Autologous platelet-rich plasma compared with whole blood for the treatment of chronic plantar fasciitis; a comparative clinical trial.
Intralesional injection of autologous blood-derived products has recently gained attention as a potential treatment for plantar fasciitis (PF). We compared platelet-rich plasma (PRP) and whole blood (WB) for the treatment of chronic PF. Patients with chronic PF received either an intralesional injection of 3 cc PRP prepared by double centrifuge technique or WB (n = 17 in each group). Overall, morning and walking pain severity were assessed by 11-point numerical rating scale, and function was assessed by the Roles and Maudsley score (RMS) at baseline and 1-month and 3 months after treatment. Ultrasonography was performed to measure plantar fascia thickness at baseline and 3 months after treatment. Pain scores were reduced over the study in the PRP (mean change = -5.00 ± 1.17 to -5.47 ± 1.46) and WB groups (mean change = -5.29 ± 2.56 to -6.47 ± 2.83), with no difference between groups (P > 0.05). One month and 3 months after treatment, successful treatment (RMS of ≤ 2) was respectively observed in 29.4% and 82.3% of the PRP and in 47.1% and 76.4% of the WB groups (P > 0.05). Also, fascia thickness was decreased in both the PRP and WB groups (mean change = -1.74 ± 1.11 vs. -1.21 ± 0.73 mm, respectively, P = 0.115). Significant improvement in pain and function, as well as decrease in plantar fascia thickness, was observed by intralesional injection of the PRP and WB in patients with chronic PF. The study results indicate similar effectiveness between PRP and WB for the treatment of chronic PF in short-term.


Derivation of a risk assessment model for hospital-acquired venous thrombosis: the NAVAL score.
Venous thrombosis (VT) is a preventable cause of death in hospitalized patients. The main strategy to decrease VT incidence is timely thromboprophylaxis in at-risk patients. We sought to evaluate the reliability of risk assessment model (RAM) data, the incremental usefulness of additional variables and the modelling of an adjusted score (the NAVAL score). We used the RAM proposed by Caprini for initial assessment. A 5 % systematic sample of data was independently reviewed for reliability. We evaluated the incremental usefulness of six variables for VT during the score modelling by logistic regression. We then assessed the NAVAL score for calibration, reclassification and discrimination performances. We observed 11,091 patients with 37 (0.3 %) VT events. Using the Caprini RAM, high-risk and moderate-risk patients were respectively associated with a 17.4 (95 % confidence interval [CI] 6.1-49.9) and 4.2 (95 % CI 1.6-11.0) increased VT risk compared with low-risk patients. Four independent variables were selected for the NAVAL score: "Age", "Admission clinic", "History of previous VT event" and "History of thrombophilia". The area under the receiver-operating-characteristic curve for the NAVAL score was 0.72 (95 % CI 0.63-0.81). The Net Reclassification Index (NRI) for the NAVAL score compared with the Caprini RAM was -0.1 (95 % CI -0.3 to 0.1; p = 0.28). We conclude that the NAVAL score is a simplified tool for the stratification of VT risk in hospitalized patients. With only four variables, it demonstrated good performance and discrimination, but requires external validation before clinical application. We also confirm that the Caprini RAM can effectively stratify VT risk in hospitalized patients in our population.


Referral to hospital: perceptions of patients, general practitioners and consultants about necessity and suitability of referral.
A sample of new referrals from general practitioners to hospital specialists was examined from the points of view of the patient, general practitioner and consultant concerned with regard to the adequacy of the general practitioners' performance before referral, his ability to have managed without referral and the suitability of the specialist seen. Little agreement was found between the opinions expressed by the three groups, although some of the opinions expressed within the groups were found to be associated with characteristics of the groups.


Medically Complex Dental Implant Patients: Controversies About Systemic Disease and Dental Implant Success/Survival.
Advances in dental implant therapy have created choices to enhance the expectations of dental practitioners and their patients with respect to oral rehabilitation at any age after childhood and regardless of, in most cases, medical disabilities. The medical status of the patient however can significantly influence the success rate of dental implant therapy. This article applies the hierarchy of scientific evidence ranging from case reports, retrospective, prospective cohort investigations, systematic reviews, and meta-analyses criteria in order to determine whether dental implant placement in medically compromised patients yields any detrimental sequelae.


The direct effects of circulating lidocaine on uterine blood flow and foetal well-being in the pregnant ewe.
We infused lidocaine intravenously into 13 pregnant ewes at a rate sufficient to maintain plasma levels between 2-4 mugm/ml, which are those commonly seen with regional anaesthesia. These levels did not change maternal blood pressure, pulse rate, cardiac output, stroke volume, total peripheral resistance, uterine blood flow or intra-amniotic pressure. Foetal blood pressure and pulse rate remained stable as did both maternal and foetal blood gases and acid-base values.


Causal relation between the pressure gradient and left ventricular ejection time in hypertrophic cardiomyopathy.
This study was designed to evaluate the relation between severity of obstruction to left ventricular outflow and left ventricular ejection time in hypertrophic obstructive cardiomyopathy. With dual catheters across the left ventricular outflow tract, the pressure gradient and corresponding left ventricular ejection time were measured in 10 patients as the pressure gradient was pharmacologically provoked or abolished, or both. The patients were studied during constant atrial pacing to avoid the potential errors introduced with heart rate correction equations. The pressure gradient was pharmacologically provoked or reduced over a range of greater than or equal to 62 mm Hg per patient. In each patient the left ventricular ejection time varied directly with the pressure gradient (mean r = 0.97, range 0.92 to 1.00). The change in magnitude of the pressure gradient varied directly with the corresponding change in the measured ejection time (mean r = 0.98, range 0.97 to 1.00). When the data from all 10 patients were pooled with use of Weissler's heart rate correction equation, the relation between the corrected left ventricular ejection time and the pressure gradient was still significant and linear (r = 0.86), but less so than in individual patients. This difference was the result of marked interpatient variability in the slope of this linear relation reflecting interpatient differences in other important factors, such as underlying myocardial contractility and stroke volume, that influence left ventricular ejection time. This study demonstrates a clear, direct and highly significant relation between the magnitude of the pressure gradient and the left ventricular ejection time in hypertrophic obstructive cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Kinetics of triglyceride rich lipoproteins: chylomicrons and very low density lipoproteins.
Lipoprotein dynamics are complex during the postprandial state. A significant rise in chylomicron concentration is associated with increased competition for LPL with VLDL particles. This results in an increased concentration of large VLDL. The concentration of small VLDL is reduced as a result of diminished conversion of large to small VLDL. Such changes, induced in the postprandial state, complicate the application and development of models that describe lipoprotein particle kinetics. The development of models that integrate chylomicron and VLDL particle information, rather than surrogate markers, together with data including other variables will provide insight into the complexity of lipoprotein metabolism in the postprandial state.


Production and physicochemical characterization of chitosan for the harvesting of wild microalgae consortia.
The use of chitosan to harvest microalgae is a strategic step that seeks to reach an economically competitive price to recover lipids, proteins, and pigments. The aim of the present work was to design low-molecular-weight chitosan from shrimp shells and its physicochemical characterization, to be used for the harvesting of wild microalgae consortia. The chitosan was obtained by chemical deacetylation of shrimp shells, and physicochemical characterization was made using the instrumental methods DSC, TGA, X-ray, FTIR, and SEM. The harvesting of wild microalgae consortia was performed by the jar test method. The obtained chitosan had a low molecular weight (169 KDa), a deacetylation degree of 83 %, a decomposition temperature (TD) of 280 °C, and a crystallinity of 38.2 %. The microalgae genera found in the consortium were Scenedesmus sp., Chlorella sp., Schroderia sp., and Chlamydomonas sp. The microalgae removal efficiency of the chitosan was 99.2 % with 20 mg L-1.


Auditory evoked potentials in children and adolescents with multiple sclerosis and neuromyelitis optica spectrum disorders.
In children, an acute demyelinating disease may evolve as a multiphasic disease with multiple relapses, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The Brainstem Auditory Evoked Potentials (BAEP) and Long-Latency Auditory Evoked Potentials (LLAEP) contribute to the identification of either retrocochlear changes or other central auditory nervous system (CANS) changes. To characterize BAEP and LLAEP in children and adolescents with MS and NMOSD and verify the diagnostic values of these potentials in each of the demyelinating diseases. The 40 participants were divided into two study groups (SG1 - MS, SG2 - NMOSD) and two comparison groups (CG1 and CG2), matched for age (9 years-17 years and 11 months) and sex. Electrophysiological hearing assessment was performed with BAEP and LLAEP. When SG1 and SG2 were compared with CG1 and CG2 regarding BAEP and LLAEP, both SG1 and SG2 presented a higher occurrence of changes. Also, individuals with MS had higher occurrences of BAEP changes, whereas individuals with NMOSD had a higher occurrence of LLAEP changes. BAEP and LLAEP in children and adolescents with MS or NMOSD showed higher latencies and lower amplitudes of some components when these individuals were compared with their peers. These procedures were highly accurate to identify demyelinating diseases. BAEP results were more abnormal in individuals with MS, while LLAEP was so with NMOSD. These findings indicate that the auditory evoked potentials are important instruments for the differential diagnosis of MS and NMOSD, and valuable to monitor disease evolution.


Interface engineering with porous graphene as deposition regulator of stable Zn metal anode for long-life Zn-ion capacitor.
The zinc (Zn) dendrite accumulation leads to poor Coulombic efficiency, continuously failing life and severe safety risks, which seriously impede the commercial application of Zn ion capacitors (ZICs). Herein, an interface engineering is proposed for the Zn metal anode to restrain the dendrite by using porous flame reduced graphene oxide (FRGO) as the ex-situ protective and regulated layer to induce the Zn crystal growth and restricts the side reactions. The FRGO possesses extensive nanoscale pores and zincophilic oxygen-containing functional groups, which can absorb Zn2+ and nucleate preferentially on the surface of FRGO, then induce the growth of Zn parallel to the graphene sheet by matching the basal (002) plane of metallic Zn to minimize lattice strain. As a result, it eliminates the tip effect and achieves the deposited Zn with a uniform and flat surface. Therefore, The FRGO on the Zn (FRGO@Zn) anode significantly reduces the nucleation overpotential and improves the cycling life during the plating/stripping process. Notably, FRGO@Zn based ZIC can achieve 91.0% capacity retention after more than 20,000 cycles at 5 A g-1, and its capacity and maximum energy density are 150.6 mAh g-1 and 118.8 Wh kg-1, respectively. This interface engineering of FRGO for the Zn metal anode has excellent application potential and theoretical guidance in the ZICs field.


The Activity of Members of the UDP-Glucuronosyltransferase Subfamilies UGT1A and UGT2B is Impaired in Patients with Liver Cirrhosis.
The impact of liver cirrhosis on the activity of UDP-glucuronosyltransferases (UGTs) is currently not well characterized. We investigated the glucuronidation capacity and glucuronide accumulation in patients with liver cirrhosis. We administered the Basel phenotyping cocktail (caffeine, efavirenz, flurbiprofen, omeprazole, metoprolol, midazolam) to patients with liver cirrhosis (n = 16 Child A, n = 15 Child B, n = 5 Child C) and n = 12 control subjects and obtained pharmacokinetic profiles of substrates and primary metabolites and their glucuronides. Caffeine and its metabolite paraxanthine were only slightly glucuronidated. The metabolic ratio (AUCglucuronide/AUCparent, MR) was not affected for caffeine but decreased by 60% for paraxanthine glucuronide formation in Child C patients. Efavirenz was not glucuronidated whereas 8-hydroxyefavirenz was efficiently glucuronidated. The MR of 8-hydroxyefavirenz-glucuronide formation increased three-fold in Child C patients and was negatively correlated with the glomerular filtration rate. Flurbiprofen and omeprazole were not glucuronidated. 4-Hydroxyflurbiprofen and 5-hydroxyomeprazole were both glucuronidated but the corresponding MRs for glucuronide formation were not affected by liver cirrhosis. Metoprolol, but not α-hydroxymetoprolol, was glucuronidated, and the MR for metoprolol-glucuronide formation dropped by 60% in Child C patients. Both midazolam and its metabolite 1'-hydroxymidazolam underwent glucuronidation, and the corresponding MRs for glucuronide formation dropped by approximately 80% in Child C patients. No relevant glucuronide accumulation occurred in patients with liver cirrhosis. Detailed analysis revealed that liver cirrhosis may affect the activity of UGTs of the UGT1A and UGT2B subfamilies according to liver function. Clinically significant glucuronide accumulation did not occur in the population investigated. NCT03337945.


APACHE II, data accuracy and outcome prediction.
From review of 122 intensive care charts, Acute Physiology and Chronic Health Evaluation (APACHE) II points were determined for eight physiological values. Using a strict interpretation of APACHE II criteria, an average of 20.6% of these points were higher and 6.7% lower than the points entered originally into an intensive care database. The resulting 1.73 points mean increase in APACHE II score increased predicted mortality from 24.8% to 27.8% and decreased the mortality ratio (observed hospital deaths devided by predicted deaths) from 1.52 (95% confidence interval: 1.11-2.03) to 1.35 (95% confidence interval: 0.99-1.81). There were few errors entering the data recorded on the audit form into the intensive care unit database with an optical mark reader and keyboard. Inaccuracy and inconsistency in data collection must be excluded before differences in mortality ratios are ascribed to intensive care unit performance.


Tracking of copper species in incineration fly ashes.
Speciation of copper in the incineration waste heat boiler (HB) and the down stream electrostatic precipitator (EP) fly ashes during the flue gas cooling down (1123-->473 K) has been studied by X-ray absorption near edge structural (XANES) spectroscopy in the present work. Copper species such as Cu(OH)(2) (59-67%), CuCl(2) (5-12%), CuO (24-26%), and a small amount of CuS (3-4%) in fly ashes were determined by semi-quantitative analyses of the XANES spectra. In the toxicity characteristics leaching procedure (TCLP) tests, about 83 and 20% of copper were leached from the EP and HB fly ashes, respectively. The relatively high leachability of copper for the EP fly ash might be due to the fact that CuCl(2) was enriched on the surfaces as observed by X-ray photoelectron spectroscopy (XPS). On the contrary, CuCl(2) was mainly encapsulated in the HB fly ashes.


Understanding the physicochemical properties of Zn-Fe LDH nanostructure as sorbent material for removing of anionic and cationic dyes mixture.
In our work, the removal of cationic and anionic dyes from water was estimated both experimentally and computationally. We check the selectivity of the adsorbent, Zn-Fe layered double hydroxide (LDH) toward three dyes. The physical and chemical properties of the synthesis adsorbent before and after the adsorption process were investigated using X-ray photoelectron spectroscopy, energy dispersive X-ray, X-ray diffraction, FT-IR, HRTEM, and FESEM analysis, particle size, zeta potential, optical and electric properties were estimated. The effect of pH on the adsorption process was estimated. The chemical stability was investigated at pH 4. Monte Carlo simulations were achieved to understand the mechanism of the adsorption process and calculate the adsorption energies. Single dye adsorption tests revealed that Zn-Fe LDH effectively takes up anionic methyl orange (MO) more than the cationic dyes methylene blue (MB) and malachite green (MG). From MO/MB/MG mixture experiments, LDH selectively adsorbed in the following order: MO > MB > MG. The adsorption capacity of a single dye solution was 230.68, 133.29, and 57.34 mg/g for MO, MB, and MG, respectively; for the ternary solution, the adsorption capacity was 217.97, 93.122, and 49.57 mg/g for MO, MB, and MG, respectively. Zn-Fe LDH was also used as a photocatalyst, giving 92.2% and 84.7% degradation at concentrations of 10 and 20 mg/L, respectively. For visible radiation, the Zn-Fe LDH showed no activity.


Sex-specific effects of excipients on oral drug bioavailability.
The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.


Use of 2-deoxyglucose in liquid media for the selection of mutant strains of Penicillium echinulatum producing increased cellulase and beta-glucosidase activities.
Mutagenesis and selection were applied to a strain of Penicillium echinulatum by treating conidia with hydrogen peroxide or 1,2,7,8-diepoxyoctane and then by incubating the conidia for 48 h in broth containing microcrystalline cellulose washed in 0.5% (w/v) aqueous 2-deoxyglucose before plating them onto cellulose agar containing 1.5% (w/v) glucose from which colonies showing the fastest production of halos of cellulose hydrolysis were selected. This process resulted in the isolation of two new cellulase-secreting P. echinulatum mutants: strain 9A02S1 showing increased cellulase secretion (2 IU ml-1, measured as filter paper activity) in submerged culture in agitated flasks containing a mineral salts medium and 1% of cellulose, and strain 9A02D1, which proved more suitable for the production of cellulases in semisolid bran culture where it produced 23 IU of beta-glucosidase per gram of wheat bran.


Protein tyrosine phosphatases in osteoclast differentiation, adhesion, and bone resorption.
Osteoclasts are large cells derived from the monocyte-macrophage hematopoietic cell lineage. Their primary function is to degrade bone in various physiological contexts. Osteoclasts adhere to bone via podosomes, specialized adhesion structures whose structure and subcellular organization are affected by mechanical contact of the cell with bone matrix. Ample evidence indicates that reversible tyrosine phosphorylation of podosomal proteins plays a major role in determining the organization and dynamics of podosomes. Although roles of several tyrosine kinases are known in detail in this respect, little is known concerning the roles of protein tyrosine phosphatases (PTPs) in regulating osteoclast adhesion. Here we summarize available information concerning the known and hypothesized roles of the best-researched PTPs in osteoclasts - PTPRO, PTP epsilon, SHP-1, and PTP-PEST. Of these, PTPRO, PTP epsilon, and PTP-PEST appear to support osteoclast activity while SHP-1 inhibits it. Additional studies are required to provide full molecular details of the roles of these PTPs in regulating osteoclast adhesion, and to uncover additional PTPs that participate in this process.


Self-perception in children with attention deficit/hyperactivity disorder.
The purpose of this study was to compare self-perceptions of children diagnosed with attention deficit/hyperactivity disorder (ADHD) with those of children not diagnosed with ADHD. Seventy-seven children aged 8-12 years composed the two groups-38 participants with ADHD and 39 control participants without ADHD. The children completed the Self-Perception Profile for Children Questionnaire designed to measure self-perceptions in school-aged children. t Tests compared differences in mean scores between the groups. The ADHD group had a significantly lower overall score and a lower score on the behavioral conduct subscale compared with children without ADHD. Findings suggest a difference in the way school-aged children with ADHD perceive themselves as compared with their peers. The cumulative effect of years of low self-esteem and negative self-perception may have significant life consequences. Attention should be focused on fostering self-esteem and positive self-perception in children with ADHD through support groups and behavioral training.


Serum autophagy protein 5 is positively related to T helper 2/T helper 1 ratio, inflammation, and exacerbation in adult asthma patients.
Autophagy protein 5 (ATG5) regulates airway epithelial cell autophagy, immune response, and inflammation, which is involved in asthma progression. This study aimed to evaluate ATG5 levels and its clinical roles in adult asthma patients. Totally, 200 adult asthma patients and 100 healthy controls (HCs) were enrolled in this case-control study. Subsequently, serum ATG5 was measured by enzyme-linked immunosorbent assay. ATG5 was increased in asthma patients compared with HCs [median (interquartile range): 44.2 (31.7-77.8) vs. 23.2 (16.7-39.2) ng/mL] (P < 0.001). In asthma patients, ATG5 was positively related to male gender (P = 0.022), a family history of asthma (P = 0.035), eosinophil count (P < 0.001), and immune globulin E (P < 0.001), while it was negatively correlated with forced expiratory volume in 1 s (FEV1)/forced vital capacity (P < 0.001) and FEV1 (Predicted) (P < 0.001). Meanwhile, ATG5 was inversely associated with T helper (Th) 1 cells (P = 0.008), while it was positively linked with Th2 cells (P < 0.001), Th2/Th1 ratio (P < 0.001), interleukin (IL)-4 (P = 0.002), and IL-4/interferon-γ ratio (P = 0.015). Additionally, ATG5 was positively correlated with tumor necrosis factor-α (P < 0.001), IL-1β (P = 0.001), IL-6 (P = 0.003), and IL-17 (P = 0.029). Notably, ATG5 was elevated in asthma patients at exacerbation compared to those at remission [median (interquartile range): 53.6 (37.6-90.0) vs. 35.6 (28.2-51.5) ng/mL] (P < 0.001). It was also noteworthy that ATG5 was positively linked with exacerbation severity in asthma patients (P = 0.005). Serum ATG5 is related to increased Th2/Th1 ratio, inflammation, exacerbation risk and severity in adult asthma patients, which serves as a candidate marker for the management of asthma. However, further validation is still needed.


Bilateral paraaortic lymphadenectomy in the presence of double inferior vena cava.
Three cases of stage IB cervical carcinoma with preoperative diagnosis of double inferior vena cava by CT scan are presented. Its importance during paraaortic lymphadenectomy and the relevant embryology of the inferior vena cava and its major anomalies are discussed.


[Are too Many Temporarily Placed Non-culpable Offenders Committed to Forensic Psychiatric Hospitals in Germany? Thoughts on the Relationship of Forensic and General Psychiatry].
From the perspective of the forensic clinics, the judiciary is increasingly ordering temporary placements according to Sec. 126a of the Code of Criminal Procedure. Three hypotheses are proposed that could (partly) explain this increase: 1) Courts' tendency to hand down this decision even in cases involving minor offences. 2) Courts' tendency to hand down this decision despite positive prognoses. 3) Changes in the reporting practices of psychiatric clinics. Overly simple explanations for the increase in temporary placements, therefore, fall short. This makes it more urgent to strengthen the primary-prevention approach. It is imperative that the small percentage of people with mental illness and an increased propensity to violence be identified and treated to prevent violence in the general psychiatric care stage. For this forensic psychiatry and general psychiatric care must be interlinked more closely.


Evaluation of the policy of empiric treatment of suspected Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.
This study was designed to measure response rates and survival in patients with acquired immunodeficiency syndrome (AIDS) and suspected Toxoplasma encephalitis treated empirically and in AIDS patients treated for biopsy-proven toxoplasmosis. AIDS patients identified at Bellevue Hospital between August 1985 and May 1986, who had abnormal computed tomographic scans of the brain and who received empiric treatment for toxoplasmosis, constitute the empirically treated cohort. A cohort with biopsy-proven toxoplasmosis was identified from Bellevue Hospital neuropathology records spanning 1981 through 1986. Patient records were reviewed with a standardized data form, and tomograms were evaluated by neuroradiologists unaware of the identity of the scans. Survival analysis was performed by the product limit method. Of 38 empirically treated patients, 26 responded clinically and radiographically within four weeks of initiation of therapy. Four of nine patients who underwent biopsy responded to treatment. There was no difference in these response rates (68% versus 44%, p = 0.24). The median survival of the empirically treated responders, from first diagnosis of AIDS to last follow-up, was 422 days. Among the 30 responders, five patients discontinued therapy and four of them had relapses. No relapses occurred in the 25 patients who continued full-dose therapy indefinitely (p = 0.0004). Sixteen of 30 patients (53%) receiving continuous therapy developed toxicity, which required a change in medication. There was no difference in the survival of patients who continued to receive sulfadiazine and pyrimethamine compared with those in whom clindamycin was substituted for sulfadiazine (median, 311 days versus 422 days, p = 0.25). A policy of empiric treatment of suspected Toxoplasma encephalitis is satisfactory, and patients who respond to such therapy and continue to take full therapeutic doses of anti-Toxoplasma drugs have relatively long survivals.


[Moderate coronary lesion with severe vasospasm and the development of collateral circulation in a patient with effort angina and ST-segment depression].
Coronary collateral circulation usually develops as a consequence of recurrent ischemia associated with severe stenosis. In exceptional cases, it can develop with moderate coronary lesions if there is severe recurrent vasospasm. In this situation, the presenting clinical features of vasospastic angina (i.e., effort angina with ST-segment depression) can be identical to those of a severe permanent lesion. We present a patient who exhibited effort angina and ST-segment depression on treadmill testing. Angiography showed severe right coronary artery stenosis and the development of coronary collateral circulation from the other main artery. After repeated intracoronary bolus injection of nitroglycerin, only a moderate stenosis was still apparent and the collateral circulation had disappeared.


Effects of vitamin D on calcium regulation in vitamin-D-deficient pigs given a phytate-phosphorus diet.
1. Vitamin-D-deficient pigs were fed on a phytate-phosphorus diet and treated with vitamin D3 (+D) to examine the time-course of adaptative changes in plasma minerals, vitamin D metabolites, parathyroid hormone (PTH) and calcium balance and intestinal Ca-binding protein (CaBP). 2. The 5-week vitamin D repletion (25 micrograms cholecalciferol/kg diet) regimen restored plasma Ca, P and alkaline phosphatase (EC 18.104.22.168) to normal, decreased PTH and markedly and rapidly increased plasma 25-hydroxycholecalciferol (25-OHD, sevenfold after 4 d) and 1,25-dihydroxycholecalciferol (1, 25(OH)2D3, 1.8-fold after 4 d). 3. CaBP concentrations were markedly elevated all along the digestive tract, especially in the distal regions. 4. Ca absorption and retention were enhanced (fourfold and sixfold respectively) by the +D diet. 5. The improved Ca absorption, coupled with increased CaBP and 1,25(OH)2D3 levels, suggest that vitamin D metabolism in phytate-P-fed pigs is sensitive to the depressed Ca availability due to phytate feeding. It also indicates that CaBP may play an important role in the adaptation of Ca absorption. 6. Persistent hypercalciuria indicates that mineral metabolism was still affected by the phytate nature of the dietary P in spite of the vitamin D treatment.


Mysteries of the transferrin-transferrin receptor 1 interaction uncovered.
How does the iron (Fe) binding protein, transferrin (Tf), bind to the transferrin receptor 1 (TfR1) to donate Fe to cells? In this issue of Cell, Cheng et al., describe the molecular structure of the human TfR1-Tf complex, This atomic model shows that Tf binds laterally to the TfR1 dimer and extends into the gap between the bottom of the receptor ectodomain and the membrane.


Primary exertional headache: updates in the literature.
Primary exertional headache (PEH) has been recognized by the International Headache Society as a primary headache diagnosis since 1994. It is an uncommon, self-limited, and short-lasting disorder that is precipitated by exertion and is frequently comorbid with migraine. PEH shares a number of features with other headache disorders, including thunderclap headache, primary cough headache, and headache associated with sexual activity. Upon its initial occurrence, PEH requires a thorough neurologic evaluation and imaging studies to help eliminate possible underlying secondary causes, including subarachnoid hemorrhage and sentinel bleed. Although PEH is incompletely understood with regard to its epidemiology and pathophysiology, it is generally considered to be a benign disorder that is self-limited and responsive to trigger avoidance and indomethacin.


Phase II evaluation of sequential hepatic artery infusion of 5-fluorouracil and hepatic irradiation in metastatic colorectal carcinoma.
Twenty-seven patients with measurable liver metastases from colorectal carcinoma were entered on a protocol of intermittent hepatic artery infusion (HAI) of 5-fluorouracil (5-FU) followed by consolidation with hepatic irradiation. Five partial responses were observed in 23 evaluable patients. Median duration of response was 3.5 months. A response was evident after chemotherapy alone in four of five responders. Hepatic irradiation converted one patient with stable disease after chemotherapy to a partial responder. Median survival for all patients was 9.0 months (range 1.5-34.0). Combined modality treatment with HAI of 5-FU followed hepatic irradiation was well tolerated but did not appear to be synergistic.


Monoterpene-induced molecular responses in Arabidopsis thaliana.
Terpenoid volatiles mediate various forms of chemical communications of plants with other organisms. In this paper we demonstrate that exposure of intact Arabidopsis thaliana plants to monoterpene volatiles results in substantial changes of the plant transcriptome and induction of methyl jasmonate (MeJA) accumulation. We used a heterologous pinII::GUS reporter system to test monoterpenes for their potential to induce a response in A. thaliana. Plants showed increased pinII-promoter activity upon exposure to different monoterpene volatiles, similar to the response induced by MeJA, mechanical wounding, or insect feeding. Microarray gene expression profiling indicated induced changes in the abundance of several hundred transcripts in wild-type plants upon either exposure to myrcene volatiles or exposure to a blend of ocimene volatiles consisting of (E)-beta-ocimene, (Z)-beta-ocimene, and allo-ocimene. Many of the monoterpene-induced transcripts are annotated as either transcription factors or as stress or defense genes including several steps in the octadecanoid pathway. Metabolite analysis showed that exposure of Arabidopsis for 2h to myrcene or ocimene induced increased tissue levels of MeJA. Octadecanoid biosynthesis (aoc) and signaling (coi1) mutants showed some reduced ocimene-induction of gene expression.


Alterations in c-Src/HER1 and estrogen receptor α signaling pathways in mammary gland and tumors of hexachlorobenzene-treated rats.
Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co-carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor α (ERα)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ERα signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ERα phosphorylation and ERα/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ERα protein content and decreases p-Y537-ERα levels and ERα/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ERα signaling pathways. HCB stimulates c-Src/HER1 pathway, but decreases ERα activity in tumors, appearing to shift them towards a higher malignancy phenotype.


[Agenesis of the femoral vein in the framework of vascular dysplasias of the lower limbs. Clinical case].
Venous dilatations of the lower limbs, especially if associated with others abnormalities, may reflect pathogenetic mechanisms far more complex and diverse than plain insufficiency of the sephena, all the way to congenital vascular anomalies of all possible types and still dubious classification. In such conditions a prerequisite of prime importance is the complete exploration of the whole arterial and venous vasculature of the limb, first of all in order to avoid rash therapeutic decisions, and then to help clarify the diagnosis and select the most appropriate treatment from among the numerous technics available.


Interactions between pesticides and components of pesticide formulations in an in vitro neurotoxicity test.
Organophosphate (OP) pesticides are often used in combination with one another and with the components of formulations. Evidence already exists for interactions in the neurotoxic effects of OPs through interference with metabolism, but there is also potential for interactions related directly to cell damage. The purpose of this work was to investigate this possibility for OPs and the components of one of their common formulations in vitro. NB2a neuroblastoma cells were induced to differentiate in the presence of the OPs diazinon and chlorpyrifos, in combination with a commercial formulation (identified as Commercial Formulation 1) of the compounds and, independently, the components of that formulation. The compounds were tested in pairs in various proportions and the resulting inhibition of neurite outgrowth was measured by light microscopy and quantitative image analysis. Interactions were determined in terms of enhanced or reduced effects of the paired compounds in comparison with the expected additive effects estimated from the effects of each compound on its own. Synergism was detected between combinations of: 10 microM chlorpyrifos and 500 nM pyrethrum; chlorpyrifos and one of the solvents (regular spirit) found in Commercial Formulation 1. All other combinations of OPs and products were additive in their neurotoxicity. The data suggest that exposure to multiple OP-containing pesticide formulations may lead to synergistic neurotoxicity by a direct mechanism at the cellular level.


Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: A national retrospective observational cohort study.
To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization. We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model. A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]). The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.


Effects of Nano-copper on Antioxidant Function in Copper-Deprived Guizhou Black Goats.
Guizhou black goats are essential to the production system in the Wumeng prairie in the Western China. This study aimed to determine the influence of nano-copper on antioxidant system in copper-deprived Guizhou black goats. We analyzed mineral contents in soil, forage, and goats' tissues. Blood parameters were also determined. The results showed that copper concentrations in soil and forage were significantly lower, and the iron content was significantly higher in affected compared with healthy area (P < 0.01). Copper concentrations in animal tissues (blood, liver, and hair) were significantly lower and iron content was significantly higher in affected compared with healthy goats (P < 0.01). After supplementation of nano-copper or copper sulfate, copper concentration in blood was significantly increased and iron content was significantly lower (P < 0.01). Compared with nano-copper group, the effect of copper sulfate was slower. Hemoglobin levels, erythrocyte count, and packed cell volume from nano-copper and copper sulfate groups were significantly higher than those in copper-deprived goats (P < 0.01). Compared with the copper-deprived Guizhou black goats, serum ceruloplasmin levels in nano-copper and copper sulfate groups were significantly increased, while serum lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and creatinine were significantly decreased (P < 0.01). Compared with the copper-deprived animals, serum superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity in nano-copper and copper sulfate groups were significantly higher, while serum malondialdehyde content was significantly lower (P < 0.01). The effect of copper sulfate group was significantly lower than that in nano-copper group (P < 0.01). Consequently, nano-copper could not only markedly increase the copper content in blood in copper-deprived Guizhou black goats but also much improves the antioxidant capacity.


The development and validation of diabetes knowledge questionnaire for the Indigenous population in Malaysia.
The study's aim was to construct and validate a diabetes mellitus knowledge questionnaire in Bahasa Malaysia for Orang Asli (OA-DKQ). The questionnaire was administered to; case (Orang Asli) and control (administrative staff) groups at baseline and retested two weeks later. The Cronbach's Alpha was used to determine internal consistency and intraclass correlation coefficient (ICC) was used to determine test-retest reliability. The OA-DKQ has an internal consistency of 0.806. These findings suggest the OA-DKQ is an acceptable instrument to assess knowledge and preventive behaviour in Orang Asli (86 words).


Genotyping of Enterocytozoon bieneusi (Microsporidia) isolated from various birds in China.
Enterocytozoon bieneusi is a common opportunistic pathogen causing diarrhea in humans and animals. However, epidemiological data on E. bieneusi infections in birds are relatively scare worldwide, especially in China. To understand the prevalence and genetic diversity of E. bieneusi in birds and to assess the zoonotic potential of bird-derived E. bieneusi isolates, 194 fecal specimens from Gruidae, Anatidae and Columbidae in Heilongjiang Province, China, were analyzed by PCR and sequencing of the single internal transcribed spacer region of the rRNA gene. The average prevalence of E. bieneusi was 22.2%, with 12.5% for Gruidae, 15.9% for Anatidae and 44.0% for Columbidae. Altogether seven genotypes of E. bieneusi were identified, including four known genotypes-Peru6 (n=29), BEB6 (n=5), D (n=3) and EbpA (n=1)-and three novel genotypes named CHN-B1 (n=1), CHN-B2 (n=3) and CHN-B3 (n=1). All the known genotypes obtained here were previously detected in humans. All the novel genotypes were clustered into the zoonotic group 1 in phylogenetic analysis. The results indicate that these birds may play a potential role in the transmission of E. bieneusi to humans.


Is There an Association Between Pain and Magnetic Resonance Imaging Parameters in Patients With Lumbar Spinal Stenosis?
A prospective multicenter cohort study. The aim of this study was to identify an association between pain and magnetic resonance imaging (MRI) parameters in patients with lumbar spinal stenosis (LSS). At present, the relationship between abnormal MRI findings and pain in patients with LSS is still unclear. First, we conducted a systematic literature search. We identified relationships of relevant MRI parameters and pain in patients with LSS. Second, we addressed the study question with a thorough descriptive and graphical analysis to establish a relationship between MRI parameters and pain using data of the LSS outcome study (LSOS). In the systematic review including four papers about the associations between radiological findings in the MRI and pain, the authors of two articles reported no association and two of them did. Of the latters, only one study found a moderate correlation between leg pain measured by Visual Analog Scale (VAS) and the degree of stenosis assessed by spine surgeons. In the data of the LSOS study, we could not identify a relevant association between any of the MRI parameters and buttock, leg, and back pain, quantified by the Spinal Stenosis Measure (SSM) and the Numeric Rating Scale (NRS). Even by restricting the analysis to the level of the lumbar spine with the most prominent radiological "stenosis," no relevant association could be shown. Despite a thorough analysis of the data, we were not able to prove any correlation between radiological findings (MRI) and the severity of pain. There is a need for innovative "methods/techniques" to learn more about the causal relationship between radiological findings and the patients' pain-related complaints. 2.


Injury prevention among young people in nursing homes: Recommendations following expert consultation forums.
Approximately 6,000 people under the age of 65 years reside in nursing homes each year in Australia. These young people in nursing homes are at risk of premature death and preventable morbidity from injuries. Choking and falls are the leading causes of premature deaths in this cohort with reported rates of 44% and 33%, respectively. To develop injury prevention recommendations for young people in Australian nursing homes. This mixed-methods study comprised two expert consultation panels and a follow-up survey. Two expert and stakeholder consultation panels used a modified nominal group technique to formulate recommendations. A short survey was subsequently given to participants to validate responses from the panels and to provide an opportunity to evaluate and rank recommendations. Ten recommendations were formulated for consideration that focused on system-wide reforms. Four were ranked as most important for implementation: education and training for nursing home staff; implementation of National Disability Insurance Scheme; support for coordinated care; and increasing residential housing stock that is appropriately designed. Extensive changes are needed to prevent injury for young people in nursing homes. Implementation should reduce the risk of injury and lead to an improved quality of life for this cohort. This study provides an evidence base for aged care practitioners to improve practice within nursing homes to reduce fatal and non-fatal injuries for young people in nursing homes.


Milk protein intake in the term infant. I. Metabolic responses and effects on growth.
Thirty healthy term infants were studied during the three first months of life. The infants were divided into three feeding groups consisting of 10 infants in each. The feeding regimens were: human milk by breast feeding, a formula (F-I) containing 1.2 g/100 ml of protein and a control formula (F-II) containing 1.6 g protein/100 ml. Both formulas were whey predominant and isocaloric. Protein intake was significantly higher with formula F-II when compared to the human milk group and to formula F-I. No significant differences with respect to weight, length and head circumference were found among the groups, but the rate of growth between 2 to 12 weeks was higher in the control formula (F-II) group. Serum albumin concentrations were normal and similar in all feeding groups. Blood urea nitrogen and urine total nitrogen concentration was significantly lower in the low protein formula I group when compared to the control formula II. After the fourth week of life the low protein formula infants had similar blood urea nitrogen and urine nitrogen concentrations as those of the breast-fed infants. The results indicate that current formulas in use provide excessive protein intakes after the first months of life.


Predictive value of immediate pain relief after lumbar transforaminal epidural injection with local anesthetics and steroids for single level radiculopathy.
To assess the predictive value of immediate pain-relief after CT-guided transforaminal epidural steroid injection (TFESI) including local anesthetics for longer-term pain relief and patients' global impression of change (PGIC) after 4 weeks. One hundred ninety-three patients (age 55.4 ± 14.9) with single-level discogenic lumbar radiculopathy and subsequent TFESI were included. Pain scores were recorded before (NRS0), 15 min (NRS15min), and 4 weeks (NRS4w) after treatment using a numerical-rating-scale (NRS; 0, no pain; 10, intolerable pain). Additionally, the PGIC was assessed after 4 weeks. Two fellowship-trained musculoskeletal radiologists evaluated nerve compression of the injected level and contrast dispersion. Spearman's rank and point-biserial correlation were applied to assess associations between outcome variables and demographics/imaging findings. A p-value < 0.05 was considered to be statistically significant. There was a significant positive correlation between immediate pain-relief and longer-term pain-reduction (r = 0.24, p = 0.001) with an odds ratio of 2.0 (CI: 1.1-3.6). A good short-term response (NRS15min ≥ 50% reduction) was associated with a persistent longer-term good response (NRS4w ≥ 50% reduction) in 59.7% (CI: 50.9-68.0%) of patients. There was no association between short-term pain-relief and PGIC after 4 weeks (p = 0.18). Extent and location of nerve compression and contrast dispersion during TFESI did not correlate with longer-term pain-relief (all p ≥ 0.07). Our results indicate a significant positive correlation between immediate post-procedural and longer-term pain relief after TFESI in patients with lumbar radiculopathy; however, no effect of short-term pain relief is seen on PGIC after 4 weeks. Patients with good longer-term outcome (≥ 50% pain reduction) are twice as likely to have already shown good immediate pain reduction after TFESI.


Strength and Performance Enhancement of Multilayers by Spatial Tailoring of Adherend Compliance and Morphology via Multimaterial Jetting Additive Manufacturing.
Material tailoring of bondlayer compliance is a known effective route to enhance performance of multilayers, and here spatial material-tailoring of compliance and morphology of the adherends is examined. Multimaterial jetting additive manufacturing (AM) allows us to realize for the first time compliance- and morphology-tailored adherends, and evaluate directly the mechanical performance, including failure, of the tensile-loaded multilayers. Adherend compliance-tailoring, unlike bondlayer tailoring, requires additional consideration due to adherend bending stiffness and moment influences on bondlayer stresses. We introduce anisotropic as well as layered/sandwich adherend tailoring to address this dependence. Numerical models show that for both sub-critical and critical bondlengths (at which shear-dominated load transfer occurs through the bondlayer), adherend tailoring reduces peak stresses significantly, particularly peel stress (reductions of 47-80%) that typically controls failure in such systems. At sub-critical bondlengths, the AM-enabled layered/sandwich adherend tailoring shows significantly increased experimental performance over the baseline multilayer: strength is increased by 20%, toughness by 48%, and strain-to-break by 18%, while retaining multilayer stiffness. The adherend tailoring demonstrated here adds to the techniques available to increase the performance of bonded multilayers, suggesting that adherend tailoring is particularly well-suited to additively manufactured multilayers, but can also have application in other areas such as layered electronics and advanced structural composite laminates.


Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.
The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.


Loss of promoter methylation contributes to the expression of functionally impaired PRDM1β isoform in diffuse large B-cell lymphoma.
The positive regulatory domain I (PRDM1) is a transcriptional repressor that plays an important role in the B-cell differentiation. PRDM1β isoform is functionally impaired and overexpressed in a subset of diffuse large B-cell lymphoma with aggressive behavior. To investigate the possible epigenetic alteration on PRDM1β expression, methylation of PRDM1β promoter was assessed in B-lymphoma cell lines by bisulfite-sequencing PCR and screened in tumor samples of DLBCL patients using MassARRAY-quantitative methylation analysis. PRDM1β expression corresponded to promoter methylation status. CpG island of PRDM1β promoter possessed significant transcriptional activity, which could be modified by methylation. Loss of promoter methylation of PRDM1β was more frequently detected in lymphoma samples than in reactive hyperplasia. Thus, demethylation of abnormal tumor suppressor gene isoform might be linked to lymphoma progression.


Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.
Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.


6-hydroxydopamine-induced Parkinson's disease-like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging-detectable alteration in adult neurogenesis.
Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non-motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[(123) I]iodophenyl)nortropane single photon emission computed tomography, DaTscan(™) ) and neuroinflammation in the SN and striatum (N,N-diethyl-2-(2-(4-(2-[(18) F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide positron emission tomography, [(18) F]DPA-714 PET) in the intranigral 6-hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ-olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin-positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.


The role of microbiota during chicken manure and pig manure co-composting.
Co-composting is an excellent and effective technology for treating livestock manure in which microorganisms play a crucial function. Therefore, this study aimed at investigating the changes of microbial interactions during co-composting. Six different addition ratios of chicken and pig manure were used in composting experiment. The results showed that the co-composting system using 60% chicken manure and 40% pig manure significantly altered the microbial diversity and community structure. In addition, the complexity and tightness of its microbial community network structure reached the maximum, as did the strength of its cooperative and competitive microbial interactions. The higher microbial abundance and microbial interaction have the potential to promote the decomposition and transformation of compost components. Therefore, this study preliminarily revealed the changes of microbial community in co-composting, which provided a theoretical basis for optimizing microbial community interaction in composting systems by mixing different ratios of materials in practice.


A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn(2+) Arsenal for Combined Treatment of Gene Regulation and Drug Delivery.
As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn(2+)-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regulation and drug delivery in a controlled manner. By means of aptamer-guided targeting and receptor-mediated endocytosis, the probes were specifically internalized into the HeLa cells and trapped in the acidic endo-/lysosomes, where the ZnO QDs as the built-in Zn(2+) arsenal were promptly dissolved to offer Zn(2+), leading to the activation of DNAzyme to cleave the substrate strands, and subsequent drug release. Meanwhile, as designed, one part of the cleaved substrate, hybridized with the overexpressed miR-21 in the target cells, thereby declining its intracellular level. Taken together, the down-regulation of miR-21 has a synergistic effect with Dox to efficiently eradicate the cancer cells. Thus, the favorable biocompatibility, cancer cell specificity and combined treatment make the probe promising for therapy of multidrug-resistant cancer and in vivo application.


Sonoporation, anti-cancer drug and antibody delivery using ultrasound.
It has been shown experimentally in cell suspensions that sonoporation could be used to deliver the anti-cancer drug Adriamycin hydrochloride (ADR) into Jurkat lymphocytes and that it could also be used to deliver goat anti-rabbit IgG and anti-mouse IgD, antibodies into human peripheral blood mononuclear cells (PBMC) and Jurkat lymphocytes. When ADR was delivered, the delivery efficiency reached 4.80+/-2.04% and control baseline (no ultrasound and no ADR) was 0.17+/-0.14%. When anti-rabbit IgD was delivered, the efficiencies were 34.90+/-1.80% (control baseline was 1.33+/-0.31%) and 32.50+/-4.36% (control baseline was 1.66+/-0.06%) respectively for Jurkat cells and PBMC. When goat anti-rabbit IgG was delivered, the efficiencies were 78.60+/-3.60% (control baseline was 1.60+/-0.00%) and 57.50+/-4.23% (control baseline was 11.30+/-0.81%) respectively for Jurkat cells and PBMC.


Natural antioxidants in meat and poultry products.
In response to recent claims that synthetic antioxidants have the potential to cause toxicological effects and consumers' increased interest in purchasing natural products, the meat and poultry industry has been seeking sources of natural antioxidants. Due to their high phenolic compound content, fruits and other plant materials provide a good alternative to conventional antioxidants. Plum, grape seed extract, cranberry, pomegranate, bearberry, pine bark extract, rosemary, oregano, and other spices functions as antioxidants in meat and poultry products. Pomegranate, pine bark extract, cinnamon, and cloves have exhibited stronger antioxidant properties than some synthetic options. Plum products, grape seed extract, pine bark extract, rosemary, and some spices all have been shown to affect the color of finished meat or poultry products; however, in some products such as pork sausage or uncured meats, an increase in red color may be desired. When selecting a natural antioxidant, sensory and quality impact on the product should be considered to achieve desired traits.


Arsenic-rich geothermal fluids as environmentally hazardous materials - A global assessment.
Arsenic-rich geothermal fluids are hazardous materials of global impact, affecting different environments (groundwater, surface water, seawater, sediments, soils, atmosphere) and human and animal health. They can be released naturally or through human activities. For the first time, a systematic global assessment of geothermal arsenic (As) in fluids of the six principal types of geothermal reservoirs and their environmental impact (e.g. freshwater sources used for drinking and irrigation), distinguishing between different uses (if any), was performed based on research of the geochemical characteristics and geotectonic setting of the formation of natural geothermal reservoirs worldwide. This will assist to further improve the sustainability of geothermal energy use, which can be an excellent environmental friendly renewable energy resource for electric power production and direct heat use. Arsenic in geothermal fluids (up to several tens of mg/L) originates especially in deep seated (several kilometers) reservoirs. Proper management of geothermal fluids during exploration, exploitation, use and disposal of resulting waste products through sustainable As mitigation strategies are essential. However, more research about As speciation and volatile As is necessary to fulfil this aim. Therefore As (and its principal species) needs to be included as parameter for standard analysis and monitoring program in any project using geothermal fluids from exploration to management of resulting wastes as base to define appropriate mitigation actions.


Migration of photoinitiators, phthalates and plasticizers from paper and cardboard materials into different simulants and foodstuffs.
The migration of photoinitiators, phthalates and plasticizers from two paper and cardboard materials into food simulants (50% and 95% EtOH and Tenax) and foodstuffs (rice, cereals and milk powder) was studied. In the case of liquid simulants migration was observed to reach the equilibrium after 60 min and depended on the material type and the physicochemical parameters of the migrants, whereas the temperature (room temperature and 60 °C) did not show significant effects. The study of migration of the compounds from a baking paper to Tenax at high temperatures (150 and 250 °C) evidenced an increment of migration when increasing temperature, except for the most volatile analytes. Finally, the migration to foodstuffs was studied using fully validated analytical protocols. Overall, the comparison of the migration rates demonstrated that Tenax was adequate for the simulation of the migration to rice and cereals, but underestimated the migration to infant milk powder, for which 95% EtOH resulted a more suitable simulant.


Diagnostic application of panels of antibodies in mucosal melanomas of the head and neck.
This article describes the use of panels of antibodies in the histopathologic diagnosis of ten malignant melanomas arising in the mucosa of the head and neck. The immunohistochemistry analysis was performed in a step-by-step manner. In the first step a panel of antibodies discriminating between carcinoma, malignant lymphoma, and melanoma was used. Staining with antivimentin and the melanoma-associated antigen, moAb NKI/C-3, was found to occur in all cases. The NKI/C-3 stained nine of 10 specimens from the first biopsy. Anti-S-100 protein, anti-HMW-MAA, and NKI-beteb was used as a panel in the second step. These stained ten of ten, five of six, and seven of seven cases, respectively. The diagnosis for melanin was confirmed by extensive sampling and a diligent search for melanin and (pre)melanosomes in different biopsy and surgical specimens. These results indicate that a step-wise application of immunohistochemistry is a very useful tool in the diagnosis of mucosal melanoma of the head and neck.


Fabricating an electroactive injectable hydrogel based on pluronic-chitosan/aniline-pentamer containing angiogenic factor for functional repair of the hippocampus ischemia rat model.
The hippocampus, a critical cerebral region involved in learning and memory formation, is especially vulnerable to ischemic defect. Here, we developed an injectable electroactive hydrogel based on pluronic-chitosan/aniline-pentamer with proper conductivity around 10-4 S/cm to achieve the functional repair of the hippocampus following the ischemic defect. FTIR, DSC, and TGA measurements were performed to assess the chemical structure and thermal stability of the synthesized hydrogel. Aniline pentamer decreased the swelling capacity, degradation, and drug release rate. Further, contact angle, melting point, and gelation time of hydrogels were enhanced by addition of aniline oligomer. Moreover, it endowed the on-demand electro-responsive drug release. Injectability of hydrogel was evaluated by rheometry, exhibiting proper gelling time at the body temperature. The ionic/electrical conductivity and desired in vitro biocompatibility with PC12 cells were also achieved. Injection of VEGF-loaded electroactive hydrogel in the hippocampal ischemic animal model resulted in decreased infarction volume, improved hippocampal dependent learning, and memory performance. Taken all together, the results confirmed that fabricated injectable hydrogel would be a suitable candidate for ischemic defect treatment and can lead to new horizons to treat neurological disorders.


IX Antonio Arrigo Award. Clinical neurophysiology in neuromuscular disorders: usefulness and limitations.
This lecture focuses on the impact of classic and modern electrophysiological techniques on the diagnostic approach to patients with neuromuscular disorders, placing emphasis on the limitations of currently used techniques and on the future prospects of clinical neurophysiology. The refinement of old techniques together with the development of new ones will hopefully improve the diagnostic capability of neurophysiology, improve understanding of the complex pathogenic mechanisms underlying neuromuscular disorders and help further the research of new therapeutic strategies.


Vermicomposting of textile mill sludge employing Eisenia fetida: Role of cow dung and tea waste amendments.
Vermicomposting of textile mill sludge (TMS) with cow dung (CD) and tea waste (TW) as amendments was done in seven different combinations using Eisenia fetida for 90 days. Results revealed that pH decreased from 7.68-8.63 to 7.09-7.59. TOC content and C/N ratio reductions were in range of 15.71-20.08% and 39.33-50.05%, respectively (P < 0.05). The macronutrients in the form of TN, TP, and TK increased 0.38-0.64, 1.07-2.27, and 0.56-1.98 times respectively after end of bioconversion process (P < 0.05), among increases in ash content and EC. The biomass and cocoon production of E. fetida increased significantly (P < 0.05), while high mortality rate of earthworms was observed in treatments containing 50% or more TMS content. The bacterial population beneficial for degradation of organic matter increased significantly over initial substrates (0th day) (P < 0.05). Increased humification index in end-product indicated better maturity of vermicompost as observed in treatments containing higher proportions of amendments. The addition of amendments favored earthworm activity which significantly decreased the heavy metal concentration (Fe, Cu, Pb, Zn) in the end-product. The study concluded that sustainable utilization of TMS could be achieved for cleaner and enriched vermicompost production by addition of amendments CD and TW in proportions of 50% and above.


Mutagenicity assessment of acrylate and methacrylate compounds and implications for regulatory toxicology requirements.
Esters of acrylic acid and methacrylic acid, more commonly known as acrylates and methacrylates, respectively, are key raw materials in the coatings and printing industry, with several of its chemical class used in food packaging. The results of over 200 short-term in vitro and in vivo mutagenicity studies available in the open literature have been evaluated. Despite differences in acrylate or methacrylate functionality or in the number of functional groups, a consistent pattern of test response was seen in a typical regulatory battery of mutagenicity tests. No evidence of point mutations was observed when acrylic acid or over 60 acrylates and methacrylates were investigated in Salmonella bacterial tests or in hprt mutation tests mammalian cells, and no evidence of a mutagenic effect was seen when tested in whole animal clastogenicity and/or aneuploidy (chromosomal aberration/micronucleus) studies. Consistent with the in vivo testing results, acrylic acid exhibited no evidence of carcinogenicity in chronic rodent cancer bioassays. In contrast, acrylic acid and the entire acrylate and methacrylate chemical class produced a consistently positive response when tested in the mouse lymphoma assay and/or other in vitro mammalian cell assays designed to detect clastogenicity. The biological relevance of this in vitro response is questioned based on the non-concordance of in vitro results with those of in vivo studies addressing the same mutagenic endpoint (clastogenicity). Thus, in short-term mutagenicity tests, the acrylates and methacrylates behave as a single chemical category, and genotoxicity behavior of a similar chemical can be predicted with confidence by inclusion within this chemical class, thus avoiding unnecessary testing.


Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow.
Alterations in liver vascular tone play an important role in chronic liver disease. The hepatic stellate cell (HSC) and mediators such as nitric oxide (NO) and hydrogen sulfide (H2S) have been implicated in regulation of vascular tone and intra-hepatic pressure. Though these have been studied in chronic liver damage, changes in response to acute liver injury induced by hepatotoxins such as dimethyl nitrosamine are not well understood. Liver injury was induced in mice by a single intra-peritoneal injection of dimethylnitrosamine (DMN), following which animals were sacrificed at 24, 48 and 72 h. Changes in vascular mediators such as NO and H2S as well as stellate cell activation was then examined. It was found that a single low dose of DMN in mice is sufficient to induce activation of hepatic stellate cells within 24 h, accompanied by oxidative stress, compromised metabolism of H2S and decreased levels of the von Willebrand factor (vWF) cleaving protease; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which functions in intravascular thrombosis. A suppression of hepatic NO levels is also initiated at this time point, which progresses further and is sustained up to 72 h, at which point the HSC activation is still present. Compromised levels of ADAMTS13 and H2S metabolism however, begin to recover by 48 h and are almost similar to control by 72 h. In conclusion, these data suggest that even moderate acute insults in the liver can have far reaching consequences on a number of mediators of vascular flow in the liver.


Inactivation of human hepatitis B virus DNA polymerase by pyridoxal 5'-phosphate.
Human hepatitis B virus (HBV) DNA polymerase activity was inhibited by pyridoxal 5'-phosphate (PLP) specifically and noncompetitively with respect to deoxythymidine triphosphate (DTTP). NaBH4 reduction of PLP-HBV core proteins resulted in the complete inactivation of HBV DNA polymerase, and PLP modification of the enzyme was though to be mediated through Schiff-base formation. HBV DNA polymerase has a Michaelis constant (Km) of 0.31 microM for dTTP and an apparent inhibition constant (Ki) of 0.2 mM for PLP. Its inactivation and modification by PLP may be useful in the study of not only the reaction mechanism of catalysis, but also the physicochemical nature of the enzyme.


Effectiveness of the new mandatory mouthguard use and orodental injuries in Dutch field hockey.
ObjectivesUp to 68% of field hockey players have experienced at least one orodental injury in their sport career. Therefore, the Royal Dutch Hockey Association (KNHB) made mouthguard use mandatory for field hockey players during competition and training from August 2015 onwards.This study evaluates the effects of the new regulations on mouthguard use and the occurrence of injuries in Dutch field hockey.MethodsA 35-item online questionnaire about mouthguard use and orodental injuries was sent to 13 field hockey clubs in the Netherlands. Absolute numbers and percentages of mouthguard ownership, mouthguard use, number and type of injuries were assessed. The results were related to comparable data before mandatory mouthguard use. Associations of gender and training frequency with the number of injuries were analysed with logistic regression.ResultsIn total, 1169 hockey players were included in the study and almost all owned a mouthguard (females:99.6%, males:93.7%), which significantly increased after implementation (p < 0.001). 90.6% of the respondents wore a mouthguard during matches and 70.1% during training. Of the 1169 players, 68(5.8%) experienced at least one orodental injury after the implementation with a total of 100 injuries. Injuries happened more often during matches (63.2%) than during training (36.8%). Lip cuts account for most of the injuries, the number of broken (p = 0.116) and knocked out teeth (p = 0.026) decreased.ConclusionAlthough mouthguard use already increased in recent years, the new regulations led to an additional increase and a successful change of attitude towards mouthguard use. Most importantly, the severity of orodental injuries decreased measurable.


Complementation between two temperature-sensitive mammalian cell mutants, each defective in the G1 phase of the cell cycle.
Two mammalian temperature-sensitive (ts) G1 cell cycle mutants of different species origin (Syrian hamster and mouse) have been tested for complementation using somatic cell hybrid analysis. All hamster-mouse hybrid clones tested were found to exhibit normal growth properties at the restrictive temperature, while neither mutant alone was capable of normal growth at this temperature. The two mutant lines therefore complement for growth in a somatic cell hybrid and most likely represent ts lesions in different cellular functions specific to the G1 phase of the cell cycle.


Stem respiration and carbon dioxide efflux of young Populus deltoides trees in relation to temperature and xylem carbon dioxide concentration.
Oxidative respiration is strongly temperature driven. However, in woody stems, efflux of CO(2) to the atmosphere (E (A)), commonly used to estimate the rate of respiration (R (S)), and stem temperature (T (st)) have often been poorly correlated, which we hypothesized was due to transport of respired CO(2) in xylem sap, especially under high rates of sap flow (f (s)). To test this, we measured E (A), T (st), f (s) and xylem sap CO(2) concentrations ([CO(2)*]) in 3-year-old Populus deltoides trees under different weather conditions (sunny and rainy days) in autumn. We also calculated R (S) by mass balance as the sum of both outward and internal CO(2) fluxes and hypothesized that R (S) would correlate better with T (st) than E (A). We found that E (A) sometimes correlated well with T (st), but not on sunny mornings and afternoons or on rainy days. When the temperature effect on E (A) was accounted for, a clear positive relationship between E (A) and xylem [CO(2)*] was found. [CO(2)*] varied diurnally and increased substantially at night and during periods of rain. Changes in [CO(2)*] were related to changes in f (s) but not T (st). We conclude that changes in both respiration and internal CO(2) transport altered E (A). The dominant component flux of R (S) was E (A). However, on a 24-h basis, the internal transport flux represented 9-18% and 3-7% of R (S) on sunny and rainy days, respectively, indicating that the contribution of stem respiration to forest C balance may be larger than previously estimated based on E (A) measurements. Unexpectedly, the relationship between R (S) and T (st) was sometimes weak in two of the three trees. We conclude that in addition to temperature, other factors such as water deficits or substrate availability exert control on the rate of stem respiration so that simple temperature functions are not sufficient to predict stem respiration.


An examination of food addiction in a racially diverse sample of obese patients with binge eating disorder in primary care settings.
The concept of food addiction in obesity and binge eating disorder (BED) continues to be a hotly debated topic yet the empirical evidence on the relationship between addictive-like eating and clinically relevant eating disorders is limited. The current study examined the association of food addiction as assessed by the Yale Food Addiction Scale (YFAS) with measures of disordered eating, dieting/weight history, and related psychopathology in a racially diverse sample of obese patients with binge eating disorder (BED). A consecutive series of 96 obese patients with BED who were seeking treatment for obesity and binge eating in primary care were given structured interviews to assess psychiatric disorders and eating disorder psychopathology and a battery of self-report measures including the YFAS to assess food addiction. Classification of food addiction was met by 41.5% (n=39) of BED patients. Patients classified as meeting YFAS food addiction criteria had significantly higher levels of negative affect, emotion dysregulation, and eating disorder psychopathology, and lower self-esteem. Higher scores on the YFAS were related to an earlier age of first being overweight and dieting onset. YFAS scores were also significant predictors of binge eating frequency above and beyond other measures. Compared to patients not classified as having food addiction, the subset of 41.5% of BED patients who met the YFAS food addiction cut-off appears to have a more severe presentation of BED and more associated pathology.


Colorectal Surgery in Patients with HIV and AIDS: Trends and Outcomes over a 10-Year Period in the USA.
HIV has become a chronic disease, which may render this population more prone to developing the colorectal pathologies that typically affect older Americans. A retrospective review of the Nationwide Inpatient Sample was performed to identify patients who underwent colon and rectal surgery from 2001 to 2010. Multivariate analysis was used to evaluate outcomes among the general population, patients with HIV, and patients with AIDS. Hospital admissions for colon and rectal procedures of patients with HIV/AIDS grew at a faster rate than all-cause admissions of patients with HIV/AIDS, with mean yearly increases of 17.8 and 2.1 %, respectively (p < 0.05). Patients with HIV/AIDS undergoing colon and rectal operations for cancer, polyps, diverticular disease, and Clostridium difficile were younger than the general population (51 vs. 65 years; p < 0.01). AIDS was independently associated with increased odds of mortality (OR 2.11; 95 % CI 1.24, 3.61), wound complications (OR 1.53; 95 % CI 1.09, 2.17), and pneumonia (OR 2.02; 95 % CI 1.33, 3.08). Risk-adjusted outcomes of colorectal surgery in patients with HIV did not differ significantly from the general population. Postoperative outcomes in patients with HIV are similar to the general population, while patients with AIDS have a higher risk of mortality and certain complications.


Palliative care needs of patients with multiple sclerosis in southeast Iran.
Due to the chronic nature of multiple sclerosis, palliative care can play a significant role in improving the quality of life and well-being of the affected patients. An essential step for developing appropriate palliative care for these patients is to determine the types of palliative care necessary, from different points of view. Therefore, this study was conducted to compare the palliative care needs from the nurses' and patients' points of view in southeast Iran in 2017. This descriptive-analytical cross-sectional study was conducted on 154 nurses working in neurology wards of teaching hospitals associated with Kerman University of Medical Sciences and 132 patients with multiple sclerosis who were referred to these hospitals in southeast Iran. The data were collected using a questionnaire for assessing the palliative care needs of patients with multiple sclerosis. Pearson correlation coefficient, independent t-test, ANOVA, chi-square, and the Mann-Whitney and Kruskal-Wallis tests were used to examine the data. Both nurses and patients mentioned the palliative needs of patients with multiple sclerosis in terms of physical, social, spiritual, psychological, and economic dimensions, respectively, but the results showed that there was a significant difference between the two groups in all dimensions of palliative needs (P < 0.0001). Given the differences in how patients and nurses prioritize palliative care needs, it is essential to consider the different dimensions of palliative needs of patients with multiple sclerosis.


Comparison of manually triggered ventilation and bag-valve-mask ventilation during cardiopulmonary resuscitation in a manikin model.
To compare a novel, pressure-limited, flow adaptive ventilator that enables manual triggering of ventilations (MEDUMAT Easy CPR, Weinmann, Germany) with a bag-valve-mask (BVM) device during simulated cardiac arrest. Overall 74 third-year medical students received brief video instructions (BVM: 57s, ventilator: 126s), standardised theoretical instructions and practical training for both devices. Four days later, the students were randomised into 37 two-rescuer teams and were asked to perform 8min of cardiopulmonary resuscitation (CPR) on a manikin using either the ventilator or the BVM (randomisation list). Applied tidal volumes (V(T)), inspiratory times and hands-off times were recorded. Maximum airway pressures (P(max)) were measured with a sensor connected to the artificial lung. Questionnaires concerning levels of fatigue, stress and handling were evaluated. V(T), pressures and hands-off times were compared using t-tests, questionnaire data were analysed using the Wilcoxon test. BVM vs. ventilator (mean±SD): the mean V(T) (408±164ml vs. 315±165ml, p=0.10) and the maximum V(T) did not differ, but the number of recorded V(T)<200ml differed (8.1±11.3 vs. 17.0±14.4 ventilations, p=0.04). P(max) did not differ, but inspiratory times (0.80±0.23s vs. 1.39±0.31s, p<0.001) and total hands-off times (133.5±17.8s vs. 162.0±11.1s, p<0.001) did. The estimated levels of fatigue and stress were comparable; however, the BVM was rated to be easier to use (p=0.03). For the user group investigated here, this ventilator exhibits no advantages in the setting of simulated CPR and carries a risk of prolonged no-flow time.


Posterior-stabilized total knee arthroplasty: a matched pair analysis of a classic and its evolutional design.
Total knee arthroplasty (TKA) designs continue to be modified to optimize patient's outcome. This study was designed to compare clinical and radiological results of classic worldwide used TKA posterior-stabilized (PS) design to those of its recent evolution. A consecutive group of 100 patients undergoing TKA using a classic cemented fixed-bearing PS TKA system was matched by age, gender, body max index to 100 patients having the newer cemented fixed-bearing PS design, both by the same manufacturer. Patients were assessed preoperatively, at 12 months and at 24 months minimum follow-up (range, 24-46) in a standard prospective fashion. The outcome assessments used were the Oxford Knee Score, the Knee Society Score, range of motion, and a satisfaction survey. A 2-sample t test comparing the 2 groups was performed. No patients were lost at follow-up. At 2-year follow-up, differences in clinical and radiological Knee Society Score (P = .09), Oxford Score (P = .08), and overall satisfaction rate did not reach statistical significance. Implant group 2 showed a statistically significant decrease in postoperative anterior knee pain (P = .006). At final follow-up, 16% of group 1 knees achieved > 130° flexion compared with 37% in group 2 (P = .0009). There were 2 revisions for any reason in group 1 and none in group 2. Design modifications applied to the newer TKA system allowed greater flexion and lower patellofemoral complications but did not appear to achieve better overall clinical scores.


Design of substrates and inhibitors of G protein-coupled receptor kinase 2 (GRK2) based on its phosphorylation reaction.
The G protein-coupled receptor kinase (GRK) family consists of seven cytosolic serine/threonine (Ser/Thr) protein kinases, and among them, GRK2 is involved in the regulation of an enormous range of both G protein-coupled receptors (GPCRs) and non-GPCR substrates that participate in or regulate many critical cellular processes. GRK2 dysfunction is associated with multiple diseases, including cancers, brain diseases, cardiovascular and metabolic diseases, and therefore GRK2-specific substrates/inhibitors are needed not only for studies of GRK2-mediated cellular functions but also for GRK2-targeted drug development. Here, we first review the structure, regulation and functions of GRK2, and its synthetic substrates and inhibitors. We then highlight recent work on synthetic peptide substrates/inhibitors as promising tools for fundamental studies of the physiological functions of GRK2, and as candidates for applications in clinical diagnostics.


Evolution of cis-regulatory elements in duplicated genes of yeast.
An increasing number of studies report that functional divergence in duplicated genes is accompanied by gene expression changes, although the evolutionary mechanism behind this process remains unclear. Our genomic analysis on the yeast Saccharomyces cerevisiae shows that the number of shared regulatory motifs in the duplicates decreases with evolutionary time, whereas the total number of regulatory motifs remains unchanged. Moreover, genes with numerous paralogs in the yeast genome do not have especially low number of regulatory motifs. These findings indicate that degenerative complementation is not the sole mechanism behind expression divergence in yeast. Moreover, we found some evidence for the action of positive selection on cis-regulatory motifs after gene duplication. These results suggest that the evolution of functional novelty has a substantial role in yeast duplicate gene evolution.


Fluorescence study of Eu chelates in solution and polymer matrix.
The fluorescence spectra of Eu chelates with different neutral ligand in methyl methacryate (MMA) solution were measured and the influence of the neutral ligand was analyzed. The chelate Eu(DBM)3(TOPO)2, which shows the strongest fluorescence intensity in the solution, has been incorporated into the poly(methyl methacryate) (PMMA) matrix. According to the fluorescence emission spectrum, its radiative properties were also predicted.


Loiasis: African eye worm.
The filarial parasite Loa loa is transmitted by Chrysops fly bites. Loiasis is endemic in rainforest areas of West and Central Africa, and sporadic cases have also been diagnosed in travellers and migrants. Whilst many infected persons are asymptomatic, microfilariae may be detected in the blood or adult worms may be seen under the skin or the sclera of the eye. Mass treatment programmes for onchocerciasis have raised concern about the risk of severe adverse effects when ivermectin is distributed in areas co-endemic for onchocerciasis and loiasis.


Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with gonadotropin-releasing hormone analogs.
A modulatory role for gonadotropin-releasing hormone (GnRH) on granulosa cell functions has been demonstrated in animals. Because human granulosa cells have specific receptors for GnRH, we have compared steroidogenesis in vitro of cells pretreated in vivo with GnRH analogs (GnRH-a) with other ovarian stimulation regimens used in in vitro fertilization (IVF) cycles. Cells from 13 patients treated with a GnRH-a for 26.8 +/- 1.1 days during pituitary desensitization and ovarian stimulation with gonadotropins were cultured. Their steroidogenesis was evaluated in basal conditions as well as after stimulation with follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). Granulosa-luteal cells from 9 women treated with a combination of clomiphene citrate (CC) and gonadotropins were also cultured. Estradiol production in response to FSH was stimulated only in the GnRH-a-treated cells. Basal, FSH-, and hCG-induced progesterone (P) accumulation was higher in the CC-treated cells. The peak of P production was delayed 2 days in the GnRH-a-treated group. Only cells pretreated in vivo with GnRH-a accumulated 20 alpha-hydroxyprogesterone in culture. The results of the present study suggest that the use of GnRH-a during a long period of time for IVF affects the steroidogenic pathway of human granulosa-luteal cells. It seems that, at least in part, this change is due to the stimulation of the metabolizing enzyme 20 alpha-hydroxysteroid dehydrogenase by GnRH-a.


Dataset concerning haematological and biochemical parameters changes in show jumping horses subjected to exercise and plasmapheresis session.
This article presents data on the effect of plasmapheresis on clinical, haematological and biochemical parameters in horses following exercise and after a plasmapheresis session. This blood filtration technique was realised on six jumping horses (plasmapheresis group) that underwent three consecutive days of graded physical exercise. The control group (n = 6) went through the same exercise but was not subjected to the plasmapheresis session. Blood was sampled before and after each exercise, also at the beginning and the end of plasmapheresis session. The presented data was obtained by measuring clinical and haemato-biochemical parameters in both groups. The heart and respiratory rates and rectal temperature were recorded. In addition, the number of red blood and white cells, platelets also of lymphocytes, monocytes, eosinophils and granulocytes were counted. Other haematological parameters including, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration were determined. Concerning the biochemical parameters, the concentrations of albumin, globulin, total protein, glucose, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, total bilirubin, lactate, creatinine kinase, urea, creatinine, calcium, sodium and potassium were measured. All parameters data were analyzed by a two-way repeated measures analysis of variance followed by Holm-Sidak post-hoc procedure to evaluate the effect of plasmapheresis and time. This paper contains data related to and supporting research articles currently published entitled "Plasmapheresis effect on haematological and biochemical parameters in athletic horses subjected to exercise" (Daden et al., 2019) [1].


Cerebral Hemodynamic Changes to Transcranial Doppler in Asymptomatic Patients with Fabry's Disease.
Patients with Fabry's disease (FD) may be asymptomatic or show a spectrum of clinical manifestations, including cerebrovascular disease, mainly affecting posterior circulation. Few and conflicting studies on cerebral blood flow (CBF) velocity by transcranial Doppler sonography (TCD) in asymptomatic FD (aFD) subjects have been published. Our study aims to assess TCD in aFD subjects to identify any preclinical CBF change. A total of 30 aFD subjects were consecutively recruited and compared to 28 healthy controls. Brain magnetic resonance imaging was normal in all participants. TCD was used to study blood flow velocity and indices of resistance of intracranial arteries from the middle cerebral artery (MCA), bilaterally, and from the basilar artery (BA). Cerebral vasomotor reactivity (CVR) was also evaluated from MCA. No difference was found between groups for MCA parameters of CBF velocity and CVR. Compared to controls, a higher mean blood flow velocity and a lower resistance index from BA were observed in FD subjects. No correlation was found between any BA-derived TCD parameter and the level of lyso-globotriaosylceramide. aFD subjects show evidence of altered CBF velocity in posterior circulation. Preclinical detection of neurovascular involvement in FD might allow appropriate management and prevention of future cerebrovascular complications and disability.