[Characteristics of afferent innervation of the ischemic heart and the development of the pain syndrome].
Pain excitation during myocardial ischemia and its electrostimulation were investigated by recording evoked potential and iris movement in cats. It has been demonstrated that pain perception of the heart declines at an early stage of ischemia, but increases noticeably after prolonged and repeated ischemia.


A case report of unilateral cerebral vasculitis in adults: keep in mind Lyme neuroborreliosis.
Lyme neuroborreliosis (LNB), due to infection of the nervous system by the spirochete Borrelia burgdorferi, occurs in 15% of Lyme disease cases. However, neurovascular involvement is uncommon, especially recurrent stroke related to cerebral vasculitis in the absence of CSF pleocytosis. We report the case of a 58-year-old man without any medical history who exhibited recurrent strokes in the same vascular territory (left internal carotid). Multiple biological screening, neuroimaging methods, and cardiovascular examinations failed to provide a diagnosis and treatment that could have prevented recurrences. Finally, B. burgdorferi sensu lato serology testing in blood and cerebrospinal fluid enabled diagnosis of LNB, in relation to a cerebral vasculitis. The patient experienced no further stroke after four weeks of doxycycline treatment. B. burgdorferi central nervous system infection must be considered in case of unexplained recurrent and/or multiple strokes, especially if cerebral vasculitis is suspected or demonstrated on neuroimaging.


Complement Activation Dramatically Accelerates Blood Plasma Fouling On Antifouling Poly(2-hydroxyethyl methacrylate) Brush Surfaces.
Non-specific protein adsorption (fouling) triggers a number of deleterious events in the application of biomaterials. Antifouling polymer brushes successfully suppress fouling, however for some coatings an extremely high variability of fouling for different donors remains unexplained. The authors report that in the case of poly(2-hydroxyethyl methacrylate) (poly(HEMA)) this variability is due to the complement system activation that causes massive acceleration in the fouling kinetics of blood plasma. Using plasma from various donors, the fouling kinetics on poly(HEMA) is analyzed and correlated with proteins identified in the deposits on the surface and with the biochemical compositions of the plasma. The presence of complement components in fouling deposits and concentrations of C3a in different plasmas indicate that the alternative complement pathway plays a significant role in the fouling on poly(HEMA) through the "tick-over" mechanism of spontaneous C3 activation. The generated C3b binds to the poly(HEMA) surface and amplifies complement activation locally. Heat-inactivated plasma prevents accelerated fouling kinetics, confirming the central role of complement activation. The results highlight the need to take into account the variability between individuals when assessing interactions between biomaterials and blood plasma, as well as the importance of the mechanistic insight that can be gained from protein identification.


Efficient circular RNA engineering by end-to-end self-targeting and splicing reaction using Tetrahymena group I intron ribozyme.
Circular RNA (circRNA) has various advantages over linear mRNA that is gaining success as a new vaccine and therapeutic agent. Thus, circRNA and its engineering methods have attracted attention recently. In this study, we developed a new in vitro circRNA engineering method by end-to-end self-targeting and splicing (STS) reaction using Tetrahymena group I intron ribozyme. We found that only the P1 helix structure of the group I intron was enough to generate circRNA by STS reaction. The efficacy of circRNA generation by STS reaction was comparable to the method using a permuted intron-exon (PIE) reaction. However, an end-to-end STS reaction does not introduce any extraneous fragments, such as an intronic scar that can be generated by PIE reaction and might trigger unwanted innate immune responses in cells, into circRNA sequences. Moreover, generated circRNA was efficiently purified by ion pair-reversed phase high-pressure liquid chromatography and used for cell-based analysis. Of note, efficient protein expression and stability with least innate immune induction by the circRNA with coxsackievirus B3 IRES were observed in cells. In conclusion, our new in vitro circRNA strategy can effectively generate highly useful circRNAs in vitro as an alternative circRNA engineering method.


Therapeutic activities of naringenin on efavirenz-induced sleep-like disorder in the midbrain of white albino mice.
Efavirenz, has proven to be effective in suppressing human immunodeficiency virus (HIV) viral load; however, complaints of sleep disorders including hallucination, and insomnia have greatly contributed to non-adherence to antiretroviral therapy. This study aimed at investigating therapeutic activities of naringenin on efavirenz-induced sleep disorder. Sixty mice were divided into six groups of control, combination antiretroviral therapy (cART), efavirenz, naringenin, naringenin/efavirenz and naringenin/cART. Efavirenz, cART, and naringenin were administered orally and daily at 15 mg/kg, 24 mg/kg and 50 mg/kg, respectively for 28 days. Post neurobehavioral test, oxidative stress, histology and immunohistochemistry for dopamine were carried out after administration process. Efavirenz (P<0.0001) and cART (P<0.01) significantly increased immobility during open field (P<0.01), escape time in seconds (sec) in Morris water maze (P<0.001) and numbers of head-twitch response (HTR) (P<0.0001). Similarly, there was a significant increase in malondialdehyde (MDA) (P<0.0001) and decreased superoxide dismutase (SOD) (P<0.001) and reduced glutathione (GSH) (P<0.001); however, naringenin-treated groups potentiated anti-oxidant function by reducing oxidative stress (P<0.01). Histological evaluation demonstrated severe neurodegeneration, vacuolization and pyknosis in efavirenz and cART compared to naringenin groups. Dopaminergic neurons using immunohistochemial antibody (tyrosine hydroxylase) staining showed poor immunoreactivity in efavirenz and cART in contrast to naringenin groups. Efavirenz and cART have the potential of inducing sleep disorder possibly due to their capability to trigger inflammation and deplete dopamine level. However, naringenin has proven to be effective in ameliorating these damages.


Potent anorexic-like effects of RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane) in the rat: a comparison with other dopamine-receptor agonists.
Modification of food intake and motor activity was investigated following administration of amphetamine (AMP), apomorphine (APO) and three novel 2-aminoindanes (2-AI): 2-di-n-propylaminoindane (JPC-60-36), 2-di-n-propylamino-5,6-dimethoxyindane (JPC-211) and 2-di-n-propylamine-4,7-dimethoxyindane (RDS-127). These compounds demonstrated dose- and time-related inhibition of food intake in male rats which were habituated to eating 4 hr each day. The ranked potencies were as follows: RDS-127 greater than AMP = APO greater than JPC-60-36 and JPC-211 was inactive. 2-di-n-Propylamine-4,7-dimethoxyindane (RDS-127) did not increase motor activity in a dose range that Significantly inhibited food intake (66% of control intake with 0.08 mumol/kg). Food intake inhibition was blocked by pimozide, but not by propranolol or phentolamine. The anorectic-like actions of RDS-127 were long-lasting (greater than 4 hr) and RDS-127 was approximately 3-fold more potent than amphetamine or apomorphine in producing increased locomotor activity; the other 2-aminoindanes were less potent in producing hyperactivity. Hyperactivity responses were blocked by pimozide, but not by alpha-methyl-p-tyrosine. These results suggest that 2-aminoindanes may modify motor behaviors, at least in part, via direct stimulation of dopamine receptors. The structure-activity relationships of 2-aminoindanes on locomotor activity and inhibition of food intake are discussed.


Myoepithelioma-like Tumor of the Vulvar Region Presenting as a Nonmyxoid Spindle-Cell Neoplasm: A Potential Histologic Mimicker of Solitary Fibrous Tumor.
A new entity termed "myoepithelioma-like tumor of the vulvar region (MELTVR)" has been proposed as a rare mesenchymal neoplasm of the vulvar area. Histologically, MELTVRs are usually similar to soft tissue myoepitheliomas; however, they have a characteristic immunoprofile, including positivity for estrogen receptor and negativity for S100 protein, and loss of SMARCB1 expression. In this first known case report of MELTVR, the authors present a case of MELTVR that was histologically categorized in a nonmyxoid spindle-cell tumor group and resembled solitary fibrous tumor rather than soft tissue myoepithelioma.


The hippocampus and dopaminergic midbrain: old couple, new insights.
Humans have a natural ability to gain new insights by generalizing from previous experience. In this issue of Neuron, Shohamy and Wagner reveal how generalizations naturally emerge during associative learning through a partnership between putatively dopaminergic circuitry in the midbrain and the hippocampus.


Genetic aspects in myasthenia gravis. A family study of 264 Finnish patients.
The prevalence of myasthenia gravis (MG) in Finland was 264 patients per 4.7 mil. inhabitants or 0.006 per cent. Of these 264 patients 19 (17 females and 2 males) were familial cases from eight families. MG occurred in 11 siblings, in two mothers and their child, and in six cousins. MG was not found in three or more successive generations. The familial MG resembled the non-familial disease. No concordance of MG among five sets of twins was found. The birth localities of gradparents seemed to have a slight tendency for accumulation, but no definite clusters were formed. Consanguinity between parents was found in seven of 192 families. An increased frequency of collagen or thyroid diseases was found both in patients and parents, but they were not specially accumulated to the relatives of familial myasthenics. Neither autosomal nor sex-linked, dominant or recessive, nor some other uniform mode of inheritance in MG could be confirmed. Some genetical predisposition to MG seems to exist, but it may be common to autoimmunity as a whole.


Spinal motion preservation surgery: indications and applications.
Fusion is one of the most commonly performed spinal procedures, indicated for a wide range of spinal problems. Elimination of motion though results in accelerated degeneration of the adjacent level, known as adjacent level disease. Motion preservation surgical methods were developed in order to overcome this complication. These methods include total disc replacement, laminoplasty, interspinous implants and dynamic posterior stabilization systems. The initial enthusiasm about these methods was followed by certain concerns about their clinical usefulness and their results. The main indications for total disc replacement are degenerative disc disease, but the numerous contraindications for this method make it difficult to find the right candidate. Application of interspinous implants has shown good results in patients with spinal stenosis, but a more precise definition is needed regarding the severity of spinal stenosis up to which these implants can be used. Laminoplasty has several advantages and less complications compared to fusion and laminectomy in patients with cervical myelopathy/radiculopathy. Dynamic posterior stabilization could replace conventional fusion in certain cases, but also in this case the results are successful only in mild to moderate cases.


The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs.
Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability. In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3- to 4-month-old db/db mouse caudal spines. We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild-type discs. Diabetic discs also contained ill-defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary. These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild-type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.


MHC-II ubiquitination.
Ubiquitinated protein detection is often troublesome since in most cases this modification reduces the half-life of targeted proteins, inducing their degradation. Furthermore, ubiquitination is reversible thanks to the action of highly specific deubiquitinases present in all eukaryotic cells. MHC molecules ubiquitination has been demonstrated to be a key event in the regulation of the potent immunostimulatory properties of activated human dendritic cells.


Deposition of Fe on graphite felt by thermal decomposition of Fe(CO)5 for effective cathodic preparation of microbial fuel cells.
In this paper, an efficient and cost-effective method to prepare cathodes for microbial fuel cells (MFCs) was developed. Fe(CO)5 was decomposed and Fe was deposited on graphite felts for cathodic preparation. The unmodified, Pt modified and Fe modified graphite felts were utilized as cathodes in MFCs and power generation was compared. The maximum power density of MFCs with unmodified, Pt modified and Fe modified cathodes were respectively 288, 866 and 925 mW/m3. The internal resistance of MFCs with unmodified, Pt modified and Fe modified cathodes were respectively 505, 384 and 278Ω. The results of multiple analyses confirmed that Fe on cathode was Fe2O3 and FeOOH and Fe(III) oxides as cathodic catalysts improved the electrochemical activity and promoted power generation. The greatest advantage of new method for cathodic preparation was the replacing manual brushing and Nafion solution and decreasing the cost.


A class of high performance metal-free oxygen reduction electrocatalysts based on cheap carbon blacks.
For the goal of practical industrial development of fuel cells, cheap, sustainable and high performance electrocatalysts for oxygen reduction reactions (ORR) which rival those based on platinum (Pt) and other rare materials are highly desirable. In this work, we report a class of cheap and high-performance metal-free oxygen reduction electrocatalysts obtained by co-doping carbon blacks with nitrogen and fluorine (CB-NF).The CB-NF electrocatalysts are highly active and exhibit long-term operation stability and tolerance to poisons during oxygen reduction process in alkaline medium. The alkaline direct methanol fuel cell with the best CB-NF as cathode (3 mg/cm(2)) outperforms the one with commercial platinum-based cathode (3 mg Pt/cm(2)). To the best of our knowledge, these are among the most efficient non-Pt based electrocatalysts. Since carbon blacks are 10,000 times cheaper than Pt, these CB-NF electrocatalysts possess the best price/performance ratio for ORR, and are the most promising alternatives to Pt-based ones to date.


Is a two-month healing period long enough to achieve osseointegration? A prospective clinical cohort study.
The aim of this study was to evaluate the effectiveness of loading at 2 months after the surgical placement of implants. A tapered implant was used. Implant stability was determined using resonance frequency analysis at implant insertion (T0; primary stability), after 2 months (T1), and at the 6-month follow-up (T2). Descriptive statistics and the t-test were used. Significance was at P ≤ 0.05. A total of 268 implants were inserted in 142 patients. No patient dropped out and no implant had failed at the 6-month follow-up. The mean implant stability quotient value (ISQ) increased over time, with a statistically non-significant difference for T0 vs. T1 (P = 0.08) and a statistically significant difference for T1 vs. T2 (P = 0.0018) and T0 vs. T2 (P = 0.000). Only 99 implants, characterized by an extremely high mean primary stability value (80.34), did not have a recorded increase in ISQ at T1. A 2-month healing period allowed the implant to achieve secondary stability, confirming the effectiveness of the loading protocol at 2 months.


Self-assembly biochar colloids mycelial pellet for heavy metal removal from aqueous solution.
To effectively improve the heavy metal removal efficiency and stability of biomass adsorbents, a novel biochar colloids-mycelial pellets (BC-MP) composite was prepared via a biological assembly method. BC-MP was successfully produced with increased surface area and multisorption sites by physical adsorption, electrostatic interaction and hydrogen-bond formation between BC and extracellular polymers on MP. To investigate the performance and mechanisms of heavy metal adsorption by BC-MP, batch experiments were conducted with cadmium (Cd (II)) as the model pollutant. Results showed that BC-MP had higher removal efficiency (57.66%) compared to BC (5.45%) and MP (38.45%), respectively, due to the synergistic effect. The maximum adsorption capacity of Cd (II) on BC-MP was 102.04 mg/g based on Langmuir isotherm model. Adsorption kinetics analysis indicated that chemical sorption was the key factor controlling the adsorption of Cd (II) onto BC-MP. Multiple characterization tests revealed that the main mechanisms of the adsorption process were surface complexation, cation exchange and precipitation. The BC-MP composite showed excellent heavy metal removal efficiency with long-term adsorption stability, suggesting its potential as a promising biosorbent for heavy metal removal from industrial wastewater.


Direct visualization of coronary sinus ostium and branches with a flexible steerable fiberoptic infrared endoscope.
Placement of electrophysiology catheters and pacing leads in the coronary sinus is challenging in some patients, particularly those with dilated cardiomyopathy. We hypothesized that cannulation of the coronary sinus and its branches can be facilitated by direct visualization. This study reports our experience with navigation into and within the coronary sinus in a closed-chest animal preparation, using a flexible steerable fiberoptic infrared endoscope that allows visualization through flowing blood. The purpose of this study was to assess the feasibility of direct visualization of endocardial structures through infrared endoscopy. Internal jugular venous access was obtained in 10 healthy mongrel dogs (weight 35-45 kg). The infrared endoscope (2900 fiber imaging bundle, wavelength 1,620 nm, frame rate 10-30/s, 320 x 256 pixels) was advanced to the coronary sinus ostium and branches by direct visualization of anatomic landmarks, such as the tricuspid valve and inferior vena cava. Localization was confirmed by fluoroscopy, contrast injection, and pathologic examination. Structures such as the tricuspid valve and inferior vena cava were visualized at distances of 1 to 2 cm, allowing successful coronary sinus identification and engagement in all 10 dogs. Coronary sinus branch images closely resembled pathologic findings. Direct visualization of the coronary sinus ostium and branches is possible through infrared endoscopy. This technique likely will facilitate coronary sinus engagement and navigation for pacing lead and catheter placement.


Three-dimensional unilateral method for the bilateral measurement of condylar movements.
Using a unilateral optoelectronic tracking system (JAWS-3D), a method was developed for the simultaneous measurement of the three-dimensional kinematics of both ipsilateral and contralateral human condyles, the latter being represented by virtual points beyond the field of vision of the camera system during the actual recording. The method leaves the subject's head unrestrained while measuring the movements of two sets of three light-emitting diodes rigidly attached to the upper and lower teeth. The Tait-Bryan angles method was employed for calculating the jaw rotations in three dimensions. Movements were referenced to both a skeletal and a dental coordinate system. The worst-case static measurement errors were 0.24 mm for a 20 mm translation and 0.71 degrees for a 35 degrees rotation. The mean dynamic measurement errors were 9.73 microns s-1 at a constant linear velocity of 200 microns s-1 and 0.73 degrees s-1 at a constant angular velocity of 149 degrees s-1. The utility of the method was demonstrated in a subject who was asked to open and close the mouth in a cyclic fashion.


Outcomes of infants born at borderline viability (23-25 weeks gestation) who received cardiopulmonary resuscitation at birth.
The practice of providing advanced resuscitative measures to infants born at borderline viability (23-25+6 weeks gestation) varies among clinicians due to perception of futility. The aim of our study was to compare mortality and major morbidities in infants born at borderline viability who did not receive cardiopulmonary resuscitation (CPR) in the delivery room (No DR-CPR) as compared to those who did (DR-CPR). A retrospective analysis of prospectively collected data of infants born between 23 and 25+6 weeks gestation who were resuscitated at birth at the study centre or admitted to neonatal intensive care unit from peripheral hospitals, over 8 years (2007-2014). The primary outcome was survival, free of disability at 2 years corrected age and secondary outcomes were survival at discharge and neonatal morbidities. Of 123 infants in the study cohort, 21 received DR-CPR. In unadjusted analysis, there was increased mortality rate in the DR-CPR group which was statistically insignificant (26.5 vs. 42.9%, P = 0.15). After adjustment for potential confounders, there was no significant difference in the mortality rate with odds ratio of 1.10 (confidence interval: 0.34-3.53, P = 0.86). Among infants who received DR-CPR for >2 min, the mortality rate was significantly higher (25.2 vs. 56.3%, P = 0.01). Survival free of disability was similar in two groups (50.9 vs. 47.6%, P = 0.78). Among infants born at borderline viability, the vast majority of infants did not receive CPR and, if CPR was prolonged for >2 min, mortality was increased. Among survivors of the small DR-CPR group, early neurodevelopmental outcomes were comparable to the No DR-CPR group.


Action spectrum of psbA gene transcription is similar to that of photoinhibition in Synechocystis sp. PCC 6803.
The photosystem II (PSII) reaction center protein D1 undergoes rapid light-dependent turnover, which is caused by photoinhibition. To identify the photoreceptor(s) involved in the light-dependent expression of the psbA gene encoding the D1 protein, we determined the action spectra of psbA transcription, PSII activity, photosynthesis and photoinhibition in Synechocystis sp. PCC 6803. In accordance with its phycobilisome antenna, PSII showed the highest activity in the spectral region from yellow to red and only low activity in the ultraviolet-A (UV-A) to green region. Photoinhibition, in turn, was fastest in UV-A to violet light and a minor peak was found in the orange region. The action spectrum of psbA transcription resembled closely that of photoinhibition, suggesting that photoinhibition creates a signal for up-regulation of the psbA gene.


Relevance of the perioperative edema index measured by bioelectrical impedance analysis for prediction of cardiovascular disease in living-donor kidney transplantation.
Perioperative management of fluid status during kidney transplantation is important, because volume overload can increase the risk of cardiovascular disease in recipients. The edema index calculated by bioelectrical impedance analysis is commonly used to correctly evaluate fluid status. We evaluated the relevance of the edema index for cardiovascular disease in kidney transplant recipients, and searched for predictors of high edema index in the perioperative period during kidney transplantation. A total of 88 recipients were included in this study. The group in which the edema index at discharge was >0.40 was termed as the "high edema index group", and that with ≤0.40 was termed as the "low edema index group". We assessed cardiovascular disease-free survival and cardiovascular disease-specific survival in the two groups by using Cox proportional regression analyses adjusted by inverse probability of treatment weighting analysis. The patients' background and conventional cardiovascular disease risk factors were assessed to estimate predictors for a high edema index. A high edema index was significantly associated with short cardiovascular disease-free survival after kidney transplantation (hazard ratio 10.01; P < 0.05) in the inverse probability of treatment weighting model. There were no significant differences in the cardiovascular disease-specific survival. In multivariate logistic regression analyses, non-pre-emptive kidney transplantation and dyslipidemia were significant independent predictors of a high edema index (odds ratio 3.59, P < 0.05 and odds ratio 4.05, P < 0.01, respectively). A high edema index is associated with the incidence of cardiovascular disease. Overhydration should be especially avoided in recipients with these factors, and their fluid volume should be carefully managed.


Evaluation of three occlusal examination methods used to record tooth contacts in lateral excursive movements.
Accurate and repeatable methods for recording tooth contacts are required for the clinical management of problems related to occlusion. A thorough understanding of the materials and procedures used in these methods is important to achieve desirable results in the treatment of such problems. This study compared three occlusal examination methods to determine the influence of materials and procedures on the number of tooth contacts recorded. Tooth contacts were analyzed at two lateral mandibular positions with each method. It was found that the method that uses black silicone recorded the highest number of tooth contacts. Thus the most frequent type of occlusal pattern observed was full-balanced occlusion. This study suggested that the disparities of results reported in literature on occlusal contact patterns could be the result of the different materials and methods used for occlusal registration.


Approaches for on-line coupling of extraction and chromatography.
This review provides an overview of the approaches available in order to perform on-line coupling of various extraction techniques with liquid and gas chromatography, for the analysis of semivolatile and nonvolatile analytes in liquid and solid samples. The main focus is on the instrumental set-up of these techniques. Selected real applications are described by way of illustration. The extraction methods suitable for on-line coupling covered in this review are: liquid-liquid extraction, solid-phase extraction, membrane-based techniques, pressurised liquid extraction, supercritical fluid extraction, and microwave- and sonication-assisted extractions. The following systems are not covered in this review: on-line coupled solid-phase extraction-liquid chromatography, purge-and-trap-GC, and membrane extraction with a sorbent interface-GC.


Connected pretopology in recombination space.
Topological features evolved from genetic operators in the recombination space play a crucial role in the course of evolution. Different crossover models generated in a recombination space can be structured by pretopological space. This paper deals with several types of connectedness properties of recombination space in three different cases of unequal crossover of recombination space structured as pretopology. It is shown that unrestricted unequal crossover is one-sidedly connected and consequently hyper-connected, apo-connected and connected as well. Restricted unequal crossover is hyper-connected and connected. Unequal sister chromatid exchange is connected.


PARP inhibitors and overall survival in ovarian cancer, reevaluation advised in all settings.
PARP inhibitors in ovarian cancer have been a breakthrough therapy of the past decade, driven by positive trial results, and supported by an original pharmacological rationale. However, with mature data, detrimental survival results led to the withdrawals, in 2022, of all approved PARP inhibitors in the most advanced settings' indication (as monotherapy in third or subsequent lines) by the US Food and Drug Administration (FDA). Two other indications, as maintenance after relapse, were also restricted. In this work, based on pooled meta-analysis in each setting, we question a unique situation in oncology: a survival benefit is seen in front-line settings, with, at the same time, a survival decrement in later lines. Either this original feature is explained by the unique biological action of PARP inhibitors-through synthetic lethality-in patients with ovarian cancer and homologous repair deficiency. Another explanation may be trial design: decrement in later lines could partly explain why beneficial results were seen in early settings, simply by avoiding late exposure to PARP inhibitors in the experimental arm in those trials. High crossover rates seen in some trials further support this alternate hypothesis. We contend our analysis and recent survival results of PARP inhibitors warrant a whole reassessment of the place of these compounds in the landscape of ovarian cancer treatments.


Development of the RTI item bank on risk of bias and precision of observational studies.
To create a practical and validated item bank for evaluating the risk of bias and precision of observational studies of interventions or exposures included in systematic evidence reviews. The item bank, developed at RTI International, was created based on 1,492 questions included in earlier instruments, organized by the quality domains identified by Deeks et al. Items were eliminated and refined through face validity, cognitive, content validity, and interrater reliability testing. The resulting item bank consisting of 29 questions for evaluating the risk of bias and precision of observational studies of interventions or exposures (1) captures all of the domains critical for evaluating this type of research, (2) is comprehensive and can be easily lifted "off the shelf" by different researchers, (3) can be adapted to different topic areas and study types (e.g., cohort, case-control, cross-sectional, and case series studies), and (4) provides sufficient instruction to apply the tool to varied topics. One bank of items, with specific instructions for focusing abstractor evaluations, can be created to judge the risk of bias and precision of the variety of observational studies that may be used in systematic and comparative effectiveness reviews.


Anticancer and immunostimulatory activity by conjugate of paclitaxel and non-toxic derivative of LPS for combined chemo-immunotherapy.
Cancer is a multifactorial syndrome; hence, multidimensional therapy with a chemo-immunotherapeutic conjugate could be more effective in curing the disease. We used SP-LPS, a bio-polymer having potent immunostimulatory activity, for conjugation with paclitaxel to make a chemo-immunotherapeutic conjugate. Its physicochemical characterization was done by HPLC, NMR and IR spectra. Stability was measured at different pH, temperature and in tissue homogenates. Chemotherapeutic and immunostimulatory activity was evaluated in vitro and also in tumor microenvironment. The conjugate self assembled into nanoparticulate structure, probably due to micelle formation. Stability was pH and temperature dependent. The conjugate exhibited chemotherapeutic and immunotherapeutic activity in vitro. In vivo antitumor activity was significantly higher and a higher percentage of activated immune cells were found in the tumor microenvironment of the conjugate-treated mice as compared to Taxol®-treated group. This conjugate is a potential chemo-immunotherapeutic compound for the treatment of cancer with advantages over present day chemotherapy with Taxol in terms of higher anticancer activity, less toxicity and ease of delivery.


Nrf2 activation mediates the protection of mouse Sertoli Cells damage under acute heat stress conditions.
Heat stress is known to negatively impact the reproductive process of livestock, which inevitably leads to a decline in animal fertility. Nuclear factor E2-related factor 2 (Nrf2) is an inducible transcription factor, which is essential for maintaining redox signal transmission against oxidative stress. However, there is no reliable research on the response mechanism of Sertoli Cells (SCs) against heat stress and the activation of Nrf2 when SCs are exposed to heat stress. Here, we used primary mouse SCs and SCs line TM4, along with Nrf2 specific inhibitor to determine the reaction mechanism of SCs to maintain intracellular redox homeostasis and self-survival by activating Nrf2. We found that acute heat stress only affected the vitality of SCs and the expression of functional molecules (tight junction-associated proteins and lactate dehydrogenase A [LDHA]) but did not cause cell apoptosis. When Nrf2 was inhibited, more cell death occurred in TM4 cells post heat stress treatment, along with a greater decrease in cell viability and a significant increase in intracellular ROS levels. Our study clarified for the first time the protective effect of Nrf2 activation on heat stress-induced SCs damage. It explained the possible reasons or mechanisms involved in the survival of SCs, the critical protective cells in the testis, which were not affected by heat stress. This study further improved the response mechanism of SCs in the reproductive injury caused by a high-temperature environment.


Glycerol affects the quantification of aspartate and glutamate in acid-hydrolyzed proteins.
Glycerol is widely used in protein isolation pathways to improve folding and solubility of the proteins of interest. Amino acid composition analysis of protein samples hydrolyzed in the presence of glycerol resulted in underestimation of aspartate and glutamate, when compared to hydrolysis in the absence of glycerol. Quantification of free asparagine, aspartic acid, glutamine and glutamic acid hydrolyzed with hydrochloric acid or methanesulfonic acid in the presence of glycerol resulted in poor recoveries of aspartate and glutamate (between 6 and 66%). Gas chromatography-mass spectrometry analysis of the hydrolyzates revealed, as expected, the presence of esterification products. The esters were formed between the primary and secondary hydroxyl groups of the glycerol and both carboxyl groups of the amino acids. Protein samples intended for compositional analysis should be free of glycerol.


Neurogenic pulmonary edema in palliative care.
Neurogenic pulmonary edema may be a complication of the terminal phase of cerebral tumors. Clinically, it is likely to be considered the "death rattle" and is likewise very distressing to attending relatives. Positional change tends to aggravate neurogenic pulmonary edema but not the "death rattle." Its occurrence may be an indication for sedation for the intractable distress of the dying patient.


Human Embryo Editing: Opportunities and Importance of Transnational Cooperation.
A recent National Academies report articulates a path forward for research, ethics, and governance of clinical applications involving genome editing. In light of recent human embryo editing developments, scientists and stakeholders from all nations should cooperate to take advantage of this historic opportunity for medicine and also basic human biology.


The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.
PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility.


A novel(ty) perspective of fear bias.
Grossmann presents an exciting and interesting theory on the function of fearfulness. In this commentary it is argued that fearfulness may be a byproduct of a larger executive functioning network and these early regulatory skills considered more broadly may be key building blocks for later cooperative behaviors.


Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer.
mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8, P<0.001). For active MMP-2, but not for MMP-9, a significant negative partial correlation (R(p)=-0.440, P<0.001) for RECK was found in tumor tissue, which was confirmed by linear regression analysis. In exploratory survival analyses we found that in patients with localized disease the RECK level in normal or tumor tissue had a significant (P=0.017) association with overall survival.


Does screening for cervical cancer affect incidence and mortality trends? The Belgian experience.
Age-specific mortality and morbidity for cervical cancer from 1956 to 1985 in Belgium show a slight decline for women aged 35-54, and a constant rate for other age groups. Population screening as done in Belgium between 1965 and 1980 failed to have any impact on these trends, which could be due to poor organization of screening or changing risk factors for cervical cancer in the population.


Hypercatabolism of the third component of complement (C3) in angioimmunoblastic lymphadenopathy.
A metabolic study with radioactively labelled C3 has been performed in a patient with angioimmunoblastic lymphadenopathy (AILD). The labelled protein was metabolized at a faster rate in the patient than in normal individuals. This indicates that the humoral immune system may be of pathogenetic significance in the AILD syndrome.


Dermatologic tumors (excluding sarcoids).
Cutaneous neoplasia represents a clinical problem with which veterinarians are commonly challenged. This article addresses equine cutaneous squamous cell carcinoma, squamous cell papilloma, melanoma, mastocytosis, and lymphosarcoma. Current concepts regarding the origin, pathogenesis, diagnosis and treatment of each neoplasm is emphasized.


Posterior ankle impingement syndrome caused by malunion of joint depressed type calcaneal fracture.
Late complications after calcaneal fracture usually resulted in lateral heel pain. Malunion of joint depressed type calcaneal fracture can result in posterior ankle impingement pain. This is caused by the posterior calcaneal bone spike formed just behind the posterior calcaneal facet. We describe a technique to resect the offending posterior calcaneal bone spike to relieve the posterior ankle impingement pain.


Functional Change from Five to Fifteen Years after Traumatic Brain Injury.
Few studies have assessed the long-term functional outcomes of traumatic brain injury (TBI) in large, well-characterized samples. Using the Traumatic Brain Injury Model Systems cohort, this study assessed the maintenance of independence between years 5 and 15 post-injury and risk factors for decline. The study sample included 1381 persons with TBI who received inpatient rehabilitation, survived to 15 years post-injury, and were available for data collection at 5 or 10 years and 15 years post-injury. The Functional Independence Measure (FIM) and Disability Rating Scale (DRS) were used to measure functional outcomes. The majority of participants had no changes during the 10-year time frame. For FIM, only 4.4% showed decline in Self-Care, 4.9% declined in Mobility, and 5.9% declined in Cognition. Overall, 10.4% showed decline in one or more FIM subscales. Decline was detected by DRS Level of Function (24% with >1-point change) and Employability (6% with >1-point change). Predictors of decline factors across all measures were age >25 years and, across most measures, having less than or equal to a high school education. Additional predictors of FIM decline included male sex (FIM Mobility and Self-Care) and longer rehabilitation length of stay (FIM Mobility and Cognition). In contrast to studies reporting change in the first 5 years post-TBI inpatient rehabilitation, a majority of those who survive to 15 years do not experience functional decline. Aging and cognitive reserve appear to be more important drivers of loss of function than original severity of the injury. Interventions to identify those at risk for decline may be needed to maintain or enhance functional status as persons age with a TBI.


Surgical management of a primary pulmonary artery sarcoma: A case report.
Pulmonary artery (PA) sarcoma is a rare tumor with an overall poor prognosis. It can often be misdiagnosed due to its nonspecific presentation and its similitude to pulmonary embolism on imaging. We, herein, describe the case of a 60-year-old male with a primary PA sarcoma for which a surgical approach was undertaken. Due to the low incidence of PA and therefore the absence of clear guidelines on the management of this disease, we also present a succinct literature review on the subject.


Lab-on-a-chip technologies for stem cell analysis.
The combination of microfabrication-based technologies with cell biology has laid the foundation for the development of advanced in vitro diagnostic systems capable of analyzing cell cultures under physiologically relevant conditions. In the present review, we address recent lab-on-a-chip developments for stem cell analysis. We highlight in particular the tangible advantages of microfluidic devices to overcome most of the challenges associated with stem cell identification, expansion and differentiation, with the greatest advantage being that lab-on-a-chip technology allows for the precise regulation of culturing conditions, while simultaneously monitoring relevant parameters using embedded sensory systems. State-of-the-art lab-on-a-chip platforms for in vitro assessment of stem cell cultures are presented and their potential future applications discussed.


Magnetic properties and heavy metal contents of automobile emission particulates.
Measurements of the magnetic properties and total contents of Cu, Cd, Pb and Fe in 30 automobile emission particulate samples indicated the presence of magnetic particles in them. The values of frequency dependent susceptibility (chi(fd)) showed the absence of superparamagnetic (SP) grains in the samples. The IRM(20 mT) (isothermal remanent magnetization at 20 mT) being linearly proportional to SIRM (saturation isothermal remanent magnetization) (R(2)=0.901), suggested that ferrimagnetic minerals were responsible for the magnetic properties of automobile emission particulates. The average contents of Cu, Cd, Pb and Fe in automobile emission particulates were 95.83, 22.14, 30.58 and 34727.31 mg/kg, respectively. Significant positive correlations exist between the magnetic parameters and the contents of Pb, Cu and Fe. The magnetic parameters of automobile emission particulates reflecting concentration of magnetic particles increased linearly with increase of Pb and Cu content, showed that the magnetic measurement could be used as a preliminary index for detection of Pb and Cu pollution.


Somatic mutations of the PPP2R1B candidate tumor suppressor gene at chromosome 11q23 are infrequent in ovarian carcinomas.
Previous studies have demonstrated frequent allelic losses of distal chromosome 11q in ovarian carcinomas. The tumor suppressor gene(s) presumably targeted by these losses have not yet been identified. PPP2R1B is a candidate tumor suppressor gene at 11q23 that has recently been shown to be mutated in a subset of colorectal and lung cancers. We evaluated 5 ovarian carcinoma cell lines and 27 primary ovarian carcinomas for allelic losses of 11q23 and for mutations in the open reading frame of PPP2R1B. We also evaluated the primary tumors for allelic losses at 17p13, another chromosomal region frequently affected by losses of heterozygosity (LOH) in ovarian cancers. 11q23 and 17p13 allelic losses were identified in 25% and 74% of the carcinomas, respectively. No mutations within PPP2R1B coding sequences were found. These findings indicate that mutations of the PPP2R1B gene are infrequent in ovarian cancer and that deletions affecting the distal portion of chromosome 11q in ovarian cancer likely target inactivation of other genes.


Highly sensitive and selective photoelectrochemical aptasensing of di-2-ethylhexyl phthalate based on graphene quantum dots decorated TiO2 nanotube arrays.
A photoelectrochemical (PEC) sensing platform for di-2-ethylhexyl phthalate (DEHP) was constructed using graphene quantum dots decorated TiO2 nanotube arrays (GQDs-decorated TiO2 NTs) as the transducer species and the anti-DEHP aptamer as the biological recognition element. GQDs were synthesized using the alkali-mediated hydrothermal method, and then anchored onto the TiO2 NTs uniformly and intimately via pronounced electrostatic interaction. Coupling GQDs with TiO2 NTs not only enhanced visible-light absorption, but promoted charge separation and transportation, exhibiting excellent photocurrent response, and PEC activity. Various means were conducted to explore morphologies, optical, structural and PEC properties of the materials. As an identification unit, the anti-DEHP aptamer molecules were immobilized on GQDs-decorated TiO2 NTs using a cross-linking coupling method. The developed PEC sensing platform exhibits excellent sensing behavior for DEHP, and provides a low detection limit of 0.1 ng/L, high selectivity and stability. Meanwhile, its application in real environmental samples was evaluated and satisfying results were achieved. Thus, the established sensing platform provides a promising tool to detect DEHP in the environment.


Reduction in portal vein blood flow by somatostatin.
Intravenous somatostatin boluses produced striking diminution in portal vein blood flow in dogs (maximally 40--55%). This effect was of rapid onset, without observable changes in hepatic artery flow, systemic blood pressure, pulse or central venous pressure. The duration of action was short, but could be sustained by continuous intravenous infusion. These observations are consistent with an endocrine role of somatostatin in the regulation of nutrient balance.


Intramyocardial hematoma with epicardial rupture following percutaneous coronary intervention.
Intramyocardial (or subepicardial) hematomas are uncommon conditions that occur mostly after myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass surgery, cardiac surgery, or chest trauma. Coronary perforation is a rare complication of PCI and the subset of patients developing an intramyocardial hematoma, usually considered a catastrophic event, is even rarer. We describe here the case of 63-year-old man in whom an intramyocardial hematoma with epicardial rupture occurred after PCI. The patient was treated conservatively with a successful outcome.


Effects of aspirin and clopidogrel on neural stem cells.
Cerebral infarction causes severe morbidity and mortality. Most patients with cerebral infarction should take antiplatelet drugs daily, so the effects of those drugs on the regeneration of the brain need to be investigated. Aspirin and clopidogrel are the most widely used antiplatelet drugs for the prevention of ischemic stroke. We investigated the effects of aspirin and clopidogrel on neural stem cells (NSCs). NSCs were dissociated from fetal rat cortex and cultured with basic fibroblast growth factor and N2 medium. To measure the effects of aspirin and clopidogrel on NSCs, NSCs were treated with several concentrations of aspirin, clopidogrel bisulfate, and clopidogrel resinate for 24 h. After the treatment, we measured cell viability by cell counting kit-8, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, trypan blue staining, flow cytometry, and lactate dehydrogenase assay. To evaluate their effects on NSC proliferation, we performed BrdU cell proliferation assay and colony-forming unit assay. We compared the intracellular protein level in the NSCs treated with aspirin and two types of clopidogrel, by proteomics analysis. Various viability tests showed that clopidogrel resinate and clopidogrel bisulfate did not affect the viability and proliferation of NSCs whereas aspirin decreased them even at low concentrations which are clinically relevant. Moreover, through the proteomics, it was confirmed that the toxicity of aspirin to NSCs might be associated with the alteration of several intracellular proteins. Taken together, these results suggest that clopidogrel resinate and clopidogrel bisulfate are safe but aspirin could be toxic to NSCs. Therefore, when these antiplatelet agents are prescribed over the long-term, the finding that aspirin could be toxic to NSCs should be considered.


Linkage mapping of quantitative trait loci for fiber yield and its related traits in the population derived from cultivated ramie and wild B. nivea var. tenacissima.
Ramie is an important natural fiber crop, and the fiber yield and its related traits are the most valuable traits in ramie production. However, the genetic basis for these traits is still poorly understood, which has dramatically hindered the breeding of high yield in this fiber crop. Herein, a high-density genetic map with 6,433 markers spanning 2476.5 cM was constructed using a population derived from two parents, cultivated ramie Zhongsizhu 1 (ZSZ1) and its wild progenitor B. nivea var. tenacissima (BNT). The fiber yield (FY) and its four related traits-stem diameter (SD) and length (SL), stem bark weight (BW) and thickness (BT)-were performed for quantitative trait locus (QTL) analysis, resulting in a total of 47 QTLs identified. Forty QTLs were mapped into 12 genomic regions, thus forming 12 QTL clusters. Among 47 QTLs, there were 14 QTLs whose wild allele from BNT was beneficial. Interestingly, all QTLs in Cluster 10 displayed overdominance, indicating that the region of this cluster was likely heterotic loci. In addition, four fiber yield-related genes underwent positive selection were found either to fall into the FY-related QTL regions or to be near to the identified QTLs. The dissection of FY and FY-related traits not only improved our understanding to the genetic basis of these traits, but also provided new insights into the domestication of FY in ramie. The identification of many QTLs and the discovery of beneficial alleles from wild species provided a basis for the improvement of yield traits in ramie breeding.


Tattooing for preservation of oral and oropharyngeal cancer resection margins.
En bloc composite cancer surgery for head and neck tumors is now available with reconstruction. Preoperative adjuvant therapy threatens the concept of wide resection because of alteration of tumor margins. Pre-irradiation tattooing at resection margins will preserve this fundamental surgical doctrine.


Anomalous origin of the right pulmonary artery from the aorta and CATCH 22 syndrome.
We report repair of anomalous origin of the right pulmonary artery from the ascending aorta in a premature neonate with a deletion in the CATCH 22 region of chromosome 22. This case suggests that the pathogenesis of anomalous origin of the right pulmonary artery involves genetically determined abnormalities of the neural crest. Repair of this defect in a premature infant can prevent the development of severe pulmonary vascular disease.


Stereotactic Body Reirradiation in Gynaecological Cancer: Outcomes and Toxicities from a Single Institution Experience.
To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.


Schizophrenia:.
In Zanzibar, as in many "third world" places, there are two health care systems, one traditional and the other "European." Among the Swahili people of East Africa spirits are believed to be the cause of disturbed behavior or "madness." Data and observations gathered during one year of mental health practice in Zanzibar and over many years of practice in the U.S. are compared to examine how cultural values shape beliefs, practices and attitudes related to "madness." Implications for occupational therapy theory and practice are drawn.


Theorems and implications of a model-independent elimination/distribution function decomposition of linear and some nonlinear drug dispositions. III. Peripheral bioavailability and distribution time concepts applied to the evaluation of distribution kinetics.
Disposition decomposition analysis (DDA) is applied to evaluate the rate and extent of drug delivery from the sampling compartment to the peripheral system, i.e., peripheral bioavailability. Four parameters are introduced which are useful in quantifying peripheral bioavailability. The compounded peripheral bioavailability, F comp, is the ratio between the total compounded amount of drug transferred to the peripheral system and the injected dose, D. The AUC peripheral bioavailability, FAUC, is the ratio between the area under the amount vs. time curves for the peripheral system and the sampling compartment. The distribution time td, is the time following an i.v. bolus at which the net transfer of drug to the peripheral system reverses in direction. The maximum peripheral bioavailability, Fmax, is the maximum fraction of an i.v. bolus dose that is present in the peripheral system at any one time. Equations are derived which permit estimation of those parameters from drug concentrations in the sampling compartment. Simple algorithms and a computer program are provided for estimating Fcomp, FAUC, td, Fmax, and other parameters relevant to DDA for drugs that exhibit a linear polyexponential bolus response. Estimates of Ecomp, FAUC, td, and Fmax are presented for several drugs.


Modeling the protective role of human eyelashes against ultraviolet light exposure.
The role of eyelashes in ocular radiation protection has been hypothesized for some time. There is however no quantitative knowledge of the shading they provide. The ocular protection provided by eyelashes is investigated in this study. A numerical model able to simulate an arbitrary source of light to illuminate a 3-dimensional head model with realistic details was used for this purpose. The eyelashes' filtering effect was studied for various light incidence angles, diameter and density of cilia. Using average values provided by literature to define their characteristics, we found that eyelashes reduce ultraviolet light received by the cornea of about 12-14%, with maximum values of 24%. These results suggest that the eyelashes can be an important element of the human eye protection system and their role should be further investigated.


Clinical experience with downsized lower energy output implantable cardioverter defibrillators. Ventak Mini II Clinical Investigators.
Technical improvements in cardioverter defibrillators technology has resulted in decrease in can size coupled with improved electrodes technology. A decrease in maximum energy output allows further decrease in device size. The aim of this study was to evaluate the feasibility of a single lead transvenous implant employing a downsized cardioverter-defibrillator (volume 59 cm3), with a related decrease in maximum energy output (29-31 joules as stored energy and 25-27 joules as delivered energy). Fifty-five patients with ventricular tachyarrhythmias were enrolled in 17 European institutions for implantation. At implantation step-down defibrillation threshold (DFT) was determined and the device was implanted only if a safety margin > or =10 joules was maintained between DFT and maximum programmable output. Implantation was performed in 54 of the 55 referred patients (98%) in a single electrode-device configuration. Step-down DFT testing was performed in 44 patients (43 finally implanted) and DFT was 7.77+/-4.41 joules (range 3-20). In 20 of the tested patients (45%) DFT was < or =5 joules, in 26 patients (59%) was < or =8 joules and in 34 patients (77%) it was < or =10 joules. No differences were found in DFT comparing patients with left ventricular ejection fraction < or = or >40% or patients treated or not with antiarrhythmic drugs or beta-blockers. Mean implant duration was 85+/-34 min. Employing a downsized cardioverter defibrillator, successful transvenous implantation can be achieved in 98% of the patients, with maintenance of adequate defibrillation safety margins despite a reduction in stored energy to 29 joules.


Ruptured Iliac Arteriovenous Fistula Presenting With Thigh Pain and Swelling: Case Report.
The presentation of abdominal arteriovenous fistulas is classically described as a triad of a pulsatile abdominal mass with a bruit, high-output heart failure, and regional venous hypertension with primarily open operative therapy. In the following case, we present the treatment of a patient who arrived with acute right heart failure and renal failure due to an arteriovenous fistula and who was successfully treated with endovascular repair.


Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer.
Transgenic mice expressing the polyoma middle T oncoprotein (PyMT) in the mammary epithelium were explored by multimodal imaging to monitor longitudinally spontaneous tumor growth and response to chemotherapy. Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), single photon emission tomography (SPECT) with [(99m)Tc]TcO4 ([(99m)Tc]TEC), X-ray computed tomography, and fluorescent confocal endomicroscopy (FCE) images were acquired during tumor progression in female PyMT mice. Imaging with [(18)F]FDG and [(99m)Tc]TEC was also performed in untreated, doxorubicin-treated, and docetaxel-treated PyMT mice. Total tumor volumes were quantified. Tumors were collected and macroscopic and histological examinations were performed. All PyMT mice developed multifocal tumors of the mammary epithelium that became palpable at 8 weeks of age (W8). Computed tomography (CT) detected tumors at W14, while a clear tumoral uptake of [(99m)Tc]TEC and [(18)F]FDG was present as early as W6 and W8, respectively. No contrast between mammary tumors and surrounding tissue was observed at any stage with [(18)F]FLT. FCE detected an angiogenic switch at W10. Lung metastases were not clearly evidenced by imaging. Doxorubicin and docetaxel treatments delayed tumor growth, as shown by [(18)F]FDG and [(99m)Tc]TEC, but tumor growth resumed upon treatment discontinuation. Tumor growth fitted an exponential model with time constant rates of 0.315, 0.145, and 0.212 week(-1) in untreated, doxorubicin, and docetaxel groups, respectively. Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [(18)F]FDG-PET and [(99m)Tc]TEC SPECT monitor tumor response to chemotherapy.


Sirolimus-eluting stent implantation for treatment of proximal left anterior descending coronary artery lesions: long-term outcome and predictors of adverse cardiac events.
Acute and long-term results after sirolimus-eluting stent (SES) implantation of proximal left anterior descending coronary artery (LAD) disease were evaluated. Although SES has been used increasingly for the treatment of LAD disease, data regarding their safety and efficacy in a real-world population are limited. We investigate the short- and long-term results in 966 patients who underwent SES implantation for stenosis of proximal LAD. The procedural success rate was 97.6%, and procedural non-Q-wave myocardial infarction (MI) rate was 14.5%. In-hospital major complications occurred in five patients (0.5%), including three deaths and two Q-wave MIs. During follow-up (20.4 +/- 8.9 months), there were 16 deaths (1.7%; 10 cardiac, 6 noncardiac), 2 Q-wave MIs, and 22 target lesion revascularizations (2.3%). Late stent thrombosis occurred in two patients (0.2%), 14 and 23 months after the procedure. The event-free survival rates for cardiac death/Q-wave MI were 98.6% +/- 0.4% at 1 year and 97.8% +/- 0.6% at 2 years. The cumulative probabilities of survival without major adverse cardiac events (MACE) were 96.7% +/- 0.6% at 1 year and 95.4% +/- 0.8% at 2 years. In multivariate analysis, stented length (HR 1.04, 95%CI 1.01-1.07, P = 0.009) and infarct-related artery (HR 5.18, 95%CI 1.09-24.64, P = 0.039) were independently related to cardiac death/Q-wave MI. In addition, stented length (HR 1.04, 95%CI 1.02-1.06, P < 0.001) and left ventricular dysfunction (HR 2.66, 95%CI 1.07-6.63, P = 0.036) were significant independent predictors of MACE. SES implantation for proximal LAD disease appears safe and effective in a real-world population, and the independent predictors of MACE included stented length and left ventricular dysfunction.


The assessment of epiphytic yeast diversity in sugarcane phyllosphere in Thailand by culture-independent method.
The diversity of epiphytic yeasts from sugarcane (Saccharum officinarum Linn.) phyllospheres in Thailand was investigated by culture-independent method based on the analysis of the D1/D2 domains of the large subunit rRNA gene sequences. Forty-five samples of sugarcane leaf were collected randomly from ten provinces in Thailand. A total of 1342 clones were obtained from 45 clone libraries. 426 clones (31.7 %) were closely related to yeast strains in the GenBank database, and they were clustered into 31 operational taxonomic units (OTUs) with a similarity threshold of 99 %. All OTU sequences were classified in phylum Basidiomycota which were closely related to 11 yeast species in seven genera including Cryptococcus flavus, Hannaella coprosmaensis, Rhodotorula taiwanensis, Jaminaea angkoreiensis, Malassezia restricta, Pseudozyma antarctica, Pseudozyma aphidis, Pseudozyma hubeiensis, Pseudozyma prolifica, Pseudozyma shanxiensis, and Sporobolomyces vermiculatus. The most predominant yeasts detected belonged to Ustilaginales with 89.4 % relative frequency and the prevalent yeast genus was Pseudozyma. However, the majority were unable to be identified as known yeast species and these sequences may represent the sequences of new yeast taxa. In addition, The OTU that closely related to P. prolifica was commonly detected in sugarcane phyllosphere.


[Control of penicillamine therapy in patients with chronic polyarthritis through urine disc electrophoresis].
D-penicillamine treatment of 50 patients with rheumatoid arthritis with negative ANF tests, was followed by means of protein disk electrophoresis of the urine. In the beginning the urine proteins were analysed every 4 weeks, later at intervals of 3 to 6 months. A glomerular proteinuria, caused by an immune-complex nephritis, can be recognized very early by this method. A glomerular proteinuria was the reason for discontinuing the treatment in 10 of the 50 patients (8 seropositive, 2 seronegative), drug fever occurred in one case with seropositive arthritis. Protein disk-elektrophoresis of the urine is an appropriate method to recognise renal damage earlier than with any other known routine method.


Bioassays for assessing jasmonate-dependent defenses triggered by pathogens, herbivorous insects, or beneficial rhizobacteria.
Jasmonates, together with other plant hormones, are important orchestrators of the plant immune system. The different hormone-controlled signaling pathways cross-communicate in an antagonistic or a synergistic manner, providing the plant with a powerful capacity to finely regulate its immune response. Jasmonic acid (JA) signaling is required for plant resistance to harmful organisms, such as necrotrophic pathogens and herbivorous insects. Furthermore, JA signaling is essential in interactions of plants with beneficial microbes that induce systemic resistance to pathogens and insects. The role of JA signaling components in plant immunity can be studied by performing bioassays with different interacting organisms. Determination of the level of resistance and the induction of defense responses in plants with altered JA components, through mutation or ectopic expression, will unveil novel mechanisms of JA signaling. We provide detailed protocols of bioassays with the model plant Arabidopsis thaliana challenged with the pathogens Botrytis cinerea and Pseudomonas syringae, the insect herbivore Pieris rapae, and the beneficial microbe Pseudomonas fluorescens. In addition, we describe pharmacological assays to study the modulation of JA-regulated responses by exogenous application of combinations of hormones, because a simultaneous rise in hormone levels occurs during interaction of plants with other organisms.


Cutaneovisceral angiomatosis with thrombocytopenia.
We describe 10 children with multiple vascular lesions of the skin and gastrointestinal tract associated with sustained, minor thrombocytopenia. In some children, there was involvement of the lung (n = 5), bone (n = 2), liver (n = 1), spleen (n = 1), and muscle (n = 1). The cutaneous lesions were congenital, multifocal, discrete, red-brown and variably blue macules and papules; in 3 children, a large dominant plaque was also present. All children developed hematemesis and/or melena and endoscopic evaluation revealed several to numerous small mucosal lesions that involved all levels of the gastrointestinal tract. Three of 5 children with pulmonary nodules had cough and 1 also had hemoptysis. Biopsies of cutaneous, gastrointestinal, and pulmonary lesions showed thin-walled, blood-filled vascular channels and variable endothelial hyperplasia. The endothelial nuclei were elongated, round, crescentic, or hobnailed. Cytoplasmic and extracellular periodic acid-Schiff positive deposits were often present in the zones of endothelial hyperplasia. The platelets were small in some children, suggesting a primary defect, possibly accounting for the thrombocytopenia. Gastrointestinal hemorrhage and hemoptysis required antiangiogenic therapy. The constellation of findings defines a congenital proliferative disorder of blood vessels with a distinctive microscopic appearance. We have termed this relatively indolent or slowly progressive disorder cutaneovisceral angiomatosis with thrombocytopenia because this designation incorporates its major clinical and histopathologic features.


Effect of lignin-based monomer on controlling the molecular weight and physical properties of the polyacrylonitrile/lignin copolymer.
In this work, lignin was grafted with acrylonitrile to control the molecular weights and molecular architecture of polyacrylonitrile (PAN)/lignin copolymer. Lignin-acrylonitrile monomer (LA-AN) and its copolymers with AN were synthesized successfully. First, lignin was aminated (LA) and then grafted with 2-chloroacrylonitrile to prepare LA-AN. The copolymerization of LA-AN and AN was carried out using 2,2-azobis(2-methylpropionitrile) as initiator. The modification, grafting, and copolymerization were confirmed with Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and X-ray photoelectron spectroscopy. Contrary to the previous studies, gel permeation chromatography showed that the molecular weight of the copolymers was increased significantly due to the presence of lignin (up to 203,944). Viscosity analysis revealed that the addition of lignin reduces the viscosity of the copolymer solution. While thermogravimetric analysis showed improvement in the degradation temperature, and lowering of the melt temperature, as revealed by differential scanning calorimetry. These findings indicated that the attaching acrylonitrile on lignin molecules result in control of the molecular weight and molecular structure of PAN/Lignin copolymers which results in enhanced solubility, spinnability, and other properties associated with molecular weight.


Contributions of cognitive function to straight- and curved-path walking in older adults.
To determine whether the cognitive function contribution to straight- and curved-path walking differs for older adults. Cross-sectional observational study. Ambulatory clinical research training center. People (N=106) aged 65 to 92 years, able to walk household distances independently with or without an assistive device, and who scored 24 or greater on the Mini-Mental State Examination. Not applicable. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) as a measure of psychomotor speed, and Trail Making Test Parts A and B (TMT-A and TMT-B) and the Trail Making Test difference score (TMT-B-A) as executive function measures of complex visual scanning and set shifting. Gait speed recorded over an instrumented walkway was used as the measure of straight-path walking. Curved-path walking was assessed using the Figure-of-8 Walk Test (F8W) and recorded as the total time and number of steps for completion. Both DSST and TMT-A independently contributed to usual gait speed (P<.001). TMT-A performance contributed to F8W time (P<.001). Neither TMT-B nor TMT-B-A contributed to usual gait speed or time to complete the F8W. For the number of steps taken to complete the F8W, TMT-A, TMT-B, and TMT-B-A (all P<.001) were independent contributors, while DSST performance was not. Curved-path walking, as measured by the F8W, involves different cognitive processes compared with straight-path walking. Cognitive flexibility and set-shifting processes uniquely contributed to how individuals navigated curved paths. The measure of curved-path walking provides different and meaningful information about daily life walking ability than usual gait speed alone.


When children shoot children. 88 unintended deaths in California.
Between 1977 and 1983, eighty-eight California children 0 to 14 years of age were unintentionally shot and killed either by other children or by themselves. The majority of cases occurred while children were playing with guns they had found. Easy accessibility to guns, the resemblance of guns to toys, and gun malfunctions were all contributing factors. Handguns, particularly those of .22 caliber, were frequently involved.


The effects of Escherichia coli STa (heat stable) toxin on the contractility of isolated human myometrium in vitro.
The purpose of the study was to assess the effects of Escherichia coli STa (heat stable) toxin on isolated human myometrial response to oxytocin. One hundred and sixteen muscle strips were obtained from the lower uterine segment of 42 women undergoing cesarean section at term. Amniotic membranes and decidua were excluded. Uterine contractility in response to cumulative doses of E. coli STa toxin was recorded, as well as uterine response to cumulative doses of oxytocin before and after incubation with STa toxin or vehicle. The 50th percentile effective oxytocin concentration (EC50) of muscle strips with and without spontaneous activity before and after the incubation with STa toxin or vehicle was calculated. A paired t test was used for comparison. Muscle strips with and without spontaneous activity responded to cumulative doses of oxytocin before and after the incubation with STa toxin or vehicle. No differences in contraction force, duration, or frequency were noted between the groups (P > 0.05). Furthermore, this toxin was not able to induce uterine contractility when tested alone. The inability of this toxin to affect myometrial response to oxytocin in this study may be due to the absence of amnion cells, chorion, or decidua. Other possible explanations for the lack of response are discussed.


Extracellular vesicles promote epithelial-to-mesenchymal transition of lens epithelial cells under oxidative stress.
Posterior capsule opacification (PCO), resulting from residual lens epithelial cell (LEC) epithelial-mesenchymal transition (EMT), abnormal proliferation, and migration, is the most common complication of cataract surgery. A recent study determined that extracellular vesicles (EVs) and reactive oxygen species (ROS) regulate the EMT process during cutaneous wound healing and tumour metastasis. However, their underlying mechanism in PCO is unclear. In this study, we examined the secreted EVs from a scratch model in vitro. We found that the production of ROS was increased after mechanical injury, especially at the wound edge, and there was an increased viability of LECs, which can be blocked by diphenyleneiodonium, an NADPH oxidase inhibitor. Cell viability and migration were increased upon treatment with 1 μM H2O2, but significantly reduced when the concentration of H2O2 increased to 100 μM. Transwell assay showed that both post-surgery LECs and LECs treated with 1 μM H2O2 significantly induced the migration of normal LECs by EV secretion. Extraction and quantification of EVs derived from injured and H2O2-treated LECs showed a similar increase in production. Co-incubation of EVs from both injured and H2O2-treated LECs with normal LECs and organ-cultured mouse lenses activated EMT, which was attenuated by a ROS inhibitor. These results suggest that EVs participate in ROS-induced lens EMT, making EVs a potential target for treating PCO.


High water temperature raised the requirements of methionine for spotted seabass (Lateolabrax maculatus).
This study evaluated the effects of dietary methionine level and rearing water temperature on growth, antioxidant capacity, methionine metabolism, and hepatocyte autophagy in spotted seabass (Lateolabrax maculatus). A factorial design was used with six methionine levels [0.64, 0.85, 1.11, 1.33, 1.58, and 1.76%] and two temperatures [moderate temperature (MT): 27 ℃, and high temperature (HT): 33 ℃]. The results revealed the significant effects of both dietary methionine level and water temperature on weight gain (WG) and feed efficiency (FE), and their interaction effect was found on WG (P < 0.05). In both water temperatures tested, fish WG increased with increasing methionine level up to 1.11% and decreased thereafter. The groups of fish reared at MT exhibited dramatically higher WG and FE than those kept at HT while an opposite trend was observed for feed intake. Liver antioxidant indices including reduced glutathione and malondialdehyde (MDA) concentrations, and catalase and superoxide dismutase (SOD) activities remarkably increased in the HT group compared to the MT group. Moreover, the lowest MDA concentration and the highest SOD activity were recorded at methionine levels between 1.11% and 0.85%, respectively, regardless of water temperatures. Expression of methionine metabolism-related key enzyme genes (mat2b, cbs, ms, and bhmt) in the liver was increased at moderate methionine levels, and higher expression levels were detected at MT compared to HT with the exception of ms gene relative expression. Relative expression of hepatocyte autophagy-related genes (pink1, atg5, mul1, foxo3) and hsp70 was upregulated by increasing methionine level up to a certain level and decreased thereafter and increasing water temperature led to significantly enhanced expression of hsp70. In summary, HT induced heat stress and reduced fish growth, and an appropriate dietary methionine level improved the antioxidant capacity and stress resistance of fish. A second-order polynomial regression analysis based on the WG suggested that the optimal dietary methionine level for maximum growth of spotted seabass is 1.22% of the diet at 27 ℃ and 1.26% of the diet at 33 ℃, then 1.37 g and 1.68 g dietary methionine intake is required for 100 g weight gain at 27 ℃ or 33 ℃, respectively.


Fast, Reliable, and Simple Point-of-Care-like Adaptation of RT-qPCR for the Detection of SARS-CoV-2 for Use in Hospital Emergency Departments.
During COVID-19 pandemics, the availability of testing has often been a limiting factor during patient admissions into the hospital. To circumvent this problem, we adapted an existing diagnostic assay, Seegene Allplex SARS-CoV-2, into a point-of-care-style direct qPCR (POC dqPCR) assay and implemented it in the Emergency Department of Clinical Hospital Center Rijeka, Croatia. In a 4-month analysis, we tested over 10,000 patients and demonstrated that POC-dqPCR is robust and reliable and can be successfully implemented in emergency departments and similar near-patient settings and can be performed by medical personnel with little prior experience in qPCR.


From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3'-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties.


Impact of staffing model conversion from a mandatory critical care consultation model to a closed unit model in the medical intensive care unit.
The intensive care unit (ICU) staffing model affects clinical outcomes of critically ill patients. However, the benefits of a closed unit model have not been extensively compared to those of a mandatory critical care consultation model. This retrospective before-after study included patients admitted to the medical ICU. Anthropometric data, admission reason, Acute Physiology and Chronic Health Evaluation II score, Eastern Cooperative Oncology Group grade, survival status, length of stay (LOS) in the ICU, duration of mechanical ventilator care, and occurrence of ventilator-associated pneumonia (VAP) were recorded. The staffing model of the medical ICU was changed from a mandatory critical care consultation model to a closed unit model in September 2017, and indices before and after the conversion were compared. A total of 1,526 patients were included in the analysis. The mean age was 64.5 years, and 954 (62.5%) patients were men. The mean LOS in the ICU among survivors was shorter in the closed unit model than in the mandatory critical care consultation model by multiple regression analysis (5.5 vs. 6.7 days; p = 0.005). Central venous catheter insertion (38.5% vs. 51.9%; p < 0.001) and VAP (3.5% vs. 8.6%; p < 0.001) were less frequent in the closed unit model group than in the mandatory critical care consultation model group. After adjusting for confounders, the closed unit model group had decreased ICU mortality (adjusted odds ratio 0.65; p < 0.001) and shortened LOS in the ICU compared to the mandatory critical care consultation model group. The closed unit model was superior to the mandatory critical care consultation model in terms of ICU mortality and LOS among ICU survivors.


Directed mutation: paradigm postponed.
Claims have been made in recent years that spontaneous mutational events are "directed" by (i) the presence in a selective medium of a single carbon source which the cells are unable to utilize (e.g. lactose), or (ii) the absence from a selective medium of an amino acid which the cells are unable to make for themselves (e.g. tryptophan). In resurrecting the previously rejected hypothesis of a "directed" origin for spontaneous mutants, it was noted that selecting for valine-resistant mutants did not allow comparable increases in colony numbers to be observed when overlays containing valine and glucose were added to plates which had accumulated (or were still accumulating) large numbers of "directed" Lac+ or Trp+ mutants. The present paper shows that Valr mutants do occur in much greater numbers if a carbon source other than glucose is added to the plates along with the valine-containing overlays; the evidence is that even small amounts (< 0.02%) of glucose in the overlays prevent the recovery of Valr mutants. From these results, it is argued that the apparent "directed" nature of the spontaneous mutation process is actually a manifestation of the long-known phenomenon of glucose repression.


Biocompatibility of a bicarbonate-buffered amino-acid-based solution for peritoneal dialysis.
Amino-acid-based peritoneal dialysis (PD) fluids have been developed to improve the nutritional status of PD patients. As they may potentially exacerbate acidosis, an amino-acid-containing solution buffered with bicarbonate (Aminobic) has been proposed to effectively maintain acid-base balance. The aim of this study was to evaluate the mesothelial biocompatibility profile of this solution in comparison with a conventional low-glucose-based fluid. Omentum-derived human peritoneal mesothelial cells (HPMC) were preexposed to test PD solutions for up to 120 min, then allowed to recover in control medium for 24 h, and assessed for heat-shock response, viability, and basal and stimulated cytokine [interleukin (IL)-6] and prostaglandin (PGE(2)) release. Acute exposure of HPMC to conventional low-glucose-based PD solution resulted in a time-dependent increase in heat-shock protein (HSP-72) expression, impaired viability, and reduced ability to release IL-6 in response to stimulation. In contrast, in cells treated with Aminobic, the expression of HSP-72 was significantly lower, and viability and cytokine-producing capacity were preserved and did not differ from those seen in control cells. In addition, exposure to Aminobic increased basal release of IL-6 and PGE(2). These data point to a favorable biocompatibility profile of the amino-acid-based bicarbonate-buffered PD solution toward HPMC.


Myelin basic protein in CSF and blood. Relationship between its presence and the occurrence of a destructive process in the brains of encephalitic patients.
Serum and CSF levels of myelin basic protein (MBP) were measured in 50 patients with encephalitis of various origins and severity. In nearly 50%, the CSF samples were found to display immunoreactivity of MBP. Positivity was found to be correlated with the severity of the clinical signs. More precisely, it corresponded to cases with suspected extensive brain destruction. No relationship could be observed with the cause of disease. Positive tests of sera were infrequent, even from patients whose CSF was rich in MBP. Longitudinal studies performed on 20 patients who were serially investigated during periods ranging from three weeks to 18 months demonstrated that after an attack, MBP liberation into the CSF persists for one to three weeks. The MBP assay should serve as an index for destruction of nervous tissue.


Molecular insight into coordination sites for substrates and their coupling kinetics in Na+ /HCO3- cotransporter NBCe1.
The secondary active transporter NBCe1 couples the transmembrane movement of Na+ and carbonate species with an apparent stoichiometry of 1Na+ :2HCO3- (the 'influx' mode) or 1Na+ :3HCO3- (the 'efflux' mode). Here, we employed molecular biology, electrophysiology and structural biology approaches to investigate the molecular mechanism for the transport coupling of Na+ and HCO3- in NBCe1. In Xenopus oocytes, decreasing extracellular [HCO3- ] from 66 to 4 mm progressively decreases the Na+ affinity of NBCe1. However, decreasing [Na+ ] from 96 to 35 mm has little effect on the HCO3- affinity. The residues responsible for the coordination of Na+ and HCO3- in the substrate pocket of NBCe1 were respectively determined by mutational and molecular simulation studies. Mutation to the residues for HCO3- coordination decreased the affinities of NBCe1 for both Na+ and HCO3- . However, mutation to the residues for Na+ coordination decreased the affinity for Na+ but had little effect on the affinity for HCO3- . Molecular simulation showed that NBCe1 has the capacity to coordinate only two ions of HCO3- or CO32- . We propose that (1) NBCe1 has an ordered substrate-binding kinetics with the binding of HCO3- preceding that of Na+ ; (2) NBCe1 operating in the influx mode moves 1Na+ + 2HCO3- , whereas NBCe1 in the efflux mode moves 1Na+ + 1HCO3- + 1CO32- . The substrate-binding kinetics of NBCe1 is distinct from the known kinetics models of many other Na+ -coupled transporters with Na+ binding preceding the driven solute. KEY POINTS: Under physiological conditions, the secondary active transporter NBCe1 can operate in the 'influx' mode with an apparent stoichiometry of 1Na+ :2HCO3- or in the 'efflux' mode with an apparent stoichiometry of 1Na+ :3HCO3- . NBCe1 has an ordered substrate-binding kinetics with HCO3- preceding the binding of Na+ . The kinetics of NBCe1 is distinct from the known kinetics of many other Na+ -driven cotransporters for which the binding of Na+ usually precedes the driven substrate. The residues responsible for the coordination of Na+ and those for carbonate species in the substrate-binding pocket of NBCe1 were determined by mutation and molecular simulation studies. The substrate-binding pocket of NBCe1 contains just two coordination sites for HCO3- or CO32- . It is proposed that NBCe1 in the influx mode moves 1Na+ + 2HCO3- across the plasma membrane, whereas NBCe1 in the efflux mode moves 1Na+ +1HCO3- +1CO32- .


Angiologic observations following radial artery flap elevation: a case report.
Since the introduction of the radial forearm flap in 1981, its inherent vascular morbidity in sacrificing the radial artery has been strongly criticized. In the present paper, a case report is presented where postoperative angiography showed an important contribution of the anterior interosseous artery to hand vascularity two years after raising a reverse flow distally based pedicle radial forearm flap for dorsal hand resurfacing. In order to analyze this finding, further vascular investigations using Color Duplex Imaging examinations for quantitative flow measurements comparing blood flow rates in both right and left forearm arteries were carried out in this patient. Contrary to expectations, results from vascular examinations revealed that overall blood flow in donor forearm arteries was greater than in the contralateral forearm, the anterior interosseous artery showing the greatest difference in blood flow. These data seem to indicate that another major vascular axis based on the anterior interosseous artery develops after removing the radial artery when harvesting the radial forearm flap and that global arterial inflow to the hand is not impaired.


Cutaneous Hyperpigmentation Secondary to High-Dose Tigecycline: A Case Report.
High-dose tigecycline therapy is gaining wide acceptance in treating infections caused by multidrug-resistant bacteria. There are no reports of cutaneous hyperpigmentation with the use of high-dose tigecycline. Here we report a case of a woman who developed reversible cutaneous hyperpigmentation within 48 h of receiving high-dose tigecycline.


HIV specific Th1 responses are altered in Ugandans with HIV and Schistosoma mansoni coinfection.
Fishing communities surrounding Lake Victoria in Uganda have HIV prevalence of 28% and incidence rates of 5 per 100 person years. More than 50% of the local fishermen are infected with Schistosoma mansoni (S. mansoni). We investigated the role of S. mansoni coinfection as a possible modifier of immune responses against HIV. Using polychromatic flow cytometry and Gran-ToxiLux assays, HIV specific responses, T cell phenotypes, antibody-dependent cell-mediated cytotoxic (ADCC) potency and titres were compared between participants with HIV-S. mansoni coinfection and participants with HIV infection alone. S. mansoni coinfection was associated with a modified pattern of anti-HIV responses, including lower frequency of bifunctional (IFNγ + IL-2 - TNF-α+) CD4 T cells, higher overall CD4 T cell activation and lower HIV ADCC antibody titres, compared to participants with HIV alone. These results support the hypothesis that S. mansoni infection affects T cell and antibody responses to HIV in coinfected individuals.


Syndesmosis Malposition Assessed on Weight-Bearing CT Is Common After Operative Fixation of Intra-articular Distal Tibia Plafond Fracture.
To evaluate reliability of measurement techniques for syndesmosis position after operative fixation of distal tibia plafond fracture on weight-bearing computed tomography (WBCT), identify risk factors for syndesmosis malposition, and determine if syndesmosis malposition is associated with higher pain and lower physical function. Prospective cohort study. Three Level 1 trauma centers. Twenty-six subjects who underwent open reduction and internal fixation of distal tibia plafond fractures with bilateral ankle WBCT 1 year or greater after injury were included in the study. Operative fixation of distal tibia plafond fracture. Fibula position in the tibia incisura, injury characteristics, and patient-reported outcomes were the main outcome measurements. Interrater reliability for syndesmosis position measurements were excellent for the Phisitkul technique on both injured and healthy ankles (intraclass correlation coefficients [ICCs]: 0.93-0.98). The Nault technique demonstrated moderate-to-excellent interrater reliability (ICCs: 0.67-0.98), apart from the angle of rotation measurement (ICCs: 0.18-0.67). Sixteen of 26 subjects (62%) had syndesmosis malposition defined as >2 mm difference comparing the tibial-fibular relationship in injured and uninjured ankles using these 2 methods. Patients with syndesmosis malposition reported lower Foot and Ankle Ability Measure: Activities of Daily Living scores; other recorded patient-reported outcomes were not significantly different. Measurement techniques for syndesmosis position on WBCT were reliable after operative fixation of distal tibia plafond fracture. Syndesmosis malposition is common after these injuries and predicted impaired physical function. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


[Immunochemical identification and physicochemical characteristics of human leukocytic beta 2-sialoglobulin (RAL-6)].
A new glycoprotein (RAL-6) was identified in human venous blood by immunochemical assay. During studies into the physicochemical properties, it was established that the glycoprotein has a mobility of beta 2-globulins and contains sialic acids. Study of RAL-6 content in tissue extracts from different organs of man and in biological fluids demonstrated the protein to be contained by pus extracts in a large quantity. The concentration of RAL-6 in hemolysates was found to be lowered in some of the diseases including those of the autoimmune nature.


A PREP Panel, Practice-Based, Evaluation of the Handling of the Kerr Demi-Ultra Light Curing Unit.
This paper describes the handling evaluation (by a group of practice-based researchers, the PREP Panel) of a recently introduced Light Curing Unit (LCU), the Kerr Demi-Ultra, which possesses a number of novel features such as its ultracapacitor power source, and the Light Emitting Diodes (LEDs) which provide the light output being placed close to the tip of the light guide. CPD/CLINICAL RELEVANCE: Testing of new devices and materials with respect to their handling is of importance, given that an easy to handle device should produce better clinical results than one which is difficult to use.


Direct determination of the degree of fibrillation of wood pulps by distribution analysis of pixel-resolved optical retardation.
We propose a new methodology for direct evaluation of the degree of fibrillation of fibrillating pulp suspensions through the pixel-resolved retardation distribution. Through simple normalization by just injecting a pulp suspension with a certain concentration into a quartz flow channel with a constant cross-sectional shape, the degree of fibrillation (i.e., the degree of bundling of cellulose molecular chains) can be directly mapped by the retardation gradation, reflecting locally high retardation (pulp fibers), smaller retardation (balloons on fibrillating pulps), and much smaller retardation close to water (dispersed nanofibers). Both the average retardation and standard deviation are found to be the direct indicators of the degree of fibrillation. We envision that the proposed methodology will become the future standard for determining the degree of fibrillation by the retardation distribution, and it will pave the way for more precise control of pulp fibrillation and more sophisticated applications of cellulose nanofiber suspensions.


The prognostic value of tumor mutational burden related 6-gene-based Risk Score in laryngeal cancer patients.
Laryngeal cancer (LC) is the second frequent malignant head and neck cancer around world, while LC patients' prognosis is unsatisfactory. This study aims to investigate the prognostic value of tumor mutation burden (TMB)-related genes in LC. LC data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. TMB values of all samples were calculated basing on mutation data. The differentially expressed genes (DEGs) between LC samples with distinct TMB were subjected to univariate and LASSO Cox regression analysis to build Risk Score. Immune cell infiltration analysis was conducted in CIBERSORT. Between high and low TMB LC samples, we identified 210 DEGs. Of which, six optimal genes were included to construct Risk Score, comprising FOXJ1, EPO, FGF5, SPOCK1, KCNF1 and PSG5. High risk LC patients had significantly poorer overall survival than low risk patients. The nomogram model constructed basing on Risk Score and gender showed good performance in predicting LC patients' survival probability. The prognostic Risk Score model, basing on six TMB-related genes (FOXJ1, EPO, FGF5, SPOCK1, KCNF1 and PSG5), was a reliable prognostic model to separate LC patients with different prognoses.


Dietary chromium - forms and availabilities.
The chromium naturally occurring in plants eluted from Sephadex G-25 at approximately 2600 D. Total chromium was quantitated with flameless atomic absorption spectrophotometry. A plant ligand tagged with radioactive chromium both in vivo and in vitro migrated on Sephadex G-25 identically to the naturally occurring chromium compound. The molecular weight of the radioactively tagged chromium compound was 2600 daltons on Sephadex G-25. Similar complexes isolated from plant species were found attached to an organic ligand. The ligand appears to have 2 components, differing in composition by an amine group. This extremely stable (KD = 9 X 10(-5)anionic complex does not contain peptide or deoxyribose units. When alfalfa was exposed to either Cr(III) or Cr(VI), only Cr(III) was isolated in this organic chromium compound. The alfalfa bioreduction system can be saturated, as evidenced by Cr(VI) isolation of ionic in those plant extracts incubated with high levels of Cr(VI) in vitro. The gastrointestinal chromium physiology studies show that the radioactively labelled plant chromium compounds remained intact through the gastrointestinal tract up to the large intestine. Some degradation products were identified in the rat cecum. Approximately 30% of the plant chromium available to the rat was absorbed across the gastrointestinal tract.