Transcriptional Regulation of Genes Involved in 3-Hydroxypropionic Acid Production in Response to Aeration of Recombinant Klebsiella pneumoniae.
We have described a metabolically engineered strain of Klebsiella pneumoniae/pUC18kan-aldHec that could convert glycerol to 3-hydroxypropionic acid (3-HP) effectively. In this study, the transcription of the genes encoding aldehyde dehydrogenase (AldH) and glycerol dehydratase (DhaB) responsible to 3-HP-biosynthesis, key enzymes in PP pathway and TCA cycle, as well as hydrogenases was observed under anaerobic, microaerobic, and aerobic conditions using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). During the fast growth and slow growth phases of cell growth, the aldH transcription levels were 7.0- and 2.1-fold enhanced under microaerobic condition, and 12.4- and 0.14-fold under fully aerobic condition, compared to the anaerobic control, while transcription of dhaB showed a downregulated manner due to aeration. Moreover, aeration increased the transcription levels of zwf, sucA, and sdhAB during the fast growth phase of the cell growth. The results also indicated that the hydrogenase 3 (hycBCDFG) and formate dehydrogenase (fdhA) mediated formate hydrogen lyase pathway was the main route to produce hydrogen and consume the excess NADH. These characteristics are useful for understanding and improving 3-HP biosynthesis in K. pneumoniae.


Coexistence of ordered and disordered phases in a nearly symmetric diblock copolymer near an order-disorder transition point.
We investigated the phase behavior near the order-disorder transition (ODT) temperature in a nearly symmetric diblock copolymer, using ultra-small-angle x-ray scattering method. In a narrow temperature range very close to the ODT temperature, we observed the scattering profiles that can be interpreted as a linear combination of the scattering from the disordered state and that from the ordered lamellar state. These profiles were stable during the observation time (50 h), revealing that the two-phase coexistence occurs at thermal equilibrium within this temperature range.


Comparative effect of 2 packages of pelvic floor muscle training on the clinical course of stage I-III pelvic organ prolapse.
To compare the effect of 2 packages of pelvic floor muscle training (PFMT) on the clinical course of pelvic organ prolapse (POP) among women attending a gynecology outpatient department in Chandigarh, India. A randomized controlled trial was conducted between August 8, 2010, and October 31, 2011. Overall, 140 women with stage I-III POP were allocated to a 24-week behavioral therapy intervention. Group A (n=70) received 1-to-1 PFMT and a self-instruction manual (SIM), whereas Group B (n=70) received SIM alone. Symptoms were assessed using the POP symptom scale (POP-ss), visual analog scale (VAS), and pelvic floor impact questionnaire-7 (PFIQ-7) scores. Marked improvements in mean POP-ss, VAS, PFIQ-7 scores were observed in both groups from baseline to week 24. However, significant between-group changes in mean POP-ss scores were observed from baseline to 6 weeks (P<0.001), 18 weeks (P=0.001), and 24 weeks (P=0.002). Significant between-group changes in mean VAS scores were observed at 18 and 24 weeks (P=0.009 and P=0.005). Significant between-group changes in mean PFIQ-7 scores were observed at 6 (P=0.001), 18 (P<0.001), and 24 weeks (P<0.001). Provision of both 1-to-1 PFMT and SIM led to greater improvements in POP symptoms than provision of SIM alone. ctri.nic.in: CTRI/2010/091/001190.


Early neuromotor predictors of cerebral palsy in low-birthweight infants.
The purpose of this study was to analyze retrospectively which neuromotor behaviors in a sample of four-month-old low-birthweight infants were most predictive of later cerebral palsy. The infants were evaluated at four months corrected age on the Movement Assessment of Infants (MAI) and were followed to between three and eight years of age. For the CP group as a whole, 17 neuromotor items from the MAI were highly significant (p less than 0.001) predictors of cerebral palsy. A further 15 items also were significant, but less highly so (p less than 0.01 to p less than 0.05). Seven items were predictive of later spastic diplegia, seven of spastic hemiplegia, and 35 items differentiated quadriplegic infants. A shorter version of the MAI should be developed to increase its over-all reliability and validity in the early detection of cerebral palsy. Only then would it be possible to implement early therapeutic intervention and to evaluate its efficacy.


Evaluation of a global health training program for pediatric residents.
At Children's Hospital of Michigan, an international health program was initiated in 2004. To evaluate the effectiveness of the program in imparting knowledge to pediatric residents. A pretest examining international health knowledge was administered to pediatric residents, and they were reexamined at the end of 1 year. Out of 20 residents who participated in the study, 11 (55%) fully participated in the international health program, and the other 9 partially participated. The mean overall pretest score was 56% and posttest score was 65.8% (P < .004). Full participant mean pretest was 57% and posttest was 69% (P < .005). Partial participant mean pretest was 55% and posttest was 62%, no significant difference (P = .10). Birth, medical education, residency training, or work history in a developing country did not impact pretest or posttest scores. Despite small numbers of participants, this evaluation suggests that knowledge in international health can be expanded through a training program.


The effect of amniotic fluid on bacterial growth in three population groups.
Eighty-five amniotic fluid from women of three racial groups in the third trimester of pregnancy were each tested for antibacterial activity against Escherichia coli, Staphylococcus aureus, Proteus mirabilis, Streptococcus faecalis, and Candida albicans. Seventy-six per cent of fluid samples from white patients were inhibitory, while the corresponding figures for Africans and Indians were 33 and 52, respectively. Of 19 African fluid samples tested against E. coli only, one proved inhibitory.


Fluctuation-enhanced electric conductivity in electrolyte solutions.
We analyze the effects of an externally applied electric field on thermal fluctuations for a binary electrolyte fluid. We show that the fluctuating Poisson-Nernst-Planck (PNP) equations for charged multispecies diffusion coupled with the fluctuating fluid momentum equation result in enhanced charge transport via a mechanism distinct from the well-known enhancement of mass transport that accompanies giant fluctuations. Although the mass and charge transport occurs by advection by thermal velocity fluctuations, it can macroscopically be represented as electrodiffusion with renormalized electric conductivity and a nonzero cation-anion diffusion coefficient. Specifically, we predict a nonzero cation-anion Maxwell-Stefan coefficient proportional to the square root of the salt concentration, a prediction that agrees quantitatively with experimental measurements. The renormalized or effective macroscopic equations are different from the starting PNP equations, which contain no cross-diffusion terms, even for rather dilute binary electrolytes. At the same time, for infinitely dilute solutions the renormalized electric conductivity and renormalized diffusion coefficients are consistent and the classical PNP equations with renormalized coefficients are recovered, demonstrating the self-consistency of the fluctuating hydrodynamics equations. Our calculations show that the fluctuating hydrodynamics approach recovers the electrophoretic and relaxation corrections obtained by Debye-Huckel-Onsager theory, while elucidating the physical origins of these corrections and generalizing straightforwardly to more complex multispecies electrolytes. Finally, we show that strong applied electric fields result in anisotropically enhanced "giant" velocity fluctuations and reduced fluctuations of salt concentration.


Why do patients with respiratory muscle paralysis require artificial hyperventilation?
The primary reason for the need of hyperventilation in patients with respiratory paralysis is the insufficiency of the inhibitory Hering-Breuer reflex. The artificial distension of the lungs with normal tidal volume cannot inhibit the respiratory centre in contrast to the normal state.


Retinol induces permeability transition and cytochrome c release from rat liver mitochondria.
Biological actions of retinoids on modulation of cellular gene expression by nuclear receptors are widely known. Recently, extra-nuclear effects of retinoids have been proposed, but remain to be better elucidated. Considering that retinoids induce apoptosis in tumor cells by an unknown mechanism, and that mitochondria play a key role in controlling apoptosis via cytochrome c (cyt c) release, we exposed rat liver mitochondria to 3-40 microM of retinol (vitamin A), and observed that retinol causes mitochondrial permeability transition (MPT) and cyt c release, in a concentration-dependent pattern. Increased superoxide anion generation and lipoperoxidation were also observed. Cyclosporin A or trolox co-administration reverted all parameters tested. In view of these findings, we conclude that retinol induces mitochondria oxidative damage, leading to MPT and cyt c release by opening of the permeability transition pore, thus suggesting a putative mechanism of apoptosis activation by retinol.


Concurrent Deep Brain Stimulation Reduces the Direct Cortical Stimulation Necessary for Motor Output.
Converging literatures suggest that deep brain stimulation (DBS) in Parkinson's disease affects multiple circuit mechanisms. One proposed mechanism is the normalization of primary motor cortex (M1) pathophysiology via effects on the hyperdirect pathway. We hypothesized that DBS would reduce the current intensity necessary to modulate motor-evoked potentials from focally applied direct cortical stimulation (DCS). Intraoperative subthalamic DBS, DCS, and preoperative diffusion tensor imaging data were acquired in 8 patients with Parkinson's disease. In 7 of 8 patients, DBS significantly reduced the M1 DCS current intensity required to elicit motor-evoked potentials. This neuromodulation was specific to select DBS bipolar configurations. In addition, the volume of activated tissue models of these configurations were significantly associated with overlap of the hyperdirect pathway. DBS reduces the current necessary to elicit a motor-evoked potential using DCS. This supports a circuit mechanism of DBS effectiveness, potentially involving the hyperdirect pathway that speculatively may underlie reductions in hypokinetic abnormalities in Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.


Can we discover novel pathways using metabolomic analysis?
Metabolomic analysis aims at the identification and quantitation of all metabolites in a given biological sample. Current data acquisition and network analysis strategies are classified on the basis of pathway elucidation and characteristics of theoretical networks. The development of metabolomic methods and tools is progressing rapidly, but an understanding of the resulting data is limited owing to a fundamental lack of biochemical and physiological knowledge about network organization in plants.


Negishi Cross-Coupling Provides Alkylated Tryptophans and Tryptophan Regioisomers.
Mild transition-metal catalysed cross-couplings enable direct functionalisation of biocatalytically halogenated tryptophans with alkyl iodides, representing a new alternative for late-stage derivatisations of halogenated aromatic amino acids. Moreover, this strategy enables preparation of (homo)tryptophan regioisomers in a simple two-step synthesis using a Pd-catalysed Negishi cross coupling. This method provides access to non-canonical constitutional surrogates of tryptophan, ready for use in peptide synthesis.


The P2 phage old gene: sequence, transcription and translational control.
The old (overcoming lysogenization defect) gene product of bacteriophage P2 kills Escherichia coli recB and recC mutants and interferes with phage lambda growth [Sironi et al., Virology 46 (1971) 387-396; Lindahl et al., Proc. Natl. Acad. Sci. USA 66 (1970) 587-594]. Specialized transducing lambda phages, which lack the recombination region, can be selected by plating lambda stocks on E. coli that carry the old gene on a prophage or plasmid [Finkel et al., Gene 46 (1986) 65-69]. Deletion and sequence analyses indicate that the old-encoded protein has an Mr of 65,373 and that its transcription is leftward. Primer extension analyses locate the transcription start point near the right end of the virion DNA. A bacterial mutant, named pin3 and able to suppress the effects of the old gene, has been isolated [Ghisotti et al., J. Virol. 48 (1983) 616-626]. In a pin3 mutant strain, carrying the old gene on a prophage or plasmid, the amount of old transcript is greatly reduced. The effect of the pin3 mutation is abolished by the wild-type allele of argU, an arginine tRNA that reads the rare Arg codons AGA and AGG, which are used for eight of the 14 Arg codons in the old gene. Thus the pin3 allele probably stalls translation of the old mRNA, causing this mRNA to be degraded. Isoelectric focusing and electrophoretic analysis identify the old gene product as a basic protein of approx. 65 kDa.


Improved Estimation of Ultrasound Thermal Strain Using Pulse Inversion Harmonic Imaging.
Thermal (temporal) strain imaging (TSI) is being developed to detect the lipid-rich core of atherosclerotic plaques and presence of fatty liver disease. However, the effects of ultrasonic clutter on TSI have not been considered. In this study, we evaluated whether pulse inversion harmonic imaging (PIHI) could be used to improve estimates of thermal (temporal) strain. Using mixed castor oil-gelatin phantoms of different concentrations and artificially introduced clutter, we found that PIHI improved the signal-to-noise ratio of TSI by an average of 213% or 52.1% relative to 3.3- and 6.6-MHz imaging, respectively. In a phantom constructed using human liposuction fat in the presence of clutter, the contrast-to-noise ratio was degraded by 35.1% for PIHI compared with 62.4% and 43.7% for 3.3- and 6.6-MHz imaging, respectively. These findings were further validated using an ex vivo carotid endarterectomy sample. PIHI can be used to improve estimates of thermal (temporal) strain in the presence of clutter.


Immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma: A systemic review and meta-analysis.
To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC). A meta-analysis was conducted, and the efficacy and safety of CPI were assessed. A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%. Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.


Risk factors for postoperative delirium on oxygen delivery-guided perfusion.
Studies have demonstrated the efficacy of oxygen delivery-guided perfusion (ODGP) in preventing postoperative acute kidney injury, but the benefit of ODGP for delirium has not been confirmed. We retrospectively investigated the risk factors for postoperative delirium in patients who underwent ODGP (with oxygen delivery index [DO2i] > 300 mL/min/m2). Consecutive patients who underwent on-pump cardiovascular surgery with ODGP from January 2018 to December 2020 were retrospectively analyzed. In addition to examining patients' DO2i during cardiopulmonary bypass (CPB), we quantified the two primary DO2 components-hematocrit (Hct) and pump flow. Delirium was defined based on the Intensive Care Delirium Screening Checklist (ICDSC). Patients were divided into three groups: no delirium (ICDSC score = 0), subsyndromal delirium (ICDSC score = 1-3), and clinical delirium (ICDSC score ≥ 4). Multivariate analysis identified only the number of red blood cell (RBC) units transfused, intubation time, and the cumulative time below the Hct threshold of 25% as predictive factors of postoperative delirium. Although patients with higher ICDSC scores had greater hemodilution during CPB, ODGP resulted in a higher pump flow, and DO2i was maintained above 300 mL/min/m2, with no significant difference between the three groups. A low Hct level during CPB with ODGP, the number of RBC units transfused, and intubation time were associated with postoperative delirium. Further investigations are needed to determine the ability of ODGP to prevent low Hct during CPB.


The silent world of assisted reproduction: A qualitative account of communication between doctors and patients undergoing in vitro fertilisation in Australia.
In vitro fertilisation (IVF) is now a common assisted reproductive technology (ART) procedure globally, with 8 million children alive today having been conceived utilising IVF. For many patients, IVF is a difficult experience with many discontinuing treatment because of emotional, relationship and financial stress, or intolerable physical side effects of hormone treatments. A qualitative study, in which 31 professionals and 25 patients from the ART sector in Australia were interviewed. The interviews were analysed using codebook thematic analysis. Our data indicates there are 'silences' within the therapeutic relationship of IVF, which may limit the capacity for patients to prepare emotionally, financially, or medically for the procedure, and may contribute to psychological distress and dissatisfaction with care. These 'silences' include what the patient 'is not told' by their clinician or 'does not hear' and what the patient feels they 'cannot say'. Drawing upon the work of Jay Katz, Charis Thompson, and Miles Little on 'silences' and performance in clinical practice, we argue that although IVF is a complex and multifaceted procedure that is often conducted in a commercial setting, the clinical and therapeutic relationship between doctor and patient remains pivotal to the experiences of patients. The 'silences' within this relationship may impact negatively on decision-making, and on the delivery and experience of care. Careful attention to the realities of IVF treatment in the clinic room (and awareness of the performances that hide them) should allow for more present and compassionate care. Such care may leave patients more satisfied with their experience and their choices, regardless of treatment outcomes. This article draws on interviews with patients who had undergone or were currently undergoing IVF, as well as a range of representatives from the ART community (including reproductive medicine specialists, general practitioners, fertility nurses, counsellors, administrators in ART businesses and embryologists).


Organic acid disorders detected by urine organic acid analysis: twelve cases in Thailand over three-year experience.
Disorders of organic acid (OA) metabolism are generally detected by qualitative analysis of urine organic acids by gas chromatography/mass spectrometry (GC/MS) which was well established in developed countries since 1980s. Confirmation of the diagnosis of organic acid disorders by OA analysis, enzyme analysis and molecular study is a difficult task in developing countries. During 2001-2004, we had analysed 442 urine samples in 365 patients and identified 12 cases of organic acid disorders. We identified the following disorders: alkaptonuria (ALK)=1, isovaleric acidemia (IVA)=3, propionic acidemia (PA)=2, methylmalonic acidemia (MMA)=3, glutaric aciduria, type I (GA-I)=1, multiple carboxylase deficiency (MCD)=1, and glutaric acidemia, type II (GA-II)=1. OA disorders had never been diagnosed in Thailand before, until GC/MS technology was introduced to Thailand in 2001. Urine OA analysis also provided a diagnostic clue to other inborn errors of metabolism including amino acid disorders, urea cycle disorders, disorders of carbohydrate metabolism, and mitochondrial fatty acid oxidation disorders. Since then, we were able to diagnose numerous disorders, which led to prompt treatment and better outcome in our patients.


Simultaneous observation of positive and negative nuclear Overhauser effects in oligopeptides due to segmental motion.
Nuclear Overhauser effect (NOE) studies of the symmetrical cystine peptides (Formula: see text) (n = 1-3) in dimethylsulfoxide, have resulted in the simultaneous observation of both positive and negative NOEs. Positive NOEs are observed on the Trp C2H and C4H protons of the indole ring upon irradiation of Trp C alpha H and C beta H2 resonances in the peptides where n = 1 and 2. Negative NOEs are observed between backbone NH and C alpha H protons. The magnitudes of the observed NOEs are sensitive to changes in molecular size and solvent viscosity. The results demonstrate that NOEs may be a useful probe of sidechain segmental motion in oligopeptides.


Cholinergic regulation of the phosphoinositide second messenger system in the guinea pig organ of Corti.
The effect of cholinergic agents on the phosphoinositide second messenger system was investigated in the cochlea of the adult guinea pig in vivo and in vitro. In vivo, phospholipids were labeled with [32P]-orthophosphate by perilymphatic perfusion and their hydrolysis assayed in 'chase' experiments with non-radioactive orthophosphate. Carbachol (1 mM) reduced the content of 32P-labeled phosphatidylinositol 4,5-bisphosphate in the organ of Corti from 31% to 21% of total 32P-lipids, indicating stimulated hydrolysis. The pharmacology of this effect was studied in detail in vitro via the release of inositol phosphates from phosphoinositides pre-labeled with 3H-inositol. Release was increased 2-fold by 1 mM carbachol, 1.6-fold by 1 mM muscarine, but was unaffected by dimethylphenylpiperazinium; the stimulation was blocked by 1 microM atropine but not mecamylamine. These responses indicate the coupling of phosphoinositides to a muscarinic receptor. Furthermore, stimulated inositol phosphate release was higher in the base of the organ of Corti than in the apex which correlates with the increased cholinergic efferent innervation of outer hair cells in the basal region. These results suggest that muscarinic-stimulated inositol phosphate release occurs at the level of the outer hair cell and thus may have an important modulatory role in auditory transduction.


Effect of nanofillers on the physico-mechanical properties of load bearing bone implants.
Bones are nanocomposites consisting of a collagenous fibre network, embedded with calcium phosphates mainly hydroxyapatite (HA) nanocrystallites. As bones are subjected to continuous loading and unloading process every day, they often tend to become prone to fatigue and breakdown. Therefore, this review addresses the use of nanocomposites particularly polymers reinforced with nanoceramics that can be used as load bearing bone implants. Further, nanocomposite preparation and dispersion modification techniques have been highlighted along with thorough discussion on the influence that various nanofillers have on the physico-mechanical properties of nanocomposites in relation to that of natural bone properties. This review updates the nanocomposites that meet the physico-mechanical properties (strength and elasticity) as well as biocompatibility requirement of a load bearing bone implant and also attempts to highlight the gaps in the reported studies to address the fatigue and creep properties of the nanocomposites.


Novel compstatin family peptides inhibit complement activation by drusen-like deposits in human retinal pigmented epithelial cell cultures.
We have used a novel human retinal pigmented epithelial (RPE) cell-based model that mimics drusen biogenesis and the pathobiology of age-related macular degeneration to evaluate the efficacy of newly designed peptide inhibitors of the complement system. The peptides belong to the compstatin family and, compared to existing compstatin analogs, have been optimized to promote binding to their target, complement protein C3, and to enhance solubility by improving their polarity/hydrophobicity ratios. Based on analysis of molecular dynamics simulation data of peptide-C3 complexes, novel binding features were designed by introducing intermolecular salt bridge-forming arginines at the N-terminus and at position -1 of N-terminal dipeptide extensions. Our study demonstrates that the RPE cell assay has discriminatory capability for measuring the efficacy and potency of inhibitory peptides in a macular disease environment.


Functional Generalized Additive Models.
We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.


Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease.
Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms. In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients. 70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= -0.5 to -0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms. Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.


Right-sided superior vena cava draining into the left atrium in a patient with persistent left-sided superior vena cava emptying into the right atrium diagnosed by echocardiography.
We present a patient with an isolated right-sided superior vena cava draining into the left atrium with a persistent left-sided superior vena cava emptying into the right atrium. During an agitated saline injection into the patient's right upper extremity intravenous line, the patient suffered an acute transient ischemic attack. To our knowledge, this is the only reported case of this rare anomaly incidentally uncovered during an echocardiogram with saline contrast study.


A mechanistic investigation of anti-elimination in (Z)-1,2-bis(arylseleno)-1-alkenes and their sulfur analogs.
The oxidation of (Z)-1,2-bis(arylseleno)-1-alkenes is known to afford alkynyl selenoxides via a unique selenoxide anti-elimination mechanism; however, to date, there have been no mechanistic studies of this reaction. During our studies of this transformation, monoselenoxides 6 and 7 were unexpectedly isolated as stable reaction intermediates. In addition, (77)Se NMR studies of the reaction mixture revealed the presence of an intramolecular Se···O interaction and the formation of alkynyl selenoxides. Meanwhile, even at higher temperatures, the reaction of a (Z)-1,2-bis(arylsulfinyl)-1-alkene, the sulfur analog of (Z)-1,2-bis(arylseleninyl)-1-alkenes, did not proceed via sulfoxide elimination but proceeded via isomerization and disproportionation. Therefore, the intramolecular Se···O interaction can be concluded to play a pivotal role in the anti-elimination reaction.


External fixation of double vertical pelvic fractures with a trapezoid compression frame.
Seventeen patients with double vertical fractures of the pelvic girdle were treated by early reduction and subsequent fixation of the pelvic ring with a trapezoid frame. This provided firm fixation of the fractured pelvis. With the frame attached, patients without associated injuries were allowed out of bed within 3 weeks and in every case the frame was removed 6 weeks after its application. External fixation of the pelvic fracture afforded relief from pain and greatly facilitated nursing. At follow-up, all the fractures had united in the position secured initially by the frame and no patient complained of pain in the sacro-iliac joints.


Adderall for All: A Defense of Pediatric Neuroenhancement.
I argue that young patients should be able to access neuroenhancing drugs without a diagnosis of ADHD. The current framework of consent for pediatric patients can be adapted to accommodate neuroenhancement. After a brief overview of pediatric neuroenhancement, I develop three arguments in favor of greater acceptance of neuroenhancement for young patients. First, ADHD is not relevantly different from other disadvantages that could be treated with stimulant medication. Second, establishing a legitimate framework for pediatric neuroenhancement would mitigate the bad effects of diversion and improve research on neuroenhancement and ADHD. Third, some pediatric patients have rights to access neuroenhancements. I then consider several objections to pediatric neuroenhancement. I address concerns about addiction, advertising, authentic development, the parent-child relationship and equal opportunity and conclude that these concerns may inform a framework for prescribing neuroenhancement but they do not justify limits on prescribing.


Surface Mechanism of Catalytic Electrodes in Lithium-Oxygen Batteries: How Nanostructures Mediate the Interfacial Reactions.
The use of catalysts is the key to boost electrode reactions in lithium-oxygen (Li-O2) batteries. In-depth understanding of the nanoscale catalytic effect at electrode/electrolyte interfaces is of great significance for guiding a design of functionally optimized catalyst. Here, using electrochemical atomic force microscopy, we present the real-time imaging of interfacial evolution on nanostructured Au electrodes in a working battery, revealing that the nanostructure of Au is directly related to the catalytic activity toward oxygen reduction reaction (ORR)/oxygen evolution reaction (OER). In situ views show that nanoporous Au with a size of ∼14 nm for ligaments and ∼5 nm for nanopores promote the nucleation and growth of discharge product Li2O2 with large size at a high discharge voltage, yet densely packed Au nanoparticles with a diameter of ∼15 nm could catalyze Li2O2 to fully decompose via the top-bottom approach at a low charge potential. In addition, the difference in the nucleation potential of Li2O2 on the electrode with hybrid nanostructures could result in an uneven distribution of discharge products, which is alleviated at a large discharge rate and the capacity of the battery is improved significantly. These observations provide deep insights into the mechanisms of Li-O2 interfacial reaction catalyzed by nanostructured catalysts and strategies for improving Li-O2 batteries.


Bosnian population data for the 15 STR loci in the Power Plex 16 kit.
The PowerPlex 16 amplification kit was used for the analysis of allele frequencies for the 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, VWA, D8S1179, TPOX and FGA) in unrelated, autochthonous healthy adults from Bosnia ( n=123 for TH01, Penta E, D16S539, CSF1PO, Penta D and TPOX, n=210 for D3S1358, D21S11, D18S51, D5S818, D13S317, D7S820, VWA, D8S1179 and FGA). The agreement with HWE was confirmed for all loci with the exception of Penta D (based on the chi(2)-test only). The combined power of discrimination (PD) and the combined power of exclusion (PE) for the 15 studied loci were 0.999999999999999997 and 0.999999, respectively.


Lattice fringe studies of (100) defects in enamel crystallites.
Lattice imperfections in the structure of shark (Nataprion brevirostrais) enamel crystallites have been studied by means of lattice-imaging in a high-resolution transmission electron microscope. Line defects exhibiting various lengths (100-2500 A) and widths (10-30 A) and demonstrating phase behaviour different from that of the host crystal were observed along the fringes representing (100) lattice planes. When defect sites were subjected to an electron beam, an annealing process was observed in which the difference in phase contrast eventually disappeared and the defect itself became an intricate part of the (100)-type lattice planes. A through-focal series of the defects show a reversal in phase contrast. By examining the contrast behaviour under certain focal conditions and by adopting the Fresnel diffraction mode, the refractive index of the defect regions was determined to be lower than that of the apatite crystal. Present findings suggest that the interlayering structure along the (100) planes is responsible for the line defects observed in enamel apatites.


Improving hyperpolarized 129 Xe ADC mapping in pediatric and adult lungs with uncertainty propagation.
Hyperpolarized (HP) 129 Xe-MRI provides non-invasive methods to quantify lung function and structure, with the 129 Xe apparent diffusion coefficient (ADC) being a well validated measure of alveolar airspace size. However, the experimental factors that impact the precision and accuracy of HP 129 Xe ADC measurements have not been rigorously investigated. Here, we introduce an analytical model to predict the experimental uncertainty of 129 Xe ADC estimates. Additionally, we report ADC dependence on age in healthy pediatric volunteers. An analytical expression for ADC uncertainty was derived from the Stejskal-Tanner equation and simplified Bloch equations appropriate for HP media. Parameters in the model were maximum b-value (bmax ), number of b-values (Nb ), number of phase encoding lines (Nph ), flip angle and the ADC itself. This model was validated by simulations and phantom experiments, and five fitting methods for calculating ADC were investigated. To examine the lower range for 129 Xe ADC, 32 healthy subjects (age 6-40 years) underwent diffusion-weighted 129 Xe MRI. The analytical model provides a lower bound on ADC uncertainty and predicts that decreased signal-to-noise ratio yields increases in relative uncertainty (ϵADC) . As such, experimental parameters that impact non-equilibrium 129 Xe magnetization necessarily impact the resulting ϵADC . The values of diffusion encoding parameters (Nb and bmax ) that minimize ϵADC strongly depend on the underlying ADC value, resulting in a global minimum for ϵADC . Bayesian fitting outperformed other methods (error < 5%) for estimating ADC. The whole-lung mean 129 Xe ADC of healthy subjects increased with age at a rate of 1.75 × 10-4 cm2 /s/yr (p = 0.001). HP 129 Xe diffusion MRI can be improved by minimizing the uncertainty of ADC measurements via uncertainty propagation. Doing so will improve experimental accuracy when measuring lung microstructure in vivo and should allow improved monitoring of regional disease progression and assessment of therapy response in a range of lung diseases.


Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation.
Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical course and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%-43.4% of colitis-type CD (n = 53), 2.3%-6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.


PPARgamma agonist rosiglitazone is neuroprotective after traumatic brain injury via anti-inflammatory and anti-oxidative mechanisms.
Peroxisome proliferator-activated receptor (PPAR)-gamma is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARgamma which was shown to induce neuroprotection in animal models of focal ischemia and spinal cord injury. We currently evaluated the therapeutic potential of rosiglitazone (6 mg/kg at 5 min, 6 h and 24 h; i.p.) following controlled cortical impact (CCI)-induced traumatic brain injury (TBI) in adult mice. CCI injury increased the cortical PPARgamma mRNA levels which were further elevated by rosiglitazone treatment. In addition, rosiglitazone treatment significantly decreased the cortical lesion volume measured at 7 days compared to vehicle treatment (by 56+/-7%; p<0.05; n=6/group). Following TBI, the spared cortex of the rosiglitazone group showed significantly less numbers of GSI-B4(+) activated microglia/macrophages and ICAM1(+) capillaries, and curtailed induction of pro-inflammatory genes IL6, MCP1 and ICAM1 compared to vehicle group. Rosiglitazone-treated mice also showed significantly less number of TUNEL(+) apoptotic neurons and curtailed induction of caspase-3 and Bax, compared to vehicle control. In addition, rosiglitazone significantly enhanced the post-TBI expression of the neuroprotective chaperones HSP27, HSP70 and HSP32/HO1, and the anti-oxidant enzymes catalase, Cu/Zn-SOD and Mn-SOD, compared to vehicle. Treatment with GW9662 (a specific PPARgamma antagonist) prevented all the above PPARgamma-mediated actions. Thus, PPARgamma activation confers neuroprotection after TBI by anti-inflammatory, anti-apoptotic and anti-oxidative mechanisms.


Differential Effects of an Emergency Department-to-Home Care Transitions Intervention in an Older Adult Population: A Latent Class Analysis.
Older adults frequently return to the emergency department (ED) within 30 days of a visit. High-risk patients can differentially benefit from transitional care interventions. Latent class analysis (LCA) is a model-based method used to segment the population and test intervention effects by subgroup. We aimed to identify latent classes within an older adult population from a randomized controlled trial evaluating the effectiveness of an ED-to-home transitional care program and test whether class membership modified the intervention effect. Participants were randomized to receive the Care Transitions Intervention or usual care. Study staff collected outcomes data through medical record reviews and surveys. We performed LCA and logistic regression to evaluate the differential effects of the intervention by class membership. Participants were ED patients (age 60 y and above) discharged to a community residence. Indicator variables for the LCA included clinically available and patient-reported data from the initial ED visit. Our primary outcome was ED revisits within 30 days. Secondary outcomes included ED revisits within 14 days, outpatient follow-up within 7 and 30 days, and self-management behaviors. We interpreted 6 latent classes in this study population. Classes 1, 4, 5, and 6 showed a reduction in ED revisit rates with the intervention; classes 2 and 3 showed an increase in ED revisit rates. In class 5, we found evidence that the intervention increased outpatient follow-up within 7 and 30 days (odds ratio: 1.81, 95% CI: 1.13-2.91; odds ratio: 2.24, 95% CI: 1.25-4.03). Class membership modified the intervention effect. Population segmentation is an important step in evaluating a transitional care intervention.


Wasted TMEM16A channels are rescued by phosphatidylinositol 4,5-bisphosphate.
Recently there has been a flurry of interest in the regulation of the homo-dimeric calcium-activated chloride channel ANO1 (also known as TMEM16A) by phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). These recent studies show that upon Ca2+ binding, PI(4,5)P2 cooperates to maintain the conductive state of ANO1. PI(4,5)P2 does so by binding to sites or modules on the protein's cytosolic side. These findings add a new function to the PI(4,5)P2 repertoire and a new dimension to ANO1 gating.


A self-directed learning intervention for radiographers rating mammographic breast density.
Subjective methods of mammographic breast density (MBD) assessment are prone to inter-reader variability. This work aims to assess the impact of a short self-directed, experiential learning intervention on radiographers' reproducibility of MBD assessment. The study used two sets of images (test and learning intervention) containing left craniocaudal and left mediolateral oblique views. The test set had MBD ratings from Volpara™ and radiologists using the fourth edition Breast Imaging and Data Systems (BI-RADS®). Seven radiographers rated the MBD of the test set before and after a self-directed learning intervention using the percentage descriptors in the fourth edition BI-RADS® Atlas. The inter-reader agreement, the agreement between radiographers and Volpara™ as well as radiologists, was assessed using a Weighted Kappa (кw). Overall, radiographers' inter-reader agreement (кw) was substantial (0.79; 95% CI: 0.70-0.87) before the intervention and almost perfect (0.84; 95% CI: 0.77-0.90) after the intervention. Before the intervention, radiographers demonstrated fair agreement with radiologists (0.24; 95% CI: -0.46-0.61) and Volpara™ (0.24; 95% CI: -0.41-0.59). A fair but slightly improved agreement was also observed between radiographers and radiologists (0.31; 95% CI: -0.33-0.64) as well as Volpara™ (0.28; 95% CI: -0.34-0.61) after the intervention. Findings demonstrate that a short duration self-directed, experiential learning intervention reduces inter-reader differences in MBD classification, but has a negligible impact on improving the agreement between inexperienced and expert readers.


Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin.
The purpose of this study was to investigate the immunoregulatory potential of Hsp60 in the skin of dogs with atopic dermatitis. Three dogs with chronic atopic dermatitis and four healthy dogs were injected intradermally with Hsp60 and phosphate-buffered saline. Biopsies were taken before testing from non-injected control skin, lesional and non-lesional atopic skin, and 48 and 72 h after injection. Analysis of cytokine messenger RNA was performed using quantitative real-time polymerase chain reaction. Forty-eight hours after Hsp60 injection, a rise in interleukin (IL)-10 was found (P = 0.034) with the highest expression levels in non-lesional atopic and control skin. A rise of transforming growth factor beta (P = 0.015) and IL-12p40 (P = 0.017) was noticed 72 h after Hsp60 injection in control skin. No significant differences were observed for the expression of IL-4, IL-12p35, and interferon gamma. The results indicate that Hsp60 is able to induce cytokines of a regulatory and Th1 phenotype in the skin. Furthermore, this study seems to provide a first indication of deficient Hsp60 response in atopic dermatitis affected skin.


Primary Cleft Lip Repair in Adults Under Local Anesthesia.
There are many adults with cleft lip deformities in developing countries. This is due to the lack of public awareness, social stigma, distance from the health center, and parents' financial condition. Lip repair under local anesthesia is safe, cost-effective and would be beneficial for the underprivileged population. A retrospective cohort study with follow-up of 1 to 8 years. Academic Hospital. Cleft lip repair was performed in 252 patients of age more than 12 years from 2012 to 2019. Patients with cleft palate, cardiopulmonary disease, who did not consent for the procedure while awake were excluded. Cleft lip surgery done under local anesthesia. Outcome measures were patients' self-satisfaction and comments of peer. Two hundred fifty-two primary cleft lip operations were done in 168 male and 84 female patients. The mean age was 23.62 years, and the mean weight was 49.66 kg. Unilateral was 227, Bilateral cleft lip 25. The postoperative period was uneventful. No case of wound dehiscence or wound infection was observed. Patients were discharged on the same day, except the ones who traveled a long distance. Cleft lip repair in adults under local anesthesia is safe and cost-effective.


Risk assessment of cheese processing tasks using the Strain Index and OCRA Checklist.
The purpose of this study was to conduct and compare two ergonomic risk assessment methods often used in occupational health research and practice: the Strain Index (SI) and Occupational Repetitive Actions (OCRA) Checklist. Seven raters used the SI and OCRA Checklist to assess task-level physical exposures to the upper extremity of workers performing 21 cheese-manufacturing tasks. Of the total task exposures assessed with both methods, nearly half (49.1%) were classified as hazardous using the OCRA Checklist while 60.2% were classified as hazardous using the SI. Although the underlying injury risk characterization constructs of the SI and OCRA Checklist differ, the results indicated that the SI and OCRA Checklist often classified job tasks into similar risk categories. The differences in risk classifications determined by the SI and OCRA Checklist for job tasks were likely related to the definition of variables measured by these assessment methods as well as the complexity of tasks evaluated. By design, the SI is specific to the distal upper extremity while the OCRA Checklist accounts for the entire upper extremity including the shoulder. When conducting risk assessments of industrial work tasks, the choice of analysis tools should be based on the purpose of the assessment and the complexity of task functions. Both the SI and OCRA Checklist yield risk assessment ratings that are similar for cheese processing tasks.


Sildenafil has little influence on cardiovascular hemodynamics or 6-km time trial performance in trained men and women at simulated high altitude.
Sildenafil improves maximal exercise capacity at high altitudes (∼4350-5800 m) by reducing pulmonary arterial pressure and enhancing oxygen delivery, but the effects on exercise performance at less severe altitudes are less clear. To determine the effects of sildenafil on cardiovascular hemodynamics (heart rate, stroke volume, and cardiac output), arterial oxygen saturation (SaO2), and 6-km time-trial performance of endurance-trained men and women at a simulated altitude of ∼3900 m. Twenty men and 15 women, endurance-trained, completed one experimental exercise trial (30 min at 55% of altitude-specific capacity +6-km time trial) at sea level (SL) and two trials at simulated high altitude (HA) while breathing hypoxic gas (12.8% FIo2) after ingestion of either placebo or 50 mg sildenafil in double-blind, randomized, and counterbalanced fashion. Maximal exercise capacity and SaO2 were significantly reduced at HA compared to SL (18%-23%), but sildenafil did not significantly improve cardiovascular hemodynamics or time-trial performance in either men or women compared to placebo and only improved SaO2 in women (4%). One male subject (5% of male subjects, 2.8% of all subjects) exhibited a meaningful 36-s improvement in time-trial performance with sildenafil compared to placebo. In this group of endurance trained men and women, sildenafil had very little influence on cardiovascular hemodynamics, SaO2, and 6-km time-trial performance at a simulated altitude of ∼3900 m. It appears that a very small percentage of endurance-trained men and women derive meaningful improvements in aerobic performance from sildenafil at a simulated altitude of ∼3900 m.


Interactions among invaders: community and ecosystem effects of multiple invasive species in an experimental aquatic system.
With ecosystems increasingly supporting multiple invasive species, interactions among invaders could magnify or ameliorate the undesired consequences for native communities and ecosystems. We evaluated the individual and combined effects of rusty crayfish (Orconectes rusticus) and Chinese mystery snails [Bellamya (=Cipangopaludina) chinensis] on native snail communities (Physa, Helisoma and Lymnaea sp.) and ecosystem attributes (algal chlorophyll a and nutrient concentrations). Both invaders are widespread in the USA and commonly co-occur within northern temperate lakes, underscoring the importance of understanding their singular and joint effects. An outdoor mesocosm experiment revealed that while the two invaders had only weakly negative effects upon one another, both negatively affected the abundance and biomass of native snails, and their combined presence drove one native species to extinction and reduced a second by >95%. Owing to its larger size and thicker shell, adult Bellamya were protected from crayfish attack relative to native species (especially Physa and Lymnaea), suggesting the co-occurrence of these invaders in nature could have elevated consequences for native communities. The per capita impacts of Orconectes (a snail predator) on native snails were substantially greater than those of Bellamya (a snail competitor). Crayfish predation also had a cascading effect by reducing native snail biomass, leading to increased periphyton growth. Bellamya, in contrast, reduced periphyton biomass, likely causing a reduction in growth by native lymnaeid snails. Bellamya also increased water column N:P ratio, possibly because of a low P excretion rate relative to native snail species. Together, these findings highlight the importance of understanding interactions among invasive species, which can have significant community- and ecosystem-level effects.


The role of topical corticosteroids in bullous pemphigoid in the elderly.
Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease. Until recently the condition was treated with oral corticosteroids. However, high-dose corticosteroids are poorly tolerated in the elderly and their use has probably contributed to the high mortality rates observed in several cohorts. Accordingly, considerable effort has been directed at identifying corticosteroid-sparing agents, such as immunosuppressant drugs, plasma exchange techniques, intravenous immunoglobulins and tetracycline, that can be used in this clinical setting. Many of these options have appeared to be useful in open series, but they have been found to be ineffective or only marginally effective when tested in randomised, controlled trials. An important breakthrough occurred with the demonstration in a large, randomised trial that a 'super-potent' topical corticosteroid (clobetasol propionate) was not only associated with a significant decrease in severe complications and mortality of BP patients, but was also more effective than oral prednisone. New strategies for BP should include topical clobetasol propionate as first-line therapy in the elderly and consider adjuvant therapy only in the very rare cases that are either resistant or intolerant to this treatment.


Apparent consumption of refined sugar in Australia (1938-2011).
In Australia, the Australian Bureau of Statistics discontinued collection of apparent consumption data for refined sugars in 1998/1999. The objectives of this study were to update this data series to determine whether it is a reliable data series that reflects consumption of refined sugars, defined as sucrose in the forms of refined or raw sugar or liquified sugars manufactured for human consumption. The study used the same methodology as that used by the Australian Bureau of Statistics to derive a refined sugars consumption estimate each year until the collection was discontinued. Sales by Australian refiners, refined sugars imports and the net balance of refined sugars contained in foods imported into, and exported from, Australia were used to calculate total refined sugars use for each year up to 2011. Per capita consumption figures were then derived. During the period 1938-2011, apparent consumption of refined sugars in Australia fell 13.1% from 48.3 to 42.0 kg per head (R(2)=0.74). Between the 1950s and the 1970s, apparent consumption was relatively stable at about 50 kg per person. In the shorter period 1970-2011, refined sugars consumption fell 16.5% from 50.3 to 42.0 kg per head, though greater variability was evident (R(2)=0.53). An alternative data set showed greater volatility with no trend up or down. The limited variability of the extended apparent consumption series and its consistency with recent national dietary survey data and sugar-sweetened beverage sales data indicate that it is a reliable data set that reflects declining intake of refined sugars in Australia.


Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients.
In an earlier study, we have demonstrated a high clinical and pathologic response rate of neoadjuvant paclitaxel (P) and cisplatin (C) for patients with locally advanced breast cancer (LABC). The current phase II study includes larger number of patients who had longer follow-up. A total of 126 consecutive patients with noninflammatory LABC (T2 >4 cm, T3 or T4, N0-N3, M0) were included in the study. Patients were scheduled to receive three to four cycles of the neoadjuvant PC (paclitaxel 135 mg m(-2) and cisplatin 75 mg m(-2) on day 1) every 21 days. Patients were then subjected to surgery and subsequently received six cycles of FAC (5-fluorouracil 500 mg m(-2), doxorubicin 50 mg m(-2), and cyclophosphamide 500 mg m(-2)) or four cycles of AC (doxorubicin 60 mg m(-2) and cyclophosphamide 600 mg m(-2)); all drugs were administered intravenously on day 1 with cycles repeated every 21 days. Patients then received radiation therapy, and those with hormone receptor-positive tumours were given adjuvant tamoxifen intended for 5 years. The median age was 41 years. Clinically, 12, 52, and 37% of patients had T2 >4 cm, T3, and T4, respectively. The mean tumour size was 7 cm (95% CI, 7.3-8.5). The clinical nodal status was N0, N1, and N2-N3 in 32, 52, and 17% of patients, respectively. Disease stage at diagnosis was IIA (2%), IIB (32%), IIIA (28%), and IIIB (39%). Clinical assessment of the primary tumour and the axillary nodal status after primary chemotherapy showed that 35 patients (28%) achieved complete response (cCR), while 80 (63%) demonstrated partial response to PC. Of patients with evaluable pathologic data of the primary tumour (123 patients), complete pathologic response (pCR) was achieved in 29 patients (24%), and an additional nine (7%) only had a microinvasive disease. Moreover, 20 of the 122 patients (16%) had no residual disease in the primary tumour or in the axillary nodes. Failure to attain cCR predicted failure to achieve pCR. At a median follow-up of 37.5 months (95% CI, 31.5-43.3), 71% were alive with no recurrence, 16% were alive with evidence of disease, and 13% were dead. Of the 122 patients who had surgery, 36 (29%) developed recurrence including one of the patients who attained pCR. The median overall or disease-free survival has not been reached with a projected 5-year overall survival (OS) and disease-free survival (DFS) of 85% (+/-4%) and 63% (+/-5%), respectively. On multivariate analysis, clinical response of the primary tumour, pathological response of the primary tumour, and the pathological nodal status were identified as independent prognostic variables for DFS. No variable, however, was identified to prognosticate OS. PC was acceptably safe. Neoadjuvant PC as used in this phase II study in a multidisciplinary strategy was highly effective. Clinical and pathologic responses remain the most important variables that predict outcome.


[Detection and prevalence of alcohol use disorders in primary health care in Catalonia].
To describe the detection by general practitioners (GP) of alcohol use disorders (AUD) and alcohol dependence, and their prevalence in primary health settings. Cross-sectional study. Twenty Catalan primary health care centres (Spain). Twenty three randomly selected GP were surveyed about alcohol and other diseases of their patients. A total of 1,372 patient interviews were collected. Patients and GPs were asked about AUD and other mental and health conditions. The Composite International Diagnostic Interview (CIDI) as the gold standard was used, as well as other structured interviews (K10 screening and World Health Organization Disability Assessment Schedule 2.0). The CIDI diagnosed 9.6% of the total sample with an AUD, and 4.8% diagnosed by GPs. CIDI could detect more AUD in young adults, while GPs diagnosed more AUD and alcohol dependence in elderly people, who also had more health conditions. GPs recognised AUD in 28.8% of patients diagnosed with CIDI, but 42.4% of patients diagnosed by GPs were not detected with CIDI. Taking both into consideration, the gold standard and the GP clinical impression, 11.7% of patients had an AUD and 8.6% an AD. GP recognise AUD better in the elderly with worst health conditions than CIDI. AUD and alcohol dependence prevalence is high in primary health care centres.


Bonobos apparently search for a lost member injured by a snare.
This is the first report to demonstrate that a large mixed-sex party of bonobos travelled a long distance to return to the location of a snare apparently to search for a member that had been caught in it. An adult male was caught in a metallic snare in a swamp forest at Wamba, Luo Scientific Reserve, Democratic Republic of the Congo. After he escaped from the snare by breaking a sapling to which the snare was attached, other members of his party assisted him by unfastening the snare from lianas in which it was caught and licked his wound and tried to remove the snare from his fingers. In the late afternoon, they left him in the place where he was stuck in the liana and travelled to the dry forest where they usually spend the night. The next morning, they travelled back 1.8 km to revisit the location of the injured male. When they confirmed that he was no longer there, they returned to the dry forest to forage. This was unlike the usual ranging patterns of the party, suggesting that the bonobos travelled with the specific intention of searching for this injured individual who had been left behind. The incident described in this report likely occurred because bonobos usually range in a large mixed-sex party and try to maintain group cohesion as much as possible.


Output control of da Vinci surgical system's surgical graspers.
The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors.


Human ferritin: effects of antigen source and fixation on leucocyte staining by immunoperoxidase technique.
The localization of ferritin was studied in peripheral blood cells and variously fixed tissues with the antibodies against ferritins isolated from human heart and spleen. The unlabelled antibody enzyme method (PAP) was used to detect the binding sites of antibodies. In peripheral blood cell smears both antisera gave rise to strong staining of polymorphonuclear (PMN) cell cytoplasm, whereas the monocytes stained relatively weakly. There were no staining differences between the two antisera. In human spleen sections the spleen ferritin antiserum stained the PMN cells and sinusoidal lining cells, whereas the heart ferritin antiserum stained only PMN cells. Neither of the two antisera stained monocytes in the spleen sections. This finding was observed in specimens fixed in Bouin's fixative, Baker's fixative and neutral formalin. However, the immunoreactivity of ferritin was totally destroyed by some other fixatives (Carnoy's fixative, formol sucrose and glutaraldehyde). These results suggest that ferritin is more readily released from monocytes than from PMN cells, and that mature spleen macrophages contain antigenic determinants of ferritin that are recognized only by anti-spleen ferritin antiserum.


Disposition of an immunoglobulin intravenous preparation in very low birth weight neonates.
To assess the disposition, tolerance, and toxicity of an intravenous preparation of immunoglobulin (IGIV) in very low birth weight (VLBW) neonates, we administered single doses of 500 or 750 mg/kg to 20 neonates with birth weights between 750 and 1500 g during the first week of life. The infusion of this product was well tolerated. Modest changes in hemoglobin, hematocrit, and total hemolytic complement occurred as expected. Hepatic toxic effects were not detected. Mean peak IgG concentrations were 1564 and 1316 mg/dL for the high-dose and low-dose groups, respectively. Mean IgG concentrations were very similar for both groups on postinfusion days 1, 4, 7, 14, 21, and 28. IgG concentrations remained above 300 mg/dL in seven of 10 infants in each group by day 21, and in six of the high-dose group and seven of the low-dose group by day 28. Mean elimination half-lives were 22.6 and 22.8 days in the high-dose and low-dose groups, respectively. These data provide a basis for assessment of potential efficacy of IGIV in the prevention of late-onset infection in VLBW neonates.


Community resilience to pandemics: An assessment framework developed based on the review of COVID-19 literature.
The COVID-19 outbreak in 2019 and the challenges it posed to communities around the world, demonstrated the necessity of enhancing the resilience of communities to pandemics. In this regard, assessment frameworks can play an essential role and guide resilience-building efforts. However, the lack of a comprehensive assessment framework has led to a focus on sectoral evaluation. This study aims to propose an integrated framework for assessing the pandemic resilience of communities. For this purpose, we rely on a systematic review of literature indexed in major academic databases. We have thoroughly analyzed a total number of 115 related documents to extract relevant criteria. Findings show that many criteria and factors affect community resilience to pandemics. By inductive content coding in MAXQDA software, we have categorized these criteria into five dimensions of Institutional, Social, Economic, Infrastructural, and Demographic. Good leadership and management, insurance and governmental support, planning and preparation, expertise and labor, and available equipment and technologies are the most important institutional criteria. Communication and collective identity, mutual support, public safety and protection, public awareness, and social justice are the influential social criteria. Economic sustainability and resource availability are criteria of economic resilience. Sufficiency of services, public spaces, housing tenure, and transportation system are the main criteria related to the built environment and infrastructural dimension. Finally, demographic resilience includes physical health, psychological well-being, life quality, and hygiene. Based on these criteria, this study develops an integrated evaluation framework that researchers can implement along with conventional assessment and ranking methods to determine the level of community resilience to pandemics.


1.5 °C pathways for the Global Industry Classification (GICS) sectors chemicals, aluminium, and steel.
To achieve the goals of the Paris Climate Agreement, decarbonization targets and benchmarks for specific industry sectors are required. This opens up a whole new research area for energy modelling because although decarbonization pathways have been developed for countries, regions, or communities, few have been developed for industry sectors. In this research, we document the development of energy scenarios for industry sectors classified under the Global Industry Classification Standard (GICS). A bottom-up energy demand analysis based on market projections for the chemical, aluminium, and steel industries forms the basis for scenario development, with the aim of completely decarbonizing the electricity and process heat supplies for these industries by 2050. We document the individual steps in the energy demand analyses based on industry-specific market projections and energy intensities. In the last step, the carbon budget is calculated. The complete decarbonization of the industries analysed seems possible based on the available technology. The online version contains supplementary material available at 10.1007/s42452-022-05004-0.


Activin in acute pancreatitis: Potential risk-stratifying marker and novel therapeutic target.
Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis.


Infection of different strains of mice with Lawsonia intracellularis derived from rabbit or porcine proliferative enteropathy.
This report describes intestinal lesions in five strains of mice infected orally with Lawsonia intracellularis-infected tissue homogenates from rabbits or pigs (RLI and PLI). BALB/cA, C3H/HeJ, C57BL/6J and ICR mice were susceptible to infection with RLI, whereas only C3H/HeJ, C57BL/6J and ICR strains were susceptible to PLI. In susceptible mice, crypt epithelial hyperplasia occurred in association with an inflammatory reaction, as in proliferative enteropathy (PE) in other species. The intestinal changes in the infected mice varied from mild to severe. Unlike rabbit or porcine PE, in which the changes are confined to the ileum, the lesions in mice were located in the caecum. Immunolabelling of L. intracellularis antigen was abundant in early infection when the epithelial hyperplasia was mild or absent. When the hyperplasia had become severe, however, immunolabelling was weak. For this reason, it is suggested that transitory infection of the epithelium induces epithelial hyperplasia. Genetic differences between mouse strains appeared to play an important role in the response to L. intracellularis infection. Moreover, the susceptibility of BALB/cA mice to RLI but not to PLI suggests that there are significant biological differences between L. intracellularis isolates from rabbit PE and porcine PE.


[Idiopathic ulnar nerve entrapment at the elbow: report of 20 cases].
We report a retrospective study of 20 patients treated for idiopathic cubital tunnel syndrome in a period of 10 years (2002-2011). The average age was 46 years. A profession at risk was present in the majority of cases. The treatment was surgical in all the cases. The indication for surgery was related to the importance of sensory-motor deficit, the long duration of symptoms, and the failure of conservative treatment. Two surgical techniques were used in this work: isolated neurolysis and neurolysis with anterior transposition of the ulnar nerve. There were no complications or recurrence of symptoms. After a mean follow-up of 12 months, our results evaluated thanks to the classification of Bishop were considered as excellent or good in 85% of cases and fair in 15% of cases. Prognosis factors were advanced age (more than 60 years), severity of the disease, and duration of symptoms (more than one year). The management of this affection must go through a better knowledge of the disease, for early diagnosis and appropriate treatment, only guarantees for a good result.


Non-invasive matrices in human biomonitoring: a review.
Humans and other living organisms are exposed to a variety of chemical pollutants that are released into the environment as a consequence of anthropogenic activities. Environmental pollutants are incorporated into the organism by different routes and can then be stored and distributed in different tissues, which leads to an internal concentration that can induce different alterations, adverse effects and/or diseases. Control measures should be taken to avoid these effects and human biomonitoring is a very useful tool that can contribute to this aim. Human biomonitoring uses different matrices to measure the target chemicals depending on the chemical, the amount of matrix necessary for the analysis and the detection limit (LOD) of the analytical technique. Blood is the ideal matrix for most chemicals due to its contact with the whole organism and its equilibrium with organs and tissues where chemicals are stored. However, it has an important disadvantage of being an invasive matrix. The development of new methodology and modern analytical techniques has allowed the use of other matrices that are less or non-invasive, such as saliva, urine, meconium, nails, hair, and semen or breast milk. The presence of a chemical in these matrices reflects an exposure, but correlations between levels in non-invasive matrices and blood must be established to ensure that these levels are related to the total body burden. The development of new biomarkers that are measurable in these matrices will improve non-invasive biomonitoring. This paper reviews studies that measure Cd, Pb, Hg, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides and phthalates in non-invasive matrices, the most used techniques for measurements and what alternative techniques are available.


Correlations between nucleotide frequencies and amino acid composition in 115 bacterial species.
We studied the correlations between amino acid composition and mononucleotide and dinucleotide frequencies in 115 bacterial genomes of varying G+C content. Observed amino acid frequencies were compared with those expected from the actual mononucleotide and dinucleotide frequencies. Both mononucleotide and dinucleotide frequencies correlate well with the amino acid frequency, with dinucleotide frequencies doing so better. Despite the strong correlations, some of the observed amino acid frequencies, in particular for Arg, Val, Asp, Glu, Ser, and Cys, were consistently different from predicted values in all genomes. We suggest that this variation from predicted values is a consequence of selection pressure at the level of amino acids, while the close correspondence to the predictions in residues such as Thr, Phe, Lys, and Asn arises only from mutation and selection pressure at the level of the nucleic acid sequences.


SCN- ions induce contraction of vascular muscle from male but not female rats.
It has been suggested that anions may play important roles in the regulation of membrane potentials, intracellular calcium and pH of vascular smooth muscle. It is, thus, possible that anions may be important in the sex-linked differences observed in contractile functions of vascular smooth muscle. With this in mind, we investigated the influence of alteration of the anionic environment, i.e., Cl- chloride ions, on the contractile activity of isolated aortic strips and rings from sexually mature male and female rats. After a few minutes of changing the incubation medium from normal chloride-containing Krebs-Ringer bicarbonate (NKRB) to a SCN- (thiocyanate) modified Krebs-Ringer bicarbonate solution (SCN-KRB; 118 mM SCN- substituted for 118 mM Cl-), resting tension increased dramatically, e.g., to about 85% of KCl maximum in males, but not in females. This increased resting tension could not be inhibited or attenuated by specific adrenergic, cholinergic, histaminergic, serotoninergic or cyclo-oxygenase inhibitors. Likewise use of a local anesthetic in high concentration (i.e., procaine HCl, 10(-3) M) also failed to inhibit or attenuate the SCN(-)-induced contractions. However, use of 5 mM EGTA, incubation in Ca2(+)-free SCN-KRB media or addition of [Mg2+]o (extracellular Mg2+) (2.4-14.4 mM) all resulted in inhibition of the enhancement of vascular tone in aortas from male animals, whereas addition of 5 mM CaNa2EDTA or removal of [Mg2+]o from SCN- KRB potentiated it. Use of intact aortic rings or aortic strips produced identical results in response to SCN-KRB and the experimental maneuvers. Our results suggest that the gender differences in the contractile responsiveness of vascular smooth muscle are probably related to anionic metabolism and distribution of Cl- ions across the vascular smooth muscle cell membranes. Chloride and other anions may mediate the diverse effects and actions of sex hormones on vascular tone, reactivity and calcium movement in vascular smooth muscle.


Medial Plantar Artery Flap for Wound Coverage of the Weight-Bearing Surface of the Heel.
Covering soft tissue defects of the heel is particularly challenging because of the highly specialized functional units unique to the plantar fat pad and the shear and compressive forces experienced in this area. The medial plantar artery fasciocutaneous flap provides the unique ability to restore both sensation and the functional units to the plantar heel by taking tissue similar to that which was lost and relocating it from a non-weight-bearing portion of the foot, while maintaining minimal host morbidity. This provides a lasting solution and may prevent future ulcerations from occurring.


Serum uric acid and multiple sclerosis.
Peroxynitrite (PN) has been implicated in multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis. Uric acid (UA) serum levels of MS patients, a natural scavenger of PN, were found lowered in some recent studies. The objective of our study was to correlate UA serum levels and several clinical parameters of MS. We also tried to investigate serum UA changes during treatment with immunomodulating or immunosuppressing drugs in the last 6 months. We measured UA serum levels in 190 patients with MS and 58 age and gender matched patients with inflammatory (IND) and non-inflammatory diseases (NIND) studied as control groups. UA levels were correlated with clinical parameters as type of the disease, duration, disability, magnetic resonance imaging (MRI) activity and female gender. In the overall MS group, patients were found to have significantly lower mean serum uric acid levels compared with the IND (p = 0.0029) and the NIND group (p < 0.0001). UA serum concentrations were not inversely correlated with duration of the disease (p = 0.87), with disability as assessed by Expanded Disability Status Scale (EDSS) score (p = 0.67) and MRI activity (p = 0.36). Treatment with immunomodulating or immunosuppressing drugs had no influence in UA levels (p = 0.85). Patients with Clinically Isolated Syndromes (CIS) were found to have significantly lower UA concentrations compared with IND and NIND patients (p = 0.009 and <0.001, respectively). Our findings suggest that lower serum UA levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide and the development of CNS inflammation and tissue damage may not have a direct effect to UA serum levels. They also provide support that the earlier increase of UA serum levels might be beneficial in the future treatment of MS.


A WISER way for simulating the performance of gratings.
Soft X-ray monochromators for synchrotron radiation sources have been continuously developed over the years, improving energy resolution and stability. Great effort has been made in improving the surface quality of the optics involved, reaching values permitting diffraction-limited images. Still, one problem has not been solved, nor fully understood, yet: groove placing errors. Nowadays, these are one of the major factors responsible for resolving the power reduction of diffraction-gratings-based X-ray monochromators. Despite decades of use of gratings, there is not yet a universally established method for predicting and simulating the effect of groove placing errors on monochromator performance. This is especially important in the new scenario of high-coherent X-ray sources, i.e. diffraction-limited storage rings and free-electron lasers. To address this problem, in this article an approach based on WISER (Wavefront propagatIon Simulation codE libRary) is presented. WISER is a physical optics simulation package, also available in the user-friendly Orange Synchrotron Radiation Suite - OASYS. Even though it was originally conceived to assess the focusing performance of X-ray mirrors in the presence of height defects, it perfectly simulates the performance of a periodic (or quasi-periodic) structure like a diffraction grating. In this article, the way to use WISER and its application to a specific case, e.g. the design of a monochromator for the upgrade of a beamline at the Advanced Light Source, are shown. A simple rule for estimating how well the grooves are placed on a grating, based on calculation of the Strehl ratio, is also presented.


Idiopathic Retroperitoneal Fibrosis With Intense Uptake of 68Ga-Fibroblast Activation Protein Inhibitor and 18F-FDG.
A 26-year-old man presented with a retroperitoneal mass with left urinary tract obstruction and hydronephrosis recently. 18F-FDG PET/CT showed the retroperitoneal mass had intense and homogeneous FDG avidity. In 68Ga-FAPI PET/CT, the retroperitoneal mass showed intense radioactivity without other organ involvements. The patient was finally diagnosed with idiopathic retroperitoneal fibrosis. After treatment, the follow-up CT showed significant decrease in size of the retroperitoneal mass. The current case indicated that idiopathic retroperitoneal fibrosis had active uptake of 68Ga-FAPI.


Identification of P2Y receptor subtypes in human muller glial cells by physiology, single cell RT-PCR, and immunohistochemistry.
Retinal Müller glial cells are known to express metabotropic P2Y receptors. The present study was conducted to identify certain subtypes of P2Y receptors in human Müller cells. The patch-clamp technique was used to measure increases of Ca(2+)-dependent K+ currents mediated by the activation of P2Y receptors in freshly isolated human Müller cells. Several P2 agonists were used. Subsequently, the cells were harvested into the patch pipette and a single cell RT-PCR was performed. Moreover, retinal tissue from organ donors was used for immunohistochemistry. The electrophysiological data were consistent with the expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes. RT-PCR revealed that mRNA for all these subtypes was present in Müller cells. However, the incidence of P2Y2 receptor mRNA was significantly lower than that of the other subtypes. Immunoreactivity for all four subtypes was found in retinal tissue, partly colocalized with immunoreactivity for vimentin. The presented data obtained by different techniques revealed that human Müller cells express P2Y1, P2Y2, P2Y4, and P2Y6 receptors. The specific roles of these receptor subtypes in retinal physiology and/or pathophysiology remain to be investigated in future studies.


Evaluation under real-life conditions of a lifestyle intervention for diabetes prevention developed by the municipal health services of Madrid, Spain.
The Diet, Physical Activity and Health (Alimentación, Actividad física y Salud, ALAS) program is an intervention implemented by the municipal health services of Madrid with the objective of reducing weight and preventing diabetes in high-risk population by improving diet and physical activity. The ALAS program combines individual visits with a 10-session group workshop that takes place over a 6-month period. This study evaluated the effectiveness of the ALAS intervention implemented under real-life conditions between 2016 and 2019. The intervention was evaluated with a pre- and post-intervention study with follow-up performed 6 and 12 months from the start of the program. The analyzed outcomes were a 5-10% reduction in the initial weight, body mass index (BMI), waist circumference and a change in glycemic status in prediabetic participants. Statistical models were adjusted by sociodemographic variables. The participants were recruited from municipal community health centers or referred by municipal occupational health services. Between 2016 and 2019, 1629 people participated in the program. At 6 months, 85% of the participants had lost weight; 43% had lost 5% or more of their initial weight, and 12% had lost 10% or more. Regarding BMI, 22.3% of participants who were initially obese were no longer obese, and 15.2% of the overweight participants achieved normal weight. A total of 35.1% of the prediabetic participants reverted to normoglycemic status. The intervention was found to be more effective for men, for those who completed the intervention and those who accessed the program through the occupational health route. Among the participants who accessed the intervention via the community, the intervention was more effective in those with a high educational level. The evaluation demonstrated the effectiveness of the ALAS program for reducing weight and the risk of developing Type 2 diabetes when applied under real-life conditions. The effectiveness of the intervention differed according to gender, access route and educational level of the participants.


The effect of propranolol on vascular responses to sympathetic nerve stimulation.
1. In an attempt to clarify the role of the sympathetic neurone in the antihypertensive action of propranolol, the effect of this drug on responses to lumbar sympathetic nerve stimulation has been studied in the perfused hind-limb of the dog. 2. No consistent reduction of maximal or submaximal responses to nerve stimulation was produced by propranolol (10 to 100 mug/kg). In contrast, potentiation of nerve-evoked response, as well as those to injected noradrenaline, usually occurred. Dexpropranolol (50 mug/kg) had no effect. 3. When neuronal uptake of noradrenaline was inhibited by desmethylimipramine or cacaine, no reduction in responses to sympathetic nerve stimulation was observed with propranolol. 4. No evidence was found, using alpha-adrenoceptor blocking drugs, that released transmitter stimulates beta-adrenoceptors in the blood vessels of the hind-limb. 5. No evidence has been found for the existence of an adrenergic neurone-blocking action of propranolol that might contribute to the antihypertensive activity in man.


Detection of point mutation in the tyrosinase gene of a Japanese albino patient by a direct sequencing of amplified DNA.
Enzymatic DNA amplification and direct DNA sequencing were used to detect a mutation in the tyrosinase gene of an albino patient. Single-base change could be detected by direct sequencing. This base change (G to A) is thought to result in an amino acid change (Arg to Gln) in tyrosinase of the patient.


Close relationship between certain nuclear and mitochondrial introns. Implications for the mechanism of RNA splicing.
We present the first indication of a direct relationship between a nuclear and a mitochondrial splicing system. The intron in the precursor of the large, nuclearly coded ribosomal RNA of two species of Tetrahymena possesses all the features of a class of fungal mitochondrial introns. Sequences conserved in mitochondrial introns of different fungal species are also found in the same order in these Tetrahymena nuclear introns, and the intron RNA can be folded to form a secondary structure similar to that proposed for mitochondrial introns by Davies et al. (1982). This "core" secondary structure brings the ends of the intron together. Furthermore, the first intron in the precursor of the large, nuclearly coded rRNA of Physarum polycephalum also has the characteristic conserved sequences and core RNA secondary structure. The limited sequence data available suggest that the intron in the large rRNA of chloroplasts in Chlamydomonas reinhardtii also resembles the mitochondrial introns. Tetrahymena large nuclear rRNA introns also have an internal sequence that can act as an adaptor by pairing with upstream and downstream exon sequences adjacent to the splice junctions to precisely align the splice junctions. These nuclear introns therefore fit the model of the role of intron RNA in the splicing process that was proposed by Davies et al. (1982), suggesting that the mechanisms of splicing may be very similar in these apparently diverse systems. It is therefore probable that the RNA secondary structures for which there is good evidence in the case of mitochondrial introns will be found to form the basis of active site structure and precise alignment in splicing and cyclization of the Tetrahymena intron "ribozyme".


Application of molecular biology techniques to the diagnosis of nontuberculous mycobacterial infections.
A total of 19,723 clinical samples were cultivated for the detection of mycobacteria from January 1995 to March 2001. The 203 strains of nontuberculous mycobacteria isolated were identified with the use of molecular techniques in combination with traditional biochemical tests. The molecular methods applied were PCR-restriction fragment length polymorphism analysis (PRA) alone or in combination with 16S rRNA and 16S-23S spacer sequencing. The patient records of those with specimens positive for mycobacteria were analysed to evaluate the clinical significance of the culture results. Twenty-five of the 124 patients analysed (20%) were regarded as having clinical mycobacteriosis. The main species associated with mycobacteriosis were: Mycobacterium avium (13 cases), M. intracellulare (2 cases), M. kansasii (5 cases), M. chelonae (2 cases), M. malmoense (1 case), M. scrofulaceum (1 case) and M. marinum (1 case). The use of PRA alone or in combination with gene sequencing provided valuable help in discerning mycobacteria at both the intra- and interspecies level, thus contributing to a faster and more efficient diagnosis and epidemiological follow-up.


Polyclonal and antigen-specific B-cell responses in patients with common variable immunodeficiency.
Antigen-specific antibody responses were investigated in 32 hypogammaglobulinemic patients with common variable immunodeficiency following in vitro sensitization of their peripheral blood lymphocyte cultures with sheep red blood-cell determinants. Anti-sheep red blood-cell antibody-secreting cells were quantitated in a hemolytic plaque assay. Amplification of T-cell help was achieved with the use of the T-cell mitogen concanavalin A or allogeneic irradiated T cells. Four patients groups, A through D, were identified. Group A was comprised of 10 patients whose cultured lymphocyte readily developed into antibody secreting cells. Cultures of 9 patients (Group B) responded suboptimally, but were enhanced following mitogen activation of autologous or exogenous T cells, and those of 7 patients (Group C) responded only when help was amplified. In 7 patients (Group D), no responses were elicited. On the simultaneous assessment of pokeweed mitogen-driven polyclonal generation of immunoglobulin-secreting cells, only 10 responders, all from groups A and B, were identified. Our observations indicate that the majority of patients with common variable immunodeficiency possesses B cells capable of producing antibody in vitro. The ability of some patients' B cells to respond only in the antigen-specific assay while failing to do so in pokeweed mitogen-stimulated cultures suggests that these two reactions are not identical in their activation pathways.


Anxiolytic properties of new chemical entity, 5TIO1.
2-[(2,6-dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile), 5TIO1, is a new 2-aminothiophene derivative with a promising pharmacological activity. The aim of this work was to evaluate the potential anxiolytic effect of 5TIO1 in animal models. In the elevated plus-maze test, 5TIO1 (0.1, 1.0 and 10.0 mg/kg, i.p) increased the time of permanence and the number of entries in the open arms. In the light/dark box test, 5TIO1 at dose of 0.1 mg/kg (i.p) also showed anxiolytic-like effect indicated by an increase in the time spent in the light box, similar to diazepam 2.0 mg/kg (i.p). 5TIO1 groups did not change locomotor and coordination activities in open field and rotarod tests, respectively, when compared to vehicle. Dose dependent process was not observed and the anxiolytic effects demonstrated were not completely reversed by flumazenil 25 mg/kg (i.p). Our results suggest that 5TIO1 can bind with other receptors, besides the benzodiazepine site of the GABA receptor in mouse brain.


The effectiveness of postoperative intervention in patients after rhinoplasty: a meta-analysis.
Rhinoplasty is the most common facial plastic surgical procedure, and the occurrence of periorbital edema and ecchymosis is normal after rhinoplasty. The goal of this study was to perform a systematic review with meta-analysis of the efficacy of postoperative care of edema and ecchymosis following rhinoplasty. Two authors independently searched the databases (PubMed, SCOPUS, Embase, Web of Science, and the Cochrane database) from inception to September 2016. We included studies that compared postoperative care methods (intervention groups) with no treatment (control group) where the outcomes of interest were edema, ecchymosis, and satisfaction rate of patients on postoperative days. Sufficient data for meta-analysis were retrieved for 11 trials with a total of 627 patients. Eyelid edema and ecchymosis during the first 7 days postoperatively were statistically decreased in the arnica administration groups versus the control group. Eyelid edema and ecchymosis during the first 24 h postoperatively were statistically decreased in the cold compression group versus the control group. The ratio of patient satisfaction was statistically higher in the tapping application group than in the control group. However, the analysis indicated that surgeons had a significant tendency to decrease intranasal packing. The administration of arnica, cold compression, and tape could reduce eyelid edema and ecchymosis. Intranasal packing was associated with more adverse effects in terms of postoperative ecchymosis compared to non-packing. However, additional trials with thorough research methodologies should be conducted to confirm the results of this study.


Correction to: Moderate Treadmill Exercise Protects Synaptic Plasticity of the Dentate Gyrus and Related Signaling Cascade in a Rat Model of Alzheimer's Disease.
The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper.


Assessment of dissolved mercury by diffusive gradients in thin films devices in abandoned ponds impacted by small scale gold mining.
In order to fulfil the Minamata Convention on Mercury, it is necessary to monitor the Hg contamination in freshwater ecosystems nearby artisanal and small scale gold mining (ASGM) areas. Since most of these ASGM communities are located in remote areas, a convenient method for sampling, preserving and transporting samples is needed. In this study we evaluated the feasibility of the diffusive gradient in thin-films (DGT) technique to detect and quantify the labile fraction of Hg and other metals (Pb, Cu, Zn, Cd, Ni, Mn and Cr) in a hard-to-reach gold mining district in the state of Chocó, Colombia. We deployed DGT at sampling sites along the Atrato river and abandoned mining ponds (AMPs) which were deserted in different periods since 1997 to 2019 (6-15 years). In average, the labile THg concentrations in AMPs (148.9 ± 43.2 ng L-1) were a 50% higher than in the river water (99.9 ± 37.4 ng L-1). In the ponds, no significant differences were found in labile Hg with respect abandonment period. Labile Ni (0.9-493.1), Mn (1.33-11.48), Cu (0.030-2.233), and Zn (0.67-10.29) (in μg L-1) were found in higher amounts than for the rest of metals. Labile concentrations of metals are related with their downstream proximity to gold mining activities, being higher in devices deployed close to ASGM sites. Moreover, this study demonstrates the feasibility of the DGT technique to sample, transport, storage, and preserve labile Hg from hard-to-reach ASGM areas.