Kinetic resolution of substituted amido[2.2]paracyclophanes via asymmetric electrophilic amination.
Planar chiral [2.2]paracyclophane derivatives are a type of structurally intriguing and practically useful chiral molecules, which have found a range of important applications in the field of asymmetric catalysis and material science. However, access to enantioenriched [2.2]paracyclophanes represents a longstanding challenge in organic synthesis due to their unique structures, which are still highly dependent on the chiral chromatography separation technique and classical chemical resolution strategy to date. In this work, we report on an efficient and versatile kinetic resolution protocol for various substituted amido[2.2]paracyclophanes, including those with pseudo-geminal, pseudo-ortho, pseudo-meta and pseudo-para disubstitutions, using chiral phosphoric acid (CPA)-catalyzed asymmetric amination reaction, which was also applicable to the enantioselective desymmetrization of an achiral diamido[2.2]paracyclophane. Detailed experimental studies shed light on a new reaction mechanism for the electrophilic aromatic C-H amination, which proceeded through sequential triazane formation and N[1,5]-rearrangement. The facile large-scale kinetic resolution reaction and diverse derivatizations of both the recovered chiral starting materials and the C-H amination products showcased the potential of this method.


Q fever epidemiology in Roumania.
A review on Q fever epidemiologic aspects in Roumania from the first case report in 1947 up to the actual cases is presented. It includes the dynamics of the number of cases, features of epidemics, results of surveys on slaughterhouse workers and laboratory-acquired cases, results of serologic surveys in domestic animals, and of wild life studies. Special attention is given to the sporadic character of the present cases in Roumania with emphasis on the seasonal repartition of cases, occupation of subjects, and urban versus rural proportion of cases. The necessity of elucidation of the mechanism of generation of actual cases is emphasized since no relation with the usual animal sources could be established.


Aurophilicity in action: stepwise formation of dinuclear Au(i) macrocycles with rigid 1,8-dialkynylanthracenes.
Two phosphane-gold(i) functions (with tri(para-tolyl)- or tri-n-butylphosphane) were attached to a 1,8-diethynylanthracene backbone. The ligand size prevents direct interaction between the gold atoms, but the initial products rearrange to form macrocyclic anions comprising two 1,8-diethynylanthracene and two gold units, linked to cationic gold(i) fragments by maximising aurophilic interactions.


Response properties and descending control of rat dorsal horn neurons with deep receptive fields.
The study was designed to obtain information on the spinal processing of input from receptors in deep somatic tissues (muscle, tendon, joint). In anaesthetized rats, the impulse activity of single dorsal horn cells was recorded extracellularly. In a pilot series, the proportion of neurons responding to mechanical stimulation of deep tissues was determined: 46.7% had receptive fields in the skin only, 35.5% could only be driven from deep tissues (deep cells), and 17.7% possessed a convergent input from both skin and deep tissues (cutaneous-deep cells). In each category, neurons with low and high mechanical thresholds were encountered. Experiments employing a reversible cold block of the spinal cord showed that deep cells with high threshold were subject to a stronger descending inhibition than low-threshold deep cells. In cutaneous-deep neurons the input combination high-threshold cutaneous and high-threshold deep was the most frequent one (48.7% of the cutaneous-deep cells). In these presumably nociceptive cells the descending inhibition had a differential action in that the input from deep tissues was more strongly affected than was the cutaneous input to the same neuron. The recording sites of the neurons with deep input were located in the superficial dorsal horn and in and around lamina V. The results suggest that in the rat a considerable proportion of dorsal horn cells receives input from deep nociceptors and that this input is controlled by descending pathways in a rather selective way.


Accelerated stochastic simulation algorithm for coupled chemical reactions with delays.
Some biochemical processes do not occur instantaneously but have considerably delays associated with them. In the existed methods which solve these chemically reacting systems with delays, averaging over a great deal of simulations is needed for reliable statistical characters. Here we present an accelerating approach, called the "Delay Final All Possible Steps" (DFAPS) approach, which does not alter the course of stochastic simulation, but reduces the required running times. Numerical simulation results indicate that the proposed method can be applied to a wide range of chemically reacting systems with delays and obtain a significant improvement on efficiency and accuracy over the existed methods.


Effect of Putrescine, 4-PU-30, and Abscisic Acid on Maize Plants Grown under Normal, Drought, and Rewatering Conditions.
The experiments were carried out with maize (Zea mays L.) seedlings, hybrid Kneja 530, grown hydroponically in a growth chamber. Twelve-day-old plants were foliar treated with putrescine, N1-(2-chloro-4-pyridyl)-N2-phenylurea (4-PU-30), and abscisic acid (ABA) at concentrations of 10(-5) m. Twenty-four hours later the plants were subjected to a water deficit program, induced by 15% polyethylene glycol (PEG; molecular weight, 6,000). Three days after drought stress half of the plants were transferred to nutrient solution for the next 3 days. The effects of the water shortage, rewatering, and plant growth regulator (PGR) treatment on the fresh and dry weights, leaf pigment content, proline level, relative water content (RWC), transpiration rate, activities of catalase and guaiacol peroxidase, hydrogen peroxide content, and level of the products of lipid peroxidation were studied. It was established that the application of PGRs alleviated to some extent the plant damage provoked by PEG stress. At the end of the water shortage program the plants treated with these PGRs possessed higher fresh weight than drought-subjected control seedlings. It was found also that putrescine increased the dry weight of plants. Under drought, the RWC and transpiration rate of seedlings declined, but PGR treatment reduced these effects. The accumulation of free proline, malondialdehyde, and hydrogen peroxide was prevented in PGR-treated plants compared with the water stress control. The results provided further information about the influence of putrescine, 4-PU-30, and ABA on maize plants grown under normal, drought, and rewatering conditions. Key Words. Maize-Putrescine-4-PU-30-ABA-Drought


Magnetoimpedance of Epitaxial Y3Fe5O12 (001) Thin Film in Low-Frequency Regime.
The atomically flat interface of the Y3Fe5O12 (YIG) thin film and the Gd3Ga5O12 (GGG) substrate plays a vital role in obtaining the magnetization dynamics of YIG below and above the anisotropy field. Here, magnetoimpedance (MI) is used to investigate the magnetization dynamics in fully epitaxial 45 nm YIG thin films grown on the GGG (001) substrates using a copper strip coil in the MHz-GHz frequency region. The resistance (R) and reactance (X), which are components of impedance (Z), allow us to probe the absorptive and dispersive components of the dynamic permeability, whereas a conventional spectrometer only measures the field derivative of the power absorbed. The distinct excitation modes arising from the resonance in the uniform and dragged magnetization states of YIG are respectively observed above and below the anisotropy field. The magnetodynamics clearly shows the visible dichotomy between two resonant fields below and above the anisotropy field and its motion as a function of the direction of the applied magnetic field. A low value of a damping factor of ∼4.7 - 6.1 × 10-4 is estimated for uniform excitation mode with an anisotropy field of 65 ± 2 Oe. Investigation of below and above anisotropy field-dependent magnetodynamics in the low-frequency mode can be useful in designing the YIG-based resonators, oscillators, filters, and magnonic devices.


Effect of cellulose reinforcement on the properties of organic acid modified starch microparticles/plasticized starch bio-composite films.
The present paper describes the preparation and characterization of polysaccharides-based bio-composite films obtained by the incorporation of 10, 20 and 30 wt% birch cellulose (BC) within a glycerol plasticized matrix constituted by the corn starch (S) and chemical modified starch microparticles (MS). The obtained materials (coded as MS/S, respectively MS/S/BC) were further characterized. FTIR spectroscopy and X-ray diffraction were used to evidence structural and crystallinity changes in starch based films. Morphological, thermal, mechanical, and water resistance properties were also investigated. Addition of cellulose alongside modified starch microparticles determined a slightly improvement of the starch-based films water resistance. Some reduction of water uptake for any given time was observed mainly for samples containing 30% BC. Some compatibility occurred between MS and BC fillers, as evidenced by mechanical properties. Tensile strength increased from 5.9 to 15.1 MPa when BC content varied from 0 to 30%, while elongation at break decreased significantly.


Systematic review of studies using platelet serotonin content to assess bioeffect of serotonin reuptake inhibitors at the serotonin transporter.
Assessment of the bioeffect of serotonin reuptake inhibitors (SRIs, including both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)) at the serotonin transporter (SERT) in patients and healthy controls can have important theoretical and clinical implications. Bioeffect at SERT has been assessed by neuroimaging of brain SERT occupancy, through in vitro measurements of platelet serotonin (5-HT) uptake, and by measuring platelet 5-HT content pre- and post-initiation of SRI administration. Studies of platelet 5-HT content were reviewed in order to (1) determine the overall apparent bioeffect of SRIs; (2) compare bioeffect across types of SRIs; (3) compare the three approaches to assessing SRI bioeffect; and (4) determine how the findings might inform clinical practice. We performed a systematic review of the published studies that measured platelet 5-HT content to assess SRI bioeffect at the platelet SERT. Studies using neuroimaging and in vitro platelet 5-HT uptake to assess SRI bioeffect were reviewed for comparison purposes. Clinical doses of SRIs typically resulted in 70-90% reductions in platelet 5-HT content. The observed bioeffect at the platelet SERT appeared similar among different SSRIs and SNRIs. The bioeffect estimations based on platelet 5-HT content were consistent with those obtained using neuroimaging to assess brain SERT occupancy and those based on the in vitro measurement of platelet 5-HT uptake. In general, excellent agreement was seen in the apparent SRI bioeffect (70-90% inhibition) among the platelet 5-HT content studies and across the three bioeffect approaches. Theoretical and practical clinical implications are discussed.


The critical period for development of secondary restenosis following post-intubation tracheal stenosis surgery.
Determining a predictable duration to restenosis very essential for reducing mortality and morbidity for tracheal stenosis surgery. The aim of this study was to determine the critical periods for secondary restenosis risk for operated patients with post-intubation tracheal stenosis (PITS) during the initial healing period. A total of 61 patients with a diagnosis of surgically treated PITS were included in the study. Treatment groups were carbon dioxide (CO2) laser and tracheal resection with primary anastomosis (TRPA). Duration to restenosis was compared with Kaplan-Meier curves between study groups. Restenosis developed in 11 (18.0%) patients and was diagnosed after a mean of 39.3 ± 38.5 (range, 22 to 155) days. Gender or Cotton-Myer grade of the PITS was not found to be risk factors for the development of stenosis. Restenosis rate was 33.3% in CO2 laser group and 10% in the TRPA group (p = .036). Duration to restenosis was detected at a median of 28 days in patients treated with CO2 laser, and a median of 30 days in patients treated with TRPA (p = .024). The most critical period for the development of restenosis after PITS treatment is the third and fourth weeks, especially in patients treated with CO2 laser.


Orthodontic bracket debonding: risk of enamel fracture.
Until now, it is not clear if various procedures of bracket debonding differ with regard to their risk of enamel fracture. Therefore, the objective of the present study was to compare these procedures biomechanically for assessing the risk of complications. An anisotropic finite element method (FEM) model of the mandibular bone including periodontal ligament, enamel, dentin, and an orthodontic bracket was created. The morphology based on the CT data of an anatomical specimen. Typical loading conditions were defined for each method of bracket debonding (compression, shearing off, twisting off). Shortly before the adhesive's break, the induced stress in enamel, periodontal ligament, and in the alveolar bone was measured. The statistical analysis of the obtained values was performed in SPSS 19.0. Relatively high stresses occurred in the enamel using frontal torque (max. 44.18 MPa). With shearing off, the stresses were also high (max. 41.96 MPa), and additionally high loads occurred on the alveolar bone as well (max. 11.79 MPa). Moderate maximum values in enamel and alveolar bone appeared during the compression of the bracket wings (max. 37.12 MPa) and during debonding by lateral torque (max. 35.18 MPa). The present simulation results indicate that the risk of enamel fracture may depend on the individual debonding procedure. Further clinical trials are necessary to confirm that. For patients with prior periodontal disease or loosened teeth, a debonding procedure by compression of the bracket wings is recommended, since here the load for the periodontal structures of the tooth is lowest.


Identifier sequences are transcribed specifically in brain.
'Identifier' or ID sequences are present in 62% of the RNA polymerase II and III transcripts made in vitro from brain nuclei but in fewer than 4% of the transcripts made from the nuclei of other tissues. An homologous 160-nucleotide cytoplasmic poly(A)+ RNA species, BC1, and a smaller species, BC2, are located in vivo exclusively in neural tissues. Cloned ID sequences are polymerase III templates in vitro. Our data suggest a model in which brain-specific polymerase III transcription of ID sequences located in introns of brain genes activates those genes in a primary manner for polymerase III transcription.


Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). II. Evaluation in a variety of clinical conditions.
Plasmas from patients with a wide variety of thrombotic and presumed prethrombotic conditions were examined for high molecular weight crosslinked fibrin degradation products (known as X-oligomers) using a two-site enzyme-linked immunospecific assay (ELISA). This assay employed a catcher-tag principle using two monoclonal antibodies (mabs) directed towards different epitopes on the complex X-oligomer fraction. In general, thrombotic events (pulmonary embolism, PE, myocardial infarction, MI, peripheral vascular disease, PVD, and disseminated intravascular coagulation, DIC) were accompanied by elevated levels of X-oligomers in the plasma. During pregnancy the value of X-oligomer assays was demonstrated to be a clear-cut marker for pre-eclampsia. Patients following a variety of forms of surgery present with heterogeneous plasma levels of X-oligomers and this may merely reflect the formation and lysis of the fibrin formed during and after surgery. The possible value of this ELISA procedure in monitoring thrombolytic therapy is discussed with a critical analysis of the data presented herein. While the assay of X-oligomer was demonstrated to be a valuable marker of fibrinolysis in plasma, more extensive data are required in order to assess whether such an assay is of diagnostic value in thrombosis-related conditions.


Correlation Between the Total Small Bowel Length and Anthropometric Measures in Living Humans: Cross-Sectional Study.
Variation in the outcome of bariatric surgery is still an unraveled phenomenon. This variation could be multifactorial. Several reports implicate the total small bowel length (TSBL) in this process. However, the basic information regarding the normal bowel length and its relation to the anthropometric parameters of the living subject is scarce. This study aims at reporting the normal total bowel length in living adult humans and its correlation with the anthropometric parameters. This study included 606 participants (380 females and 226 males). Their mean age was 39.8 ± 11 years, weight = 135.7 ± 29.7 kg, height = 165 ± 9 cm, and BMI = 49.5 ± 7.5 kg/m2. The mean TSBL was 630 ± 175 cm. There was a statistically significant but very weak positive correlation but between the TSBL and both weight and height. Males had significantly higher weight and were significantly taller compared with females. TSBL was significantly longer in males at 661.5 ± 186 cm versus 612 ± 164 cm in females. The study reports an average TSBL greater than what is reported in the literature from living humans with a greater range of variation. There is no clinically important correlation between the TSBL and the weight and height of the individual participants in this series.


In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has resulted in significant global morbidity, mortality, and societal disruption. Currently, effective antiviral drugs for the treatment of SARS-CoV-2 infection are limited. Therefore, safe and effective antiviral drugs to combat COVID-19 are urgently required. In previous studies, we showed that 3-indoleacetonitrile, a plant growth hormone produced by cruciferous (Brassica) vegetables, is effective in treating influenza A virus infection. However, the molecular mechanisms underlying these effects remain unclear. Herein, we demonstrated that 3-indoleacetonitrile exhibits broad-spectrum antiviral activity and is effective against HSV-1 and VSV infections in vitro. This phenomenon prompted us to study its role in the anti-SARS-CoV-2 process. Interestingly, 3-indoleacetonitrile exhibited antiviral activity against SARS-CoV-2 in vitro. Importantly, tail vein injection of 3-indoleacetonitrile resulted in good antiviral activity in mouse models infected with WBP-1 (a mouse adaptation of the SARS-CoV-2 strain). Mechanistically, 3-indoleacetonitrile promoted the host interferon signalling pathway response and inhibited autophagic flux. Furthermore, we demonstrated that 3-indoleacetonitrile induced an increase in mitochondrial antiviral-signalling (MAVS) protein levels, which might be attributed to its inhibition of the interaction between MAVS and the selective autophagy receptor SQSTM1. Overall, our results demonstrate that 3-indoleacetonitrile is potently active against SARS-CoV-2 in vitro and in vivo, which may provide a foundation for further clinical testing for the treatment of COVID-19. In addition, considering its broad-spectrum antiviral effect, it should be explored whether it also has an effect on other viruses that threaten human health.


A vehicle-mounted dual-smog chamber: Characterization and its preliminary application to evolutionary simulation of photochemical processes in a quasi-realistic atmosphere.
Smog chambers are the effective tools for studying formation mechanisms of air pollution. Simulations by traditional smog chambers differ to a large extent from real atmospheric conditions, including light, temperature and atmospheric composition. However, the existing parameters for mechanism interpretation are derived from the traditional smog chambers. To address the gap between the traditional laboratory simulations and the photochemistry in the real atmosphere, a vehicle-mounted indoor-outdoor dual-smog chamber (JNU-VMDSC) was developed, which can be quickly transferred to the desired sites to simulate quasi-realistic atmosphere simultaneously in both chambers using "local air". Multiple key parameters of the smog chamber were characterized in the study, demonstrating that JNU-VMDSC meets the requirements of general atmospheric chemistry simulation studies. Additionally, the preliminary results for the photochemical simulations of quasi-realistic atmospheres in Pearl River Delta region and Nanling Mountains are consistent with literature reports on the photochemistry in this region. JNU-VMDSC provides a convenient and reliable experimental device and means to study the mechanism of atmospheric photochemical reactions to obtain near-real results, and will make a great contribution to the control of composite air pollution.


The relationship between three well-characterized polymorphisms of the angiotensin converting enzyme gene and lung cancer risk: a case-control study and a meta-analysis.
The gene encoding angiotensin converting enzyme (ACE) is a promising candidate for lung cancer. We aimed to assess three well-characterized polymorphisms of the ACE gene (A-240T, I/D, A2350G) and lung cancer in Chinese people, and complete a meta-analysis of the association of I/D polymorphism with lung cancer. In our case-control study, a total of 684 patients with lung cancer and 602 age-matched controls were recruited. Genotyping was performed using polymerase chain reaction (PCR) and ligase detection reactions (LDR) techniques. Single-locus analysis indicated that carriers of the A-240T allele had a significantly increased risk for lung cancer under additive (odds ratio (OR)=1.2; 95% confidence interval (CI): 1.02-1.42; P=0.027) and recessive (OR=1.8; 95% CI: 1.24-2.63; P=0.002) models, and that DD genotype carriers were 1.97 times more likely to develop lung cancer (95% CI: 1.25-3.11; P=0.004) compared with those with the I allele under the recessive model. However, no significance was observed in further haplotype analysis (P>0.05). In a meta-analysis of ACE gene insertion-deletion (I/D) polymorphism from six studies with 1183 lung cancer patients and 1065 controls, we failed to detect any significant association (overall OR=1.09; 95% CI: 0.84-1.41). A low probability of publication bias was observed. Our results suggest that ACE gene A-240T polymorphism might be a genetic marker for the development of lung cancer in Chinese people.


Osteoarthritis-associated basic calcium phosphate crystals alter immune cell metabolism and promote M1 macrophage polarization.
A number of studies have demonstrated that molecules called 'alarmins' or danger-associated molecular patterns (DAMPs), contribute to inflammatory processes in the OA joint. Metabolic reprogramming of immune cells, including macrophages, is emerging as a prominent player in determining immune cell phenotype and function. The aim of this study was to investigate if basic calcium phosphate (BCP) crystals which are OA-associated DAMPs, impact on macrophage phenotype and metabolism. Human monocyte derived macrophages were treated with BCP crystals and expression of M1 (CXCL9, CXCL10) and M2 (MRC1, CCL13)-associated markers was assessed by real-time PCR while surface maturation marker (CD40, CD80 & CD86) expression was assessed by flow cytometry. BCP induced metabolic changes were assessed by Seahorse analysis and glycolytic marker expression (hexokinase 2(HK2), Glut1 and HIF1α) was examined using real-time PCR and immunoblotting. Treatment with BCP crystals upregulated mRNA levels of CXCL9 and CXCL10 while concomitantly downregulating expression of CCL13 and MRC1. Furthermore, BCP-treated macrophages enhanced surface expression of the maturation makers, CD40, CD80 and CD86. BCP-treated cells also exhibited a shift towards glycolysis as evidenced by an increased ECAR/OCR ratio and enhanced expression of the glycolytic markers, HK2, Glut1 and HIF1α. Finally, BCP-induced macrophage activation and alarmin expression was reduced in the presence of the glycolytic inhibitor, 2-DG. This study not only provides further insight into how OA-associated DAMPs impact on immune cell function, but also highlights metabolic reprogramming as a potential therapeutic target for calcium crystal-related arthropathies.


1,2,4-triazole-assisted metal-organic framework-derived nitrogen-doped carbon nanotubes with encapsulated Co4N particles as bifunctional oxygen electrocatalysts for rechargeable zinc-air batteries.
The design of high-performance oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) dual-functional catalysts is not only important for the further applications of zinc-air batteries (ZABs) but also a major challenge in the field of energy conversion. The cheap 1,2,4-triazole (1,2,4-TZ) can be decomposed easily by heat, making it a high research value in carbon catalysts derived from metal-organic frameworks (MOFs). Here, Co4N particles encapsulated at the top of N-doped carbon nanotubes (Co4N@NCNTs) were conveniently prepared by 1,2,4-TZ-assisted pyrolysis of Co-MOF-74 for the first time. Owing to the excellent activity of Co4N particles and the highly graphitized N-doped carbon nanotubes (NCNTs), Co4N@NCNTs obtained at 900 °C (Co4N@NCNT-900) exhibited astonishing catalytic performance in both ORR and OER, and high reversible oxygen bifunctional activity (ΔE = 0.685 V). Moreover, Co4N@NCNT-900 displayed a larger discharge power density (122 mW cm-2), a better specific capacity (811.8 mAh g-1), and more excellent durability during the ZAB test, implying that Co4N@NCNT-900 can act as a bifunctional high active catalyst in ZABs.


The restructuring of dopamine receptor subtype gene transcripts in c-fos KO mice.
Although c-Fos protein is one of the principal molecules in intracellular signaling, c-fos gene disruption is associated with alterations in neuronal functions that do not correspond to its importance in function. The aim of the study was to evaluate the changes of dopaminergic system together with acetylcholinesterase (AChE) in c-fos disruption (KO). KO male mice showed an increase in D₁-like receptor (279% of WT) and D₂-like receptor (345% of WT) binding sites in the cortex. On the gene expression level (assessed by real-time PCR), lower quantities of D₁R-mRNA (0.64) and D₅R-mRNA (0.6) were found in females when compared to males in the frontal cortex, higher D₂R-mRNA in the parietal (1.43) and temporal (2.64) cortex and lower AChE-mRNA (0.67). On the contrary, female striatum contained higher level of D₂R-mRNA (1.62) and AChE-mRNA (1.57) but lower level of D₃R-mRNA (0.73). Hypothalamic D₁R-mRNA, D₂R-mRNA and D₄R-mRNA were higher in females (1.38, 1.63, and 1.68, respectively). Disruption of c-fos increased selectively D₅R-mRNA (1.31) in male parietal cortex, D₂R-mRNA (1.72) in male temporal cortex, and cerebellar D₂R-mRNA in both males (1.43) and females (1.42), respectively. In females, we found rather decrease in DR-mRNA. Multiple correlations in mRNA quantities (in WT mice) were found, which changed considerably upon c-fos KO. Main interactions in WT were inter-regional, CNS of KO underwent an extensive restructuring comprising intraregional interactions in the frontal cortex, hypothalamus, and cerebellum. These changes in DR (between others) could be considered as one of the adaptive mechanisms in c-fos KO mice.


Pattern abnormalities induced by ectopic expression of the Drosophila gene hairy are associated with repression of ftz transcription.
The pair-rule segmentation gene hairy (h) is expressed and required in alternate metameres in the early Drosophila embryo. We show that h expression outside these domains, driven by an hsp70 promoter, suppresses the expression of fushi tarazu (ftz). The kinetics of action favor h acting directly as a transcriptional repressor. The resulting pattern defects, and the patterns of en and Ubx activity, can be explained if h acts via ftz and other pair-rule genes in the establishment of stable en domains. We present evidence that ftz is required for the initiation of Ubx transcription, but not for its maintenance.


Cross-sectional echocardiographic detection of aortic ring abscess in bacterial endocarditis.
The diagnosis of aortic ring abscess by cross-sectional echocardiography has not been reported. In this paper, a case of bacterial endocarditis of the aortic valve extending to the aortic ring and the mitral valve is reported. The role of cross-sectional echocardiography in defining the anatomic distortion of the aortic valve in bacterial endocarditis and its complications is emphasized. This study would indicate that early diagnosis of aortic ring abscess is feasible by cross-sectional echocardiography.


A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT induced urothelial tumors.
Rats engrafted with transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors were treated with purpurin derivatives and red light (greater than 590 nm., 360 joules/cm.2). Treated and control tumors were harvested 12 days after treatment and dry weights compared. At doses of 5.0 micrograms./gm. and 2.5 micrograms./gm. body weight, the purpurins designated NT1 and NT2, when combined with light, caused statistically significant (p less than 0.02) tumor regression when compared to light shielded controls. At 1.0 micrograms./gm. body weight, NT1 and light also induced significant tumor regression (p less than 0.02). Purpurins, which have strong absorption bands above 650 nm. and can be synthesized with a high degree of purity, appear to have potential as photosensitizers for photodynamic therapy.


How Does Environmental and Occupational Exposure Contribute to Carcinogenesis in Genitourinary and Lung Cancers?
Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.


Comparison of diffusion-weighted high-resolution CBF and spin-echo BOLD fMRI at 9.4 T.
The quantification of blood oxygenation-level dependent (BOLD) functional MRI (fMRI) signals is closely related to cerebral blood flow (CBF) change; therefore, understanding the exact relationship between BOLD and CBF changes on a pixel-by-pixel basis is fundamental. In this study, quantitative CBF changes induced by neural activity were used to quantify BOLD signal changes during somatosensory stimulation in alpha-chloralose-anesthetized rats. To examine the influence of fast-moving vascular spins in quantifying CBF, bipolar gradients were employed. Our data show no significant difference in relative CBF changes obtained with and without bipolar gradients. To compare BOLD and CBF signal changes induced by neural stimulation, a spin-echo (SE) sequence with long SE time of 40 ms at 9.4 T was used in conjunction with an arterial spin labeling technique. SE BOLD changes were quantitatively correlated to CBF changes on a pixel-by-pixel and animal-by-animal basis. Thus, SE BOLD-based fMRI at high magnetic fields allows a quantitative comparison of functional brain activities across brain regions and subjects.


Does antenatal care timing influence stillbirth risk in the third trimester? A secondary analysis of perinatal death audit data in South Africa.
To explore stillbirth risk across gestation in three provinces of South Africa with different antenatal care schedules. Retrospective audit of perinatal death data using South Africa's Perinatal Problem Identification Programme. In 2008, the Basic Antenatal Care Programme was introduced in Limpopo and Mpumalanga provinces, reducing appointments to five visits at booking, 20, 26, 32, 38 weeks and 41 weeks if required. In the Western Cape province seven appointments remained at booking, 20, 26, 32, 34, 36, 38 and 41 weeks if required. All audited stillbirths (n = 4211) between October 2013 to August 2015 in Limpopo, Mpumalanga and Western Cape. Stillbirth risk (26-42 weeks of gestation, >1000 g) across gestation was calculated using Yudkin's method. Stillbirth risk was compared between provinces and relative risks were calculated between Limpopo/ Mpumalanga and Western Cape. Stillbirth risk across gestation. Stillbirth risk peaked at 38 weeks of gestation in Limpopo (relative risk [RR] 3.11, 95% CI 2.40-4.03, P < 0.001)and Mpumalanga (RR 3.09, 95% CI 2.37-4.02, P < 0.001) compared with Western Cape, where no peak was observed. Stillbirth risk at 38 weeks gestation in Limpopo and Mpumalanga were statistically greater than both the 37 and 39 weeks gestation within provinces (P < 0.001). As expected, a peak at 41 weeks of gestation was observed in all provinces. The increased period of stillbirth risk occurs after a 6-week absence of antenatal care. This calls for a refocus on the impact of reduced antenatal care visits during the third trimester. Reduced antenatal care in the third trimester may increase stillbirth risk.


Evaluation of resins for on-bead screening: a study of papain and chymotrypsin specificity using PEGA-bound combinatorial peptide libraries.
TentaGel, ArgoGel and PEGA resins were evaluated for on-bead biological screening, using a fluorescently-labelled peptide attached to each and assayed for papain activity. Peptide attached to PEGA was cleaved in near quantitative yield at the expected sites, whilst an identical sequence on TentaGel and ArgoGel beads was hydrolysed in very low yields and nonspecifically on ArgoGel. The compatibility of PEGA with enzymes was further demonstrated by the determination of subsite specificities of papain and chymotrypsin using PEGA-bound peptide libraries, which proved to be similar to those observed in free solution.


Phylogenetic analysis of condensation domains in the nonribosomal peptide synthetases.
Condensation (C) domains in the nonribosomal peptide synthetases are capable of catalyzing peptide bond formation between two consecutively bound various amino acids. C-domains coincide in frequency with the number of peptide bonds in the product peptide. In this study, a phylogenetic approach was used to investigate structural diversity of bacterial C-domains. Phylogenetic trees show that the C-domains are clustered into three functional groups according to the types of substrate donor molecules. They are l-peptidyl donors, d-peptidyl donors, and N-acyl donors. The fact that C-domain structure is not subject to optical configuration of amino acid acceptor molecules supports an idea that the conversion from l to d-form of incorporating amino acid acceptor occurs during or after peptide bond formation. l-peptidyl donors and d-peptidyl donors are suggested to separate before separating the lineage of Gram-positive and Gram-negative bacteria in the evolution process.


Renal tubular epithelial cell necroptosis promotes tubulointerstitial fibrosis in patients with chronic kidney disease.
Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), ultimately predisposes patients to end-stage renal disease. However, there is no effective therapy for renal fibrosis. Our earlier studies proved that RIP3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury. Under transmission electron microscopy (TEM), we found morphological changes in the necrosis of human renal tissue, and the percentage of necrotic cells increased significantly in patients with stages 2 and 3a CKD. Immunofluorescence analyses showed that the percentages of TUNEL+ /RIP3+ double-positive and TUNEL+ /MLKL+ double-positive tubular epithelial cells in renal tubules of patients with stages 2 and 3a CKD were significantly increased compared to those in control patients without renal disease. Immunohistochemistry analyses of renal biopsy specimens from patients with CKD revealed RIP3, MLKL, and p-MLKL upregulation in patients with stages 2 and 3a CKD, suggesting that necroptosis of renal tubular epithelial cells in CKD patients occurs, and the peak of necroptosis was in stages 2 and 3a CKD. We showed that profibrotic factor proteins (TGF-β1, Smad2 and Smad3) and fibroblast activation markers (α-SMA and Vimentin) were specifically upregulated in stage 2 and 3a CKD patients. In addition, Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with TGF-β1 and collagen-I. We also showed that RIP1/3 or MLKL inhibitors decreased the expression of RIP3, MLKL, TGF-β1, and Smad3 in HK-2 cells treated with TNF-α. FGF-2, α-SMA, Vimentin and FN were overexpressed in the hRIFs cultured with the supernatant of necroptotic HK-2 cells, whereas necroptosis blockers (Nec-1s, GSK'872 and NSA) and TGF-β1/Smad3 pathway antagonists (LY364947 and SIS3) reduced FGF-2, α-SMA, Vimentin and FN levels. Collectively, necroptosis of renal tubular epithelial cells in CKD patients occurs, and the peak of necroptosis was in stages 2 and 3a CKD. Renal tubular epithelial cell necroptosis mediates renal tubulointerstitial fibrosis in patients with chronic kidney disease, which is related to the TGF-β1/Smad3 signaling pathway.


Real-time CT-guided percutaneous placement of LV pacing leads.
The aim of this study was to assess the feasibility of real-time computed tomographic (CT) imaging to guide the percutaneous placement of left ventricular (LV) leads in an animal model. Cardiac resynchronization therapy has been shown to improve morbidity and mortality in patients with chronic heart failure. However, placement of the coronary sinus lead can be challenging and may require a more aggressive surgical approach. Nine swine were placed in a real-time CT scanner to define the safest percutaneous access strategy. Under real-time CT guidance, a 3.5-F pacing lead was placed percutaneously in the anterolateral LV epicardium (n = 6 swine) or to the posterolateral wall after the creation of intentional left pneumothorax (n = 3 swine) in a tangential (n = 12) or perpendicular (n = 1) approach. Pacing parameters and CT images were assessed during 30-min follow-up. Necropsy findings were compared with real-time CT images. CT imaging successfully defined the safest percutaneous access route in all 13 lead placements and guided the therapeutic creation of pneumothoraces. Needle trajectory remained within 5 mm of the access route defined on CT imaging. LV lead placement under CT guidance was successful in all attempts within 19 ± 7 min. The mean pacing thresholds was 2.5 ± 1.5 V, the mean R wave amplitude was 11.2 ± 5.6 mV, and the mean impedance was 686 ± 103 Ω and remained unchanged after tangential placement during 30-min follow-up. Although no cardiac complications were observed with tangential lead placement (12 of 12), the perpendicular approach resulted in a pericardial effusion requiring pericardiocentesis. At necropsy, CT images correlated well with the in situ pathological results. Percutaneous placement of LV pacing leads under CT guidance is feasible and might offer an alternative to more invasive surgical approaches in patients with complicated coronary sinus lead placement.


[Replacement of Bauhin's valve with an end-to-end telescope anastomosis between the ileum and transverse colon. Experimental study in dogs].
A method of a telescope anastomosis for prevention of reflux was developed experimentally in dogs. After the resection of 40 cm of ileum and colon ascendens the ileal part was intussuscepted into the colon and fixed by seromuscular stiches. The vessels were left untouched. The intussuscepted part measured 3-4 cm. No ileus was observed in the 24 weeks. Glass balls of 1.2 cm diameter could pass through. Barium enema as well as air insufflation of different pressures showed no reflux. The serosa was covered pretty soon by a granular tissue and later on by normal mucosa.


[Effect of transfection of enhanced green fluorescent protein gene on neuron-like differentiation of rat mesenchymal stem cells].
To determine the effect of transfection of enhanced green fluorescent protein (EGFP) on neuron-like differentiation of rat mesenchymal stem cells (rMSC) with plasmid vector. In vitro cultured rMSC was transfected with plasmid vector containing EGFP, and its surface marker and differentiation neuron-like cells were detected. Results There was no significant difference in the morphology and surface markers between the EGFP-rMSC and rMSC. The cell surface markers of EGFP-rMSC including expression of CD44(+),CD11b (-) and CD45(-) remained similar to those of rMSC. EGFP-rMSC presented the differentiated potential to neuron-like cells. There was no statistical difference in the positive ratio of neuron-like differentiation between the EGFP-rMSC and rMSC (P> 0.05). EGFP does not affect the neuron-like differentiation potential of rMSC, and can be used as the trace marker in the study of differentiation potential of rMSC.


Comparability of the Effectiveness of Different Types of Exercise in the Treatment of Achilles Tendinopathy: A Systematic Review.
Achilles tendinopathy (AT) is a common condition both in athletes and the general population. The purpose of this study is to highlight the most effective form of exercise in managing pain-related symptoms and functional capacity as well as in a return to life activities, ensuring the quality of life of patients with AT, and creating a protocol to be used in rehabilitation. We conducted a systematic review of the published literature in Pubmed, Scopus, Science Direct, and PEDro for Randomised Controlled Trials concerning interventions that were based exclusively on exercise and delivered in patients 18-65 years old, athletes and non-athletes. An amount of 5235 research articles generated from our search. Five met our inclusion criteria and were included in the review. Research evidence supports the effectiveness of a progressive loading eccentric exercise program based on Alfredson's protocol, which could be modified in intensity and pace to fit the needs of each patient with AT. Future research may focus on the optimal dosage and load of exercise in eccentric training and confirm the effectiveness of other type of exercise, such as a combination of eccentric-concentric training or heavy slow resistance exercise. Pilates could be applied as an alternative, useful, and friendly tool in the rehabilitation of AT.


An approach to the self regulatory mechanism of substance P actions: II. Biological activity of new synthetic peptide analogs related both to enkephalin and substance P.
Analogs of substance P in which the N-terminal part of native peptide was replaced by an enkephalin active fragment have been synthesized. We found this peptide to be as active as substance P on the GPI test. The analogs were completely inactive on GPI opiate test; the opiate activity was observed on MVD and RVD tests. Surprisingly, we found that SP-activity was reduced by naloxone.


Attentional sampling of visual and auditory objects is captured by theta-modulated neural activity.
Recent evidence suggests that visual attention alternately samples two behaviourally relevant objects at approximately 4 Hz, rhythmically shifting between the objects. Whether similar attentional rhythms exist in other sensory modalities, however, is not yet clear. We therefore adapted and extended an established paradigm to investigate visual and potential auditory attentional rhythms, as well as possible interactions, on both a behavioural (detection performance, N = 33) and a neural level (EEG, N = 18). The results during unimodal attention demonstrate that both visual- and auditory-target detection fluctuate at frequencies of approximately 4-8 Hz, confirming that attentional rhythms are not specific to visual processing. The EEG recordings provided evidence of oscillatory activity that underlies these behavioural effects. At right and left occipital EEG electrodes, we detected counter-phasic theta-band activity (4-8 Hz), mirroring behavioural evidence of alternating sampling between the objects presented right and left of central fixation, respectively. Similarly, alpha-band activity as a signature of relatively suppressed sensory encoding showed a theta-rhythmic, counter-phasic change in power. Moreover, these theta-rhythmic changes in alpha power were predictive of behavioural performance in both sensory modalities. Overall, the present findings provide a new perspective on the multimodal rhythmicity of attention.


In vitro synergy of β-lactam combinations against KPC-producing Klebsiella pneumoniae strains.
Double carbapenem therapy has been promoted as an alternative treatment for infections due to carbapenemase-producing Enterobacteriaceae where carbapenemase inhibitors are unavailable or when other agents have demonstrated toxicity with equally limited evidence. The capacity of other β-lactams and β-lactamase inhibitors to provide synergistic activity with carbapenems is unclear. This study sought to investigate the in vitro synergistic potential of other β-lactam/β-lactamase combinations with meropenem against KPC producers. Time-kill assays were performed on 24 unique strains of KPC-producing Klebsiella pneumoniae. Combinations evaluated included meropenem or imipenem with one of the following: ertapenem, piperacillin/tazobactam or ceftolozane/tazobactam. Concentrations used for each drug were those considered physiologically attainable in patients with a time above the concentration exceeding 40%-50% of the dose interval. Combinations were considered to be synergistic when they reduced bacterial cfu/mL by ≥2 log10 at 24 h as compared with the single most active agent. The combination of piperacillin/tazobactam with meropenem was found to be synergistic against 70.8% of the isolates, followed by ertapenem with meropenem (58.3%) and ceftolozane/tazobactam with meropenem (41.7%). The piperacillin/tazobactam combination was found to be more bactericidal than the other combinations, with 58.3% of isolates demonstrating a ≥4 log10 cfu/mL reduction at 24 h, as compared with 37.5% for ertapenem and 20.8% for ceftolozane/tazobactam combinations. The combination of piperacillin/tazobactam with meropenem may be a potential therapy against KPC-producing K. pneumoniae when other therapies are unavailable or prohibitively toxic.


Complications during anaesthesia in patients with Duchenne's muscular dystrophy (a retrospective study)
The purpose of this retrospective study was to estimate the frequency and severity of anaesthetic complications in patients with Duchenne's muscular dystrophy (DMD). Forty-four boys with DMD were exposed to anaesthesia and surgery 84 times during a period of 22 years (1965-86). The procedures took place at 15 different hospitals. Retrospective examination of the case records showed: 19 cases with local analgesia without any complications, and 18 of 65 general anaesthetics with minor or more serious complications. In ten cases an increase in body temperature above 37.5 degrees C was seen, five had abdominal pain and dark-coloured urine after surgery, and three had a critical perioperative course with a resemblance to malignant hyperthermia. The complications were almost exclusively related to the use of succinylcholine. The use of succinylcholine was dispersed through all ages. Three out of the eight patients with severe complications occurred 1.5, 2.5 and 4 years before the neuromuscular disease was diagnosed. Thus an unusual course of anaesthesia in male children calls for further investigation. Although it has been stated before that succinylcholine is contraindicated in patients with Duchenne's muscular dystrophy, the drug continues to be used.


Internal hernia associated with colostomy after laparoscopic abdominoperineal resection.
We herein describe a case with an internal hernia that developed after laparoscopic abdominoperineal resection for rectal cancer. The small intestine passed through the space between the sigmoid colon loop of the stoma and the abdominal wall. Internal hernias associated with colostomy are rare; however, the condition is an important complication, because it causes ischemia in both the herniated intestine and the sigmoid colon pulled through the abdominal wall as a stoma.


How much do we need to worry about venous thromboembolism after hospital discharge? A study of colorectal surgery patients using the National Surgical Quality Improvement Program database.
It is well recognized that the increased risk of a postoperative venous thrombotic event extends beyond the inpatient treatment period. The purpose of this study was to determine the 30-day incidence and risk factors associated with the occurrence of early postdischarge symptomatic venous thromboembolic events in patients who have undergone major colorectal surgery. The National Surgical Quality Improvement Program database was queried for patients who had undergone a colon or rectal resection during the study period (2005-2008). Patient demographics, preoperative risk factors, and operative variables were recorded. The primary outcomes were occurrence of deep venous thrombosis requiring therapy or pulmonary embolism within 30 days after initial surgery. The occurrence of postdischarge venous thromboembolic events was calculated from the days to primary outcome and days from operation to discharge. Univariate and multivariate linear regression models incorporating pre- and intraoperative variables as well as the occurrence of a major or minor complication were used to evaluate the effect of these clinical factors on the early postdischarge venous thromboembolic event rate. A total of 52,555 patients were included in the initial analysis. A total of 240 deep venous thromboses were diagnosed in the postdischarge setting giving a postdischarge incidence of 0.47%. One hundred thirty cases of a pulmonary embolus were diagnosed (0.26% incidence) with 30 patients having a concurrent deep venous thrombosis and pulmonary embolus. The overall cumulative postdischarge symptomatic venous thromboembolic incidence was 0.67% (n = 340). Obesity, preoperative steroid use, "bleeding disorder," ASA class III, and postoperative (major and minor) complications were all independently associated with an increased risk of an early postdischarge venous thromboembolic event. This study has identified risk factors that may help stratify patients into different risk profiles and offer prolonged prophylaxis to patients at increased risk on the basis of preoperative risk factors and postoperative complications.


Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.
A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint. Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression. A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence. This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.


Latex proteins downregulate inflammation and restores blood-coagulation homeostasis in acute Salmonella infection.
Calotropis procera latex protein fraction (LP) was previously shown to protect animals from septic shock. Further investigations showed that LP modulate nitric oxide and cytokines levels. To evaluate whether the protective effects of LP, against lethal bacterial infection, is observed in its subfractions (LPPII and LPPIII). Subfractions (5 and 10 mg/kg) were tested by i.p. administration, 24 h before challenging with lethal injection (i.p.) of Salmonella Typhimurium. LPPIII (5 mg/kg) which showed higher survival rate was assayed to evaluate bacterial clearance, histopathology, leukocyte recruitment, plasma coagulation time, cytokines and NO levels. LPPIII protected 70% of animals of death. The animals given LPPIII exhibited reduced bacterial load in blood and peritoneal fluid after 24 h compared to the control. LPPIII promoted macrophage infiltration in spleen and liver. LPPIII restored the coagulation time of infected animals, increased IL-10 and reduced NO in blood. LPPIII recruited macrophages to the target organs of bacterial infection. This addressed inflammatory stimulus seems to reduce bacterial colonisation in spleen and liver, down regulate bacterial spread and contribute to avoid septic shock.


Effect of estradiol and progesterone on the isometric tension developed by longitudinal and circular isthmus of rabbit fallopian tube.
The effect of estradiol and progesterone on the isometric tension developed by longitudinal and circular muscle of isthmus of rabbit fallopian tube to various agonists was studied. The isometric tension developed was reduced by about 50% under progesterone dominance as compared to estrogen dominance. This inhibition was of non-specific nature and did not involve adrenergic receptors. The non-specific effect of progesterone may have a role in regulating the entry of ova into the isthmus after their initial retention at the ampullary--isthmic junction.


Production of 6-oxo-prostaglandin F1 alpha, PGF2 alpha and PGE2 by sheep uterine tissue.
Incubation in vitro of sheep uterine tissue revealed that although both caruncular and non-carunuclar endometrium can synthesize appreciabel quantities of PGF2 alpha, PGE2 and 6-oxo-PGF2 alpha, the myometrium synthesizes predominantly 6-oxo-PGF1 alpha. Non-caruncular endometrium contained more 6-oxo-PGF1 alpha than either the myometrium or the caruncles, while myometrial tissue possessed less PGF2 alpha than either caruncular or non-caruncular endometrium.


Nitrogen removal from summer to winter in a field pilot-scale multistage constructed wetland-pond system.
A pilot-scale multistage constructed wetland-pond (MCWP) system with a "pre-ecological oxidation pond, two-stage horizontal subsurface flow constructed wetland (HSCW) and surface flow constructed wetland (SFCW) as the core and postsubmerged plant pond" as the process was used to treat actual polluted river water in the field, and the variation in nitrogen removal from summer to winter was investigated. The results showed that the average total nitrogen (TN) removal efficiency in the MCWP was approximately 40.74%. The significant positive correlation between the daily highest temperature and the TN removal efficiency of the whole system was fitted with a nonlinear curve (R2 = 0.7192). The TN removal load rate in the HSCWs was 2.7-3.7 times that in the SFCW. The SFCW, which had high-density plants (35 plants/m2), increased the proportion of nitrogen removed by plant harvesting and microbial function. The TN transformed by Iris pseudacorus L. accounted for 54.53% in the SFCW. Furthermore, bacteria completed the nitrogen cycle in the SFCW through a variety of nitrogen removal pathways. This research not only investigated the TN removal performance in an MCWP system but also made it possible to predict the TN removal efficiency according to the daily highest temperature from summer to winter in the field.


Synthesis and evaluation of γ-lactam analogs of PGE₂ as EP4 and EP2/EP4 agonists.
To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl ω-chain moiety of the γ-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented.


The present state of trend detection and prediction in patient monitoring.
An investigation has been carried out into the suitability of the following techniques for trend detection and forecasting in patient monitoring: Cusum; Trigg's Tracking Signal; The Patient Condition Factor; The Patient Alarm Warning System; Box-Jenkins models and the Harrison-Stevens Bayesian approach. The latter holds considerable promise since it is flexible and can be implemented on a microprocessor. Consideration has also been given to the need for a better knowledge of the statistical properties of the variables to be monitored and the problems of combining trends detected in severable variables.


Pulmonary sequelae and lung repair in survivors of the adult respiratory distress syndrome.
The high in-hospital mortality of ARDS has not diminished over the past 10 years, despite improvements in supportive intensive care. Much of the mortality arises from infections, particularly sepsis and pneumonia, and from organ failure, especially kidney failure. The rapid advances in understanding the interlocking pathophysiologic mechanisms of ARDS have not yet been translated into therapeutic trials of new methods for diminishing the injury or for stimulating normal repair. In part, this is because it is difficult to predict which high-risk patients will develop ARDS and then intervene early in the injury process. Patients in whom the risk for ARDS is extremely high have a very high mortality even without ARDS, thereby making efficacy of an early or prophylactic therapy quite difficult to prove. In spite of severe pathologic abnormalities, including fibrosis, early in the course of ARDS, most survivors return to almost normal pulmonary function. The few cases that have been studied with serial biopsies demonstrate resolution of fibrosis. This amazing recovery poses many fascinating questions about how the lung repairs itself. Given the heterogeneous causes of ARDS and the large number of structural, cellular, and biochemical abnormalities described, one can postulate that any one of numerous factors is important in normal repair. Most promising of these are the degree of basement membrane damage, the control of type II cell proliferation and differentiation, the control of collagen synthesis, the anatomic localization of fibrosis, and the control of collagenase action. These interactions of epithelial and mesenchymal tissues probably recreate the process of lung development in the injured adult lung. At a clinical level, the role of oxygen toxicity remains a significant issue. Oxygen acting as an oxidant may be partially responsible for the small airways disease seen in approximately one quarter to one third of survivors. The mortality data stress the need for better ways of preventing and diagnosing lung infections. Better definition of the clinical factors that put survivors at risk for persistent loss of lung function is also needed, and could define a subgroup in which trials of agents designed to improve repair would be most worthwhile. More information about the long-term pathologic course, though difficult to obtain, would also be very important. Perhaps some registry of ARDS survivors would permit closer follow-up and make available more late autopsy pathology when these people die of other causes. The rapid time course of ARDS provides an ideal testing ground for agents designed to either decrease lung injury or stimulate repair.(ABSTRACT TRUNCATED AT 400 WORDS)


What doctors need to know: Prescribing or not for the oldest old.
Given the global increase in the number of people over the age of 85, there is a growing body of work concerning this group, termed the oldest old. Much of this work is confined to the literature specialising in geriatrics and the more generic health care papers refer to 'older people' with little definition of what is meant by 'older'. Iatrogenesis (ill health caused by doctors) is a major issue and general practitioners (GPs) need practical help in prescribing for the oldest old. This paper presents a narrative review of the literature on prescribing and the oldest old. The results showed that all papers sourced referred to prescribing for the 'old' as those aged over 65, with only scant mention of oldest old. Yet prescribing for the oldest old involves clinical judgement and knowledge of the patient. It includes weighing up what will do good, cause no harm and is acceptable to the individual. GPs have to make treatment choices mostly in isolation from colleagues, during time-limited consultations and with few relevant guidelines on managing multi-morbidities in the oldest old. A major issue in prescribing for people over the age of 85 is that guidelines for diseases are based on trials with younger adults, outline the best practice for one disease in isolation (i.e. not in the presence of other diseases) and take little account of the interactions between the drugs used in managing several diseases in frail older people. There is a growing body of work, however, calling for specialist services for the oldest old.


Active immunization of NMRI mice against Serratia marcescens. II. K-antigen extracts.
The minimal active immunogenic doses (intraperitoneal administration) of crude K-antigen extracts of Serratia marcescens for NMRI mice were 80 ng. Following ultracentrifugation (300,000 x g, 16 h), supernatant fluids of three K-antigen extracts were free of contaminating DNA, RNA, and 2-keto-3-deoxy-D-manno-octonic acid (KDO), and the contents of Limulus amoebocyte lysate-reactive lipopolysaccharide (LPS) had been reduced from 100- to 1000-fold. The minimal active immunogenic doses of two ultracentrifuged K-antigen extracts were 2 and 10 micrograms, respectively. A mucoid strain of S. marcescens (SM 20-M; serotype O6/O14:H12) yielded nonmucoid (= SM 29-NM) variants that had lost most of the O6/O14 O-antigen (LPS) and all of the SM 29-M K-antigen extract reactivity (ELISA test) and which were ca. 5-fold less mouse-virulent. Crude K-antigen extracts from S. marcescens strain SM 29-M and variant SM 29-NM failed to protect NMRI mice against strain SM 29-M.


The effect of changes in temperature and humidity on the accuracy of von Frey hairs.
A series of von Frey hairs was subjected to changes in temperature and relative humidity (RH) simulating those encountered on a neonatal intensive care unit. The effect of each environmental change on their calibrated value was monitored. It was found that changes in RH significantly affected their calibration, whereas changes in temperature had a smaller effect. The results of the study indicate that the environmental conditions in which von Frey hairs are used should be taken into account.


The effects of prostacyclin on early ultrastructural changes in the neuron nuclei of the motor cortex in rabbits after complete 20-min cerebral ischemia.
Twelve rabbits underwent 20-min of complete cerebral ischemia. They were given PGI2 for 3 min before and during ischemia and for 15 min after ischemia. Control animals with complete cerebral ischemia over the same period of time were not given PGI2 medication. The animals treated with PGI2 were found to have recovered bioelectric activity of the cerebral cortex in half the time that it took the control group. A positive effect of PGI2 on some parameters of the peripheral blood system after ischemia was observed. Under the conditions of this experiment PGI2 did not effect the ultrastructural changes in motor cortex neuron nuclei. The changes were manifested in numerous vesicular structures and nuclear inclusions. The inclusions took the forms of clusters, rodlets, and lattices constructed of filaments and/or tubules. The number of vesicular structures and inclusions grew with the lapse in time after ischemia.


Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience.
Marfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known. Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome. An FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3-19 years) with suspected MFS. This study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy.


Construction of a lipid metabolism-related and immune-associated prognostic signature for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues. As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholine acyltransferase 1, PLA2G1B, and SMPD4 were proved significantly high expression while ACSL6 and LCAT were remarkably low expression in our 15 pairs of matched HCC and normal tissues by qRT-PCR. Under different conditions, the overall survival (OS) of patients in low-risk group was prolonged than that in high-risk group. Moreover, the as-constructed signature was an independent factor, which was remarkably associated with gender, histologic grade, and platelet level of HCC patients. In addition, the receiver operating characteristic (ROC) curve analysis confirmed the good potency of the model. Functional enrichment analysis further revealed that lower fatty acid (FA) oxidation and higher infiltration of immunocytes were detected in patients from the high-risk group compared with those in the low-risk group. Our findings indicate that the lipid metabolism-related signature shows prognostic significance for HCC.


Mixed germ cell-sex cord stromal tumour of the testis and ovary: comparison and contrast.
Mixed germ cell-sex cord stromal tumours (MGC-SCSTs) of the testis and ovary differ significantly in their histological appearance, clinical behaviour, and molecular genetics. Until recently, the germ cells of testicular MGC-SCST were considered to be invariably histologically bland, whereas those from neoplasms that arise in the ovary have histological features characteristic of premalignancy. However, a recent histological and molecular genetic study demonstrated histological abnormalities and multiple chromosomal losses and gains in a small subset of testicular cases, thus providing the first evidence that testicular MGC-SCSTs can exceptionally show histological and molecular abnormalities. All cases of testicular MGC-SCST reported to date have been clinically benign, whereas ovarian examples are sometimes the precursor of a malignant germ cell neoplasm that can be clinically aggressive. Both genetic and epigenetic influences likely account for dissimilarities in these uncommon gonadal neoplasms.


Developing a predictive model for distinguishing invasive nail unit melanoma from nail unit melanoma in situ.
Clinical information that distinguishes invasive nail unit melanoma from nail unit melanoma in situ before surgery would aid physicians in the decision-making process and estimating prognosis. However, limited information is available on the detailed demographic and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ for differential diagnosis. This study aimed to investigate the demographic data and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ and establish a predictive model for differentiating these two forms of nail unit melanoma. A retrospective observational study of ninety-seven patients diagnosed with nail unit melanoma (59 in situ and 38 invasive cases) in four healthcare centres in South Korea (three tertiary referral hospitals and one second referral hospital) from March 2014 to December 2019. A multivariable analysis revealed that ulcer (odds ratio = 21.6, confidence interval = 2.1-219.8, P = 0.009), total melanonychia (odds ratio = 17.6, confidence interval = 3.0-104.0, P = 0.002), nail plate destruction (odds ratio = 10.9, confidence interval = 2.0-59.4, P = 0.006) and polychromia (odds ratio = 5.3, confidence interval = 1.36-20.57, P = 0.016) were distinctive dermoscopic features of invasive nail unit melanoma. A predictive model with scores ranging from 0 to 6 points demonstrated a reliable diagnostic value (C-statistic = 0.902) in differentiating invasive nail unit melanoma from nail unit melanoma in situ. Invasive nail unit melanoma and nail unit melanoma in situ have different dermoscopic features. A predictive model based on morphologic dermoscopic features could aid in differentiating invasive nail unit melanoma from nail unit melanoma in situ.


A genome-wide proteome array reveals a limited set of immunogens in natural infections of humans and white-footed mice with Borrelia burgdorferi.
Humans and other animals with Lyme borreliosis produce antibodies to a number of components of the agent Borrelia burgdorferi, but a full accounting of the immunogens during natural infections has not been achieved. Employing a protein array produced in vitro from 1,292 DNA fragments representing approximately 80% of the genome, we compared the antibody reactivities of sera from patients with early or later Lyme borreliosis to the antibody reactivities of sera from controls. Overall, approximately 15% of the open reading frame (ORF) products (Orfs) of B. burgdorferi in the array detectably elicited an antibody response in humans with natural infections. Among the immunogens, 103 stood out on the basis of statistical criteria. The majority of these Orfs were also immunogenic with sera obtained from naturally infected Peromyscus leucopus mice, a major reservoir. The high-ranking set included several B. burgdorferi proteins hitherto unrecognized as immunogens, as well as several proteins that have been established as antigens. The high-ranking immunogens were more likely than nonreactive Orfs to have the following characteristics: (i) plasmid-encoded rather than chromosome-encoded proteins, (ii) a predicted lipoprotein, and (iii) a member of a paralogous family of proteins, notably the Bdr and Erp proteins. The newly discovered antigens included Orfs encoded by several ORFs of the lp36 linear plasmid, such as BBK07 and BBK19, and proteins of the flagellar apparatus, such as FliL. These results indicate that the majority of deduced proteins of B. burgdorferi do not elicit antibody responses during infection and that the limited sets of immunogens are similar for two different host species.


Experimental Trypanosoma evansi infection in South American coati (Nasua nasua): hematological, biochemical and histopathological changes.
The course of an experimental Trypanosoma evansi infection in coatis (Nasua nasua, carnivora, Procyonidae) was followed for 262 days. Hematological analysis of the infected coatis revealed a marked decline in hemoglobin, packed-cell volume, and total erythrocyte count. An intense anemia followed the first wave of parasitemia and persisted until the end of the experimental period. Biochemical analysis showed increased serum levels of alanine aminotransferase and aspartate aminotransferase and decreased albumin. The main histopathological features consisted of myocarditis with the presence of degenerate cardiac fibers and meningoencephalitis. This study has shown that coatis infected with T. evansi develop a chronic disease.


Utilization of cervical cancer screening service and associated factors among women of reproductive age group in Ilu Abba Bor zone, southwestern Ethiopia, 2019: Cross-sectional study.
Cervical cancer is one of the severest risks to women's life. It is the main reason for more than half million of morbidity and 266,000 deaths worldwide annually. The aim of this study was to assess the level of cervical cancer screening service utilization and associated factors among women of the reproductive age group coming for health care service to public health facilities of Ilu Abba Bor zone, southwestern Ethiopia, 2019. An institutional-based cross-sectional study design was employed from 1 May to 30 May 2019. Participants were selected by systematic random sampling technique. Data were collected using a pretested questionnaire and entered into Epi data 3.1 and exported to SPSS version 23 for analysis. Multivariable logistic regression was used to observe the factors associated with cervical cancer screening utilization service. An adjusted odds ratio with a 95% confidence interval was used. Variables with a p-value of <0.05 were considered to be statistically significant. From a total of 259 women involved in the study, about 19 (7.3%) of the study participants had been screened for cervical cancer at least once in the past 3 years during the study period. Educational status: primary (grade 1-8) (adjusted odds ratio = 3; 95% confidence interval = (1.15-7.91)), secondary (grade 9-12) (adjusted odds ratio = 4.21; 95% confidence interval = (1.04-7.46)), and tertiary (grade 12+) (adjusted odds ratio = 6.01; 95% confidence interval = (3.01-11.35)), nulliparous (adjusted odds ratio = 0.256; 95% confidence interval = (0.105-0.642)), and looking for information about cervical cancer (adjusted odds ratio = 3.4; 95% confidence interval = (1.8-6.2)) were significant factors associated with utilization of cervical cancer screening service. The study revealed that there was low cervical cancer screening service utilization in the study area. Educational status, parity, and looking for cervical cancer information were independently associated with cervical cancer screening utilization service. There is need to improve women's education, dissemination of information about importance of cervical cancer screening, and focus on nulliparous women to have good practice of cervical cancer screening.


State of the epidemiological evidence on physical activity and cancer prevention.
Physical activity is a modifiable lifestyle risk factor that has the potential to reduce the risk of most major cancer sites. We examined the strength, consistency, dose-response and biological plausibility of an association between physical activity and risk of colon, breast, endometrium, lung, prostate, ovarian, gastric, rectal, pancreatic, bladder, testicular, kidney and haematological cancers. We also estimated the population-attributable risk (PAR) for physical inactivity and cancer in 15 European countries. There is convincing or probable evidence for a beneficial effect of physical activity on the risk of colon, breast and endometrial cancers. The evidence is weaker for ovarian, lung and prostate cancers and generally either null or insufficient for all remaining cancers. Several hypothesised biological mechanisms include a likely effect of physical activity on insulin resistance, body composition, sex steroid hormones and a possible effect on vitamin D, adipokines, inflammation and immune function. Somewhere between 165,000 and 330,000 cases of the six major cancers (breast, colon, lung, prostate, endometrium and ovarian) could have been prevented in 2008 in Europe alone if the population had maintained sufficient levels of physical activity. There is strong and consistent evidence that physical activity reduces the risk of several of the major cancer sites, and that between 9% and 19% of cancer cases could be attributed to lack of sufficient physical activity in Europe. Public health recommendations for physical activity and cancer prevention generally suggest 30-60 min of moderate or vigorous-intensity activity done at least 5d per week.


[Total hip arthroplasty - The choice of the femoral component: cemented or uncemented?]
The shape of the femoral canal is variable, much more variable than most contemporary designs of femoral components would suggest or can accomodate. Several studies have demonstrated the clinical importance of a close match between the dimensions of the femur and the implanted prosthesis. The clinical significance ofbone implant proximal fit has been noted for cementless mode fixation. A practical consequence of the variability of the proximal endosteal canal is that different femoral components may be needed for all the patients of the population. For the autors, the choice of the technique (cement or cementless), and the choice of the optimal femoral stem (standard or custom-made implant) depends on two radiologic parameters: I.C.M. and I.E.F.; these parameters are defined and analysed.


The effect of preoperative sodium-glucose cotransporter 2 inhibitors on the incidence of perioperative metabolic acidosis: A retrospective cohort study.
Sodium-glucose cotransporter 2 inhibitors are a novel class of anti-hyperglycemic agents. Although several cases of perioperative euglycemic diabetic ketoacidosis have been linked to these medications, the association remains unclear. This study aimed to examine the association between sodium-glucose cotransporter 2 inhibitor use and the incidence of perioperative metabolic acidosis with euglycemia, the surrogating outcome of perioperative euglycemic diabetic ketoacidosis. This was a retrospective, matched cohort study, which was conducted in the intensive care unit of a tertiary care facility in Japan. We identified patients aged 20 years or older with diabetes mellitus who received pharmacologic therapy and were admitted to the intensive care unit after elective surgery between April 2014 and March 2019. We extracted the following data from the electronic medical record for matching: age, sex, surgery year, surgical site, hemoglobin A1c level, and prescription for sodium-glucose cotransporter 2 inhibitors. Eligible patients were divided into two groups, those who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2-i group) and those who were not (control group). For each patient in the SGLT2-i group, we randomly selected four patients from the control group matched for the extracted characteristics. The primary outcome was the incidence of metabolic acidosis with an elevated anion gap and euglycemia. The secondary outcome was the lowest pH value of each patient during their ICU stay. A total of 155 patients were included in this study. Patients receiving sodium-glucose cotransporter 2 inhibitors had comparable characteristics to control participants; however, the proportions of patients undergoing dialysis were not similar. Metabolic acidosis with euglycemia was seen in 7/31 (22.6%) patients receiving sodium-glucose cotransporter 2 inhibitors and in 10/124 (8.1%) control patients (p = 0.047). This study shows that the use of sodium-glucose cotransporter 2 inhibitors is associated with a significantly higher incidence of metabolic acidosis with euglycemia. Patients receiving sodium-glucose cotransporter 2 inhibitors who are scheduled to undergo invasive surgical procedures should be closely monitored for the development of euglycemic diabetic ketoacidosis.


Higher circulating levels of proneurotensin are associated with increased risk of incident NAFLD.
Neurotensin (NT), an intestinal peptide able to promote fat absorption, is implicated in the pathogenesis of obesity. Increased levels of proneurotensin (pro-NT), a stable NT precursor fragment, have been found in subjects with nonalcoholic fatty liver disease (NAFLD); however, whether higher pro-NT levels are associated with an increased NAFLD risk independently of other metabolic risk factors is unsettled. Ultrasound-defined presence of NAFLD was assessed on 303 subjects stratified into tertiles according to fasting pro-NT levels. The longitudinal association between pro-NT levels and NAFLD was explored on the study participants without NAFLD at baseline reexamined after 5 years of follow-up (n = 124). Individuals with higher pro-NT levels exhibited increased adiposity, a worse lipid profile, and insulin sensitivity as compared to the lowest tertile of pro-NT. Prevalence of NAFLD was progressively increased in the intermediate and highest pro-NT tertile as compared to the lowest tertile. In a logistic regression analysis adjusted for several confounders, individuals with higher pro-NT levels displayed a raised risk of having NAFLD (OR = 3.43, 95%CI = 1.48-7.97, p = 0.004) than those in the lowest pro-NT tertile. Within the study cohort without NAFLD at baseline, subjects with newly diagnosed NAFLD at follow-up exhibited higher baseline pro-NT levels than those without incident NAFLD. In a cox hazard regression analysis model adjusted for anthropometric and metabolic parameters collected at baseline and follow-up visit, higher baseline pro-NT levels were associated with an increased risk of incident NAFLD (HR = 1.52, 95%CI = 1.017-2.282, p = 0.04). Higher pro-NT levels are a predictor of NAFLD independent of other metabolic risk factors.


Clobetasol-induced milia.
Milia developed in two patients with different chronic dermatoses after 2 weeks of treatment with clobetasol propionate ointment. Routine histologic and immunohistochemical analysis showed the cysts to be of eccrine gland origin.


Parry Romberg Syndrome.
Parry Romberg syndrome is a rare condition with unknown etiopathogenesis characterized by unilateral hemiatrophy of face leading to cosmetic disability which may be complicated by neurological features such as epilepsy, headache, trigeminal neuralgia etc. Management comprises of reconstructive surgery and symptomatic treatment. Prognosis is variable, it may progress to involve entire face with neck or it may stop in progression to some extent.


Evaluation of the susceptibility trends to meropenem in a nationwide collection of clinical isolates in Japan: a longitudinal analysis from 2002 to 2006.
The meropenem susceptibility surveillance study was performed between 2002 and 2006 in Japan. Meropenem resistance against Pseudomonas aeruginosa was nearly constant at about 10% during the period. For all species of the bacteria tested, the MIC(90) of meropenem in 2006 was not more than 4-fold higher than that in 2002 and 2004.


CORE MUSCLE ACTIVITY DURING THE CLEAN AND JERK LIFT WITH BARBELL VERSUS SANDBAGS AND WATER BAGS.
While the traditional clean and jerk maneuver implies simultaneous participation of a large number of muscle groups, the use of this exercise with some variations to enhance core muscle activity remains uninvestigated. The purpose of this study was to compare the muscle activity during clean and jerk lift when performed with a barbell, sandbag and a water bag at same absolute load. Descriptive, repeated-measures study. Twenty-one young fit male university students (age: 25 ± 2.66 years; height: 180.71 ± 5.42 cm; body mass: 80.32 ± 9.8 kg; body fat percentage: 12.41 ± 3.56 %) participated. Surface electromyographic (EMG) signals were recorded from the anterior deltoid (AD), external oblique (OBLIQ), lumbar erector spinae (LUMB), and gluteus medius (GM) and were expressed as a percentage of the maximum voluntary isometric contraction (MVIC). There were no significantly significant differences for AD muscle activity between conditions, whereas muscle activation values for OBLIQ (60%MVIC), GM (29%MVIC) and LUMB (85%MVIC) were significantly higher during the water bag power clean and jerk maneuver when compared with the other conditions. The clean and jerk is an exercise that may be used to enhance core muscle activity. Performing the maneuver with water bags resulted in higher core muscle activity compared with sandbag and standard barbell versions. 3.


'I actually thought that I was going to die': Lessons on the rip current hazard from survivor experiences.
Rip currents are strong, narrow, fast-flowing currents of water that occur on many beaches and in Australia contributing to 26 drowning deaths and several thousand lifeguard/lifesaver rescues each year. Educating the public about the rip current hazard is a primary focus of beach safety practitioners, but there has been a lack of qualitative research exploring the firsthand experiences of being caught in a rip current to assist in this regard. The aim of this study was to analyse interviews of rip current survivors to understand more about how people react when unintentionally caught in a rip current in order to help guide future public education to mitigate rip current drowning. Semi-structured interviews were conducted with 56 individuals (primarily Australian-born) about their experience of being caught in a rip current. Interviewees were recruited via an online survey and varied in age and self-reported swimming ability. Thematic analysis revealed three key temporal elements to the rip current experience: Before the Rip in which lack of awareness and knowledge, complacency, over-confidence, and attitude were prevalent themes; During the Rip which identified panic and temporary inhibition of decision-making, physical response, prior experience, and relationships with other beach users as themes; and After the Rip where post-rip effects and rip safety messaging and education were key themes. The importance of experiential immersion was a prevalent thread throughout all phases of the thematic analysis. Our research shows that being caught in a rip current can be an intense and traumatic experience and that lessons learned from survivors have significant implications for improving existing and future rip current education efforts. In this regard, we provide several recommendations based on evidence-based insights gained from our interviews including the development of immersive rip current experience using virtual reality. Despite the prevalence of rip currents causing drowning deaths and rescues, there has been a lack of qualitative research on firsthand experiences to aid in public education. These interviews emphasise the intense and traumatic nature of being caught in a rip current, underscoring the need for improved rip current education to aid in prevention of this, often harrowing, experience.


Endometrial Cytology During the Different Phases of the Estrous Cycle in Jennies: New Evidences.
Since in the mare and other animal species such as bitches and cats, the endometrial cell pattern varies depending on the phase of the estrous cycle, the aim of this study was to describe and quantify the endometrial cytological (EC) findings in cycling jennies. EC of eight nonpregnant jennies by cytobrush (CB) at diestrus (day 1 and day 14) and estrous (day 21) were evaluated. All slides were stained with Wright´s stain and microscopically examined at both 400× and 1000× magnification. Seven high-power fields (400×) were assessed in each smear and the endometrial epithelial cells and neutrophils (PMNs) were counted. Endometrial epithelial cells were classified as intact, distorted or fragmented and, on the basis of the presence of dense groups, in monolayer or single clusters. Cytoplasmic characteristics, such as vacuolation or streaming and size, form, position of nuclear characteristics, including karyorrhexis, were recorded. Background aspect, as clear, proteinaceous, or debris, was also considered. In general, sampling by CB provided a yield of cells and clumped endometrial epithelial cells in many smears, being more abundant in estrus than early and late diestrus. Individual endometrial epithelial cells, during estrous, presented a columnar morphology, ciliated or not ciliated and basal nuclei. During diestrus phase, endometrial epithelial cells presented a more cuboidal ciliated or not ciliated morphology. Moderate amount of proteinacious material and red blood cells (RBC) was also observed. Non variation in the percentage of PMNs during diestrus was obtained, but lower and segmented PMNs in CB smears were shown in estrous. This study provides new insights on the physiological changes of endometrial epithelial cells in cycling jennies during the estrus cycle. The CB technique represents a suitable and adequate method for endometrial evaluation, taking into account cytological and/or cytopathological purposes also in jennies.


Effect of individualized occupational therapy on social functioning in patients with schizophrenia: A five-year follow-up of a randomized controlled trial.
This study aimed to evaluate the long-term effects of adding individualized occupational therapy (IOT) to a three-months group occupational therapy (GOT) on social functioning in inpatients with schizophrenia or schizoaffective disorder at a follow-up investigation five-years after discharge. Initially, patients were randomly assigned to GOT + IOT or GOT alone, with 102 patients, 48 in GOT + IOT and 54 in GOT alone, completing the five years follow-up. The primary outcome was change in social functioning assessed by the Social Functioning Scale (SFS) from baseline to five-year follow-up. Other outcomes included Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), Intrinsic Motivation Inventory (IMI), Global Assessment of Functioning (GAF), Positive and Negative Syndrome Scale (PANSS), and Client Satisfaction Questionnaire-8 (CSQ-8). There were significant improvements for the GOT + IOT group over GOT in the SFS total score, which could be explained by improvements in withdrawal/social engagement, interpersonal communication, pro-social activities, recreation, and independence-competence. Multiple regression analysis showed that the period from hospitalization to commencing occupational therapy, type of occupational therapy, BACS motor speed, BACS executive function, and IMI interest/enjoyment were significantly associated with SFS total score. Our findings suggest that adding IOT to GOT may improve the long-term outcome on social functioning in schizophrenic patients. However, the long time period between intervention and follow-up and the unavailability of treatment information during the follow-up period has to be mentioned as a limiting factor of this study.


When Staying Home Is Not Safe: An Investigation of the Role of Attachment Style on Stress and Intimate Partner Violence in the Time of COVID-19.
Intimate partner violence (IPV) is a major public health concern, with increasing rates of IPV being seen around the world during the COVID-19 pandemic. Previous research has linked the perpetration of IPV and other forms of sexual violence to aspects of romantic attachment psychology, with insecure anxious/preoccupied attachment most often linked to higher rates of IPV. Stressful events typically activate the attachment system and may either aggravate or disrupt its regulatory functioning. In the present study, we investigated whether COVID-related PTSD and depressive symptoms were associated with increased IPV perpetration and whether this relationship was moderated by levels of attachment security. Our findings indicated that higher COVID-related PTSD was significantly associated with increased IPV perpetration in securely attached individuals, whereas depressive symptoms was significantly associated with decreased IPV perpetration in securely attached individuals. IPV perpetration by insecure individuals was consistently high regardless of COVID-related PTSD or depressive symptoms. These findings suggest that COVID-related PTSD may erode adaptive attachment functioning, particularly among the previously secure, which can have important consequences for secure individuals and their intimate partners. The present findings may explain some of the recent increase in IPV cases worldwide and serve to raise awareness and motivate clinical interventions to more efficiently help both victims and perpetrators of IPV stay safe while staying home.


Relation between catecholamine-induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia.
1. The effect of catecholamines on cyclic adenosine 3'5'-monophosphate (cyclic AMP) production in isolated rat superior cervical ganglia has been measured under experimental conditions in which they also produce ganglion hyperpolarization.2. (+/-)Isoprenaline (1 muM) increased cyclic AMP levels by 8-100 times after 15 min incubation at 25 degrees C. Half-maximal stimulation occurred at about 0.03 muM. This was due to stimulation of beta-receptors, since it was prevented by 1 muM-propranolol but not by 1 muM-phentolamine.3. The alpha-agonists phenylephrine (100 muM), dopamine (100 muM) and clonidine (1 muM) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 muM) was also ineffective at 37 degrees C in the presence of 10 mM-theophylline.4. Exogenous cyclic AMP (0.01-1 mM) hyperpolarized the ganglion. This effect was replicated by other adenosine compounds, most effectively by adenosine and by adenosine 5'-monophosphate, and was antagonized by theophylline. Dibutyryl cyclic AMP was weaker than cyclic AMP.5. Neither theophylline nor the non-xanthine phosphodiesterase inhibitor, Ro 20-1724, enhanced the hyperpolarizing actions of noradrenaline or dopamine.6. Since catecholamine-induced hyperpolarization of the isolated rat ganglion is induced via alpha-receptors, whereas cyclic AMP-production is induced via beta-receptors, it is concluded that cyclic AMP is unlikely to mediate the hyperpolarization. The effect of exogenous cyclic AMP may be due to an action on external adenosine-receptors.


Molecular insights into the impacts of iron(III) ions on membrane fouling by alginate.
Molecular mechanisms responsible for the filtration behaviors of sodium alginate (SA) in presence of different iron(III) ion concentration were explored in this study. It was found that specific filtration resistance (SFR) of alginate mixtures (1.0 gSA/L) firstly increased and then decreased to a trough with iron(III) concentration increase from 0 to 2.5 mM. Alginate mixture interacting with 0.1 mM iron(III) possessed an SFR as high as 1.65 × 1014 m kg-1, which could be explained by Flory-Huggins lattice theory related with gel filtration. Optical observation showed significant morphology transition (from gel to granular solids) of foulant layers with iron(III) concentration increase. A series of characterizations indicated the change of microstructure, pH and surface charge of alginate mixture with iron(III) concentration. Density functional theory (DFT) simulation suggested that iron(III) ion preferentially forms coordination bonds with three terminal carboxyl groups of alginate chains, facilitating elongation and cross-linking of alginate chains. Such a coordination mode induces formation of a slime and homogeneous gel, corresponding to high SFR. Continuous increase in iron(III) concentration leads to non-terminal coordination, which makes alginate chains more clustered and coiled. This effect, together with effects of the reduced surface charge and electric double layer compression, significantly decrease SFR of alginate mixtures. This study provided deep molecular insights into effects of iron(III) ions on alginate fouling.