The domains of slow bacterial growth.
Commonly used culture systems, e.g., batch culture and the chemostat, work poorly for defining the behavior of slowly growing bacteria, i.e., cultures with mass doubling times, tD, longer than 10-12 h. This has slowed the process of understanding how bacteria behave at the longer tD's that embrace most of their existence. Culture systems are identified that give useful access to these longer doubling times. When these slow-growth systems are used with nutrient-limited populations, it is found that cellular concentrations of guanosine 5'-diphosphate 3'-diphosphate, the main effector of the stringent response, commence rising above basal levels at tD's longer than 12 h until, at a tD of 60-70 h, the level is reached that causes the interdiction of protein and ribosome synthesis characteristic of the response. The abrupt onset of the stringent response in eubacteria at a particular tD, corresponding to a specific rate of nutrient uptake, makes oft-used growth equations that do not account for this onset, e.g., those of Monod or Pirt, poor descriptors of slow growth. A serious imbalance between lateral and transverse wall formation rates which, unless corrected, would lead to abnormal cell division can be inferred to develop at tD's longer than 10-12 h. The necessary correction may be supplied by the effects of increased levels of guanosine 5'-diphosphate 3'-diphosphate on transverse wall synthesis.


Demonstration of Sindbis virus antigen in Lowicryl-embedded cultured cells by immunogold staining.
Eight monoclonal antibodies (MAbs) were tested for the use in immunogold staining of Sindbis virus (SIN) antigen in cultured Baby Hamster kidney (BHK) cells. The antibodies were directed against the capsid (C) protein (5) or against the glycoprotein E1 (3), respectively. Four out of five anti-C MAbs and two out of three anti-E1 Mabs reacted on frozen sections, whereas two of the anti-C antibodies and none of the anti-E1 antibodies reacted on Lowicryl K4M-embedded cells. The MAbs reacting, in particular the anti-C Mabs which react on Lowicryl K4M-sections, will allow further studies of the pathogenesis and replication of alphaviruses on the cellular level. The results also confirm the conformation-dependence of the glycoprotein epitopes.


Osteocalcin as an index of osteoblast function during and after ovine pregnancy.
Fetal and neonatal calcium requirements impose heavy demands on maternal bone and mineral homeostasis. The functional response of maternal osteoblasts to this stress is poorly understood. Therefore, plasma osteocalcin (OC) levels were measured by homologous RIA in age-matched nonpregnant, pregnant, and postpartum ewes to evaluate osteoblast function. In pregnant ewes from day 35 of gestation to term, the plasma OC level was suppressed to 8.2 +/- 0.5 micrograms/liter (mean +/- SEM; n = 36) compared with age-matched nonpregnant ewes (18.3 +/- 1.1 micrograms/liter; n = 39; P less than 0.0005). Plasma OC rose to the nonpregnant value by day 20 postpartum and was elevated above this level for the following 40 days (e.g. 44.0 +/- 5.0 micrograms/liter at 48-53 days; P less than 0.0005). The timing of changes in plasma OC levels and weaning did not correlate. The validity of plasma OC measurement as a marker of osteoblast function was assessed by determining the OC plasma production and clearance rates using an [125I]ovine OC infusion method. The OC plasma production rates in matched controls (n = 6), pregnant (n = 9), and 48-53-day postpartum sheep (n = 7) were 1.5 +/- 0.2, 0.5 +/- 0.04 (P less than 0.001 vs. control), and 3.6 +/- 0.6 mg/day (P less than 0.005 vs. pregnant sheep), respectively. In one ewe studied longitudinally, the OC plasma production rate increased by 15 days after parturition and achieved a 10-fold elevation at 49 days postpartum. The OC plasma clearance rate (3.3 +/- 0.3 liters/h) was the same in control, pregnant, and postpartum ewes. It is concluded that 1) changes in plasma OC levels during and after ovine pregnancy reflected changes in OC production, 2) plasma OC measurements are likely to be a useful index of osteoblast function in pregnancy, and 3) osteoblast function appears to be depressed during ovine pregnancy and enhanced markedly in the interval 20-60 days postpartum. The relationship between osteoblast function, as indicated by OC production, and bone formation remains to be clarified.


Chronic thromboembolic pulmonary hypertension following long-term peripherally inserted central venous catheter use.
A 36-year-old woman presented with recurrent pulmonary emboli (PE) despite oral anticoagulation. She was a type I diabetic with severe gastroparesis requiring insertion of multiple long-term peripherally inserted central catheters (PICC) over a 10-year period. Imaging at presentation demonstrated a PICC-associated mobile mass in the right atrium and signs of pulmonary hypertension (PH). She was thrombolyzed and fully anticoagulated, and diabetic management without PICC strongly recommended. PH persisted, however, and she developed chronic thromboembolic pulmonary hypertension (CTEPH), for which successful pulmonary endarterectomy (PEA) surgery led to symptomatic and hemodynamic improvement. This was the first case of CTEPH reported related to long-term PICC use outside the setting of malignant disease, and a novel observation that the PEA specimen contained multiple plastic fragments. Long-term PICC placement increases the risk of CTEPH, a life-threatening, albeit treatable, complication.


Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma.
Mesenchymal stem cells (MSCs) are multi-potent progenitor cells with ability to differentiate into multiple lineages, including bone, cartilage, fat, and muscles. Recent research indicates that MSCs can be efficiently recruited to tumor sites, modulating tumor growth and metastasis. However, the underlying molecular mechanisms are not fully understood. Here, we first demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), when mixed with human cholangiocarcinoma cell lines QBC939 in a xenograft tumor model, significantly increased the cancer cells proliferation and metastatic potency. MSCs and their conditioned media (MSC-CM) could improve the drug resistance of tumor when the compound K (CK) as an anti-cancer drug, a major intestinal bacterial metabolite of panaxoside, was administered to xenograft tumor mice. Furthermore, MSCs greatly increased the colony formation and invasion of cholangiocarcinoma cells QBC939 and Mz-ChA-1. Immunochemistry studies of cholangiocarcinoma tissue chips and transplantation tumor from nude mice showed that the expression of β-catenin was important for cholangiocarcinoma development. We further demonstrated that MSCs and MSCs-CM could promote proliferation and migration of cholangiocarcinoma cells through targeting the Wnt/β-catenin signaling pathway. hUC-MSCs or MSCs-CM stimulated Wnt activity by promoting the nuclear translocation of β-catenin, and up-regulated Wnt target genes MMPs family, cyclin D1 and c-Myc. Together, our studies highlight a critical role for MSCs on cancer metastasis and indicate MSCs promote metastatic growth and chemoresistance of cholangiocarcinoma cells via activation of Wnt/β-catenin signaling.


Human erythrocyte band 3 polymorphism (band 3 Memphis): characterization of the structural modification (Lys 56----Glu) by protein chemistry methods.
Band 3 variants occur rather frequently in different populations. Based on sodium dodecyl sulfate (SDS)-polyacrylamide electrophoretic properties, a widespread polymorphism (band 3 Memphis) has been previously described. It corresponds to a protein that has been hypothesized to be elongated in its N-terminal cytoplasmic domain. Band 3 from a heterozygote subject for this polymorphism and that displays a normal reactivity towards stilbene disulfonates has been isolated and its primary structure determined by protein chemistry. Reverse-phase high performance liquid chromatography tryptic peptide mapping showed, as the only difference with controls, that the enzymatic cleavage between the two N-terminal peptides did not occur, yielding a 69 residue-long fragment. Further cleavages of this peptide (cyanogen bromide, V8 protease), amino acid composition, and sequence analyses demonstrated that the lysine at position 56 was replaced by a glutamic acid. Thus, surprisingly, a single amino acid change is responsible for the large difference in the electrophoretic behavior. This result suggests that single amino acid substitutions may similarly be involved in the structural modification of several other protein variants, described as elongated or shortened based only on SDS-polyacrylamide electrophoresis studies. When deletions/insertions were confirmed by sequence analysis, their extent was often different from that expected from electrophoresis.


Ontogeny of the middle ear and auditory sensitivity in the Natterjack toad (Epidalea calamita).
In most anuran amphibians, acoustic communication is of prime importance for mate localization and selection. The tympanic middle ear increases auditory sensitivity and directionality and is therefore expected to be favoured by natural selection. However, especially within the family of true toads (Bufonidae) there is a tendency for species to lose parts of the middle ear apparatus and consequently have a reduced sensitivity to high-frequency sounds (above 1 kHz). Part of the explanation for this may be that development of the middle ear is especially slow in bufonids, and thus the middle ear would be more likely to be lost or non-functional in paedomorphic species. However, a timeline of development of the middle ear has not been established previously. The goal of the present study was to investigate middle ear development in a toad species that has a well-known natural history and acoustic communication behaviour. We made a detailed study of anatomy and biophysics of the middle ear with measurements of auditory sensitivity across age in post-metamorphic natterjack toads (Epidalea calamita). The tadpoles and toadlets were raised in the laboratory, so their exact age was known, their auditory sensitivity was measured using auditory brainstem responses, and middle ear development and function were assessed by anatomical studies and laser vibrometry. We found that the developmental stage of the middle ear depends on the size of the toad rather than its age. The middle ear was functional at the earliest at a snout-vent length of 40 mm, which for these toads was around 500 days post-metamorphosis, close to the time of first reproduction. The functional, adult-like middle ear was shown to have 30 dB increased sensitivity to the dominant frequency of the mating call compared with sensitivities measured in newly metamorphosed individuals.


Novel approach to vancomycin level monitoring: Impact of a multidisciplinary monitoring system on timing of vancomycin levels.
A novel approach to vancomycin level monitoring is described. Vancomycin trough orders were added to the medication ordering system of a large teaching hospital and were generated when vancomycin was ordered. Pharmacists adjusted the order time so that the level was drawn appropriately. After pharmacist validation, the trough order appeared within the nursing medication list, and nurses were required to document when the level was drawn. Outcomes were evaluated before (retrospective group) and after (prospective group) implementation of this initiative. Among all patients for whom a vancomycin level was drawn, 24.0% of patients in the retrospective group had their first vancomycin level drawn within 2 hours of true trough, compared with 87.2% of patients in the prospective group (p < 0.0001). Among all patients receiving vancomycin, significantly more patients in the prospective group had a level drawn within 2 hours of the true trough compared with the retrospective group (71.9% versus 20.6%, p < 0.0001). Further, significantly more patients in the prospective group had a vancomycin level ordered compared with the retrospective group (100.0% versus 90.8%, p < 0.0001). The mean ± S.D. time from true trough that vancomycin levels were drawn was much longer in the retrospective group (184.9 ± 84.8 minutes versus 58.3 ± 60.7 minutes in the prospective group, p < 0.0001). A novel multidisciplinary approach to vancomycin trough monitoring involving automatic generation of trough orders, pharmacist validation of trough orders, and inclusion of trough orders in the nursing medication administration record was successful in significantly improving timing of vancomycin trough levels.


Imaging and Management of Fibroepithelial Lesions of the Breast: Radiologic-Pathologic Correlation.
Fibroepithelial lesions (FELs) are among the most common breast masses encountered by breast radiologists and pathologists. They encompass a spectrum of benign and malignant lesions, including fibroadenomas (FAs) and phyllodes tumors (PTs). FAs are typically seen in young premenopausal women, with a peak incidence at 20-30 years of age, and have imaging features of oval circumscribed hypoechoic masses. Although some FA variants are especially sensitive to hormonal influences and can exhibit rapid growth (eg, juvenile FA and lactational adenomas), most simple FAs are slow growing and involute after menopause. PTs can be benign, borderline, or malignant and are more common in older women aged 40-50 years. PTs usually manifest as enlarging palpable masses and are associated with a larger size and sometimes with an irregular shape at imaging compared with FAs. Although FA and FA variants are typically managed conservatively unless large and symptomatic, PTs are surgically excised because of the risk of undersampling at percutaneous biopsy and the malignant potential of borderline and malignant PTs. As a result of the overlap in imaging and histologic appearances, FELs can present a diagnostic challenge for the radiologist and pathologist. Radiologists can facilitate accurate diagnosis by supplying adequate tissue sampling and including critical information for the pathologist at the time of biopsy. Understanding the spectrum of FELs can facilitate and guide appropriate radiologic-pathologic correlation and timely diagnosis and management of PTs. Published under a CC BY 4.0 license. Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.


The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection-evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology.
Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.


Peripheral intrapulmonary lipoma: a case report and review of the literature.
Lipomas are common benign tumours, but intrathoracic lipomas are rare and peripheral lung lipomas are exceptionally rare. Eight cases have been described in the world literature. We report a case of lipoma arising in the periphery of the left lower lung in a 54-year old woman. Grossly, it was presented as a well- circumscribed, thinly encapsulated, rounded, pale yellow mass. A wedge resection was done of the left lung and the microscopic findings revealed lipoma of the lung. The present paper recapitulates the macroscopic and microscopic features, the treatment and the differential diagnosis of this rare neoplasm.


Bruck syndrome: second antenatal diagnosis.
Bruck syndrome is characterized by the association of arthrogryposis and osteogenesis imperfecta. It is a distinct autosomal recessive disorder associated with normal collagen I. The main features are osteoporosis, long bone bowing and scoliosis due to vertebral deformities and congenital joint contractures. We describe a French girl who was born with ankle and wrist contractures (second antenatal discovery).


Thermo-dependence of noxious mechanical heterotopic stimulation-dependent modulation of the spinal dorsal horn response to somatosensory stimulation.
Despite the frequent clinical hyper- or hypothermia cases, thermal-dependence of the endogenous pain modulation system at the spinal cord is not well understood. We evaluate spinal dorsal horn neuronal network responses during mechanical heterotopic noxious stimuli (HNS) at three different body temperatures (34; 37 or 40°C) by measuring lumbar cord dorsum potentials activated by electrical stimulation of the ipsilateral sural nerve in adult thiopental anesthetized rats. A noxious clamp was applied randomly to the tail, right hindpaw, right forepaw, muzzle and left forepaw. HNS induced a decrease of the N wave amplitude and duration at 37°C. This effect was reduced at 40°C for both amplitude (-18.2% for 37-40°C; P<0.0005) and duration (-16.4% for 37-40°C; P<0.0001). P wave did not show neither amplitude nor duration changes at neither 3 tested temperatures. Clinical range changes of temperature could modify pain sensation, moreover, hyperthermia increases nociceptive sensory input to dorsal horn, and could exacerbate pain sensation in individuals with fever.


Umifenovir effectively inhibits IL-10 dependent persistent Coxsackie B4 virus infection.
Coxsackie virus cannot be completely eliminated due to restrictive replication and impaired immune response, thus causing persistent infection. IL-10 plays a decisive role in the course of persistent viral infection. Umifenovir is a broad-spectrum antiviral drug, with certain treatment effects on Coxsackie virus infection. Previously, we showed that in addition to inhibiting Coxsackie B4 (CVB4) infection, Umifenovir also down-regulates IL-10 induced by persistent CVB4 virus infection in vitro and in vivo. Here, BALB/c mouse spleen cells infected with CVB4 were used as a model to explore the mechanism by which Umifenovir affects IL-10 expression. We found that subcellular localization of p38 and MAPK-activated protein kinase 2 (MK2) played a very important role in IL-10 secretion, and Umifenovir significantly prevented p38-MK2 complex from exiting the cell nucleus. This in turn blocked the biological functions of the latter pathway, and inhibited the high expression of IL-10 induced by CVB4. These findings suggest that Umifenovir is a potential anti-CVB4 drug; most importantly, Umifenovir could be used to treat IL-10 induced persistent viral infection.


Slip of fluid molecules on solid surfaces by surface diffusion.
The mechanism of fluid slip on a solid surface has been linked to surface diffusion, by which mobile adsorbed fluid molecules perform hops between adsorption sites. However, slip velocity arising from this surface hopping mechanism has been estimated to be significantly lower than that observed experimentally. In this paper, we propose a re-adsorption mechanism for fluid slip. Slip velocity predictions via this mechanism show the improved agreement with experimental measurements.


[On metabolic therapeutics G-I-K in surgery of cardiac patients].
The basic principles of the metabolic therapeutics with glucose-insulin-potassium solutions, already proposed by Dr. Demetrio Sodi Pallares, are exposed. Chronologic succession of this treatment during the preoperative, transoperative and postoperative phases of heart surgery, as well as some personal observations of one of the authors, are described. The glucose-insulin-potassium solution is a powerful system, providing very useful energy to protect the injured myocardium during cardiovascular surgery. Many publications support this assertion. The most recent ones indicate a reduction of low output syndromes due to interventions on coronary arteries, as well as a significant diminution of circulating fatty acids after primary angioplasty. The mentioned solution, in higher concentrations than the initial one, could become routine therapeutics in medicine and surgery centers, in general.


Interferon production in adults with respiratory syncytial viral infection.
Respiratory syncytial virus may cause repeated infections and appreciable illness in adults as well as children. Factors associated with immunity and recovery are poorly understood. We studied 37 adults with natural respiratory syncytial viral illness and eight experimentally infected volunteers for nasal interferon production. Their response was compared to that of 25 adults with influenza. Interferon was detected in only six of those with natural respiratory syncytial virus and in none of those with experimental infection. The quantities of interferon were low (geometric mean, 6 U/mL) and did not appear to affect viral shedding. In contrast, 24 of influenza patients produced interferon and in greater quantities (geometric mean, 116 U/mL). This suggests that interferon is not involved in recovery from respiratory syncytial viral infection and might indicate a lack of a local cell-mediated response that could relate to the often prolonged course and shedding observed with respiratory syncytial virus.


The in vivo performance of a novel thermal accelerant agent used for augmentation of microwave energy delivery within biologic tissues during image-guided thermal ablation: a porcine study.
To investigate the effects of a novel caesium-based thermal accelerant (TA) agent on ablation zone volumes following in vivo microwave ablation of porcine liver and skeletal muscle, and to correlate the effects of TA with target organ perfusion. This prospective study was performed following institutional animal care and use committee approval. Microwave ablation was performed in liver and resting skeletal muscle in eight Sus scrofa domesticus swine following administration of TA at concentrations of 0 mg/mL (control), 100 mg/mL and 250 mg/mL. Treated tissues were explanted and stained with triphenyltetrazolium chloride (TTC) for quantification of ablation zone volumes, which were compared between TA and control conditions. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. General mixed modelling with a log-normal distribution was used for all quantitative comparisons (p = 0.05). A total of 28 ablations were performed in the liver and 18 in the skeletal muscle. The use of TA significantly increased ablation zone volumes in a dose-dependent manner in both the porcine muscle and liver (p < 0.01). Both the absolute mean ablation zone volume and percentage increase in ablation zone volume were greater in the resting skeletal muscle than in the liver. In one swine, a qualitative mitigation of heat sink effects was observed by TTC and H&E staining. Non-lethal polymorphic ventricular tachycardia was identified in one swine, treated with intravenous amiodarone. The use of a novel TA agent significantly increased mean ablation zone volumes following microwave ablation using a porcine model. The relationship between TA administration and ablation size was dose-dependent and inversely proportional to the degree of target organ perfusion, and a qualitative reduction in heat-sink effects was observed.


National survey of emergency department alcohol screening and intervention practices.
We describe current alcohol screening and brief intervention practices in emergency departments (EDs) at Level I and Level II trauma centers and characterize ED directors' attitudes and perceived barriers associated with these practices among injured patients in the ED. ED directors at Level I and Level II trauma centers were surveyed about current alcohol screening and intervention practices in the ED, as well as knowledge, attitudes, and perceived barriers to these practices. Nearly half (46.0%) of ED directors surveyed responded. The majority (64.5%) reported using a serum alcohol level to routinely screen for unhealthy alcohol use; only 23.6% routinely use standardized instruments. Sixty-five percent of ED directors support screening and 70% support intervention among injured ED patients. Only 15% reported having formal screening and intervention policies in their ED, and 9% reported offering brief alcohol intervention by trained personnel. The most commonly perceived barriers to implementation are provider time (83%) and financial resources (55%). Of injured patients identified as exhibiting alcohol misuse, few (12%) receive brief intervention conducted by trained personnel. Current alcohol screening and brief intervention practices are lagging behind national guidelines. Although the majority of ED directors support the idea of alcohol screening and intervention, these beliefs have not yet been translated to routine clinical care.


Embedding learning from adverse incidents: a UK case study.
Purpose This paper reports on a regionally based UK study uncovering what has worked well in learning from adverse incidents in hospitals. The purpose of this paper is to review the incident investigation methodology used in identifying strengths or weaknesses and explore the use of a database as a tool to embed learning. Design/methodology/approach Documentary examination was conducted of all adverse incidents reported between 1 June 2011 and 30 June 2012 by three UK National Health Service hospitals. One root cause analysis report per adverse incident for each individual hospital was sent to an advisory group for a review. Using terms of reference supplied, the advisory group feedback was analysed using an inductive thematic approach. The emergent themes led to the generation of questions which informed seven in-depth semi-structured interviews. Findings "Time" and "work pressures" were identified as barriers to using adverse incident investigations as tools for quality enhancement. Methodologically, a weakness in approach was that no criteria influenced the techniques which were used in investigating adverse incidents. Regarding the sharing of learning, the use of a database as a tool to embed learning across the region was not supported. Practical implications Softer intelligence from adverse incident investigations could be usefully shared between hospitals through a regional forum. Originality/value The use of a database as a tool to facilitate the sharing of learning from adverse incidents across the health economy is not supported.


Improved fluorescence method for identifying sex chromatin in formalin-fixed tissue.
An improved fluorescence method for demonstrating sex chromatin in formalin-fixed tissue is described. Deparaffinized sections are pretreated with pronase, then acid hydrolysis, before staining with quinacrine dihydrochloride and mounting in buffered Gelvatol. Optimized fluorescence of nuclei allows recognition of either Y chromatin or Barr body in interphase nuclei. The method is a useful tool in sexing early conceptuses and teratomata using an extensive paraffin-block storage resource.


Structure-Based Reactivity Profiles of Reactive Metabolites with Glutathione.
Therapeutic agents can be transformed into reactive metabolites under the action of various metabolic enzymes in vivo and then covalently combine with biological macromolecules (such as protein or DNA), resulting in increasing toxicity. The screening of reactive metabolites in drug discovery and development stages and monitoring of biotransformation in post-market drugs has become an important research field. Generally, reactive metabolites are electrophilic and can be captured by small nucleophiles. Glutathione (GSH) is a small peptide composed of three amino acids (i.e., glutamic acid, cysteine, and glycine). It has a thiol group which can react with electrophilic groups of reactive metabolic intermediates (such as benzoquinone, N-acetyl-p-benzoquinoneimine, and Michael acceptor) to form a stable binding conjugate. This paper aims to provide a review on structure-based reactivity profiles of reactive metabolites with GSH. Furthermore, this review also reveals the relationship between drugs' molecular structures and reactive metabolic toxicity from the perspective of metabolism, giving a reference for drug design and development.


Reduction of opioid use after orthopedic surgery: a scoping review.
The opioid epidemic is one of the biggest public health crises of our time, and overprescribing of opioids after surgery has the potential to lead to long-term use. The purpose of this review was to identify and summarize the available evidence on interventions aimed at reducing opioid use after orthopedic surgery. We searched CENTRAL, Embase and Medline from inception until August 2019 for studies comparing interventions aimed at reducing opioid use after orthopedic surgery to a control group. We recorded demographic data and data on intervention success, and recorded or calculated percent opioid reduction compared to control. We included 141 studies (20 963 patients) in the review, of which 113 (80.1%) were randomized controlled trials (RCTs), 6 (4.3%) were prospective cohort studies, 16 (11.4%) were retrospective cohort studies, 5 (3.6%) were case reports, and 1 (0.7%) was a case series. The majority of studies (95 [67.4%]) had a follow-up duration of 2 days or less. Interventions included the use of local anesthetics and/or nerve blocks (42 studies [29.8%]), nonsteroidal anti-inflammatory drugs (31 [22.0%]), neuropathic pain medications (9 [6.4%]) and multimodal analgesic combinations (25 [17.7%]. In 127 studies (90.1%), a significant decrease in postoperative opioid consumption compared to the control intervention was reported; the median opioid reduction in these studies was 39.7% (range 5%-100%). Despite these reductions in opioid use, the effect on pain scores and on incidence of adverse effects was inconsistent. There is a large body of evidence from randomized trials showing the promise of a variety of interventions for reducing opioid use after orthopedic surgery. Rigorously designed RCTs are needed to determine the ideal interventions or combination of interventions for reducing opioid use, for the good of patients, medicine and society.


Water-soluble UV curable urethane methyl acrylate coating: preparation and properties.
Two kinds of water-soluble and ultraviolet (UV) curable oligomers were synthesized and characterized. The oligomers were evaluated as resins for water-based UV curable coating. The rheology of the two oligomers' aqueous solutions was investigated in terms of solid fraction, pH dependence, and temperature dependence. The solutions were found to be Newtonian fluid showing rather low viscosity even at high solid fraction of 0.55. The drying process of the coatings and the properties of the cured coatings were studied by comparing them with water-dispersed UV-curable polyurethane methyl acrylate. It was evident that the water-soluble coating dried more slowly; and that the overall properties were inferior to those of the water-dispersed coating.


Attitudes vs. Purchase Behaviors as Experienced Dissonance: The Roles of Knowledge and Consumer Orientations in Organic Market.
This research focuses on the incongruity between positive attitudinal responses but a lack of purchase behavior in organic markets. According to cognitive dissonance theory, consumer orientations toward the benefits attributed to organic products (environmental protection, health, hedonic) relieve the dissonance that results from this attitude-behavior incongruity. Knowledge also functions as a transmitter, from positive attitudes to purchase behaviors, thereby reducing the incongruity. Using quota sampling in a survey study, this paper tests the hypotheses from linear regression models. The results show that orientations and knowledge improve the congruity between attitudes and purchase behaviors toward organic products. Moreover, interaction effects arise between the environmental protection orientation and knowledge and between the hedonic orientation and knowledge. Increasing knowledge mitigates the difference between attitudes and purchase behaviors, especially for consumers with environmental protection or hedonic orientations. These findings have several important implications for research and practice.


Polyclonal immunoglobulin G from patients neutralizes human immunodeficiency virus type 1 primary isolates by binding free virions, but without interfering with an initial CD4-independent attachment of the virus to primary blood mononuclear cells.
We investigated the relationship between human immunodeficiency virus type 1 (HIV-1) primary isolate (PI) antibody-mediated neutralization and attachment to primary blood mononuclear cells (PBMC). Incubation of PIs with immunoglobulin G (IgG) purified from infected patients did not inhibit attachment of the viruses with PBMC, but partial to complete neutralization was achieved. Neutralization of PIs already fixed on the cells was achieved by some IgG samples only and was of limited intensity compared to the former neutralization protocol. On the contrary, the binding of IgG to free virions was shown to be sufficient to reach potent neutralization, as the infectivity of IgG-PI complexes purified from the bulk of antibodies before addition to PBMC was strongly diminished compared to mock-treated controls. Monoclonal antibodies to the CDR2 domain of CD4 completely inhibited the infection of PBMC without interfering with the attachment of PIs to the cells, suggesting that, under these experimental conditions, the initial attachment of viruses to PBMC involves alternative cellular receptors. This initial interaction may also involve other components of the viral envelope than gp120, as partial depletion of the surface glycoproteins of primary viral particles that resulted in an almost complete loss of infectivity did not impair attachment to PBMC. A limited inhibition of attachment was observed when interfering with putative interactions with cellular heparan sulfate, whereas no effect was observed for cellular CD147 or nucleolin or for virion-incorporated cyclophilin A. Altogether, our results favor a mechanism of neutralization of HIV-1 PIs by polyclonal IgG where antibodies predominantly bind free virions and neutralize without interfering with the attachment to PBMC, which, in this model, is mainly CD4 independent.


H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage.
Radiotherapy is one of the most widespread and efficient strategies to fight malignant tumors. Despite its broad application, the mechanisms of radiation-DNA interaction are still under investigation. Theoretical models to predict the effects of a particular delivered dose are still in their infancy due to the difficulty of simulating a real cell environment, as well as the inclusion of a large variety of secondary processes. This work reports the first experimental study of the ion-molecule reactions of the H2O˙+ and OH+ ions, produced by photoionization with synchrotron radiation, with a furan (c-C4H4O) molecule, a template for deoxyribose sugar in DNA. The present experiments, performed as a function of the collision energy of the ions and the tunable photoionization energy, provide key parameters for the theoretical modelling of the effect of radiation dose, like the absolute cross sections for producing protonated furan (furanH+) and a radical cation (furan˙+), the most abundant products, which can amount up to 200 Å2 at very low collision energies (<1.0 eV). The experimental results show that furanH+ is more fragile, indicating how the protonation of the sugar component of the DNA may favor its dissociation with possible major radiosensitizing effects. Moreover, the ring opening of furanH+ isomers and the potential energy surface of the most important fragmentation channels have been explored by molecular dynamics simulations and quantum chemistry calculations. The results show that, in the most stable isomer of furanH+, the ring opening occurs via a low energy pathway with carbon-oxygen bond cleavage, followed by the loss of neutral carbon monoxide and the formation of the allyl cation CH2CHCH2+, which instead is not observed in the fragmentation of furan˙+. At higher energies the ring opening through the carbon-carbon bond is accompanied by the loss of formaldehyde, producing HCCCH2+, the most intense fragment ion detected in the experiments. This work highlights the importance of the secondary processes, like the ion-molecule reactions at low energies in the radiation damage due to their very large cross sections, and it aims to provide benchmark data for the development of suitable models to approach this low collision energy range.


Morphology, Biochemistry, and Pathophysiology of MENX-Related Pheochromocytoma Recapitulate the Clinical Features.
Pheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Because such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, we characterized a spontaneous animal model (multiple endocrine neoplasia [MENX] rats) that develops endogenous PCCs with complete penetrance. Urine was longitudinally collected from wild-type (wt) and MENX-affected (mutant) rats and outputs of catecholamines and their O-methylated metabolites determined by mass spectrometry. Adrenal catecholamine contents, cellular ultrastructure, and expression of phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine, were also determined in wt and mutant rats. Blood pressure was longitudinally measured and end-organ pathology assessed. Compared with wt rats, mutant animals showed age-dependent increases in urinary outputs of norepinephrine (P = .0079) and normetanephrine (P = .0014) that correlated in time with development of tumor nodules, increases in blood pressure, and development of hypertension-related end-organ pathology. Development of tumor nodules, which lacked expression of N-methyltransferase, occurred on a background of adrenal medullary morphological and biochemical changes occurring as early as 1 month of age and involving increased adrenal medullary concentrations of dense cored vesicles, tissue contents of both norepinephrine and epinephrine, and urinary outputs of metanephrine, the metabolite of epinephrine. Taken together, MENX-affected rats share several biochemical and pathophysiological features with PCC patients. This model thus provides a suitable platform to study the pathogenesis of PCC for preclinical translational studies aimed at the development of novel therapies for aggressive forms of human tumors.


[Problems in anesthesia and resuscitation in the surgical treatment of brain neoplasms].
The Authors analyse and discuss some particular problems related to anaesthesia in neurosurgery according to the patient's clinical and neurological status and to the surgical treatment. The evaluation of systemic and neurological physiopathology during pre-, per- and post-operative periods are important for this analysis. Therefore anaesthesia and intensive care methods are attentively discussed. Intracranial pressure, cerebral blood flow, metabolism, intracranial space-occupying lesions and surgical techniques are the main factors interfering with anaesthesia in neurological surgery.


Efficient algorithms for folding and comparing nucleic acid sequences.
Fast algorithms for analysing sequence data are presented. An algorithm for strict homologies finds all common subsequences of length greater than or equal to 6 in two given sequences. With it, nucleic acid pieces five thousand nucleotides long can be compared in five seconds on CDC 6600. Secondary structure algorithms generate the N most stable secondary structures of an RNA molecule, taking into account all loop contributions, and the formation of all possible base-pairs in stems, including odd pairs (G.G., C.U., etc.). They allow a typical 100-nucleotide sequence to be analysed in 10 seconds. The homology and secondary structure programs are respectively illustrated with a comparison of two phage genomes, and a discussion of Drosophila melanogaster 55 RNA folding.


The association between an endothelial nitric oxide synthase gene polymorphism and coronary heart disease in young people and the underlying mechanism.
With the development of molecular biological technology, the association between genes and diseases has drawn increasing attention of researchers; the endothelial nitric oxide synthase (eNOS) gene has been reported to be a candidate gene for cardiovascular disease (CHD). The present study aimed to investigate the association between a polymorphism of eNOS and the risk of CHD in young people (≤40 years old), in addition to the underlying mechanism. A total of 234 cases of CHD in young individuals were collected as the CHD group and 228 cases of healthy individuals as the control group. Peripheral blood was collected and the genotype of the eNOS G894T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism, the gene frequency was calculated and the distributions of genotype and allele frequency between the two groups were compared. Bioinformatics tools were employed to analyze the differences in the local protein structures of the eNOS G894T polymorphism and the biological mechanism was preliminary discussed. The results demonstrated that there were significant differences in the distribution of genotype frequency and allele frequency of the eNOS G894T gene polymorphism between the CHD group and control group (P<0.05). The risk of CHD in GT and TT genotypes were higher compared with the GG genotype (P<0.05). The G894T polymorphism led to Glu298Asp mutation of encoded protein, which is within the active site of eNOS, and partial structures of the protein were converted from random coil to α‑helix. In conclusion, the eNOS G894T gene polymorphism was associated with the occurrence and development of CHD in young people. The potential mechanism is that the G894T polymorphism leads to altered protein structure, which affects the function of eNOS in generating nitric oxide and cardiovascular diastole. The results of the present study suggested a potential target gene for the prevention and treatment of CHD in young people (≤40 years old).


Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice.
Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting β-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes. The overexpression of betatrophin did not affect the ADMSCs in terms of proliferation, differentiation and morphology. However, the co-culture of human islets with ADMSCs overexpressing betatrophin (ADMSCs-BET) induced islet proliferation, β-cell specific transcription factor expression, and the islet production of insulin under the stimulation of glucose or KCl and Arg. In addition, ADMSCs-BET enhanced the anti-inflammatory and anti-apoptotic effects of the co-cultured islets compared with ADMSCs cultured alone. In mice with STZ-induced diabetes, the transplantation of ADMSCs-BET ameliorated the hyperglycemia and weight loss associated with STZ-induced diabetes; ADMSCs-BET also significantly enhanced the ratio of β-cells per islet compared to the transplantation of ADMSCs alone. Thus, our study demonstrates a novel strategy for inducing β-cell regeneration. ADMSCs-BET may replace insulin injections by increasing the number of endogenous insulin-producing cells in patients with diabetes. This combined strategy of ADMSC transplantation and gene therapy may prove to be a useful therapy for the treatment of diabetes.


Magnetic Resonance Imaging of Gynecological Malignancies: Role in Personalized Management.
Gynecological malignancies are a leading cause of mortality and morbidity in women and pose a significant health problem around the world. Currently used staging systems for management of gynecological malignancies have unresolved issues, the most important being recommendations on the use of imaging. Although not mandatory as per the International Federation of Gynecology and Obstetrics recommendations, preoperative cross-sectional imaging is strongly recommended for adequate and optimal management of patients with gynecological malignancies. Standardized disease-specific magnetic resonance imaging protocols help assess disease spread accurately and avoid pitfalls. Multiparametric imaging holds promise as a roadmap to personalized management in gynecological malignancies. In this review, we will highlight the role of magnetic resonance imaging in cervical, endometrial, and ovarian carcinomas.


Differential binding properties of Ga1NAc and/or Ga1 specific lectins.
Grouping of lectin binding properties, based on determinant structure rather than monosaccharide inhibition pattern, should facilitate the selection of lectins as structural probes for glycans as well as for the interpretation of the distribution and the properties of the carbohydrate chains on the cell surface. Based on the binding specificities studied with glycan by precipitin-inhibition, competitive-binding and hemagglutinin-inhibition assays, twenty Ga1 and/or Ga1NAc specific lectins have been divided into six classes according to their specificity for the disaccharide as all or part of the determinants and Ga1NAc alpha 1----Ser(Thr) of the peptide chain. The differential affinities of these lectins were characterized by quantitative precipitin assay. Abbreviation of the following six lectin determinants can also be used to classify these lectins. (1) F determinant (GalNAc alpha 1----3GalNAc, Forssman specific disaccharide). (2) A (Af) determinant (GalNAc alpha 1----3Gal, Human blood group A specific disaccharide; Af, fucosylated A, (GalNAc alpha 1----3 [LFuc alpha 1----2]Gal). (3) Tn determinant (GalNAc alpha 1----0 to Ser (Thr) of the protein core, Tn antigen). (4) T determinant (T antigen, Gal beta 1----3GalNAc alpha 1----0 to Ser (Thr) of the protein core, the mucin type sugar sequence on the human erythrocyte membrane or Gal beta 1----3GalNAc beta 1---- at the nonreducing end of ganglioside). (5) I and II determinants (human blood group type I and II carbohydrate sequences). Most of the lectins reactive to Gal beta 1----4GlcNAc (II) are also reactive to Gal beta 1----3GlcNAc (I). Lectin I (II) determinants (i.e. Gal beta 1----3 (4) GlcNAc residues) can be found at the nonreducing end of the carbohydrate chains derived from either N-glycosidic or O-glycosidic linkages. (6) B determinant (Gal alpha 1----3Gal, Human blood group B specific disaccharide). Their carbohydrate specificities are classified as following: (Table see text). The differential binding properties of lectins can be defined from comparisons of their carbohydrate specificities listed above.


Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population.
Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China. An increased frequency of variants was observed in exon 7 of the MSH2 gene; there was a statistical difference (P < 0.05) between the colorectal cancer (CRC) group (6/82, or 7.32%) or the gastric cancer (GC) group (8/105, or 7.62%) and the controls (1/112, or 0.89%). The odds ratio (OR) was 8.76 for CRC and 9.15 for GC, suggesting an association between the presence of variants in exon 7 of the MSH2 gene and risk of gastrointestinal cancer in the studied population. In addition, MSH2 1168T showed trends toward association with CRC and GC in young (<50 yr) sporadic disease patients (OR = 10.97 and 17.15, respectively). The c.1168C>T (p.Leu390Phe), c.1255C>A (p.Gln419Lys), and c.1261C>A (p.Leu421Met) in exon 7 and c.518T>G (p.Leu173Arg) in exon 3 of MSH2 were suspected as predisposing to gastrointestinal cancer. Variants c.505A>G (p.Ile169Val), c.1221C>G (p.Leu407Leu) and c.1223A>G (p.Tyr408Cys) in MSH2 and c.655 A>G (p.Ile219 Val) and c.927C>T (p.Pro309Pro) in MLH1 might be merely polymorphisms. Consequences of the variant c.2101C>A (p.Gln701Lys) in MLH1 remain to be elucidated.


Stability analysis of a run-of-river diversion hydropower plant with surge tank and spillway in the head pond.
Run-of-river hydropower plants usually lack significant storage capacity; therefore, the more adequate control strategy would consist of keeping a constant water level at the intake pond in order to harness the maximum amount of energy from the river flow or to reduce the surface flooded in the head pond. In this paper, a standard PI control system of a run-of-river diversion hydropower plant with surge tank and a spillway in the head pond that evacuates part of the river flow plant is studied. A stability analysis based on the Routh-Hurwitz criterion is carried out and a practical criterion for tuning the gains of the PI controller is proposed. Conclusions about the head pond and surge tank areas are drawn from the stability analysis. Finally, this criterion is applied to a real hydropower plant in design state; the importance of considering the spillway dimensions and turbine characteristic curves for adequate tuning of the controller gains is highlighted.


Nattokinase Promotes Post-stroke Neurogenesis and Cognition Recovery via Increasing Circulating Irisin.
The therapeutic potential of treatments for post-stroke cognitive impairment (PSCI) is severely limited by the autonomic regeneration capacity of the adult brain. Nattokinase (NK), a serine protease from the traditional food natto, has many beneficial effects on the cardiovascular system by modulating the blood system. While the role of blood factors in neurogenesis and cognition is well-established, it remains unclear whether NK can serve as an anti-PSCI agent through these factors. Our study demonstrates that NK protects against acute ischemic stroke and impressively promotes neurogenesis in rat models by increasing peripheral blood irisin, leading to improved cognitive functions. Our findings demonstrate NK to be a promising candidate for treating PSCI, and we also highlight irisin as a novel target of NK, suggesting its potential role in the peripheral blood-to-brain axis.


Computerized clinical decision support for medication prescribing and utilization in pediatrics.
Accurate and informed prescribing is essential to ensure the safe and effective use of medications in pediatric patients. Computerized clinical decision support (CCDS) functionalities have been embedded into computerized physician order entry systems with the aim of ensuring accurate and informed medication prescribing. Owing to a lack of comprehensive analysis of the existing literature, this review was undertaken to analyze the effect of CCDS implementation on medication prescribing and use in pediatrics. A literature search was performed using keywords in PubMed to identify research studies with outcomes related to the implementation of medication-related CCDS functionalities. Various CCDS functionalities have been implemented in pediatric patients leading to different results. Medication dosing calculators have decreased calculation errors. Alert-based CCDS functionalities, such as duplicate therapy and medication allergy checking, may generate excessive alerts. Medication interaction CCDS has been minimally studied in pediatrics. Medication dosing support has decreased adverse drug events, but has also been associated with high override rates. Use of medication order sets have improved guideline adherence. Guideline-based treatment recommendations generated by CCDS functionalities have had variable influence on appropriate medication use, with few studies available demonstrating improved patient outcomes due to CCDS use. Although certain medication-related CCDS functionalities have shown benefit in medication prescribing for pediatric patients, others have resulted in high override rates and inconsistent or unknown impact on patient care. Further studies analyzing the effect of individual CCDS functionalities on safe and effective prescribing and medication use are required.


Multicomponent One-pot Reactions Towards the Synthesis of Stereoisomers of Dipicolylamine Complexes.
Reported are multi-component one-pot syntheses of chiral complexes [M(L(R) OR')Cl2 ] or [M(L(R) SR')Cl2 ] from the mixture of an N-substituted ethylenediamine, pyridine-2-carboxaldehyde, a primary alcohol or thiol and MCl2 utilizing in-situ formed cyclized Schiff bases where a C-O bond, two stereocenters, and three C-N bonds are formed (M=Zn, Cu, Ni, Cd; R=Et, Ph; R'=Me, Et, nPr, nBu). Tridentate ligands L(R) OR' and L(R) SR' comprise two chiral centers and a hemiaminal ether or hemiaminal thioether moiety on the dipicolylamine skeleton. Syn-[Zn(L(Ph) OMe)Cl2 ] precipitates out readily from the reaction mixture as a major product whereas anti-[Zn(L(Ph) OMe)Cl2 ] stays in solution as minor product. Both syn-[Zn(L(Ph) OMe)Cl2 ] and anti-[Zn(L(Ph) OMe)Cl2 ] were characterized using NMR spectroscopy and mass spectrometry. Solid-state structures revealed that syn-[Zn(L(Ph) OMe)Cl2 ] adopted a square pyramidal geometry while anti-[Zn(L(Ph) OMe)Cl2 ] possesses a trigonal bipyramidal geometry around the Zn centers. The scope of this method was shown to be wide by varying the components of the dynamic coordination assembly, and the structures of the complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Syn complexes were isolated as major products with Zn(II) and Cu(II) , and anti complexes were found to be major products with Ni(II) and Cd(II) . Hemiaminals and hemiaminal ethers are known to be unstable and are seldom observed as part of cyclic organic compounds or as coordinated ligands assembled around metals. It is now shown, with the support of experimental results, that linear hemiaminal ethers or thioethers can be assembled without the assistance of Lewis acidic metals in the multi-component assembly, and a possible pathway of the formation of hemiaminal ethers has been proposed.


Bone marrow transplantation retinopathy.
Bone marrow transplantion (BMT) is the treatment of choice for both malignant and nonmalignant disorders of the bone marrow. BMT retinopathy occurs after a latent period of 6 months and usually recovers after a few weeks. We present a case of BMT retinopathy (BMT) in a patient with a high-degree of non-Hodgkin lymphoma. We analysed the funduscopic and angiographic findings, and the evolution of the case. After a period of two and a half years we observed the spontaneous complete resolution of the fundus lesions and the recovery of visual acuity All of this confirm the theory that BMT retinopathy does not progress beyond the ischemic microvascular stage.


Adaptive self-regulation: meeting others' expectations of leadership and performance.
The authors used longitudinal multisource field data to examine core aspects of the adaptive self-regulation model (A. S. Tsui & S. J. Ashford, 1994) in terms of linkages between self-monitoring, discrepancy in manager match-to-position, 5 measures of leadership, and manager performance. At Time 1, 64 superiors of focal managers rated the managers' matches to their positions within the organization; at Time 3, they rated the managers' performance. At Time 2, the 64 focal managers completed a measure of self-monitoring, and 192 subordinates rated the focal managers' leadership behaviors. Results of partial least squares analysis revealed that discrepancy in manager match-to-position was associated with reductions in laissez faire and passive management-by-exception behaviors and increases in transformational leadership behavior. Self-monitoring was positively associated with all 5 leadership behaviors. Performance was related positively to transformational leadership behavior and negatively to passive management-by-exception and contingent-reward behaviors


The effects of body image perceptions and sociocommunicative orientations on self-esteem, depression, and identification and involvement in the gay community.
The purpose of this study was to examine how nonverbally communicated messages based on weight and physical appearance related to antifat attitudes, image fixation, and discrimination based on physical appearance and weight on bisexual, gay, and lesbian people. Using an Internet-based sample of 233 participants (88% Anglo/Saxon or Caucasian), the results indicated Richmond and Valencic's (2000) conceptualization of image fixation negatively related to an individual's self-esteem and positively related to reported levels of depression. Results also indicated people with highly assertive and responsive communicative behaviors were less likely to hold antifat attitudes and less likely to dislike fat people. Differences between gay/bisexual males and lesbian/bisexual females were also analyzed, and gay/bisexual males had significantly higher levels of image fixation, antifat attitudes, dislike of fat people, weight locus of control, perceptions of self physical/weight discrimination, and depression than lesbian/bisexual females. The results also indicated lesbian/bisexual females had significantly higher levels of self-esteem and interaction and involvement within the bisexual and gay and lesbian community than gay/bisexual men.


Risk Stratification in Pulmonary Arterial Hypertension, Update and Perspectives.
Risk stratification in pulmonary arterial hypertension (PAH) is crucial in assessing patient prognosis. It serves a prominent role in everyday patient care and can be determined using several validated risk assessment scores worldwide. The recently published 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines underline the importance of risk stratification not only at baseline but also during follow-up. Achieving a low-risk status has now become the therapeutic goal, emphasising the importance of personalised therapy. The application of these guidelines is also important in determining the timing for lung transplantation referral. In this review, we summarise the most relevant prognostic factors of PAH as well as the parameters used in PAH risk scores and their evolution in the guidelines over the last decade. Finally, we describe the central role that risk stratification plays in the current guidelines not only in European countries but also in Asian countries.


Iridium complex catalyzed germylative coupling reaction between alkynes and iodogermanes--a new route to alkynylgermanium and alkynylgermasilicon compounds.
The new reaction of terminal alkynes with iodogermanes proceeding in the presence of an Ir(I)-complex [{Ir(μ-Cl)(CO)2}2] (I) and NEt((i)Pr)2, as a hydrogen iodide acceptor, leads to the formation of functionalized alkynylgermanes. This reaction occurs via direct activation of the C(sp)-H bond in the starting alkyne. Detailed stoichiometric experiments using [Ir(cod)(CCPh)(PCy3)] (IVa) and iodogermane were performed and resulted in a proposal of a reasonable mechanism for the germylative coupling reaction between alkynes and iodogermanes.


Schistura andrewi, a new species of loach (Teleostei: Nemacheilidae) from Mizoram, northeastern India.
Schistura andrewi, a new species of loach, is described from a tributary of Kaladan River in Mizoram, northeastern India. It is distinguished from its congeners in having the following combination of characters: long axillary pelvic lobe; complete lateral line with 82-95 pores; 2 unbranched dorsal and anal fin rays; 6-7 broad, wider than interspace, black bars on the body; 2 rows of black spots horizontally across the dorsal fin; a deeply emarginate caudal fin, with 2 vertical rows of black spots across the fin, and 9 + 8 branched caudal fin rays.


Elevated corneal epithelial lines in Acanthamoeba keratitis.
Elevated corneal epithelial lines are another clinical sign in Acanthamoeba corneal infection. In this report, one patient wore extended wear soft contact lenses, and another wore daily wear soft contact lenses. Both patients used distilled water and salt tablets in their lens care. Histopathologic examination of these lines revealed trophozoites and cysts. In one of the patients following penetrating keratoplasty, Acanthamoeba castellani and Acanthamoeba polyphaga were cultured by impression cytology of an epithelial line, as well as from the bulbar and tarsal conjunctiva. In the other patient who did not undergo penetrating keratoplasty, these lines appeared in the cornea one month after initial symptoms.


An artificial PPR scaffold for programmable RNA recognition.
Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism in eukaryotic cells. Although recent computational and structural studies have provided insights into RNA recognition by PPR proteins, their highly insoluble nature and inconsistencies between predicted and observed modes of RNA binding have restricted our understanding of their biological functions and their use as tools. Here we use a consensus design strategy to create artificial PPR domains that are structurally robust and can be programmed for sequence-specific RNA binding. The atomic structures of these artificial PPR domains elucidate the structural basis for their stability and modelling of RNA-protein interactions provides mechanistic insights into the importance of RNA-binding residues and suggests modes of PPR-RNA association. The modular mode of RNA binding by PPR proteins holds great promise for the engineering of new tools to target RNA and to understand the mechanisms of gene regulation by natural PPR proteins.


The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina.
Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 polymorphism (G→A) was reported to alter the binding of transcription factors to this region, influencing IFNG production. Using a case-control study, we found an association between the AA and AG genotypes and tuberculosis resistance (AA vs. GG: odds ratio (OR) = 0.235, p-value = 0.012; AG vs. GG: OR = 0.303, p-value = 0.044; AA vs. AG: OR = 0.776, p-value = 0.427; AA + AG vs. GG: OR = 0.270, p-value = 0.022). Moreover, Mtb-antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants (p-value = 0.034) and presented the greatest percentage of CD4⁺IFNG⁺ lymphocytes (p-value = 0.035), in comparison with GG carriers. No association between the polymorphism and clinical parameters of tuberculosis severity was detected. However, our findings indicate that the rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker of tuberculosis resistance in the Argentinean population.


In situ hybridization: application to the study of gene expression during experimental hepatocarcinogenesis and human hepatocellular carcinoma.
The possibility of detecting specific mRNA directly within tumor cells offered by the in situ hybridization (ISH) technique has provided a new dimension to the study of experimental and human hepatocarcinogenesis. The combination of ISH and immunocytochemical techniques on the same or adjacent tissue sections provides a more complete picture of the various changes in gene expression. ISH may also detect posttranscriptional abnormalities of gene expression at the cellular level, such as expression of mRNA with no protein translation, or translation with decreased efficiency. Undoubtedly, the development of the ISH technique will open a new area for the understanding of the complex molecular events leading to cancer.


Antibiotic consumption in southern and eastern Mediterranean hospitals: results from the ARMed project.
The intensity of antibiotic use in hospital settings is recognized as possibly the most important factor for the selection of antimicrobial resistance. Hospitals are therefore being encouraged to undertake surveillance and benchmarking of antimicrobial consumption patterns with a view to identify and rectify possible evidence of overuse or misuse. As part of the ARMed project, antibiotic use in 25 hospitals from the southern and eastern Mediterranean countries of Cyprus, Egypt, Jordan, Lebanon, Malta, Tunisia and Turkey was assessed prospectively for 24 months during the years 2004-05. The surveillance focused primarily on systemic antibiotics used in hospital care, aggregated at the level of the active substance, in accordance with the Anatomic Therapeutic Chemical (ATC) classification. The median total antibiotic use during the study period was 112 defined daily doses per 100 bed-days (DDD/100BD), with an inter-quartile range of 84-428 DDD/100BD. The most common antibiotic groups prescribed were the extended-spectrum and combination penicillins, first- and third-generation cephalosporins and quinolones. Overall, a predominant consumption of wide-spectrum agents was noted, with a significant correlation between the levels of use of third-generation cephalosporins and carbapenems. Emphasis on wide-spectrum agents could explain one possible factor behind the documented high prevalence of resistance in important pathogens within these same hospitals and suggests the need for improved antibiotic stewardship and prescribing programmes, which may well be applicable to the whole region.


A chronically implantable gallbladder cannula for dogs.
A gallbladder cannula suitable for chronic implantation in the dog is described. The device is simple to operate, inexpensive to construct, durable, and easy to implant. With the cannula in place, measurements of hepatic and biliary drug kinetics, as well as enterohepatic function, in the awake nonstressed animal are possible. Minimal postoperative care is required after implantation of the device.


Protein binding and concentrations of cephaloridine and cefazolin in serum and interstitial fluid of dogs.
Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.


A Langevin equation approach to electron transfer reactions in the diabatic basis.
A linear Langevin equation that governs the population dynamics of electron transfer reactions is derived. The noise in the Langevin equation is eliminated by treating the diabatic population fluctuations as the relevant variables, leaving only the memory kernel responsible for the population relaxation. Within the memory kernel, the diabatic coupling is treated perturbatively and a second order expansion is found to give a simple closed form expression for the kernel. The accuracy of the second order truncation is maximized by performing a fixed rotation of the diabatic electronic states that minimizes the first order free energy of the system and thus minimizes the effect of the perturbation on the thermodynamics. The resulting two-hop Langevin equation (THLE) is then validated by applying it to a simple spin-boson model, where exact results exist. Excellent agreement is found in a wide parameter range, even where the perturbation is moderately strong. Results obtained in the rotated electronic basis are found to be consistently more accurate than those from the unrotated basis. These benchmark calculations also allow us to demonstrate the advantage of treating the population fluctuations instead of the populations as the relevant variables, as only the former lead to reliable results at long time. Thus, the THLE appears to provide a viable alternative to established methods--such as Ehrenfest dynamics or surface hopping--for the treatment of nonadiabatic effects in electron transfer simulations.


Analysis of potential risk factors in the survival of patients with primary retroperitoneal liposarcoma.
The present work is an observational study of a series of variables regarding overall survival and disease-free survival in patients diagnosed with primary liposarcoma. The study is prospective with retrolective data collection that includes all patients with primary liposarcoma referred to Hospital Son Espases University Hospital, Palma de Mallorca, Spain from January 1990 to December 2019. The study includes 50 patients and the compartment surgery was performed in 18 patients (36%) of cases. The mean overall survival of the sample was 15.57 years (95% CI: 12.02-19.12) and the mean disease-free survival was 6.70 years (95% CI: 4.50-8.86). Compartment surgery has not shown benefits in terms of overall survival and disease-free survival. The ASA classification (≥3) predicts a poor prognosis in both overall survival and disease-free survival. Resection with free margins, described on the pathological results and defined in this work as R0, show better disease-free survival.


Microproteome of dentoalveolar tissues.
Proteomic analysis of extracellular matrices (ECM) of dentoalveolar tissues can provide insights into developmental, pathological, and reparative processes. However, targeted dissection of mineralized tissues, dental cementum (DC), alveolar bone (AB), and dentin (DE), presents technical difficulties. We demonstrate an approach combining EDTA decalcification and laser capture microdissection (LCM), followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), to analyze proteome profiles of these tissues. Using the LCM-LC-MS/MS approach, a total of 243 proteins was identified from all tissues, 193 proteins in DC, 147 in AB, and 135 proteins DE. Ninety proteins (37% of total) were common to all tissues, whereas 52 proteins (21%) were overlapping in only two. Also, 101 (42%) proteins were exclusively detected in DC (60), AB (15), or DE (26). Identification in all tissues of expected ECM proteins including collagen alpha-1(I) chain (COL1A1), collagen alpha-1(XII) chain (COL12A1), biglycan (BGN), asporin (ASPN), lumican (LUM), and fibromodulin (FMOD), served to validate the approach. Principal component analysis (PCA) and hierarchical clustering identified a high degree of similarity in DC and AB proteomes, whereas DE presented a distinct dataset. Exclusively and differentially identified proteins were detected from all three tissues. The protein-protein interaction network (interactome) of DC was notable for its inclusion of several indicators of metabolic function (e.g. mitochondrial proteins, protein synthesis, and calcium transport), possibly reflecting cementocyte activity. The DE proteome included known and novel mineralization regulators, including matrix metalloproteinase 20 (MMP-20), 5' nucleotidase (NT5E), and secreted phosphoprotein 24 (SPP-24 or SPP-2). Application of the LCM-LC-MS/MS approach to dentoalveolar tissues would be of value in many experimental designs, including developmental studies of transgenic animals, investigation of treatment effects, and identification of novel regenerative factors.


Occurrence of geohelminths in the soil of children's playgrounds and green areas in the city of Wrocław, Poland.
Pets, strays, and wild animals that excrete dispersal forms of parasites into the soil may be a threat in urban areas. The aim of the study was to determine the level of contamination with geohelminth eggs in community playgrounds (fenced and unfenced), playgrounds in city parks, and a transect found along the banks of the River Oder. In 74 out of 424 examined soil samples, the presence of geohelminths was confirmed (Toxocara spp., Ancylostomatidae and Trichuris spp.). The highest prevalence was noted for Toxocara spp. roundworms. Both total and mean number of eggs in the examined samples, as well as the general prevalence, proved to be diversified in almost all types of development that were compared. Areas near the river emerged as places most exposed to the appearance of geohelminth eggs; playgrounds in city parks were less likely sites; community playgrounds in the city centre were the least common places.


Molecular Evolution of the Major Arthropod Chemoreceptor Gene Families.
The evolutionary origins of the three major families of chemoreceptors in arthropods-the odorant receptor (OR), gustatory receptor (GR), and ionotropic receptor (IR) families-occurred at the base of the Insecta, Animalia, and Protostomia, respectively. Comparison of receptor family sizes across arthropods reveals a generally positive correlation with their widely disparate complexity of chemical ecology. Closely related species reveal the ongoing processes of gene family evolution, including gene duplication, divergence, pseudogenization, and loss, that mediate these larger patterns. Sets of paralogous receptors within species reveal positive selection on amino acids in regions likely to contribute to ligand binding and specificity. Ligands of many ORs and some GRs and IRs have been identified; however, ligand identification for many more chemoreceptors is needed, as are structures for the OR/GR superfamily, to improve our understanding of the molecular evolution of these ecologically important receptors in arthropods.


Five-year success rate of resin-bonded fixed partial dentures: A systematic review.
To assess and compare the 5-year success rate of resin-bonded fixed partial dentures (RBFPDs) fabricated from different materials. An electronic search on 3 databases from January 1965 to March of 2017 was done for human randomized clinical trials (RCTs), and prospective and retrospective cohort studies. The key words used in the search were: Bridge OR bridges OR fixed partial OR fixed dental AND resin bonded OR Maryland OR ceramic bonded. Quality assessment was done using the Newcastle-Ottawa scale. Success was defined as the RBFPDs remaining in situ and not having experienced debonding, biological failures, or mechanical failures at the examination visit. Meta analyses of the included studies showed an estimated 5-year success rate of 88.18% for the metal framework RBFPDs and 84.41% for the nonmetal framework RBFPDs. The estimated 5-year success rate for each nonmetal material category was 92.07% for zirconia, 94.26% for In-Ceram alumina, and 84.83% for fiber-reinforced composite. The failure rate was not statistically significant among the single, double, and multiple retainers RBFPDs (P > .05). Technical complications were the main reason for failures. The 5-year clinical performance of RBFPDs is similar to the performance of conventional fixed partial dentures (FPDs) and implant-supported crowns. Clinicians should consider using RBFPDs more often because their clinical performance is similar to the performance of conventional FPDs and implant-supported crowns.


Positron emission tomography: physics, instrumentation, and image analysis.
Positron emission tomography (PET) is a noninvasive diagnostic technique that permits reconstruction of cross-sectional images of the human body which depict the biodistribution of PET tracer substances. A large variety of physiological PET tracers, mostly based on isotopes of carbon, nitrogen, oxygen, and fluorine is available and allows the in vivo investigation of organ perfusion, metabolic pathways and biomolecular processes in normal and diseased states. PET cameras utilize the physical characteristics of positron decay to derive quantitative measurements of tracer concentrations, a capability that has so far been elusive for conventional SPECT (single photon emission computed tomography) imaging techniques. Due to the short half lives of most PET isotopes, an on-site cyclotron and a radiochemistry unit are necessary to provide an adequate supply of PET tracers. While operating a PET center in the past was a complex procedure restricted to few academic centers with ample resources, PET technology has rapidly advanced in recent years and has entered the commercial nuclear medicine market. To date, the availability of compact cyclotrons with remote computer control, automated synthesis units for PET radiochemistry, high-performance PET cameras, and user-friendly analysis workstations permits installation of a clinical PET center within most nuclear medicine facilities. This review provides simple descriptions of important aspects concerning physics, instrumentation, and image analysis in PET imaging which should be understood by medical personnel involved in the clinical operation of a PET imaging center.


HIV status and type of coronary stent placed in patients presenting with ST-elevation myocardial infarction.
Drug-eluting stents (DES) outperform bare-metal stents (BMS) in reducing target vessel revascularization following a percutaneous coronary intervention (PCI). Little is known about the types of stents placed in HIV-positive patients presenting with ST-segment elevation myocardial infarctions (STEMIs). We used the 2003-2013 National Inpatient Sample to identify adults of 18 years or older presenting with STEMI. We evaluated differences in stent type placed following STEMIs on the basis of HIV status. Temporal trends in the use of PCI, DES, and BMS were studied on the basis of HIV status. Of 1 695 947 patients with STEMI, 5887 (0.3%) were HIV-positive patients. Following STEMIs, HIV-positive patients were equally likely to have PCI compared with HIV-negative patients [adjusted odds ratio (AOR): 1.04, 95% confidence interval (CI): 0.89-1.21, P=0.63]. However, HIV-positive patients were less likely to have DES (AOR: 0.83, 95% CI: 0.73-0.94, P=0.003) and more likely to have BMS (AOR: 1.26, 95% CI: 1.11-1.45, P=0.001). Over the 11-year period observed, there were increases in PCI following STEMIs in both HIV-positive and HIV-negative patients (all Ptrend<0.001). There were significant increases in the use of DES in HIV-negative patients [adjusted odds ratio (AOR) per year: 1.07, 95% CI: 1.06-1.09, Ptrend<0.001] and significant decreases in the use of BMS (AOR per year: 0.93, 95% CI: 0.92-0.94, Ptrend<0.001). Significant trends showing changed practice patterns in the use of DES and BMS among HIV-positive patients were not observed. Over a decade, there were significant increases in the use of PCI following STEMIs in both HIV-negative and HIV-positive patients. Although HIV-positive patients presenting with STEMIs were as likely as HIV-negative patients to undergo PCI, they were less likely to be treated with DES and more likely to receive BMS. Highlighting these observations will hopefully bring renewed attention to best practices for all STEMI patients.


A study of balloon type on calcified coronary lesion predilation: A finite element analysis.
Calcified coronary lesions have been one of the more difficult types of lesion for interventional treatment, and angioplasty is required to break the calcification before stent implantation so that the stent can expand smoothly, however, it remains unclear which type of angioplasty is optimal for different calcified lesions. In this study, a finite element approach was used to model normal balloons, cutting balloons, and AngioSculpt balloons. In addition, calcified lesions of different degrees, thicknesses, and lengths were modeled according to Intravascular ultrasound (IVUS) calcification grade. The above three balloons were used to pretreat calcified lesions, and the brittle fracture module for calcification was used to detect fracture success, to facilitate virtual stent implantation after predilation. The simulation results showed that with a thickness of less than 0.3 mm, balloons were unable to deal with calcified plaques in lesions of less than 120°, for 180° calcified lesions the cutting balloon fractured the calcified material at 1.2 MPa, the AngioSculpt balloon produced multiple fractures at 0.8 MPa for 270° calcified plaques, but was unable to fracture calcified lesions with a thickness of 0.4 mm. Based on these results, we conclude that the length of the lesion did not affect calcification fracture, while the thickness of the lesion did. In calcified lesions of approximately 180°, the cutting balloon showed the best predilation results, while the AngioSculpt balloon was optimal for 270°. In annular calcification, all three balloons were unable to fracture the lesion.


A case of eccrine porocarcinoma characterized by a progressive increase in the level of Ki-67 index: case report and review of literature.
Eccrine porocarcinoma is an extremely rare skin adnexal malignant neoplasia with highly invasive and metastatic potential. We report an additional case of eccrine porocarcinoma with intracranial metastases. This case is characterized by a complete record of the progress of eccrine porocarcinoma, its immunohistochemistry after three operations showed a progressive increase in the level of Ki-67 index. We herein report a case of a 37-year-old-male with eccrine carcinoma occurring on the left posterior occipital scalp which invaded the skull and dura, presenting with progressive headache. This patient has performed three surgeries in total. During the last hospitalization, he underwent an extended surgical resection, lymphadenectomy, myocutaneous flap transplantation and vascular anastomosis in our institution. After surgery, he was treating with radiotherapy at 200 Gray in 12 fractions. But one year after the operation, he developed chest tightness, imaging examination and biopsy puncture revealed pulmonary metastasis. Intracranial metastasis of eccrine porocarcinoma is a late event with poor prognosis. This case emphases on that progressively increased level of Ki-67 index may predict more chance to occur the intracranial metastasis of scalp eccrine porocarcinoma, long-term follow-up and appropriately dense follow-up interval is necessary.


A Rare Case of Premenarchal Ovarian Abscess Presenting as an Acute Abdomen.
Ovarian abscesses are usually seen in females of reproductive age group. They may occur secondary to urinary tract infections, pelvic inflammatory diseases, or gastrointestinal infections. They are uncommon in premenarchal females. They can be either managed conservatively with antibiotics and analgesics or may require surgery. In this case report, we present the case of a 6-year-old female who presented to us with an acute abdomen, which was diagnosed as a case of ovarian abscess and improved on exploration and drainage.


Imaging in staging of malignant lymphoma: a systematic review.
Computed tomography (CT) is currently the most commonly used means for staging malignant lymphoma. 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), FDG-PET/CT fusion, and whole-body magnetic resonance imaging (WB-MRI) are potential alternatives. The purpose of this study was to systematically review published data on the diagnostic performance of CT, FDG-PET, FDG-PET/CT fusion, and WB-MRI in staging of malignant lymphoma. In addition, technical aspects, procedures, advantages, and drawbacks of each imaging modality are outlined. Three CT studies, 17 FDG-PET studies, and 4 FDG-PET/CT fusion studies were included in this systematic review. The studies were of moderate methodological quality and used different scoring systems to stage malignant lymphoma. CT remains the standard imaging modality for initial staging of malignant lymphoma, while FDG-PET has an essential role in restaging after treatment. Early results suggest that FDG-PET/CT fusion outperforms both CT alone and FDG-PET alone. Data on the diagnostic performance of WB-MRI are lacking. Future well-designed studies, expressing their results according to the Ann Arbor staging system, are needed to determine which imaging modality is most accurate and cost-effective in staging malignant lymphoma.


Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma.
Toll-like receptor 6 (TLR6) is one of a series of highly conserved innate immune receptors. We resequenced TLR6 in DNA samples from 24 African Americans, 23 European Americans, and 24 Hispanic Americans, identifying 53 SNPs, 22 with an allele frequency >5%. Significant differences in SNP frequencies among the three populations were noted. In all, 11 SNPs caused amino-acid changes, including one with a frequency >5% in all three populations. Utilizing this SNP (Ser249Pro), we performed exploratory nested case-control disease-association studies, including one involving 56 African Americans with asthma and 93 African American controls. The minor allele of this SNP was associated with decreased risk for asthma (odds ratio 0.38, 95% CI 0.16-0.87, P=0.01), an effect consistent with the known biology of the toll-like receptors. Although replication of this finding in other, larger samples is needed, variation in TLR6 may have relevance to the pathogenesis of immunologically mediated diseases.


Anxiety Management in Primary Care: Implementing the National Institute of Clinical Excellence Guidelines.
More than 40 million Americans suffer from anxiety disorders, ranking them as one of the most common mental health disorders in America. The purpose of this pilot study was to educate providers on the National Institute Clinical Excellence (NICE) anxiety guidelines and monitor providers' perceived competence in managing anxiety. Results showed perceived competence increased significantly pre-intervention to immediately post-intervention (p=0.001), and data revealed the scores did not change significantly immediately post-to six-weeks post (p=0.170). Providers who implemented the guidelines into practice had significantly higher scores (p=0.026) than those who did not implement the guidelines.


Outcomes Following Surgery for Common Peroneal Nerve Intraneural Ganglion Cysts: A Case Series and Systematic Review.
Intraneural ganglia are a rare cause of common peroneal nerve palsy. Although several treatment modalities exist, surgical intervention is recommended, especially in the setting of neurological dysfunction. We present a case series and systematic review on the clinical outcomes following surgical excision of common peroneal nerve intraneural ganglia. We performed a retrospective chart review of all patients who had undergone surgery for common peroneal nerve intraneural ganglia at Queen Elizabeth Hospital in Birmingham, UK, from 2012 to 2022. Demographic and pre- and postoperative findings were collected. A comprehensive literature search of MEDLINE and EMBASE databases was also performed to identify similar studies. Data were subsequently extracted from included studies and qualitatively analyzed. Five patients at our center underwent procedures to excise intraneural ganglia. There was a male preponderance. Pain, foot drop, and local swelling were the common presenting features. Postoperatively, all patients who completed follow-up demonstrated improved motor function with no documented cyst recurrence. The systematic review identified 6 studies involving 128 patients with intraneural ganglia treated with surgery. Similar findings were reported, with objective and subjective measures of foot and ankle function and symptoms improving after surgical intervention. The recurrence rate varied from 0% to 25%, although most recurrences were extraneural. Excision of intraneural ganglia is associated with symptomatic relief and functional improvement. Recurrence rates are relatively low and are rarely intraneural.


Experimental observation of a superfluid gyroscope in a dilute Bose-Einstein condensate.
We have observed a three-dimensional gyroscopic effect associated with a vortex in a dilute Bose-Einstein condensed gas. A condensate with a vortex possesses a single quantum of circulation, and this causes the plane of oscillation of the scissors mode to precess around the vortex line. We have measured the precession rate of the scissors oscillation. From this we deduced the angular momentum associated with the vortex line and found a value close to Planck's over 2pi per particle, as predicted for a superfluid.


Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown dramatic effects against that tumors harboring EGFR activating mutations in the EGFR intracytoplasmic tyrosine kinase domain and resulted in cell apoptosis. Unfortunately, a number of patients ultimately developed resistance by multiple mechanisms. Thus, elucidation of the mechanism of resistance to EGFR-TKIs can provide strategies for blocking or reversing the situation. Recent studies suggested that redundant kinase activation plays pivotal roles in escaping from the effects of EGFR-TKIs. Herein, we aimed to characterize several molecular events involved in the resistance to EGFR-TKIs mediated by redundant kinase activation.


Silicon nanocluster prepared using ion beam mixing technique.
In this work, we present the results of modification of absorption band gap of Silicon nanoclusters (Si-nc) prepared by ion beam mixing on pre-irradiated fused silica. 30 keV Ar+ ions at fluences of 5 x 10(16) to 4 x 10(17) cm(-2) were used to create defects in fused silica glass before introducing Si atoms in the substrate. Si was introduced in the substrates by ion beam mixing using 30 keV Ar+ ions at fluence 1 x 10(17) cm(-2). From UV-Vis absorption spectra, band-gap of Si-nc has been determined for samples prepared at different ion beam-mixing parameters. The absorption edge shifts towards higher energies and size of the silicon nanoclusters decreases with an increase in ion beam fluence used for pre-mixing irradiation.


Sensory Recalibration from Visually Amplified Rotations While Walking.
Recent work has pointed to the advantages of using distorted reality to foster sensorimotor adaptations. Here we evaluate the extent to which a visuomotor discrepancy created within the large CAVE2 Hybrid Reality Environment might induce an adaptive effect in walking. This experiment specifically studied the consequences of exposure to a rotational gain that made it appear as though the subjects were turning more than actual by a ratio of 3 to 2. We then studied subjects' abilities make turns while blindfolded before and after the experience. This brief training period (~5 minutes) resulted in slightly larger turns. Such rapid adaptive responses can be interpreted as an alteration of the motor plan and possibly a recalibration of proprioceptive and vestibular senses caused by the alteration of visual input. This study provides preliminary evidence of the possibilities of using distorted reality to constructively enhance motor training and rehabilitation.


[Effect of inhibitors of energy-dependent Ca2+-transporting systems on ATP-hydrolase activity of smooth muscle actomyosin].
Comparative investigation of of smooth muscle actomyosine ATP-ase sensitivity to some inhibitors of energy-dependent Ca(2+)-transporting systems has been carried out. It is proved that the ATP-ase of actomyosine is nonselectively inhibited by thapsigargin (imaginary inhibition constant Ki is equal 29.4 +/- 5.2 nM), cyclopiazonic acid (Ki = 626 +/- 118 nM), eosin Y (Ki = 70 +/- 14 nM) and p-chlormercurybenzoate (Ki = 380 +/- 151 nM). The data obtained could be used for the further development of the ideas about regularities of Ca(2+)-dependent control of the smooth muscles contraction-relaxation.


Prediction of ischemic stroke in young Indians: is thrombophilia profiling a way out?
Stroke in the young is attributed to the prevalence of thrombophilia, however, reports explaining the cause mechanisms from Indian populations are largely not known. The information about the association of inherited thrombophilia and occurrence of stroke is still missing. Therefore, we describe here 52 cases of young ischemic stroke of which 22 cases were of recurrent stroke and 30 cases of first episode stroke along with an equal number of healthy controls. Imaging techniques (CT/MRI/Doppler studies) were used to identify the type and location of infarcts among various regions of the brain. All the patients and controls were screened for hypercoagulable state by employing Pro C global test. Those tested positive for the latter were evaluated for conventional thrombophilic factors, activity levels of protein C and protein S, antithrombin III levels, plasma homocysteine levels and presence of activated protein C resistance, lupus anticoagulant, methylenetetrahydrofolate reductase (MTHFR C677T) and prothrombin G20210A polymorphisms. Out of 52 cases there were 22 cases of recurrent stroke and 30 cases of first ischemic stroke. Infarcts were single in 39 out of 52 cases and multiple in 13 cases. Among the different regions of brain internal capsule infarcts were seen in 13 of 52 (25%) cases, and cerebellum, basal ganglion and midbrain infarcts were seen in five cases (9.6%) each and remaining infarcts were in other anatomical regions of the brain. Left middle cerebral artery territory was involved in 17 of 52 (32.7%) cases. The prevalence of individual thrombophilia among cases ranged from 28.8% (15/52) for protein S and 11.5% (6/52) for protein C deficiencies respectively. All cases of protein C were protein S deficient. Five cases of protein C deficiency patients were of 25 years and younger as compared with one case in the at least 25 years age group. Plasma homocysteine levels were elevated in three cases (5.7%) as compared with normal levels in controls. Homozygous MTHFR C677T was seen in three cases, whereas heterozygosity for the same was observed in five cases. Out of three homozygous cases for C677T MTHFR polymorphism, two of these patients had hyperhomocysteinemia. None of the five cases of heterozygous C677T MTHFR polymorphism had hyperhomocysteinemia. All patients were found to be negative for prothrombin G20210A mutation. The results of the present study suggest that protein S deficiency alone or protein S deficiency in combination with protein C deficiency as well as hyperhomocysteinemia are significantly associated with ischemic stroke in young Indians.


A novel method for the evaluation of virus-induced gene silencing efficiency.
Virus-induced gene silencing (VIGS) is an important tool for studying gene function. However, a number of factors highly restrict the application of VIGS, such as unstable efficiency and tissue-specific silencing. We developed a novel evaluation method for improving the applicability of VIGS vectors. In this method, 4 indexes were defined and utilized to evaluate VIGS efficiency by silencing the endogenous phytoene desaturase (PDS) gene with a tobacco rattle virus-based VIGS vector. To illustrate the reliability of this evaluation method, we assessed the silencing efficiency of SpPDS and SpMPK1 in Solanum pimpinellifolium. The silencing results of SpPDS showed that an optical density at 600 nm of 2.0 was more suitable than 1.0 for VIGS in S. pimpinellifolium. This suggests that the proposed evaluation method is a valid technique for optimizing the VIGS system of plants. Moreover, the SpMPK1 gene was highly silenced in the 4th-9th leaves with a 50-95% reduction in transcription levels, further demonstrating that this method can be used to select highly silenced candidates for further experiments, particularly when the target gene shows no phenotypic change after being silenced.


Relationship between chromaffin cells and blood vessels in the rat adrenal medulla: a transmission electron microscopic study combined with blood vessel reconstructions.
The rat adrenal medulla architecture was examined using a combination of medullary blood vessel reconstructions and transmission electron microscopy. The peripheral radicles of the central vein and the medullary capillaries of the medullary arteries were thus precisely identified in the electron microscopic observations. The observations confirmed that the peripheral segments of the central vein were sinusoidal vessels with an attenuated and fenestrated endothelial wall. No ultrastructural differences were observed between segments lined by epinephrine-storing cells and those lined by norepinephrine-storing cells. The findings suggest that these peripheral segments of the adrenal central vein were sites of cortical hormonal effects on the adrenal medulla. The vessel structure does not support the hypothesis that medullary chromaffin-cell development is controlled by selective distribution of adrenal blood vessels.