Regional variation in ICD implantation rates: the shocking truth?
There is considerable disparity in the implantation of ICDs across the UK, with a fourfold difference between regions with the highest and lowest implantation rates.


HY-1 induces G(2)/M cell cycle arrest in human colon cancer cells through the ATR-Chk1-Cdc25C and Weel pathways.
The novel aroylthiourea analogue of podophyllotoxin HY-1 (4β-[benzoyl-thioureido]-4-deoxypodophyllotoxin) was synthesized in our laboratory with the aim of developing multitargeted DNA topoisomerase II inhibitors. The compound showed significant antiproliferative effects on seven cancer cell lines and induced G2 /M phase arrest in HCT116 cells. Moreover, HY-1 showed a potent inhibitory effect on topoisomerase II-mediated kinetoplast DNA decatenation in a dose-dependent manner. Our results showed that cdc2 phosphorylation and decreased cdc2 kinase acitivity through the ATR-Chk1-Cdc25C and Weel pathways were the central mechanisms for G2 /M phase arrest in human colon cancer cells.


Regulation of survivin and caspase/Bcl-2/Cyto-C signaling by TDB-6 induces apoptosis of colorectal carcinoma LoVo cells.
Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism. The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo. Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells. Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/Cyto-C signaling. The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo. Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2. TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment.


Anaesthetic drugs in the elderly.
The outcome of surgery in the elderly depends on the skill of the surgeon and the expertise of the anaesthetist caring for the patient. This anaesthetic proficiency depends initially on the application of the detailed knowledge of the drugs used during anaesthesia, and on the understanding of the way changes in the elderly patients' physiology with ageing affects both kinetic and dynamic facets of pharmacology. However, the very diversity of the elderly population makes their precise response to drugs unpredictable, and, therefore, clear, unequivocal guidance on practice is limited. The important changes in both physiology and pharmacokinetics with ageing are discussed before covering the specific drugs used in current anaesthetic practice in the United Kingdom. This review covers the drugs used primary for the induction and maintenance of anaesthesia, and only covers related fields where there are changes in recent practice that raise issues of importance during surgery. This review, therefore, deals mainly with the anaesthetic vapours and intravenous drugs, and with neuromuscular blocking agents. The restriction of space and the enormity of the subject demand that the areas covered in this review are solely limited to the major classes of drugs used routinely in general anaesthetic practice in the United Kingdom. The detailed pharmacokinetics and pharmacodynamics of drugs also used in the post-operative period, such as the wide variety of opiates, and of drugs mainly used in general medical practice, but occasionally used as premedicants or supplements during anaesthesia, have been monitored only in passing.


A single amino acid determines the catalytic efficiency of two alkenal double bond reductases produced by the liverwort Plagiochasma appendiculatum.
Alkenal double bond reductases (DBRs) catalyze the NADPH-dependent reduction of the α,β-unsaturated double bond of many secondary metabolites. Two alkenal double bond reductase genes PaDBR1 and PaDBR2 were isolated from the liverwort species Plagiochasma appendiculatum. Recombinant PaDBR2 protein had a higher catalytic activity than PaDBR1 with respect to the reduction of the double bond present in hydroxycinnamyl aldehydes. The residue at position 56 appeared to be responsible for this difference in enzyme activity. The functionality of a C56 to Y56 mutation in PaDBR1 was similar to that of PaDBR2. Further site-directed mutagenesis and structural modeling suggested that the phenol ring stacking between this residue and the substrate was an important determinant of catalytic efficiency.


Strategies to intervene on causal systems are adaptively selected.
How do people choose interventions to learn about causal systems? Here, we considered two possibilities. First, we test an information sampling model, information gain, which values interventions that can discriminate between a learner's hypotheses (i.e. possible causal structures). We compare this discriminatory model to a positive testing strategy that instead aims to confirm individual hypotheses. Experiment 1 shows that individual behavior is described best by a mixture of these two alternatives. In Experiment 2 we find that people are able to adaptively alter their behavior and adopt the discriminatory model more often after experiencing that the confirmatory strategy leads to a subjective performance decrement. In Experiment 3, time pressure leads to the opposite effect of inducing a change towards the simpler positive testing strategy. These findings suggest that there is no single strategy that describes how intervention decisions are made. Instead, people select strategies in an adaptive fashion that trades off their expected performance and cognitive effort.


Latamoxef for the prophylaxis of abdominal surgical wound infection: a controlled clinical trial.
In a series of 236 abdominal operations, patients were allocated at random to receive a single intravenous dose of either 1 g cephaloridine or 1 g latamoxef (at induction of anesthesia) for the prophylaxis of postoperative wound infection. Of the 116 patients given latamoxef, one developed major and seven minor wound infections, whereas five major and 21 minor infections occurred in the cephaloridine group (P less than 0.01). Latamoxef has now replaced cephaloridine as our prophylactic antibiotic of choice in potentially contaminated abdominal operations.


Biomass-Derived Heteroatom-Doped Carbon Aerogels from a Salt Melt Sol-Gel Synthesis and their Performance in Li-S Batteries.
An ionothermal sol-gel strategy to synthesize hierarchically porous carbon aerogels doped with different heteroatoms is presented by using biomass precursors in a scalable process. Morphologically similar but chemically different materials are used to study the influence of heteroatoms in Li-S batteries. The materials show capacities as high as 1290 mAh g(-1) in the first cycle using 50 wt % S loading. Heteroatom doping reduces the capacity fading and the polarization throughout cycling. Zeta potential measurements reveal positive surface charges for heteroatom-doped carbons and indicate attractive interactions with polysulfides causing reduced fading. A polysulfide-selective sorption study reveals strongly different adsorption behavior depending on the carbon's chemical composition. Interestingly, the polysulfide fraction is also crucial. The results indicate that improved adsorption of long-chain polysulfides to doped carbons is related to improved capacity retention.


Determination of the iron(IV) local spin states of the Q intermediate of soluble methane monooxygenase by Kβ X-ray emission spectroscopy.
Soluble methane monooxygenase (sMMO) facilitates the conversion of methane to methanol at a non-heme FeIV2 intermediate MMOHQ, which is formed in the active site of the sMMO hydroxylase component (MMOH) during the catalytic cycle. Other biological systems also employ high-valent FeIV sites in catalysis; however, MMOHQ is unique as Nature's only identified FeIV2 intermediate. Previous 57Fe Mössbauer spectroscopic studies have shown that MMOHQ employs antiferromagnetic coupling of the two FeIV sites to yield a diamagnetic cluster. Unfortunately, this lack of net spin prevents the determination of the local spin state (Sloc) of each of the irons by most spectroscopic techniques. Here, we use Fe Kβ X-ray emission spectroscopy (XES) to characterize the local spin states of the key intermediates of the sMMO catalytic cycle, including MMOHQ trapped by rapid-freeze-quench techniques. A pure XES spectrum of MMOHQ is obtained by subtraction of the contributions from other reaction cycle intermediates with the aid of Mössbauer quantification. Comparisons of the MMOHQ spectrum with those of known Sloc = 1 and Sloc = 2 FeIV sites in chemical and biological models reveal that MMOHQ possesses Sloc = 2 iron sites. This experimental determination of the local spin state will help guide future computational and mechanistic studies of sMMO catalysis.


Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.


A report on the association of influenza B virus with respiratory tract infection of hospitalized children in Saudi Arabia.
Influenza viruses are recognized as one of the major causes of respiratory tract infection in young children and elderly people throughout the world. In this report, influenza B virus was detected when 200 clinical samples of nasopharyngeal aspirates, collected from hospitalized children aged from one month to three years with respiratory tract infections, were tested by Reverse Transcription Polymerase Chain Reaction (RT-PCR). PCR products on the conserved regions sequence of the non-structural gene identified the presence of influenza B virus in the clinical samples. This finding is important and it may become a real threat if not well considered. Due to massive mutations that influenza virus type B undergone, high protective measured should be taken. Therefore, further characterization and isolation of the virus are essentially needed.


A macro cell-attached patch-clamp study of the properties of the Na current in the vicinity of the motor endplate region of frog single interosseal skeletal muscle fibres.
A macro cell-attached patch-clamp technique using large (16 microns) electrodes was developed to study the properties of the Na current (INa) in the motor endplate region of frog interosseal muscle fibres (resting potential approx.-99 mV). The fibre isolation procedure allows the formation of gigaOhm seals and thus a good voltage-clamp control of the patch. At 22 degrees C, in the presence of 110 mM external [Na] and of K channel blockers, INa activates at -49.6 +/- 1.9 mV, reaches a maximum of 4.33 +/- 0.66 mA/cm2 at -7.5 +/- 2.5 mV and reverses at Vrev equal to +63.2 +/- 1.9 mV. There is no evidence for the presence of a tubular INa. When the [Na] in the recording pipette is changed, Vrev exactly follows the Nernst equation for Na ions. An internal [Na] of 9.69 mM is determined. The Na conductance is maximum (63.56 +/- 7.03 mS/cm2) at +8.9 +/- 3.0 mV and markedly decreases for potentials positive to +25 mV. In contrast, the Na permeability (maximum of 6.13 +/- 0.95 x 10(-4) cm/s at +51.4 +/- 5.6 mV) remains more constant at positive potentials. The Na channels are half-inactivated at -68.9 mV and half-activated at -37.9 mV. At the potential at which INa is maximum, the half-time of activation is 223.9 +/- 10.5 microseconds, the time to peak 365.7 +/- 13.5 microseconds and the time constant of inactivation 260.7 +/- 11.2 microseconds. The time constant of reactivation at -100 mV is 1.44 +/- 0.19 ms. These and other results show that INa can be adequately studied with this technique.


Studies on quantitative relationships between the structure and in vitro tuberculostatic potency of 2-cyanomethylbenzimidazole derivatives.
Quantitative relationships were studied between in vitro tuberculostatic potency and physico chemical parameters relating to the structure of 2-cyanomethylbenzimidazoles. The activity of the compounds was found to be mathematically described as a square function of molar refractivity of the substituent or the RM values and a linear function of the wavelength at the absorption maximum or the connectivity index for the aromatic ring in the substituent. The equation was obtained, statistically significant on the 99% level and describing of about 83% of variance in activity data, which may be of value for the design of new active derivatives.


The early mineralization of enamel. Fine structural observations on the cellular localization of calcium with the potassium pyroantimonate technique.
The potassium pyronatimonate technique was used to study the cellular distribution of calcium during the early mineralization of enamel in rat molar tooth germs at the electron microscope level. Differing patterns of calcium distribution were observed in the ameloblast seemingly associated with the appearance of Tomes' process. In the early secretory ameloblast calcium pyroantimonate deposits were observed within the Golgi apparatus, within coated vesicles, within mitochondria and associated with the inner aspect of the cell membrane. However, with the development of Tomes' process the ameloblast no longer demonstrated these discrete deposits of calcium pyroantimonate. Instead they showed a diffuse cytoplasmic staining pattern with no preference for any particular organelle.


Analytical methods for the determination of folic acid in a polymeric micellar carrier.
Amphiphilic copolymers have been the object of growing scientific interest due to their ability to form polymeric micelles in aqueous environments entrapping lipophilic drugs in their inner core. In this study, polyvinylalcohol substituted with oleic acid was employed as an amphiphilic micellar carrier for folic acid (FA), a model drug similar for its chemical-physical characteristics to methotrexate. In order to investigate the stability of the polymeric micelles, the drug incorporation and the kinetic aspects of drug release from these systems, selective analytical methods are required. The development of three analytical methods suitable for selectively identifying and reliably determining FA contained in the micelles and in the delivery systems is reported. UV derivative (first and second order) spectrophotometry was first applied to the aqueous solution of the FA containing micelles obtained at pH 9.0 and provided a characteristic spectral profiling with sharp peaks, related to the analyte, whose amplitude was used for quantitative application. A second approach involved a solid phase extraction (strong anion exchanger), which provided an effective clean up of the FA micelles solution, allowing accurate analysis to be performed also by a conventional spectrophotometric method. A RP-HPLC method, selectively supplying the FA separation from the micelles' components, was then used as a reference method to determine the accuracy of the spectrophotometric methods. These methods were applied to various micelle composition and to the delivery system study.


Prevalence of gastroesophageal reflux disease in major depressive disorder: a population-based study.
Gastroesophageal reflux disease (GERD) is a common physical disease among psychiatric patients. We conducted this study to investigate the prevalence and risk of GERD in patients with major depressive disorder (MDD) in Taiwan. We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. The study subjects included 4790 patients with MDD and 728,749 people in the general population during 2005. Distributions of GERD as well as age, gender, income, region of residence, and medical comorbidities, such as diabetes mellitus, hypertension, renal disease, hyperlipidemia, and ischemic heart disease, in the 2 groups were examined by χ(2)-tests. Multivariate logistic regression models were used to analyze the associations between MDD and GERD. The 1-year prevalence rates of GERD in patients with MDD and the general population were 3.75% and 1.05%, respectively. The prevalence rate of GERD was significantly higher in patients with MDD in all age, sex, insurance amount, region, and urbanicity subgroups (all p < 0.001). The multivariate logistic regression analysis showed that patients with MDD were significantly associated with an increased rate for GERD ([Odds Ratio] = 3.16; 95% Confidence Interval = 2.71-3.68; p < 0.001). The prevalence of GERD was significantly higher in patients with MDD. In clinical practice, psychiatrists should pay attention to the possibility of GERD symptoms, such as heartburn, regurgitation, or dysphagia, and should consider consulting Gastroenterology specialists when clinically indicated.


Immunohistochemical features of the human retina and retinoblastoma.
The immunohistochemical features of 24 retinoblastoma specimens from 22 patients, 15 with unilateral and 7 with bilateral disease, were examined by the labelled streptavidin biotin (LSAB) method and compared with those of specimens from the remaining morphologically normal retina. In the normal retina, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin were detected in astrocytes and/or Müller cells. Neurofilament protein was seen in axons of the ganglion cells, synaptophysin was present in both plexiform layers, bcl-2 oncoprotein was seen in ganglion cells and bipolar cells, and neuron-specific enolase (NSE) was detected in ganglion cells, bipolar cells and photoreceptor cells and in their cell processes. While retinoblastoma (Rb) protein expression was noted in ganglion cells, bipolar cells, and some photoreceptor cells, p53 protein was not expressed at all. In all retinoblastomas, strong NSE expression and weak bcl-2 expression was observed in almost all tumour cells and synaptophysin was localized in rosette-forming cells, while tumour cells were devoid of S-100, GFAP, vimentin and neurofilament protein. These findings support the view that retinoblastomas are composed of neuron-committed cells. In addition, no Rb protein expression was detected in retinoblastomas, whereas p53 expression was found in 18 cases (75%).


The impact of heterogeneous environmental regulation on high-quality economic development in China: based on the moderating effect of digital finance.
Under the new normal of economic growth, implementing environmental regulation policies and developing digital finance have become essential factors affecting high-quality economic development. This study aims to examine whether environmental regulation has a positive effect on high-quality economic development and what impact digital finance has in the process of environmental regulation affecting high-quality economic development. This study uses the panel data of 30 provinces in China from 2011 to 2019 to measure the high-quality economic development by using the entropy-TOPSIS method based on constructing an indicator system for high-quality economic development. Then, environmental regulations are classified into four categories: economic, command based, legal, and supervised, and digital finance is included in the analysis framework. The impact of heterogeneous environmental regulations on high-quality economic development and the indirect influence mechanism played by digital finance are empirically analyzed. The results show that command-based environmental regulation significantly hinders improving economic development quality. In contrast, supervised environmental regulation plays a significant positive role and can therefore serve as an essential driver of high-quality economic development. In addition, digital finance plays a significant positive moderating role in the influence of environmental regulation on the economy's high-quality development level. After the robustness test, the conclusion is still valid. Further heterogeneity analysis shows that the impact of environmental regulation on high-quality economic development and the moderating effect of digital finance differ across dimensions of economic quality development and have regional heterogeneity. The research findings are conducive to formulating appropriate environmental regulation policies and giving full play to the positive role of digital finance, providing support for promoting high-quality economic development.


Use of recombinant plasmids to characterize collagen RNAs in normal and transformed chick embryo fibroblasts.
Two recombinant plasmids containing chick collagen DNA sequences have been used to characterize messenger RNAs for pro-alpha1 (type I) and pro-alpha2 collagen. Poly(A)-containing RNA from chick embryo calvaria and long bones, tissues which are very active in collagen synthesis, were electrophoresed on agarose gels containing methylmercuric hydroxide and transferred to diazobenzyloxymethyl paper; these covalently bound RNAs were hybridized to 32P-labeled pro-alpha1 or pro-alpha2 collagen DNA sequences derived from the recombinant plasmids. The pro-alpha1 collagen probe identified two RNAs, a major species of 5000 bases and a minor species of 7100 bases; the pro-alpha2 collagen probe hybridized to a major species very similar in size to the pro-alpha1 mRNA, about 5200 bases, and a minor species of 5700 bases. It is possible that the 7100 and 5700 base RNAs represent precursors of pro-alpha1 and pro-alpha2 collagen mRNA, respectively. When similar hybridization experiments were performed with RNA from chick embryo fibroblasts, both the pro-alpha1 and pro-alpha2 collagen mRNAs were observed, as well as their corresponding larger species. With RNAs from fibroblasts transformed by Rous sarcoma virus, however, the levels of all RNA species which hybridized with the pro-alpha1 and pro-alpha2 collagen DNA probes were significantly reduced.


Paget's disease of bone and hyperparathyroidism: coincidence or causal relationship?
We studied 173 patients with Paget's disease and 105 patients with hyperparathyroidism. Nine patients were found to have both disorders.


Relationship between models of care and key rehabilitation milestones following unilateral transtibial amputation: a national cross-sectional study.
To identify different models of care (MOC) post transtibial amputation (TTA) and relate these to achievement of rehabilitation milestones. Retrospective analysis of rehabilitation milestone data and a survey of MOC in 10 vascular centres. NHS Scotland vascular centres. All unilateral TTA between January 2011 and December 2014 (n = 643). Time (in days) to achieve the following rehabilitation milestones: compression therapy, early walking aid, casting for a prosthetic limb, prosthetic delivery, inpatient discharge and final discharge from rehabilitation. MOC were scored according to seven key aspects of service provision. The mean age of the cohort was 67 [standard deviation (SD) 13] years, 76% were male and 63% had peripheral arterial disease and diabetes. The median number of days to achieve rehabilitation milestones varied between centres {compression therapy six [interquartile range (IQR) 0-12], early walking aid 14 (IQR 10-27), prosthetic casting 39 (IQR 27-71), prosthetic delivery 53 (IQR 36-87), inpatient discharge 53 (IQR 29-85) and final discharge from rehabilitation 141 (IQR 92-209)}. Only two centres included all seven key aspects of service provision within their MOC. Vascular centres that achieved the optimal MOC achieved the rehabilitation milestones more quickly than other vascular centres. A positive association was found between optimal MOC and early achievement of rehabilitation milestones post TTA. Key aspects of service provision associated with a quicker time to achieve rehabilitation milestones included: use of a postoperative rigid dressing, specialist physiotherapy input in the early postoperative period, daily inpatient gym sessions and inpatient prosthetic provision. To the authors' knowledge, this is the first study to document MOC following TTA and to relate these to the achievement of rehabilitation milestones.


Positive correlation of plasma PCSK9 levels with HbA1c in patients with type 2 diabetes.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be involved in not only lipid metabolism but also glucose homeostasis. Glycated haemoglobin (HbA1c ) is a 'gold standard' for monitoring long-term glycaemic control. However, the correlation of plasma PCSK9 levels with HbA1c remains undetermined. We consecutively enrolled 805 subjects undergoing coronary angiography, including 176 patients with type 2 diabetes mellitus (T2DM) and 629 non-diabetic patients. The baseline characteristics were collected, and serum PCSK9 level was assessed by ELISA. Univariable regression analysis and multiple-variable regression analysis were used to examine the associations of PCSK9 with HbA1c . Furthermore, the HbA1c was compared across the tertiles of PCSK9 levels. And also, PCSK9 levels were compared in poorly controlled (HbA1c ≥ 7.0%) and well-controlled (HbA1c < 7.0%) patients with T2DM. PCSK9 levels were positively correlated with low-density lipoprotein cholesterol in both T2DM and non-T2DM. Univariable regression analysis revealed a positive association between PCSK9 and HbA1c in patients with T2DM (β = 0.255, p = 0.001) but not in patients without diabetes (β = 0.061, p = 0.128). Multiple-variable regression analysis exhibited that PCSK9 was independently correlated with HbA1c in T2DM after adjustment for traditional atherosclerotic risk factors (β = 0.197, p = 0.020). Moreover, HbA1c level was higher in patients with the highest tertile of PCSK9 than that in the lowest tertile (p = 0.042). Additionally, higher levels of PCSK9 were found in poorly controlled group compared with the well-controlled group (p = 0.029). Data suggest a positive correlation of PCSK9 levels with HbA1c in patients with T2DM but not in patients without T2DM, indicating a potential role of PCSK9 in T2DM. Copyright © 2015 John Wiley & Sons, Ltd.


Laparoscopic prosthetic hiatal reinforcement for large hiatal hernia repair.
Large hiatal hernia (LHH) is defined by a hiatal defect larger than 6cm; repair is indicated whenever it becomes symptomatic. As the risk of recurrence after most techniques is relatively high, laparoscopic repair with prosthetic reinforcement of the hiatus has been proposed to reduce the recurrence rate. Our technique and outcomes are reported. Laparoscopic prosthetic hiatal reinforcement was performed in 58 patients between August 1997 and October 2009. Prolene(®), Mersilene(®), Goretex(®), and Parietex(®) were the four types of prosthetic material used. Since January 2004, the double-sided V shaped Crurasoft(®) mesh was introduced. Surgical evaluation was based on anatomical and functional criteria: the anatomical results included the presence of recurrent hiatal hernia or esophageal stricture as evaluated by an upper gastrointestinal (UGI) series; functional evaluation was based on a questionnaire concerning long-term patient satisfaction according to the Visick score. Median follow-up was 51 months. Postoperative UGI series were performed during the initial hospitalization in 37 patients: results were judged to be satisfactory. A routine follow-up UGI series was obtained at 8 months and one year in 46 patients. Two patients underwent reoperation for lower esophageal stricture at 6 months and 16 months. Forty-five patients (77.6%) were reevaluated. Of these, 29 patients (64.4%) were free of symptoms with a good quality of life, eight patients (17.7%) complained of moderate dysphagia and two patients (4.4%) had severe dysphagia. Four patients (8.9%) had moderate pyrosis while severe pyrosis requiring long term PPI treatment was observed in three patients (6.7%). No prosthesis-induced ulceration or perforation was noted. Late follow-up UGI series, performed in 21 patients, showed two patients with severe stricture and a single case of recurrence, but neither of these patients required surgical management. The addition of mesh reinforcement to surgical repair of large hiatal defects is safe and beneficial in terms of quality of life.


Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients.
The treatment of choice for advanced non-small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH. The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options. The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs. Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.


Impacts of Air Velocity Treatments under Summer Conditions: Part II-Heavy Broiler's Behavioral Response.
Broiler chickens exposed to heat stress adapt to various behavioral changes to regulate their comfortable body temperature, which is critical to ensure their performance and welfare. Hence, assessing various behavioral responses in birds when they are subjected to environmental changes can be essential for assessing their welfare under heat-stressed conditions. This study aimed to evaluate the effect of two air velocity (AV) treatments on heavy broilers' behavioral changes from 43 to 54 days under summer conditions. Two AV treatments (high and low) were applied in six poultry growth chambers with three chambers per treatment and 44 COBB broilers per chamber from 28 to 61 days in the summer of 2019. Three video cameras placed inside each chamber (2.44 m × 2.44 m × 2.44 m in dimension) were used to record the behavior of different undisturbed birds, such as feeding, drinking, resting, standing, walking, panting, etc. The results indicate that the number of chickens feeding, drinking, standing, walking, sitting, wing flapping, and leg stretching changed under AV treatments. High AV increased the number of chickens feeding, standing, and walking. Moreover, a two-way interaction with age and the time of day can affect drinking and panting. This study provides insights into heavy broilers' behavioral changes under heat-stressed conditions and AV treatments, which will help guide management practices to improve birds' performance and welfare under commercial conditions in the future.


Mechanisms of Compound Sophora flavescens (Kushen) Decoction for the Treatment of Ulcerative Colitis based on Network Pharmacology and Molecular Docking Technology.
The compound Sophora flavescenes (Kushen) decoction was found to reduce the inflammatory symptom of Ulcerative Colitis (UC). However, there exists a very limited understanding of the molecular pharmacological mechanisms. This study aimed to explore the mechanism of compound Sophora flavescens (Kushen) decoction in treating ulcerative colitis from the perspective of network pharmacology. Active components and potential targets of compound Sophora flavescens (Kushen) decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. GeneCards and other databases were used to predict and screen ulcerative colitis-related genes. Cytoscape software was applied to construct the "drugactive component-disease-target" network. GO function and KEGG pathway enrichment analyses revealed the potential pathway of the compound Sophora flavescenes (Kushen) decoction for UC. After the screening, a total of 124 active ingredients and 163 potential therapeutic targets for UC were obtained from the compound Sophora flavescens (Kushen) decoction. Protein interaction network analysis showed that 15 key targets could be identified for the possible treatment of UC. GO and KEGG analyses showed that the active ingredients in the compound Sophora flavescens (Kushen) decoction were mainly enriched in 2556 biological processes and 172 signaling pathways. The study showed that the compound Sophora flavescens (Kushen) decoction has therapeutic effects on UC through multi-component, multi-target, and multi-pathway.


Normal serum pepsinogen I levels in adults: a population-based study with special reference to Helicobacter pylori infection and parietal cell antibodies.
Low serum pepsinogen I (PG I) values are common in subjects with advanced corpus atrophy with or without parietal cell antibodies (PCA). Elevated values are usual during Helicobacter pylori infection. PG I levels were determined in two randomly selected cross-sectional adult population samples using the Gastroset PGI test kits. The sera (408 in 1973 and 504 in 1994), tested earlier for H. pylori infection and now for PCA, represented subjects living in Vammala, Finland. In the PCA-negative population, the mean (+/-SD) PG I level was significantly higher in men than in women among both H. pylori-negative (88.13+/-34.16 microg/l versus 72.43+/-29.31 microg/l; p<0.0001) and H. pylori-positive (110.50+/-50.59 microg/l, versus 97.74+/-44.82 microg/l, p<0.0001) subjects; the difference between all H. pylori-positive and -negative subjects was also significant (p<0.001). In the 10-year age groups, age had no impact on the mean PG I levels in H. pylori-negative subjects (p=0.860). In the PCA-positive population, the 10 H. pylori-positive subjects had higher mean PG I levels (112.96+/-53.62 microg/l) than the 13 H. pylori-negative subjects (32.57+/-27.59 microg/l; p=0.002); the latter mean was also significantly lower than that of the PCA- and H. pylori-negative subjects (80.08+/-32.69 microg/l; p<0.0001). Men had higher normal PG I values than women, but there was no significant variation by age. H. pylori infection was associated with elevated PG I levels and a small decrease with increasing age. Non-infected PCA-positive subjects showed the lowest mean PG I level.


Placenta Percreta With Invasion into the Urinary Bladder.
Placenta percreta is a rare condition, which can lead to significant morbidity and potentially mortality. We present a case of a 38-year-old woman who presented at 24 weeks gestation with vaginal bleeding and was found to have complete placenta previa with placenta percreta invading the urinary bladder. Her hospital course was complicated by bilateral pulmonary emboli. She underwent an exploratory laparotomy, repeat Caesarean section, and total abdominal hysterectomy. Because of placental invasion into the bladder, the procedure was complicated by bladder and ureteral injuries for which urology carried out repair. Postoperatively, the patient had a persistent bladder leak until postoperative day #39.


Inhibitor-assisted refolding of protease: a protease inhibitor as an intramolecular chaperone.
Pleurotus ostrearus proteinase A inhibitor 1 (POIA1), which was discovered as a protease inhibitor, is unique in that it shows sequence homology to the propeptide of subtilisin, which functions as an intramolecular of a cognate protease. In this study, we demonstrate that POIA1 can function as an intramolecular chaperone of subtilisin by in vitro and in vivo experiments. The specific cleavage between POIA1 and the mature region of subtilisin BPN' occurred in a refolding process of a chimera protein, and Bacillus cells transformed with a chimera gene formed a halo on a skim milk plate. The mutational analyses of POIA1 in the chimera protein suggested that the tertiary structure of POIA1 is required for such a function, and that an increase in its ability to bind to subtilisin BPN' makes POIA1 a more effective intramolecular chaperone.


KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations.
The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. The nosology of autosomal recessive forms is complex as most mapped loci have been identified in only one or a few families and account for only a small percentage of patients. We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3 in two patients from the original linked family. In addition, wide genome scan and candidate gene analysis were performed in a second family of Palestinian origin. We identified a single homozygous mutation, p.R350G, that was found to cosegregate with the disease in the SPG30 kindred and was absent in 970 control chromosomes while affecting a strongly conserved amino acid at the end of the motor domain of KIF1A. Homozygosity and linkage mapping followed by mutation screening of KIF1A allowed us to identify a second mutation, p.A255V, in the second family. Comparison of the clinical features with the nature of the mutations of all reported KIF1A families, including those reported recently with hereditary sensory and autonomic neuropathy, suggests phenotype-genotype correlations that may help to understand the mechanisms involved in motor neuron degeneration. We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa.


GABA stimulation and blockade in the hypothalamus and midbrain: effects on feeding and locomotor activity.
Microinjections of the gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BM) (100 ng), into the anterolateral hypothalamus (LH) increased ingestion of sweet milk. A subsequent injection of BM 48 hrs. later produced a type of kindling effect consisting of feeding related automatisms, such as gnawing and biting. The behavioral effects of injections of 100 ng of GABA into the LH were variable. GABA injections into the ventromedial hypothalamus (VMH) reliably increased food intake. GABA injections into the origin of the nigrostriatal dopamine (DA) neurons in the substantia nigra (SN) suppressed it. Similar injections into the origin of the mesolimbic DA cells in the ventral tegmental area (VTA) had no effect on feeding behavior. Following BM injections into the SN, a moderate increase in tilt box activity was observed. A second injection of the GABA blocker 6 days later exaggerated this effect. Short latency extreme hyperactivation was accompanied by unidirectional barrel rolling which persisted until blocked by local injections of GABA.


Developing an Intervention to Reduce Harm in Hospitalized Patients: Patients and Families in Research.
Patient safety-focused research may be strengthened by the inclusion of patients and family members in research design; yet, published methodologies for doing so are scarce. This study engaged patients and families in research design of an intervention to increase patient/family engagement, with reduction of harm in hospitalized patients. The study design team convened a Patient Safety Advisory Panel to explore potential testable interventions to increase patient/family engagement with safety. They explored the preferred intervention, Speak Up-My Advocate for Patient Safety (MAPS), through multistakeholder focus groups. Participants emphasized the importance of including patient/family when designing interventions. Regarding the Speak Up-MAPS intervention, perceptions from stakeholders were mixed, including the value and potential complexity, role confusion, and cost of the proposed advocate role. Intentional inclusion of the patient/family in research is important and practical. Both strengths and challenges of the proposed intervention were identified, indicating the need for further study.


The effects of medium chain triglyceride (MCT) supplementation using a C8:C10 ratio of 30:70 on cognitive performance in healthy young adults.
The brain can utilise medium chain triglycerides (MCTs) as an alternative fuel to glucose, and research has shown that MCT ingestion improves cognitive function in diseased and/or elderly individuals. The aim of this study is to determine if these improvements can also be observed in young, healthy adults. Furthermore, we aim to establish the ideal dosage and timeframe necessary for an effect. Participants were divided equally into three groups of 10 (Placebo (0 g), 12 g and 18 g MCT/day) and were supplemented for 4 weeks. The supplement had a C8:C10 ratio of 30:70. Participants visited the laboratory once a week for 5 weeks (baseline, test weeks 1-4) to undergo a battery of cognitive tests; Trail Making, Digit Span, Spatial Span, Covert Shift of Attention, and Rapid Visual Information Processing. After 2-3 weeks of supplementation, MCT ingestion enhanced performance in cognitive tasks, including: Trail Making A/B and Digit Span Forwards/Backwards (ps<0.001) when compared to a placebo group taking a carbohydrate gel. In Spatial Span Backwards, there was a significant main effect of group (p = 0.002). Where significance was seen, there were main effects of time after 2-3 weeks (ps<0.05). There was minimal difference between the two MCT intervention groups in most measures (ps>0.05). There were also null results in tasks measuring attention and reaction time (ps>0.05). MCT ingestion improved cognitive performance after 2-3 weeks, with minimal difference between taking 12 g and 18 g MCT/day groups, suggesting a possible dose-response threshold at 12 g MCT/day when supplementing over a short period.


INTRAHEPATIC CHOLANGIOJEJUNOSTOMY FOR MALIGNANT HILAR BILIARY OBSTRUCTION: APPROACH TO THE LEFT HEPATIC DUCT.
Biliary enteric anastomosis for relief of biliary obstruction caused by malignancy at the confluence of the bile ducts can be difficult due to non availability of an adequate length of duct for anastomosis. This paper describes an approach to the left hepatic duct to decompress the biliary tree and its successful application in 11 of 12 patients who presented with malignant hilar obstruction.


Influence of digestive morphology on resource partitioning in Amazonian ungulates.
Resource partitioning of diet and habitat use was studied in the entire Amazonian ungulate community of Northeastern Peru, which comprises the red brocket deer (Mazama americana), grey brocket deer (M. gouazoubira), collared peccary (Tayassu tajacu), white-lipped peccary (T. pecari), and lowland tapir (Tapirus terrestris). Each ungulate species partitioned at least one type of resource from every other species. Digestive morphology had a greater influence on resource partitioning of diet than body size. Neither digestive morphology nor body size were related to segregation of habitats. However, species with similar diets partitioned habitats, whereas species with different diets often used the same type of forest. Increases in habitat breadth of ungulates were positively correlated with increases in dietary breadth.


Beta-adrenergic receptor activity of cerebral microvessels is reduced in aged rats.
The effect of age on beta- (beta) adrenergic receptor number (Bmax) and adenylate cyclase (AC) activity was determined in microvessels isolated from male F-344 rats at 3, 18, and 24 months of age. Scatchard analysis of [125I]iodocyanopindolol (ICYP) binding indicated reduced Bmax (fmol/mg) of microvessels isolated from 24 month old rats (27.2 +/- 4.9) compared with 3 month old (50.4 +/- 5.2) and 18 month old rats (p less than 0.01) (61.4 +/- 7.6). The basal AC activity (pmol cAMP/mg) in 24 month old rats (32.0 +/- 6.7) and in 18 month old rats (30.4 +/- 2.1) were significantly reduced compared to the basal activity in the young (50.1 +/- 4.2). The net isoproterenol or NaF stimulated AC activity in 24 month old rats (zero and 15.6 +/- 8.5 respectively) was also reduced compared to young rats (10.1 +/- 3.9 and 166.0 +/- 21.2 respectively). It is concluded that aging is associated with reduced isoproterenol stimulated AC activity of cerebral microvessels. This reduction is the product of reduced beta-adrenergic receptor number and reduced activity of AC in aged rat cerebral microvessels.


[Pituitary and COVID-19: review].
A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world since was first scientifically described in December 2019. At present approximately 400 million people have suffered from the disease, almost 6 million people have died.SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are expressed in several endocrine glands, including the pituitary, pancreas, thyroid, ovaries, and testes. Thus, the endocrine glands may be a direct target for SARS-CoV-2. The main risk factors for severity of the COVID-19 are obesity, arterial hypertension, diabetes mellitus (DM), vertebral fractures, which potentially predisposes patients to a severe course of COVID-19.In this review, we present current data on the course of COVID-19 in patients with hypothalamic-pituitary diseases, and also discuss treatment for endocrinopathies during to COVID-19.


The Nature and Risk Factors of Minimal Associated Pathological Lesions of Vocal Folds at Two Hospitals in the Gulf Area.
To identify the possible risk factors related to etiology of the minimal associated pathological lesions (MAPLs) of the vocal folds and their impacts on the recurrence of lesion. This analytical cross-sectional study included 200 subjects presented with dysphonia to the Phoniatrics/Voice Clinics in two hospitals in Gulf region (KSA and UAE). Same number of matched voluntaires from the same hospitals (hospital staffs, employees and their relatives) and relatives of subjects with typical voice quality were included as well. Both groups underwent a simple questionnaire consists of 15 items related to previously accused risk factors of MAPLs. The bivariant analysis by Fisher's exact test showed that male gender, presence of kids, misuse of voice, alcohol, gastroesophageal reflux diseases and voice handicapping are associated with significant risk to have MAPLs with P values < 0.001 for all except for alcohol (P = 0.015). Welch's t test revealed higher smoking index in subject than control groups with significant difference (P < 0.001). In contrast, spices, family shouting and nearby industry were not potent risk factors in our study group. Vocal trauma especially in females and children is a potent risk factor for vocal fold nodules and cysts. The gastroesophageal reflux is a suggested risk factor for Reinke's edema and contact granuloma. Smoking is the risk factor for MAPLs particularly polyp, contact granuloma, and Reinke's edema. Also, alcohol consumption is a possible risk factors for Reinke's edema. Identification of risk factors of the MAPLs is an important step in planning therapy. Risk factors which are highly related to a specific type of MAPLs should be involved in any planned program for protection, voice rehabilitation and/or prevention of recurrence of that lesion.


Outcome of partial and full pulpotomy in cariously exposed mature molars with symptoms indicative of irreversible pulpitis: A randomized controlled trial.
The aim of this study was to assess and compare the clinical and radiographic outcome of partial pulpotomy and full pulpotomy using Biodentine in cariously exposed mature molar teeth with symptoms indicative of irreversible pulpitis. This study is an unicentric, double-arm, randomized superiority clinical trial with parallel experimental groups, registered under CTRI (CTRI/2019/12/022559). Fifty mature permanent molar teeth with carious exposures with symptoms indicative of irreversible pulpitis were randomly allocated equally into two groups. Partial pulpotomy (PP) and full pulpotomy (FP) were performed in the first and second group, respectively, following standardized protocols. Exposed pulp tissue was removed up to a depth of 2-3 mm for partial pulpotomy, whereas complete coronal pulp tissue was removed up to the level of root orifices for full pulpotomy. Haemostasis was achieved with placement of 2.5% sodium hypochlorite-moistened cotton pellets placed on amputated pulp tissue for a maximum of 10 min. Biodentine was used as the pulp capping material. Pain scores were evaluated using 11-point Visual Analogue Scale (VAS) preoperatively, at 24 h, 48 h and 7th day after the intervention(s). Clinical and radiographic evaluation was done at 3 months, 6 months and 1 year. The data were statistically analysed using chi-squared test, Mann-Whitney U-test, Friedman's test and Wilcoxon signed-rank test. The significance level was pre-determined at p < .05. Cumulative survival probabilities were assessed at 12 months using Kaplan-Meier analysis. Intra-group analysis of pain scores revealed significant reduction in pain scores preoperatively and at 24 h, 48 h and 7th day in both the groups. However, the difference in the pain score(s) reduction between both the groups was not statistically significant at any time interval (p > .05). At 1-year follow-up, the success rate was 88% (22/25) and 91.6% (22/24) for PP and FP respectively (p > .05). Partial pulpotomy showed comparable results to full pulpotomy in terms of clinical/radiographic treatment outcome. If the long-term results remain the same, partial pulpotomy can be proposed as an alternative treatment modality for mature teeth with cariously exposed pulp tissue presenting with signs of symptomatic irreversible pulpitis.


Evolving perspectives on the sources of the frequency-following response.
The auditory frequency-following response (FFR) is a non-invasive index of the fidelity of sound encoding in the brain, and is used to study the integrity, plasticity, and behavioral relevance of the neural encoding of sound. In this Perspective, we review recent evidence suggesting that, in humans, the FFR arises from multiple cortical and subcortical sources, not just subcortically as previously believed, and we illustrate how the FFR to complex sounds can enhance the wider field of auditory neuroscience. Far from being of use only to study basic auditory processes, the FFR is an uncommonly multifaceted response yielding a wealth of information, with much yet to be tapped.


Flash evoked potentials from rat superior colliculus.
In view of reports that the superior colliculus evoked potential from rats is uniquely sensitive to toxic gases, the present study characterized normal flash evoked potentials from unanesthetized rats. The waveform was complex, with at least 5 positive and 5 negative peaks. The waveform originated in the SGS layer, and some components were stable over time if conditions of light intensity, stimulus frequency and dark adaptation were held constant. The greater complexity of the waveforms reported here compared to those described by others can be attributed to both an intense flash stimulus and unanesthetized preparation.


Symmetry breaking and effects of nutrient walkway in time-dependent bone remodeling incorporating poroelasticity.
Bone is an extraordinary biological material that continuously adapts its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness, across different scales, from the sub-microscopic constituents within osteons-where the cyclic activity of osteoblasts, osteoclasts, and osteocytes redesigns shape and percentage of mineral crystals and collagen fibers-up to the macroscopic level, with growth and remodeling processes that modify the architecture of both compact and porous bone districts. Despite the intrinsic complexity of the bone mechanobiology, involving coupling phenomena of micro-damage, nutrients supply driven by fluid flowing throughout hierarchical networks, and cells turnover, successful models and numerical algorithms have been presented in the literature to predict, at the macroscale, how bone remodels under mechanical stimuli, a fundamental issue in many medical applications such as optimization of femur prostheses and diagnosis of the risk fracture. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford's law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields to change homeostasis states, local saturation conditions, and reorients the bone density rate, in this way affecting growth and remodeling. Through two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, it is highlighted that the present model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium-long term, unpredictable with the standard approach. A real study case of a femur is also considered at the end in order to show the effectiveness of the proposed remodeling algorithm.


Sensory processing sensitivity predicts performance in an emotional antisaccade paradigm.
Sensory Processing Sensitivity (SPS) is a common, heritable, and evolutionarily conserved trait, describing inter-individual differences in responsiveness and a more cautious approach to novel stimuli. It is associated with increased activation of brain regions involved in awareness, integration of sensory information, and empathy during processing of emotional faces. Furthermore, SPS is related to better performance in a visual detection task. Even though SPS is conceptualized to be closely related to traits characterized by pausing before acting, no study to date has assessed the relation between SPS and inhibitory control in a behavioral inhibition task. The present study fills this gap by investigating how SPS influences individual performance on two different antisaccade paradigms including emotional face stimuli. In addition, we assessed self-reported mood, anxiety, and depressiveness. Results showed that SPS was related to faster processing speed on the emotional, but not the classic antisaccade paradigm. Moreover, SPS predicted inhibitory control speed above mood and depressiveness. Our results provide evidence that higher SPS participants show superior inhibitory abilities, especially during the processing of emotional stimuli. This is in line with earlier findings showing better performance in a visual detection task as well as increased brain activation during emotional face processing.


Meal size and frequency: effect on potentiation of the thermal effect of food by prior exercise.
Prior exercise potentiates the thermic effect of a carbohydrate meal. The purpose of this study was to determine if meal size or feeding pattern influences this response. Two groups of healthy, normal-weight young women exercised for 45 min on a cycle ergometer at 70% of maximal aerobic capacity. Once aerobic capacity returned to pre-exercise baseline, the thermic effect of food (TEF) was determined by indirect calorimetry over a 2-h period. One group of subjects ingested a 2510-kJ meal and the other a 5020-kJ meal. As a control, subjects ingested the test meal without prior exercise. In addition, subjects ingesting the 5020-kJ meal were studied for an additional 2 h. In a separate trial, these subjects ingested a 5020-kJ meal in two equal portions after a bout of exercise, the second portion 120 min after the first. TEF was less for the 2510-kJ meal compared with the 5020-kJ meal for both the control [mean (SE), 76 (17) vs 158 (19) kJ.2h-1, P < 0.01), and prior exercise [124 (23) vs 197 (24) kJ.2h-1, P < 0.01) trials. However, the same increment in TEF resulted from the prior bout of exercise [48 (9) vs 40 (8) kJ.2h-1 for 2510-and 5020-kJ meals, respectively). TEF was 31% lower when the 5020-kJ meal was given in two portions compared with one [281 (30) vs 369 (41) kJ.4h-1, P < 0.05]. No difference in TEF was found between the first and second 2510-kJ portion.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-generated rapid taps directed to the opposite forearm in man: anticipatory reduction in the muscle activity of the target arm.
A brief hammer tap applied passively (by the experimenter) to the forearm elicits a short-latency reflex response in the forearm flexors and extensors. When the same tap is performed actively (by the subject) using the opposite forearm, the reflex response is preceded by a short-lasting anticipatory reduction in the muscle activity appearing around the impact. This anticipatory reduction is interpreted as an alternative mode of feedforward motor control associated with damping of kinetic impulses generated within the bimanual system.


Investigation of potential rhizospheric isolate for cypermethrin degradation.
Rhizoremediation is the use of plant-microbe interaction for the enhanced degradation of contaminants. Rhizosphere bioremediation of pyrethroid pesticides will offer an attractive and potentially inexpensive approach for remediation of contaminated soil. The present study was done with the aim of establishment of highly effective remediation method using plant with degradative rhizosphere and isolation of naturally occurring rhizosphere associated potential degrader providing the possibility of both environmental and insitu detoxification of cypermethrin contamination. The remediation efficacy of Pennisetum pedicellatum was investigated using green house pot culture experiments in cypermethrin amended potting soil mix (10, 25, 50, 75 and 100 mg/kg) for periodic evaluation of changes in concentration. Total proportion of cypermethrin degraders was found to be higher in rhizosphere soil compared to bulk soil. The cypermethrin degrading strain associated with rhizosphere capable of surviving at higher concentrations of cypermethrin was designated as potential degrader. On the basis of morphological characteristics, biochemical tests and 16S rDNA analysis, isolate was identified as Stenotrophomonas maltophilia MHF ENV 22. Bioremediation data of cypermethrin by strain MHF ENV22 examined by HPLC and mass spectroscopy, indicated 100, 50 and 58 % degradation within the time period of 72, 24 and 192 h at concentrations 25, 50 and 100 mg/kg, respectively. This is the first report of effective degradation of cypermethrin by Stenotrophomonas spp. isolated from rhizosphere of Pennisetum pedicellatum. Rhizoremediation strategy will be of immense importance in remediation of cypermethrin residues to a level permissible for technogenic and natural environment.


Paraplegia in women.
In the period 1965-80, 125 women were treated because of paralysis or paresis of the lower extremities resulting from spinal trauma. In this report the causes of trauma, as well as the clinical and functional treatment of this group are discussed. The most frequent causes of trauma were falls from heights, from a tree, a ladder, a horse-cart as well as suicidal jumps and road accidents. It was ascertained that the results of treatment of spinal cord injuries in the upper thoracic segment are worse than in its lower part. These results do not differ from men with similar degrees and neurological levels of spinal cord injury. On the other hand the duration of treatment is longer in women than in men with the same degree of spinal cord lesion, amounting on the average to 17.4 weeks.


Serological study of ovine toxoplasmosis in Colombia: epidemiological study of a field outbreak.
A serological study, using the indirect haemagglutination test, of an outbreak of toxoplasmosis in a flock of blackface sheep is described. The serological aspects of the disease are discussed with reference to this incident, and possible sources of infection are suggested.


Compressive Remodeling Alters Fluid Transport Properties of Collagen Networks - Implications for Tumor Growth.
Biomechanical alterations to the tumor microenvironment include accumulation of solid stresses, extracellular matrix (ECM) stiffening and increased fluid pressure in both interstitial and peri-tumoral spaces. The relationship between interstitial fluid pressurization and ECM remodeling in vascularized tumors is well characterized, while earlier biomechanical changes occurring during avascular tumor growth within the peri-tumoral ECM remain poorly understood. Type I collagen, the primary fibrous ECM constituent, bears load in tension while it buckles under compression. We hypothesized that tumor-generated compressive forces cause collagen remodeling via densification which in turn creates a barrier to convective fluid transport and may play a role in tumor progression and malignancy. To better understand this process, we characterized the structure-function relationship of collagen networks under compression both experimentally and computationally. Here we show that growth of epithelial cancers induces compressive remodeling of the ECM, documented in the literature as a TACS-2 phenotype, which represents a localized densification and tangential alignment of peri-tumoral collagen. Such compressive remodeling is caused by the unique features of collagen network mechanics, such as fiber buckling and cross-link rupture, and reduces the overall hydraulic permeability of the matrix.


The effect of Community Based Education and Service (COBES) on medical graduates' choice of specialty and willingness to work in rural communities in Ghana.
Career choices and placements of healthcare professionals in rural areas are a major problem worldwide, and their recruitment and retention to these areas have become a challenge to the health sector. The purpose of this study was to investigate the effect of Community Based Education and Service (COBES) on medical graduates' choice of specialty and willingness to work in a rural area. This cross sectional survey was conducted among 56 pioneering graduates that followed a Problem Based Learning/Community Based Education and Service (PBL/COBES) curriculum. Using a mixed methods approach, open-and closed-ended questionnaire was administered to 56 graduates. Cross tabulation using Chi-square test were used to compare findings of the quantitative data. All qualitative data analysis was performed using the principles of primary, secondary and tertiary coding. All 56 graduates answered and returned the questionnaire giving a 100 % response rate. 57.1 % (32) of them were male. Majority of them lived in towns (41.1 %) and cities (50 %) prior to medical school. A significant number of graduates (53.6 %,) from the cities, without any female or male predominance said COBES had influenced their choice of specialty. Again, a significant proportion of graduates from the towns (60.9 %,) and cities (67.8 %,), indicated that COBES had influenced them to work in the rural area. However, there was no significant difference between males and females from the towns and cities regarding the influence of COBES to work in the rural area. Qualitative data supported the finding that COBES will influence graduates willingness to work in the rural area The majority of graduates from the towns and cities in Ghana, with a male predominance, indicated that COBES may have influenced their choice of specialty and willingness to practice in the rural areas despite their town or city based upbringing.


High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Māori to phaeochromocytoma/paraganglioma.
Phaeochromocytomas (PCC) and paragangliomas (PGL; together PPGL) are rare tumours of the adrenal medulla or extra-adrenal paraganglia. They may secrete catecholamines with significant cardiovascular effects. Management of PPGL is predominantly surgical, despite the anaesthetic risks related to potential haemodynamic instability. Meticulous pre-treatment and intra-operative management are required to improve cardiovascular outcomes. There are limited local data regarding the incidence of PPGL and the clinical characteristics of individuals diagnosed with these tumours in New Zealand. We undertook a retrospective study investigating the local practice and patient characteristics with an additional focus on intra-operative haemodynamic stability and post-operative outcomes. Electronic patient records were searched for individuals with a diagnosis of PPGL. Clinical records and electronic databases were interrogated for pre-operative, intra-operative and post-operative data points. Particular attention was paid to rates and types of germline mutations, intra-operative haemodynamic stability and post-operative renal and cardiovascular outcomes. We identified 49 individuals with PPGL, of whom 34 were from the local area. This gave a local incidence of PPGL of around five cases per million people per year. Māori were significantly over-represented in our cohort, with this being in part due to high rates of the SDHB R46Q mutation. Over 95% of our cohort met pre-specified pre-operative blood pressure parameters. Intra-operative monitoring revealed a tendency to hypotension, but this did not translate into adverse post-operative outcomes, which were infrequent. Māori were over-represented due to high rates of germline SDHB R46Q mutations. There were few post-operative adverse outcomes in this contemporary cohort.


Eight enteric-coated 50 mg diclofenac sodium tablet formulations marketed in Saudi Arabia: in vitro quality evaluation.
To evaluate in vitro quality of enteric-coated 50 mg diclofenac sodium tablet formulations on Saudi market. A reference and seven generic (G1-7) formulations were commercially available in December 2019/January 2020 and were assessed within 25-75% of manufacture-expiration period. Weight variation (range as% difference from mean, n = 20), active substance content (ASC, mean (SD) as% difference from label, n = 20), hardness (mean (SD), n = 10), and friability (% weight loss, n = 20) were 97-103%, 102.0% (3.4%), 15.4 (1.1) kg, and 0.24%, respectively, for the reference. For G2-7, they were ≤ ±5%, 98.6% (4.0%) to 109.9% (1.8%), 11.9 (0.9) to 18.3 (0.8) kg, and ≤ 0.00 to 0.75%, respectively. G1 ASC, hardness, and friability were 111.3% (1.7%), 20.1 (1.7) kg, and 1.10%, respectively. Disintegration time (n = 6) and dissolution profile (n = 8) were also determined. No formulation disintegrated or released ˃ 0.1% of label ASC in 0.1 N HCl for 2 h. The reference disintegrated in 15:00 min:seconds and released a mean (range) of 100% (99-103%) of label ASC by 45 min in phosphate buffer (pH = 6.8). G1-7 disintegrated in 8:53 to 20:37 min:seconds and released 81% (69-90%) (G1) to 109%. Except for borderline performance of G1, all formulations passed in vitro quality tests according to United States Pharmacopoeia.


Does corporate social responsibility result in better hotel guest attitudinal and behavioral loyalty?
This study aims to determine whether and how investing in corporate social responsibility (CSR) practices results in better attitudinal and behavioral loyalty. It seeks to comprehend the path linking CSR and customer loyalty through customer-company identification (C-CI), trust, and satisfaction as mediators. Partial least squares (PLS)-based structural equation modeling was applied to examine the theoretical model using SMART PLS. The data were collected through online questionnaires from 385 customers of Morocco's three-, four- and five-star hotels. The results conclude that CSR practices significantly contribute to customer loyalty through the mediating components of C-CI and trust. Surprisingly, unlike previous studies, the influence of CSR on customer satisfaction is insignificant. CSR influences customer satisfaction only through C-CI and trust. Moreover, the relationships between mediators, rarely explored by previous researchers, revealed that C-CI contributes to trustworthiness and customer satisfaction. Trust can also generate customer satisfaction.


[Effect of mydriasis and accommodation on intraocular pressure and pigment release in patients with the pigment dispersion syndrome].
To determine if mydriasis and accommodation affect intraocular pressure (IOP) and pigment release in patients with the pigment dispersion syndrome (PDS). Seventeen patients (34 eyes) diagnosed with PDS were included in the study (10 men and 7 women). Tonometry was performed on all patients before, and at 1 and 2 hours after mydriasis and before, and at 1 and 2 hours after sustained reading. The statistical analysis was performed using the paired T-test. In both tests the differences in intraocular pressure values were not statistically significant. Pigment liberation occurred in 11.8% of patients after mydriasis but was not associated with an increase in IOP. Accommodation during sustained reading did not cause significant pigment release or an IOP rise.


Radical processes in lipids. Selectivity of hydrogen abstraction from lipids by benzophenone triplet.
Laser photolysis techniques have been used to measure the reactivity of benzophenone triplet (3BZP) toward various fatty acids and two glycerides in benzene solution. Eight compounds varying both in number and in the configuration of olefinic bonds have been examined. It has been found that the rate constant for hydrogen abstraction from these compounds by 3BZP may be related to the number of secondary, allylic and doubly allylic hydrogens in each molecule by the equation: kH = [0.023[H sec] + 0.112[H allylic] + 1.78[H doubly allylic]] x 10(7) M-1s-1


Ultrasound assessment of placental function: the effectiveness of placental biometry in a low-risk population as a predictor of a small for gestational age neonate.
The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks' gestation. Placental length and thickness were measured by two sonographers in 520 singleton pregnancies. Uterine artery Doppler studies and a placental morphological assessment were also performed. Placental size was correlated with the birthweight centiles at delivery. A placental length <10th centile between the gestational age of 18 and 24 weeks is a significant factor associated with SGA neonate [odds ratio (OR) = 2.8, 95% CL, 1.1-6.9]. An abnormal uterine artery Doppler is a significant factor for SGA neonate (OR = 3.4, 95% CL, 1.6-7.4). There was a weak relationship between cord insertion <2 cm from the placental margin and an SGA neonate (OR = 1.8, 95% CL, 0.4-8.2). We have provided reference ranges for placental length and thickness from 18 to 24 weeks' gestation. A single measurement of placental length incorporated into the anatomy scan may assist in the early detection of a group at risk of delivering an SGA neonate.


Fabrication of PEG-carboxymethylcellulose hydrogel by thiol-norbornene photo-click chemistry.
Both poly(ethylene glycol) (PEG) and carboxymethylcellulose (CMC) are biocompatible polymers, which have been widely utilized in biomedical fields. In this study, we demonstrated the fabrication of pH-sensitive PEG-CMC hydrogels based on thiol-norbornene photo-click reaction and characterized their properties, such as swelling ratio, stiffness, degradation, and protein drug release. For the hydrogel fabrication, tetra-arm PEG and CMC were functionalized with norbornene groups and thiol groups, respectively. The hydrogels fabricated with varying concentration (0-3%) of CMCSH and a fixed concentration (4%) of PEG4NB by orthogonal step-growth photopolymerization showed high gel fractions (∼0.85). The presence of CMCSH in hydrogel did not affected gel point (∼4 s) but significantly prolonged completion time of gelation. Swelling ratios of PEG-CMC increased from ∼32 to ∼60 and the shear elastic modulus decreased from ∼3000 to ∼600 Pa with an increase of CMCSH content (0-3%). PEG-CMC hydrogel containing more CMCSH not only underwent slower hydrolytic bulk degradation but also showed a slower BSA release in acidic condition. These results indicate thiol-norbornene PEG-CMC hydrogel has potential as pH-sensitive protein drug carrier.


The lived experience of gender dysphoria in autistic young people: a phenomenological study with young people and their parents.
Gender dysphoria is distress in relation to incongruence between an individual's gender and sex assigned at birth. Gender clinics offer support for gender dysphoria, and there is a higher prevalence of autism in young people attending such clinics than in the general population. We aimed to investigate the lived experiences of autistic young people who have experienced gender dysphoria, and their parents, using a multi-perspectival IPA design. Young autistic people aged 13-17 years (n = 15), and their parents (n = 16), completed in-depth interviews about the young person's experience of gender dysphoria. We analysed each individual transcript to generate individual themes, and for each of the dyads, developed themes which acknowledged the similarities and differences in parent-child perspectives. The first superordinate theme was coping with distress which had two subordinate themes; understanding difficult feelings and focus on alleviating distress with external support. This theme described how young people were overwhelmed by negative feelings which they came to understand as being about gender incongruence and looked to alleviate these feelings through a gender transition. The second superordinate theme was working out who I am which had two subordinate themes: the centrality of different identities and needs and thinking about gender. This theme described how young people and their parents focused on different needs; while young people more often focused on their gender-related needs, parents focused on autism-related needs. We conclude that young people and parents may have different perspectives and priorities when it comes to meeting the needs of autistic young people who experience gender dysphoria.


Ultrasonically and fluoroscopically guided therapeutic percutaneous catheter drainage of the gallbladder.
Percutaneous gallbladder drainage was performed in 16 poor surgical risk patients; 13 had acute cholecystitis, 1 had cholangitis and septicemia, 1 had undergone removal of a gallbladder calculus, and 1 had pancreatic carcinoma with bile duct occlusion. Catheterization and drainage of the gallbladder succeeded primarily in all patients. Catheter dislodgement occurred within 24 h in 1 patient without any side effects. One 87-year-old patient died 14 h after the insertion of the catheter from reasons unrelated to the drainage procedure. Percutaneous removal of gallbladder calculi failed in 3 patients, 2 of whom had been successfully treated for cholecystitis by catheter drainage. Percutaneous gallbladder drainage is a fast, low-risk, inexpensive procedure well suited for the treatment of acute, poor surgical risk patients.


Highly pathogenic avian influenza virus (H5N1) in domestic poultry and relationship with migratory birds, South Korea.
During the 2006-2007 winter season in South Korea, several outbreaks of highly pathogenic avian influenza virus (H5N1) were confirmed among domestic poultry and in migratory bird habitats. Phylogenetic analysis showed that all isolates were closely related and that all belong to the A/bar-headed goose/Qinghai/5/2005-like lineage rather than the A/chicken/Korea/ES/2003-like lineage.


Electron microscopical identification of the committed precursor cell of the megakaryocyte compartment of rat bone marrow.
In the rat bone marrow, cells of the megakaryocyte line of differentiation are the only hemopoietic cells which show cytochemically demonstrable Acetylcholineesterase activity (AchE; EC 18.104.22.168). A small number of morphologically unrecognizable cells exhibit AchE activity in their Golgi complexes. These cells are identified as committed precursor cells of the MK compartment.


The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes.
Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.


Important prognostic significance of lymph node density in patients with node positive oral tongue cancer.
Lymph node density (LND) has been described as a prognostic factor for survival in patients with head and neck squamous cell carcinoma, particularly of the oral cavity. The aim of this study was to determine the prognostic significance of LND in patients with node positive oral tongue squamous cell carcinoma (OTSCC). Patients with pathological node positive OTSCC were identified in a retrospective review of prospectively collected data. The optimal cut-point for LND was determined using the minimum P-value method and the log-rank test. The impact of this LND cut-point on time to disease progression and overall survival was determined. In 72 patients with OTSCC, an LND of 14.3% was found to have the greatest separation using the log-rank test (P < 0.001). LND ≤14.3% was predicted for longer time to disease progression with a median time of 73 months compared to 9.4 months in patients with an LND >14.3% (hazard ratio: 3.43; 95% confidence interval: 1.76-6.70; P < 0.001). LND was also a significant predictor of overall survival with a median overall survival with LND ≤14.3% of 82.3 months, compared with 14.7 months in patients with an LND >14.3% (hazard ratio: 3.28; 95% confidence interval: 1.61-6.68; P = 0.001). Patients with an LND >14.3% experienced a higher rate of regional recurrence. Our findings confirm the prognostic significance of LND in patients with node positive OTSCC, with a similar LND cut-point value to other published series. Improving regional control in these high-risk patients may improve outcome.


Role of Magnesium Transporter Subtype 1 (MagT1) in the Osteogenic Differentiation of Rat Bone Marrow Stem Cells.
In the present study, we investigated the role of magnesium transporter subtype 1 (MagT1), a selective Mg transporter protein, in the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Osteogenic differentiation was monitored by the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), collagen-1 (COL-1) and runt-related transcription factor 2 (RUNX2), and extracellular matrix mineralization of rBMSCs. The expression of MagT1 increased with osteogenic differentiation of rBMSCs, suggesting the importance of intracellular Mg homeostasis to cell differentiation. Alteration of intracellular Mg homeostasis by culture condition with low extracellular Mg significantly reduced the osteogenic differentiation markers ALP, OCN, COL-1, and RUNX2 gene expressions. MagT1 knockdown during the differentiation period also reduced osteogenic differentiation and the extent of matrix mineralization of rBMSCs. In conclusion, our results indicate that Mg and MagT1 play an important role in osteogenic differentiation of rBMSCs and may be involved in the bone regeneration.


Biological properties and clinical application of propolis. VII. Investigation of immunogenic properties of ethanol extract of propolis (EEP).
Under experimental conditions parenteral administration of ethanol extract of propolis (EEP) solutions to rabbits induced no synthesis of antibodies as investigated by means of ring precipitation, double diffusion gel precipitation and complement fixation test.


Fabrication and application of chitosan-based biomass composites with fire safety, water treatment and antibacterial properties.
In this work, a biomass composite material (CS@NC@PA-Na) was prepared from chitosan (CS), nano-cellulose (NC) and sodium phytate (PA-Na). The prepared products were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffraction (XRD). The fire/water safety and antimicrobial properties of the CS@NC@PA-Na were fully studied. The results indicated CS@NC@PA-Na (50 mg) could effectively reduce the concentration of methyl orange by 85 % under 30 min adsorption. Meanwhile, only 5 wt% CS@NC@PA-Na could increase the limiting oxygen index (LOI) value of epoxy resin composite from 24.5 to 30.1 %, and decrease the peak heat/smoke release rate by 29.5 and 33.3 %, respectively. Moreover, CS@NC@PA-Na also exhibited excellent antibacterial effect. This work provides an efficient, feasible and eco-friendly route for large-scale production of multi-functional CS-based biomass materials that could be used in the fields of fire safety and environmental conservation.


Ribavirin and pegylated interferon treatment for hepatitis C was associated not only with semen alterations but also with sperm deoxyribonucleic acid fragmentation in humans.
To report the effects of ribavirin plus pegylated interferon on semen parameters and sperm DNA integrity in a man given treatment for hepatitis C. Case report. University-affiliated teaching hospital. None. A 37-year-old man given treatment with ribavirin and pegylated interferon for hepatitis C. Semen parameters (sperm count, motility, round cells), sperm protamination state measured by sperm chromatin structure assay, and sperm DNA fragmentation measured by terminal uridine nick-end labeling assay. The percentage of progressive spermatozoa and the number of motile sperm per ejaculate decreased during treatment. The round cell/spermatozoa ratio, which reflects spermatogenic abnormality, increased from 2.6% +/- 1.4% to 23.6% +/- 13.0% during treatment and returned to baseline value 4 months later. Moreover, the sperm DNA fragmentation index (as measured by sperm chromatin structure assay) increased very markedly during treatment (from 14.5% before to 69.2% at 7 months of treatment) and remained elevated 8 months later. This study reports for the first time not only quantitative but also qualitative alterations of spermatogenesis with DNA packaging abnormalities and emphasizes the need for prospective clinical studies. While the results of other studies are awaited, the alterations that persisted 8 months after treatment argue for a longer contraception period after treatment discontinuation in men.


Clinical reasoning and cognitive processes.
Expected utility theory, and the Bayesian probability theory on which it is based, form the normative basis of most work in medical decision analysis. Recent work in the psychology of judgments and decisions indicates that people do not conform to the axioms of this theory and that these deviations occur in clinical reasoning as well as in the psychology laboratory. At issue is what to do now. The authors argue that the important next steps lie at the interface between descriptive, prescriptive, and normative accounts, all of which affect each other. They point to examples in which the simplest application of supposedly normative theory seems inappropriate, and suggest ways in which the tension between normative and descriptive models may be resolved.


Sodium toxicity in peritoneal dialysis: mechanisms and "solutions".
The major trials in peritoneal dialysis (PD) have demonstrated that increasing peritoneal clearance of small solutes is not associated with any advantage on survival, whereas sodium and fluid overload heralds higher risk of death and technique failure. On the other hand, higher sodium and fluid overload due to loss of residual kidney function (RKF) and higher transport membrane is associated with poor patient and technique survival. Recent experimental studies also show that, independently from fluid overload, sodium accumulation in the peritoneal interstitium exerts direct inflammatory and angiogenetic stimuli, with consequent structural and functional changes of peritoneum, while in patients with Chronic Kidney Disease sodium stored in interstitial skin acts as independent determinant of left ventricular hypertrophy. Noteworthy, this tissue pool of sodium is modifiable being removed by dialysis. Therefore, novel PD strategies to optimize sodium removal, including the use of bimodal and/or low-sodium solutions, are actively tested. Nonetheless, a holistic approach aimed at preserving peritoneal function and the kidney may represent the key of therapy success in the hard task of preserving adequate sodium balance in PD patients. In this review, we describe the available evidence on sodium toxicity in PD, either related or unrelated to fluid overload, and we also discuss about possible "solutions" to preserve or restore sodium balance in PD patients.


Emergency medicine trainees' perceived barriers to training and credentialing in point-of-care ultrasound: A cross-sectional study.
Point-of-care ultrasound (POCUS) is an important tool in emergency medicine (EM), with the Australasian College for Emergency Medicine (ACEM) recommending core modalities as part of fellowship training. In Australia, acquisition of these skills is certified via credentialing but is currently poorly undertaken by EM trainees. We performed a cross-sectional survey of EM trainees across two academic teaching hospitals in Gold Coast, Queensland, between December 2018 and January 2019, to determine the current state of training and perceived barriers to credentialing in POCUS. Fifty-two (59%) eligible EM trainees participated. Although credentialing rates (15%) were low amongst respondents, the majority agreed that it was necessary (69%) and should form part of ACEM training (88%). Amongst these trainees, we identified the desire for increased POCUS training and several barriers including time constraints and the credentialing process itself. Although there is general agreement amongst EM trainees for POCUS credentialing, barriers such as time limitations and technical difficulties were prohibitive for many. We propose the development of an internal structured POCUS training programme within mandatory training time to address these issues.


Dermatological adverse drug reactions of anticancer drugs: International data of pharmacovigilance: VigiBase®.
In the 2000s, newer generations of drugs appeared on the market called drugs of targeted therapy (TT) drugs. The introduction of TT in oncology has profoundly changed the prognosis of many cancers but also introduced a wide variety of adverse drugs reactions (ADR), including in particular dermatological adverse drug reactions (DADRs). We investigated the evolutions of the notifications of DADRs of anticancer drugs since 2000s in international pharmacovigilance data. For this purpose, we separated non-targeted therapy and targeted therapy. During the period from 01/01/2000 to 31/12/2017, 1,226,252 ICSRs (8.7%) were related to anticancer drugs, among them concerning anticancer drugs, 192,108 cases (15.6%) contained at least one MedDRA term for "skin and subcutaneous tissue disorders" system organ classes. The DADRs of anticancer drugs are in constant increase on the period 2000 to 2017, from 0.91% to 1.90% of the total ADR of Vigibase®. The number of DADRs drugs in the non-targeted therapies class remained stable during this period, while the DADRs of targeted therapy drugs increased and exceeded those of non-targeted therapy in recent years. Using a disproportionality analysis, we found that targeted therapy drugs are associated with a higher risk of reporting DADRs of the type: dermatitis acneiform, hair color changes, acne, and hyperkeratosis and skin toxicity. While, non-targeted therapy drugs are associated with a higher risk of reporting DADRs of the type: skin hyperpigmentation, nail discoloration, dermatitis exfoliative, Hyperhidrosis and alopecia. TT drugs are used more and more for cancer indications and even beyond. This problematic of DADR will become more and more common and should benefit from specialized support with the organization of a coordinated network of professionals.


Studies on the synaptic interconnection between bulbar respiratory neurones of cats.
In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol.l-1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) R beta-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents. All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases. The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in R beta-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones. In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon. It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs. The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones.


Prevalence of vitamin D deficiency and its associated risk factors among rural population of the northern part of the Persian Gulf.
Accumulating evidence indicates that vitamin D deficiency has been increased globally over the last two decades. However, the majority of these studies are concerned with cities and there is scant information regarding the prevalence of vitamin D in rural areas. The main aim of this study was to investigate the prevalence of vitamin D deficiency and its associated risk factors among the rural population in Bushehr province which shares the longest border with the Persian Gulf. The rural inhabitants of more than 25 years old from three mountainous, plain, and seashore areas of Bushehr province were selected through a stratified multi-cluster random sampling method. After obtaining the participants' demographic and anthropometric data and their past medical history, serum 25-hydroxyvitamin D [25(OH)D] was measured using ELISA. A total of 1806 (means ±SD, 46± 14years old) rural subjects (35 % males and 65 % females) participated in this study. The prevalence of vitamin D deficiency, insufficiency, and sufficiency were 28 %, 50 %, and 22 %, respectively. The deficiency of vitamin D in women was higher than in men (OR=1.27, 95 % CI: 1.05 to 1.54, P=0.04). There was a positive significant correlation between age and serum vitamin D levels. Men with vitamin D deficiency had higher BMI (P=0.008); this association was not observed among women (P=0.7). There was no significant difference between the food item's consumption frequencies, and vitamin D status (P>0.05). The mountainous, and plain areas had the highest and lowest vitamin D levels, respectively. Although, Bushehr province is located in a sunny part of Iran, the prevalence of vitamin D deficiency was high among its rural population. The shift of their lifestyle patterns and rapid industrialization in these rural areas may be responsible. Therefore, the enrichment of dietary sources with vitamin D and the use of vitamin D supplements are recommended to tackle the high prevalence of vitamin D deficiency in the rural population of the northern part of the Persian Gulf.


Ethyl 2-{[5-(3-chloro-phen-yl)-1-phenyl-1H-pyrazol-3-yl]-oxy}acetate.
The title compound, C(19)H(17)ClN(2)O(3), was synthesized by the reaction of 5-(3-chloro-phen-yl)-1-phenyl-1H-pyrazol-3-ol and ethyl 2-bromo-acetate. In the crystal, the C- and N-linked benzene rings are twisted by 45.15 (3) and 53.55 (3)°, respectively, from the plane of the bridging 1H-pyrazole ring.


Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: A double blinded randomized controlled trial with one year follow-up.
To compare the effectiveness of intra-articular injection (IAI) of Platelet-Rich Plasma (PRP) with Triamcinolone Hexacetonide (TH) and Saline Solution (SS), in patients with knee osteoarthritis (OA). A randomized controlled trial, with blinded patients and assessor. Outpatient rheumatology service. Patients with knee osteoarthritis grades II and III. Patients received IAI with PRP, 40 mg TH, or SS. Patients were assessed at baseline and after 4, 8, 12 e 52 weeks with: visual analogue scale (VAS) for pain at rest and movement, WOMAC questionnaire, Timed to Up and Go test, 6-min walk test, percentage of improvement, goniometry, quality of life SF-36 questionnaire, Likert scale and Kelgreen & Lawrence (KL) radiographic scale (only at baseline and 52 weeks). 100 patients were studied, with a mean age of 67.13(6.56) years. The TH group was superior for: percentage of improvement (versus SS group from 4 to 52 weeks); WOMAC total and pain (versus PRP group at 4 weeks); and WOMAC stiffness (versus SS group at 12 weeks). The SS group was inferior for WOMAC function (from 8 to 52 weeks). The PRP group showed lowest radiographic progression [TH 17 (51.51%) to 24 (72.72%); SS 17 (51.51%) to 30 (90.90%); PRP 20 (58.82%) to 21 (61.76%)]. The Triamcinolone Hexacetonide group was superior for percentage of improvement and WOMAC, pain and stiffness. For the WOMAC function, the Platelet-Rich Plasma group and Triamcinolone Hexacetonide group were superior to the Saline group. The Platelet-Rich Plasma group showed the lowest radiographic progression at 52 weeks of follow-up.


Complete Genome Sequences of Seven EA Cluster Microbacteriophages, Bustleton, MillyPhilly, Riyhil, Phriends, Pherbot, PrincePhergus, and TinSulphur.
Seven EA cluster microbacteriophages were isolated from soil collected around Philadelphia, PA, using the bacterial host Microbacterium foliorum All of these phages have a highly conserved genome with regions of diversity localized to the 3' end. In phage Phriends (EA1 cluster), this region contains an orpham gene with no known function.