Rice Bran and Its Potential To Complement the Nutritional Needs of Children and Elderly.
Rice bran is an agro-industrial by-product of low added value that can be used to complement human nutritional needs. In this work, the profile of minerals, fatty acids and amino acids in brown rice bran was determined, aiming to evaluate its potential to complement the nutritional needs of different age groups, according to recommendations of regulatory agencies. The brown rice bran was supplied by a rice processing industry located in the south of the state of Rio Grande do Sul. Minerals were quantified using an emission spectrometer; the fatty acid profile was determined by gas chromatography and the amino acids were quantified by high-performance liquid chromatography with fluorescence (HPLC-FL). The main minerals were phosphorus (P), magnesium (Mg), potassium (K) and calcium (Ca) (2,933, 1,029, 211 and 56 mg / 100 g of rice bran). Saturated, monounsaturated and polyunsaturated fatty acids in rice bran were 22.4, 36.2 and 34.5% of lipid content, respectively. The polar, neutral and charged amino acids represented 8.8, 9.3 and 12.8% of the protein content, respectively. The composition of this co-product of rice supply chain is a good alternative to the new demand on plant-based food supplying the recommended daily intake (RDI) of national and international food polices.


Production and characterization of a Tie2 agonist monoclonal antibody.
The Tie2 receptor and its known ligands, the angiopoietins, play a critical role in endothelial cell differentiation during the process of angiogenesis. Recent experimental observations indicate that the agonistic ligand, angiopoietin-1, can stimulate endothelial cell sprouting and act as a chemo-attractant in vitro and induce increased and enhanced angiogenesis both alone and in conjunction with vascular endothelial growth factor (VEGF) in vivo. Here, we present a monoclonal antibody (MAb), which binds to the extracellular portion of the Tie2 receptor and elicits similar agonist effects. Upon MAb binding to the native Tie2 receptor of cultured human umblical vein endothelial cells (HUVEC), there is a rapid increase in receptor autophosphorylation with a concomitant enhancement in the recruitment and association of the signalling intermediates Grb2 and SH-PTP2. The antibody further demonstrates functional activity in vascular tissues. In vitro, the antibody promotes the survival of cultured HUVEC and elicits a dose dependent outgrowth and branching of microvessels from cultured explants of rat aorta. When administered in vivo, the antibody enhances the vascularization of subcutaneous Matrigel implants in mice. Together these data suggest that the antibody is capable of acting as a surrogate ligand for Tie2 and further confirms the role of Tie2 in the differentiation of endothelial cells during angiogenesis.


Peroperative drill-generated noise levels in ear surgery.
A simple technique for the measuring of sound intensities produced by drilling in ear surgery is presented. In 6 patients the sound level from drilling in the mastoid exceeded 100 dBA. The drilling device should be so designed as to avoid acoustic trauma. Furthermore, a surgical technique should be selected, which minimizes the noise levels and duration of exposure as far as is possible.


Electrocatalysis for Continuous Multi-Step Reactions in Quasi-Solid-State Electrolytes Towards High-Energy and Long-Life Aluminum-Sulfur Batteries.
Aluminum-sulfur (Al-S) batteries of ultrahigh energy-to-price ratios are a promising energy storage technology, while they suffer from a large voltage gap and short lifespan. Herein, we propose an electrocatalyst-boosting quasi-solid-state Al-S battery, which involves a sulfur-anchored cobalt/nitrogen co-doped graphene (S@CoNG) positive electrode and an ionic-liquid-impregnated metal-organic framework (IL@MOF) electrolyte. The Co-N4 sites in CoNG continuously catalyze the breaking of Al-Cl and S-S bonds and accelerate the sulfur conversion, endowing the Al-S battery with a shortened voltage gap of 0.43 V and a high discharge voltage plateau of 0.9 V. In the quasi-solid-state IL@MOF electrolytes, the shuttle effect of polysulfides has been inhibited, which stabilizes the reversible sulfur reaction, enabling the Al-S battery to deliver 820 mAh g-1 specific capacity and 78 % capacity retention after 300 cycles. This finding offers novel insights to design Al-S batteries for stable energy storage.


The Drosophila IMP-E2 gene encodes an apically secreted protein expressed during imaginal disc morphogenesis.
During metamorphosis, the steroid hormone 20-hydroxyecdysone induces morphogenesis of imaginal discs, including the formation of appendages. IMP-E2 is an ecdysone-dependent, single-copy Drosophila gene, whose transcripts accumulate rapidly in imaginal discs in response to the hormone. The IMP-E2 product is secreted at the apical surface of the disc epithelium in association with disc morphogenesis. The product is also secreted apically by the embryonic ectoderm during mid embryogenesis. The deduced primary structure of the protein reveals the presence of 16, short 3-amino acid repeat motifs (such as EIK and EVK) toward the N-terminal end of the protein, and three long, uncharged domains, containing 43 to 78 residues each, toward the C-terminal end. The predicted structure of the protein suggests that it may participate in multimolecular aggregates. Although the temporal and spatial expression of the IMP-E2 gene are consistent with a role in disc morphogenesis, its specific functions remain to be determined.


Chromatin organization in isolated nuclei: flow cytometric characterization employing forward and perpendicular light scatter.
Flow cytometric perpendicular and forward light scatters have been employed to evaluate whether the changes in chromatin organization due to ionic strength, Mg++ concentration and pH, visible in electron microscopy, can be monitored by flow cytometry. The average intensity of the perpendicular light scatter signal increased as nuclear chromatin became decondensed by lowering the ionic strength or releasing H1 histone at low pH values. These results indicate that flow cytometry signals and in particular the perpendicular light scatter allow the detection of the conformational transitions in chromatin and may therefore be useful for studying cell cycle associated morphological changes in isolated nuclei.


Mitotic chiasmata and other quadriradials in mitomycin C-treated Bloom's syndrome lymphocytes.
Mitotic chiasmata and other quadriradials (QRs) were studied by Q-banding in mitomycin C-treated and untreated lymphocytes from two sibs with Bloom's syndrome. The frequency of chiasmata was very significantly increased by the mitomycin treatment in cells from both sibs. Chiasmata occurred throughout the chromosomes, but were favored in Q-dark regions, particularly at borders between dark and light regions (Kuhn, 1976). No significant difference was found in the distribution of chiasmata among chromosome regions in treated and untreated material. This differs from the reported action of mitomycin C on cultured lymphocytes of normal persons, where chiasmata are concentrated at secondary constrictions and centromeres. Adjacent counterparts to mitotic chiasmata, and chromatid translocations between non-homologous chromosomes, also occurred in the treated material, but with a much lower frequency than mitotic chiasmata. This again differs from the effects of mitomycin C on lymphocytes of normal persons, where chiasmata account for 20% or less of total QRs.


Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women.
Leptin (LEP) and adiponectin (ADIPOQ) genes encode adipokines that are mainly secreted by adipose tissues, involved in energy balance and suspected to play a role in the pathways linking adiposity to impaired glucose and insulin homeostasis. We have thus hypothesized that LEP and ADIPOQ DNA methylation changes might be involved in obesity development and its related complications. The objective of this study was to assess whether LEP and ADIPOQ DNA methylation levels measured in subcutaneous (SAT) and visceral adipose tissues (VAT) are associated with anthropometric measures and metabolic profile in severely obese men and women. These analyses were repeated with DNA methylation profiles from blood cells obtained from the same individuals to determine whether they showed similarities. Paired SAT, VAT and blood samples were obtained from 73 severely obese patients undergoing a bioliopancreatic diversion with duodenal switch. LEP and ADIPOQ DNA methylation and mRNA levels were quantified using bisulfite-pyrosequencing and qRT-PCR respectively. Pearson's correlation coefficients were computed to determine the associations between LEP and ADIPOQ DNA methylation levels, anthropometric measures and metabolic profile. DNA methylation levels at the ADIPOQ gene locus in SAT was positively associated with BMI and waist girth whereas LEP DNA methylation levels in blood cells were negatively associated with body mass index (BMI). Fasting LDL-C levels were found to be positively correlated with DNA methylation levels at LEP-CpG11 and -CpG17 in blood and SAT and with ADIPOQ DNA methylation levels in SAT (CpGE1 and CpGE3) and VAT (CpGE1). These results confirm that LEP and ADIPOQ epigenetic profiles are associated with obesity. We also report associations between LDL-C levels and both LEP and ADIPOQ DNA methylation levels suggesting that LDL-C might regulate their epigenetic profiles in adipose tissues. Furthermore, similar correlations were observed between LDL-C and LEP blood DNA methylation levels suggesting a common regulatory pathway of DNA methylation in both adipose tissues and blood.


Kangaroo mother care and skin-to-skin care in preterm infants in the neonatal intensive care unit: A bibliometric analysis.
The desire to understand and the growing interest in research on the effects of kangaroo mother care in preterm infants in the neonatal intensive care unit have led to a significant increase in the number of manuscripts published in this field over the past decade. It is therefore necessary to regularly review the state of knowledge on this phenomenon in order to identify progress and constraints, to stimulate reflection, and to encourage progress in future research. The aim of this study was to determine the current state of scientific production in relation to kangaroo mother care in preterm infants in the neonatal intensive care unit through bibliometric analysis. This study presents a review of 212 published papers from the Scopus database (1990-2019). Two processing software applications were used: VOSviewer and SciMAT. In addition, through a keyword analysis, this study established the hot spot research trends to be developed in future work. The study adhered to the PRISMA-ScR guidelines for quality improvement studies as part of the EQUATOR network. Our results show that research in this field is going through a time of high productivity and we could sort this growing body of work into different periods, highlighting the most important topics.The analysis shows that most research in this field is focused on five motor topics. These are: prematurity, male, psychology, intensive care neonatal, and major clinical study. The analysis also allowed us to identify four basic and cross-disciplinary topics that need to be developed and that emerge as future research directions: preterm infants, child-parent relations, child development, and skin-to-skin contact. The main contribution of this work is the creation of a knowledge map on the research in this field. This article provides information on how we can shape the future to provide optimal care for these infants and their parents.


Requirement of glycolytic and mitochondrial energy supply for loading of Ca(2+) stores and InsP(3)-mediated Ca(2+) signaling in rat hippocampus astrocytes.
A major consequence of brain hypoxia and hypoglycemia, which induces the detrimental effects of stroke, is impaired ATP supply. However, it is not yet clear to which degree reduced cellular ATP production affects Ca(2+) homeostasis and Ca(2+) signaling of glia cells. Here we studied in cultured hippocampal astrocytes the influence of inhibition of cellular energy supply on Ca(2+) load of intracellular stores. Inhibition of glycolysis in the presence of substrates for mitochondrial respiration resulted in an average drop of intracellular ATP levels by 35%. Inhibition of oxidative phosphorylation reduced intracellular ATP on average by 16%. With inhibition of both glycolysis and mitochondrial ATP production, intracellular ATP level was drastically reduced (84%). In astrocytes in Ca(2+)-free buffer, cytosolic [Ca(2+)](i) was dramatically increased due to inhibition of glycolysis, even in the presence of mitochondrial substrates. However, only a minor increase of [Ca(2+)](i) was observed with inhibitors of mitochondrial ATP synthesis. Remarkably, the moderate reduction of ATP levels found with inhibitors of glycolysis caused a severe loss of Ca(2+) from cyclopiazonic acid (CPA)-sensitive Ca(2+) stores. Consequently, inhibition of glycolysis reduced P2Y receptor- or thrombin receptor-evoked Ca(2+) responses on average by 95%, whereas a reduction of only 26% was found with mitochondrial inhibitors. In conclusion, glycolysis is the most important source of ATP for the maintenance of Ca(2+) load in stores that are required for transmitter-induced signaling. These results are consistent with the concept that a local ATP source in the vicinity of endoplasmic reticulum Ca(2+) pumps is required.


9-cis retinoic acid induces the expression of the uncoupling protein-2 gene in brown adipocytes.
The expression of uncoupling protein-2 (UCP2) mRNA is up-regulated during the differentiation of brown adipocytes in primary culture. When differentiation of brown adipocytes is impaired, UCP2 mRNA expression is down-regulated. 9-cis Retinoic acid causes a dose-dependent induction of UCP2 mRNA levels in brown adipocytes, whereas all-trans retinoic acid has no effect. Specific agonists of retinoid X receptors (RXR) induce UCP2 mRNA expression, whereas specific activators of retinoic acid receptors do not. 9-cis Retinoic acid, acting through RXR receptors, is identified as a major regulator of the expression of the UCP2 gene in the brown fat cell.


[Changes in the major duodenal papilla detected during reoperations for benign diseases of the biliary tract].
Benign diseases of the major duodenal papilla were detected in 77 of 120 patients (64.1%) reoperated upon after cholecystectomy in 1968-1984. Active surgical tactics for diseases of the papilla resulted in less amount of reoperations in this disease (from 7.8% to 2.7%). Good results were obtained in 54 of 60 patients examined in the remote period after surgery.


[Photically released trains of potentials following local application of ethosuximide into the corpus geniculatum laterale].
The influence of ethosuximide injected into the lateral geniculate body (LGB) on photically evoked afterdischarges (PhAD) and recruiting responses (PhR) after 0,3/s or 7/s light flash series was compared with the effect of intraperitoneally administered ethosuximide in freely moving albino rats with chronic electrodes. Whereas i. p. application of ethosuximide reduces or abolishes photically evoked afterdischarges and recruiting, administration into the LGB does not change these potentials or the photic evoked potential. This points to an action not immediately in the LGB.


Dynamic CE-MRA for endoleak classification after endovascular aneurysm repair.
To evaluate the value of dynamic contrast enhanced magnetic resonance angiography (CE-MRA) for classification of endoleaks after endovascular aneurysm repair (EVAR). Twenty-eight patients, between 2 days and 54 months after EVAR, were evaluated with CTA, MRI and dynamic CE-MRA. The additional diagnostic value of the dynamic 3D CE-MRA was evaluated by determining the ability of the dynamic series in pinpointing the site of inflow of an endoleak. An endoleak was detected in 23 patients. Seventeen of the 23 dynamic series were technically successful (no disturbing artifacts limiting the diagnostic value). Using MRI our findings were: 2 type I, 6 type II, 1 type III, no type IV endoleaks and in 14 cases classification could not be made. The classification results for MRI plus the dynamic CE-MRA were: 2 type I, 12 type II, 1 type III, no type IV endoleaks and in eight cases classification could not be made. In six cases the dynamic MRA allowed classification of the endoleak, which was not possible with the non-dynamic images alone (p=0.091, Fisher exact). This pilot study shows that dynamic CE-MRA can have additional value in the classification of endoleaks. Dynamic CE-MRA might obviate the need for diagnostic digital subtraction angiography and aid planning for intervention.


Bu-2470, a new peptide antibiotic complex. I. Production, isolation and properties of Bu-2470 A, B1 and B2.
A strain of Bacillus circulans produced a complex of basic peptide antibiotics designated Bu-2470, which was found to contain four active components, A, B1, B2a and B2b. Bu-2470 A specifically inhibited various Pseudomonas species including P. aeruginosa, P. maltophilia and P. putida, but otherwise its antibacterial spectrum was limited to certain Gram-negative organisms. Bu-2470 B1 and B2 (B2a + B2b) showed broad antibiotic activity against Gram-positive and Gram-negative bacteria including Pseudomonas species. The physicochemical and biological properties of Bu-2470 B1 and B2 are very similar to those of the octapeptin group of antibiotics.


Gastric intramural pseudocyst: computed tomographic diagnosis.
The authors describe a case of pancreatic pseudocyst presenting as an intramural gastric mass on upper gastrointestinal examination (UGI) and computed tomography (CT) of the abdomen. The correct diagnosis of this rare entity was suggested preoperatively on the basis of the radiographic findings presented herein.


Reanalysis of N2-lung clearance index and the comparison to SF6-lung clearance index and magnetic resonance imaging.
Since the finding and correction of an error in previous spiroware software versions commonly used with the Exhalyzer D for multiple-breath washout (MBW) analysis, there has been an ongoing discussion about its impact on MBW results. In this study, we reanalyzed previously published findings with the corrected spiroware version 3.3.1. In total, 31 infants and preschool children with cystic fibrosis (CF) (mean age 2.3 ± 0.8 years) and 20 healthy controls (mean age 2.3 ± 1.1 years) underwent consecutive sulfure hexafluoride (SF6)- and nitrogen (N2)-MBW. In addition, children with CF underwent chest magnetic resonance imaging (MRI) on the same day. After reanalysis of MBW data, the corrected N2-lung clearance index (LCI) decreased by 10-15% in both groups (P = 0.001) but remained significantly higher than the SF6-LCI (P<0.01). Diagnostic agreement between the MBW results remained moderate with a persistent correlation between SF6- and N2-MBW. The corrected upper limit of normal of the N2-LCI changed classification of nine children with CF, eight of which were within the normal range after correction. The correlation between the different LCI values and the chest MRI scores remained significant with strongest correlation with the MRI perfusion score. Consequently, the corrected N2-LCI is significantly lower than the previous N2-LCI, but key results published before are not affected by the reanalysis.


Controlling gastrointestinal nematodes in cattle by Bacillus species.
In this study, we tested the in vitro and in vivo larvicidal activity of Bacillus species against gastrointestinal nematodes in cattle, and their viability in the presence of anthelmintics. For in vitro tests, cattle feces naturally infected with trichostrongylides were incubated with spore suspensions of Bacillus circulans (Bcir), B. thuringiensis var. osvaldocruzi (Bto), B. thuringiensis var. israelensis (Bti) or B. thuringiensis var. kurstaki (Btk). Subsequently, residual larvae were counted and identified. All of the Bacillus species showed 60% or more larvicidal effects. Bcir and Bti were selected to be incubated with anthelmintics (moxidectin, nitroxynil and levamisole), and after 24, 72, and 144h, their viability was evaluated. Bti showed highest drug resistance, maintaining a concentration of 1×107CFU/mL. Based on this result, Bti was selected for in vivo tests on calves naturally infected with gastrointestinal nematodes. The calves were dived into four groups: Group 1, Bti suspension of ∼1×109CFU orally administered; Group 2, Bti suspension of ∼1×109CFU orally administered with levamisole (subcutaneously, 150mg); Group 3, only levamisole (subcutaneously, 150mg), and Group 4 untreated. Then 24 and 48h after treatment, larvae numbers were counted. We observed a reduction of 84%, 100%, and 100% after 48h of treatment, respectively, for Groups 1, 2 and 3 treatments in comparison with the untreated. The tested Bacillus species showed larvicidal activity against bovine trichostrongylides, and its association with anthelmintics. It may serve as a promising integrated alternative for control of gastrointestinal nematodes in cattle.


Anti-tumor effects of Atractylenolide I on bladder cancer cells.
Atractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas. However, little is known about the effects of ATR-1on bladder cancer. In the present study, the anti-tumor activity of ATR-1 was examined on bladder cancer cells both in vivo and in vitro. MTT assay was used to assess the cytotoxic effect of ATR-1. Cell cycle distribution and apoptosis levels were evaluated using flow cytometry. Western blotting assay was applied to measure the levels of proteins associated with the apoptotic pathway, cell cycle progression and PI3K/Akt/mTOR signaling pathway. Tumor models in nude mice were induced by injection of T-24 and 253J human bladder cancer cells. ATR-1 inhibited bladder cancer cell proliferation, arrested cell cycle in G2/M phase through up-regulation of p21 and down-regulation of cyclin B1, CDK1 and Cdc25c. Meanwhile, ATR-1 also triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Mechanism investigation indicated that ATR-1 exerts its anti-tumor effect also relies on the inhibition of PI3K/Akt/mTOR signaling pathway. Finally, mice studies showed that ATR-1 blocked the T-24 or 253J-induced xenograft tumor growth without noticeable toxicity. ATR-1 may be served as a potential therapeutic agent for the treatment of bladder cancer.


Cryoballoon ablation for atrial fibrillation in patients with heart failure with mildly reduced and preserved ejection fraction.
Limited data are available on the outcomes of cryoballoon ablation (CBA)-based pulmonary vein isolation (PVI) for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The present study aimed to evaluate the safety and effectiveness of CBA in such patients. Consecutive patients with AF referred for CBA-based PVI from two highly experienced electrophysiology centres were included in this retrospective study. Of 651 patients undergoing CBA, 471 cases were divided into four groups: No HF (n = 255), HFpEF (n = 101), HFmrEF (n = 78), and HF with reduced ejection fraction (n = 37). Similar early recurrence of atrial arrhythmia was found among groups (16.2% vs. 15.4% vs. 14.9% vs. 12.2%, P = 0.798), and no significant difference of long-term sinus rhythm (SR) maintenance was identified among the HFmrEF, HFpEF, and No HF groups (71.8% vs. 75.2% vs. 79.6%, P = 0.334). CBA is safe for patients with HFmrEF and HFpEF with similar complications compared with the No HF group (3.8% vs. 4.0% vs. 3.1%, P = 0.814). The reassessment of cardiac function after CBA showed that patients with HF indicated beneficial outcomes. Left atrial diameter (LAD) and left ventricular ejection fraction were significantly improved in the HFmrEF group. There were 41.6% of patients in the HFpEF group who were completely relieved from HF. LAD and New York Heart Association (NYHA) were associated with recurrence in the HFpEF and HFmrEF groups, and the maintenance of SR was an independent predictor of NYHA improvement for all HF groups. Patients with HFmrEF and HFpEF could benefit from CBA with high SR maintenance and significant HF improvement.


Articular cartilage in the knee: mapping of the physiologic parameters at MR imaging with a local gradient coil--preliminary results.
The authors designed and constructed a local gradient coil that produces large gradients and short rise times and connects to their clinical system. In a cadaveric patellar cartilage specimen, the coil was used to acquire images of the physiologic parameters T1, T2, proton density, and apparent diffusion coefficient. Variations in these parameters were evident in regions of normal and abnormal cartilage.


Lingual nerve damage after mandibular third molar surgery: a randomized clinical trial.
The objective of this study was to clinically evaluate the frequency, type, and risk factors for lingual nerve damage after mandibular third molar surgery with reference to lingual flap retraction. A total of fifty-five patients referred for bilateral mandibular third molar removal were included in this study. Each patient was randomly allotted to have the procedure performed on 1 side (experimental group) with lingual flap retraction. On the opposite side (control group), the same procedure was performed without lingual flap retraction. Lingual nerve damage occurred in 9.1% in the experimental group in which lingual flap retraction was performed. In the control group, damage to the lingual nerve was not observed. The difference was statistically significant (P <.001) as measured by the Cochran test. Lingual nerve retraction represented a risk factor to temporary lingual nerve damage during mandibular third molar surgery.


2,4,5-Tris(pyridin-4-yl)-1H-imidazole monohydrate.
In the crystal structure of the title compound, C(18)H(13)N(5)·H(2)O, adjacent mol-ecules are linked by O-H⋯N and N-H⋯O hydrogen bonds, generating a chain propagating along [001].


Invasive micropapillary carcinomas arising 42 years after augmentation mammoplasty: a case report and literature review.
There has been no definitive consensus regarding the causal relationships between foreign bodies in the breast and carcinogenesis. This report describes the first case of invasive micropapillary carcinomas after augmentation mammoplasty. Multiple tumors located in immediate contact with the siliconomas suggested a causal link between the siliconomas and carcinomas. This report presents the case of a 64-year-old female who underwent liquid silicone injections for augmentation mammoplasty 42 years previously. Eight years before admission, siliconomas of the left breast were removed due to pain and discomfort. The patient visited the hospital for further treatment of newly diagnosed carcinoma of the left breast. Images showed multiple tumors located in various areas of the left breast. The pathological findings of the left breast showed each tumor to be solitary and not continuous with the others. The tumors were diagnosed to be invasive micropapillary carcinomas, and they all came into immediate contact with the residual siliconomas. The siliconomas were therefore suspected to have played a causative role in the development of the breast cancer. This rare case of multiple invasive micropapillary carcinomas following augmentation mammoplasty provides evidence that siliconomas may lead to carcinomas. Although a causal relationship was not established unequivocally, we review evidence that suggest silicone gel may cause cell damage responsible for carcinoma development.


Antimicrobial, spectral, magnetic and thermal studies of Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes of the Schiff base derived from oxalylhydrazide.
The Schiff base ligand, oxalyl [( 2 - hydroxybenzylidene) hydrazone] [corrected].H(2)L, and its Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes were prepared and tested as antibacterial agents. The Schiff base acts as a dibasic tetra- or hexadentate ligand with metal cations in molar ratio 1:1 or 2:1 (M:L) to yield either mono- or binuclear complexes, respectively. The ligand and its metal complexes were characterized by elemental analyses, IR, (1)H NMR, Mass, and UV-Visible spectra and the magnetic moments and electrical conductance of the complexes were also determined. For binuclear complexes, the magnetic moments are quite low compared to the calculated value for two metal ions complexes and this shows antiferromagnetic interactions between the two adjacent metal ions. The ligand and its metal complexes were tested against a Gram + ve bacteria (Staphylococcus aureus), a Gram -ve bacteria (Escherichia coli), and a fungi (Candida albicans). The tested compounds exhibited high antibacterial activities.


Catalytic efficiency, kinetic co-operativity of oligomeric enzymes and evolution.
The catalytic performance of an enzyme, whether it is monomeric or oligomeric, depends on extra costs of energy in passing from the initial ground state to the various transition states, along the reaction co-ordinate. The improvement, during evolution, of the catalytic performance of individual subunits implies that three structural requirements are met in the course of an enzyme reaction: the unstrained enzyme subunits exist in the ground states under two conformations, one corresponding to the non-liganded state and the other to the liganded state; the inter-subunit strain is relieved in the various transition states; the subunits bound to the various transition states S not equal to, X not equal to and P not equal to have the same conformation. These structural requirements are precisely those which have been used to derive structural rate equations for polymeric enzymes. When subunits are loosely coupled, their arrangement controls the various rate constants, but not the extra costs of energy required to reach the various transition states. Moreover, one cannot expect the rate curve to display any sigmoidicity under these conditions. If subunits are tightly coupled and if the strained non-liganded and half-liganded states are destabilized with respect to the corresponding unstrained states, that is if they contain more conformational energy, the oligomeric enzyme is more catalytically efficient than the ideally isolated subunits. Moreover, if the available conformational energy of the half-liganded state is more than twice that of the non-liganded state, kinetic co-operativity is positive and the rate curve is sigmoidal. It is therefore the extent of inter-subunit strain in the half-liganded state which controls the appearance of sigmoidal kinetic behaviour. If subunits are tightly coupled but if inter-subunit strain is relieved in both the non-liganded and fully-liganded states, the half-liganded state controls both the catalytic efficiency of the enzyme and the sigmoidicity of the rate curve. Sigmoidicity and high catalytic efficiency are to be observed when this half-liganded state is destabilized relative to the corresponding unstrained state.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical Guidelines to Address Low Back Pain: Using the Evidence to Guide Physical Therapist Practice.
Low back pain (LBP) is a common musculoskeletal condition, a leading cause of disability, and one of the costliest medical conditions. Due to the adverse impact of LBP and the rising costs associated with it, there is a great need to implement consistent, evidence-based practice to improve the quality of care for patients suffering from LBP. It is critical that health care practitioners take steps to reduce reliance on pharmacologic interventions, such as opioids, and promote nonpharmacologic interventions for treating and managing LBP. Synthesized and summarized new research in an update to a clinical practice guideline (CPG), published in the November 2021 issue of JOSPT, supports health care providers as they adopt and implement nonpharmacologic interventions. J Orthop Sports Phys Ther 2021;51(11):533-534. doi:10.2519/jospt.2021.0507.


Self-assembled calcium pyrophosphate nanostructures for targeted molecular delivery.
Nanostructured, inorganic microspheres have many industrial applications, including catalysis, electronics, and particularly drug delivery, with several advantages over their organic counterparts. However, many current production methods require high energy input, use of harmful chemicals, and extensive processing. Here, the self-assembly of calcium pyrophosphate into nanofibre microspheres is reported. This process takes place at ambient temperature, with no energy input, and only salt water as a by-product. The formation of these materials is examined, as is the formation of nanotubes when the system is agitated, from initial precipitate to crystallisation. A mechanism of formation is proposed, whereby the nanofibre intermediates are formed as the system moves from kinetically favoured spheres to thermodynamically stable plates, with a corresponding increase in aspect ratio. The functionality of the nanofibre microspheres as targeted enteric drug delivery vehicles is then demonstrated in vitro and in vivo, showing that the microspheres can pass through the stomach while protecting the activity of a model protein, then release their payload in intestinal conditions.


Between relativism and pluralism: Philosophical and political relativism in Feyerabend's late work.
Relativism is one of the most problematic terms associated with philosophical discourse, with Feyerabend considered among the most important twentieth century theorists subscribing to it. This paper provides a detailed overview of relativist positions advanced in Feyerabend's mid-to-late work and investigates the associated epistemic and political applications. Emphasis is placed on how Feyerabend supported certain aspects of relativism, and at what stage he rejected others. It is noted that Feyerabend had already imposed limitations on relativism in Farewell to Reason, in which he entertained the possibility of epistemic definition within stable contexts, and advanced the notion that opportunities and equality associated with political and cultural units could only be valid within a democratic system. In Conquest of Abundance, political relativism is largely discarded, while epistemological relativism is increasingly treated as an appeal for diversity in all areas. In this re-reading of his work, it becomes clear that Feyerabend was already advocating a moderate form of epistemic and political relativism in the middle of his career, which he subsequently developed in the direction of "ontological pluralism" in his later work. This paper thus shows that Feyerabend's relativism should not be completely rejected, but rather that it continues to offer interesting food for thought.


Superiority of targeted neonatal echocardiography for umbilical venous catheter tip localization: accuracy of a clinician performance model.
To compare targeted neonatal echocardiography (TnECHO) and antero-posterior (AP) chest radiographs in the localization of the umbilical venous catheter (UVC) tip and to determine the accuracy of UVC tip localization by TnECHO when performed by a trained cohort of pediatric housestaff physicians. Prospective, observational study of consecutive neonates requiring UVC insertion, in a tertiary care center, in an 18-month period. Chest radiographs reporting optimal position of the UVC tip were compared with the TnECHO results of the pediatric cardiologist. The latter was also compared with the results of TnECHO performed by the pediatric housestaff physicians. Thirty neonates with birth weight ranging between 270 and 4490 g and gestational age ranging between 24 and 44 weeks were enrolled. Nine patients (27%) required UVC tip repositioning as the cardiologist performed TnECHO revealed sub-optimal tip position despite optimal position on chest radiography. Among them, four had the UVC tip in the right atrium and five in the left atrium. Compared with the cardiologist, the housestaff physicians had reported TnECHO with a high-accuracy rate (area under the receiver operating characteristic curve=0.81). TnECHO is superior to chest radiography for identifying malpositioned catheters. TnECHO performed by pediatric housestaff physicians with basic training, demonstrated high-accuracy rates.


Transition Management in Grazing Systems: Pragmatism Before Precision.
Grazing cows undergo a similar degree of metabolic stress and immune dysregulation to those reported in high-yielding housed cows consuming total mixed rations, but the ability to manage daily nutrient intake is much less. Feed quality varies from day-to-day and weather can greatly influence amount consumed on any given day. Transition cow management, therefore, tends to revolve around pragmatism as opposed to precision. Mid- and late-gestation management of body condition score is essential to a smooth transition period.


Localization of CEA, beta-HCG, SP1, and keratin in the tissue of lung carcinomas. An immunohistochemical study.
One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA and beta-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1, CEA and SP1 could be demonstrated in 80% of the studied cases, while beta-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.


[Clinical use of the Canon R10 autorefractometer for determining refraction in children with strabismus].
Using a Canon R 10 Autofractor, refraction was measured in 131 children with squint. Measurements before and after cycloplegia were compared to a reference measurement (taken with the Rodenstock PR 50 hand-held refractometer after cycloplegia). In 80% of the cases the power and axis of the cylinder equalled the reference measurements. Due to accommodation, 40% of the values for spherical equivalents before cycloplegia were false. After cycloplegia 80% of the spherical equivalents were also in agreement with the reference measurement. The short examination time and the interesting fixation target facilitate multiple measurements in children. As a result, refraction can be measured more reliably with the R 10 Autorefractor than with the hand-held refractometer in children from age 2 1/2 or 3. Retinoscopy is only indispensable in cases where it is difficult or impossible to use an autorefractor, i.e., on children aged under 2 1/2 and those with extreme head tilt.


Testosterone and persistence in mice.
In view of previous studies showing that testosterone increases persistence of food searching in chicks, a single factorially-designed experiment was carried out to investigate whether a similar phenomenon occurs in male mice. Using a runway test, it was found that testosterone, injected into castrated mice, did increase persistence. It was also shown that intact males resembled more the testosterone-injected than control-injected castrates, and that females resembled neither intact males nor either group of castrates. A larger number of training trials was found to affect feeding latencies in a similar way to testosterone. Comparison of two strains differing in emotional reactivity (BALB/c and Porton) showed differences consistent with their reactivity levels.


Occurrence and Safety Evaluation of Antimicrobial Compounds Triclosan and Triclocarban in Water and Fishes of the Multitrophic Niche of River Torsa, India.
Personal care product (PCP) chemicals have a greater chance of accumulation in the aquatic environments because of their volume of use. PCPs are biologically active substances that can exert an adverse effect on the ecology and food safety. Information on the status of these substances in Indian open water ecosystems is scarce. In this paper, we report the incidence of two synthetic antimicrobials, triclosan (TCS), including its metabolite methyl-triclosan (Me-TCS) and triclocarban (TCC) in Torsa, a transboundary river flowing through India. In water TCS and TCC were detected at levels exceeding their respective PNEC (Predictive No Effect Concentration). Both the compounds were found to be bioaccumulative in fish. TCS concentration (91.1-589 µg/kg) in fish was higher than that of TCC (29.1-285.5 µg/kg). The accumulation of residues of the biocides varied widely among fishes of different species, ecological niche, and feeding habits. Me-TCS could be detected in fishes and not in water. The environmental hazard quotient of both TCS and TCC in water indicated a moderate risk. However, the health risk analysis revealed that fishes of the river would not pose any direct hazard to human when consumed. This is the first report of the occurrence of these PCP chemicals in a torrential river system of the eastern Himalayan region.


Associations between two novel rSNPs in 5'-flanking region of the bovine casein gene cluster and milk performance traits.
Ten evolutionary conservative sequences with high identity level to homological sequences in other mammal species were revealed in 5'-flanking region of casein's genes cluster. Five novel SNPs located inside of the evolutionary conservative regions were identified. The binding sites were revealed to be present in one allelic variant of four detected SNPs. So these SNPs were considered as rSNPs. Significant differences of allelic frequencies were revealed between beef cow's group and dairy cow's group in two rSNPs (NCE4, NCE7, p<0.001). Different alleles of those two rSNPs were shown to be associated with some milk performance traits in Black-and-White Holstein dairy cows. Significant difference of protein percentage has been found between cows with G/G and A/A genotypes (P<0.05) and A/G and A/A genotypes (P<0.05) for NCE4 polymorphism. The groups of animals with genotypes G/G and A/G for NCE7 polymorphism were significantly different in milk yield at the first lactation (kg) (P<0.01), milk fat yield (kg) (P<0.05) and milk protein yield (kg) (P<0.01). For the last trait the difference was significant also between cows with genotypes G/G and A/A for rSNP NCE7 (P<0.05).


[Study on different responses of rats' small intestine mucous membrane and bladder transitional epithelium in the same carcinogenic urine environment].
To preliminarily verify the tentative idea of replacement of bladder transitional epithelium with small intestine mucous membrane to prevent recurrence of carcinoma of bladder. A certain segment of small intestine was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder. BBN was used to 11 control rats that did not undergo operation. Bladder carcinoma failed to be found in the transplanted small intestine mucous membrane in all experimental rats except one. After stimulation of BBN, carcinoma of urinary bladder occurred in all rats' bladder transitional epithelium. 1) The carcinogenic substances in the urine of rats suffering from BBN-induced bladder carcinoma are carcinogenic only to bladder transitional epithelium and have no effect on small intestine epithelium. 2) Bladder transitional epithelium may be more sensitive to the urine carcinogenic substances and easier to be cancerized than small intestine epithelium. 3) The tentative idea of substitution of small intestine mucous membrane for bladder transitional epithelium to prevent the recurrence of bladder carcinoma is worth further studying.


Fast onset of action of sublingual immunotherapy in house dust mite-induced allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial.
To investigate how quickly an allergic rhinitis (AR) patients' symptoms will improve with sublingual immunotherapy (SLIT). Double-blind placebo study. This is a multicenter, randomized, double-blind, placebo-controlled study of SLIT used to treat house dust mite-induced AR. A total of 120 AR patients, aged 4 to 60 years, were treated for 6 months and randomized into two groups: 1) SLIT with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farina (D.f.) extract (n = 60) ; and 2) matched placebo controls (n = 60). Symptom, medications received, and a visual analog scale score were recorded during the whole study. Serum-specific IgE and IgG4 to D. p. and D. f. were assessed before and after the treatment. Eighty-five patients (70.8%) completed the study. Twelve patients (20%) chose to withdraw from the SLIT group, but none because of serious adverse effects. The total symptom and visual analog scores VAS in the SLIT group decreased significantly when compared to the placebo controls (P <0.05) after week 14, as well as for the significant (P <0.05) improvement of all individual AR symptoms in the SLIT group (e.g., sneezing, nasal discharge, itching, and nasal obstruction) after week 22. There was a significant (P <0.05) increase of IgG4 to both D.f. and D.p. in the SLIT, but not in the placebo group after treatment. SLIT with a mixture of D.f. and D.p. extract is an effective and safe treatment for patients with house dust mite-induced AR. Its onset of action can be observed as early as 14 weeks after treatment.


Imaging the spine for tumour and trauma--a national audit of practice in Irish hospitals.
The provision of appropriate spinal imaging in cases of acute injury as a consequence of trauma or tumour is becoming ever more challenging. This study assessed the use of multimodal radiological investigations in the management of spinal cord compression as a result of trauma and metastatic cancer in all major Irish hospitals. We conducted a questionnaire of thirty four hospitals in an effort to assess the provision of these services to patients with possible spinal cord compromise. In all public hospitals the Emergency Department and/or the Orthopaedic Registrars were contacted and asked a series of questions relating to spinal clearance, spinal clearance protocols, CT and MRI scanning facilities and on site orthopaedic services. All centres participated in the study. 67.64% of centres routinely used a protocol in spinal clearance. In 87% of hospitals the Emergency department were responsible for clearing the spine. 85.3% of hospitals had CT availability during normal working hours (9-5) dropping to 47% availability after hours. MRI was available in 50% of hospitals, with surprisingly just two centres providing out of hours MRI imaging services. The provision of radiological services in the management of suspected spinal injuries in Irish hospitals is inadequate in comparison to international best practice. This is most marked in relation to CT and MRI.


Newly Developed Pediatric Membrane Oxygenator that Suppresses Excessive Pressure Drop in Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation (ECMO).
This article developes a pediatric membrane oxygenator that is compact, high performance, and highly safe. This novel experimental approach, which imaging the inside of a membrane oxygenator during fluid perfusion using high-power X-ray CT, identifies air and blood retention in the local part of a membrane oxygenator. The cause of excessive pressure drop in a membrane oxygenator, which has been the most serious dysfunction in cardiovascular surgery and extracorporeal membrane oxygenation (ECMO), is the local retention of blood and air inside the oxygenator. Our designed blood flow channel for a membrane oxygenator has a circular channel and minimizes the boundary between laminated parts. The pressure drop in the blood flow channel is reduced, and the maximum gas transfer rates are increased by using this pediatric membrane oxygenator, as compared with the conventional oxygenator. Furthermore, it would be possible to reduce the incidents, which have occurred clinically, due to excessive pressure drop in the blood flow channel of the membrane oxygenator. The membrane oxygenator is said to be the "last stronghold" for patients with COVID-19 receiving ECMO treatment. Accordingly, the specification of our prototype is promising for low weight and pediatric patients.


Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes.
The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.


Randomized clinical trial comparing cold knife conization of the cervix with and without lateral hemostatic sutures.
Compare blood loss during cold knife conization of the cervix with and without lateral hemostatic sutures in the cervical branches of the uterine arteries. Randomized clinical trial. Hospital de Clínicas de Porto Alegre (HCPA). 102 patients that underwent cold knife conization. Women that underwent cold knife conization of the cervix were randomized to undergo the procedure with or without lateral hemostatic sutures. blood loss measured in grams. operative time and postoperative intervention. Only the participants were blinded to group assignment. From March 2009 to August 2012, patients were randomly assigned to one of the study groups. There were no differences in amount of blood loss between patients that underwent the procedure with and without sutures (p = 0.39). Operative time was shorter in the group without suture (p = 0.020). There were no differences in intervention due to bleeding (p = 0.20). Blood loss was greater among menstruating women than for menopausal women (p = 0.011). There were no differences in amount of blood lost between smoking and nonsmoking patients (p = 0.082). Lateral hemostatic sutures do not affect the amount of intraoperative bleeding or the number of postoperative interventions. Their use is not necessary because they result in longer operative time, have a higher cost due to the use of suture material and pose the risk of ureter lesion in case the sutures are not placed at a lower position in the cervix. ClinicalTrials. gov identifier: NCT02184975.


Spontaneous tumor rejection is not always due to a complete cellular rejection.
In this paper we have studied whether there is a correlation between efficacy of hosts to reject tumor cells spontaneously and the induction of cytotoxic macrophages in these recipients due to injection (immunization) with tumor cells. Results show that there is no cause-effect relationship between macrophage cytotoxicity and tumor rejection in vivo. This lack of cause-effect relationship is greatly influenced by differences in immunogenicity between the various tumor cell lines as well as by the release of tumor-factors by some of these tumors.


Molecular weight and hydrodynamic properties of apolipoprotein B in guanidine hydrochloride and sodium dodecyl sulfate solutions.
The apolipoprotein B polypeptide of human serum low density lipoprotein exists (after reduction of disulfide bonds) as a random coil with a molecular weight of 250,000 in concentrated solutions of guanidine hydrochloride. With intact disulfide bonds, there is a limited restraint on the polypeptide conformation in this denaturing solvent. In the presence of saturating amounts of bound sodium dodecyl sulfate, the apolipoprotein is dimeric and highly asymmetric. This work substantiates the monomeric molecular weight of 250,000 for apolipoprotein B reported by others (Smith, R., Dawson, J.R., and Tanford, C. (1972) J. Biol. Chem. 247, 3376-3381) and demonstrates that the dimeric state of the polypeptide extant in vivo is maintained in micellar detergent solution.


Parameters of Heart Rate Variability in Male Wistar Rats under Conditions of Different Motor Activity.
We studied heart rate variability indexes in freely moving male Wistar rats at rest and under conditions of increased motor activity (treadmill exercise). Some regularities were revealed in the dynamics of HR, RRNN, Mo, indicator of the adequacy of regulation processes, VLF (msec2, %), HF, LF (%), LF/HF, and IC that characterize changes in the neurohumoral regulation and shifts in the level of cardiac rhythm control at the different stages of the experiment. It was found that changes in motor activity of male Wistar rats were accompanied by the transition of the functional state of the organism to a new level of regulation, which was confirmed by the dynamics of HR, RRNN, Mo, LF, VLF, LF/HF, and IC. These findings can be used as prognostic indicators for assessment of regulatory mechanisms in the body.


A multifunctional CeO2@SiO2-PEG nanoparticle carrier for delivery of food derived proanthocyanidin and curcumin as effective antioxidant, neuroprotective and anticancer agent.
The nanoparticle systems could effectively overcome the drug delivery challenges of food bioactive compounds. In this study, a novel and effective multifunctional PEG modified CeO2@SiO2 nanoparticle (CSP-NPs) system was successfully fabricated. Food derived proanthocyanidin (PAC) and curcumin (Cur) were loaded onto CSP-NPs and formed as PAC-NPs and Cur-NPs. Fourier transform Infrared spectra, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and dynamic light scattering were used to characterize the prepared NPs. CSP-NPs, PAC-NPs and Cur-NPs displayed spherical shape with about 35-45 nm size. The bioactivity analysis revealed that CSP-NPs system could effectively deliver PAC and Cur to exhibit strong antioxidant activity, potent neuroprotective effect against Aβ1-42-mediated toxicity in PC-12 cells (recovered cell viability from 57.5% to 81.0% at the dose of 25 μg/mL) and effective antiproliferative effects on HepG2 and Hela cells. Besides, all prepared nanoparticles (0-100 µg/ml) used in this study showed no significant toxicity on cell models of antioxidative and neuroprotective activities, excepting for cancer cells, suggesting that these nanoparticles had the potential of being utilized in drug delivery. Therefore, CSP-NPs might be a promising delivery system for hydrophilic molecule proanthocyanidin and hydrophobic molecule curcumin against the oxidative damage, neurodegenerative diseases and cancer, which could facilitate the application of food derived nutrients in functional foods industry.


Safety and efficacy of concomitant ablation for atrial fibrillation in rheumatic mitral valve surgery: A meta-analysis.
This review aimed to evaluate the safety and efficacy of concomitant surgical ablation (SA) for patients with atrial fibrillation (AF) undergoing rheumatic mitral valve (MV) surgery. A systematic search of relevant studies focusing on SA for patients with AF undergoing rheumatic MV surgery was performed. The primary outcomes included mortality, efficacy, and complications. Four randomized controlled trials (RCTs) and four observational studies covering 1931 patients met the inclusion criteria. In RCTs, no significant differences in reoperation for bleeding, low cardiac output syndrome, thromboembolic events, and early (risk ratio [RR], 2.07; 95% confidence intervals [CI], 0.37-11.40; p = .41) and midterm all-cause death (RR, 1.07; 95% CI, 0.40-2.88; p = .89) were noted between the SA group and the nonablation group. These results were similar to those obtained from observational studies. However, ablation was associated with a higher incidence of permanent pacemaker implantation (RR, 2.44; 95% CI, 1.15-5.18; p = .02) in observational studies but not in RCTs (RR, 2.03; 95% CI, 0.19-21.26; p = .56). Furthermore, additional SA was significantly more effective in sinus rhythm (SR) restoration than MV surgery alone at discharge and at the 12-month and 3-year follow-ups. Concomitant SA during rheumatic MV surgery does not increase perioperative adverse events. In addition, SA promotes considerable restoration of SR. Although some evidence exists that permanent pacemaker implantation is more common after ablation, not all studies support this notion.


Progressive cone-rod dystrophy and high myopia in a Finnish family.
Progressive cone-rod dystrophy was diagnosed in a 35-year-old man (the proband). In the family study, 29 of the relatives were examined. The brother of the proband was also found to have cone-rod dystrophy. In the family of the mother of the proband, there were four men who had high myopia possibly connected with cone-rod dystrophy. The other relatives had no signs of cone-rod dystrophy or high myopia. The relatives not examined were reported healthy with no eye trouble. The disorder could be autosomal recessive hereditary if only the confirmed cone-rod dystrophy of the proband and his brother is taken in consideration. However, no relationships between the families of the mother and father of the proband could be found going back to the year 1830. Therefore, the autosomal recessive inheritance was not established. The most probable mode of inheritance would be X-chromosomal recessive if high myopia and cone-rod dystrophy are thought to be parts of the same syndrome.


Anterior shoulder instability.
Current concepts for the diagnosis and treatment of anterior dislocation and subluxation, including classification of injuries, are presented. The pathophysiology, clinical and radiologic examination, and treatment protocols are discussed.


Strychnine decreases the voltage-dependent Ca2+ current of both Aplysia and frog ganglion neurons.
1. The effects of strychnine on the voltage-dependent Ca2+ current (ICa) were studied in physically isolated Aplysia neurons and enzymatically dissociated frog sensory neurons of the dorsal root ganglion. Neurons were studied under the internal perfusion and the voltage clamp condition. 2. Strychnine decreased the ICa with threshold concentrations for effect at 1 to 10 microM. The depression of ICa increased with strychnine dose without effects on the current-voltage relation of ICa. The effects of low concentrations of strychnine were reversible, but recovery was incomplete at higher concentrations. The potency of strychnine was about 10 times less than that of diltiazem, an organic Ca2+ antagonist. At 100 microM the ICa of Aplysia neurons was reduced to about half of the control. This concentration of strychnine also reduced the peak amplitude of ICa of frog sensory neurons. 3. These results indicate that, in addition to its actions on transmitter responses and on Na+ and K+ currents, strychnine has effects on ICa that have not previously been appreciated.


[Value of radiological examination in patients with pheochromocytoma. Results in four cases (author's transl)].
The authors report 4 cases of pheochromocytoma and analyse the interest of the different x ray examinations. The authors show the interest of angiography, particularly selective angiography, for small tumors, ectopic and multiple abdominal localisations, and metastases. The benign or malignant nature of the tumor, in the absence of metastases, is difficult to assess by x ray examinations alone.


Depolarization of brain cortex slices and synaptosomes by lithium. Determination of K+-equilibrium potential in cortex slices.
K+-equilibrium potential was determined in brain cortex slices of rat by measuring 86Rb+ distribution between the extra- and intracellular space. The ratio of internal to external Rb+ concentration was 39 +/- 1.8, corresponding to a resting membrane potential of 93.8 mV. Li+ (1-126 mM) decreased the membrane potential in both cortex slices and synaptosomes in a concentration-dependent manner. The presence of 1 mM Li+ was enough to cause a slight but distinct depolarization. During incubation in Li+-containing medium slices took up K+; however, for depolarization the presence of extracellular Li+ seemed to be necessary.


Albumin-globulin ratio: a novel predictor of sepsis after flexible ureteroscopy in patients with solitary proximal ureteral stones.
To identify predictors of sepsis after flexible ureteroscopy (fURS) in patients with unilateral, solitary, proximal ureteral stones and evaluate the association between albumin-globulin ratio (AGR) and sepsis. Overall, 759 patients who underwent fURS were retrospectively enrolled. Univariate and multivariate logistic regression analyses were performed to identify predictors of sepsis after fURS in patients with solitary proximal ureteral stones. Then A nomogram was generated using the predictors. Sepsis occurred in 43 patients (5.7%), and 6 (0.8%) of them developed septic shock. Univariate analysis showed that age, female sex, albumin concentration, globulin concentration, AGR, pre-operative fever, white blood cell (WBC) count, urine culture (UC) result, urine WBC count, and urine nitrite result were predictors of sepsis. Multivariate analysis identified AGR <1.2 [odds ratio (OR) =2.810, 95% confidence interval (CI): 1.245-6.342, P=0.013] and positive UC (OR =10.520, 95% CI: 4.489-24.653, P<0.001) as independent predictors. When AGR <1.2 and positive UC were combined, area under the receiver operator characteristic curve was 0.825. Then patients were categorized by different AGR level ("≥1.4", "1.2-1.4", "1.0-1.2", "<1.0"), and corresponding sepsis rates were 27.7%, 9.8%, 4.5% and 2.5%. Positive UC and low AGR were independent predictors of post-fURS sepsis. Cautious pre-operative evaluation and optimized treatment strategy should be considered to minimize infectious complications.


Identification of DUSP7 as an RNA Marker for Prognostic Stratification in Acute Myeloid Leukemia: Evidence from Large Population Cohorts.
The problem of prognostic stratification in acute myeloid leukemia (AML) patients still has limitations. The expression profile data and clinical features of AML patients were obtained from multiple publicly available sources, including GSE71014, TCGA-LAML, and TARGET-AML. Single-cell analysis was performed using the TISCH project. All the analysis was conducted in the R software. In our study, three public AML cohorts, GSE71014, TARGET-AML, and TCGA-AML, were selected. Then, we identified the prognosis-related molecules through bioinformatic analysis. Finally, the DUSP7 was noticed as a risk factor for AML patients, which has not been reported previously. Biological enrichment analysis and immune-related analysis were performed to illustrate the role of DUSP7 in AML. Single-cell analysis indicated that the DUSP7 was widely distributed in various cells, especially in monocyte/macrophages and malignant. Following this, a prognosis model based on DUSP7-derived genes was constructed, which showed a good prognosis prediction ability in all cohorts. Our results preliminarily reveal the role and potential mechanism of DUSP7 in AML, providing direction for future research.


How tropical cyclone flooding caused erosion and dispersal of mercury-contaminated sediment in an urban estuary: The impact of Hurricane Harvey on Buffalo Bayou and the San Jacinto Estuary, Galveston Bay, USA.
Hurricane Harvey (Harvey), a slow-moving storm, struck the Texas coast as a category 4 hurricane. Over the course of 53 days, the floodwaters of Harvey delivered 14 × 109 m3 of freshwater to Galveston Bay. This resulted in record flooding of Houston bayous and waterways, all of which drained into the San Jacinto Estuary (SJE,) with its main tributaries being Buffalo Bayou and the San Jacinto River. The lower SJE and lower Buffalo Bayou has experienced up to 3 m of land subsidence in the past 100 years and, as a result, prior to Hurricane Harvey, up to 2 m of sediment within the upper seabed contained an archive of high concentrations of Total Hg (HgT) and other particle-bound and porewater contaminants. Within the SJE, Harvey eroded at least 48 cm of the sediment column, resulting in the transport of an estimated 16.4 × 106 tons of sediment and at least 2 tons of Hg into Galveston Bay. This eroded sediment was replaced by a Harvey storm deposit of 7.73 × 106 tons of sediment and 0.96 tons within the SJE, mostly sourced from Buffalo Bayou. Considering that the frequency of slow-moving tropical cyclones capable of delivering devastating rainfall may be increasing, then one can expect that delivery of Hg and other contaminants from the archived sediment within urbanized estuaries will increase and that what happened during Harvey is a harbinger of what is to come.


Electron microscope visualization of RNA transcription and processing in Saccharomyces cerevisiae by Miller chromatin spreading.
The Miller chromatin spreading technique for electron microscopic visualization of gently dispersed interphase chromatin has proven extremely valuable for analysis of genetic activities in vivo. It provides a unique view of transcription and RNA processing at the level of individual active genes. The budding yeast Saccharomyces cerevisiae has also been an invaluable model system for geneticists and molecular biologists. In this chapter, we describe methods for applying the Miller chromatin-spreading method to Saccharomyces cerevisiae. This allows one to use electron microscopic visualization of a gene of interest to study effects of specific mutations on gene activity. We are applying the method to study transcription and processing of ribosomal RNA.


Tandem mass spectrometry identifies proteins phosphorylated by cyclic AMP-dependent protein kinase when sea urchin sperm undergo the acrosome reaction.
The exocytotic acrosome reaction (AR), which is required for fertilization, occurs when sea urchin sperm contact the egg jelly (EJ) layer. Among other physiological changes, increases in adenylyl cyclase activity, cAMP and cAMP-dependent protein kinase (PKA) activity occur coincident with the AR. By using inhibitors of PKA, a permeable analog of cAMP and the phosphodiesterase inhibitor IBMX, we show that PKA activity is required for AR induction by EJ. A minimum of six sperm proteins are phosphorylated by PKA upon exposure to EJ, as detected by a PKA substrate-specific antibody. The phosphorylation of these proteins and the percentage of acrosome reacted sperm can be regulated by PKA modulators. The fucose sulfate polymer (FSP), a major component of EJ, is the molecule that triggers sperm PKA activation. Extracellular Ca(2+) is required for PKA activation. Six sperm proteins phosphorylated by PKA were identified by tandem mass spectrometry (MS/MS) utilizing the emerging sea urchin genome. Based on their identities and localizations in sperm head and flagellum, the putative functions of these proteins in sperm physiology and AR induction are discussed.


The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine.
Clinically, cancer drug therapy is still dominated by chemotherapy drugs. Although the emergence of targeted drugs has greatly improved the survival rate of patients with advanced cancer, drug resistance has always been a difficult problem in clinical cancer treatment. At the current level of medicine, most drugs cannot escape the fate of drug resistance. With the emergence and development of gene detection, liquid biopsy ctDNA technology, and single-cell sequencing technology, the molecular mechanism of tumor drug resistance has gradually emerged. Drugs can also be updated in response to drug resistance mechanisms and bring higher survival benefits. The use of new drugs often leads to new mechanisms of resistance. In this review, the multi-molecular mechanisms of drug resistance are introduced, and the overcoming of drug resistance is discussed from the perspective of the tumor microenvironment.


Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy.
Subcutaneous implantable cardioverter-defibrillator (S-ICD) is a promising option for patients with hypertrophic cardiomyopathy (HCM). Patients with HCM can present markedly abnormal electrocardiograms (ECGs), and there are no data on what percentage of patients with HCM fail the prerequisite S-ICD vector screening. The purpose of this study was to determine the failure rate of the prerequisite vector screening using 1 or 2 acceptable vectors stratified for risk profile for sudden cardiac death and predictors of failure. ECG recordings from consecutive patients with HCM simulating the S-ICD sensing vectors were analyzed with the S-ICD screening tool. Eligibility was defined by 1 or 2 appropriate vectors. Medical history, ultrasound characteristics, and 12-lead ECG characteristics were analyzed and the individual arrhythmic risk at 5 year was determined to study potential predictors of failure. One hundred sixty-five (118 men; mean age 51 ± 16 years) patients were analyzed. Twenty-two patients (13%) had a high risk of sudden cardiac death, 33 (20%) had intermediate to high risk, and 110 (67%) had low risk. Twenty-six patients (16%) had no suitable vector, including 8 of 22 high-risk patients (36%). The primary cause of failure was high T-wave voltages in 25% of the vectors analyzed. T-wave inversions in >2 leads on the surface 12-lead ECG (odds ratio 15.6; 95% confidence interval 4.9-50.3; P < .001) and prior myectomy (odds ratio 8.4; 95% confidence interval 2.1-33.1; P = .002) were significantly associated with screening failure in a multivariable model. Currently available preimplant screening algorithms recommended by the manufacturer are associated with a significant failure rate in patients with HCM, particularly in the high-risk subgroup.


A short-term comparison of the effects of clomiphene citrate and conjugated equine estrogen in menopausal/castrate women.
An attempt was made to assess the potential role for an antiestrogen in the hormone replacement therapy of menopausal women who have a contraindication to estrogen use. Two groups of menopausal or castrate women were given either conjugated equine estrogen or clomiphene citrate in a cyclic manner for 25 days each month for 3 months. The effects were measured after 3 months and compared with baseline values. Clomiphene lowered FSH slightly, but had no effect on subjective vasomotor symptoms. With respect to bone metabolism, it produced no change in plasma parathyroid hormone level, whereas estrogen lowered it; both compound lowered serum calcium but clomiphene had less effect. The hydroxyproline/creatinine ratio was decreased more by clomiphene than by the estrogen. These findings are consistent with a beneficial effect on bone. Clomiphene had no adverse effects on clotting parameters and showed effects similar to those of conjugated equine estrogens on certain measures of lipid metabolism.


Complications of abdominal stoma surgery.
This study was undertaken to review and summarize the complications of ileostomy and colostomy creation and subsequent closure. The English-language medical literature for at least the past 15 years was reviewed comprehensively. Complications of surgery for the creation of end, loop, and "end loop" stomas are presented. Technical factors, which might influence complication rates, are discussed. Optimal management of ostomy complications is presented, especially for peristomal hernias. Similarly, techniques and complications for stoma closure are analyzed. Stoma creation is not a trivial undertaking; careful surgical technique minimizes complications (which are relatively frequent), and promotes good ostomy function. Peristomal hernias are difficult to cure permanently. The morbidity of ileostomy and colostomy closure is also appreciable.


Cost-effectiveness of probiotics for necrotizing enterocolitis prevention in very low birth weight infants.
To examine the cost-effectiveness of prophylactic probiotics on necrotizing enterocolitis (NEC) prevention in very low birth weight (VLBW) infants. We built a decision-analytic model using TreeAge. Effectiveness was assessed using quality-adjusted life-years (QALY). Primary outcome was an incremental cost-effectiveness ratio (ICER) expressed as cost per QALY gained. Costs were expressed in 2017 US dollars. Deterministic and probabilistic sensitivity analyses (SA) were performed. For the base case analysis, the ICER of probiotics versus no probiotics for the prevention of NEC in VLBW infants was $1868/QALY. SA revealed that probiotics became cost-saving at a NEC rate of 6.5% and higher or with incremental NEC cost of $37,500 or higher. Our model demonstrated that prophylactic probiotics were a cost-effective strategy in NEC reduction. SA confirmed that the model is customizable to various clinical settings and thus, can aid in understanding the economic impact of this intervention.


Fluid Management in Pediatric Urology: A Review of the Literature and Call for a Change in Practice.
We investigate the intravenous fluid ordering practices of pediatric urologists. We also provide evidence for the use of isotonic fluids and, thus, establish a new standard for the field. An online questionnaire was distributed via the listserve of the American Academy of Pediatrics Section on Urology. For 3 patient scenarios the respondents were asked to select which intravenous fluid they would prescribe and which infusion rate they would choose. Fluid choices were listed as lactated Ringer solution, normal saline, 0.45% normal saline, 5% dextrose in lactated Ringer solution, 5% dextrose in 0.45% normal saline, none and other (with write-in option). Infusion rate choices were listed as maintenance (defined according to the Holliday-Segar 4-2-1 nomogram), ½x maintenance, 1.5x maintenance, 2x maintenance and other (with write-in option). A final question probed physician reason(s) for selections. The survey had a 35% response rate. The majority of respondents use 5% dextrose in 0.45% normal saline, and the most common infusion rate is 1.5x maintenance. Additionally, choices for fluid use and infusion rate were based on a combination of physician training and personal experience. Only 13% of respondents stated that they routinely avoid isotonic fluids. A PubMed® literature search demonstrated that the general pediatric and surgical specialty literature discourages hypotonic fluids and favors the judicious use of isotonic hydration and dextrose. A change in pediatric urology needs to occur such that isotonic fluids at maintenance rate become the standard, with the addition of dextrose and/or increasing of rate only for carefully selected patients.


The Effect of Omeprazole on Serum Concentrations of Theophylline, Pepsinogens A and C, and Gastrin in Elderly Duodenal Ulcer Patients.
With the aim of verifying the effect of omeprazole treatment on theophyline serum concentration in elderly peptic ulcer patients, we studied 10 male subjects aged >65 years (mean age = 75.2, range = 67--86) with chronic obstructive bronchopneumonia and endoscopically diagnosed duodenal ulcer in acute phase. All subjects were treated with a slow-release formulation of theophylline 200 mg b.i.d. plus omeprazole 20 mg daily for 4 weeks. In all subjects serum concentrations of azote, creatinine, theophylline were determined at the beginning and after 1 and 4 weeks; at the beginning and end of the study, pepsinogen group A (PGA), pepsinogen group C(PGC) and gastrin were measured. Statistical analysis was performed with the Student's t-test for paired data. The results showed no statistically significant differences after 1 and 4 weeks of omeprazole treatment in serum concentrations of theophylline (T(0) = 7.4, T(1 week) = 7.5, T(4 weeks) = 6.0, p = ns), azote (T(0) = 45.2, T(1 week) = 30.5, T(4 weeks) = 36.1, p = ns), creatinine (T(0) = 1.27, T(1 week) = 1.02, T(4 weeks) = 1.16, p = ns), PGA (T(0) = 99.5, T(4 weeks) = 126.2, p = ns), and PGC (T(0) = 10.6, T(4 weeks) = 12.1, p = ns); however serum gastrin increased from T(0) = 70.2 plus minus 13.2 to T(4 weeks) = 130.3 plus minus 18.3 (p < 0.0001). It was concluded that (1) serum concentration of theophylline is not affected by the concomitant omeprazole treatment lasting 1 month in elderly patients suffering from chronic obstructive bronchopneumonia and peptic ulcer, (2) modifications of dosages of theophylline and/or omeprazole are not necessary in the elderly with normal renal function, (3) the increase in fasting serum gastrin after 4 weeks of treatment may indicate that omeprazole 20 mg daily is efficacious in inhibiting gastric acid secretion in the elderly people.


Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from Citrus microcarpa.
Two novel type III polyketide synthases, quinolone synthase (QNS) and acridone synthase (ACS), were cloned from Citrus microcarpa (Rutaceae). The deduced amino acid sequence of C. microcarpa QNS is unique, and it shared only 56-60% identities with C. microcarpa ACS, Medicago sativa chalcone synthase (CHS), and the previously reported Aegle marmelos QNS. In contrast to the quinolone- and acridone-producing A. marmelos QNS, C. microcarpa QNS produces 4-hydroxy-N-methylquinolone as the "single product" by the one-step condensation of N-methylanthraniloyl-CoA and malonyl-CoA. However, C. microcarpa ACS shows broad substrate specificities and produces not only acridone and quinolone but also chalcone, benzophenone, and phloroglucinol from 4-coumaroyl-CoA, benzoyl-CoA, and hexanoyl-CoA, respectively. Furthermore, the x-ray crystal structures of C. microcarpa QNS and ACS, solved at 2.47- and 2.35-Å resolutions, respectively, revealed wide active site entrances in both enzymes. The wide active site entrances thus provide sufficient space to facilitate the binding of the bulky N-methylanthraniloyl-CoA within the catalytic centers. However, the active site cavity volume of C. microcarpa ACS (760 Å(3)) is almost as large as that of M. sativa CHS (750 Å(3)), and ACS produces acridone by employing an active site cavity and catalytic machinery similar to those of CHS. In contrast, the cavity of C. microcarpa QNS (290 Å(3)) is significantly smaller, which makes this enzyme produce the diketide quinolone. These results as well as mutagenesis analyses provided the first structural bases for the anthranilate-derived production of the quinolone and acridone alkaloid by type III polyketide synthases.


Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung.
Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent.


Quantum limit to nonequilibrium heat-engine performance imposed by strong system-reservoir coupling.
We show that finite system-reservoir coupling imposes a distinct quantum limit on the performance of a nonequilibrium quantum heat engine. Even in the absence of quantum friction along the isentropic strokes, finite system-reservoir coupling induces correlations that result in the generation of coherence between the energy eigenstates of the working system. This coherence acts to hamper the engine's power output, as well as the efficiency with which it can convert heat into useful work, and cannot be captured by a standard Born-Markov analysis of the system-reservoir interactions.


Impact Of COVID-19 Pandemic and Updated Utilization Patterns of Sacroiliac Joint Injections from 2000 to 2020 in The Fee-For-Service (FFS) Medicare Population.
Among the multiple causes of low back and lower extremity pain, sacroiliac joint pain has shown to be prevalent in 10% to 25% of patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis. Over the years, multiple Current Procedural Terminology (CPT) codes have evolved with the inclusion of intraarticular injections, nerve blocks, and radiofrequency neurotomy, in addition to percutaneous sacroiliac joint fusions. Previous assessments of utilization patterns of sacroiliac joint interventions only included sacroiliac joint intraarticular injections, since the data was not available prior to the introduction of new codes. A recent assessment revealed an increase of 11.3%, and an annual increase of 1.2% per 100,000 Medicare population from 2009 to 2018, showing a decline in growth patterns. During the past 2 years, the COVID-19 pandemic has also had significant effects on the utilization patterns of sacroiliac joint interventions. The impact of the COVID-19 pandemic and analysis of growth patterns of sacroiliac joint interventions (intraarticular injections, nerve blocks, radiofrequency neurotomy, arthrodesis and fusion) was evaluated from 2010 to 2019 and 2010 to 2020, with a comparative analysis from 2019 to 2020 to assess the impact of the COVID-19 pandemic. To update utilization patterns of sacroiliac joint interventions with assessment of the impact of the COVID-19 pandemic. The Centers for Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS) Master dataset was utilized in the present analysis. The results of this evaluation demonstrated a significant impact of the COVID-19 pandemic with a 19.2% decrease of utilization of sacroiliac joint intraarticular injections from 2019 to 2020. There was a 23.3% increase in sacroiliac joint arthrodesis and a 5.3% decrease for sacroiliac joint fusions with small numbers from 2019 to 2020. However, data was not available for sacroiliac joint nerve blocks and sacroiliac joint radiofrequency neurotomy as these codes were incorporated in 2020. Overall, from 2010 to 2019, sacroiliac joint intraarticular injections showed an annual increase of 0.9% per 100,000 Medicare population. Sacroiliac joint arthrodesis and fusion showed an annual increase from 2010 to 2020 per 100,000 Medicare population of 29% for arthrodesis and 13.3% for fusion. Limitations of this study include a lack of inclusion of Medicare Advantage patients constituting approximately 30% to 40% of the overall Medicare population. As with all claims-based data analyses, this study is retrospective and thus potentially limited by bias. Finally, patients who are non-Medicare are not part of the dataset. The study shows the impact of the COVID-19 pandemic with a significant decrease of intraarticular injections of 19.2% from 2019 to 2020 per 100,000 Medicare population. These decreases of intraarticular injections are accompanied by a 5.3% decrease of fusion, but a 23.3% increase of arthrodesis from 2019 to 2020 per 100,000 Medicare population. Overall, the results showed an annual increase of 0.9% per 100,000 Medicare population for intraarticular injections, a 35.4% annual increase for sacroiliac joint arthrodesis and an increase of 15.5% for sacroiliac joint fusion from 2010 to 2019.


A case of vaginoplasty without grafting.
Many techniques have been used to create a neovagina in patients with vaginal agenesis, and several surgical procedures involve the use of a graft. Grafting techniques are associated with intraoperative and postoperative morbidity and complications, at both the donor and the recipient site. A 17-year-old patient with Mayer-Rokitansky-Kuster-Hauser syndrome complicated by unilateral pelvic kidney underwent successful vaginoplasty without the use of a graft, followed by insertion of a vaginal stent for 12 weeks. She had a functional, well-healed, and fully epithelialized neovagina by 6.5 months postoperatively. Patients undergoing surgical vaginoplasty may benefit from this simple surgical technique, thereby avoiding the morbidity associated with the alternative grafting techniques commonly used in practice.


Aloe vera.
We review the scientific literature regarding the aloe vera plant and its products. Aloe vera is known to contain several pharmacologically active ingredients, including a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and a substance(s) that inhibits thromboxane formation in vivo. Scientific studies exist that support an antibacterial and antifungal effect for substance(s) in aloe vera. Studies and case reports provide support for the use of aloe vera in the treatment of radiation ulcers and stasis ulcers in man and burn and frostbite injuries in animals. The evidence for a potential beneficial effect associated with the use of aloe vera is sufficient to warrant the design and implementation of well-controlled clinical trials.


Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells.
Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.


Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function.
The human platelet thrombin receptor is activated when thrombin cleaves its receptor's amino-terminal extension to reveal a new amino terminus that functions as a tethered peptide ligand. Exactly how this "agonist peptide domain" remains cryptic within the uncleaved receptor and becomes functional after receptor cleavage is unknown. In this report we define the structural features of the thrombin receptor's agonist peptide domain important for receptor activation. Studies with mutant thrombin receptors have suggested that agonist peptide domain residues 2-6 contained determinants critical for receptor activation, and the synthetic peptide SFLLR-NH2 representing the 1st 5 amino-terminal residues of the agonist peptide domain was sufficient to specify agonist activity. Acetylating or removing the agonist peptide's amino-terminal ammonium group greatly attenuated agonist activity. Agonist peptide residue Phe2 was vital for agonist function; residues Leu4 and Arg5 individually played less important roles. These structure-function relationships held for both platelet activation and activation of the cloned receptor expressed in transfected mammalian cells. Our studies suggest that structures at the extreme amino terminus of the thrombin receptor's agonist peptide domain, in particular the free ammonium group of Ser1 and the phenyl ring of Phe2, are critical for receptor activation and that the agonist function of this domain is expressed when receptor proteolysis unmasks such determinants. In addition to revealing details of the thrombin receptor's proteolytic triggering mechanism, these studies open avenues to the development of drugs targeting the thrombin receptor and to further definition for the role of the thrombin receptor in cellular regulation.


Recurrent testis cancer: seeding from retroperitoneal nodes after complete remissions by chemotherapy.
Routine retroperitoneal lymph node dissection is generally not required after a complete remission is achieved by chemotherapy in initially disseminated nonseminomatous testis cancer. However, in patients with multiple relapses retroperitoneal lymph node dissection should be considered even if the retroperitoneum is unremarkable by radiographic staging. We report on a patient with initial stage III disease in whom a complete clinical response to chemotherapy was achieved multiple times but there was repeatedly re-seeding of the lungs from an undetected focus of nodal cancer later proved by retroperitoneal lymph node dissection. Controversies in management as well as potential mechanisms of drug resistance are discussed.


Nickel speciation in the presence of different sources and fractions of dissolved organic matter.
This study evaluated nickel (Ni) speciation in the presence of different fractions (humic acid (HA), fulvic acid (FA)) and sources (natural sediment, Suwannee River, peat moss) of dissolved organic matter (DOM) at Ni concentrations toxicologically relevant to the freshwater amphipod, Hyalella azteca. The free Ni ion, Ni(2+), was measured in reconstituted water (with or without DOM) using a miniaturized ion-exchange technique (IET). Ni speciation from these experiments was compared to calculated results obtained from equilibrium modelling (WHAM, Model VI). While it is known that Ni will complex with DOM, it was found that under acutely toxic Ni exposure concentrations ([Ni(Total)]=5mg/L, or 85.1 microM) representative surface-water DOC concentrations ( approximately 10mg/L) played little or no role in Ni speciation. Conversely, at sublethal Ni exposure concentrations ([Ni(Total)]=0.2 and 0.5 microg/L, or 3.4 and 8.51 microM, respectively) DOM significantly affected Ni speciation with [Ni(2+)] decreasing with increasing concentration of DOM. It was found that for similar concentrations of DOC (same fraction, different sources), the measured Ni(2+) concentrations were reduced (relative to the control), but similar to one another. Conversely, at similar DOC concentrations, the HA fraction reduced Ni(2+) levels to a greater extent than the associated FA fraction. Overall, this study provides proof of principle that Suwannee River and peat humic substances are suitable analogues for natural sediment pore-water DOM when evaluating Ni bioavailability in freshwater.


Removal of pesticides from white and red wines by microfiltration.
The aim of this work is the investigation of microfiltration in removing pesticides from a white and a red Greek wine. Six membranes with pore size 0.45μm were investigated. Two mixtures of 23 and 9 pesticides, and single pesticide solutions were added in the wine. The pesticides tested belong to 11 chemical groups. Solid phase extraction (SPE) followed by gas chromatography (GC) with electron capture detector (ECD) were performed to analyze pesticide residues of the filtered fortified wine. Distinct behavior was exhibited by each membrane. Cellulose acetate and cellulose nitrate showed higher mean pesticide removal for both wines, followed by polyethersulfone, regenerated cellulose, and polyamides. The filtration effectiveness was correlated to the membrane type and to the pesticide chemical structure and properties (octanol-water partition coefficient, water solubility) and compared for the wines tested. In most cases, the more hydrophobic pesticides (pyrethroids and aldrin) showed higher removal from red wine than white wine. Adsorption on membranes was increased by increasing hydrophobicity and decreasing hydrophilicity of organic pesticide molecule. The removal of each pesticide from its single solution was generally higher than that from its mixtures, allowing the estimation of the antagonistic and synergistic effects of pesticides in the mixtures.


Locoregional therapies of liver metastases in a rat CC531 coloncarcinoma model results in increased resistance to tumour rechallenge.
Locoregional treatments like photodynamic therapy (PDT), radiofrequency ablation (RFA) or hepatic artery infusion (HAI) of chemotherapeutics may be applied for unresectable colorectal liver metastases. We evaluated the effect of these treatments on the immune response in a rat colon tumour liver metastases model. Wag/Rij rats were inoculated at day 0 with CC531 tumour cells at two sites in the liver. At day 15, one of two tumours was treated with RFA or PDT, or the liver was treated by HAI. Twelve days later (day 27), rats were rechallenged locally with CC531 cells in the liver or systemically with CC531 cells in the femoral vein. At day 42, tumour growth in liver and lungs was determined. RFA, PDT and HAI were very effective in liver tumour eradication, but following RFA or PDT there was no inhibitory effect on untreated nearby liver tumours. Outgrowth after local rechallenge was, however, significantly inhibited in RFA-, PDT- and HAI-treated rats, whereas all control rats showed outgrowth of a third liver tumour. After systemic rechallenge, control rats developed lung metastases whereas treated rats did not, but this difference was not statistically significant. These results show that following PDT, RFA and HAI resistance to local and possibly systemic tumour rechallenge is increased. This may be partly due to the induction or enhancement of a cellular immune response.


[Ophthalmologic complications of low-dosage tamoxifen in the treatment of breast carcinoma].
Two out of 20 patients treated for metastatic or non-metastatic breast cancer with tamoxifen (20 mg 2 dd) developed bilateral secondary tapetoretinal degeneration. In one patient in whom the medication was stopped there was still slight progression of degeneration afterwards. In the other patient tamoxifen was continued under strict ophthalmological control. The total doses have been 7.3 g and 43.8 g respectively.


Acupuncture combined with Tongxieyaofang for diarrhea-type irritable bowel syndrome: A protocol for meta-analysis.
As a traditional Chinese medicine external treatment method, acupuncture is characterized by simple operation, significant treatment effect and few side effects. Tong-Xie-Yao-Fang (TXYF), a Chinese patent medicine, combined with acupuncture has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). However, the efficacy and safety of TXYF combined with acupuncture for the treatment of IBS-D are unclear. This study aims to investigate verify the efficacy and safety of TXYF combined with acupuncture for IBS-D. Randomized controlled trials of TXYF combined with acupuncture for all IBS-D will be searched in PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database from inception to October 20, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. Based on the current evidence, the potential rank of the efficacy and safety of TXYF plus acupuncture for IBS-D will be assessed. The findings of the study will provide helpful evidence for the efficacy and safety of TXYF combined with acupuncture in the treatment of IBS-D, facilitating clinical practice and further scientific studies.


The brain's orienting response (novelty P3) in patients with unilateral temporal lobe resections.
The brain's orienting response is a biologically primitive, yet critical cognitive function necessary for survival. Though based on a wide network of brain regions, the lateral prefrontal cortex and posterior hippocampus are thought to play essential roles. Indeed, damage to these regions results in abnormalities of the novelty P3 or P3a, an event-related potential (ERP) sign of the orienting response. Like other ubiquitous markers of orienting, such as the galvanic skin response, the P3a habituates when novel events are repeated. Here, we assessed habituation of the P3a in patients who had undergone unilateral anteromedial resection of the medial temporal lobe (AMTL), including the entire hippocampus, for relief of pharmacologically intractable epilepsy. Eight left- and 8 right-AMTL patients and 16 age- and education-matched controls heard frequent standard tones, infrequent targets (requiring reaction times) and equally infrequent, unique novel, environmental sounds. The novel sounds repeated 2 blocks after their first presentation. In controls, novel repetition engendered a reduction in P3a amplitude, but this was not the case in either left- or right-AMTL patients. We conclude that bilaterally intact hippocampi are necessary for the brain to appreciate that a repetition of a novel sound has occurred, perhaps due to disruptions in ipsilateral hippocampal-prefrontal pathways and/or between the left and right hippocampi.