Using existing data to predict and quantify the risks of GM forage to a population of a non-target invertebrate species: a New Zealand case study.
Determining the effects of genetically modified (GM) crops on non-target organisms is essential as many non-target species provide important ecological functions. However, it is simply not possible to collect field data on more than a few potential non-target species present in the receiving environment of a GM crop. While risk assessment must be rigorous, new approaches are necessary to improve the efficiency of the process. Utilisation of published information and existing data on the phenology and population dynamics of test species in the field can be combined with limited amounts of experimental biosafety data to predict possible outcomes on species persistence. This paper presents an example of an approach where data from laboratory experiments and field studies on phenology are combined using predictive modelling. Using the New Zealand native weevil species Nicaeana cervina as a case study, we could predict that oviposition rates of the weevil feeding on a GM ryegrass could be reduced by up to 30% without threat to populations of the weevil in pastoral ecosystems. In addition, an experimentally established correlation between feeding level and oviposition led to the prediction that a consistent reduction in feeding of 50% or higher indicated a significant risk to the species and could potentially lead to local extinctions. This approach to biosafety risk assessment, maximising the use of pre-existing field and laboratory data on non-target species, can make an important contribution to informed decision-making by regulatory authorities and developers of new technologies.


Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.
The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P < .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P < .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.


[Migration and uneven aging in the regions of France].
Regional differences in the rate of demographic aging in France are examined. The author notes that "contrary to popular belief, of the two factors that contribute to aging, natural trends (births and deaths) still have the edge over the effect of population migrations across regions. The only exception to this is in the Paris area, due to the influence of Paris itself, where youthfulness caused by migrations is on a more or less equal footing with 'natural' aging. Conversely, migration contributes the most to the increase in the average age in the western French regions, with the joint effects of young people leaving and the over-60s returning." (SUMMARY IN ENG AND GER AND SPA)


[Bilateral atraumatic epiphysiolysis of the head of the tibia].
We report above a 14-year old boy, who suffered from a bilateral epiphyseal fracture type Salter/Harris II of the proximal tibia within four weeks without having an adequate trauma. Accompanying injuries were not found. On the left side we performed a osteosynthesis by K-wires due to an dorsal flexion of the epiphyseal fragment, the other side was treated conservatively with an plaster tutor. On both sides we achieved a correct axis and length in a uncomplicated healing with free joint movement. On the base of the result of our treatment we show a literature review of this rare form of epiphysiolysis.


System design and experimental research of lower esophageal sphincter stimulator for treatment of gastroesophageal reflux disease.
Electrical stimulation therapy (EST) of lower esophageal sphincters (LES) is a new technique for the treatment of gastroesophageal reflux disease (GERD). In this paper, an implantable LES stimulator with wireless power transmission is proposed for the treatment of GERD. The LES stimulator is composed of an implantable pulse generator (IPG), an external controller, and a wireless power transmission module. The IPG, whose area is 31×21 mm2, is designed to generate voltage-regulated constant-current stimulation pulses. The external controller allows for wireless programming of the IPG via a Bluetooth Low Energy (BLE) module. The wireless power transmission module provides power for the IPG. According to the measurement of output stimulus waveforms, the proposed LES stimulator is capable of delivering electrical stimulations with a current ranging between 0 and 8 mA. To evaluate the safety and efficacy of the proposed LES stimulator, experiments were performed on 12 male New Zealand white rabbits. Esophageal manometry was performed before and after the procedure and the LES pressure (LESP) has been recorded. The mean LESP is increased significantly in the stimulation group than the sham group (stimulation group: 9.25±1.24 mmHg vs 13.99 ±1.28 mmHg, p<;0.05; sham group: 9.00±1.22 mmHg vs 9.23±1.27 mmHg, p=0.267). The results show that the electrical stimulation delivered by the LES stimulator can safely and effectively increase resting LES pressure in acute animal models, suggesting that the implantable LES stimulator is a perspective approach for treating GERD in clinics.


Role of cysteine in activation and allosteric regulation of maize phosphoenolpyruvate carboxylase.
The effect of 5-5'-dithiobis-2-nitrobenzoate (DTNB) on the kinetic parameters and structure of phosphoenolpyruvate carboxylase purified from maize (Zea mays L.) has been studied. The V(max) is found to be independent of the presence of this thiol reagent. The K(m) is increased upon oxidation of cysteines by DTNB. At a substrate concentration higher than K(m) (3.1 millimolar Mgphosphoenolpyruvate), a significant reversible decrease of the activity is observed. Malate has little effect in preventing the modification of these cysteines. The V type inhibition by malate was also studied at a saturating phosphoenolpyruvate level (9.3 millimolar Mgphosphoenolpyruvate). In the presence of 50 micromolar DTNB, up to 60% inhibition is caused by 15 millimolar malate; however, in the presence of both 50 micromolar DTNB and 50 millimolar dithiothreitol (DTT) this inhibition is reduced to 20%. The presence of DTT alone increases the size of the phosphoenolpyruvate carboxylase molecule as determined by light scattering. The activity at nonsaturating substrate concentration is increased by 36% in the presence of DTT. The oligomerization equilibrium between the dimer and the tetrameric form of the enzyme is affected by cysteine. The K(m) for the substrate, the sensitivity toward malate, and the size of the enzyme are found to be modified upon incubation in the presence of DTT.


Corneal topography and the hirschberg test.
A simple trigonometric analysis of the Hirschberg test with the assumption that the corneal surface is spherical predicts a sinusoidal dependence of the corneal reflex displacement on the angle of ocular rotation. A comparison with corneal reflex photographs demonstrates that at angles larger than 50 prism diopters (26 deg) the reflex displacements are larger than predicted by the spherical model. This discrepancy may be accounted for by incorporating a more general description of the corneal topography into the geometric analysis. The linear Hirschberg relation that is seen in typical data is accounted for by a relative flattening of the peripheral cornea by ~ 20% of the apical curvature. This geometric analysis of the functional dependence of the Hirschberg relation on the corneal topography can be expressed as an integral equation. Differentiation yields a second-order differential equation for the corneal topography in terms of the Hirschberg data. If the Hirschberg relation is assumed to be linear, a quadratic dependence is found for the corneal curvature. A similar differential approach can be formulated for the Placido disk. In this sense the corneal topography problem given in terms of Placido disk data is shown to be wellformulated. The relative simplicity of the Hirschberg geometry is seen to stem from the alignment of the light source with the eye of the observer.


Identification of the Extracytoplasmic Function σ Factor σP Regulon in Bacillus thuringiensis.
Bacillus thuringiensis and other members of the Bacillus cereus family are resistant to many β-lactams. Resistance is dependent upon the extracytoplasmic function sigma factor σP. We used label-free quantitative proteomics to identify proteins whose expression was dependent upon σP. We compared the protein profiles of strains which either lacked σP or overexpressed σP. We identified 8 members of the σP regulon which included four β-lactamases as well as three penicillin-binding proteins (PBPs). Using transcriptional reporters, we confirmed that these genes are induced by β-lactams in a σP-dependent manner. These genes were deleted individually or in various combinations to determine their role in resistance to a subset of β-lactams, including ampicillin, methicillin, cephalexin, and cephalothin. We found that different combinations of β-lactamases and PBPs are involved in resistance to different β-lactams. Our data show that B. thuringiensis utilizes a suite of enzymes to protect itself from β-lactam antibiotics. IMPORTANCE Antimicrobial resistance is major concern for public health. β-Lactams remain an important treatment option for many diseases. However, the spread of β-lactam resistance continues to rise. Many pathogens acquire antibiotic resistance from environmental bacteria. Thus, understanding β-lactam resistance in environmental strains may provide insights into additional mechanisms of antibiotic resistance. Here, we describe how a single regulatory system, σP, in B. thuringiensis controls expression of multiple genes involved in resistance to β-lactams. Our findings indicate that some of these genes are partially redundant. Our data also suggest that the large number of genes controlled by σP results in increased resistance to a wider range of β-lactam classes than any single gene could provide.


First Presentation of Systemic Lupus Erythematosus in a 24-Year-Old Male following mRNA COVID-19 Vaccine.
The SARS-CoV-2 viral pandemic has had an immeasurable global impact, resulting in over 5 million deaths worldwide. Numerous vaccines were developed in an attempt to quell viral dissemination and reduce symptom severity among those infected. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of antinuclear autoantibodies (ANAs) with heterogenic clinical manifestations, secondary to immune complex deposition in a multitude of organ systems. There are scarcely reported cases of SLE development following COVID-19 mRNA vaccination. We present a case of a 24-year-old male without preexisting conditions or family history of autoimmune disorders, presenting with SLE following the first dose of the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine.


Structural bases of T cell antigen receptor recognition in celiac disease.
Celiac disease (CeD) is a human leukocyte antigen (HLA)-linked autoimmune-like disorder that is triggered by the ingestion of gluten or related storage proteins. The majority of CeD patients are HLA-DQ2.5+, with the remainder being either HLA-DQ8+ or HLA-DQ2.2+. Structural studies have shown how deamidation of gluten epitopes engenders binding to HLA-DQ2.5/8, which then triggers an aberrant CD4+ T cell response. HLA tetramer studies, combined with structural investigations, have demonstrated that repeated patterns of TCR usage underpins the immune response to some HLADQ2.5/8 restricted gluten epitopes, with distinct TCR motifs representing common landing pads atop the HLA-gluten complexes. Structural studies have provided insight into TCR specificity and cross-reactivity towards gluten epitopes, as well as cross-reactivity to bacterial homologues of gluten epitopes, suggesting that environmental factors may directly play a role in CeD pathogenesis. Collectively, structural immunology-based studies in the CeD axis may lead to new therapeutics/diagnostics to treat CeD, and also serve as an exemplar for other T cell mediated autoimmune diseases.


An efficient and economic site-specific deuteration strategy for NMR studies of homologous oligonucleotide repeat sequences.
We describe herein the use of a 2H-labeling strategy to achieve specific assignments of considerably overlapped cross peaks in the 1H-NMR spectrum of a DNA trinucleotide repeat sequence. Our strategy focuses on site-specific 2H-labeling of base moieties to simplify the NMR spectral regions which contain the major portion of the structural information. To achieve efficient preparation of 2H8- or 2H6-labeled DNA and RNA nucleosides and nucleotides, the existing synthetic and purification procedures were significantly improved. Our experiments demonstrate that pyrimidine H6 deuteration reactions may be carried out using non-deuterated base reagents with DMSO-d6 as a 2H donor. These reactions are simple and economic to perform and produce base deuterated nucleosides and nucleotides in high yield. The 2H-labeled residues have been incorporated into oligonucleotides with minor modifications of the existing reaction conditions. Using the homologous CGG repeat sequence, d(CGG)5, as an example, the effectiveness of the site-specific base deuteration strategy is demonstrated. In the otherwise extensively overlapped spectra of d(CGG)5, 2H-labeling has permitted unambiguous identification of a sequential connectivity at a central CG step and confirmation of several other NOE assignments. This information is critical for elucidation of the structure and the folding of the CGG repeat sequences and will contribute to the intensive effort to understand the mechanisms of triplet expansion, which has been implicated in the development of a number of hereditary neurodegenerative diseases. In addition to the two dimensional spectral simplification in a key spectral region using site-specific 2H8/2H6-labeling, the potential applications of the prescribed strategy in homonuclear three dimensional experiments are also discussed.


Serum GADD45a methylation is a useful biomarker to distinguish benign vs malignant prostate disease.
Prostate-specific antigen (PSA) screening for prostate cancer results in a large number of unnecessary prostate biopsies. There is a need for specific molecular markers that can be used in combination with PSA to improve the specificity of PSA screening. We examined GADD45a methylation in blood DNA as a molecular marker for prostate cancer diagnosis. The study included 82 men, with PSA levels >4 ng ml(-1) and/or abnormal digital rectal exam, who underwent prostate biopsy. We compared GADD45a methylation in DNA from serum and buffy coat in 44 patients (22 prostate cancer and 22 benign). GADD45a methylation in serum DNA was examined in 82 patients (34 cancer and 48 benign). There was no significant difference in buffy coat GADD45a methylation between cancer and benign patients. Serum GADD45a methylation was significantly higher in cancer than in benign patients. Classification and regression tree predictive model for prostate cancer including risk groups defined by PSA, free circulating DNA (fcDNA) level and GADD45a methylation yielded specificity of 87.5%, sensitivity of 94.1% and receiver operator characteristic curve area of 0.937. Serum GADD45a methylation in combination with PSA and fcDNA level was useful in distinguishing benign from prostate cancer patients.


Effects of haemodialysis on taste for salt in relation to changes in blood constituents.
Taste sensitivity and preference for sodium chloride in bread and pea soup were assessed before and after haemodialysis in 12 female chronic renal failure patients. Blood samples were also taken pre- and post-dialysis and analysed for zinc, sodium and renin. The patients demonstrated an increased sensitivity to, and decreased preference for, sodium chloride in both bread and pea soup following dialysis. These taste changes were found to correlate with pre- to post-dialysis changes in the zinc levels in the blood. Patients receiving a more severely sodium-restricted diet showed a greater sensitivity to the taste of sodium chloride in the foods tested. Renin levels dropped in all patients following dialysis, the size of the change correlating with the size of the change in body weight.


Bacteria and cells as alternative nano-carriers for biomedical applications.
Nano-based systems have received a lot of attention owing to their particular properties and, hence, have been proposed for a wide variety of biomedical applications. These nanosystems could be potentially employed for diagnosis and therapy of different medical issues. Although these nanomaterials are designed for specific tasks, interactions, and transformations when administered to the human body affect their performance and behavior. In this regard, bacteria and other cells have been presented as alternative nanocarriers. These microorganisms can be genetically modified and customized for a more specific therapeutic action and, in combination with nanomaterials, can lead to bio-hybrids with a unique potential for biomedical purposes. Literature regarding bacteria and cells employed in combination with nanomaterials for biomedical applications is revised and discussed in this review. The potential as well as the limitations of these novel bio-hybrid systems are evaluated. Several examples are presented to show the performance of these alternative nanocarriers. Bio-hybrid systems have shown their potential as alternative nanocarriers as they contribute to better performance than traditional nano-based systems. Nevertheless, their limitations must be studied, and advantages and drawbacks assessed before their application to medicine.


Synthesis, rotational dynamics, and photophysical characterization of a crystalline linearly conjugated phenyleneethynylene molecular dirotor.
We report the synthesis, crystal structure, solid-state dynamics, and photophysical properties of 6,13-bis((4-(3-(3-methoxyphenyl)-3,3-diphenylprop-1-yn-1-yl)phenyl)ethynyl)-5,7,12,14-tetrahydro-5,14:7,12-bis([1,2]benzeno)pentacene (1), a molecular dirotor with a 1,4-bis((4-ethynylphenyl)ethynyl)benzene (BEPEB) chromophore. The incorporation of a pentiptycene into the molecular dirotor provides a central stator and a fixed phenylene ring relative to which the two flanking ethynylphenylene rotators can explore various torsion angles; this allows the BEPEB fluorophore dynamics to persist in the solid state. X-ray diffraction studies have shown that molecular dirotor 1 is packed so that all the BEPEB fluorophores adopt a parallel alignment, this is ideal for the development of functional materials. Variable temperature, quadrupolar echo (2)H NMR studies have shown that phenylene rotator flipping has an activation energy of 9.0 kcal/mol and a room temperature flipping frequency of ∼2.6 MHz. Lastly, with measurements in solution, glasses, and crystals, we obtained evidence that the fluorescence excitation and emission spectra of the phenyleneethynylene chromophores is dependent on the extent of conjugation between the phenylene rings, as determined by their relative dihedral angles. This work provides a promising starting point for the development of molecular dirotors with polar groups whose amphidynamic nature will allow for the rapid shifting of solid-state absorption, fluorescence, and birefringence, in response to external electric fields.


Active particles with broken symmetry.
We discuss and analyze the driving a polar active particle with a head-tail asymmetry based on the dynamics of an internal motor variable driven by an energy depot and a broken symmetry of friction with respect to the internal degree of freedom. We show that such a driving may be advantageous for driving large masses with small energy uptake from the environment and exhibits interesting properties such as resonance-driven optimal propulsion.


[Effect of bioceramics on biological activity of microorganisms].
Biomaterials that come into contact with microorganisms in the middle ear or paranasal sinuses should be tested before clinical application. Thus, it is necessary to test the influence exerted on bacterial growth by biomaterials used as bone substitutes in head and neck surgery before implantation. In this study, Bioverit, Al2O3 ceramic, and glass carbon were subjected to contamination with typical microorganisms in the middle ear and paranasal sinuses such as Staphylococcus aureus, Streptococcus pneumoniae and salivarius, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Candida albicans. In the suspension test, all gram-negative species were inhibited, but gram-positive microorganisms and Candida albicans were not affected. The Al2O3 ceramic showed the largest inhibition effect while growth inhibition of glass carbon was low. Streptococcus pneumoniae and salivarius can use glass carbon as a nutrient. In contrast, Bioverit and Al2O3 ceramic could not improve the growth of all tested microorganisms. In conclusion, we think that Bioverit is suitable for implantation in bacterially contaminated regions of the head and neck, whereas glass carbon is unsuitable for this application in reconstructive surgery.


Effects of the V(2)-receptor antagonist OPC-41061 and the loop diuretic furosemide alone and in combination in rats.
This study was conducted to characterize the diuretic effect of OPC-41061, a nonpeptide vasopressin V(2)-receptor antagonist, and furosemide by administering each alone and in combination in conscious male rats. OPC-41061 at 1 and 10 mg/kg and furosemide at 10 and 100 mg/kg dose-dependently increased urine volume to the same extent. The high dose of OPC-41061 (10 mg/kg) markedly elevated electrolyte-free water clearance (E-CH(2)o) to a positive value. In contrast to OPC-41061, furosemide elevated only electrolyte clearance but not E-CH(2)o. The differences in diuretic profile reflected the changes in serum sodium and hormone levels. OPC-41061 dose-dependently elevated serum sodium concentration, but furosemide tended to decrease it. The high dose of furosemide (100 mg/kg) significantly elevated serum renin activity and aldosterone concentration, indicating that furosemide activated the renin-angiotensin-aldosterone system (RAA-system). On the other hand, OPC-41061 did not affect these parameters. When OPC-41061 was administered concomitantly with furosemide, OPC-41061 significantly increased urine volume and E-CH(2)o, and decreased urinary osmolality compared with furosemide alone. OPC-41061 dose-dependently elevated serum osmolality and sodium concentration even when administered in combination with the high dose of furosemide. These results suggest that OPC-41061 produces aquaresis leading to increased serum sodium without affecting the RAA-system. On the other hand, furosemide produced natriuresis, leading to decreased serum sodium level and activation of the RAA-system. It was also demonstrated that OPC-41061 produced an additive diuretic effect and elevated serum sodium level in the presence of furosemide.


Views on helper/cytotoxic lineage choice from a bottom-up approach.
There has been speculation as to how bi-potent CD4(+) CD8(+) double-positive precursor thymocytes choose their distinct developmental fate, becoming either CD4(+) helper or CD8(+) cytotoxic T cells. Based on the clear correlation of αβT cell receptor (TCR) specificity to major histocompatibility complex (MHC) classes with this lineage choice, various studies have attempted to resolve this question by examining the cellular signaling events initiated by TCR engagements, a strategy referred to as a 'top-down' approach. On the other hand, based on the other correlation of CD4/CD8 co-receptor expression with its selected fate, other studies have addressed this question by gradually unraveling the sequential mechanisms that control the phenotypic outcome of this fate decision, a method known as the 'bottom-up' approach. Bridging these two approaches will contribute to a more comprehensive understanding of how TCR signals are coupled with developmental programs in the nucleus. Advances made during the last two decades seemed to make these two approaches more closely linked. For instance, identification of two transcription factors, ThPOK and Runx3, which play central roles in the development of helper and cytotoxic lineages, respectively, provided significant insights into the transcriptional network that controls a CD4/CD8 lineage choice. This review summarizes achievements made using the 'bottom-up' approach, followed by a perspective on future pathways toward coupling TCR signaling with nuclear programs.


Cell-penetrating peptides are excluded from the mitochondrial matrix.
CPPs (cell-penetrating peptides) facilitate cellular uptake of covalently attached macromolecules, through an as yet controversial mechanism that either involves direct membrane passage or a type of endocytosis. We investigated the potential of the CPPs penetratin and Tat to act as mitochondria-targeting vectors by testing whether they were internalized by isolated mitochondria, and by mitochondria within cells in culture. We also tested peptides conjugated to the mitochondria-targeting moiety triphenylphosphonium. We found no evidence for mitochondrial uptake by penetratin, Tat or their triphenylphosphonium conjugates. This result suggests that CPPs are unsuitable as mitochondria-targeting vectors, and implies an endocytic mode of cellular uptake for CPPs.


Global dynamics of a delayed alcoholism model with the effect of health education.
An alcohol consumption model with health education and three time delays is formulated and analyzed. The alcoholism generation number is defined. Two steady states of the model are found. At the same time, the corresponding global dynamics of the model are analyzed respectively in four cases with different time delays. Then, the effects of health education and three time delays in controlling the alcohol problem are discussed. Some numerical simulation results are also given to support our theoretical predictions.


A review of corneal melting after Boston Keratoprosthesis.
Use of the Boston Keratoprosthesis (B-KPro) has grown significantly, both in the United States and overseas over the course of the last decade. It is the most frequently employed keratoprosthesis for the management of complex corneal blindness. Improving outcomes and reductions in devastating complications such as corneal melting and infection have motivated this increase in use. We review the epidemiology and pathophysiology of corneal melting following B-KPro as well as the advances in B-KPro design and postoperative care that have halted the occurrence of melting. Eyes with autoimmune diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, and mucous membrane pemphigoid remain particularly vulnerable to corneal melt, leak, and extrusion. The development of new strategies to prevent melting in eyes with autoimmune disease is crucial to improve the outcomes of this group of patients, as they are often those with the most desperate need for visual rehabilitation with a B-KPro.


Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium.
In mammals, all-trans retinoic acid (ATRA) is instrumental to spermatogenesis. It is synthesized by two retinaldehyde dehydrogenases (RALDH) present in both Sertoli cells (SCs) and germ cells (GCs). In order to determine the relative contributions of each source of ATRA, we have generated mice lacking all RALDH activities in the seminiferous epithelium (SE). We show that both the SC- and GC-derived sources of ATRA cooperate to initiate and propagate spermatogenetic waves at puberty. In adults, they exert redundant functions and, against all expectations, the GC-derived source does not perform any specific roles despite contributing to two-thirds of the total amount of ATRA present in the testis. The production from SCs is sufficient to maintain the periodic expression of genes in SCs, as well and the cycle and wave of the SE, which account for the steady production of spermatozoa. The production from SCs is also specifically required for spermiation. Importantly, our study shows that spermatogonia differentiation depends upon the ATRA synthesized by RALDH inside the SE, whereas initiation of meiosis and expression of STRA8 by spermatocytes can occur without ATRA.


Depressive disorder and incident diabetes mellitus: the effect of characteristics of depression.
The purpose of this study was to test the hypothesis that clinically significant depression detected in a population sample increases the risk of diabetes mellitus. The authors examined the effect of characteristics of depression frequently found in the community on the risk of incident diabetes mellitus. A large community sample of adults aged > or = 55 years (N=4,803) was assessed at baseline in a longitudinal three-wave epidemiological enquiry using a psychiatric interview and the Geriatric Mental State Schedule. Cases of depression were diagnosed according to standardized criteria, and diabetes was assessed using a risk factors questionnaire. Follow-up evaluations, conducted 2.5 and 5 years later, were completed to determine the incidence of diabetes. At baseline, 379 case subjects with depression were identified. The risk of incident diabetes mellitus was higher among subjects with depression when compared with nondepressed subjects, and the association remained significant after controlling for potential confounders, including diabetes risk factors. The estimated rate of diabetes mellitus attributable to depression was 6.87%. An increased risk of diabetes mellitus was also associated with the following characteristics of depression: nonsevere depression, persistent depression, and untreated depression. Treatment with antidepressants was not associated with an increased risk of diabetes mellitus. Clinically significant depression is associated with a 65% increased risk of diabetes mellitus. Characteristics of depression frequently found in the community, namely nonsevere depression, persistent depression, and untreated depression, may play a role in the development of diabetes in a predominantly elderly adult population.


Ultrasonography and magnetic resonance imaging of the brain in hypoxic full-term newborns.
The aim of this article was to review the studies on diagnostic and prognostic value of radiological investigations (cranial sonography, Doppler ultrasonography, and magnetic resonance imaging) in the detection of hypoxic-ischemic brain injuries in full-term newborns. A systematic search of studies on the diagnostic and prognostic possibilities of radiological investigations for the detection of hypoxic-ischemic injuries in full-term newborns was performed. A total of 13 prospective and 4 retrospective studies that analyzed the incidence of hypoxic-ischemic cerebral injuries, determined by means of cranial sonography, Doppler sonography, and magnetic resonance imaging, and associations with the stages of hypoxic-ischemic encephalopathy and long-term neurodevelopmental outcomes were included in this systematic review. Magnetic resonance imaging detects lesions in 75%-100% of cases. Magnetic resonance imaging performed at the age of 7-11 days demonstrated a high sensitivity (100%) and negative predictive value (100%) to predict unfavorable outcomes at 4 years of age. In newborns with hypoxic-ischemic encephalopathy, substantial cerebral hemodynamic alterations are detected after birth. The sensitivity and negative predictive value of cerebral blood flow velocities (peak systolic flow velocity, end-diastolic flow velocity) changes at 12±2 hours of age to predict the severity of hypoxic-ischemic encephalopathy and unfavorable outcomes at 18 months of age were found to be high (90% and 94%, respectively). A low resistive index (<0.56) at the age of 1-3 days had a specificity of 95% to predict unfavorable outcomes at 3 years of age. The data on the diagnostic and prognostic potential of cranial sonography are limited scarce and contrary.


Arthritis due to tuberculosis, fungal infections, and parasites.
Tuberculous, fungal, and parasitic infections infect millions of people throughout the world. While other problems usually overshadow their rheumatologic manifestations, nearly all these infections can involve bone or joints and may on occasion present with rheumatologic symptoms. The classic model of these diseases presenting as chronic monoarticular arthritis is still generally valid but other presentations, such as tenosynovitis with atypical mycobacterial infections, erythema nodosum with leprosy, coccidioidomycosis and histoplasmosis, and reactive arthritis with schistosomiasis and helminthic infections, are now well established. The most dramatic change in the epidemiology of tuberculous infections in recent years is the increasing incidence in patients with the acquired immunodeficiency syndrome (AIDS). Mycobacterium avium complex infections in particular have increased dramatically and are a major problem in the later stages of AIDS. Reports of septic arthritis and tenosynovitis due to M. avium are likely to increase over the next few years.


Mutagenesis of transmembrane domain 11 of P-glycoprotein by alanine scanning.
The biochemical and genetic analyses of P-glycoprotein (P-gp) have indicated that the membrane-associated regions of P-gp play an important role in drug recognition and drug transport. Predicted transmembrane domain 11 (TM11) maps near a major drug binding site revealed by photoaffinity labeling, and mutations in this domain alter the substrate specificity of P-gp. To investigate further the role of TM11 in P-gp function in general, and substrate specificity in particular, each of the 21 residues of TM11 of the P-gp isoform encoded by the mouse mdr3 gene was independently mutated to alanine, or to glycine in the case of endogenous alanines. After transfection and overexpression in Chinese hamster ovary cells, pools of stable transfectants were analyzed for qualitative or quantitative deviations from the profile of resistance to vinblastine, adriamycin, colchicine, and actinomycin D displayed by the wild-type protein. While mutations at eight of the positions had no effect on P-gp function, 13 mutants showed a 2-10-fold reduction of activity against one of the four drugs tested. Although the phenotype of individual mutants was varied, replacements at most mutation-sensitive positions seemed to affect the drug resistance profiles rather than the overall activity of the mutant P-gp. When TM11 was projected in a alpha-helical configuration, the distribution of deleterious and neutral mutations was not random but segregated with a more hydrophobic (mutation-insensitive) face and a more hydrophilic (mutation-sensitive) face of a putative amphipathic helix. The alternate clustering pattern of deleterious vs neutral mutations in TM11 together with the altered drug resistance profile of deleterious mutants suggest that the more hydrophilic face of the TM11 helix may play an important structural or functional role in drug recognition and transport by P-gp. Finally, the conservation of the two residues most sensitive to mutations (Y949 and Y953) in TM11, and in the homologous TM5, of all mammalian P-gps and also in other ABC transporters, suggests that these residues and domains may play an important role in structural as well as mechanistic aspects common to this family of proteins.


Redox properties of tyrosine and related molecules.
Redox reactions of tyrosine play key roles in many biological processes, including water oxidation and DNA synthesis. We first review the redox properties of tyrosine (and other phenols) in small molecules and related polypeptides, then report work on (H20)/(Y48)-modified Pseudomonas aeruginosa azurin. The crystal structure of this protein (1.18Å resolution) shows that H20 is strongly hydrogen bonded to Y48 (2.7-2.8Å tyrosine-O to histidine-N distance). A firm conclusion is that proper tuning of the tyrosine potential by a proton-accepting base is critical for biological redox functions.


OSHA's final bloodborne pathogens standard: Part II.
The Bloodborne Pathogens Standard has specific requirements for employee hazard communication and training as well as management of regulated waste, contaminated laundry, and housekeeping procedures. OSHA recognizes the benefits of prophylactic use of hepatitis B vaccine and requires that it be made available, at no charge, to all employees who have occupational exposure to blood or other potentially infectious materials. The goal of the Bloodborne Pathogens Standard is to reduce the occupational risk of morbidity and mortality associated with diseases such as hepatitis B and human immunodeficiency virus (HIV).


Spatiotemporal expansion of human brucellosis in Shaanxi Province, Northwestern China and model for risk prediction.
Human brucellosis imposes a heavy burden on the health and economy of endemic regions. Since 2011, China has reported at least 35,000 human brucellosis cases annually, with more than 90% of these cases reported in the northern. Given the alarmingly high incidence and variation in the geographical distribution of human brucellosis cases, there is an urgent need to decipher the causes of such variation in geographical distribution. We conducted a retrospective epidemiological study in Shaanxi Province from January 1, 2005 to December 31, 2018 to investigate the association between meteorological factors and transmission of human brucellosis according to differences in geographical distribution and seasonal fluctuation in northwestern China for the first time. Human brucellosis cases were mainly distributed in the Shaanbei upland plateau before 2008 and then slowly extended towards the southern region with significant seasonal fluctuation. The results of quasi-Poisson generalized additive mixed model (GAMM) indicated that air temperature, sunshine duration, rainfall, relative humidity, and evaporation with maximum lag time within 7 months played crucial roles in the transmission of human brucellosis with seasonal fluctuation. Compared with the Shaanbei upland plateau, Guanzhong basin had more obvious fluctuations in the occurrence of human brucellosis due to changes in meteorological factors. Additionally, the established GAMM model showed high accuracy in predicting the occurrence of human brucellosis based on the meteorological factors. These findings may be used to predict the seasonal fluctuations of human brucellosis and to develop reliable and cost-effective prevention strategies in Shaanxi Province and other areas with similar environmental conditions.


Optimising the biogas production from leather fleshing waste by co-digestion with MSW.
Waste from the leather industry, known as limed leather fleshing (LF), has a low C:N (3.2) and an alkaline pH of 11.4. This is a major disadvantage for anaerobic digestion due to ammonia toxicity for methanogenesis. This study describes co-digestion of LF with biodegradable fraction of municipal solids waste optimised over a range of C:N and pH to minimise ammonia and to maximise biogas yield. The optimum conditions were found with a blend that provided C:N of 15 and pH of 6.5 and the cumulative biogas yield increased from 560 mL using LF fraction alone, to 6518 mL with optimum blend. At higher pH of 8.5, unionised ammonia was high (2473 mg L(-1)) coincided with poor biogas yield (47 m Ld(-1)) that confirms ammonia toxicity. By contrast at a pH of 4.5 the ammonia was minimum (510 mg L(-1)), but high VFA (26,803 mg L(-1)) inhibited the methanogens. Biomass activity measured using ATP correlated well with biogas yield as reported previously.


Localization Reliability Improvement Using Deep Gaussian Process Regression Model.
With the widespread use of the Global Positioning System, indoor positioning technology has attracted increasing attention. Many systems with distinct deployment costs and positioning accuracies have been developed over the past decade for indoor positioning. The method that is based on received signal strength (RSS) is the most widely used. However, manually measuring RSS signal values to build a fingerprint database is costly and time-consuming, and it is impractical in a dynamic environment with a large positioning area. In this study, we propose an indoor positioning system that is based on the deep Gaussian process regression (DGPR) model. This model is a nonparametric model and it only needs to measure part of the reference points, thus reducing the time and cost required for data collection. The model converts the RSS values into four types of characterizing values as input data and then predicts the position coordinates using DGPR. Finally, after reinforcement learning, the position coordinates are optimized. The authors conducted several experiments on a simulated environment by MATLAB and physical environments at Tianjin University. The experiments examined different environments, different kernels, and positioning accuracy. The results showed that the proposed method could not only retain the positioning accuracy, but also save the computation time that is required for location estimation.


MicroRNA-34a Promotes Ischemia-Induced Cardiomyocytes Apoptosis through Targeting Notch1.
Myocardial apoptosis occurs during myocardial ischemia. This study aimed to determine the effect of microRNA-34a (miR-34a) in ischemia-induced myocardial apoptosis. Mainly, SD rats were subjected to myocardial ischemia by ligaturing the left anterior descending branch of coronary artery. After rats had myocardial infarction, HE staining and TUNEL staining confirmed a significant increase in apoptosis. The expression of miR-34a was noticeably upregulated, while the expression of Notch1 was downregulated. An increase in caspase-3 and a decrease in Bcl-2/Bax ratio were observed in myocardium. Similar results were observed in the in vitro model of cardiomyocyte ischemia and anoxia of this study. When rat cardiomyocytes were administered with serum starvation and microaerophilic system, apoptosis-related proteins were significantly increased. However, transfecting the miR-34a inhibitor into the cardiomyocyte before the serum starvation and hypoxia treatment could increase the ratio of Bcl-2/Bax and downregulate the expression of caspase-3, as well as prevent cardiomyocytes from apoptosis. As opposed to the abovementioned points, the upregulation of miR-34a expression by transfecting miR-34a mimics induced Notch1 reduce and apoptosis-related proteins increase apparently, while upregulation of Notch1 could stimulate apoptosis attributed to miR-34a. Mechanistically, we demonstrated that Notch1 is a direct target of miR-34a. In conclusion, our current results suggested that miR-34a significantly stimulates ischemia-induced cardiomyocytes apoptosis by targeting Notch1.


Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion.
Histone deacetylases play a key role in regulating transcription and other cellular processes by catalyzing the hydrolysis of epsilon-acetyl-lysine residues. For this reason, inhibitors of histone deacetylases are potential targets for the treatment of cancer. A subset of these enzymes has previously been shown to require divalent metal ions for catalysis. Here we demonstrate that histone deacetylase 8 (HDAC8) is catalytically active with a number of divalent metal ions in a 1:1 stoichiometry with the following order of specific activity: Co(II) > Fe(II) > Zn(II) > Ni(II). The identity of the catalytic metal ion influences both the affinity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the Michaelis constant, with Fe(II)- and Co(II)-HDAC8 having K(M) values that are over 5-fold lower than that of Zn(II)-HDAC8. These data suggest that Fe(II), rather than Zn(II), may be the in vivo catalytic metal. In further support of this hypothesis, recombinant HDAC8 purified from E. coli contains 8-fold more iron than zinc before dialysis, and the HDAC8 activity in cell lysates is oxygen-sensitive. Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes.


Effect of interspecies quorum sensing on the formation of aerobic granular sludge.
Quorum sensing (QS) is a form of microbial communication that relies on small signal molecules to regulate group behaviors such as biofilm formation in response to population density. In this study, we attempted to apply the paradigm of bacterial QS to aerobic granular sludge (AGS) formation for wastewater treatment. An essential element of interspecies QS signals, boron, was added to a sequencing batch reactor (SBR) to stimulate AGS growth. Bioassays elaborated the activity of autoinducer-2 (AI-2). We found that boron accelerated AGS growth, resulting in improved settlement performance and increased biomass in the SBR. During continuous SBR operation, the AGS showed an obvious increase in AI-2 activity, which implies that interspecies QS was closely associated with AGS formation. Analysis of EPS showed that boron stimulated tryptophan production, and increased the hydrophobia of AGS. From these results, it was speculated that the addition of boron may have promoted the formation of boron complexed to (R)-4, 5-dihydroxy-2,3-pentanedione (DPD) as the precursor of AI-2, which resulted in accelerated interspecies QS. The results also suggested QS as a novel regulation target for the biogranulation process, such as AGS formation.


Iron fortification of infant milk formula: the effect on iron status and immune function.
We conducted a randomized double-blind trial of a cow's milk infant formula with increased iron fortification in order to confirm its safety and to measure its effects on iron status and immune function. A group of full-term, well nourished and healthy infants was followed from the age of 3 months to 1 year. A control group of 74 infants was given a commercially available infant formula containing 8.3 mg Fe/100g. The test group of 75 infants received a similar formula with 40 mg Fe/100 g. The formula with the extra iron proved to be safe and, when compared with the control group, the children in the test group had significantly improved iron status as reflected by the proportion of children classed as normal (25 of 61 cf. 44 of 65; p less than 0.003), and by the mean values of the haemoglobin concentration (11.5 cf. 11.9 g/dl; p = 0.04), red cell distribution width (15.5% cf. 14.4%; p = 0.0005), red cell zinc protoporphyrin (3.4 cf. 4.0 micrograms/g Hb; p = 0.04) and ferritin (29 cf. 17.3 micrograms/l; p = 0.004). The extra iron fortification depressed zinc concentration in plasma (90.6 cf. 83.5 micrograms/l; p = 0.05). There was no significant difference between the two groups for laboratory measures of immune function or for incidence of infection. No adverse effects such as infection could be attributed to the increased iron. We conclude that iron fortification of cow's milk infant formula may be safely increased to 40 mg/100 g (i.e. by a factor of 4.8 over the common concentration of 8.3 mg/100 g), but that this has less than the expected effect on iron status. Further studies are required to define (a) the long-term role of facilitators of iron absorption such as ascorbic acid, (b) the interaction of iron with absorption of divalent trace elements such as zinc, and (c) the effect of iron status on immune function and susceptibility to infection.


p16 (CDKN2/cyclin-dependent kinase-4 inhibitor/multiple tumor suppressor-1) gene is not altered in uterine cervical carcinomas or cell lines.
The p16 (CDKN2/cyclin-dependent kinase-4 inhibitor/multiple tumor suppressor-1) gene is frequently altered in cell lines and some types of cancers. To assess whether alterations of this gene are important in the pathogenesis of cervical cancer, we examined 41 primary tumors and 8 cell lines, using Southern blot and polymerase chain reaction-single strand conformation polymorphism analyses. We did not detect any deletions or mutations, which indicates that inactivation of the p16CDKN2 gene is not critical in the tumorigenesis of cervical cancer or in establishment of cervical cancer cell lines.


Tat mediates apoptosis in vivo in the rat central nervous system.
The HIV-1 transactivator of transcription, Tat, mediates apoptosis in neurons and may cause AIDS-associated neurologic disorders, which include dementia and loss of motor control. Here we investigate the ability of Tat to stimulate apoptosis in the rat central nervous system in vivo. Using the TUNEL assay, treatment of rat pheochromocytoma (PC12) cells with 1.0 microgram/ml of Tat for 24 h was found to stimulate apoptosis. Further, electrophoresis of DNA from Tat-treated PC12 cells demonstrated fragmentation. To investigate Tat mediated apoptosis in vivo, 20 microgram of Tat was infused into the striatum of Sprague-Dawley rats. Histochemical analysis (TUNEL) of the Tat-infused area demonstrated apoptosis. Further, these rats demonstrated postural deviation ipsilateral to the infusion. These data demonstrate that Tat stimulates apoptosis in vivo and causes neurologic dysfunction in the intact animal.


The TEA transcription factor Tec1 confers promoter-specific gene regulation by Ste12-dependent and -independent mechanisms.
In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.


The first case report of Kyphoscoliotic Ehlers-Danlos syndrome of chinese origin with a novel PLOD1 gene mutation.
Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up. This is the first case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.


Prevalence and correlates of multiple cardiovascular risk factors in children with chronic kidney disease.
Although prevalence of traditional cardiovascular risk factors (CVRF) has been described in children with CKD, the frequency with which these CVRF occur concomitantly and the clinical characteristics associated with multiple CVRF are unknown. This study determined the prevalence and characteristics of multiple CVRF in children in the Chronic Kidney Disease in Children study. Using cross-sectional data from first follow-up visits, we determined the prevalence of four CVRF: hypertension (casual BP >95(th) percentile or self-reported hypertension with concurrent use of anti-hypertensive medication), dyslipidemia (triglycerides >130 mg/dl, HDL <40 mg/dl, non-HDL >160 mg/dl, or use of lipid-lowering medication), obesity (BMI >95(th) percentile), and abnormal glucose metabolism (fasting glucose >110 mg/dl, insulin >20 μIU/ml, or HOMA-IR >2.20, >3.61, or >3.64 for those at Tanner stage 1, 2 to 3, or 4 to 5, respectively) in 250 children (median age 12.2 years, 74% Caucasian, median iohexol-based GFR 45.2 ml/min per 1.73 m(2)). Forty-six percent had hypertension, 44% had dyslipidemia, 15% were obese, and 21% had abnormal glucose metabolism. Thirty-nine percent, 22%, and 13% had one, two, and three or more CVRF, respectively. In multivariate ordinal logistic regression analysis, glomerular disease and nephrotic-range proteinuria were associated with 1.96 (95% confidence interval, 1.04 to 3.72) and 2.04 (95% confidence interval, 0.94 to 4.43) higher odds of having more CVRF, respectively. We found high prevalence of multiple CVRF in children with mild to moderate CKD. Children with glomerular disease may be at higher risk for future cardiovascular events.


Easily missed trauma of bones and ligaments.
While most fractures and dislocations are easily detected by radiographic and physical examination, some traumatic events are overlooked because the normal radiographic anatomy is not appreciated. Furthermore, certain routine radiographic views are inadequate to detect specific injuries. "Chip" or "sprain" fractures are often considered minor injuries when they actually connote significant injury to ligaments and capsules. These injuries are usually dismissed by the primary care physician, who does not believe them serious enough to warrant consulting an orthopedic surgeon. However, some are also overlooked by radiologists and orthopedic surgeons. If these injuries are not treated adequately, permanent loss of function or death may result. With these thoughts in mind, we will describe some of these injuries and discuss the radiographic anatomy, the knowledge of which should preclude some of the serious mistakes of diagnosis.


Objective evaluation of two differently-shaped permanent expander prostheses used for breast reconstruction.
When a breast is being reconstructed with an implant, a capsule of connective tissue always forms around the implant and a capsular contracture can develop. Radiotherapy increases the incidence of capsular contracture. To evaluate the results after breast reconstruction with differently-shaped textured implants, and the effect of radiotherapy on the softness of the reconstruction, 140 patients given permanent breast expander prostheses between 1994 and 2000 were studied. In 99 patients a round implant and in 41 an anatomically-shaped implant was used. Radiotherapy was given to 24 patients. For objective assessment, applanation tonometry was recorded when the desired breast volume was achieved, and 6 and 12 months later. This study showed that, regardless of the shape of the implant, the softness of the breast reconstruction was similar, as shown by the contact area of the applanation tonometry disc. Radiotherapy transiently reduced the softness of the breast.


The effect of Pilates exercise on body composition in sedentary overweight and obese women.
Pilates is a popular exercise approach among women. Still there is poor empirical quantitative evidence indicating a positive effect of Pilates exercises on body composition. The aim of our study is to determine the effects of Pilates exercises on body composition in sedentary overweight and obese women. Thirty-seven women, aged between 30 to 50 (43.79±4.88) years, included the study. Subjects are randomly divided into Pilates group (N.=19) and control group (N.=18). Pilates exercises was given for 90 minutes, 3 times/week, for 8 week with a gradual strength increase of 11-17 in the Rating of Perceived Exercise. Control group did not participate in any physical activity program. Bioelectric Impedance Analysis was used for determine the body composition of participants. Weight, Body Mass Index (BMI), body fat mass, lean body mass, waist, abdomen and hip circumference were measured at pre- and post-training period. In Pilates group, weight, BMI, fat percentage, waist, abdomen and hip circumference decreased significantly after training (P<0.05) while no significant difference was observed in lean body mass (P>0.05). In control group, abdomen and hip circumference increased significantly (P<0.05) as the other parameters showed the tendency for an increase, but no significant difference (P<0.05). The results of this study indicate that 8 weeks Pilates exercises have positive effects on body composition in sedentary overweight and obese women. Pilates exercises can be applied for improving body composition.


Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia.
The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting. Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65-74 vs. 75-84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis. Of 1439 patients, 363, 352, and 106 were aged 65-74, 75-84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65-74-, 75-84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%). Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.


The Black Death in Hereford, England: A demographic analysis of the Cathedral 14th-century plague mass graves and associated parish cemetery.
This study explores the paleoepidemiology of the Black Death (1348-52 AD) mass graves from Hereford, England, via osteological analysis. Hereford plague mortality is evaluated in the local context of the medieval city and examined alongside other Black Death burials. The Hereford Cathedral site includes mass graves relating to the Black Death and a 12th-16th century parish cemetery. In total, 177 adult skeletons were analyzed macroscopically: 73 from the mass graves and 104 from the parish cemetery. Skeletal age-at-death was assessed using transition analysis, and sex and stress markers were analyzed. The age-at-death distributions for the mass graves and parish cemetery were significantly different (p = 0.0496). Within the mass graves, young adults (15-24 years) were substantially over-represented, and mortality peaked at 25-34 years. From 35 years of age onwards, there was little variation in the mortality profiles for the mass graves and parish cemetery. Males and females had similar representation across burial types. Linear enamel hypoplasia was more prevalent within the mass graves (p = 0.0340) whereas cribra orbitalia and tibial periostitis were underrepresented. Mortality within the Hereford mass graves peaked at a slightly older age than is seen within plague burials from London, but the overall profiles are similar. This demonstrates that young adults were disproportionately at risk of dying from plague compared with other age groups. Our findings regarding stress markers may indicate that enamel hypoplasia is more strongly associated with vulnerability to plague than cribra orbitalia or tibial periostitis.


[Anterior approach in low cervical fractures prodited by hyperflexion or tear drop].
Hyperflexion or teardrop fracture of low cervical vertebrae is characterised by ligament affectation of the entire intervertebral segment, the vertebral body, primarily its anteroinferior third and, frequently, spinal medullar affectation. This series presents the clinical symptoms, diagnosis, surgical approach, and post surgical evolution in 30 patients with tear drop fractures. Over the last 30 years, thirty patients with tear drop fractures at the low cervical spine (C3-C7) were admitted to our Neurosurgical Service. Diagnostic studies included simple radiographs, computerised axial tomography (CT), and magnetic resonance imaging (MRI), all of which evidenced the instability of the damaged segment due to osteoligamentous affectation, and a primarily vertebral body fracture. Patients' neurological status was according to the Frankel' scale adapted to the American Spinal Injury Association scale (ASIA). 11 patients were included in grade A, 5 in B, 3 in grade C, 2 in grade D and 9 grade E of neurological affectation. Surgery through an anterior approach was performed, an average of 5 days after placement of halo traction, which had been placed on admission to the hospital. Surgery consisted in vertebral corporectomy and placement of a plate and a graft from the iliac crest. The patients' neurological evolution was favourable in all cases with incomplete medullar lesions. There were 11 patients with complete lesions, or Frankel grade A affectation; two died due to other associated lesions and the other nine showed no neurological improvement after surgery. The degree of arthrodesis was good and only one patient required an a combined anterior-posterior approach. We conclude that teardrop fractures were associated with severe neurological affectation in more than 50% of our patients, and that these fractures provoke instability requiring arthrodesis, generally via an anterior approach.


A microPLC-based approach for determining kinase-substrate specificity.
Phosphorylation is central to signal transduction in living organisms. The specificity of phosphorylation ensures signaling fidelity. Understanding substrate specificity is essential for novel assay development in drug discovery. In this study, we have developed an innovative approach to study protein kinase and its substrate specificity. Using 24 micro parallel liquid chromatography, we studied the reaction kinetics for two different peptide substrates commonly associated with protein kinase A (PKA): Kemptide (Leu-Arg-Arg-Ala-Ser-Leu-Glu) and CREBtide (Lys-Arg-Arg-Glu-Ile-Leu-Ser-Arg-Arg-Pro-Ser-Tyr-Arg). The phosphorylation of each substrate was monitored in real time, and the kinetic parameters (V(max), K(m), k(cat), and k(cat) K(m)) were determined for a variety of initial conditions. The results from several kinetic experiments indicated that Kemptide had higher V(max) and k(cat) values compared to CREBtide under the same assay conditions. However, both substrates had a similar k cat)/K(m) value, suggesting that both substrates have similar specificity constants for PKA. We further analyzed the reaction kinetics of ATP for both PKA/substrate complexes. Interestingly, we found that there was a fivefold difference in the specificity constants for ATP affinity to the two complexes, suggesting that even though the sequence differences between the two substrates do not affect their independent interactions with PKA, the differences do have a secondary effect on each enzyme's interaction with ATP and significantly alter the ATP consumption and thus phosphorylation. This novel approach has a broad application for studying enzyme functions and enzyme/substrate specificity.


Poststudy Point-of-Care Oral Fluid Testing in Human Immunodeficiency Virus-1 Vaccinees.
Experimental human immunodeficiency virus (HIV)-1 vaccines frequently elicit antibodies against HIV-1 that may react with commonly used HIV diagnostic tests, a phenomenon known as vaccine-induced seropositivity/seroreactivity (VISP/VISR). We sought to determine, under clinic conditions, whether a patient-controlled HIV test, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, detected HIV-1 vaccine-induced antibodies. Plasma assessment of HIV-1 cross-reactivity was examined in end-of-study samples from 57 healthy, HIV-uninfected participants who received a candidate vaccine that has entered Phase 2B and 3 testing. We also screened 120 healthy, HIV-uninfected, unblinded HIV-1 vaccine participants with VISP/VISR for an assessment using saliva. These participants came from 21 different parent vaccine protocols representing 17 different vaccine regimens, all of which contained an HIV-1 envelope immunogen. OraQuick ADVANCE was compared with results from concurrent blood samples using a series of commercial HIV screening immunoassays. Fifty-seven unique participant plasma samples were assayed in vitro, and only 1 (1.8%) was reactive by OraQuick ADVANCE. None of the 120 clinic participants (0%; 95% confidence interval, 0% to 3.7%) tested positive by OraQuick ADVANCE, and all were confirmed to be uninfected by HIV-1 viral ribonucleic acid testing. One hundred eighteen of the 120 (98.3%) participants had a reactive HIV test for VISP/VISR: 77 (64%) had at least 1 reactive fourth-generation HIV-1 diagnostic test (P < .0001 vs no reactive OraQuick ADVANCE results), and 41 (34%) only had a reactive test by the less specific third-generation Abbott Prism assay. These data suggest that this widely available patient-controlled test has limited reactivity to HIV-1 antibodies elicited by these candidate HIV-1 vaccines.


A view on EGFR-targeted therapies from the oncogene-addiction perspective.
Tumor cell growth and survival can often be impaired by inactivating a single oncogen- a phenomenon that has been called as "oncogene addiction." It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. a critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the "EGFR addiction" phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.


D-dimer elevation and paresis predict thromboembolic events during bevacizumab therapy for recurrent malignant glioma.
The major side-effects of bevacizumab in glioma treatment are venous thromboembolic events (VTE). We retrospectively evaluated factors potentially predictive of thromboembolic events. Bevacizumab, alone or in combination with chemotherapy was used as salvage therapy for recurrence in malignant glioma every two weeks. None but one patient received anti-coagulants. Before each bevacizumab cycle differential blood cell count, kidney and liver parameters, D-dimers, neurological status, body-mass index, vital signs and signs of venous thrombosis were assessed. Thirty-eight patients received 428 cycles of bevacizumab. In five patients (13%), six VTE were observed. These complications were preceded four weeks before the onset of symptoms by D-dimer elevation above 0.865 mg/l [p<0.0001; sensitivity=89% (95% confidence interval=83-93%); specificity=89% (95% CI=52-100%)]. An existing hemiparesis constituted a 27-fold risk elevation for thrombotic complication (p<0.0001, χ(2)-test). D-Dimer elevation or hemiparesis predict VTE under bevacizumab and chemotherapy, four weeks before the event becomes clinically apparent. Future investigations should determine if prophylactic anti-coagulants for patients at risk may reduce the risk of VTE.


Surface Immobilization of pH-Responsive Polymer Brushes on Mesoporous Silica Nanoparticles by Enzyme Mimetic Catalytic ATRP for Controlled Cargo Release.
Peroxidase mimetic catalytic atom transfer radical polymerization (ATRP) was first used to install tertiary amine-functionalized polymer brushes on the surface of mesoporous silica nanoparticles (MSNs) in a facile and highly efficient manner. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes-grafted MSNs were fabricated by biocompatible deuterohemin-β-Ala-His-Thr-Val-Glu-Lys (DhHP-6)-catalyzed surface-initiated ATRP (SI-ATRP). The resulting organic⁻inorganic hybrid nanocarriers were fully characterized by Fourier transform-infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), SEM, TEM, Elemental analysis, Zeta-potential, and N₂ adsorption⁻desorption isotherms, which demonstrated the successful coating of pH-responsive polymers on the MSN surface. Rhodamine 6G (Rh6G) dyes were further loaded within the mesopores of this nanocarrier, and the release of Rh6G out of MSNs in a controlled fashion was achieved upon lowing the solution pH. The electrostatic repulsion of positively-charged tertiary ammonium of PDMAEMAs in acidic environments induced the stretching out of polymer brushes on MSN surfaces, thus opening the gates to allow cargo diffusion out of the mesopores of MSNs.


A developmental look at an auditory illusion: the precedence effect.
Infants aged 2 and 6 months were tested with the precedence effect, an auditory phenomenon involving sound localization. Each infant was tested with two types of stimuli: sound from a single loudspeaker and precedence-effect sounds produced by the same sound put through two loudspeakers, with one output leading the other by 7 msec. Older infants localized precedence-effect stimuli as they did single-source stimuli, indicating that they perceived this phenomenon as expected. Two-month-olds turned their heads toward single-source sounds, but did not localize precedence-effect sounds, suggesting that that more difficult perceptual task had not been achieved at this age. In general, head-turning toward sound proved far more difficult to elicit in younger infants. A click train was ineffective, but a tape-recorded human voice elicited above-chance low-level turning. The developmental changes in auditory behavior are discussed in terms of the rapid growth of the auditory cortex.


Predominance of Staphylococcus Correlates with Wound Burden and Disease Activity in Dystrophic Epidermolysis Bullosa: A Prospective Case-Control Study.
Recessive dystrophic epidermolysis bullosa is characterized by skin blistering and wounds. To uncover the changes in the skin and mucosal microbiome related to age and disease progression and microbiome impact on clinical and inflammatory laboratory parameters, swabs from wounded and unwounded skin, oral mucosa, and stool samples of 28 children with recessive dystrophic epidermolysis bullosa and 28 healthy controls were subjected to 16S-ribosomal RNA gene sequencing. Skin microbiome of patients with recessive dystrophic epidermolysis bullosa showed significantly reduced alpha diversity compared with that of healthy controls and showed significantly early, age-dependent predominance of Staphylococcus aureus, first in wounded skin and then in unwounded skin. These findings were more pronounced in the severe disease with higher abundances of S. aureus than in intermediate disease. S. aureus abundance correlated significantly with both acute and chronic wound burden. Changes in oral mucosal and gut microbiome were discrete, with no significant differences in alpha diversity. Our findings show that children with recessive dystrophic epidermolysis bullosa experience skin microbiome changes early in life. Longitudinal studies should confirm that dysbiosis starts in wounds and later extends to unwounded skin. The predominance of S. aureus significantly correlates with wound burden and disease activity and, to some extent, with systemic inflammation.


Resettlement experiences and alternatives in Thailand.
Problems concerning the resettlement of those made homeless by the construction of dams to create reservoirs in Thailand are considered. The authors attempt "firstly, to examine the rationale for spontaneous and planned resettlement in Thailand. Secondly, the determinants of the success or failure of resettlers are explored with reference to selected planned resettlement projects. Finally, resettlement alternatives for prospective reservoir evacuees are proposed."


[Study on the cause of tuberculosis recurrence by Mycobacterium tuberculosis genotyping method].
To study the contribution of exogenous reinfection to tuberculosis recurrence. Mycobacterium tuberculosis isolates from patients who had experienced 2 successive tuberculosis episodes during the years from January 1999 to March 2004 were genotyped by mycobacterial interspersed repetitive units (MIRU) method. The cause of tuberculosis recurrence was determined by comparing the MIRU pattern of Mycobacterium tuberculosis isolates responsible for different tuberculosis episodes from patients. Of 37 qualified patients with recurrent tuberculosis, the isolates from 25 patients in their two tuberculosis episodes showed different MIRU patterns, indicating that 68% recurrent patients were due to exogenous reinfection. The exogenous reinfection rate decreased with the age from 3/3 (under 30 years) to 73% (11/15, 30 to 60 years) and 58% (11/19, over 60 years). The frequency of exogenous reinfection increased with the tuberculosis recurrent interval. Within 6 months, the exogenous reinfection accounted for 58% (7/12) of all the recurrence, while for the time more than one year, the percentage increased to 79% (11/14). Exogenous reinfection was a major cause of tuberculosis recurrence in Shanghai. MIRU genotyping method is useful to study the cause of tuberculosis recurrence.


[Studies on Chlamydia pneumoniae, strain TWAR infection. 2. Seroepidemiology of TWAR on healthy controls and patients with acute respiratory infections].
To determine of Chlamydia pneumoniae, TWAR infection is common in Japan. The author performed a spot antibody prevalence study of adults and children living in Okayama prefecture. This study was carried out by microplate immunofluorescence antibody technique (MFA) using in situ inclusions of Chlamydia pneumoniae (TW-183), Chlamydia trachomatis (L2) and Chlamydia psittaci (Cal 10) as antigens respectively. And each chlamydial antiserum IgG, IgA, IgM titers were determined by the dilution and point for specific staining of the inclusions. The author studied people with and without evidence of acute respiratory infections, as determined by physical examination and medical history. 2050 sera of 1477 cases were collected from both groups between 1987 and 1989. The criteria for judgement the positivity of antibodies to chlamydia species are as follows: By comparing the IgG antibody titers determined with different chlamydia antigen, a case was regarded as having an antibody specific to a particular chlamydia species when the titer was highest for that strain and the titer was greater than x 64. In cases which blood was collected more than once, the point in time at which IgG showed the highest titer was used. TWAR specific antibody was detected to be 52/143 cases (36.4%) of healthy children (age 0-15) and 319/531 cases (60.1%) of healthy adults (age 16-85). It was also detected to be 134/478 cases (27.9%) of child patients with acute respiratory infections (age 0-15), and 231/325 cases (71.1%) of adult patients (age 16-95).(ABSTRACT TRUNCATED AT 250 WORDS)


Development of agroecology in Austria and Germany.
Background: Transforming food systems is necessary to address the global issues of severe biodiversity loss, hunger, and malnutrition as well as the consequences of the rapidly advancing climate change. Agroecology as a systemic approach has been recognised as a promising path of change exemplified in various case studies strengthening this transformation. The aim of this study is to get insight specifically for Austria and Germany in providing an overview of the advancement in agroecology in both countries and identify agroecology-related initiatives. Methods: 21 interviews with experts were conducted to determine the recognition, understanding, and development of agroecology in Austria and Germany in terms of movement, practice, policies, education, and research. In addition, information about agroecology-related initiatives was collected from interviews with 24 representatives of initiatives and literature analysis. Data was analysed according to five activity categories under which agroecology manifest: movement, practice, living lab, science and research infrastructure, and training and education. Results: Results show that the term agroecology is not commonly used in Austria and Germany, where the concept is mainly associated to a scientific discipline. Practices considered agroecological are implemented primarily through organic agriculture, which is very developed in Austria and to a lesser extent in Germany. Many networks, food policy councils, associations, and scientific projects related to agroecology exist, each with specific purposes and ambitions to change farming and food systems. While most selected initiatives do not explicitly refer to agroecology, all follow certain agroecological principles and aim at contributing to accelerate the agroecological transition. Conclusions: Clarifying the concept of agroecology, overcoming economic and political barriers as well as fostering participation of a multitude of stakeholders in the transition is essential for the future development of agroecology in Austria and Germany.


1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists.
3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A2B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A2B adenosine receptors (ARs). 1,8-disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A2B ARs, but generally less potent at A1 and A2A, and much less potent at A3 ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A2B ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthine (17) was the most selective compound of the present series, exhibiting a K(i) value of 53 nM at human A2B ARs and showing greater than 180-fold selectivity versus human A1 ARs. Compound 17 was also highly selective versus rat A1 ARs (41-fold) and versus the other human AR subtypes (A2A > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another polar analogue bearing a carboxylate function, exhibited a K(i) value of 24 nM for A2B ARs, 49-fold selectivity versus human and 20-fold selectivity versus rat A1 ARs, and greater than 150-fold selectivity versus human A2A and A3 ARs. 8-[4-(2-Hydroxyethylamino)-2-oxoethoxy)phenyl]-1-propylxanthine (29) and 1-butyl-8-[4-(4-benzyl)piperazino-2-oxoethoxy)phenyl]xanthine (35) were among the most potent A2B antagonists showing K(i) values at A2B ARs of 1 nM, 57-fold (29) and 94-fold (35) selectivity versus human A1, ca. 30-fold selectivity versus rat A1, and greater than 400-fold selectivity versus human A2A and A3 ARs. The new potent, selective, water-soluble A2B antagonists may be useful research tools for investigating A2B receptor function.


Hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery: is there any impact of fractionation schedule?
The optimal schedule for palliative external beam radiotherapy (EBRT) in patients with bladder tumors with hematuria unfit for surgery remains undefined. This study aimed to assess the clinical hemostatic efficacy and safety of two EBRT hypofractionated schedules. From February 2008 to October 2017, 31 patients were referred to our department for palliative hemostatic bladder irradiation. EBRT consisted of two schedules: "continuous" treatment (CRT) was delivered following consecutive 3-10 weekdays (3-6Gy/fraction (fr), to a total dose of 18-30Gy) (n=14); the "discontinuous" schedule (DRT) consisted of 23Gy in 4fr (6.5Gy/fr on days 1 and 3, followed by 5Gy/fr on days 15 and 17; n=12). The primary endpoint was the rate of hemostatic control (HC) at the end of the radiation course. Other endpoints included mid-term HC, toxicities and overall survival. Comparative analyses were performed by exact Fisher test with a cut-off of 0.05 for statistical significance. The rate of HC at the end of EBRT was 92% (n=24) with no differences between CRT and DRT (100% vs 86%; p=0.48). The median follow-up was 6 months, HC was achieved in 15/26 (58%) patients at the last follow-up, without meaningful differences between CRT and DRT (50% vs 67%; p=0.45). Three and two patients developed acute grade ≤2 diarrhea in CRT and DRT groups, respectively. Our study suggests that both hypofractionated "continuous" and "discontinuous" EBRT are well tolerated and represent acceptable schedules for patients with limited life expectancy. DRT schedule could be preferred for departments' organization to increase the slots for the treatment of other referred patients for radiotherapy.


Influence of Resin Cement Thickness and Elastic Modulus on the Stress Distribution of Zirconium Dioxide Inlay-Bridge: 3D Finite Element Analysis.
The mechanical properties and the thickness of the resin cement agents used for bonding inlay bridges can modify the clinical performance of the restoration such as debonding or prosthetic materials fracture. Thus, the aim of this study was to evaluate the stress distribution and the maximum strain generated by resin cements with different elastic moduli and thicknesses used to cement resin-bonded fixed partial denture (RBFPD). A three-dimensional (3D) finite element analysis (FEA) was used, and a 3D model was created based on a Cone-Beam Computed Tomography system (CBCT). The model was analyzed by the Ansys software. The model fixation occurred at the root of the abutment teeth and an axial load of 300 N was applied on the occlusal surface of the pontic. The highest stress value was observed for the Variolink 0.4 group (1.76 × 106 Pa), while the lowest was noted for the Panavia 0.2 group (1.07 × 106 Pa). Furthermore, the highest total deformation value was found for the Variolink 0.2 group (3.36 × 10-4 m), while the lowest was observed for the Panavia 0.4 group (2.33 × 10-4 m). By means of this FEA, 0.2 mm layer Panavia F2.0 seemed to exhibit a more favorable stress distribution when used for cementation of posterior zirconium-dioxide-based RBFPD. However, both studied materials possessed clinically acceptable properties.


Water equivalent plastic scintillation detectors in radiation therapy.
A review of the dosimetric characteristics and properties of plastic scintillation detectors for use in radiation therapy is presented. The detectors show many desirable qualities when exposed to megavoltage photon and electron beams, including water equivalence, energy independence, reproducibility, dose linearity, resistance to radiation damage and near temperature independence. These detectors do not require the usual conversion and/or correction factors used to convert the readings from common dosemeters to absorbed dose. Due to their small detecting volume, plastic scintillation detectors exhibit excellent spatial resolution. Detector performance, in certain specific cases, can be affected by radiation-induced light arising in the optical fibres that carry the scintillator signal to a photodetector. While this effect is negligible for photon beams, it may not be ignored for electron beams and needs to be accounted for.


Knowledge and Attitude of Pharmacy Students Regarding Geriatric Care: Questionnaire-Based Analysis in Malaysia.
There is a predicted growth of up to 17% in an older adult of Malaysian above 60 years of age by 2040. This will increase the workload of almost every healthcare provider to ensure optimal geriatric care. This study aimed to assess pharmacy students' knowledge and attitudes towards geriatric pharmacy education and older patients to determine their preparation in delivering appropriate medical care to the geriatric population. Self-administered questionnaires were distributed among pharmacy students in different Malaysian universities. The survey included several sections to assess multiple aspects such as sociodemographic information, assessment of knowledge using a validated 28-item Geriatric Knowledge Assessment Scale (GKAS), and attitudes towards geriatrics education. The response rate was around 70% of the respondents. The mean (± standard deviation) age of the cohort was 22.28 (±1.12) years. Despite around 78% of pharmacy students claiming that their knowledge of geriatric care is adequate, their GKAS score showed that only around 20% have high geriatric knowledge. Around 80% of them showed a positive attitude on the importance of taking courses focused on geriatric care and demonstrated interest to further knowledge and training in geriatric care. However, more than half of the students were uncertain of their answers towards their attitudes regarding older patients. Given the growing role of pharmacists in the ageing population, this study highlights the importance of geriatric care education among potential pharmacists. Therefore, we urge the need to improve/develop geriatrics education and training into the pharmacy curriculum to ensure sufficient preparation for actual practice after graduation.


Mini-access for retroperitoneal laparoscopy.
The purpose of this study was to establish the feasibility of primary mini-access to the retroperitoneal space to perform certain retroperitoneoscopic procedures in which an enlarged port is not required for extraction of the specimen. Mini-laparoscopy or needlescopic laparoscopy has been performed in the past via the transperitoneal route, but this has not yet been reported for a retroperitoneoscopic procedure. Through a 5-mm primary access and 3- or 5-mm secondary ports, retroperitoneoscopic surgery was performed in seven adults for ureterolithotomy, renal biopsy, simple nephrectomy, nephropexy, cyst decortication, or drainage of a subphrenic abscess. The access technique used was a mini-version of a previously described percutaneous access technique with some modifications. The retroperitoneoscopic procedure was successful in all seven patients, and no complications developed. The operative time, blood loss, analgesic intake, and length of hospital stay were comparable with those of a standard retroperitoneoscopic procedure. However, the cosmetic results were better. Mini-retroperitoneoscopy is feasible and is a better alternative for patients in whom the whole procedure can be performed through 5-mm or smaller ports.


Determination of gatifloxacin in human plasma by liquid chromatography/electrospray tandem mass spectrometry.
Gatifloxacin is an advanced-generation, 8-methoxyfluoroquinolone that is active against a broad spectrum of pathogens, including antiobiotic resistant Streptococcus pneumoniae. Development of a rapid, sensitive and selective method for the determination of gatifloxacin in human plasma is essential for understanding the pharmacokinetics of the drug when administered orally or intravenously. Solid phase extraction (SPE) using Oasis HLB was used to extract gatifloxacin and the internal standard ciprofloxacin from plasma. A method based on liquid chromatography/electrospray tandem mass spectrometry (LC/ESI-MS/MS) was developed and validated to quantitate gatifloxacin in human plasma. The precursor and major product ions of the analyte were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Mechanisms for the formation of collision-induced dissociation products of gatifloxacin are proposed. Linear calibration curves were generated from 10--1000 ng/mL with coefficients of determination greater than 0.99. The interday and intraday precision (%RSD) was less than 6.0% and accuracy (%error) was less than 5.4% for gatifloxacin. The limit of detection (LOD) for the method was 500 pg/mL based on a signal-to-noise ratio of 3.


Modulation of Respiratory System by Limb Muscle Afferents in Intact and Injured Spinal Cord.
Breathing constantly adapts to environmental, metabolic or behavioral changes by responding to different sensory information, including afferent feedback from muscles. Importantly, not just respiratory muscle feedback influences respiratory activity. Afferent sensory information from rhythmically moving limbs has also been shown to play an essential role in the breathing. The present review will discuss the neuronal mechanisms of respiratory modulation by activation of peripheral muscles that usually occurs during locomotion or exercise. An understanding of these mechanisms and finding the most effective approaches to regulate respiratory motor output by stimulation of limb muscles could be extremely beneficial for people with respiratory dysfunctions. Specific attention in the present review is given to the muscle stimulation to treat respiratory deficits following cervical spinal cord injury.


Bipolar Disorder and/or Creative Bipolarity: Robert Schumann's Exemplary Psychopathology - Combining Symptomatological and Psychosocial Perspectives with Creativity Research.
The psychopathological condition of Robert Schumann has been a prominent object of study in psychiatry since his hospitalization in 1854. Renowned psychiatrists have diagnosed Schumann with syphilis, schizophrenia, and bipolar and personality disorders. Until today, these analyses of his symptomatology have led to contradictory results. Recent discussion has suggested that his hospitalization was due to professional failure and separation wishes on the part of his wife, her family, and her friends. In line with this hypothesis is the opinion that the separation insisted upon by Clara Schumann was reinforced by the economic interests of the psychiatrist who kept Schumann in custody for 2 years until his death in 1856. In this article, we trace the complex interaction of bipolar vulnerability and pathogenic life events with hypersensitive talent and "creative bipolarity," defined as the capacity, motivation, and resilience to transform emotional stress and cognitive inconsistency into coherent artistic products. Finally, we present our conclusions about comprehensive psychiatric and psychotherapeutic treatment with respect to "creative bipolarity."


Liposome-Mediated In Situ Formation of Type-I Heterojunction for Amplified Photoelectrochemical Immunoassay.
Exploiting innovative sensing mechanisms and their rational implementation for selective and sensitive detection has recently become one of the mainstream research directions of photoelectrochemical (PEC) bioanalysis. In contrast to existing conventional strategies, this study presents a new liposome-mediated method via in situ combining ZnInS nanosheets (ZIS NSs) with SnS2 to form a ZIS NSs/SnS2 type-I heterojunction on fluorine-doped tin oxide (FTO) electrodes for highly sensitive PEC immunoassays. Specifically, alkaline phosphatase (ALP)-encapsulated liposomes were confined within 96-well plates by sandwich immunorecognition and subsequently subjected to lysis treatment. Enzymatically produced H2S by the released ALP was then directed to react with Sn(IV) to engender the ZIS NSs/SnS2 type-I heterojunction on the FTO/ZIS NSs-Sn(IV) electrode, resulting in a change in the photogenerated electron-hole transfer path of the photoelectrode and reduction in current signaling. Exemplified by heart-type fatty acid binding protein (h-FABP) as a target, the constructed PEC sensor showed good stability and selectivity in a biosensing system. Under optimal conditions, the as-prepared sensing platform displayed high sensitivity for h-FABP with a dynamic linear response range of 0.1-1000 pg/mL and a lower detection limit of 55 fg/mL. This research presents the liposome-mediated PEC immunoassay based on in situ type-I heterojunction establishment, providing a new protocol for analyzing various targets of interest.