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The rapid fixation of a rare allelic form of alpha-glycerol phosphate dehydrogenase is related to a loss of competitive ability in nature of factory-reared screwworm flies. The increase in frequency results from selection for survival under conditions of domestication and rapid development at high constant temperatures in the factory. | Screw Worm Infection |
A comparison of hysterosalpingography (HSG) with endoscopy in the evaluation of tubal function in 117 infertile women is presented. Results were in accord in 55% of the patients. Correction for endoscopic error and the limitations of HSG increased the positive correlation to 74%. Twenty-three patients (20%) with abnormal findings at HSG were normal with endoscopy. Ten patients (8%) had normal HSG but abnormal endoscopic findings. Fifteen patients (12%) with positive findings by HSG had different positive findings at endoscopy. Additional endoscopic findings in 47 patients are listed. Review of 26 patients with endoscopy-confirmed endometriosis revealed that 14 (54%) had a normal HSG and normal history and pelvic examination. Although HSG should be the method of choice as part of the basic evaluation, an infertile woman should undergo endoscopy before the evaluation is considered complete or final. | Culdoscopy |
Acyl-ACP thioesterase (TE) catalyzes the hydrolysis of thioester bonds during type II fatty acid synthesis and directly determines fatty acid chain length. Most TEs are responsible for recognition of 16:0 and 18:1 substrates, while specific TEs interrupt acyl-ACP elongation at C8-C14. However, the acyl selection mechanism of TE has not been thoroughly elucidated to date. In this study, the crystal structure of the C12-specific thioesterase FatB from Umbellularia californica, which consists of two independent hotdog domains, was determined. An uncanonical Asp-His-Glu catalytic network was identified on the C-terminal hotdog domain, whereas the substrate binding pocket was determined to be on the N-terminal hotdog domain. Moreover, we elucidated UcFatB's substrate selection mechanism, which is accommodated by several unconservative amino acids on the beta5, beta2, and beta4 sheets and enclosed by T137 on the alpha1 helix. On this basis, the C12-specific TE was rationally redesigned toward C14 selectivity by tuning the substrate binding pocket capacity. The T137G mutant demonstrated comparative relative activity on C14 substrates compared to C12 substrates in vitro. Furthermore, the reconstructed UcFatB_T137G achieved C14 fatty acid content up to 40% in contrast to 10% C14 from the wild type in engineered E. coli cells. The unraveled substrate selection mechanism of TE provides a new strategy for tailoring fatty acid synthesis. | Thiolester Hydrolases |
Regional lymph node metastasis is one of the important indicators of cutaneous malignant melanoma. Newly formed lymphatic vessels are considered to provide a route whereby tumor cells can migrate to the lymph nodes. Both vascular endothelial growth factors (VEGF) -C and -D have been confirmed to participate in tumor lymphangiogenesis, but the prognostic significance of VEGF-C, VEGF-D, and lymphangiogenesis in cutaneous malignant melanoma remains controversial. To clarify the effects of these factors and to evaluate the relationships between lymphangiogenesis, lymph node metastasis, and prognosis in patients with malignant melanoma, the expressions of VEGF-C, VEGF-D, and their receptor (VEGFR) -3 were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction. The expressions of both VEGF-C and VEGF-D proteins were concomitantly detected in the cytoplasm of the malignant cells. VEGF-C and VEGF-D expressions were associated with VEGFR-3 expression and were significantly correlated with both peritumoral lymphangiogenesis and lymph node metastasis. The incidence of peritumoral lymphatic vessels was significantly higher in lymph node metastatic melanomas than that in nonmetastatic melanomas. Univariate and multivariate analyses indicated that VEGF-C and VEGF-D were independent prognostic factors for overall survival and disease-free survival in patients with malignant melanoma. This study suggests that both VEGF-C and VEGF-D are involved in peritumoral lymphangiogenesis and lymphatic metastasis. VEGF-C and VEGF-D expression may be clinically useful indicators for prognostic evaluation in patients with cutaneous malignant melanoma." | Vascular Endothelial Growth Factor Receptor-3 |
Left-right patterning and lateralised behaviour is an ubiquitous aspect of plants and animals. The mechanisms linking cellular chirality to the large-scale asymmetry of multicellular structures are incompletely understood, and it has been suggested that the chirality of living cells is hardwired in their cytoskeleton. We examined the question of biased asymmetry in a unique organism: the slime mould Physarum polycephalum, which is unicellular yet possesses macroscopic, complex structure and behaviour. In laboratory experiment using a T-shape, we found that Physarum turns right in more than 74% of trials. The results are in agreement with previously published studies on asymmetric movement of muscle cells, neutrophils, liver cells and growing neural filaments, and for the first time reveal the presence of consistently-biased laterality in the fungi kingdom. Exact mechanisms of the slime mould's direction preference remain unknown. | Physarum polycephalum |
Pheochromocytoma is a rare tumor, but it represents a potentially curable form of hypertension. In patients with inherited pheochromocytoma, benign and bilateral tumors are more common. The diagnosis of pheochromocytoma rests in biochemical confirmation of catecholamine excess. Plasma-free metanephrine levels are arguably the most sensitive and specific test for the biochemical diagnosis of pheochromocytoma in high-risk patient populations. A timed 24-hour urine collection for total catecholamines and metabolic products (eg, vanillylmandelic acid and metanephrines) is the favored confirmatory test. Localization is most commonly accomplished with high-resolution computed tomography imaging, but magnetic resonance imaging can also be used. If both of these imaging modalities are nonlocalizing or equivocal, then radiolabeled meta-iodobenzylguanidine or somatostatin can be used to identify an adrenal or extra-adrenal tumor (paraganglioma). These imaging modalities can be used in the evaluation of patients with suspected or confirmed recurrent or metastatic disease. Systemic therapies for the treatment of patients with recurrent or metastatic disease have been disappointing. Radiation therapy is best applied for palliative relief of pain associated with bony metastases. In the absence of radiographic evidence for local tumor invasion, laparoscopic resection of small- to medium-sized (< 6 cm) pheochromocytomas is indicated. Abundant evidence indicates that this approach is safe and well tolerated and results in more rapid recovery and less long-term wound morbidity compared to open anterior or posterior adrenalectomy. Open anterior adrenalectomy is appropriate for patients with large or recurrent tumors, suspected or documented locoregional invasion, or for those patients in whom a laparoscopic approach is technically contraindicated. For selected patients with pheochromocytoma in the von Hipple-Lindau syndrome or multiple endocrine neoplasia type 2 setting in which the cumulative incidence of clinical bilateral tumors is high, a cortical-sparing approach may minimize the risk of Addisonian complications. | Pheochromocytoma |
Social relationships among spouses, family members, and friends are known to affect physical and mental health. In particular, long-lasting bonds between socio-sexual partners have profound effects on cognitive, social, emotional, and physical well-being. We have previously reported that pair bonding in monogamous prairie voles (Microtus ochrogaster) is prevented by a single prolonged stress (SPS) paradigm, which causes behavioral and endocrine symptoms resembling post-traumatic stress disorder (PTSD) patients in rats (Arai et al., 2016). Since fear memory function is crucial for anxiety-related disorders such as PTSD, we investigated the effects of pair bonding on fear learning in prairie voles. We applied an SPS paradigm to male prairie voles after the cohabitation with a male (cage-mate group) or female (pair-bonded group). The cage-mate group, but not the pair-bonded group, showed enhanced fear response in a contextual fear conditioning test following the SPS treatment. Immunohistochemical analyses revealed that cFos-positive cells in the central amygdala were increased in the pair-bonded group after the contextual fear conditioning test and that oxytocin immunoreactivity in the paraventricular nucleus of the hypothalamus was significantly higher in the pair-bonded group than the cage-mate group. This pair-bonding dependent blunting of fear memory response was confirmed by a passive avoidance test, another fear-based learning test. Interestingly, intracerebroventricular injection of an oxytocin receptor antagonist 30 min before the passive avoidance test blocked the blunting effect of pair bonding on fear learning. Thus, pair bonding between socio-sexual partners results in social buffering in the absence of the partner, blunting fear learning, which may be mediated by oxytocin signaling. | Ornipressin |
The aim of this paper was to evaluate the role of bcl-2 in the susceptibility of the MCF7 ADR human breast carcinoma line overexpressing the P-170 glycoprotein (P-170) to various drugs. The sensitivity to four multidrug resistance (MDR)-related drugs (doxorubicin (ADR), vincristine (VCR), vinblastine (VBL), actinomycin D (ACTD)) and three MDR-non-related drugs (cisplatin (DDP), bischloroethylnitrosourea (BCNU), 5-fluorouracil (5-FU)) was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay in three bcl-2-overexpressing clones obtained from the MCF7 ADR line. We found that the bcl-2-overexpressing clones show increased resistance to DDP and BCNU, while no difference to 5-FU were observed between the control cells and bcl-2 transfectants. Surprisingly, bcl-2-overexpressing clones displayed an increased sensitivity compared with the control cells to the MDR-related drugs ADR, VCR, VBL and ACTD. Focusing on DDP and ADR, we found that the increased resistance of the bcl-2 transfectants to DDP was correlated to their ability to prevent apoptosis, while the enhanced sensitivity to ADR was associated with an increased ADR accumulation and a decreased ADR efflux. Moreover, while bcl-2 overexpression does not induce changes in P-170 glycoprotein expression, it did induce a reduction of the adenosine triphosphate (ATP) levels and basal protein kinase C (PKC) activity, both of which have a crucial role in the regulation of the MDR phenotype. In conclusion, the effect of bcl-2 on antineoplastic sensitivity observed in this study underscores the idea that bcl-2 may have distinct biological effects depending on the anticancer drug used. | Genes, bcl-2 |
PURPOSE: To estimate the prevalence of psychiatric morbidity and dual diagnosis in a population of decedents with positive drug toxicology and evaluate changes over time between 2001-2002 and 2011-2012. MATERIALS AND METHODS: A total of 520 autopsied drug users with positive toxicology were included in the study from 2001 to 2002 and from 2011 to 2012. Materials included autopsy reports, toxicological screening during autopsy and data from the Danish national health registers, including psychiatric diagnoses from psychiatric hospitals and ambulatory functions, dispensed prescription use from pharmacies and registered treatment for drug use disorders. RESULTS: In 2001-2002, 63.3% of the decedents had only positive toxicology, 22.5% also had psychiatric morbidity, and 14.2% had a dual diagnosis. In 2011-2012, 56.4% had only positive toxicology, 26.1% also had psychiatric morbidity, and 17.5% had a dual diagnosis. None of the changes were significant. Decedents with only positive toxicology became older at time of death over time; decedents with psychiatric morbidity and a dual diagnosis did not. The prevalence of nonprescribed psychotropic medication, methadone and benzodiazepines increased. CONCLUSION: Decedents with psychiatric morbidity and dual diagnosis did not increase their lifespan over a 10-year period. Decedents with only positive toxicology increasingly consumed nonprescribed psychotropic medication and may have suffered from undiagnosed psychiatric disorders. The prevalence of prescribed and nonprescribed benzodiazepines and methadone increased and may have contributed to premature mortality. | Diagnosis, Dual (Psychiatry) |
The structure of the papillomatous junction between epidermis and dermis (papillomatous netting, PN) in the skin of cetaceans (white whales, bowhead, and gray whales) and sirens (American manatee, dugong) was studied and compared using histophysiological and morphogeometric methods. The relative extent of PN development proved to be similar in members of both orders, but significant differences were found in PN configuration, the volume of free area of grille", the degree of skin vertical compression, and skin density, which influence buoyancy. The differences are discussed from the viewpoint of species biology." | Dugong |
Eight pigeons were exposed to a two-component multiple schedule. In each component, four-peck sequences across left and right keys were reinforced according to a variability threshold contingency. In one condition, only infrequently occurring response sequences were reinforced in each component, thereby generating highly variable sequences. In a separate condition, when the variability threshold contingency was lenient in each component, sequences were much less variable. In each condition, reinforcer magnitude was manipulated across components, and the larger reinforcer magnitude produced less variability than the smaller reinforcer magnitude. These results suggest that larger reinforcers hinder the reinforcement of behavioral variability. The results are interpretable in terms of the larger reinforcer inducing a greater level of behavioral repetition, particularly as the time to reinforcement was approached. This effect may have implications for reinforcing behavioral variability in humans. | Reinforcement, Psychology |
NASA's Gravity Recovery and Interior Laboratory (GRAIL) spacecraft revealed the crust of the Moon is highly porous, with ~4% porosity at 20 km deep. The deep lying porosity discovered by GRAIL has been difficult to explain, with most current models only able to explain high porosity near the lunar surface (first few kilometers) or inside complex craters. Using hydrocode routines we simulated fracturing and generation of porosity by large impacts in lunar, martian, and Earth crust. Our simulations indicate impacts that produce 100-1000 km scale basins alone are capable of producing all observed porosity within the lunar crust. Simulations under the higher surface gravity of Mars and Earth suggest basin forming impacts can be a primary source of porosity and fracturing of ancient planetary crusts. Thus, we show that impacts could have supported widespread crustal fluid circulation, with important implications for subsurface habitable environments on early Earth and Mars. | Planets |
The mouse is the most commonly used mammalian model to study disease, including kidney disease. However, close attention needs to be paid to the differences and effects of genetic background. The default choice of most investigators is to use C57BL/6 mice, but not all C57BL/6 mice are the same. Ever since the C57BL/6 line was first established, differences in the genetic background have risen between substrains, which have major implications in the phenotypes expressed in kidney disease. Furthermore, considering that C57BL/6 substrains are relatively resistant to kidney damage, there can be major benefits in selecting other mouse inbred strains when studying kidney disease. These strains can show more similar responses regarding kidney damage as in humans, and results may therefore translate better to human application. Genetically diverse mice, such as the Diversity Outbred mice, allow investigators to study kidney phenotypes with comparable levels of genetic diversity as seen in humans, which yield results that more closely reflect the variation in human disease outcomes due to genetic variation. Hence, embracing the genetic diversity that is present in mice can lead to better translational research methods. Investigators need to always take into consideration that genetic background is a variable that can alter results significantly, and optimization of translational research asks for careful strain selection and more rigorous reporting of the genetic background that is being used in experiment. | Genetic Background |
Theileria annulata is an intracellular protozoan parasite that infects B cells and macrophages of ruminants. Macrophages infected with T. annulata are de-differentiated and display tumour cell properties and a metastatic behaviour. How parasitized cells adapt their morphology, motility and invasive behaviour has not yet been addressed in detail. In this study, I investigated the regulation of host cell actin dynamics in T. annulata-transformed macrophages and how this affects host cell morphology and motility. T. annulata was found to promote the formation of filamentous-actin-rich podosome-type adhesions (PTAs) and lamellipodia, and to establish a polarized morphology of the infected cell. Characteristic for parasite-dependent host cell polarization is that infected cells display a single, persistent lamellipodium. Src kinases--in particular Hck--are required for the polar extension of this lamellipodium. Hck does so by promoting the clustered assembly of PTAs and accumulation of proteins of the Ezrin, Radixin, Moesin (ERM) family in lamellipodia. Polar accumulation of PTAs and ERM proteins correlates with focal matrix degradation underneath lamellipodia. These findings suggest that T. annulata equips its host cell with properties to adhere and invade. These properties are likely to promote the motile behaviour required for dissemination of infected cells in vivo. | Theileria annulata |
Sulphamonomethoxine (SMM), sulphadimidine (SDD), sulphadiazine (SDZ) and their N4-acetyl derivatives (AcSMM, AcSDD and AcSDZ) were intravenously injected into Goettingen miniature pigs and deacetylation was evaluated from plasma concentration-time curves, renal excretion, and rate constants obtained from pharmacokinetic analysis, using a non-linear least-squares method. Deacetylated metabolite was detected in both plasma and urine after intravenous injection of AcSMM, AcSDD and AcSDZ. The area under the curve (AUC) values for the deacetylated metabolite were significantly higher than those for acetyl derivatives after AcSMM and AcSDD administration, but significantly lower after AcSDZ. After AcSMM and AcSDD injection, the concentration ratio between deacetylated metabolite and acetyl derivative was almost constant in the terminal linear phase and similar to that seen after injection of sulphonamide. After AcSDZ injection, however, a constant ratio was not observed. These results indicate that deacetylation can have a significant effect on the pharmacokinetics of SMM and SDD, but not on those of SDZ in pigs. The rate constant for deacetylation was significantly higher than that for acetylation for SMM and SDD, but significantly lower for SDZ. It is, therefore, concluded that deacetylation may be a determinant of the pharmacokinetics of SMM and SDD in pigs. It was, however, not a determinant of SDZ pharmacokinetics because N4-acetylation is not the main elimination route in pigs. | Sulfamonomethoxine |
PURPOSE: This phenomenological study tried to understand the essence of the transitional care experience of medicaid case managers and its structural meaning. In addition, it was attempted to establish a system of transitional care and seek support measures for medicaid case managers. METHODS: The participants of this study were 7 medicaid case managers who had spent more than 1 year and 6 months in medicaid pilot project. Data were collected with individual in-depth interviews from June to December 2021. The data were analyzed by Giorgi's phenomenological analysis method. RESULTS: The seven constituents derived from the results of this study were 'struggle to establish a living environment', 'dedication to supporting independent living', 'anxiety about safety', 'pressure on care responsibilities', 'distress in building the pilot project', 'pride in role', and 'expectation for improvement'. CONCLUSION: The study results provide a comprehensive understanding of the transition care reality for medicaid case managers. They also shed light on managers' perceptions and attitudes. These findings can serve as fundamental information for establishing support measures for medicaid case managers and transitional care systems. | Case Managers |
Preparedness to recognize and appropriately manage medical emergencies in the dental environment includes the following: current BLS certification for all office staff; didactic and clinical courses in emergency medicine; periodic office emergency drills; telephone numbers of EMS or other appropriately trained health care providers; emergency drug kit and equipment, and the knowledge to properly use all items. This update on office emergencies and emergency kits replaces the previous Association report, prepared in 1980 by the Council on Dental Therapeutics. | Emergency Treatment |
BACKGROUND: Pediatric status epilepticus occurs in about 44/100.000 children per year with an unknown cause in about a third of patients. One cause can be the ingestion of plants containing toxins that target the central nervous system. Here we describe an ingestion of water hemlock resulting in a status epilepticus. METHODS: We studied in detail the clinical, laboratory, electrophysiological, and radiological features of a patient with status epilepticus. RESULTS: A 9-year-old boy presented to the pediatric emergency department for sudden onset of nausea, vomiting, and status epilepticus approximately one hour after the patient had bitten into the root of a water plant in an inner-city park. Bilateral tonic-clonic seizures could only be terminated after administration of midazolam, lorazepam, and finally propofol. Cranial MRI, cerebrospinal fluid, and EEG findings were largely unremarkable. The ingested plant was identified as water hemlock through a detailed search with the help of a drawing issued by the patient with the help of the medical team. The specific toxicological analysis for water hemlock verified the presence of cicutoxin and cicudiol in the blood sample. The patient was discharged, levetiracetam was weaned off four weeks later, and he has remained seizure free since. CONCLUSIONS: Given the considerable percentage of cases of unknown etiology in new-onset pediatric status epilepticus, it is important to consider plant intoxication as a possible cause. | Cicuta |
Catastrophes can occur without warning and inevitably cause short-term and long-term problems. In disaster zones, having an action plan to alleviate difficulties can reduce or prevent many long-lasting complications. One of the most critical and urgent issues is sanitation. Water, energy, personnel, transportation, and the allocation of resources in disaster areas tend to become very limited during emergencies. Sanitation systems suffer in the process, potentially leading to crises due to unsafe and unhygienic surroundings. This article explores the problems of current sanitation practices in disaster areas and identifies the essential characteristics of sustainable sanitation systems. This study also presents a plan for an innovative and sustainable sanitation system using a waterless, portable, private toilet, in addition to a procedure for collecting and disposing waste. The system is agronomic, is socially acceptable, prevents contact with human waste, and can be used for individuals or families. Environmental pollution and social problems (such as sexual harassment) can be reduced both during and after restoration. | Toilet Facilities |
BACKGROUND: Dislocation of the knee is a serious and potentially limb-threatening injury. There are three types of dislocation around the knee joint: patellofemoral, tibiofemoral, and tibiofibular. Tibiofemoral dislocation is the variant that is deemed the most serious, with a higher risk of compromise to the popliteal artery and common peroneal nerve. Although simultaneous dislocations of two types have been described, there has been no such description of all three types occurring simultaneously. CASE PRESENTATION: We present a case of a 40-year-old hairdresser who suffered a fall off her moped in Spain, and simultaneously dislocated all three articulations around the knee. Diagnosis was achieved with clinical examination, plain films, and computed tomography and magnetic resonance imaging scans. Management consisted of initial surgical debridement and reduction with stabilization of the affected joints. CONCLUSION: Dislocation of the knee is an uncommon but life changing and potentially limb-threatening injury. It should always be suspected in trauma patients who present with multiligamentous knee injuries. The main concern is of neurovascular compromise to the lower leg, namely, the popliteal artery and common peroneal nerve. The treatment of multiligamentous knee injuries for most patients is surgical treatment with physiotherapy and adequate stabilization of the knee joint. Close monitoring of progress of the knee in terms of persistent laxity, range of movement, and functional status is required for at least 1-year post injury. Current evidence suggests that, despite good functional outcomes for knee dislocations in the short term, the prevalence of post-traumatic osteoarthritis is high in the long term. | Knee Dislocation |
OBJECTIVES: The aim of the present exploratory clinical study was to evaluate LD as an add-on therapy for treating nightmares. METHODS: Thirty-two subjects having nightmares (ICD-10: F51.5) at least twice a week participated. Subjects were randomly assigned to group: A) Gestalt therapy group (= GTG), or B) Gestalt and lucid dreaming group therapy (= LDG). Each group lasted ten weeks. Participants kept a sleep/dream diary over the treatment. Examinations with respect to nightmare frequency and sleep quality (Pittsburgh Sleep Quality Index) were carried out at the beginning, after five and ten weeks and at a follow-up three months later. RESULTS: Concerning nightmare frequency, a significant reduction was found in both groups after the ten-week-study and at the follow-up (Wilcoxon test: P </= 0.05). Significant reduction in dream recall frequency could only be observed in the GTG (Wilcoxon test: P </= 0.05). For subjects having succeeded in learning lucid dreaming, reduction was sooner and higher. Sleep quality improved for both groups at the follow-up (P </= 0.05, Wilcoxon test). Only the LDG showed significant improvement at the end of therapy (P </= 0.05). CONCLUSION: Lucid dreaming, in combination with Gestalt therapy, is a potent technique to reduce nightmare frequency and improve the subjective quality of sleep. | Gestalt Therapy |
Open or accessible chromatin typifies euchromatic regions and helps define cell type-specific transcription programs. DNA replication massively disorders chromatin composition and structure, and how accessible regions are affected by and recover from this disruption has been unclear. Here, we present repli-ATAC-seq, a protocol to profile accessible chromatin genome-wide on replicated DNA starting from 100,000 cells. In this method, replicated DNA is labeled with a short 5-ethynyl-2'-deoxyuridine (EdU) pulse in cultured cells and isolated from a population of tagmented fragments for amplification and next-generation sequencing. Repli-ATAC-seq provides high-resolution information on chromatin dynamics after DNA replication and reveals new insights into the interplay between DNA replication, transcription, and the chromatin landscape." | Chromatin Immunoprecipitation Sequencing |
Annual and daily levels of the two major oxides of nitrogen (NOX), nitric oxide (NO) and nitrogen dioxide (NO2) are still rising in the atmosphere of the urban environment and in close proximity to automobile and airport traffic. Although oxides of nitrogen give rise to other phytotoxic pollutants such as ozone they are also in their own right damaging to plant health. This injury is not normally visible but is reflected in poorer growth and loss of productivity in terms of value and amenity. Few if any reviews have considered the effects of atmospheric concentrations of NOX as separate phytotoxic agents especially at the metabolic level. This paper is an attempt to remedy this deficiency and to promote an understanding of the problem. | Nitrogen Oxides |
OBJECTIVE: Fat necrosis (FN) is a well-known complication in plastic surgery. Excision of symptomatic FN has been the gold standard, but it often results in contour irregularities that require subsequent treatment. Different alternative surgical and nonsurgical management strategies have been described; however, there are currently no guidelines. This literature review aims to provide an overview of available treatment options and current management standards to support clinical decision making. METHOD: A literature search in the databases PubMed, Embase (via Ovid), and Web Of Science was carried out to identify eligible articles. The search strategy included combinations of the following terms: Fat necrosis "AND (treatment OR management OR therapy). Six articles discussing or reporting management strategies of FN in a plastic surgery context were included. RESULTS: A variety of techniques were used to manage symptomatic FN. Asymptomatic or small lesions can be treated conservatively. Oil cyst and moderately sized areas of symptomatic FN can effectively be treated by aspiration, ultrasound-assisted liposuction, or needle aeration. Calcified and large areas of FN require excision and debridement of necrotic fat tissue CONCLUSION: At present, there is no consensus on the management of symptomatic FN. The authors propose a new classification system to aid the guidance of management of symptomatic FN." | Fat Necrosis |
We study gelation in suspensions of model colloidal particles with short-ranged attractive and long-ranged repulsive interactions by means of three-dimensional fluorescence confocal microscopy. At low packing fractions, particles form stable equilibrium clusters. Upon increasing the packing fraction the clusters grow in size and become increasingly anisotropic until finally associating into a fully connected network at gelation. We find a surprising order in the gel structure. Analysis of spatial and orientational correlations reveals that the gel is composed of dense chains of particles constructed from face-sharing tetrahedral clusters. Our findings imply that dynamical arrest occurs via cluster growth and association. | Colloids |
Protonophores can be considered as candidates for anti-obesity drugs and tools to prevent excessive reactive oxygen species production in mitochondria by means of a limited decrease in the mitochondrial potential. Experimentally used protonophores are weak acids that can carry protons across a membrane in a neutral (protonated) form, and they come back in an anionic (deprotonated) form. A cationic derivative of rhodamine 19 and plastoquinone (SkQR1) was recently shown to possess uncoupling activity in mitochondria and in intact cells. In this article, we studied the mechanism of action of SkQR1 and its plastoquinone-lacking analog (C12R1) on a planar bilayer lipid membrane by applying voltage jumps. The steady-state current was proportional to the C12R1 concentration in a manner as if the monomeric form of the carrier were operative. As predicted by the carrier model, at high pH, when rhodamines were mainly deprotonated, the current changed immediately following a jump in the applied potential and then remained constant. By contrast, at low pH, the current relaxed from an initially high value to a lower value since the protonated carrier cations were redistributed in the membrane. An inverse pH dependence was revealed with the anionic protonophore CCCP. The dependence of the SkQR1 protonophorous activity on voltage exhibited an increase at high voltages, an effect that might facilitate mild (self-limited) uncoupling of mitochondria. | Plastoquinone |
Erysipelothrix rhusiopathiae is a thin, non-sporulating, gram-positive rod found worldwide and hosted by many domestic or savage animals, birds, fish, and shell/fish. It is extremely resistant in the external environment (soil, surface waters). Human infection is prevalently related to occupational exposure to sick or infected contaminated animals (anthropozoonosis). Frequently, the disease manifests itself as an acute cellulitis on the skin around the gate of entry. Systemic infection is uncommon, most commonly involving the endocardium or joints. We present a case of subacute E. rhusiopathiae endocarditis in a male patient at occupational hazard for this infection (animal genitor in a zoo). The patient was treated with cefoperazone, the course being favorable. Later on, he required mitral valvuloplasty. | Erysipelothrix Infections |
Ionic liquids (ILs) and deep eutectic solvents (DESs) debuted with a promise of a superior sustainability footprint due to their low vapor pressure. However, their toxicity and high cost compromise this footprint, impeding their real-world applications. Fortunately, their property tunability through a rational selection of precursors, including bioderived ones, provides a strategy to ameliorate toxicity, lower cost, and endow new functions. This Review discusses whether ILs and DESs are sustainable solvents and how they contribute to sustainable chemical processes. | Ionic Liquids |
By means of extratympanic phonometry, the middle ear muscular reflex activity in the startle reaction was measured in a control series, in patients with otosclerosis and in patients with operation cavaties without a functioning tensor tympani muscle. In comparison with the stapedius reflex, the startle reflex was found to be much more variable regarding latency, amplitude, and configuration. It was characterized by pronounced fatigue and a high alertness dependence. The period of latency was about 60 msec. It was possible to elicit a distinct startle reflex in operation cavities without a functioning tensor tympani muscle, probably because of contraction of the Eustachian tube muscles. | Ear, Middle |
OBJECTIVE: The study objective was to evaluate outcomes of pulmonary vein stenosis repair in a large single-center cohort. METHODS: Clinical data from a pulmonary vein stenosis registry were retrospectively reviewed identifying patients who underwent pulmonary vein stenosis repair. The primary/index operation was defined as the patient's first pulmonary vein stenosis operation during the study period. RESULTS: Between January 2007 and August 2019, 174 patients underwent pulmonary vein stenosis repair. Bilateral pulmonary vein stenosis occurred in 111 patients (64%); 71 patients (41%) had 4-vessel disease. Fifty-nine patients (34%) had primary pulmonary vein stenosis. Median age was 9 months (interquartile range, 5-27) and weight was 6.5 kg (4.7-10.2). Surgical techniques evolved and included ostial resection, unroofing, reimplantation, sutureless, modified sutureless, and a newer anatomically focused approach of pulmonary vein stenosis resection with lateralization or patch enlargement of the pulmonary vein-left atrium connection. Twenty-three patients (13%) required reoperation. Cumulative 2-year incidence of postoperative transcatheter intervention (balloon dilation +/- stenting) was 64%. One-, 2-, and 5-year survivals were 71.2%, 66.8%, and 60.6%, respectively. There was no association between surgery type and reoperation rate (hazard ratio, 2.38, P = .25) or transcatheter intervention (hazard ratio, 0.97, P = .95). The anatomically focused repair was associated with decreased mortality on univariate (hazard ratio, 0.38, P = .042) and multivariable analyses (hazard ratio, 0.19, P = .014). Antiproliferative chemotherapy was also associated with decreased mortality (hazard ratio, 0.47, P = .026). CONCLUSIONS: This large single-center surgical pulmonary vein stenosis experience demonstrates encouraging midterm results. A new anatomically focused repair strategy aims to alleviate pulmonary vein angulation to minimize turbulence and shows promising early outcomes. Continued follow-up is required to understand longer-term outcomes for this surgical approach. | Stenosis, Pulmonary Vein |
BACKGROUND: Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued. METHODS: Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg.kg(-1) body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography. RESULTS: Caffeine was associated with higher peak saccade velocities (472 +/- 60 degrees s(-1)) compared to placebo (455 +/- 62 degrees s(-1)). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine. CONCLUSIONS: These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued. | Eye Movements |
OBJECTIVES: To compare the transfer accuracy of two digital transfer trays, the three-dimensional printed (3D printed) tray and the vacuum-formed tray, in the indirect bonding of labial brackets. MATERIALS AND METHODS: Ten digital dental models were constructed by oral scans using an optical scanning system. 3D printed trays and vacuum-formed trays were obtained through the 3Shape indirect bonding system and rapid prototyping technology (10 in each group). Then labial brackets were transferred to 3D printed models, and the models with final bracket positioning were scanned. Linear (mesiodistal, vertical, buccolingual) and angular (angulation, torque, rotation) transfer errors were measured using GOM Inspect software. The mean transfer errors and prevalence of clinically acceptable errors (linear errors of </=0.5 mm and angular errors of </=2 degrees ) of two digital trays were compared using the Mann-Whitney U-test and the Chi-square test, respectively. RESULTS: The 3D printed tray had a lower mean mesiodistal transfer error (P < .01) and a higher prevalence of rotation error within the limit of 2 degrees (P = .03) than did the vacuum-formed tray. Linear errors within 0.5 mm were higher than 90% for both groups, while torque errors within 2 degrees were lowest at 50.9% and 52.9% for the 3D printed tray and vacuum-formed tray, respectively. Both groups had a directional bias toward the occlusal, mesial, and buccal. CONCLUSIONS: The 3D printed tray generally scored better in terms of transfer accuracy than did the vacuum-formed tray. Both types of trays had better linear control than angular control of brackets. | Models, Dental |
Heart failure, the leading cause of hospitalization of elderly patients, is correlated with myocardial fibrosis (ie, deposition of excess extracellular matrix proteins such as collagen). A key regulator of collagen homeostasis is lysyl oxidase (LOX), an enzyme responsible for cross-linking collagen fibers. Our objective was to ameliorate age-related myocardial fibrosis by disrupting collagen cross-linking through inhibition of LOX. The nonreversible LOX inhibitor beta-aminopropionitrile (BAPN) was administered by osmotic minipump to 38-week-old C57BL/6J male mice for 2 weeks. Sirius Red staining of myocardial cross sections revealed a reduction in fibrosis, compared with age-matched controls (5.84 +/- 0.30% versus 10.17 +/- 1.34%) (P < 0.05), to a level similar to that of young mice at 8 weeks (4.9 +/- 1.2%). BAPN significantly reduced COL1A1 mRNA, compared with age-matched mice (3.5 +/- 0.3-fold versus 15.2 +/- 4.9-fold) (P < 0.05), suggesting that LOX is involved in regulation of collagen synthesis. In accord, fibrotic factor mRNA expression was reduced after BAPN. There was also a novel increase in Ly6C expression by resident macrophages. By interrupting collagen cross-linking by LOX, the BAPN treatment reduced myocardial fibrosis. A novel observation is that BAPN treatment modulated the transforming growth factor-beta pathway, collagen synthesis, and the resident macrophage population. This is especially valuable in terms of potential therapeutic targeting of collagen regulation and thereby age-related myocardial fibrosis. | Aminopropionitrile |
Greek fir (Abies cephalonica Loudon) belongs to the Mediterranean fir species and is widely distributed in the mountains of Central and Southern Greece. Considering a climatic scenario, infestation by pathogens or insects and fire episodes, it has been proposed that Mediterranean firs could be in danger in some parts of their present range but, on the other hand, could also replace other species in more northern zones with temperate humid climates (e.g., silver fir, Abies alba Mill.). As fir species are generally highly productive and therefore important for commercial forestry, they have traditionally been involved in conventional tree improvement programs. A lot of effort has been put into the development of vegetative propagation methods for firs, in order to rapidly gain the benefits of traditional breeding to be utilized in reforestation. The present paper provides up to date information on protocols for somatic embryogenesis (i.e., the most promising in vitro method for vegetative propagation) of Greek fir. Moreover, the protocols for cryopreservation and long-term storage of embryogenic material are described as well. | Abies |
Previously reported (S)-5'-C-aminopropyl-2'-arabinofluoro-thymidine (5ara-T) and newly synthesized (S)-5'-C-aminopropyl-2'-arabinofluoro-5-methyl-cytidine (5ara-(Me)C) analogs were incorporated into a series of antisense gapmers containing multiple phosphorothioate (PS) linkages and locked nucleic acids (LNAs) in their wing regions. The functional properties of the gapmers were further evaluated in vitro. Compared with the positive control, for the LNA-wing full PS gapmer without 5ara modification, it was revealed that each gapmer could have a high affinity and be thermally stable under biological conditions. Although the cleavage pattern was obviously changed; gapmers with 5ara modification could still efficiently activate E. coli RNase H1. In addition, incorporating one 5ara modification into the two phosphodiester linkages could reverse the destabilization in enzymatic hydrolysis caused by fewer PS linkages. In vitro cellular experiments were also performed, and the Lipofectamine((R)) 2000 (LFA)+ group showed relatively higher antisense activity than the LFA-free group. KN5ara-10, which contains fewer PS linkages, showed similar or slightly better antisense activity than the corresponding full PS-modified KN5ara-3. Hence, KN5ara-10 may be the most promising candidate for KNTC2-targeted cancer therapy. | Nucleic Acid Probes |
Electron tomography is becoming one of the most used methods for structural analysis at nanometric scale in biological and materials sciences. Combined with chemical mapping, it provides qualitative and semiquantitative information on the distribution of chemical elements on a given sample. Due to the current difficulties in obtaining three-dimensional (3D) maps by energy-filtered transmission electron microscopy (EFTEM), the use of 3D chemical mapping has not been widely adopted by the electron microscopy community. The lack of specialized software further complicates the issue, especially in the case of data with a low signal-to-noise ratio (SNR). Moreover, data interpretation is rendered difficult by the absence of efficient segmentation tools. Thus, specialized software for the computation of 3D maps by EFTEM needs to include optimized methods for image series alignment, algorithms to improve SNR, different background subtraction models, and methods to facilitate map segmentation. Here we present a software package (EFTEM-TomoJ, which can be downloaded from http://u759.curie.fr/fr/download/softwares/EFTEM-TomoJ), specifically dedicated to computation of EFTEM 3D chemical maps including noise filtering by image reconstitution based on multivariate statistical analysis. We also present an algorithm named BgART (for background removing algebraic reconstruction technique) allowing the discrimination between background and signal and improving the reconstructed volume in an iterative way. | Imaging, Three-Dimensional |
BACKGROUND: Minimal data exist regarding the activity, membership, training, and medical oversight of search and rescue (SAR) teams. OBJECTIVE: Our objective was to describe these characteristics in the Intermountain West SAR organizations. METHODS: A contact list was generated and electronic surveys were sent to SAR officials in each Intermountain West county. Results were descriptively analyzed. RESULTS: Of the contacted jurisdictions, 56% (156) responded to the survey. The annual average call volume was 29 missions (range, 5 to 152). Multiple levels of medical training were represented on SAR teams, ranging from first aid/cardiopulmonary resuscitation providers to the physician level, and 79% of teams provided some medical training to their membership. Of the SAR medical professionals, 23% had formal wilderness medical training. Local emergency medical services provided 60% of the medical care on SAR missions rather than SAR personnel. Formal physician medical oversight was present in 41% of the SAR teams. These physicians participated in a range of SAR activities including medical protocol drafting (including expanded scope of practice), medical trainings, mission participation, medical consultation, and prescribing medications for field use. The majority (69%) of those physicians were trained in emergency medicine, and 45% of the active medical directors had protocols allowing for an expanded scope of practice due to the remote nature of SAR medical care. CONCLUSIONS: Intermountain West SAR teams vary in their activity, composition, training, and level of medical oversight. This study confirms that opportunities exist for physician integration with SAR teams in the studied states and likely throughout the United States. | Wilderness |
BACKGROUND: The admission cardiotocograph (CTG) is a commonly used screening test consisting of a short (usually 20 minutes) recording of the fetal heart rate (FHR) and uterine activity performed on the mother's admission to the labour ward. OBJECTIVES: To compare the effects of admission CTG with intermittent auscultation of the FHR on maternal and infant outcomes for pregnant women without risk factors on their admission to the labour ward. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 May 2011) (CENTRAL) (The Cochrane Library 2011 Issue 2 of 4), MEDLINE (1966 to 17 May 2011), CINAHL (1982 to 17 May 2011), Dissertation Abstracts (1980 to 17 May 2011) and the reference list of retrieved papers. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing admission CTG with intermittent auscultation of the FHR for pregnant women between 37 and 42 completed weeks of pregnancy and considered to be at low risk of intrapartum fetal hypoxia and of developing complications during labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and quality, and extracted data. Data were checked for accuracy. MAIN RESULTS: We included four trials involving more than 13,000 women. All four studies included women in labour. Overall, the studies were at low risk of bias. Although not statistically significant using a strict P < 0.05 criterion, data are consistent with women allocated to admission CTG having, on average, a higher probability of an increase in incidence of caesarean section than women allocated to intermittent auscultation (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.00 to 1.44, four trials, 11,338 women, T(2) = 0.00, I(2) = 0%). There was no significant difference in the average treatment effect across included trials between women allocated to admission CTG and women allocated to intermittent auscultation in instrumental vaginal birth (RR 1.10, 95% CI 0.95 to 1.27, four trials, 11,338 women, T(2) = 0.01, I(2) = 38%) and fetal and neonatal deaths (RR 1.01, 95% CI 0.30 to 3.47, four trials, 11339 infants, T(2) = 0.00, I(2) = 0%).Women allocated to admission CTG had, on average, significantly higher rates of continuous electronic fetal monitoring during labour (RR 1.30, 95% CI 1.14 to 1.48, three trials, 10,753 women, T(2) = 0.01, I(2) = 79%) and fetal blood sampling (RR 1.28, 95% CI 1.13 to 1.45, three trials, 10,757 women, T(2) = 0.00, I(2) = 0%) than women allocated to intermittent auscultation. There were no differences between groups in other secondary outcome measures. AUTHORS' CONCLUSIONS: Contrary to continued use in some clinical areas, we found no evidence of benefit for the use of the admission cardiotocograph (CTG) for low-risk women on admission in labour.We found no evidence of benefit for the use of the admission CTG for low-risk women on admission in labour. Furthermore, the probability is that admission CTG increases the caesarean section rate by approximately 20%. The data lacked power to detect possible important differences in perinatal mortality. However, it is unlikely that any trial, or meta-analysis, will be adequately powered to detect such differences. The findings of this review support recommendations that the admission CTG not be used for women who are low risk on admission in labour. Women should be informed that admission CTG is likely associated with an increase in the incidence of caesarean section without evidence of benefit. | Heart Auscultation |
The results of a comparative study of the luciferin-luciferase systems of seven species of bioluminescing oligochaetes-Henlea petushkovi, Henlea rodionovae, Fridericia heliota (Enchytraeidae), Microscolex phosphoreus (Acanthodrilidae), Pontodrilus litoralis (Megascolecidae), Eisenia lucens, and Avelona ligra (Lumbricidae)-are presented. | Oligochaeta |
A patient with Felty's syndrome (FS) and persistent profound neutropenia developed recurrent infections and sepsis syndrome. No impairment of granulocyte-macrophage colony development was observed in vitro. Marrow morphology revealed an absence of mature neutrophil forms despite administration of granulocyte-colony stimulating factor (G-CSF). However, pretreatment with bolus cyclophosphamide (CY) permitted the growth factor to relieve this impairment of late myeloid maturation and resulted in a brisk, albeit short, burst of neutrophilia. This suggests that immune interference in myelopoiesis can be overcome by growth factor administration if immune activity is adequately dampened by immunosuppressive therapy. | Felty Syndrome |
In adipocytes, the glucose transporter GLUT4 recycles between intracellular storage vesicles and the plasma membrane. GLUT4 is internalized by a clathrin- and dynamin-dependent mechanism, and sorted into an insulin-sensitive storage compartment. Insulin stimulation leads to GLUT4 accumulation on the cell surface. The N-terminal F5QQI motif in GLUT4 has been shown previously to be required for sorting of the protein in the basal state. Here, we show that the FQQI motif is a binding site for the medium chain adaptin micro1, a subunit of the AP-1 adaptor complex that plays a role in post-Golgi/endosomal trafficking events. In order to investigate the role of AP-1 and AP-2 in GLUT4 trafficking, we generated 3T3-L1 adipocytes expressing HA-GLUT4-GFP and knocked down the AP-1 and AP-2 complex by RNAi, respectively. In AP-1 and AP-2 knockdown adipocytes, GLUT4 accumulates at the cell surface in the basal state, consistent with a role of AP-1 in post-endosomal sorting of GLUT4 to the insulin-sensitive storage compartment, and of AP-2 in clathrin-mediated endocytosis. Our data demonstrate a dual role of the F5QQI motif and support the conclusion that the AP complexes direct GLUT4 trafficking and endocytosis. | Transcription Factor AP-1 |
Tattooing has recently regained popularity in medicine. Cosmetic blepharopigmentation for eyelid enhancement by permanent eyeliner has received considerable attention. In addition, permanent pigmentation has been used for eyebrow simulation, camouflaging of scars, nipple areolar pigmentation following breast reconstruction, and the management of several other pigment disorders. This article emphasizes the principles and technique of blepharopigmentation. | Tattooing |
Although crisis helplines are an established method of suicide prevention, there is little research on their operation in developing countries. This paper reviews calls (N = 14,344) to the only suicide prevention hotline in Bangladesh during the first five years of the helpline's operation. Call characteristics were recorded on checklists, compiled, and analyzed. Results indicate that callers are about half male, mostly between the ages of twenty and thirty-nine, and mostly not suicidal. Callers display a wide range of reasons for calling, with relationship issues, mental illness/substance abuse, and emotions constituting the majority of calls. | Hotlines |
During pregnancy, the Fetal Membrane (FM) is subjected to mechanical stretching that may result in preterm labor. The structural integrity of the FM is maintained by its collagenous layer. Disconnection and reconnection of molecular bonds between collagen fibrils is the fundamental process that governs the irreversible mechanical and supramolecular changes in the FM. At a critical threshold strain, bundling and alignment of collagen fibrils alter the super-molecular structure of the collagenous layer. Recent studies indicate that these changes are associated with inflammation and/or expression of specific proteins that are known to be related to uterine contractions and labor. The potential healing of stretching-induced damages in the FM by mediators involved in mechano-transduction is discussed. | Extraembryonic Membranes |
This study provides pharmacological evidence on the spasmolytic activity of Tagetes erecta L. (marigold or cempasuchil) on the guinea-pig ileum and presents data on its mechanism of action. The relaxant effect on KCl contractions was more marked with aqueous (AqEx) than with ethanol extracts (EtEx) of T. erecta flowers (55.6â¯+/-â¯11.0 vs 21.1â¯+/-â¯4.4%, respectively). In addition, the aqueous extract antagonized contractions elicited by EFS, but not by acetylcholine (73.5â¯+/-â¯1.9 vs 14.5â¯+/-â¯5.3%, respectively). These effects were not diminished by hexamethonium or L-NAME, but this extract caused a rightward shift in the Ca(2+) concentration-response curves like that of verapamil. Quercetin and rutin, two flavonoids present in this plant, also showed spasmolytic effects (95.7â¯+/-â¯2.8 and 27.9â¯+/-â¯7.1%, respectively). Interestingly, in tissues without spasmogens, the extract induced contractions superimposed on their spontaneous activity. These results support the traditional use of T. erecta as a spasmolytic in folk medicine and suggest mainly that quercetin could be partly responsible for this effect. The spasmolytic effect appears to involve voltage-gated calcium channels, but not the nitric oxide pathway or the release of neurotransmitters from enteric neurons. Nevertheless, this plant could produce colic or stomachache as adverse effects in clinical situations in which these symptoms are not originally present. | Tagetes |
The cardiopulmonary effects of a ketamine/ acepromazine combination was studied in ten cats subjected to a 25% whole blood volume loss. Test parameters included cardiac output, measured via thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for cardiac index, stroke volume and systemic vascular resistance were calculated from these data. Posthemorrhage, cardiac output, cardiac index, stroke volume, heart rate and measurements of arterial blood pressure were significantly decreased (p less than 0.05). Following the induction of ketamine/ acepromazine anesthesia, cardiac output, cardiac index, stroke volume and heart rate showed mild but statistically insignificant declines and were above their respective posthemorrhage values 120 min into ketamine/ acepromazine anesthesia. Measurements of arterial blood pressure showed further declines from their respective posthemorrhage values that were statistically significant (p less than 0.05). Following hemorrhage, respiratory rate increased significantly (p less than 0.05), associated with a fall in arterial CO2 tension. During ketamine/ acepromazine anesthesia, respiratory rate showed a dramatic and significant decline (p less than 0.05) with arterial CO2 tension rising to prehemorrhage values. Systemic vascular resistance, arterial O2 tension and pH remained essentially unchanged throughout the experimental period. | Acepromazine |
Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many patients fail to respond to anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion of 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitized mice to both TNF-dependent and TNF-independent death. Here we show that TNF-independent IEC death after A20 and Abin-1 deletion was rescued by germ-free derivation or deletion of MyD88, while deletion of Trif provided only partial protection. Combined deletion of Ripk3 and Casp8, which inhibits both apoptotic and necroptotic death, completely protected against death after acute deletion of A20 and Abin-1 in IECs. A20- and Abin-1-deficient IECs were sensitized to TNF-independent, TNFR1-mediated death in response to lymphotoxin alpha (LTalpha) homotrimers. Blockade of LTalpha in vivo reduced weight loss and improved survival when combined with partial deletion of MyD88. Biopsies of inflamed colon mucosa from patients with IBD exhibited increased LTA and IL1B expression, including a subset of patients with active colitis on anti-TNF therapy. These data show that microbial signals, MyD88, and LTalpha all contribute to TNF-independent intestinal injury." | Myeloid Differentiation Factor 88 |
The use of a pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of the pharmacological effect of diazepam was explored. The analysis examined the effects of diazepam (0.28 mg/kg) on the wheel-tracking and digit-symbol substitution performance of young healthy adults. Both free-plasma drug concentration and relative amount of diazepam bound to the benzodiazepine receptor were calculated and compared to the behavioral measures across time. Performance was more significant correlated with relative receptor occupancy (RRO) than with unbound plasma-drug levels. For both tasks hysteresis plots indicated greater similarity between time profiles of performance and RRO than between those of performance and blood concentration alone. These results provide support for the inclusion of both receptor binding kinetics and plasma pharmacokinetics as the bases for the prediction of the pharmacologic activity of diazepam. | Nordazepam |
BACKGROUND: Hepatectomy is the first-line treatment for alveolar echinococcosis (AE) if complete resection is feasible. However, a strategy for the treatment of patients with AE in whom the tumor cannot be resected completely remains to be defined. STUDY DESIGN: Data were retrospectively collected from 188 consecutive patients between 1984 and 2009. Overall survival (OS), progression-free survival (PFS), and risk factors were analyzed in patients classified into 3 groups (group A: complete resection, group B: reduction surgery, and group C: drainage or exploratory laparotomy). RESULTS: In group A (n = 119), the 10-, 15-, and 20-year OS was 98.9%. In group B (n = 63), the 10-, 15-, and 20-year OS was 97.1%, 92.8%, and 61.9%. In group C (n = 6), the 10- and 15-year OS was 50.0% and 33.3%. Patients in groups A and B had better prognoses than those in group C (p < 0.001). In group A, the 10-, 15-, and 20-year PFS was 96.5%, 94.4%, and 94.4%. In group B, the 10-, 15-, and 20-year PFS was 87.1%, 71.6%, and 61.4%. In group C, the 10- and 15-year PFS was 50.0% and 33.3%. Patients in group A had better PFS than those in groups B and C (p < 0.001). Curability was the only independent factor for both OS and PFS by multivariate analysis. CONCLUSIONS: Although the most effective therapy for AE is complete resection, a better prognosis can be achieved by reduction surgery and/or adjuvant albendazole therapy for patients with AE that cannot be completely resected. | Anticestodal Agents |
AIMS: Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are two popular regenerative treatments for periodontal infrabony lesions. Both have been used in conjunction with other regenerative materials. We conducted a Bayesian network meta-analysis of randomized controlled trials on treatment effects of GTR, EMD and their combination therapies. MATERIAL AND METHODS: A systematic literature search was conducted using the Medline, EMBASE, LILACS and CENTRAL databases up to and including June 2011. Treatment outcomes were changes in probing pocket depth (PPD), clinical attachment level (CAL) and infrabony defect depth. Different types of bone grafts were treated as one group and so were barrier membranes. RESULTS: A total of 53 studies were included in this review, and we found small differences between regenerative therapies which were non-significant statistically and clinically. GTR and GTR-related combination therapies achieved greater PPD reduction than EMD and EMD-related combination therapies. Combination therapies achieved slightly greater CAL gain than the use of EMD or GTR alone. GTR with BG achieved greatest defect fill. CONCLUSION: Combination therapies performed better than single therapies, but the additional benefits were small. Bayesian network meta-analysis is a promising technique to compare multiple treatments. Further analysis of methodological characteristics will be required prior to clinical recommendations. | Alveolar Bone Loss |
Cell polarity is inherent to the process of asymmetric cell division, which relies on the asymmetric distribution of multiple polarity proteins and cell-fate determinants in the cell cortex. The establishment and maintenance of cell polarity require the orchestration of numerous cellular processes. These include cytoplasmic movements, cytoskeleton dynamics, and different signaling events. Equally relevant is the plasma membrane composition, such as the lipid environment that endows particular membrane subdomains with specific characteristics. Sorting receptors and sorting determinants, including posttranslational modifications, also contribute to cell polarization. Together, all these mechanisms would be expected to have great relevance in the context of asymmetric cell division, an essential process in both physiological and pathological conditions. | Asymmetric Cell Division |
The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. | Prostate |
Concerns among patients and physicians that health plans would deny coverage for medically necessary services has brought about legislation mandating independent medical review (IMR) of denied services. Among 1,400 cases submitted in California, the most common areas for dispute were cancer care, endocrine/metabolic care (especially for obesity), orthopedic care, and neurological disorders. Surgery and pharmacy services constituted 52 percent of cases. In 58 percent of cases, IMR upheld the health plan's decision, while in 33 percent of cases the health plan's decision was overturned, which suggests that external IMR provides additional patient protection in California's health care system. | Insurance Claim Review |
Calonectria pseudonaviculata and C. henricotiae are the causal agents of boxwood blight, a devastating disease of boxwood that has caused significant economic impact on the nursery and landscape industries in the U.S. and in Europe. The two species are genetically distinct and are found in different geographic areas but are difficult to distinguish based on morphology and pathogenicity. Fast, accurate, and inexpensive methods to detect and differentiate these species is critical in stopping the spread of the disease. We designed primer pairs based on available sequences of four conserved regions-calmodulin, histone H3, internal transcribed spacer, and beta-tubulin-and tested their ability to differentiate the two Calonectria species. Here we report three primer pairs derived from sequence differences in the histone H3 region that can be used to specifically detect C. pseudonaviculata, C. henricotiae, or both species. Specificity of these primers was tested against nine isolates of C. pseudonaviculata, three isolates of C. henricotiae, 13 other Calonectria species, and five isolates from related genera using conventional and real-time PCR. These are the first primers available that can be used with either a multiplexed conventional PCR or SYBR-based real-time PCR to specifically detect and differentiate the two fungal species. | Buxus |
The aim of this in vitro study was to determine how frequent a seemingly accurate working length ending radiographically 0 to 2 mm short of the radiographic apex resulted in an instrumentation beyond the apical foramen. Under simulated clinical conditions working lengths of 169 root canals were radiographically determined in 91 extracted teeth. In all cases the measuring files adjusted to the final working length (Iwork) were located 0 to 2 mm short of the radiographic apex. Iwork was subsequently compared with the actual reference length (Iref) representing the distance between the apical foramen and the coronal reference. Instrumentation beyond the apical foramen (Iwork > ref) occurred in premolars in 51% (95% confidence interval: 36%; 66%) of the cases, in molars in 22% (95% confidence interval: 14%; 30%), and in anterior teeth in no case. These results suggest that in premolars and molars a radiographically working length ending 0 to 2 mm short of the radiographic apex provides, more often than expected, a basis for unintentional overinstrumentation. | Pulpectomy |
The Zika virus infection outbreak in Brazil in 2014 to 2015 resulted in the identification of previously unknown consequences of the disease, including the notorious microcephaly among many defects in fetuses born to women infected during pregnancy. A number of individuals were involved in this remarkable discovery, from the detection of viral circulation in the country to the studies on the causal link with congenital abnormalities and the provision of awareness and social support to families affected by the disease. In this article, we review the background to this experience, describing aspects of the epidemiology, medical research, and scientific response to the Zika virus outbreak in Brazil. | Microcephaly |
Craniosynostosis is a skull malformation because of premature fusing of one or more cranial sutures. The most common types of craniosynostosis are scaphocephaly (with the sagittal suture fused) and trigonocephaly (with the metopic suture fused). In this paper we describe and discuss how finite element analysis and three-dimensional modeling can be used for preoperative planning of the correction of craniosynostosis and for the postoperative evaluation of the treatment results. We used the engineering software MIMICS MATERIALISE to obtain three-dimensional geometry from computed tomography scans, and applied finite element method for the sake of biomechanical analysis. These simulations help to improve the surgical treatment, making it more accurate, safer, and faster. | Craniosynostoses |
Platelets are anucleate cell-fragments derived predominantly from megakaryocytes in the bone marrow and released in the blood circulation, with a normal count of 150 000-40 000 per mul and a lifespan of approximately 10 days in humans. A primary role of platelets is to aid in vascular injury site-specific clot formation to stanch bleeding, termed hemostasis. Platelets render hemostasis by a complex concert of mechanisms involving platelet adhesion, activation and aggregation, coagulation amplification, and clot retraction. Additionally, platelet secretome can influence coagulation kinetics and clot morphology. Therefore, platelet defects and dysfunctions result in bleeding complications. Current treatment for such complications involve prophylactic or emergency transfusion of platelets. However, platelet transfusion logistics constantly suffer from limited donor availability, challenges in portability and storage, high bacterial contamination risks, and very short shelf life (~5 days). To address these issues, an exciting area of research is focusing on the development of microparticle- and nanoparticle-based platelet surrogate technologies that can mimic various hemostatic mechanisms of platelets. On the other hand, aberrant occurrence of the platelet mechanisms lead to the pathological manifestation of thrombosis and thromboinflammation. The treatments for this are focused on inhibiting the mechanisms or resolving the formed clots. Here, platelet-inspired technologies can provide unique platforms for disease-targeted drug delivery to achieve high therapeutic efficacy while avoiding systemic side-effects. This review will provide brief mechanistic insight into the role of platelets in hemostasis, thrombosis and thromboinflammation, and present the current state-of-art in the design of platelet-inspired nanomedicine for applications in these areas. | Thromboinflammation |
There are different insulin analogues with various pharmacokinetic characteristics, such as, rapid-acting, long-acting, or intermediate-acting analogues. Since insulin tends to form amyloid aggregates, it is of particular interest to measure characteristic times of formation of amyloid aggregates and compare those to action times for insulin and its analogues. For the study we have chosen one of the insulin analogues - insulin Lispro, which is a fast acting insulin analog. It is usually thought of amyloid aggregation as a nucleation-dependent process. We have estimated the size of the primary nucleus to be one monomer and the size of the secondary nucleus to be around zero in both insulin and Lispro insulin aggregation processes. The main structural element of insulin and Lispro insulin amyloid fibrils is a rounded ring oligomer of about 6-7 nm in diameter, about 2-3 nm in height and about 2 nm in diameter of the hole. Fibrils of several mum in length are produced due to interaction of such oligomers. The packing of ring oligomers in fibrils differs because of the difference in their orderliness. Though the initial stages of fibril formation (monomer, oligomer) are similar, the further process depends on the unique sequence of each peptide. Namely the sequence affects the final morphology of mature amyloids. These observations allow us to conclude that formation of fibrils by short peptides occurs via and by means of oligomer ring structures. Such an important issue as the nature of polymorphism of insulin amyloid fibrils has been settled by us. The role of early oligomeric aggregates in such processes as nucleation and aggregation of amyloid fibrils has been examined. | Insulin Lispro |
Eukaryotic proteins can be modified through attachment to various small molecules and proteins. One such modification is conjugation to ubiquitin and ubiquitin-like proteins (UBLs), which controls an enormous range of physiological processes. Bound UBLs mainly regulate the interactions of proteins with other macromolecules, for example binding to the proteasome or recruitment to chromatin. The various UBL systems use related enzymes to attach specific UBLs to proteins (or other molecules), and most of these attachments are transient. There is increasing evidence suggesting that such UBL-protein modification evolved from prokaryotic sulphurtransferase systems or related enzymes. Moreover, proteins similar to UBL-conjugating enzymes and UBL-deconjugating enzymes seem to have already been widespread at the time of the last common ancestor of eukaryotes, suggesting that UBL-protein conjugation did not first evolve in eukaryotes. | Ubiquitins |
The reversible conversion between D-glucose 6-phosphate and D-fructose 6-phosphate catalyzed by yeast phosphoglucoisomerase was studied by phase sensitive two-dimensional 13C-[1H] EXSY NMR spectroscopy at 150.869 and 125.759 MHz, using 13C-enriched substrates in the C2 position of the D-hexose 6-phosphates. The shape of the build-up curves of the cross-peaks associated with the 13C2 resonances of the alpha- and beta-anomers of both D-[2-13C]glucose 6-phosphate and D-[2-13C]fructose 6-phosphate reveals that phosphoglucoisomerase selectively catalyzes the reversible conversion between alpha-D-[2-13C]glucose 6-phosphate and beta-D-[2-13C]fructose 6-phosphate. Quantitative analysis of the build-up curves by three different methods allowed us to conclude that phosphoglucoisomerase not only selectively channels the latter isomerization but also considerably accelerates the anomerization of both D-hexose 6-phosphates. The rate constants of anomerization were indeed much higher in the presence than in the absence of enzyme. The major finding in the present study consists in the anomeric specificity of phosphoglucoisomerase toward the beta-anomer of D-fructose 6-phosphate both as a substrate and a product, contrary to previous proposals. This finding supports recent evidence suggesting the direct channelling of beta-D-fructose 6-phosphate from phosphoglucoisomerase to phosphofructokinase. | Fructosephosphates |
Spermatogonial stem cells (SSCs) are one of the most significant stem cells with the potentials of self-renewal, differentiation, transdifferentiation and dedifferentiation, and thus, they have important applications in reproductive and regenerative medicine. They can transmit the genetic and epigenetic information across generations, which highlights the importance of the correct establishment and maintenance of epigenetic marks. Accurate transcriptional and post-transcriptional regulation is required to support the highly coordinated expression of specific genes for each step of spermatogenesis. Increasing evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play essential roles in controlling gene expression and fate determination of male germ cells. These ncRNA molecules have distinct characteristics and biological functions, and they independently or cooperatively modulate the proliferation, apoptosis and differentiation of SSCs. In this review, we summarized the features, biological function and fate of mouse and human SSCs, and we compared the characteristics of lncRNAs and circRNAs. We also addressed the roles and mechanisms of lncRNAs and circRNAs in regulating mouse and human SSCs, which would add novel insights into the epigenetic mechanisms underlying mammalian spermatogenesis and provide new approaches to treat male infertility. | Spermatogonia |
A simple and sensitive indirect spectrophotometric method for the assay of meloxicam (MX), tenoxicam (TX) and piroxicam (PX) in pure and in pharmaceutical formulations by flow injection analysis (FIA) has been proposed. The method is based on the oxidation of these drugs by a known excess of N-bromosuccinimide (NBS) in an acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple color. The absorbance values increased linearly with increasing concentrations of the drugs. Variables, such as the acidity, reagent concentrations, flow rate of reagents and other FI parameters were optimized to produce the most sensitive and reproducible results. The system obeyed Beer's low over concentration ranges of 10 - 160, 20 - 200 and 10 - 160 microg/ml for MX, TX and PX, respectively. The common excipients and additives did not interfere with their determinations. The method was successfully applied to the determinations of MX, TX and PX in various pharmaceutical preparations. The results obtained by the proposed method were found to be in good agreement with those found by the official HPLC methods. | Meloxicam |
In August 2008, forty dogs out of 400 developed oral warts in a breeding farm in Korea. Canine oral papilloma infection is a common disease in dogs. However, there has been no report of an outbreak of canine oral papillomavirus (COPV) in a group of dogs or in dog breeding farms in Korea, and the genetic analysis of COPV in Korea has yet to be performed. This study diagnosed canine oral papilloma from the oral samples of these dogs based on histopathological examination and immunohistochemistry. Polymerase chain reaction was applied to amplify the corresponding products using preexisting primer sets for COPV and a universal human papillomavirus targeting L1 gene. Further genetic analysis of the major viral capsid gene L1 confirms the sequences of Korean COPV, which shows a close relationship to previously reported COPV. This study describes the histopathological and immunohistochemical characteristics of canine oral papilloma in a group of breeding dogs in Korea and discloses the complete L1 gene sequences of Korean COPV. | Lambdapapillomavirus |
Mechanisms regulating adipocyte lipolysis are reviewed in three stages. The first stage examines plasma membrane hormone receptors and G-proteins. The primary regulators of adipose tissue lipolysis, the catecholamines, bind to the alpha 2, beta 1, beta 2, and beta 3 adrenergic receptors. The alpha 2 receptor couples with Gi-proteins to inhibit cyclic AMP formation and lipolysis, while the beta receptors couple with Gs-proteins to stimulate cyclic AMP formation and lipolysis. The beta 1 receptor may mediate low level catecholamine stimulation, while the beta 3 receptor, which is activated by higher levels of catecholamines, may deliver a more sustained signal. The second stage examines the regulation of cyclic AMP, the intracellular messenger that activates protein kinase A. Adenylyl cyclase synthesizes cyclic AMP from ATP and is regulated by the G-proteins. Phosphodiesterase 3B hydrolyzes cyclic AMP to AMP and is activated and phosphorylated by both insulin and the catecholamines norepinephrine and epinephrine. The third stage focuses on the rate-limiting enzyme of lipolysis, hormone-sensitive lipase (HSL). This 82 to 88 kDa protein is regulated by reversible phosphorylation. Protein kinase A activates and phosphorylates the enzyme at 2 sites, and 3 phosphatases have been implicated in HSL dephosphorylation. The translocation of HSL from the cytosol to the lipid droplet in response to lipolytic stimulation may be facilitated by a family of lipid-associated droplets called perilipins that are heavily phosphorylated by protein kinase A and dephosphorylated by insulin. As the mechanisms regulating adipocyte lipolysis continue to be uncovered, we look forward to the challenges of integrating these findings with research at the in situ and in vivo levels. | Catecholamines |
BACKGROUND: Gleditsia sinensis Lam. (Leguminosae), a dioecious perennial arbor, demonstrates important medicinal properties and economic value. These properties can be harnessed depending on the sex of the plant. However, the sex of the plants is difficult to identify accurately through morphological methods before the flowering. RESULTS: We used bulked segregant analysis to screen sex-specific simple sequence repeat (SSR) markers in G. sinensis. Five male and five female plants were pooled to form the male and female bulks, respectively, and subjected to whole-genome sequencing. After high-throughput sequencing, 5,350,359 sequences were obtained, in which 2,065,210 SSRs were searched. Among them, the number of duplicated SSRs was the highest. The male plants could reach 857,874, which accounted for 60.86% of the total number of male plants. The female plants could reach 1,447,603, which accounted for 56.25% of the total model of the female plants. Among all the nucleotide repeat types, the A/T-rich motif was the most abundant. A total of 309,516 female strain-specific SSRs were selected by clustering. After designing the primers, the male and female gene pools were amplified, and five pairs of primers (i.e., 27, 34, 36, 39, and 41) were found to amplify the differential bands in the male and female gene pools. Using the five pairs of primers, we performed PCR verification on 10 individuals of known sex, which constructed the gene pool. The female plants amplified a single fragment of lengths (i.e., 186, 305, 266, 203, and 260 bp) and no male plant strip, thereby completing the identification of the male and female sexes of the G. sinensis. CONCLUSIONS: This study provides accurate sex identification strategies between female and male plants, thus improving the utilization rate of G. sinensis resources. | Gleditsia |
Starch degradation in barley endosperm provides carbon for early seedling growth, but the control of this process is poorly understood. We investigated whether endosperm cell wall degradation is an important determinant of the rate of starch degradation. We identified iminosugar inhibitors of enzymes that degrade the cell wall component arabinoxylan. The iminosugar 1,4-dideoxy-1, 4-imino-l-arabinitol (LAB) inhibits arabinoxylan arabinofuranohydrolase (AXAH) but does not inhibit the main starch-degrading enzymes alpha- and beta-amylase and limit dextrinase. AXAH activity in the endosperm appears soon after the onset of germination and resides in dimers putatively containing two isoforms, AXAH1 and AXAH2. Upon grain imbibition, mobilisation of arabinoxylan and starch spreads across the endosperm from the aleurone towards the crease. The front of arabinoxylan degradation precedes that of starch degradation. Incubation of grains with LAB decreases the rate of loss of both arabinoxylan and starch, and retards the spread of both degradation processes across the endosperm. We propose that starch degradation in the endosperm is dependent on cell wall degradation, which permeabilises the walls and thus permits rapid diffusion of amylolytic enzymes. AXAH may be of particular importance in this respect. These results provide new insights into the mobilization of endosperm reserves to support early seedling growth. | Imino Furanoses |
Tracheobronchomalacia is a central airway disease characterised by weakness of the wall and dynamic decrease in the tracheal lumen and the large bronchi, particularly while exhaling. It is more common in middle age and the elderly with previous exposure to cigarettes. It causes chronic symptoms such as cough, dyspnea, increase in recurrent infections, and poor secretion management, but it can also progress to chronic respiratory failure and death. It is usually confused with other common diseases like chronic obstructive pulmonary disease (COPD) or asthma. Its causes can be congenital or acquired and its diagnosis involves the dynamic assessment of the airway with tomography and fibrobronchoscopy. It is classified as mild, moderate or severe depending on the degree of collapse of the airway when exhaling. Management consists of a primary phase, in which concomitant diseases must be controlled, such as COPD, asthma or gastro-oesophageal reflux. In diffuse moderate to severe symptomatic tracheobronchomalacia tracheobronchoplasty must be considered with strengthening of the posterior wall. Silicone and Y" stents can be used to identify patients who could potentially benefit from surgical treatment as well as being used for the definitive symptomatic treatment with high surgical risk. More prospective studies need to be done in order to standardise certain common criteria for the management of this usually under-diagnosed disease." | Tracheomalacia |
Short rib polydactyly syndromes (SRPS) are a group of inherited autosomal recessive skeletal dysplasias. It is characterized by the triad of micromelia, polydactyly and short horizontal ribs with or without visceral involvement. We report a case of SRPS-2 in a fresh stillborn and discuss the differential diagnosis." | Short Rib-Polydactyly Syndrome |
AIMS: Iron deficiency (ID) is a frequent finding in patients with chronic and acute heart failure (AHF) along the full spectrum of left ventricular ejection fraction (LVEF). Iron deficiency has been related to ventricular systolic dysfunction, but its role in right ventricular function has not been evaluated. We sought to evaluate whether ID identifies patients with greater right ventricular dysfunction in the setting of AHF. METHODS AND RESULTS: We prospectively included 903 patients admitted with AHF. Right systolic function was evaluated by tricuspid annular plane systolic excursion (TAPSE) and the ratio TAPSE/pulmonary artery systolic pressure (TAPSE/PASP). Iron deficiency was defined, according to European Society of Cardiology criteria, as serum ferritin <100 mg/dL (absolute ID) or ferritin 100-299 mg/dL and transferrin saturation (TSAT) <20% (functional ID). The relationships among the exposures with right ventricular systolic function were evaluated by multivariate linear regression analyses. The mean age of the sample was 74.3 +/- 10.6 years, 441 (48.8%) were female, 471 (52.2%) exhibited heart failure with preserved ejection fraction, and 677 (75.0%) showed ID. The mean LVEF, TAPSE, and TAPSE/PASP were 49 +/- 15%, 18.6 +/- 3.9 mm, and 0.45 +/- 0.18, respectively. The median (interquartile range) amino-terminal pro-brain natriuretic peptide was 4015 (1807-8775) pg/mL. In a multivariable setting, lower TSAT and ferritin were independently associated with lower TAPSE (P < 0.05 for both comparisons). Transferrin saturation (P = 0.017), and not ferritin (P = 0.633), was independently associated with TAPSE/PASP. CONCLUSION: In AHF, proxies of ID were associated with right ventricular dysfunction. Further studies should confirm these findings and evaluate the pathophysiological facts behind this association. | Anemia, Iron-Deficiency |
12/15-Lipoxygenases (12/15-LOX) are members of the LOX family, which are expressed in mammals by monocytes and macrophages following induction by the T helper type 2 cytokines, interleukins-4 and -13. They oxygenate free polyenoic fatty acids but also ester lipids and even complex lipid-protein assemblies such as biomembranes and lipoproteins. The primary oxidation products are either reduced by glutathione peroxidases to corresponding hydroxy derivatives or metabolized into secondary oxidized lipids including leukotrienes, lipoxins and hepoxilins, which act as lipid mediators. Examination of knockout and transgenic animals revealed important roles for 12/15-LOX in inflammatory diseases, including atherosclerosis, cancer, osteoporosis, angiotension II-dependent hypertension and diabetes. In vitro studies suggested 12/15-LOX products as coactivators of peroxisomal proliferator activating-receptors (PPAR), regulators of cytokine generation, and modulators of gene expression related to inflammation resolution. Despite much work in this area, the biochemical mechanisms by which 12/15-LOX regulates physiological and pathological immune cell function are not fully understood. This review will summarize the biochemistry and tissue expression of 12/15-LOX and will describe the current knowledge regarding its immunobiology and regulation of inflammation. | Arachidonate 12-Lipoxygenase |
An RNA-binding protein places a surface helix, beta-ribbon, or loop in an RNA helix groove and/or uses a cavity to accommodate unstacked bases. Hence, our strategy for predicting RNA-binding residues is based on detecting a surface patch and a disparate cleft. These were generated and scored according to the gas-phase electrostatic energy change upon mutating each residue to Asp(-)/Glu(-) and each residue's relative conservation. The method requires as input the protein structure and sufficient homologous sequences to define each residue's relative conservation. It yields as output a priority list of surface patch residues followed by a backup list of surface cleft residues distant from the patch residues for experimental testing of RNA binding. Among the 69 structurally non-homologous proteins tested, 81% possess a RNA-binding site with at least 70% of the maximum number of true positives in randomly generated patches of the same size as the predicted site; only two proteins did not contain any true RNA-binding residues in both predicted regions. Regardless of the protein conformational changes upon RNA-binding, the prediction accuracies based on the RNA-free/bound protein structures were found to be comparable and their binding sites overlapped as long as there are no disordered RNA-binding regions in the free structure that are ordered in the corresponding RNA-bound protein structure. | RNA-Binding Proteins |
INTRODUCTION: Inhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment. METHODS: Post hoc analysis of the AIR-BX1 studies and two trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis (QOL-B) respiratory symptom scale, were extracted as representing severity of nine distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on-treatment cycle and mixed models were used to evaluate changes across the full 16-week trial. RESULTS: Aztreonam improved cough (difference 0.22, 95% CI 0.08-0.37; p=0.002), sputum production (0.30, 95% CI 0.15-0.44; p<0.0001) and sputum colour (0.29, 95% CI 0.15-0.43; p<0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p<0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82, 95% CI 1.12-8.53; p=0.011 for sputum production and 5.02, 95% CI 1.19-8.86; p=0.01 for sputum colour). In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbation (hazard ratio 1.83, 95% CI 1.02-3.28; p=0.042). CONCLUSION: Baseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to better identify inhaled antibiotic responders and to evaluate patient response to treatment. | Aztreonam |
A facile, convenient and high yielding synthesis of a combinatorial library of 3-alkanoyl/aroyl/heteroaroyl-2H-chromene-2-thiones has been developed by the condensation of easily accessible beta-oxodithioesters and salicylaldehyde/substituted 2-hydroxybenzaldehydes under solvent-free conditions. The assessment of radical scavenging capacity of the compounds towards the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was measured and these compounds were found to scavenge DPPH free radical efficiently. Five selected compounds were able to protect curcumin from the attack of sulfur free radical generated by radiolysis of glutathione (GSH). The newly synthesized compounds exhibited profound antioxidant activities. Five of them rendered comparatively high antioxidant capacity. | Thiones |
Vancomycin-sensitive, -intermediate, and -heterointermediate methicillin-resistant Staphylococcus aureus isolates were tested by using E-tests to explore the interaction of methicillin and vancomycin. For the vancomycin-intermediate and -heterointermediate strains both drugs showed antagonism at concentrations below their MICs but synergy at methicillin concentrations near the MIC. This property could be used to screen for heterointermediate S. aureus strains. | Methicillin |
The Board of Education has a significant role in the psychiatric prevention of criminal and psychiatric disorders. Two hundred and seventy-four children were seen over a two year period and their diagnostic groupings are presented. Follow-up was possible on 150 of the children and it was found that 70 percent of them were better. The findings and conclusions from this sample are presented. | Preventive Psychiatry |
Increasing evidence has shown that specificity protein 1 (Sp1) is abnormally increased in the brains of subjects with Alzheimer's disease (AD) and transgenic AD models. However, whether the Sp1 activation plays a critical role in the AD pathogenesis and selective inhibition of Sp1 activation may have a disease-modifying effect on the AD-like phenotypes remain elusive. In this study, we reported that Sp1 mRNA and protein expression were markedly increased in the brain of APPswe/PS1dE9 transgenic mice, whereas chronic administration of mithramycin A (MTM), a selective Sp1 inhibitor, potently inhibited Sp1 activation in the APPswe/PS1dE9 mice down to the levels of wild-type mice. Specifically, we found that MTM treatment resulted in a significant improvement of learning and memory deficits, a dramatic reduction in cerebral Abeta levels and plaque burden, a profound reduction in tau hyperphosphorylation, and a marked increase in synaptic marker in the APPswe/PS1dE9 mice. In addition, MTM treatment was powerfully effective in inhibiting amyloid precursor protein (APP) processing via suppressing APP, beta-site APP cleaving enzyme 1 (BACE1), and presenilin-1 (PS1) mRNA and protein expression to preclude Abeta production in the APPswe/PS1dE9 mice. Furthermore, MTM treatment strongly inhibited phosphorylated CDK5 and GSK3beta signal pathways to reduce tau hyperphosphorylation in the APPswe/PS1dE9 mice. Collectively, our findings provide evidence that Sp1 activation may contribute to the AD pathogenesis and may serve as a novel therapeutic target in the treatment of AD. The present study highlights that selective Sp1 inhibitors may be considered as disease-modifying therapeutic agents for AD. | Plicamycin |
Major advances in our understanding of the neurology/pathology, anatomy/physiology, and molecular biology of the cerebellum have opened a new door for cerebellar ataxias (CAs). We have now entered in the 'era of therapies'. Cures are knocking at the door. We discuss the hot topics in the therapeutic protocols available for CAs, including aminopyridines, noninvasive cerebellar stimulation, anti-oxidant drugs and therapies for immune-mediated cerbellar ataxias (IMCAs), topics emphasized in this issue. The history of the cerebellum is a typical example of the importance of apparently divergent and multi-disciplinary approaches. | Cerebellar Ataxia |
The case of a 51 year-old female patient, who underwent a cholecystectomy four years ago is presented. She approached the surgical department at the Hospital Belen of Trujillo, Peru, suffering of abdominal pain for the past four months and with the presence of a mass located in the epigastrium occupying part of the right hypochondrium. A thoracic x-ray showed an encysted left pleural effusion, and an abdominal echography was compatible with a pancreatic pseudo-cyst. An exploratory laparectomy was performed and a 15x9 cm mass was found in the sub-hepatic area. This mass had a semisolid consistency with a rounded shape and multiple adherences to the upper omentum and the liver. In the macroscopic exam, after the dissection of the cyst, a 25x42 cm gauze was found inside the mass which was full of biliary fluid. Due to the unspecific clinical and image diagnosis it was decided to carry out a review of this topic, which is suspected of being under-recorded in this country. | Surgical Sponges |
Ethanol is a molecule of fundamental interest in combustion, astrochemistry, and condensed phase as a solvent. It is characterized by two methyl rotors and trans (anti) and gauche conformers, which are known to be very close in energy. Here we show that based on rigorous quantum calculations of the vibrational zero-point state, using a new ab initio potential energy surface (PES), the ground state resembles the trans conformer, but substantial delocalization to the gauche conformer is present. This explains experimental issues about identification and isolation of the two conformers. This leak" effect is partially quenched when deuterating the OH group, which further demonstrates the need for a quantum mechanical approach. Diffusion Monte Carlo and full-dimensional semiclassical dynamics calculations are employed. The new PES is obtained by means of a Delta-machine learning approach starting from a pre-existing low level density functional theory surface. This surface is brought to the CCSD(T) level of theory using a relatively small number of ab initio CCSD(T) energies. Agreement between the corrected PES and direct ab initio results for standard tests is excellent. One- and two-dimensional discrete variable representation calculations focusing on the trans-gauche torsional motion are also reported, in reasonable agreement with experiment." | Spectrophotometry, Infrared |
T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population - i.e., within the naive or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naive T cells. We report that human naive CD8 T cells (T(N)) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (T(Mem)). Following in vitro co-culture with activated central memory cells (T(CM)), ~3% of the T(N) acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the T(N) acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naive and activated memory. Pseudotime trajectory analysis provided further evidence that T(N) with an activated/memory or hybrid phenotype were derived from T(N). Our data reveal a non-cytotoxic function of T(Mem) with potential to activate autologous T(N) into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation. | Immunological Memory Cells |
Trichomonas gallinae is a protozoan parasite commonly found in columbids, passerines, and several raptor species. Although T. gallinae is thought to spread between individuals and across species through shared water sources, little research has been conducted regarding the persistence of T. gallinae in the environment. To determine the persistence of T. gallinae in various communal water sources, we inoculated 1 x 10(6) trichomonads into 500 mL samples of distilled water, quarry water, bird bath water, and rain barrel water in two replicates. Aliquots of 0.5 mL were collected from each source at -1, 0, 15, 30, and 60 min; aliquots were incubated at 37 C and examined for trichomonads by light microscopy for five consecutive days. Live trichomonads were observed in all samples and at all sampling times except prior to inoculation (-1 min). The pH of water sources ranged from an average of 5.9 to 7.4 postsampling. Our findings indicate that T. gallinae can persist for up to 60 min in various water treatments and thus be infectious for birds drinking T. gallinae-contaminated water. | Trichomonas |
PREMISE OF THE STUDY: Understanding the flexibility of monocot genomes requires a phylogenetic framework, which so far is available for few of the ca. 2800 genera. Here we use a molecular tree for the South American genus Alstroemeria to place karyological information, including fluorescent in situ hybridization (FISH) signals, in an explicit evolutionary context. METHODS: From a phylogeny based on plastid, nuclear, and mitochondrial sequences for most species of Alstroemeria, we selected early-branching (Chilean) and derived (Brazilian) species for which we obtained 18S-25S and 5S rDNA FISH signals; we also analyzed chromosome numbers, 1C-values, and telomere FISH signals (in two species). KEY RESULTS: Chromosome counts for Alstroemeria cf. rupestris and A. pulchella confirm 2n = 16 as typical of the genus, which now has chromosomes counted for 29 of its 78 species. The rDNA sites are polymorphic both among and within species, and interstitial telomeric sites in Alstroemeria cf. rupestris suggest chromosome fusion. CONCLUSIONS: In spite of a constant chromosome number, closely related species of Alstroemeria differ drastically in their rDNA, indicating rapid increase, decrease, or translocations of these genes. Previously proposed Brazilian and Chilean karyotype groups are not natural, and the n = 8 chromosomes in Alstroemeria compared to n = 9 in its sister genus Bomarea may result from a Robertsonian fusion. | Alstroemeria |
PURPOSE: To evaluate the performance of Holladay 1 and SRK/T formulas with the axial length (AL) adjustment methods including the linear and nonlinear versions of Wang-Koch AL adjustment methods and Cooke-modified AL (CMAL); and to determine whether the CMAL should be extended to the latest Barrett Universal II, Ladas Super formula (LSF), and Emmetropia Verifying Optical formulas in highly myopic eyes. DESIGN: Retrospective, consecutive case-series study. METHODS: A total of 164 eyes of 164 patients with AL >/=26.0 mm were included and divided into 2 groups: AL <28.0 mm (Group 1) and AL >/=28.0 mm (Group 2). The average arithmetic spherical equivalent prediction error (PE), mean absolute PE, median absolute error (MedAE), and the percentage of eyes within +/-0.25 diopter (D), +/-0.50 D, and +/-1.0 D of PE were determined. RESULTS: The Holladay 1 formulas showed the smallest MedAE when combined with the first linear or nonlinear version of Wang-Koch AL adjustment methods, both in total and in subgroups. The SRK/T formula displayed the highest prediction accuracy in combination with the first linear version of Wang-Koch adjustment method in total and subgroups. The CMAL reduced the absolute PE of LSF in total (P = .003) and in Group 1 (P = .017). CONCLUSIONS: The Holladay 1 and SRK/T formulas combined with specific AL adjustment methods had accuracy similar to the fourth-generation formulas for highly myopic eyes. Moreover, the CMAL can improve the accuracy of the LSF for highly myopic eyes. | Axial Length, Eye |
The measurement of the time at which normal colony-forming ability returns in irradiated cultures of Micrococcus radiodurans tsI held at 30 degrees C can be used to estimate the time of completion of recombination repair. By comparing the times to complete such repair in populations given increasing radiation doses it is possible to calculate the rate of recombination repair. The rate was independent of the radiation dose; recombination could repair in one minute the damage caused either by 1-2 krad gamma radiation or 4 X 10(-6) J mm-2 u.v. radiation. The time taken for the normal rate of DNA synthesis to return in irradiated M. radiodurans tsI was measured under conditions identical to those used to measure recombination repair. The delay in DNA synthesis was 1-0 min per 1-2 krad gamma radiation and 1-0 min per 5-6 X 10(-6) J mm-2 u.v. radiation. The data suggest that the normal rate of DNA synthesis resumes immediately after the completion of recombination repair of gamma-induced damage, but before the completion of recombination repair of u.v.-induced damage. It is postulated that cell death at the lethal dose of u.v. radiation is caused by a second round of replication of DNA which is still being repaired by recombination. | Micrococcus |
Since it can display the gastric folds, as well as the gastric wall and the exogastric area, sonography is a reliable way of diagnosing the giant hypertrophy of the gastric mucosa (Menetrier's disease). The characteristic pastterns are: --a considerable thickening of the gastric folds and wall, --a high sonolucency, --the presence of the intra-mural cysts, --some hilly" deformations in the exogastric part of the stomach, --occasionally, a mesenteric lipomatosis." | Gastritis, Hypertrophic |
Klinefelter's syndrome (KS) is the most common sex chromosomal aberration among men, with estimated prevalence of about 1 in 500 newborn males. The classical phenotype of KS is widely recognized, but many affected subjects present only very mild signs. While the association between KS and infertility has been well documented, few studies have investigated sexual function in the KS patients. In the present paper we reviewed studies addressed to emotional processing and sexual function in KS. We searched the following databases Medline, Pubmed, Embase, for Klinefelter's syndrome, sexuality. We focus on the peculiar contribution of genetic and hormonal background, which characterizes sexual dysfunction in KS. Abnormal structure and function of the emotional brain circuits have been described in KS. These alterations were less pronounced when the patients underwent to testosterone replacement therapy suggesting that they were mediated by testosterone deficiency. Accordingly, clinical studies indicate that sexual dysfunctions, eventually present in KS, are not specifically associated with the syndrome but are related to the underlying hypogonadism. In conclusion, androgen deficiency more than chromosomal abnormality is the major pathogenic factor of sexual dysfunction in KS." | Sex Chromosome Disorders of Sex Development |
A study of the relationship between mycobacterial species and their carotenoid pigments was carried out. According to the carotenoid pigments contained, the mycobacterial species tested were divided into four groups: the first group of Mycobacterium kansasii and M. marinum, which formed principally only beta-carotene; the second group of M. gordonae, M. scrofulaceum, M. szulgai, M. xenopi, M. flavescens, M. phlei, M. rhodesiae, M. neoaurum, and M. aichiense, which formed beta-carotene and a zeaxanthin-like substance; the third group of M. aurum and M. obuense, which formed beta-carotene and an eschscholtzxanthin-like substance; and the fourth group of M. chubuense and M. tokaiense, which formed beta-carotene and zeaxanthin- and eschscholtzxanthin-like substances. The common carotenoid pigment throughout the genus Mycobacterium was beta-carotene and the hypophasic carotenoids differed according to the species. | Cyclohexenes |
Surgical resection and perioperative adjuvant therapy are widely accepted standard treatments for gastrointestinal cancer. However, body composition changes, such as weight loss and skeletal muscle loss, are unavoidable during these treatments. Several studies have shown that perioperative body composition changes are affected by multimodal treatment for gastrointestinal cancer. This review summarizes the background, current status, and future perspectives of perioperative body composition changes in the multimodal treatment of gastrointestinal cancer. Recent studies have described the body composition changes observed in the early period after surgery and during adjuvant therapy. Changes in the body composition might affect adjuvant chemotherapy toxicity after surgery and postoperative complications after neoadjuvant therapy. The mechanisms underlying body composition changes during multimodal therapy are multifactorial and include systemic inflammation, reduced nutrient intake, and physical inactivity. Several approaches have been tested to maintain the body composition, and especially prevent skeletal muscle wasting, during multimodal therapy. Although the ideal approach for managing body composition changes in gastrointestinal cancer patients remains unclear, recent studies support the combination of multiple approaches rather than a single approach. | Neoadjuvant Therapy |
One of the most important problems of Kashar cheese producers is mold and yeast spoilage during storage. Williopsis saturnus var. saturnus killer yeast has been reported to have an antagonistic effect on mold and yeast reproduction. In this study, the antifungal effect of a whey protein concentrate (WPC) coating containing W. saturnus was investigated in Kashar cheese. WPC with or without W. saturnus (7 log CFU/g) or W. saturnus without coating was applied on the surface of Kashar cheese samples and stored at 4 degrees C for 56 days. Microbiological, chemical, physical and sensory properties of cheese samples were assessed. After 56 days of storage, the numbers of lactic acid bacteria were not affected by WPC containing W. saturnus; however, the population of W. saturnus increased by 1 log CFU/g. Application of W. saturnus reduced the growth of other yeasts and molds (P < 0.05). Chemical, physical and sensory properties of all coated cheeses remained unchanged. In a conclusion, use of WPC coatings containing W. saturnus can potentially minimize mold and yeast spoilage of cheese during storage. | Williopsis |
Normocytic normochromic anemia is a common complication in chronic kidney disease and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. The introduction of ESAs into clinical practice was a success story, mediating an increase in hemoglobin concentrations without the risk for recurrent blood transfusions and improving quality of life substantially. However, recombinant ESAs are still expensive and require a parenteral route of administration. Moreover, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm. This, together with changes in ESA reimbursement policy in some countries, has resulted in a significant reduction in ESA prescribing and the hemoglobin level targeted during therapy. Several attempts are being made to develop new drugs with improved characteristics and/or easier manufacturing processes compared with currently available ESAs, including new treatment approaches that may indirectly improve erythropoiesis. We give an update on the new investigational strategies for increasing erythropoiesis, examining in depth their characteristics and possible advantages in the clinical setting and the caveats to be aware of at the present stage of development. | Hematinics |
BACKGROUND: Shift work has been associated with an increased risk of cardiovascular disease (CVD). However, there is a need for more studies to determine whether there is an interaction between shift work and other risk factors of CVD, thereby increasing the risk of CVD in shift workers. AIMS: To discern whether shift work and parental mortality from myocardial infarction (MI) or sudden cardiac death (SCD) interact to increase the risk of MI in men. METHODS: A case-control dataset was used to assess interaction between shift work and parental history of CVD, using death from MI or SCD, or death before age 65, on an additive scale. Results were reported as relative excess risk due to interaction, attributable proportion due to interaction (AP) and synergy index (SI). RESULTS: There was an interaction between shift work and paternal mortality from MI or SCD, when both factors were present [SI = 2.39; 95% confidence interval (CI) 1.02âÂÂ5.6 and AP = 0.4; 95% CI 0.08âÂÂ0.73]. CONCLUSIONS: Paternal mortality from MI or SCD interacts with shift work to increase the risk of MI in men. | Parental Death |
HMGB1 is a member of the high-mobility group protein superfamily that has been widely studied as nuclear proteins that bind DNA, stabilize nucleosomes and facilitate gene transcription. A series of recent discoveries revealed a cytokine activity of HMGB1, that when secreted into the extracellular milieu, mediates downstream inflammatory responses in endotoxemia, arthritis and sepsis. HMGB1 is properly defined as a cytokine because it stimulates proinflammatory responses in monocytes/macrophages, is produced during inflammatory responses in vivo in standardized models of systemic and local inflammation, mediates delayed endotoxin lethality, and is required for the full expression of inflammation in animal models of endotoxemia, sepsis and arthritis. HMGB1 is either actively secreted by monocytes/macrophages or passively released from necrotic cells from any tissue. These pathways are central for the biology of HMGB1 as a cytokine, since they provide key mechanisms that integrate the inflammatory response to infectious and non-infectious cell injuries. Receptor signal transduction of HMGB1 occurs in part through the receptor for advanced glycation end-products (RAGE) expressed on monocytes/macrophages, endothelial cells, neurons and smooth-muscle cells. HMGB1 is a late-acting cytokine, because it first appears in the extracellular milieu 8-12 h after the initial macrophage response to proinflammatory stimuli. Knowledge of the cytokine role of HMGB1 has implications for understanding downstream cytokine cascades, regulation of delayed innate immune responses and targeting treatment towards these processes. Effectiveness of delayed treatment with HMGB1 blockade up to 24 h after induction of experimental sepsis offers a unique window of opportunities to allow rescue from lethal sepsis. | HMGB1 Protein |
Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome, due to their complexicity and diversity. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against seven clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimum inhibitory concentrations (MICs) ranging from 4-512 microg/mL. Time-kill kinetics of all AMPs at 3x MIC values against strains PAO1 and LES431 showed complete kill within 10 min to 4 h, although P15s was not bactericidal against PAO1. All AMPs significantly inhibited biofilm formation by strains PAO1 and LES431, and induction of resistance assays showed no decrease in activity against these strains. AMP cytotoxicity against human lung cells was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PAO1 and LES431 bacterial membrane lipids, efficiently permeabilising the P. aeruginosa membrane. Transcriptome and metabolome analysis revealed increased catalytic activity at the cell membrane and promotion of beta-oxidation of fatty acids. Finally, tests performed with the Galleria mellonella infection model showed that Lynronne 1 and 2 were efficacious in vivo, with a 100% survival rate following treatment at 32 mg/kg and 128 mg/kg, respectively. This study illustrates the therapeutic potential of microbiome-derived AMPs against P. aeruginosa infections. | Pseudomonas Infections |
Isolated limb infusion involves administrating cytotoxic drugs in a patient with malignant melanoma confined to one limb, and which is not surgically resectable. It provides palliation in cases where cutaneous disease is extensive. | Infusions, Intra-Arterial |
BACKGROUND: Though vertebroplasty is a well-known and extremely effective procedure in experienced hands, it is a much more difficult procedure to learn than standard spinal pain injection procedures. We therefore present a simplified, methodical approach to vertebroplasty that can be adopted by trained interventionalists. Many practitioners who attend hands-on cadaver workshops lack confidence to apply this technique in live patients. OBJECTIVES: To present a methodical, reproducible, and proven technique. To provide strategies on pre-procedure and post-procedure care in order to optimize outcomes in vertebroplasty patients. STUDY DESIGN: A step-by-step tutorial is presented outlining the steps in the vertebroplasty procedure. A discussion of anatomic considerations, pre-procedure patient selection issues, and post-procedure management is also presented. METHODS: Sections are presented on anatomy, patient selection, a 10-step technique on performance of vertebroplasty, a discussion of how this technique is advantageous, and post-procedure management. RESULTS: This technique has been proven in clinical practice for over 1,500 vertebroplasties and has been well-received the past 4 years by hundreds of trainees taught at numerous hands-on courses (Stryker Interventional Pain, Arthrocare, and Society of Interventional Radiology). CONCLUSION: A basic tutorial is presented for the beginner who is interested in vertebroplasty. This safe and reproducible technique has been proven in clinical practice. The anatomic considerations, patient selection issues, technique, and post-procedure management has been taught and well received by hundreds of physicians at numerous hands on courses within the United States and Canada. | Injections, Intralesional |
To determine the presence, quantity and distribution of androgen (AR) and oestrogen receptors (ER) in the antler velvet (AV), samples were collected from adult and yearling pampas deer males, as well as skin from the ventrolateral abdominal area (ASK). Samples were analysed with ligand-binding assays for AR and ER activity and processed for AR and ERbeta immunohistochemistry. There was more content of AR in adults than in yearling males (p = 0.02), as well as a category and type of tissue interaction (p = 0.03). There was more ER content in adults than in yearling males (p = 0.005) and in the AV than in the skin (p = 0.0001). The AR-positive score (PS) was greater in AV than in ASK in the surface stroma (p = 0.0007). In the intermediate epidermis, the AR PS was greater in adults than in yearling males (p = 0.04) and in the ASK than in the AV (p < 0.0001). There was a male category and type of tissue interaction for AR PS in the sebaceous glands (p = 0.014). The ERbeta PS in the surface stroma was greater in ASK than in AV (p = 0.004) and tended to be greater in yearling than in adult males (p = 0.093). The ERbeta PS in the intermediate epithelium and the sebaceous glands was greater in adults than in yearlings (p = 0.004 and p = 0.007, respectively). In conclusion, we reported for the first time the presence of AR and ER in the velvet skin of growing antlers in pampas deer males. Therefore, the velvet skin is sensitive to both androgens and oestrogens. Furthermore, the greater content of oestrogen receptors in the velvet of adult males suggests that adults are more sensitive to this hormone than yearlings, and thus, oestrogens have greater importance in velvet activity regulation in adult males. | Antlers |
Social regulation is ubiquitous in the US healthcare system, and American healthcare organizations claim to be among the most regulated institutions in the world. Yet relatively little is known about the impact of social regulation on these organizations' performance, or about the characteristics or determinants of effective regulatory strategies and approaches. This paper explores the use of social regulation in US healthcare, drawing on the wider literature on regulation in other countries and settings and on the growing body of general regulatory theory. It offers a framework for analysing and comparing regulatory arrangements, presents the findings from an exploratory qualitative study of regulators and regulated organizations, and concludes by developing a framework of the emergent characteristics of effective regulation which might be used in future evaluations of healthcare regulation." | Facility Regulation and Control |
INTRODUCTION: A case of endophthalmitis after dropless cataract surgery with intravitreal Tri-Moxi associated with severe vision loss. CASE SUMMARY: An 82-year-old male developed severe vision loss in the left eye 24 days after dropless cataract surgery with intravitreal Tri-Moxi injection. Best corrected visual acuity was hand motion in the left eye. Intraocular pressure was 13, with inferior keratic precipitates, 4 + cell with 1 mm layered hypopyon, and a plaque on the posterior capsule that blocked direct exam of the posterior segment. Ultrasonography revealed extensive vitritis without retinal or choroidal detachments. CONCLUSION: Endophthalmitis resolved and vision improved after management with vitreous tap, intravitreal and fortified topical antibiotics, and subsequent prompt pars plana vitrectomy. Vitreous sample grew fluoroquinolone-resistant staphylococcus epidermidis." | Tobramycin, Dexamethasone Drug Combination |
BACKGROUND: Several studies have shown that patients with a unilateral amputation have an increased risk of developing osteoarthritis (OA) in the knee of their sound leg. OBJECTIVE: The first objective was to investigate whether amputees are more frequently affected by gon-, cox- or polyarthritis as well as back pain or spinal disorders. We hypothesized that mobile and active transfemoral amputees more often experience OA and spinal disorders than non-amputees. The second objective was to compare the mean age of the patients with OA. PATIENTS: Patients with a unilateral transfemoral amputation (n = 1,569) and five abled-body control groups (each n = 1,569) matched in terms of age and gender resulting in total of 9,414 participants. METHODS: Groups were analyzed regarding the prevalence of six selected diagnoses regarding musculoskeletal disorders. RESULTS: A significantly decreased prevalence of OA and specific disorders of the spine in transfemoral amputees compared to a control group was found. The amputees with OA are significantly younger than patients with OA in the control group. CONCLUSION: The results from the presented study contradict previously published literature. Apparently circumstances of life play an important role, like physical work and strenuous activities which are likely to be underrepresented in the amputee group. The results of the study need to be used cautiously due to the major limitation of the study which is the lack of detail in individual patients caused by the methodology. | Spinal Osteochondrosis |
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