 1.23; 95% CI 0.88-1.74). In subgroup analyses, ARBs were associated with increased mortality and rehospitalization in individuals with moderate to severe cognitive impairment and with increased rehospitalization in those aged < 85 years. Our findings align with prior data and suggest that clinicians can prescribe either ARBs or ACEIs post-AMI for secondary prevention in NH residents, although the subgroup findings merit further scrutiny and replication. Providers should consider factors such as patient preferences, class-specific adverse events, and costs when prescribing.


The restructuring of institutional long-term care in St. John's: impact of supply-induced demand on planning.
Restructuring of institutional long-term care was undertaken using predictions of future bed need with assumptions made on incidence rates of clients defined by type of disability, survival, and demographic changes. Recent substantial increase in the population rate of clients seeking placement across all degrees of disability, coincident with new facilities for those with modest disability, occurred. Consequently, more appropriate housing and supervised care beds, and more limited downsizing of nursing homes will be required.


Depressive symptoms in Chinese children and adolescents: parent, teacher, and self reports.
Most studies of depressive symptoms in children and adolescents have been conducted in Western countries. This study was designed to examine depressive symptoms and age and gender differences in children and adolescents in China. Participants consisted of two community samples of children and adolescents (n1=4858, n2=1362) in Shandong, China. Child Behavior Checklist (CBCL), Teacher Report Form (TRF) and Youth Self Report (YSR) were used to assess depressive symptoms. Using American norms, the prevalence rates of depression in Chinese children and adolescents were 5.9% with self report, 0.9% with parent report, and 0.8% with teacher report. Self and teacher-reported depressive symptoms were significantly increased with age for both boys and girls. Compared with American norms, self-reported depressive scores were significantly higher in Chinese adolescents, while parent and teacher-reported scores were significantly lower in Chinese children. Our study lacks clinical assessment of depressive symptoms and the study is comprised of two separate samples where parent and teacher reports and youth reports could not be compared directly. The prevalence of self-reported depressive symptoms in Chinese children and adolescents are much higher than those reported by either parents or teachers. Depressive symptoms are increased with age but do not differ between boys and girls.


The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein.
The transcription factor Atonal homolog 1 (Atoh1) plays crucial roles in the differentiation of intestinal epithelium cells. Although we have reported that the Atoh1 protein was degraded in colon cancer by aberrant Wnt signaling, a recent study has indicated that the Atoh1 protein is expressed in mucinous colon cancer (MC) and signet ring cell carcinoma (SRCC). However, the roles of the Atoh1 protein in MC are unknown. To mimic MC, a mutated Atoh1 protein was stably expressed in undifferentiated colon cancer cells. Microarray analysis revealed the acquisition of not only the differentiated cell form, but also malignant potential by Atoh1 protein stabilization. In particular, Atoh1 enhanced Wnt signaling, resulting in the induction of Lgr5 as a representative stem cell marker with the enrichment of cancer stem cells. Moreover, the fluorescent ubiquitination-based cell cycle indicator system with time-lapse live imaging demonstrated cell cycle arrest in the G0/G1 phase by Atoh1 protein stabilization. In conclusion, the Atoh1 protein regulates malignant potential rather than the differentiation phenotype of MC, suggesting the mechanism by which MC and SRCC are more malignant than non-mucinous adenocarcinoma.


Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery.
The gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss. We investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB. Prospective cohort of adults undergoing RYGB (n=44) at San Francisco academic hospitals. We analyzed 6-month changes in PYY, ghrelin, bone turnover markers, and BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We calculated the uncoupling index (UI), reflecting the relative balance of bone resorption and formation. Postoperatively, there was a trend for an increase in PYY (+25pg/mL, p=0.07) and a significant increase in ghrelin (+192pg/mL, p<0.01). PYY changes negatively correlated with changes in spine BMD by QCT (r=-0.36, p=0.02) and bone formation marker P1NP (r=-0.30, p=0.05). Relationships were significant after adjustments for age, sex, and weight loss. No consistent relationships were found between ghrelin and skeletal outcomes. Mean 6-month UI was -3.3; UI correlated with spine BMD loss by QCT (r=0.40, p=0.01). Postoperative PYY increases were associated with attenuated increases in P1NP and greater declines in spine BMD by QCT. Uncoupling of bone turnover correlated with BMD loss. These findings suggest a role for PYY in loss of bone mass after RYGB and highlight the relationship between intestinal and skeletal metabolism.


Activity of some aminoglycoside antibiotics against true fungi, Phytophthora and Pythium species.
To investigate the in vitro antifungal and antioomycete activities of some aminoglycosides against true fungi and Phytophthora and Pythium species and to evaluate the potential of the antibiotics against Phytophthora late blight on plants. Antifungal and antioomycete activities of aminoglycoside antibiotics (neomycin, paromomycin, ribostamycin and streptomycin) and a paromomycin-producing strain (Streptomyces sp. AMG-P1) against Phytophthora and Pythium species and 10 common fungi were measured in potato dextrose broth (PDB) and on seedlings in pots. Paromomycin was the most active against Phytophthora and Pythium species with a minimal inhibitory concentration of 1-10 microg ml(-1) in PDB, but displayed low to moderate activities towards other common fungi at the same concentration. Paromomycin also showed potent in vivo activity against red pepper and tomato late blight diseases with 80 and 99% control value, respectively, at 100 microg ml(-1). In addition, culture broth of Streptomyces sp. AMG-P1 as a paromomycin producer exhibited high in vivo activity against late blight at 500 microg freeze-dried weight per millilitre. Among tested aminoglycoside antibiotics, paromomycin was the most active against oomycetes both in vitro and in vivo. Data from this study show that aminoglycoside antibiotics have in vitro and in vivo activities against oomycetes, suggesting that Streptomyces sp. AMG-P1 may be used as a biocontrol agent against oomycete diseases.


YidC occupies the lateral gate of the SecYEG translocon and is sequentially displaced by a nascent membrane protein.
Most membrane proteins are co-translationally inserted into the lipid bilayer via the universally conserved SecY complex and they access the lipid phase presumably via a lateral gate in SecY. In bacteria, the lipid transfer of membrane proteins from the SecY channel is assisted by the SecY-associated protein YidC, but details on the SecY-YidC interaction are unknown. By employing an in vivo and in vitro site-directed cross-linking approach, we have mapped the SecY-YidC interface and found YidC in contact with all four transmembrane domains of the lateral gate. This interaction did not require the SecDFYajC complex and was not influenced by SecA binding to SecY. In contrast, ribosomes dissociated the YidC contacts to lateral gate helices 2b and 8. The major contact between YidC and the lateral gate was lost in the presence of ribosome nascent chains and new SecY-YidC contacts appeared. These data demonstrate that the SecY-YidC interaction is influenced by nascent-membrane-induced lateral gate movements.


Design of High Performance Si/SiGe Heterojunction Tunneling FETs with a T-Shaped Gate.
In this paper, a new Si/SiGe heterojunction tunneling field-effect transistor with a T-shaped gate (HTG-TFET) is proposed and investigated by Silvaco-Atlas simulation. The two source regions of the HTG-TFET are placed on both sides of the gate to increase the tunneling area. The T-shaped gate is designed to overlap with N+ pockets in both the lateral and vertical directions, which increases the electric field and tunneling rate at the top of tunneling junctions. Moreover, using SiGe in the pocket regions leads to the smaller tunneling distance. Therefore, the proposed HTG-TFET can obtain the higher on-state current. The simulation results show that on-state current of HTG-TFET is increased by one order of magnitude compared with that of the silicon-based counterparts. The average subthreshold swing (SS) of HTG-TFET is 44.64 mV/dec when V g is varied from 0.1 to 0.4 V, and the point SS is 36.59 mV/dec at V g = 0.2 V. Besides, this design cannot bring the sever Miller capacitance for the TFET circuit design. By using the T-shaped gate and SiGe pocket regions, the overall performance of the TFET is optimized.


Contribution of prednisolone to the primary endocrine treatment of advanced breast cancer.
Two hundred and four patients with progressive locally advanced or metastatic breast cancer not controllable by local therapy alone, and who had had no prior systemic therapy for advanced disease, were treated by primary endocrine therapy according to menopausal status. Premenopausal patients received ovarian irradiation (O) whilst postmenopausal patients received tamoxifen 10 mg b.d. (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg b.d. (P). In 180 evaluable patients, T + P induced significantly more responses than T alone (26/73 vs 9/72, P less than 0.01) and the addition of P to O in premenopausal patients also induced more responses than O alone (7/16 vs 4/19), but this difference was not significant and accrual of premenopausal patients continues. There was a trend for patients receiving T + P to have a longer survival than those receiving T alone (median 25 vs 16 months). These trends occurred in patients with tumours positive for oestrogen receptors and when receptor status was unknown; patients with receptor-negative tumours had a negligible response to endocrine treatment. P mitigated the occurrence of hypercalcaemia and tumour flare sometimes seen with T alone.


When the camera eats first: Exploring how meal-time cell phone photography affects eating behaviours.
Advances in cell phone technology have the potential to disrupt eating patterns. In this research, we focused on the camera function of a cell phone, characterizing: (i) the extent to which this function is used during meals; (ii) whether meal-time photographers show signs of pathological eating; and (iii) whether the act of taking food photographs alters the amount and enjoyment of food eaten. In the first study, we used the experience sampling method to track one week of meals from 137 young adults. Although we observed a low base rate of meal-time photography (5.44% of the 1140 meals captured), phone users who engaged in this practice had higher external eating scores than those who did not. That is, these meal-time photographers were more likely to eat in response to external cues (e.g. the sight of palatable food) than to internal cues of hunger. However, when participants were randomly assigned to take either food or non-food photographs within a lab setting (Study 2), we found no evidence that the type of photography influenced either the amount or enjoyment of food eaten. Taken together, our findings suggest a limited role for cell phone photography in an obesogenic environment.


Worldwide prevalence of suicidal ideation and suicide plan among people with schizophrenia: a meta-analysis and systematic review of epidemiological surveys.
Schizophrenia is a severe psychiatric disorder with high premature mortality rates. This is a meta-analysis and systematic review of the prevalence of suicidal ideation (SI) and suicide plan (SP) among people with schizophrenia. PubMed, Web of Science, Embase, and PsycINFO were systematically searched from their respective inception to October 10, 2020. Data on prevalence of SI and/or SP were synthesized using the random effects model. Twenty-six studies covering 5079 people with schizophrenia were included for meta-analysis. The lifetime and point prevalence of SI were 34.5% (95% CI: 28.2-40.9%), and 29.9% (95% CI: 24.2-35.6%), respectively. The lifetime prevalence of SP was 44.3% and the point prevalence of SP ranged between 6.4 and 13%. Subgroup and meta-regression analyses revealed that source of patients, survey countries, and sample size were significantly associated with the point prevalence of SI, while male proportion and quality assessment scores were significantly associated with the lifetime and point prevalence of SI. Survey time and mean age were significantly associated with lifetime prevalence of SI. Both SI and SP are common in people living with schizophrenia, especially in males and inpatients. Routine screening and effective interventions for SI and SP should be implemented in this population.


Sex ratio and natural selection in humans: a comparative analysis of two Caucasian populations.
In the course of the last century industrialized countries have experienced significant changes in mortality rates. Since the sex ratio of a population may be considered a function of, among other factors, differential mortality in the two sexes, it is expected to correlate with changes in sex-specific mortality rates. In this paper secular changes in the sex ratio at birth and after the action of relevant components of early selection (stillbirth, mortality within the first month and within the first year of life) have been studied in the Italian and in the USA White populations. The results can be summarized as follows. (i) In the past, extra male-specific mortality appeared to reduce the relatively large values of the sex ratio observed at birth, and this held true in both populations. (ii) In more recent times, male-specific mortality has been decreasing in all age groups, and the sex ratios before and after the action of early selection now tend to identical values. Therefore, it can be envisaged that in the near future the sex ratio observed at birth will be maintained up to the reproductive age. If the reproductive value is stabilized by natural selection, as is likely, new relationships between sex ratio and selection may be expected to develop in a relatively short time.