Embryonic stem cell therapy for diabetes mellitus.
There is a compelling need to develop novel therapies for diabetes mellitus. Recent successes in the transplantation of islets of Langerhans are seen as a major breakthrough. However, there is huge disparity between potential recipients and the availability of donor tissue. Human embryonic stem cells induced to form pancreatic beta cells could provide a replenishable supply of tissue. Early studies on the spontaneous differentiation of mouse embryonic stem cells have laid the foundation for a more directed approach based on recapitulating the events that occur during the development of the pancreas in the mouse. A high yield of definitive endoderm has been achieved, and although beta-like cells can be generated in a step-wise manner, the efficiency is still low and the final product is not fully differentiated. Future challenges include generating fully functional islet cells under Xeno-free and chemically defined conditions and circumventing the need for immunosuppression.


Tracing environmental aetiological factors of chronic kidney diseases in the dry zone of Sri Lanka-A hydrogeochemical and isotope approach.
Chronic kidney disease of unknown aetiologies (CKDu) is increasingly recognized in tropical regions and is now considered a global health problem. A detailed hydrogeochemical investigation has been performed in three CKDu hotspots in Sri Lanka to assess the geo-environmental aetiological factors influencing this disease. A total of 71 ground- and 26 surface water samples were collected from Girandurukotte, Wilgamuwa and Nikawewa regions and analysed for major constituents and trace elements. The affected regions are dominated by Ca-Mg-HCO3 facies groundwater that is mainly controlled by silicate weathering. Higher levels of fluoride associated with higher hardness is the main feature of groundwater from CKDu regions compared to non-CKDu regions. Results showed that 65% of the wells in the affected regions exceeded the fluoride concentration of 0.5mg/L. Environmental isotopes of groundwater in the CKDu regions are represented by the regression line of δ2H=5.42δ18O-3.59 (r2=0.916) with a clear isotopic differentiation between local precipitation and groundwater. None of the trace elements exceeded the recommended scales and in most cases levels are negligible in both surface and groundwater in study areas. Therefore, the involvement of trace elements such as Cd, As and Pb can be ignored as causative factors for CKDu. This study highlights the synergistic influence of fluoride and hardness that could enhance the disease, and thereby refute earlier theories that attribute trace elements as causative factors for CKDu. Higher hardness in drinking water also restricts sufficient water uptake, particularly by farmers and which affects the physiological, biochemical and nutritional requirements.


Monitoring the role of Mn and Fe in the As-removal efficiency of tetravalent manganese feroxyhyte nanoparticles from drinking water: An X-ray absorption spectroscopy study.
The implementation of amorphous tetravalent manganese feroxyhyte (TMFx) nanoparticles, prepared via co-precipitation synthesis, as an efficient As(V)-removal material is investigated using X-ray absorption fine structure (XAFS) spectroscopy at the Fe-, Mn- and As-K-edges. The optimum synthesis conditions and chemical composition of the TMFx adsorbent were determined by the degree of polymerization in the adsorbents' microstructure. Under synthesis into mildly acidic conditions, the change in the polymerization of the metal-oxyhydroxyl chains (metal=Fe, Mn) provides more adsorption sites at edges and corner sites in the bonding environment of Fe and Mn, respectively, thereby enhancing As uptake. After exposure to As-polluted water, similar microstructural changes related to As-bidentate and monodentate geometries are generated: As(V) preferentially occupies the high energy adsorption sites ((2)C complexes) available in the Mn-oxyhydroxyl groups and the low energy edge sites offered by Fe ((2)E complexes). It is revealed that optimum arsenic-removal by TMFx occurs into mildly acidic synthesis pH and for iron to manganese molar ratio equal to 3.


Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia and rHuEPO requirement in ESRD patients with central venous catheters: a pilot study.
In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane. Sixteen subjects with CVCs were included in a prospective two-arm crossover 12-month study. The primary endpoints were the rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12 g/dl were 135 ± 59 and 101 ± 57 IU/kg/week with polysulfone and PSVE, respectively (P = 0.14). The ESA indexes were 12.1 ± 5.2 and 8.7 ± 5.2 (P < 0.0001) with polysulfone and PSVE, respectively. A trend towards consensual changes in protein glycoxidation, antioxidant, and inflammatory markers was observed. In conclusion, the study suggests a role for PSVE in the reduction of ESA index in HD patients with CVCs.


Characterization of a thermostable endo-beta-1,4-D-galactanase from the hyperthermophile Thermotoga maritima.
A putative endo-beta-1,4-D-galactanase gene of Thermotoga maritima was cloned and overexpressed in Escherichia coli. The recombinant enzyme hydrolyzed pectic galactans and produced D-galactose, beta-1,4-D-galactobiose, beta-1,4-D-galactotriose, and beta-1,4-D-galactotetraose. The enzyme displayed optimum activity at 90 degrees C and pH 7.0. It was slowly inactivated above pH 8.0 and below pH 5.0 and stable at temperatures up to 80 degrees C.


[GreenLight laser therapy for benign prostatic hyperplasia: dilemma of reimbursement in the DRG system].
KTP or GreenLight laser vaporization of the prostate has increasingly become an established approach in the last 5 years. Since the additional costs for this treatment were initially not included in the DRG system, there was an extra possibility in 2000-2007 for billing these services as so-called new methods of examination and treatment. Since 2008 there is a new DRG (M11Z) for this procedure, but it does not cover the costs incurred. The reasons for this are to be found in the inhomogeneous assignment of costs by the clinics conducting the calculations. An improved cost reflection can only be expected by concerted action on the part of those hospitals designated as calculators that administer GreenLight laser therapy.


A novel recombinant Salmonella vaccine enhances the innate immunity of NK cells against acute myeloid leukaemia cells Kasumi-1 in vitro.
Minor histocompatibility antigen HA-1-specific cytotoxic lymphocyte (CTL) clones have apparent anti-leukaemic efficacy, and the AML/ETO gene is a special fusion gene in leukaemic cells. Thus, we hypothesised that a vaccine targeting HA-1 and AML/ETO could stimulate NK cells to target leukaemia cells. Furthermore, we packaged the vaccine using attenuated Salmonella to enhance its immuno-activity. Expression of the NK cell-activating ligand ULBP2 was notably elevated upon packaging in a co-recombinant group. An AML/ETO single plasmid gave the weakest vaccine. The level of miR-182, which targets ULBP2, significantly decreased with increasing IFN-γ and granzyme B in a co-recombinant group. In summary, DNA vaccines including AML/ETO and HA-1 fragments significantly enhance the innate immunity of NK cells in vitro.


Evaluation and management of plateau iris syndrome: case report and review.
This article documents a case of plateau iris syndrome and provides a review of the current concepts regarding the pathogenesis, diagnosis, and management of this condition. A patient who had patent peripheral iridotomies O.D. and O.S. to treat previous episodes of acute angle closure came to clinic with unilaterally elevated intraocular pressures, narrow anterior chamber angles, and a flat iris configuration. The patient was diagnosed with plateau iris syndrome. The clinician must be aware of, and be able to distinguish, the clinical signs that are characteristic of plateau iris syndrome. An understanding of the mechanisms involved in the development of this type of primary angle closure may facilitate its appropriate diagnosis and management.


Intra-aortic balloon pump-assisted major hepatectomy in a case with coronary disease.
Clinically, we often encounter cancer patients who also have cardiovascular disease such as coronary artery disease. We experienced a case of severe coronary artery disease and a large hepatocellular carcinoma in a 69-year-old man. To reduce the risk of a perioperative cardiovascular event during mesohepatectomy, an elective intra-aortic balloon pump (IABP) was used. After an uneventful recovery, the patient was discharged on day 15. While IABP is frequently introduced in cardiac surgery, there have been few reports of its use during liver surgery. Here, we present IABP-assisted major hepatectomy as an option in a patient with both cancer and coronary artery disease.


Pregnancies after ultrasound-guided fallopian insemination with cryostored donor semen.
Twenty-nine patients, previously treated unsuccessfully with a median 9.5 cycles of conventional intracervical donor insemination, were offered fallopian catheterization on the side of the dominant follicle and direct insemination at the presumed site of fertilization, the ampullary-isthmic junction. Forty-five of 50 cycles were associated with successful tubal catheterization and 6 of these cycles were conceptional. Five viable intrauterine pregnancies resulted. We conclude: (1) that direct sperm transfer to the fallopian tubes is possible without the need for anesthesia or operation; and (2) that at the time of ovulation, the fallopian tube isthmus can be catheterized without later interfering with ovum or embryo transport to the uterus. Optimum timing for fallopian catheterization in relation to ovulation and the risk of side effects both remain to be established.


Application of ultrasonication as pre-treatment for freeze drying: An innovative approach for the retention of nutraceutical quality in foods.
Freeze drying (FD) is an important and highly effective technology in food industry for retaining the quality in final dried product. This drying technique is performed at lower temperatures, restricting the damage suffered by thermally sensitive ingredients. However, FD consumes large amount of energy and required more time than conventional drying methods. The utilization of ultrasonic technology (US) as pre-treatment before FD represents a promising alternative in accelerating the drying process, decreases energy consumption and maintaining quality as compared to the non pre-treated sample. This review summarizes research progress and current studies in ultrasonic as pre-treatment for freeze drying (US + FD) technique. The impact of US + FD on phytochemical, color, texture and micro-structure of food are well summarized. The review also suggests that the optimised US treatment parameters are required to improve heat and mass transfer in food samples which help in speed up the drying process and reduction of drying time.


Calcium channel 'agonist' BAY K 8644 inhibits calcium antagonist binding to brain and PC12 cell membranes.
BAY K 8644, a drug that elicits calcium-dependent muscle contraction, inhibits binding of the voltage-dependent calcium channel antagonist [3H]nitrendipine to brain and PC12 pheochromocytoma cell membranes. This effect is due to high-affinity (Ki = 4.5 nM) competitive inhibition at the binding site for dihydropyridine calcium antagonists. Allosteric sites that mediate calcium channel blockade by non-dihydropyridine calcium antagonists are not similarly affected. Our findings indicate that BAY K 8644 is active at central, as well as peripheral, calcium channels and are compatible with a multi-state model of the voltage-dependent calcium channel in which antagonist drugs promote a closed state of the channel, while BAY K 8644 promotes an open state.


Textile Masks and Surface Covers-A Spray Simulation Method and a "Universal Droplet Reduction Model" Against Respiratory Pandemics.
The main form of COVID-19 transmission is via "oral-respiratory droplet contamination" (droplet: very small drop of liquid) produced when individuals talk, sneeze, or cough. In hospitals, health-care workers wear facemasks as a minimum medical "droplet precaution" to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, for asymptomatic individuals, not wearing masks in public could easily cause the spread of COVID-19. The prevention of "environmental droplet contamination" (EnvDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote "public droplet safety," we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal "community droplet reduction solution" is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8 m, the minimum distance recommended for COVID-19 "social distancing." All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30 cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10 cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a "community droplet reduction solution" (i.e., face covers/scarfs/masks and surface covers) will reduce COVID-19 EnvDC and thus the risk of transmitting/acquiring COVID-19.


Nucleotide sequence of the gene encoding the RNA subunit (M1 RNA) of ribonuclease P from Escherichia coli.
The gene encoding the RNA subunit (M1 RNA) of RNAase P (EC 188.8.131.52) from Escherichia coli has been isolated, and its complete nucleotide sequence, including flanking regions, has been determined. The promoter region, similar to others near genes under stringent control, and the site of transcription termination have been identified. The transcript from the gene (M1 RNA) can be drawn in a secondary structure that has approximately 60% G-C base pairs. One hairpin loop of this hypothetical structure has five contiguous nucleotides complementary to invariant nucleotides in the TpsiCG loop of all E. coli tRNAs. The M1 gene, when subcloned in the plasmid pBR325, can be amplified. It directs production of functional M1 RNA. In an E. coli strain thermosensitive for RNAase P function, the size of the gene transcript is the same as in wild-type E. coli, but less mature M1 RNA is made in the mutant cells.


Potential secondary inoculum sources of Botrytis cinerea and their influence on bunch rot development in dry Mediterranean climate vineyards.
Epidemiological studies have described the life cycle of B. cinerea in vineyards. However, there is a lack of information on the several infection pathways and the quantitative relationships between secondary inoculum and bunch rot at harvest. Over two seasons, different spray programmes were used to determine key phenological stages for bunch rot development. Secondary inoculum sources within the bunch were also studied. The relative importance of flowering was evidenced in the given conditions, as treatments that included two fungicide applications at flowering were the most effective. In 2010, under conducive meteorological conditions for B. cinerea development after veraison, an extra application provided significantly higher control. Infections of necrotic tissues inside the bunch and latent infections developed mainly during flowering, while very low quantities of B. cinerea conidia were recovered from the fruit surface at veraison. Regression analysis correlated the incidence of latent infections and B. cinerea incidence on calyptras and aborted fruits at veraison with incidence of Botrytis bunch rot at harvest, presenting R2 = 0.95 for the overall regression model. This work points out key phenological stages during the season for bunch rot and B. cinerea secondary inoculum development and relates quantitatively inoculum sources at veraison to bunch rot at harvest. Recommendations for field applications of antibotrytic products are also suggested.


Randomized, prospective comparison of first- and second-generation cephalosporins as infection prophylaxis for cardiac surgery.
Surgical wound infections after cardiovascular surgery may be life threatening and are resource intensive. Second-generation cephalosporins are purported to have a broader antimicrobial spectrum than first-generation cephalosporins and, therefore, may be more efficacious for infection prophylaxis. We have conducted a randomized prospective study of 702 patients undergoing open heart surgery to test the hypothesis that the second-generation cephalosporin, cefuroxime, will be more efficacious for infection prophylaxis than the first-generation cephalosporin, cefazolin. Patients were randomized to receive cefazolin 1 g intravenously every 8 hours for 48 hours begun 1 hour preoperatively plus 1 g after 4 hours of surgery (8 doses, n = 425) or cefuroxime 1.5 g 1 hour prior to surgery plus 1.5 g every 12 hours for 3 additional doses (4 doses, n = 277). Infection was defined as a draining wound with or without a positive culture. There was no difference in the wound infection rate between the groups (p = 0.68). Chest wound infections occurred in 2.1% of patients treated with cefazolin and 2.9% of patients treated with cefuroxime (p = 0.79). The rate of true mediastinitis requiring exploration and drainage was 0.7% in both groups (p = 0.084). Leg infections occurred in 6.6% of cefazolin-treated patients and 5.6% of cefuroxime-treated patients (p = 0.83). The second-generation cephalosporin, cefuroxime, did not reduce the incidence of wound infection when compared with the first-generation cephalosporin, cefazolin. Since institutional antibiotic acquisition and administration costs vary, careful analysis of these factors will allow determination of the most cost-effective infection prophylaxis regimen in cardiac surgery.


[Creation of an inter-sector COVID-19 care unit for psychiatric patients].
The COVID-19 health crisis forced Charles-Perrens General Hospital in Bordeaux to convert a conventional psychiatric unit into a specific unit to care for patients with mental disorders who are potentially infected with the SARS-Cov-2 virus. Resources and competences from across the hospital were mobilised to enable the unit's health professionals to accomplish this mission. This article looks back at the experience.


Can Botulinum Toxin Type A effectively treat neuropathic pain in spinal cord injury?: A protocol of systematic review and meta-analysis.
This protocol aims to assess the efficacy and safety of Botulinum Toxin Type A (BTTA) for the treatment of neuropathic pain (NPP) in patients with spinal cord injury (SCI). We will retrieve databases in Cochrane Library, EMBASE, MEDLINE, Excerpta Medica Database, PsychINFO, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the beginning to the March 1, 2020. We will consider any potential studies on assessing the efficacy and safety of BTTA for the treatment of NPP in patients with SCI without limitations of language and publication status. Cochrane risk of bias will be used to assess the risk of bias for all included trials. RevMan 5.3 software will be utilized to synthesize the extracted data and to analyze those data. This study will appraise the efficacy and safety based on the current evidence of BTTA for the treatment of NPP in patients with SCI. This study will exert high quality clinical trials for exploring the efficacy and safety of BTTA in treating NPP in patients with SCI. PROSPERO CRD42020170474.


Clinical trial: a randomized controlled cross-over study of flupenthixol + melitracen in functional dyspepsia.
Functional dyspepsia is a prevalent condition associated with diminished quality of life (QoL) and high economic burden. To study the efficacy of a combination of flupenthixol and melitracen (F + M) with anxiolytic and antidepressant properties in functional dyspepsia using a randomized controlled cross-over design. Patients met the Rome III criteria for functional dyspepsia and a validated questionnaire was used to exclude those with anxiety or depression. Moreover, patients had to have failed a trial of acid-suppressive therapy and Helicobacter pylori eradication when positive. End points included subjective global symptom relief and QoL assessed by the Nepean Dyspepsia Index (NDI). Twenty-five patients (14 females, 11 males; mean age = 34.3 +/- 9.9 years) were enrolled and 24 completed the 8-week study. There was a significant improvement in subjective global symptom relief with F + M vs. placebo (ITT: 73.9% vs. 26.1%, P = 0.001) and a significant drop in the NDI score vs. placebo (ITT: -9.0 +/- 11.9 vs. -2.4 +/- 8.9, P = 0.03). No difference was noted whether the initial treatment was F + M or placebo. No significant side effects were noted. A combination of F and M is safe and effective in the short-term treatment of functional dyspepsia. F + M is associated with significant improvement in QoL independent of the presence of anxiety or depression.


Use of cardiac troponin I (cTnI) levels to diagnose severe hypoxia and myocardial injury induced by perinatal asphyxia in neonatal dogs.
Prolonged perinatal asphyxia and subsequent severe hypoxia are the main causes of mortality in neonatal dogs in the first days of life. In medicine, specific cardiac biochemical markers, such as troponin I, are used to diagnose ischemic and nonischemic myocardial injury in asphyxiated newborns after birth. Thus, the objectives of this study were to compare the levels of cardiac troponin I (cTnI) between asphyxiated and nonasphyxiated newborn dogs and evaluate the correlations of cTnI levels with the modified Apgar score, the levels of oxygen saturation, blood glucose, and lactatemia, and blood gas parameters. This study aimed to determine the possible use of cTnI as a marker of severe hypoxia and myocardial ischemic injury in neonatal dogs. Fifteen animals in a eutocic vaginal delivery group (VG), 15 animals in a cesarean section group (CG), and 13 animals in a hypoxia (asphyxiated) group (HG) were evaluated. The animals in the asphyxiated group were from dystocic deliveries and born by vaginal delivery or cesarean section. All groups were evaluated at birth and after 60 min. The newborns in the VG and CG exhibited mixed acidosis (respiratory acidosis due to increased partial pressure of CO2 (pCO2) and metabolic acidosis due to reduced pH and bicarbonate (HCO3) levels, base excess/deficit in the extracellular fluid compartment (BEecf), and increased lactate levels) due to transient physiological hypoxemia at birth. The cTnI levels in the VG and CG were within the reference standards for healthy dogs. No correlations between cTnI level and the other parameters were observed in the VG and CG. Newborns in the HG exhibited prominent mixed acidosis (p < 0.05) due to severe hypoxemia. The Apgar score and blood gas parameters showed that these dogs were born asphyxiated, and they presented low vitality and the need for resuscitation maneuvers. The cTnI levels in the HG were significantly higher than those in the VG and CG (p < 0.05) and above the reference standards for healthy dogs, which indicated ischemic myocardial injury. The cTnI level was negatively correlated (p < 0.05) with the parameters Apgar score, heart rate, peripheral oxygen saturation (sO2) level, reflex score, and total carbon dioxide (TCO2) level and positively correlated (p < 0.01) with lactate level. This study showed that asphyxiated newborn dogs have higher serum cTnI levels than nonasphyxiated newborn dogs; thus, the cTnI can be used as a marker of severe hypoxia and ischemic myocardial damage in newborn dogs.


Tissue-specific targeting of Hsp26 has no effect on heat resistance of neural function in larval Drosophila.
Hsp26 belongs to the small heat-shock protein family and is normally expressed in all cells during heat stress. We aimed to determine if overexpression of this protein protects behavior and neural function in Drosophila melanogaster during heat stress, as has previously been shown for Hsp70. We used the UAS-GAL4 expression system to drive expression of Hsp26 in the whole animal (ubiquitously), in the motoneurons, and in the muscles of wandering third-instar larvae. There were slight increases in time to crawling failure and normalized excitatory junction potential (EJP) area for some of the transgenic lines, but these were not consistent. In addition, Hsp26 had no effect on the temperature at failure of EJPs, normalized EJP peak amplitude, and normalized EJP half-width. Overexpression larvae had a similar number of motoneuronal boutons and length of nerve terminals as controls, indicating that the occasional protective effects on locomotion were not due to changes at the synapse. We conclude that overexpression had a small thermoprotective effect on locomotion and no effect on neural function. As it has been shown that Hsp26 requires action of other Hsps to reactivate the denatured proteins to which it binds, we propose that at least in larvae, the function of Hsp26 was masked in the relative absence of other Hsps.


Spatial and temporal characteristics of visual motion perception involving V5 visual cortex.
The anatomical substrates of the perception of motion have not yet been established in a detailed way on an individual level. The aim of this study was to develop a systematic procedure for mapping the visual cortex using Transcranial Magnetic Stimulation (TMS). The results showed that such an individual and detailed map of the spatial and temporal characteristics of motion perception can be constructed using TMS.


Adriamycin treatment of advanced vulvar carcinoma.
Four consecutive patients with measurable recurrent squamous cell carcinoma of the vulva were treated with Adriamycin, in small doses approximately 45 mg/square meter of body surface area every 3 weeks. Three patients achieved objective regression of nodal metastases and residual tumor with clinical subjective benefit. Tumor control was maintained for 32, 31+, and 28+ weeks.


Get out or die trying: Peptide- and protein-based endosomal escape of RNA therapeutics.
RNA therapeutics offer great potential to transform the biomedical landscape, encompassing the treatment of hereditary conditions and the development of better vaccines. However, the delivery of RNAs into the cell is hampered, among others, by poor endosomal escape. This major hurdle is often tackled using special lipids, polymers, or protein-based delivery vectors. In this review, we will focus on the most prominent peptide- and protein-based endosomal escape strategies with focus on RNA drugs. We discuss cell penetrating peptides, which are still incorporated into novel transfection systems today to promote endosomal escape. However, direct evidence for enhanced endosomal escape by the action of such peptides is missing and their transfection efficiency, even in permissive cell culture conditions, is rather low. Endosomal escape by the help of pore forming proteins or phospholipases, on the other hand, allowed to generate more efficient transfection systems. These are, however, often hampered by considerable toxicity and immunogenicity. We conclude that the perfect enhancer of endosomal escape has yet to be devised. To increase the chances of success, any new transfection system should be tested under relevant conditions and guided by assays that allow direct quantification of endosomal escape.


Growth and payment adequacy of medicare postacute care rehabilitation.
In the early 1990s, Medicare experienced rapid growth in the number of providers furnishing postacute care (PAC). Spending grew at an even faster pace than the supply of providers. By the late 1990s, the U.S. Congress required the Centers for Medicare & Medicaid (formerly the Health Care Financing Administration) to design and implement prospective payment systems (PPSs) for the 4 PAC settings. Congress intended that the new payment systems moderate growth in spending for PAC. Instead, prospective payment generally has accelerated growth in spending and generated high profits among providers. This article presents growth trends in providers and Medicare spending. It discusses the Medicare Payment Advisory Commission's (MedPAC) assessment of payment adequacy for 2006 and 2007 for the 4 postacute sectors and problems with the PPSs that result in misaligned payments and costs. This article also reviews MedPAC's studies to compare patient-assessment instruments for 3 of the 4 settings and to compare outcomes across settings for joint-replacement patients.


A waveform independent cell identification method to study long-term variability of spike recordings.
Extracellular potential recordings are important in neuroscience; however the variability of spike waveforms has not been extensively studied to date. This study examines the variability of spike recordings within and between sessions. Place cell recordings were used in order to identify the cells across successive sessions. Place cells allow neuron spike recordings to be identified across different sessions using place fields, which are independent of the cell's spike waveform. The results show that the distribution of the residues within a session does not follow a normal distribution, a t-distribution is more suitable. The results also show that the amplitude of the spikes can vary largely between successive sessions (up to 47%), this is an important factor to be considered in long term spike recording systems.


Translation of the Gothenburg Trismus Questionnaire-2 into Telugu and its Validation for use in Indian Patients.
Trismus refers to restriction in the ability to open the mouth. Comprehensive evaluation of trismus and its treatment outcomes needs a multidimensional, self-administered, trismus specific tool. In the present scenario, Gothenburg trismus questionnaire is the only reliable instrument to quantify trismus. Translation of this questionnaire helps in providing standardized documentation of trismus related problems and to obtain a patient's perspective on treatment outcomes within various populations. The aim of this study was to translate the Gothenburg trismus questionnaire-2 (GTQ 2) into Telugu (one of the Indian Languages) and validation of the translation for its effective use in regional Telugu speaking patients. The GTQ 2 was translated according to the guidelines framed by the International Society for Pharmacoeconomics and Outcomes Research: (1) forward translation, (2) reconciliation and back translation, (3) cognitive debriefing, and (4) pilot testing. The psychometric properties of the translated version were evaluated by testing its internal consistency, construct validity, known-group validity and floor and ceiling effects. Patients who reported with or without trismus to the Head and Neck Oncology outpatient clinic were enrolled for the study. Comparison of the GTQ scores was done using Mann-Whitney U-test. The Pearson correlation coefficient was used for assessing convergent and divergent validity. Internal Consistency was calculated using Cronbach's alpha coefficient. The translated version of the GTQ 2 was administered to 60 patients (30 trismus patients and 30 non-trismus patients). GTQ 2 was successfully translated without any significant issues. Construct validity of the translated version was confirmed and it has a good internal consistency (α > 0.7). The translated instrument can differentiate between those with and without trismus (p < 0.0005). A valid and reliable Telugu version of the Gothenburg Trismus Questionnaire-2 is now available for the benefit of Indian patients. The online version contains supplementary material available at 10.1007/s13193-021-01369-7.


The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.
Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.


Letter to Editor: Observations of Deception in Urine Drug Testing.
Determining deception in urine drug testing. Some of the patients undergoing urine drug tests have not taken the prescribed drug and attempt to deceive the laboratory test by placing the parent drug in the collection cup. One of the ways to determine if this is occurring is to monitor the major metabolite of the drug. By using the metabolite/parent drug ratio this attempt at deception can be uncovered. Of the five drugs we examined, oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl, we found buprenorphine to be the most prevalent drug to this type of deception. Deception can be identified using the metabolite/parent drug ratio.


[Cytology in uropathological diagnostics].
Cytology in uropathological diagnostics is mainly performed for oncological purposes. The assessment of malignancy by urothelial cell morphology is therefore decisive; however, cytology is only sensitive enough to detect high-grade tumor cells and the different low-grade tumors cannot be reliably diagnosed. Thus, the four-tier classification system of cytological findings (i.e. negative, atypical cells but significance uncertain, suspicious and positive) refers to high-grade tumor cells only. Furthermore, for valid cytological diagnostics not only the cytological specimen but also clinical information on cystoscopy findings and, if applicable, a biopsy should be evaluated together. In difficult differential diagnostic settings, e.g. differentiation between reactive versus neoplastic atypia or difficult to access lesions in the upper urinary tract, additional fluorescence in situ hybridization of cytological preparations might be helpful. At the moment there are no indications for further immunocytology or additional biomarker tests.


Midwives' and obstetricians' perceptions of risk and its impact on clinical practice and decision-making in labour: An integrative review.
Risk and risk assessment are increasingly affecting how maternity services are governed with rates of intervention continuing to rise in obstetric-led services for low-risk women. This review synthesises original research that examines how perceptions of risk impact on midwives' and obstetricians' facilitation of care for low-risk women in labour. A five stage process for conducting integrative reviews was employed. A robust search strategy incorporated electronic searches in The Cochrane Database of Systematic Reviews, EBSCO, EMBASE and Scopus from 2009 to 2014. The initial search resulted in the retrieval of 2429 articles which were reduced to 14 through a systematic process. The results of this review revealed an over-arching theme of an assumption of abnormality in the birthing process leading to unnecessary intervention and surveillance. Three sub-themes are presented under this central theme - (1) external influences on risk perception that include practice guidelines and professional responsibility; (2) influence of personal fears and values on risk perception focusing on differing attitudes to physiological birth; (3) impact of professionals' perceptions of risk on women's decision-making in labour. Practice is influenced by an assumption of birth as abnormal and is compounded by issues such as institutional risk management, lack of midwifery responsibility, fear of involvement in adverse outcomes and personal values regarding physiological birth. These findings suggest that a shift in focus away from risk and towards health and wellbeing in the planning of maternity care may go some way towards providing a solution to the increasing intervention rates for low-risk women.


Semipermeable membranes for improving the histochemical demonstration of enzyme activities in tissue sections. V. Isocitrate: NADP+ oxidoreductase (decarboxylating) and malate: NADP+ oxidoreductase (decarboxylating).
Improved histochemical techniques for the demonstration of NADP+-specific isocitrate dehydrogenase and malate dehydrogenase in tissue sections are described. With these techniques a semipermeable membrane is interposed between the incubating solutions and the tissue sections preventing diffusion of enzymes into the medium during incubation. In the histochemical system the NADP+-dependent enzymes catalyze the electron transfer from threo-Ds-isocitrate or L-malate into NADP+. Phenazine methosulphate and menadione serve as intermediate electron acceptors between reduced coenzyme and nitro-BT. Sodium-azide and amytal are incorporated into the incubating-medium to block electron transfer to the cytochromes. For demonstrating enzyme activities in sections containing non-specific alkaline phosphatase, a phosphatase inhibitor is added into the incubation media. Problems involved in the histochemical demonstration of both enzymes are discussed.


Co-exposures of acid rain and ZnO nanoparticles accelerate decomposition of aquatic leaf litter.
The pattern of acid rain is dependent on the ratio of SO42- and NO3-, which change may affect the dissolution activity of dull heavy metals in the aquatic environment and further complicate the ongoing challenge of ecosystem stability and increase risks. In this study, we assessed the combined effects of acid rain (SO42-: NO3- was 2:1, 1:1, and 1:2) and ZnO nanoparticles (30 ng L-1) on plant litter decomposition through a microcosm experiment. The highest dissolution of ZnO nanoparticles was achieved when the SO42-: NO3- ratio was 1:2, and there were no significant differences among other treatments. The fungal biomass showed significant decreases under acute exposures but tended to be adaptive during chronic exposures. The co-exposure significantly stimulated the activities of leucine-aminopeptidase, glycine-aminopeptidase, polyphenol oxidase, and cellobiohydrolase. Besides, the fungal diversity and the relative abundance of some functional genera (e.g. Anguillospora) were enhanced when the SO42-: NO3- ratio was 1:2 and 2:1. In conclusion, the decomposition rate of plant litter was increased by 123-204% by co-exposures. Collectively, the findings underline the importance of considering environmental context to assess nanoparticle toxicity.


Pixel-level annotated dataset of computed tomography angiography images of acute pulmonary embolism.
Pulmonary embolism has a high incidence and mortality, especially if undiagnosed. The examination of choice for diagnosing the disease is computed tomography pulmonary angiography. As many factors can lead to misinterpretations and diagnostic errors, different groups are utilizing deep learning methods to help improve this process. The diagnostic accuracy of these methods tends to increase by augmenting the training dataset. Deep learning methods can potentially benefit from the use of images acquired with devices from different vendors. To the best of our knowledge, we have developed the first public dataset annotated at the pixel and image levels and the first pixel-level annotated dataset to contain examinations performed with equipment from Toshiba and GE. This dataset includes 40 examinations, half performed with each piece of equipment, representing samples from two medical services. We also included measurements related to the cardiac and circulatory consequences of pulmonary embolism. We encourage the use of this dataset to develop, evaluate and compare the performance of new AI algorithms designed to diagnose PE.


Fetal MRI versus postnatal imaging in the MR-compatible incubator.
One of the aims of fetal magnetic resonance imaging (MRI) is to avoid postnatal scanning. However, clinicians sometimes wish to have postnatal confirmation of prenatal findings. This study's purpose was to check whether there was indeed the added value of neonatal MRI performed in the MR-compatible incubator (INC) after fetal examination. Material consists of 25 neonates (14 girls) who underwent prenatal and postnatal MRI in a 1.5 T scanner, the latter in INC. Mean time of prenatal MRI was 30th gestational week, of postnatal MRI-16th day of life. In 14 cases (56 %) postnatal findings were the same as prenatal ones. In 11 (44 %) postnatal MRI showed some different/new/more precise results, in two the differences were attributed to other factors than the advantage of postnatal MRI over prenatal one. Altogether then postnatal results were partly discordant with prenatal ones in 9/25 cases (36 %). In most cases there was no added value of postnatal MRI as compared to prenatal one. This value lied in small details that could not have been noticed on prenatal MRI or required contrast medium administration to be noticed. On the other hand, MR examination performed with use of the dedicated neonatal coils in the MR-compatible incubator is a safe and reliable method of visualization of these small details with better spatial resolution thus helping to establish final diagnosis, treatment plan and prognosis.


Single-field sterile-scrub, preparation, and dwell for laparoscopic hysterectomy.
Type VII laparoscopic hysterectomy is classified as a "clean-contaminated" procedure because the surgery involves contact with both the abdominal and vaginal fields. Because the vulva has traditionally been perceived as a separate but contaminated field, operating room guidelines have evolved to require that surgeons gloved and gowned at the abdominal field either avoid contact with the urethral catheter, the uterine manipulator, and the introitus or change their gloves and even re-gown after any contact with those fields. In the belief that the perception of the vaginal field as contaminated stems from inadequate preoperative preparation instructions, we have developed a rigorous abdomino-perineo-vaginal field preparation technique to improve surgical efficiency and prevent surgical site infections. This thorough scrub, preparation, and dwell technique enables the entire abdomino-perineo-vaginal field to be safely treated as a single sterile field while maintaining a low rate of surgical site infection, and should be further investigated in randomized studies.


Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis.
To review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. A literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect. There was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted. Although significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.


The Effect of July Admission on Inpatient Morbidity, Mortality, and Discharge Disposition After Endovascular Coiling in Subarachnoid Hemorrhage.
To investigate effect of July admission on short-term outcome after endovascular coiling of patients with subarachnoid hemorrhage (SAH) owing to ruptured aneurysms. Data from the National Inpatient Sample (2012-2014) were gathered. Adult patients with SAH who underwent endovascular therapy at a teaching hospital were identified. Admissions during July were compared with other months as well as based on admission quarter (AQ): AQ1 (July to September), AQ2 (October to December), AQ3 (January to March), and AQ4 (April to June). Outcome measures included inpatient morbidity (death, iatrogenic stroke, or myocardial infarction), inpatient mortality, and nonroutine discharges. The National Inpatient Sample database yielded 8515 patients with a diagnosis of SAH who underwent endovascular coiling between 2012 and 2014. Among these, 665 (7.8%) were admitted in July, and 7850 (92.2%) were admitted in other months. Overall, there were no differences in any of the examined outcomes, including morbidity (15.0% vs. 17.3%, P = 0.513), mortality (10.5% vs. 11.8%, P = 0.665), or nonroutine discharge (57.1% vs. 59.7%, P = 0.567), for patients admitted in July versus other months. Based on AQ, 24.5% of patients were admitted in AQ1, 26.0% in AQ2, 23.8% in AQ3, and 25.7% in AQ4. Similar to July versus other month admissions, there were no significant differences in outcomes based on AQ. Based on findings of this national investigation, patients with SAH owing to ruptured aneurysms who undergo endovascular therapy during the beginning of the academic year in July may not have worse short-term outcome compared with patients with admissions during other months.


Comparison between inhibition of protein kinase C and antagonism of calmodulin by tamoxifen analogues.
A variety of analogues of tamoxifen were tested for inhibition of protein kinase C (PKC) activity in MCF-7 breast cancer cells. These results were compared with the calmodulin antagonism exhibited by the analogues as measured by inhibition of calmodulin-dependent cyclic AMP phosphodiesterase. The same structural features that enhanced PKC inhibition also led to an increase in calmodulin antagonism, namely 4-iodination and elongation of the basic side-chain. The most potent analogue has a 4-iodine substituent and eight carbon atoms in its basic side-chain with IC50 values of 38 microM for PKC inhibition and 0.3 microM for calmodulin antagonism, which compares with 92 and 6.8 microM, respectively, for tamoxifen. Some selectivity was achieved with a ring-fused analogue that retained the potency of tamoxifen as a PKC inhibitor, but lacked calmodulin antagonism.


Feedback regulation between plasma membrane tension and membrane-bending proteins organizes cell polarity during leading edge formation.
Tension applied to the plasma membrane (PM) is a global mechanical parameter involved in cell migration. However, how membrane tension regulates actin assembly is unknown. Here, we demonstrate that FBP17, a membrane-bending protein and an activator of WASP/N-WASP-dependent actin nucleation, is a PM tension sensor involved in leading edge formation. In migrating cells, FBP17 localizes to short membrane invaginations at the leading edge, while diminishing from the cell rear in response to PM tension increase. Conversely, following reduced PM tension, FBP17 dots randomly distribute throughout the cell, correlating with loss of polarized actin assembly on PM tension reduction. Actin protrusive force is required for the polarized accumulation, indicating a role for FBP17-mediated activation of WASP/N-WASP in PM tension generation. In vitro experiments show that FBP17 membrane-bending activity depends on liposomal membrane tension. Thus, FBP17 is the local activator of actin polymerization that is inhibited by PM tension in the feedback loop that regulates cell migration.


Grouping and characterization of putative glycosyltransferase genes from Panax ginseng Meyer.
Glycosyltransferases are members of the multigene family of plants that can transfer single or multiple activated sugars to a range of plant molecules, resulting in the glycosylation of plant compounds. Although the activities of many glycosyltransferases and their products have been recognized for a long time, only in recent years were some glycosyltransferase genes identified and few have been functionally characterized in detail. Korean ginseng (Panax ginseng Meyer), belonging to Araliaceae, has been well known as a popular mysterious medicinal herb in East Asia for over 2,000 years. A total of 704 glycosyltransferase unique sequences have been found from a ginseng expressed sequence tag (EST) library, and these sequences encode enzymes responsible for the secondary metabolite biosynthesis. Finally, twelve UDP glycosyltransferases (UGTs) were selected as the candidates most likely to be involved in triterpenoid synthesis. In this study, we classified the candidate P. ginseng UGTs (PgUGTs) into proper families and groups, which resulted in eight UGT families and six UGT groups. We also investigated those gene candidates encoding for glycosyltransferases by analysis of gene expression in methyl jasmonate (MeJA)-treated ginseng adventitious roots and different tissues from four-year-old ginseng using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). For organ-specific expression, most of PgUGT transcription levels were higher in leaves and roots compared with flower buds and stems. The transcription of PgUGTs in adventitious roots treated with MeJA increased as compared with the control. PgUGT1 and PgUGT2, which belong to the UGT71 family genes expressed in MeJA-treated adventitious roots, were especially sensitive, showing 33.32 and 38.88-fold expression increases upon 24h post-treatments, respectively.


A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD2-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.
Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D2 (PGD2) production and PGD2-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120 (free fatty acid receptor 4), which is expressed in intestine, could be activated by polyunsaturated fatty acids (PUFA), thereby mediating secretion of glucagon-like peptide-1 (GLP-1). Dysfunction of GPR120 results in obesity in both mice and humans. To reveal the relationship between PGD2-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function with gene and protein expression, histological, and behavioral analysis in GPR120 knockout (KO) mice. In the current study, we discovered notable neuroinflammation (increased PGD2 production and microglial activation) and neurodegeneration (declines in neurogenesis, hippocampal volume, and cognitive function) in GPR120 KO mice. We also found that Hematopoietic-prostaglandin D synthase (H-PGDS) was expressed in microglia, microglia were activated by PGD2, H-PGDS expression was upregulated in GPR120 KO hippocampus, and inhibition of PGD2 production attenuated this neuroinflammation. GPR120 KO mice exhibited reduced intestinal, plasma, and intracerebral GLP-1 contents. Peripheral administration of a GLP-1 analogue, liraglutide, reduced PGD2-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice. Our results suggest that neurological phenotypes in GPR120 KO mice are probably caused by dysfunction of intestinal GPR120. These observations raise the possibility that intestinal GLP-1 secretion, stimulated by intestinal GPR120, may remotely contributed to suppress PGD2-microglia-provoked neuroinflammation in the hippocampus.


Supra-molecular assembly of a lumican-derived peptide amphiphile enhances its collagen-stimulating activity.
C16-YEALRVANEVTLN, a peptide amphiphile (PA) incorporating a biologically active amino acid sequence found in lumican, has been examined for its influence upon collagen synthesis by human corneal fibroblasts in vitro, and the roles of supra-molecular assembly and activin receptor-like kinase ALK receptor signaling in this effect were assessed. Cell viability was monitored using the Alamar blue assay, and collagen synthesis was assessed using Sirius red. The role of ALK signaling was studied by receptor inhibition. Cultured human corneal fibroblasts synthesized significantly greater amounts of collagen in the presence of the PA over both 7-day and 21-day periods. The aggregation of the PA to form nanotapes resulted in a notable enhancement in this activity, with an approximately two-fold increase in collagen production per cell. This increase was reduced by the addition of an ALK inhibitor. The data presented reveal a stimulatory effect upon collagen synthesis by the primary cells of the corneal stroma, and demonstrate a direct influence of supra-molecular assembly of the PA upon the cellular response observed. The effects of PA upon fibroblasts were dependent upon ALK receptor function. These findings elucidate the role of self-assembled nanostructures in the biological activity of peptide amphiphiles, and support the potential use of a self-assembling lumican derived PA as a novel biomaterial, intended to promote collagen deposition for wound repair and tissue engineering purposes.


Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders.
To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.


Tooth stiffness with composite veneers: a strain gauge and finite element evaluation.
This study was conducted to determine the impact of composite veneer procedures on the functional properties of incisors. Ten extracted human maxillary central incisors were mounted in pairs in a nylon ring. One strain gauge was bonded along the long axis of each tooth on the center of the lingual surface. Each pair formed half of a Wheatstone bridge circuit and was wired to eliminate all but the voltage resulting from experimentally applied procedures. The teeth were ramp-loaded to 50 N near the incisal edge on the lingual surface. Loading was performed on the unaltered teeth, teeth with preparations and restored teeth. Two-dimensional finite element (FE) models were generated to evaluate each test condition. Relative stiffness, compared with the unaltered tooth, was calculated from measurements with the strain gauge steps and from the FE models. A relative stiffness value of unity represents recovery of stiffness to the level of the unaltered tooth. Both methods of evaluation demonstrated a decrease in mean relative stiffness with each subsequent reduction in tooth structure. The composite restoration increased its mean relative stiffness compared to its corresponding preparation but never to the level of the unaltered tooth. Across all procedures, the two-dimensional FE model correlated well in both direction and magnitude with the experimental strain gauge method (R = 0.83). A resin composite veneer does not restore the stiffness to the level of an unaltered tooth.


Extractability and phytotoxicity of heavy metals and essential elements from plastics in soil solutions and root exudates.
Plastic waste is increasing and is a serious environmental problem. Among the threats associated with plastics is the release of contaminants into the environment. This study aimed to evaluate the efficiency of metals release from plastics (low-density polyethylene (LDPE), polyethylene terephthalate (PET), and polypropylene (PP)) as affected by different soil solution types, artificial root exudates, and distilled water. The extent of metal release varied depending on the type of solution and plastic used. Metals were leached most effectively from plastics in soil solutions, followed by root exudates, and least effectively by distilled water. LDPE released the highest concentrations of Cu and Na into solution, PP released the greatest amount of Fe, and PET released the most Cr. The efficiencies of Mg and Zn release from the plastics (PP and PET) varied by solution type. Among the plastics studied, LDPE exhibited the strongest ability to adsorb metals, such as Fe, Cr, Mg, and Zn from soil solutions. The amount of metal released from the plastics was also dependent on pH, dissolved organic carbon (DOC) concentrations, and the electrical conductivity (EC) of the solutions. Moreover, plastic extracts were found to have negative effects on germination and growth in Lepidium sativum.


Prognostic value of post-treatment metabolic tumor volume from 11C-methionine PET/CT in recurrent malignant glioma.
We investigated the diagnostic and prognostic significance of metabolic parameters from 11C-methionine (MET) positron emission tomography (PET) in patients with malignant glioma. The MET-PET was examined in 42 patients who had been previously treated with adjuvant treatment for malignant glioma. Both ratios of maximal MET uptake of the tumors to those of the contralateral normal gray matter (T/N ratio) and metabolic tumor volume (MTV) were estimated in each lesion. The diagnostic performance for recurrence was investigated in all enrolled patients. A definitive diagnosis was done with pathologic confirmation or clinical follow-up. Among recurrent patients, we evaluated the prognostic value of metabolic parameters (T/N ratio and MTV) as well as clinical factors. Among 42 patients, 35 patients were revealed with recurrence. Both T/N ratios (p = 0.009) and MTV (p = 0.001) exhibited statistical significance to differentiate between recurrence and post-treatment radiation effect. A T/N ratio of 1.43 provided the best sensitivity and specificity for recurrence (91.4 and 100 %, respectively), and a MTV of 6.72 cm3 provided the best sensitivity and specificity (77.1 % and 100 %, respectively). To evaluate the prognostic impact, different cutoffs of MTV were examined in patients with recurrent tumor and a threshold of 60 cm3 was determined as a best cutoff value to separate the patients in two prognostic groups. Univariate analysis revealed improved overall survival (OS) for patients with Karnofsky performance scale (KPS) score ≥70 (p < 0.001) or MTV <60 cm3 (p = 0.049). Multivariate analysis showed that patients with KPS score ≥70 (p < 0.001; hazard ratio = 0.104; 95 % CI, 0.029-0.371) or MTV < 60 cm3 (p = 0.031; hazard ratio = 0.288; 95 % CI, 0.093-0.895) were significantly associated with a longer OS. However, T/N ratio was not correlated with patients' outcome. Metabolic parameters had the diagnostic value to differentiate recurrence from post-treatment radiation effect. Compared with T/N ratio, MTV was an independent significant prognostic factor with KPS score in patients with recurrent tumor. Our study had a potential to manage these patients according to prognostic information using MET-PET.


Low prevalence of Moraxella catarrhalis in the patients who suffered from conjunctivitis in the southwest of Iran.
Moraxella catarrhalis is a non-motile Gram-negative diplococcus bacterium that contributed to several human infections including conjunctivitis. This study aimed to reveal the prevalence of M. catarrhalis in patients who suffered from conjunctivitis in Ahvaz city, southwest of Iran. Out of 100 conjunctiva swab specimens, M. catarrhalis was isolated only from one (1%) conjunctivitis cases using the culture method. This strain was isolated from a 34 years old female patient. Also, the results of the polymerase chain reaction (PCR) were in agreement with the culture method, and the specimen that showed positive culture was also positive for specific gene of M. catarrhalis. The remaining 99 specimens did not show positive results with any of the culture and PCR methods.


Diencephalic syndrome as sign of tumor progression in a child with neurofibromatosis type 1 and optic pathway glioma: a case report.
We describe the case of a 3-year-old child, diagnosed with familial neurofibromatosis type 1 (NF1) and asymptomatic optic pathway tumor at the age of two, who developed diencephalic syndrome (DS) due to tumor progression 1 year after diagnosis. Magnetic resonance imaging disclosed an enlarging hypothalamic contrast-enhanced mass. Because of the tumor progression, in terms of tumor volume and DS, chemotherapy (CT) treatment was started according to the international protocol for progressive low-grade glioma, with rapid clinical improvement in terms of gain weight and DS resolution. Interestingly, tumor volume was unchanged after CT. This case report highlights the following facts: (1) optic pathway glioma (OPG) in young children with NF1 may have definitive growth potentials and thus, they are worth an accurate clinical follow-up; (2) also, OPG occurring in NF1 patients can be responsible for DS in case of hypothalamus involvement; (3) consequently, the child's growth pattern must be included among the clinical parameters, which must be specifically evaluated during the follow-up of children, with or without NF1, bearing an OPG; and, finally, (4) that DS can improve after CT, even in face of a stable tumor volume.


Changes in 2-aminoisobutyric acid and cycloleucine uptake produced by 2,4-dichlorophenoxyacetic acid in Chinese hamster ovary cells.
The effect of dichlorophenoxyacetic acid on the transport of two non-metabolizable amino acids, 2-aminoisobutyric acid (AIB) and cycloleucine (CL) was studied in chinese hamster ovary (CHO) cells. The herbicide did not exert any direct effect on the AIB transport. However, when the pesticide was in contact with the cells for 24 h an inhibition of the uptake was observed. Removal of the pesticide from the culture medium restored the influx of the amino acids which reached maximum values 1 h before cell division. The transport kinetics showed changes in Vmax but no variations in Km. These results may indicate that 2,4-dichlorophenoxyacetic acid produces a decrease in the carrier number but without modification of the affinity.


Repellent activities of essential oils rich in sesquiterpenoids from Saussurea amara (L.) DC. and Sigesbeckia pubescens Makino against two stored-product insects.
The essential oils (EOs) from aerial parts of Saussurea amara (L.) DC. (SAEO) and Sigesbeckia pubescens Makino (SPEO) were analyzed for their chemical composition by GC-MS, and their repellent activities against adults of the red flour beetle, Tribolium castaneum Herbst, as well as the booklouse, Liposcelis bostrychophila Badonnel, were evaluated for the first time. Results of GC-MS analysis indicated that both SAEO and SPEO were characterized by high content of sesquiterpenoids (relative content > 70%) including oxygenated sesquiterpenoids. The two oil samples and their major component caryophyllene oxide exerted beneficial repellent effects on T. castaneum and L. bostrychophila at 2 and 4 h post-exposure. At 4 h post-exposure, the PR value of caryophyllene oxide could still reach 92% (class V) against T. castaneum at minimum testing concentration of 3.15 nL/cm2, and this compound was observed to result in the greatest repellency (PR = 100%) against L. bostrychophila at 12.63 nL/cm2. This work confirmed the potent repellent efficacy of SAEO and SPEO for controlling pest damage and suggested their potential to be developed into botanical repellents.


The relationship between body mass index and poor self-rated health in the South Korean population.
This study aimed to examine the association between body mass index (BMI) and self-rated health (SRH) in Korean adults. The study included 214,997 adults who participated in the 2016 Korean Community Health Survey. Participants were categorized into four groups according to WHO Asian classification based on their BMI: underweight (<18.5 kg/m2), normal-weight (18.5-22.9 kg/m2), overweight (23.0‒24.9 kg/m2), obese (25.0‒29.9 kg/m2), and severely obese (≥30.0 kg/m2). Multivariate Poisson regression analysis with sampling weights and robust variance estimators was performed to evaluate the relationship between BMI categories and poor SRH. A J-shaped association was observed between BMI and poor SRH in both sexes. Compared to normal-weight subjects, the age, lifestyle, and comorbidities adjusted prevalence rate ratios (PRRs) in men for poor SRH were 1.73 (95% confidence interval [CI], 1.60-1.88) for underweight, 0.87 (95% CI, 0.83-0.92) for overweight, 0.98 (95% CI, 0.93-1.03) for obese, and 1.79 (95% CI, 1.63-1.97) for severely obese. In women, compared to normal-weight subjects, the age, lifestyle, and comorbidities adjusted PRRs for poor SRH were 1.33 (95% CI, 1.26-1.41) for underweight, 1.02 (95% CI, 0.98-1.06) for overweight, 1.15 (95% CI, 1.10-1.19) for obese, and 1.42 (95% CI, 1.31-1.53) for severely obese. Associations between underweight and SRH were stronger at older ages than at younger ages, whereas those between high BMI and SRH were stronger at younger ages than at older ages. This cross-sectional study using a nationally representative survey observed a J-shaped relationship between BMI and poor SRH. This association differed depending on age and presence or absence of comorbidities.


Ossifying renal tumor of infancy.
A renal ossifying tumor of infancy is a rare event with few cases having been published, and the etiology has not yet been established. We report on two new cases of this unusual neoplasm. A 2-year-old boy presented with intermittent painless gross hematuria. After several diagnostic procedures, an open pyelolithotomy was performed and the histological diagnosis of renal tumor of infancy was finally made. The history of the second case is very similar. An 8-week-old infant presented with gross hematuria. As in the first case, an open pyelolithotomy was performed and a tumor entirely covered with blood clots was found in the renal pelvis and completely removed. A histological diagnosis of renal ossifying tumor of infancy was made. Using the literature available, the histological criteria and biological behavior are discussed, together with the diagnostic and therapeutic algorithm for this tumor. In infants with gross hematuria and a calcified (non-)invasive mass in the pelvi-calceal system, renal ossifying tumor should be considered in the differential diagnosis. MRI or CT scan offers a good diagnostic guide.


Decreasing trends in total suspended solids and cumulative effects of nonpoint source projects in the Cuyahoga River Watershed, OH.
Using the US EPA's Grants Reporting and Tracking System (GRTS), we test if completion of best management practices (BMPs) through the Clean Water Act Section (§)319 National Nonpoint Source Program was associated with a decreasing trend in total suspended solids (TSS) load (metric tons/year). The study area chosen had 21 completed projects in the Cuyahoga River watershed in northeastern Ohio from 2000 to 2018. The §319 projects ranged from dam removal, floodplain/wetland restoration to stormwater projects. There was an overall decreasing trend in TSS loads. We identified three phases of project implementation and completion, where phase 1 had ongoing projects, but none completed (2000-2004). The steepest decrease in loads, identified as phase 2 (2005-2011), was associated with completion of low-head dam modification and removal projects on the mainstem of the Cuyahoga River. A likely decreasing trend was associated with projects completed in the tributaries, such as natural channel design restoration and stormwater green infrastructure (phase 3). Pairing sediment reduction estimates from projects with the river's flow normalized TSS loading trend, we estimated that the §319 effort may account for a small fraction of the TSS load reduction. Other stream restoration projects (non-§319) have also been done in the Cuyahoga watershed by other organizations. However, trying to compile these other projects is challenging in larger watersheds having multiple municipalities, agencies, and nonprofits doing restoration without better coordinated record keeping and monitoring. While a decreasing trend in a pollutant load is a desirable water quality outcome, determining what contributed to that trend remains difficult.


Friedreich's ataxia II. Biochemical studies in cultured cells.
Pyruvate and palmitate oxidations by cultured fibroblast suspensions were measured in optimized conditions and proved to be within normal range in the cells from Friedreich's patients. But when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia but are more likely to be related to membrane abnormalities in Friedreich's cells.


[In vitro bactericidal activity of tobramycin and amikacin alone or in combination against Pseudomonas aeruginosa isolated from patients with cystic fibrosis].
The bactericidal kinetic of 60 P. aeruginosa isolates (40 from cystic fibrosis sputum and 20 from various origins) was studied. Liquid medium micromethod was performed. Bacteria were incubated with tobramycin and amikacin alone at several concentrations and combined with piperacillin, cefsulodin, ceftazidim, imipenem, and ciprofloxacin at concentrations obtained in vivo. When used alone, tobramycin showed the most rapid bactericidal activity, whatever the concentration used. The bactericidal activity (greater than or equal to 99.99% killing of the inoculum) was obtained in 5 hours, with 1 or 2 x MIC of the majority of the strains, with the 2 aminoglycosides. No difference was found between tobramycin and amikacin, when combinated with an antibiotic which provides a notable increase of the rapidity of the bactericidal activity. The combination of amikacin plus imipenem was more rapidly bactericidal: 48% of strains; 26% were synergistically inhibited by amikacin plus ciprofloxacin. When correlated with the susceptibility patterns of studied micro-organisms, the results were rather unpredictive.


High-flux wavelength tunable XUV source in the 12-40.8 eV photon energy range with adjustable energy and time resolution for Tr-ARPES applications.
High-order harmonic generation (HHG) has a broad spectrum covering vacuum ultraviolet to extreme ultraviolet (XUV) bands, which is useful for applications involving material analyses at different information depths. Such an HHG light source is perfect for time- and angle-resolved photoemission spectroscopy. Here, we demonstrate a high-photon flux HHG source driven by a two-color field. Applying a fused silica compression stage to reduce the driving pulse width, we obtained a high XUV photon flux of 2 × 1012 phs/s @21.6 eV on target. We designed a classical diffraction mounted (CDM) grating monochromator that can achieve a wide range of photon energy from 12 to 40.8 eV, while the time resolution is improved by reducing the pulse front tilt after the harmonic selection. We designed a spatial filtering method to adjust the time resolution using the CDM monochromator and significantly reduced the pulse front tilt of the XUV pulses. We also demonstrate a detailed prediction of the energy resolution broadening which is caused by the space charge effect.


Discrimination of Breast Cancer with Microcalcifications on Mammography by Deep Learning.
Microcalcification is an effective indicator of early breast cancer. To improve the diagnostic accuracy of microcalcifications, this study evaluates the performance of deep learning-based models on large datasets for its discrimination. A semi-automated segmentation method was used to characterize all microcalcifications. A discrimination classifier model was constructed to assess the accuracies of microcalcifications and breast masses, either in isolation or combination, for classifying breast lesions. Performances were compared to benchmark models. Our deep learning model achieved a discriminative accuracy of 87.3% if microcalcifications were characterized alone, compared to 85.8% with a support vector machine. The accuracies were 61.3% for both methods with masses alone and improved to 89.7% and 85.8% after the combined analysis with microcalcifications. Image segmentation with our deep learning model yielded 15, 26 and 41 features for the three scenarios, respectively. Overall, deep learning based on large datasets was superior to standard methods for the discrimination of microcalcifications. Accuracy was increased by adopting a combinatorial approach to detect microcalcifications and masses simultaneously. This may have clinical value for early detection and treatment of breast cancer.


[Acute calcific prevertebral tendinitis: case report and literature review].
Prevertebral calcific tendinitis is an uncommon cause of acute neck pain characterized by the identification of calcifications at C1-C2 level and the presence of a liquid collection at the prevertebral space which causes the displacement of the prevertebral radiographic line in imaging studies. It is very important to identify this rare, benign and self-limiting pathology, in order not to confuse it with other diseases that could erroneously lead to inappropriate treatment.


Nangibotide attenuates osteoarthritis by inhibiting osteoblast apoptosis and TGF-β activity in subchondral bone.
Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA.


Designing HPMC matrices with improved resistance to dissolved sugar.
High concentrations of dissolved sugars can accelerate in vitro drug release in certain hydroxypropyl methylcellulose (HPMC) matrices (Williams et al., 2009). This study investigated the potential for common formulation variables to modulate sucrose sensitivity, and explored if more resistant formulations could be designed. In a model matrix containing 30% HPMC (Methocel™ K4M), the inclusion of sugar as a tablet diluent was a key factor. Lactose:microcrystalline cellulose mixtures, dextrose and d-xylose all produced highly swollen, erodible matrices in 0.7M sucrose (37°C), which collapsed and rapidly released remaining drug after 1-4h. This suggests internal and external sugars combine to disrupt the diffusion barrier properties of the gel layer. In contrast, matrices containing microcrystalline cellulose as the sole diluent provided extended release for 10h. Small particle size (<63μm) and high or low viscosity HPMC (Methocel™ K100M or K100LV) also improved sugar resistance. Knowledge of these variables allowed a significantly more resistant HPMC matrix to be designed which provided extended release for >16h in 0.9M sucrose. By judicious selection of excipient properties, the tolerance of HPMC matrices to high sucrose environments can be significantly improved.


Human alpha(1,3/1,4)-fucosyltransferases discriminate between different oligosaccharide acceptor substrates through a discrete peptide fragment.
Five different human alpha(1,3)-fucosyltransferase (alpha(1,3)-Fuc-T) genes have been cloned. Their corresponding enzymes catalyze the formation of various alpha(1,3)- and alpha(1,4)-fucosylated cell surface oligosaccharides, including several that mediate leukocyte-endothelial cell adhesion during inflammation. Inhibitors of such enzymes are predicted to operate as anti-inflammatory agents; in principle, the isolation or design of such agents may be facilitated by identifying peptide segment(s) within these enzymes that interact with their oligosaccharide acceptor substrates. Little is known, however, about the structural features of alpha(1,3)-Fuc-Ts that dictate acceptor substrate specificity. To begin to address this problem, we have created and functionally characterized a series of 21 recombinant alpha(1,3)-Fuc-T chimeras derived from three human alpha(1,3)-Fuc-Ts (Fuc-TIII, Fuc-TV, and Fuc-TVI) that maintain shared and distinct polypeptide domains and that exhibit common as well as idiosyncratic acceptor substrate specificities. The in vivo acceptor substrate specificities of these alpha(1,3)-Fuc-T chimeras, and of their wild type progenitors, were determined by characterizing the cell surface glycosylation phenotype determined by these enzymes, after expressing them in a mammalian cell line informative for the synthesis of four distinct alpha(1,3)- and alpha(1,4)-fucosylated cell surface oligosaccharides (Lewis x, sialyl Lewis x, Lewis a, and sialyl Lewis a). Our results indicate that as few as 11 nonidentical amino acids, found within a "hypervariable" peptide segment positioned at the NH2 terminus of the enzymes' sequence-constant COOH-terminal domains, determines whether or not these alpha(1,3)-Fuc-T can utilize type I acceptor substrates to form Lewis a and sialyl Lewis a moieties.


Extraintestinal manifestations in inflammatory bowel disease: Prevalence and predictors in Indian patients.
There is a paucity of reports on extraintestinal manifestations (EIMs) in patients with inflammatory bowel diseases (IBD) from Asia and India. From May 2011 to October 2012, consecutive IBD patients underwent a detailed history and physical examination, also by trained rheumatologist, dermatologist, and ophthalmologist, about whether they experienced any EIM at the time of inclusion or in the past. The disease phenotype/severity and location was classified according to the Montréal classification. All underwent magnetic resonance imaging (MRI) of sacroiliac joints, liver function test (LFT), transabdominal ultrasound, and dual energy X-ray absorptiometry (DEXA) scanning at neck femur (bilateral) and L4-L5 spine. One hundred twenty patients were analyzed, 62 had Crohn's disease (CD) and 58 had ulcerative colitis (UC). Thirty-eight percent had at least one while 20% suffered from multiple EIMs. Except for uveitis and episcleritis, the frequency of individual EIMs did not differ between CD and UC patients. Twenty-three percent had peripheral arthritis, 18% had ankylosing spondylitis, and 13% had ophthalmological manifestations. Mucocutaneous manifestations, aphthous stomatitis and pyoderma gangrenosum (PG), were seen in 9%. None had erythema nodosum (EN) or primary sclerosing cholangitis (PSC). Fifty percent of patients had either osteopenia or osteoporosis on DEXA. Multivariable analysis revealed female gender, Hindu religion, severe disease, and steroid usage were significantly associated with the presence of EIMs. The prevalence of EIM is similar to that reported from Europe and USA, albeit higher than that previously reported in Asian patients. Female sex, religion, severe disease, and steroid use were associated with EIM.


Stability of neural networks and solitons of field theory.
The layers of a feed-forward neural network are interpreted as a cascade of field theories. The stability of the neural network is interpreted as the topological stability of kink solutions. An explicit example is shown for a three-class problem with their field theoretical Lagrangian equations.


Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.
We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.


Strain measurement in the left ventricle during systole with deformable image registration.
The objective of this study was to validate a deformable image registration technique, termed Hyperelastic Warping, for left ventricular strain measurement during systole using cine-gated, non-tagged MR images with strains measured from tagged MRI. The technique combines deformation from high resolution, non-tagged MR image data with a detailed computational model, including estimated myocardial material properties, fiber direction, and active fiber contraction, to provide a comprehensive description of myocardial contractile function. A normal volunteer (male, age 30) with no history of cardiac pathology was imaged with a 1.5 T Siemens Avanto clinical scanner using a TrueFISP imaging sequence and a 32-channel cardiac coil. Both tagged and non-tagged cine MR images were obtained. The Hyperelastic Warping solution was evolved using a series of non-tagged images in ten intermediate phases from end-diastole to end-systole. The solution may be considered as ten separate warping problems with multiple templates and targets. At each stage, an active contraction was initially applied to a finite element model, and then image-based warping penalty forces were utilized to generate the final registration. Warping results for circumferential strain (R(2)=0.75) and radial strain (R(2)=0.78) were strongly correlated with results obtained from tagged MR images analyzed with a Harmonic Phase (HARP) algorithm. Results for fiber stretch, LV twist, and transmural strain distributions were in good agreement with experimental values in the literature. In conclusion, Hyperelastic Warping provides a unique alternative for quantifying regional LV deformation during systole without the need for tags.


Sensitivity and accuracy in recording His-Purkinje activity by surface-averaged electrocardiography.
A clinical evaluation of the surface-averaged ECG (SAE) to record His-Purkinje activity (HPA) was made on 70 patients who underwent His bundle electrograms (HBE). The recorded signals first judged as HPA in 43 patients by the noninvasive method alone were later verified in 37 patients by HBE; the accuracy of the HPA recordings (predictive value) was 86.0%. The HPA-V interval measured noninvasively had a high correlation with the HV interval by HBE (r = 0.89, p less than 0.01). The verified detection rate in all 70 patients was 52.9%: HPA was detected in 12 of 18 patients (66.7%) with sclerotic and hypertensive heart disease (Group I), five of 19 patients (26.3%) with rheumatic heart disease (Group II), 11 of 17 patients (64.7%) with congenital heart disease (Group III), and nine of 16 patients (56.2%) with miscellaneous conditions (Group IV). The detection rate was markedly lower in Group II than in other groups (Group II vs Group I or III, p less than 0.025). The PR segment was significantly longer in the patients in whom HPA was detected than in those in whom it was not detected (71.5 +/- 22.3 msec vs 43.9 +/- 19.5 msec, p less than 0.001). His-Purkinje activity (HPA) was detected in 32 of 52 recordings (61.5%) with sinus rhythm and seven of 20 recordings (35.0%) with atrial fibrillation, including two recordings in each of two cardioverted patients (p less than 0.05). We conclude that the surface-averaged ECG (SAE) has clinically acceptable sensitivity and accuracy except in patients with rheumatic heart disease, short PR segments or atrial fibrillations.


(Too) Anxious to help? Social support provider anxiety and cardiovascular function.
Provider factors, such as anxiety, may be important in understanding effects of received social support (SS), which are less consistently positive than those of perceived SS. Due to the dyadic nature of support, anxiety on the part of the provider was predicted to influence the effectiveness of received SS. This laboratory study examined effects of SS provider anxiety within unacquainted dyads on cardiovascular reactivity during acute stress. 148 participants were assigned to support roles, and each dyad was randomized to low or high provider anxiety. Results include that SS provider anxiety resulted in greater blood pressure reactivity and less recovery toward baseline diastolic blood pressure within the dyad. Overall, it appears provider anxiety contributes to less effective SS for recipients and that health costs may accompany providing and receiving support under nonoptimal conditions.


Mutagen content of wines contaminated with common yeasts.
Wines exhibiting a microbial haze were collected and their microbial contents identified. Contaminant yeast species were cultured in grape musts under controlled conditions and extracts of the resultant wines were assayed for mutagen content using four strains of Salmonella in the Ames Salmonella/microsome/faecalase system. The wine extracts exhibited some toxicity to Salmonella but no mutagen content. It would appear that mutagen content is more a function of the grape species and must preparation than of microbial metabolism during fermentation.


Fistula excision and peripheral grafts in the treatment of persistent limbal wound leaks.
Most small scleral wound leaks at the limbus are treated successfully with suturing, patching, bandage lenses, or cyanoacrylate adhesive, but occasionally a wound leak may continue and a fistula may develop. Although rare, most such fistulas are usually associated with cataract surgery or trauma. Failure of a scleral fistula to close may be due to epithelialization or chronic necrosis of the lumen. In three cases, persistent fistulas of the limbal sclera were excised with a trephine, and a peripheral graft using corneal donor tissue was used to seal the circular defect. This resulted in permanent wound closure and provided a tissue diagnosis of epithelial downgrowth (2 cases) and chronic scleral necrosis (1 case).


An alternative method for the determination of estrogens in surface water and wastewater treatment plant effluent using pre-column trimethylsilyl derivatization and gas chromatography/mass spectrometry.
A procedure using pre-column trimethylsilyl derivatization and gas chromatography/ mass spectrometry (GC/MS) was developed and applied in determining trace estrogens in complex matrix. Main conditions were optimized, including pH value, salinity of water sample, elution reagents, clean procedure, derivative solvent and temperature. The optimized method was used to determine steroid estrogens in surface water and effluents of wastewater treatment plant (WWTP). Low detection limits of 0.01, 0.03, 0.03, 0.07, 0.09 and 0.13 ng/l for DES, E1, E2, EE2, E3 and E(V), respectively were obtained under optimism condition. No apparent interferences appeared in chromatography in comparison with ultrapure water blank. Mean recovery ranged from 72.6% to 111.0% with relative standard deviation of 1.1-4.6% for spiked surface water, and from 66.6% to 121.1% with relative standard deviation of 1.5-4.7% for spiked effluent of WWTP. The results suggested that the optimized method provides a robust solution for the determination of trace steroid estrogens in complex matrix.


Microbial carbohydrate-binding toxins - From etiology to biotechnological application.
Glycan-recognizing toxins play a significant role in the etiology of many diseases afflicting humanity. The carbohydrate recognition domains of these toxins play essential roles in the virulence of many microbial organisms with multiple modes of action, from promoting pore formation to facilitating the entry of toxic enzymatic subunits into the host cell. Carbohydrate-binding domains with an affinity for specific glycan-based receptors can also be exploited for various applications, including detecting glycobiomarkers, as drug delivery systems, and new generation biopharmaceutical products and devices (e.g. glycoselective capture of tumor-derived exosomes). Therefore, understanding how to efficiently express and purify recombinant toxins and their carbohydrate-binding domains can enable opportunities for the formulation of innovative biopharmaceuticals that can improve human health. Here, we provide an overview of carbohydrate-binding toxins in the context of biotechnological innovation. We review 1) structural characteristics concerning the toxins' mode of action; 2) applications and therapeutic design with a particular emphasis on exploiting carbohydrate-binding toxins for production of anti-tumor biopharmaceuticals; discuss 3) possible ways to manufacture those molecules at a bioreactor scale using microbial expression systems, and 4) their purification using their affinity for glycans.


Disperse Orange 3 as a resonance Raman probe for measuring membrane order.
Resonance Raman spectra of azobenzene derivatives were examined in the presence of lipid membranes to find a probe that can distinguish different membrane phases. The NO2 symmetric stretching band of 4-(4-nitrophenylazo)aniline, also known as Disperse Orange 3 (DO3), is downshifted by about 4 cm(-1) on the phase transition of phosphatidylcholine membranes from the liquid crystalline to the gel phase. A comparable downshift also occurs when DO3 is bound to cholesterol-containing membranes in the liquid-ordered phase. Our results demonstrate that Raman spectrum of DO3 is a unique tool for measuring the molecular order of lipids in membranes.


From adaptive resolution to molecular dynamics of open systems.
We provide an overview of the Adaptive Resolution Simulation method (AdResS) based on discussing its basic principles and presenting its current numerical and theoretical developments. Examples of applications to systems of interest to soft matter, chemical physics, and condensed matter illustrate the method's advantages and limitations in its practical use and thus settle the challenge for further future numerical and theoretical developments.


Association between bacterial strain type and host biomarkers in Clostridium perfringens infected goats.
The study project was designed to determine the effects of Clostridium perfringens type D infection on hematological and biochemical parameters in goats. Purposive blood samples were collected from 6 healthy and 12 diseased goats positive for C. perfringens infection. Neither the animals nor their mother were vaccinated against Clostridium perfringens from whom samples were obtained. Study was carried out in two different topographic areas; hilly (district Swat) and plain (district Mardan) of Khyber Pakhtunkhwa, Pakistan but nonsignificant (P > 0.05) statistical difference was recorded between the prevalence of Clostridium perfringens infected goats. Mean erythrocytes count (RBC) and hemoglobin level decreased significantly (P < 0.05) while the white blood cells (WBC) increased significantly (P < 0.05) in diseased animals compared to the healthy animals. However non-significant differences (P > 0.05) were observed in packet cell volume (PCV) and platelets count in healthy and diseased animals. According to biochemical analysis, a significant increase (P < 0.05) in liver enzymes, total bilirubin, serum creatinine, blood urea and glucose was recorded in diseased goats. . The results demonstrated that fluctuation in most of the mean hematological values remained within the normal range however the mean liver enzymes, total bilirubin, serum creatinine, blood urea and glucose levels gone beyond the normal levels which demonstrated severe damages to liver and kidneys.


Inhibitory effect of simultaneous intraportal administration of 5-fluorouracil, uracil and degradable starch microspheres on experimental hepatic micrometastasis, is of colon cancer.
This study was designed to examine the optimal regimen of 5-fluorouracil (5-FU), uracil and degradable starch microspheres (DSM) to prevent the hepatic metastasis of colorectal cancer. BALB/C mice were used as a model of hepatic micrometastasis of mouse transplantable colorectal cancer, Colon 26. We intraportally administered to the mice 5-FU at a dose of 34.8 mg/kg body weight; uracil at the dose equal to, or 8 times higher than that of 5-FU in molar weight and DMS at a dose of 5 mg/kg body weight. We investigated the hepatic and serum concentrations of 5-FU and uracil and the inhibitory effect of various combinations of the three substances on hepatic metastasis. The study showed that concurrent use of 5-FU with uracil at a dose 8 times higher than that of 5-Fu could keep 5-FU concentration high in hepatic tissue and relatively low in serum. This tendency became more marked with the presence of DSM. These findings support the previous study results that uracil antagonizes breakdown of 5-FU in the liver and with the aid of DSM, retards excretion of 5-FU from the liver. Further investigations for clinical application of this method will lower the incidence of hepatic metastasis of colorectal cancer.