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Herpes zoster results from reactivation of the varicella zoster virus (VZV). Zoster sine herpete (ZSH) is an uncommon manifestation of VZV infection and presents with similar symptoms but without the vesicular rash. We describe an unusual case of lateral sinus thrombosis (LST) that developed during the clinical course of ZSH in the C2 distribution. A 55-year-old woman presented with a 3-day history of left temporal and postauricular pain, nausea, vomiting, and mild photophobia. She denied otalgia, otorrhea, and hearing loss. Examination revealed hyperesthesia in the left C2 nerve root distribution without evidence of herpetic rash. A computed tomography scan showed minimal fluid in the left mastoid cavity (not mastoiditis) and thrombus within the left lateral and sigmoid dural sinus. Magnetic resonance imaging and magnetic resonance angiogram confirmed these findings. Laboratory studies revealed elevated neurotrophic immunoglobulin G levels to VZV. Hypercoagulable studies were normal. She was subsequently treated with Neurontin, acyclovir, and anticoagulation. Her symptoms improved, and she was discharged 3 days later. LST is generally a complication of middle ear infection. Nonseptic LST, however, may result from dehydration, oral contraceptive use, coagulopathy, or thyroid disease. This unusual case raises the suspicion that thrombosis resulted from VZV associated thrombophlebitis in the ipsilateral cerebral venous sinuses along the second cervical nerve root distribution. A high index of suspicion is necessary in such cases so that a different treatment course can be identified and antiviral medication initiated promptly. | Zoster Sine Herpete |
OBJECTIVES: Several classification schemes have been proposed to categorize mandibular defects following surgical resection; however, there is a paucity of data to guide an optimal reconstruction. This study examines the feasibility of using a geometric algorithm to simplify and determine the optimal reconstruction for a given mandibular defect. This algorithm is then applied to three different mandible defect classification schemes to correlate the defect type and number of bony segments required for reconstruction. METHODS: Computed tomography (CT) scans of 48 mandibles were decomposed into curvilinear representations and analyzed using the Ramer-Douglas-Peucker algorithm. In total, 720 mandibular defects were created and subsequently analyzed utilizing three commonly referenced classification systems. For each defect, the number of bony segments required to reconstruct each defect was computed. RESULTS: A wide variance in the number of segments needed for optimal reconstruction was observed across existing classifications. A six-segment total mandible reconstruction best reconstituted mandibular form in all 48 mandibles. CONCLUSION: Defect classification schemes are not adaptable to predicting the number of fibula segments required for a given defect. Additionally, cephalometric templates may not be applicable in all clinical settings. The Ramer-Douglas-Peucker algorithm is well suited for providing case-specific predictions of reconstruction plans in a reproducible manner. LEVEL OF EVIDENCE: IV Laryngoscope, 130:E619-E624, 2020. | Mandibular Reconstruction |
We here report the discovery of isoquinoline-based biaryls as a new scaffold for colchicine domain tubulin inhibitors. Colchicinoid inhibitors offer highly desirable cytotoxic and vascular disrupting bioactivities, but their further development requires improving in vivo robustness and tolerability: properties that both depend on the scaffold structure employed. We have developed isoquinoline-based biaryls as a novel scaffold for high-potency tubulin inhibitors, with excellent robustness, druglikeness, and facile late-stage structural diversification, accessible through a tolerant synthetic route. We confirmed their bioactivity mechanism in vitro, developed soluble prodrugs, and established safe in vivo dosing in mice. By addressing several problems facing the current families of inhibitors, we expect that this new scaffold will find a range of in vivo applications towards translational use in cancer therapy. | Tubulin Modulators |
The development of dialysis by early pioneers such as Willem Kolff and Belding Scribner set in motion several dramatic changes in the epidemiology, economics and ethical frameworks for the treatment of kidney failure. However, despite a rapid expansion in the provision of dialysis - particularly haemodialysis and most notably in high-income countries (HICs) - the rate of true patient-centred innovation has slowed. Current trends are particularly concerning from a global perspective: current costs are not sustainable, even for HICs, and globally, most people who develop kidney failure forego treatment, resulting in millions of deaths every year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible and offer improved patient outcomes. Nephrology researchers are increasingly engaging with patients to determine their priorities for meaningful outcomes that should be used to measure progress. The overarching message from this engagement is that while patients value longevity, reducing symptom burden and achieving maximal functional and social rehabilitation are prioritized more highly. In response, patients, payors, regulators and health-care systems are increasingly demanding improved value, which can only come about through true patient-centred innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalysed, promoted and fostered through international collaboration and harmonization. | Sorption Detoxification |
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model. METHODS: Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl(4)) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored. RESULTS: Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFalpha, IL-1beta and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of alpha-SMA and TGFbeta1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFkappaB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice. CONCLUSIONS: Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH. | Corn Oil |
Eccrine angiomatous hamartoma is a rare entity characterized histologically by the combination of proliferative eccrine and vascular elements. It generally arises before puberty, as solitary or multiple lesions, with a heterogeneous clinical appearance, affecting predominantly the distal extremities, with or without associated pain or hyperhidrosis. It may require surgical treatment due to cosmetic concern, progressive enlargement or the presence of pain or excessive hyperhidrosis. We report five congenital cases of eccrine angiomatous hamartoma, emphasizing a clinically uncommon tumor-like appearance, with numerous telangiectasias on their surfaces resembling vascular lesions, in two of them. | Sweat Gland Diseases |
Despite the fact that external cervical resorption (ECR) is a well-known and rather frequently met condition, the driving force of this phenomenon still remains unclear. Recently, hypoxia has been linked to ECR. Thus, the aim of this work was to investigate the existence of hypoxia in ECR and hypothesize on its role at the time of extraction. This work is a case study of a tooth with ECR. ECR diagnosis was based on clinical and radiographic examination with cone-beam computed tomographic imaging. The extracted tooth was further analyzed by using nanofocus computed tomographic imaging and immunohistology. To investigate the 3-dimensional extent and pattern of ECR, in vivo cone-beam computed tomographic imaging and ex vivo nanofocus computed tomographic imaging were used. Different histologic stains were used to investigate the presence of a hypoxic environment and to gain a better insight into the involved cells, neuronal structures, and remodeling process during ECR. A higher distribution of hypoxia-inducible factor 1a-positive cells was found in the apical part of the resorption area when compared with the coronal area of the resorption. In addition, a similar distribution of hypoxia-inducible factor 1a-positive odontoblasts was observed in the pulp. Three-dimensional analysis of the calcification of the pulp revealed the formation of pulp stones in areas with higher hypoxia. Histology showed that remodeling during ECR can occur according to a layered pattern. This investigation confirms the presence of hypoxia in ECR and shows that there is a gradient of hypoxia within the ECR lesion and surrounding tooth structure. The hypoxic environment within the pulp is also indicated by the formation of pulp stones. | Tooth Apex |
AIMS: To describe the concentration of Zn in bulk tank milk (BTM) in a sample of New Zealand dairy farms, investigate the association between the method of Zn administration for facial eczema prophylaxis and Zn concentrations in BTM and investigate the relationship between the concentration of Zn in serum and that in BTM. METHODS: Multiple BTM samples (n = 3,330) collected during milk pick-up by the milk tanker driver were stored and tested for 121 farms, in Northland (n = 50), Waikato (n = 51) and Southland (n = 20) from February to May 2017. Enrolled farms provided retrospective information on the type of Zn supplementation (if any) used for the prevention of facial eczema and the timeframe over which supplementation occurred. In addition, the concentration of Zn in serum was measured in blood samples collected from >/=15 cattle per farm for 22 farms from Northland (n = 11) and Waikato (n = 11), and compared against the concentrations of Zn in BTM on the day of blood sampling. A linear mixed model was used to model log Zn concentrations in BTM using method of Zn supplementation, region, milk fat and protein percentage, volume of milk, and frequency of milk pick-up as risk factors. A mixed logistic regression model was used to assess the relationship between Zn concentrations in BTM and the presence of cows with a concentration of Zn in serum of >/=20 micromol/L. RESULTS: The median Zn concentration in BTM was 67.9 (min 38.9, max 146.6) micromol/L. The median range of Zn concentrations for repeated samples of BTM within farm was 22.6 micromol/L. In comparison to farms that did not use any form of Zn supplementation, farms that supplemented Zn through a slow-release capsule, oral drench, in feed or a combination of in-feed and water were associated with increased concentrations of Zn in BTM (p < 0.001). There was no difference in Zn concentrations in BTM between farms that administered Zn through the water only and farms that did not administer Zn (p = 0.22). Every 15.3 mumol/L increase in Zn concentration in BTM was associated with 2.2 times (95% CI=1.7-2.9) the odds of a cow having Zn concentration in serum >/=20 mumol/L. CONCLUSION AND CLINICAL RELEVANCE: Zn concentration in BTM is highly variable between farms, days and Zn administration method. Zn concentration in BTM content has modest potential as a way to signal whether a herd has achieved the high Zn status considered to be protective against FE. | Eczema |
During its life cycle, the malaria parasite Plasmodium falciparum is found intracellular to human erythrocytes, where its survival and ability to multiply critically depends on the control of the environment redox state. Thioredoxin is a small protein containing 104 amino acids that is part of the parasite specific redox system. During the catalytic cycle it alternates between a reduced and oxidised form. Here we report the complete resonance assignment of Plasmodium falciparum thioredoxin in its oxidized form by heteronuclear multidimensional spectroscopy. The obtained chemical shifts differ significantly from those reported earlier for this protein in its reduced state. | Protozoan Proteins |
Phenotyping for isoniazid inactivation in Canadian Eskimos and Indians showed that the former are all fast acetylators, while only 63.4% of the Indians examined belonged to the same group. Further studies are suggested to confirm this initial finding.During the investigation metabolic studies were carried out to devise a reliable urine test for phenotyping of isoniazid inactivators, to replace the fall-off technique which required venipunctures. The simplicity of the new urine test makes it suitable for mass examinations. | Isoniazid |
Traditionally, hospitals have denied the true intricacy of their organization by forcing all reporting relationships into a single structure. To address this complexity, Sunnybrook has developed three independent, yet interrelated, organization dimensions. Three structures--the traditional, the clinical unit and the programmatic dimension--provide a better link of accountability by holding departments responsible for the efficiency of their operations, holding physicians accountable for the resource implication of volume and case mix, and ensuring that the activities of the hospital's departments and clinical units are in line with hospital's overall mission and programs." | Hospital Bed Capacity, 500 and over |
AIMS: In this study, we sought to determine the pathogenic ability of endophytic fungi recovered from the spines of Calamus castaneus, a common rattan palm growing in the forests of Peninsula Malaysia. METHODS AND RESULTS: Ten endophytic fungal isolates were selected for pathogenicity tests: Colletotrichum boninense, Colletotrichum fructicola, Colletotrichum cliviae, Diaporthe hongkongensis, Diaporthe arengae, Diaporthe cf. nobilis, Neopestalotiopsis saprophytica, Neopestalotiopsis formicarum, Fusarium solani and Fusarium oxysporum. These endophytes were tested against leaves of bertam (Eugeissona sp.), oil palm (Elaeis guineensis) and mango (Mangiferae indica) and the fruits of chilli (Capsicum annum), tomato (Solanum lycopersicum) and banana (Musa acuminata). The fungal isolates showed infectivity against bertam, oil palm and mango leaves with degrees of virulence ranging from low to moderate, whereas infectivity against chilli, tomato and banana ranged from low to very high. CONCLUSIONS: Fungal endophytes isolated from the spines of C. castaneus are pathogenic to different crop plants with differing degrees of virulence or aggressiveness. SIGNIFICANCE AND IMPACT OF THE STUDY: Spines of C. castaneus can harbour fungal pathogens of a number of different crops as endophytes. The ability of the fungal endophytes to colonize and infect different crops demonstrate their importance towards agricultural crops. There is a possibility the endophytes behave as latent pathogen. When conditions become favourable, the fungal endophytes transform to pathogenic form and potentially infect other plants. | Calamus |
Valeriana jatamansi is an important temperate herb that is used in the pharmaceutical and essential oil industries. In India, this species is now on the verge of extinction due to the over-exploitation of its rhizomes from its natural habitat. It is hypothesized that the variations in bioactive compounds in its essential oil are very high among the wild populations as well as cultivated sources. Thus, this study was conducted to evaluate the chemical profiling of essential oil of four wild populations (Rupena, Kugti, Garola, and Khani) and two cultivated sources (CSIR-IHBT, Salooni), which were distilled at three consecutive days. The variation in oil concentration in roots/rhizomes was found significant (p </= 0.05), and the maximum value (0.35%) was registered with the population collected from Kugti and Khani. In essential oil, irrespective of population and distillation day, patchouli alcohol was the major compound, which ranged from 19 to 63.1%. The maximum value (63.1%) was recorded with the essential oil obtained from Garola's population and distilled on the first day. The percentage of seychellene was abruptly increased with subsequent days of extraction in all the populations. The multivariate analysis revealed that the essential oil profiles of Rupena, Kugti, Garola, and CSIR-IHBT populations were found to be similar during the first day of distillation. However, during the second day, Rupena, Kugti, Khani, and CSIR-IHBT came under the same ellipse of 0.95% coefficient. The results suggest that the population of Kugti is superior in terms of oil concentration (0.35%), with a higher proportion of patchouli alcohol (63% on the first day). Thus, repeated distillation is recommended for higher recovery of essential oil. Moreover, repeated distillation can be used to attain V. jatamansi essential oil with differential and perhaps targeted definite chemical profile. | Dipsacales |
Partial tubal atresia is a rare anomaly of unknown pathogenesis. It can occur unilaterally or bilaterally, mainly including the proximal isthmic portion or the proximal ampullary segment ('mid-portion'), and is especially associated with uterine anomalies. Any more extensive pelvic surgery, including preoperative diagnosis of associated urological anomalies, must be well planned in such patients. Salpingostomy and fimbrial approximation is a realistic option in patients with congenital ampullary atresia who wish to have a child. A MEDLINE search was performed and 18 patients found with partial atresia of different tubal portions. This report describes a further patient and reviews the available literature. | Fallopian Tubes |
Protein-ligand blind docking is a powerful method for exploring the binding sites of receptors and the corresponding binding poses of ligands. It has seen wide applications in pharmaceutical and biological researches. Previously, we proposed a blind docking server, CB-Dock, which has been under heavy use (over 200 submissions per day) by researchers worldwide since 2019. Here, we substantially improved the docking method by combining CB-Dock with our template-based docking engine to enhance the accuracy in binding site identification and binding pose prediction. In the benchmark tests, it yielded the success rate of approximately 85% for binding pose prediction (RMSD < 2.0 A), which outperformed original CB-Dock and most popular blind docking tools. This updated docking server, named CB-Dock2, reconfigured the input and output web interfaces, together with a highly automatic docking pipeline, making it a particularly efficient and easy-to-use tool for the bioinformatics and cheminformatics communities. The web server is freely available at https://cadd.labshare.cn/cb-dock2/." | GTP-Binding Protein Regulators |
Bezoars are usually encountered in patients with altered gastric anatomy or function. Symptomatic, large phytobezoars or trichobezoars may require endoscopic fragmentation or surgical removal. Foreign bodies of the stomach are usually a self-limited problem, because at least 90% pass without symptoms, in patients with normal gastrointestinal anatomy. Endoscopic removal should be considered for sharp, pointed, or long objects, or in patients with altered anatomy, such as intestinal stricture. | Bezoars |
Augmin is a protein complex that binds to spindle microtubules (MTs), recruits the potent MT nucleator, gamma-tubulin, and thereby promotes the centrosome-independent MT generation within mitotic and meiotic spindles. Augmin is essential for acentrosomal spindle assembly, which is commonly observed during mitosis in plants and meiosis in female animals. In many animal somatic cells that possess centrosomes, the centrosome- and augmin-dependent mechanisms work cooperatively for efficient spindle assembly and cytokinesis. Yeasts have lost the augmin genes during evolution. It is hypothesized that their robust MT nucleation from the spindle pole body (SPB), the centrosome-equivalent structure in fungi, compensates for the lack of augmin. Intriguingly, however, a gene homologous to an augmin subunit (Aug6/AUGF) has been found in the genome of filamentous fungi, which has the SPB as a robust MT nucleation centre. Here, we aimed to clarify if the augmin complex is present in filamentous fungi and to identify its role in mitosis. By analysing the Aug6-like gene in the filamentous fungus Aspergillus nidulans, we found that it forms a large complex with several other proteins that share weak but significant homology to known augmin subunits. In A. nidulans, augmin was enriched at the SPB and also associated with spindle MTs during mitosis. However, the augmin gene disruptants did not exhibit growth defects under normal, checkpoint-deficient, or MT-destabilised conditions. Moreover, we obtained no evidence that A. nidulans augmin plays a role in gamma-tubulin recruitment or in mitotic cell division. Our study uncovered the conservation of the augmin complex in the fungal species, and further suggests that augmin has several functions, besides mitotic spindle MT nucleation, that are yet to be identified. | Spindle Pole Bodies |
Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins. | Choroid Plexus Neoplasms |
A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA-mediated transformation occurs via three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of amino acids, it is operationally simple, and it can be scaled up to provide multigram quantities of diazirine. Interestingly, we also demonstrated that this transformation could be applied to dipeptides without racemization. Furthermore, (14)N(2) and (15)N(2) isotopomers can be obtained, emphasizing a key trans-imination step when using (15)NH(3). In addition, we report the first experimental observation of (14)N/(15)N isotopomers directly creating an asymmetric carbon. Finally, the (15)N(2)-diazirine from l-tyrosine was hyperpolarized by a parahydrogen-based method (SABRE-SHEATH), demonstrating the products' utility as hyperpolarized molecular tag. | Diazomethane |
PURPOSE OF REVIEW: The authors discuss the most relevant information in the field of rotavirus vaccines published from October 2007 to June 2009; new information on the virus, host response and disease burden that relate to our understanding of vaccine mechanisms and impact are discussed. The review will focus on the role of the vaccines for the developing world but this does not preclude the relevance of these vaccines for children living in the industrialized world. RECENT FINDINGS: Immune mechanisms involved in rotavirus-associated immunity potentially relevant for vaccine-associated immunity continue to be identified including anti-NSP4 antibodies, cellular and mucosal mechanisms. Rotavirus-associated disease burden is high, causing approximately 40% of diarrhea-associated hospitalizations in children less than 5 years of age worldwide; G12, G8 and P[6] antigenic types emerging in developing countries are increasing in prevalence and may share worldwide circulation with the other five more common serotypes. The two currently available vaccines, based on different immune concepts, (VP7/VP4 homotypic specificity for RotaTeq vs. homotypic and heterotypic specificity for Rotarix) have demonstrated high and sustained efficacy in middle and high-income countries. Recent efficacy and effectiveness studies demonstrate acceptable protection levels in the poorest countries of the world against most antigenic types, leading to universal vaccine recommendation. Postlicensure surveillance has not detected any signal of increased risk for intussusception in children vaccinated with any of the two vaccines. SUMMARY: Rotavirus vaccines are well tolerated and provide adequate protection against moderate to severe disease in high, middle and low-income regions. Partnerships between governments, industry, and funding agencies will now be urgently needed to promote vaccine use, especially in the less privileged countries of the world. | Rotavirus Vaccines |
The major fatty acids (greater than 10%) of Entomophthora egressa were C16:0 and C18:1 . Minor fatty acids, which varied with the stage of fungal development, included C11:0, C12:0, C13:0, C14:0, C15:0, C16;1, C17:0, C18:0, C18:2, C18:3 C:201, C20:2, C20:3, C20:4, C20:5 and two unidentified unsaturated fatty acids. Differences were observed between the total fatty acid levels of C12:0, C14:0, C17:0, C18:0, and C20:5 and the degree of unsaturation of the fatty acids of 37-h protoplasts grown in modified Grace's medium and a simplified growth medium (SGM). The levels of C12:0, C14:0, C18:1, C20:4, and C20:5 decreased and the levels of C18:0 and C20:2 increased with the formation of spherical hyphal body (shb)initials. With the production of mature shb increased levels of C12:0, C14:0, C15:0, C18:1, C20:4, and C20:5 were detected. During the germination of the shb the levels of C14:0, C16:1, C18;1, and C20:4 increased, whereas C15:0 and C20:5 levels declined. The fatty acid levels, except for C12:0, C13:0, and C20:2, remained constant during the mycelial stage. The degree of fatty acid unsaturation decreased during early stages of development (protoplasts through shb initials). In SGM the degree of fatty acid unsaturation was lowest during the shb initial stage and highest during the shb stage. The total lipid level increased during shb maturation and declined during shb germination. | Entomophthora |
A growing number of researchers are focusing their attention on the possibility that thyroid hormone metabolites, particularly 3,5-diiodothyronine (T2), may actively regulate energy metabolism at the cellular, rather than the nuclear, level. Due to their biochemical features, mitochondria have been the focus of research on the thermogenic effects of thyroid hormones. Indeed, mitochondrial activities have been shown to be regulated both directly and indirectly by T2-specific pathways. Herein, we describe the effects of T2 on energy metabolism. | Diiodothyronines |
Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number of functional secondary metabolites, including anti-inflammatory pigments (such as monascin and ankaflavin [AK]), monacolins, and dimerumic acid. These secondary metabolites have anti-inflammatory, anti-oxidative, and anti-tumor activities. We found that AK positively regulates several transcription factors associated with the prevention of metabolic syndrome and other diseases, including peroxisome proliferator-activated receptor (PPAR)-gamma, PPAR-alpha, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AK reduced hyperglycemia and enhanced pancreatic function via PPAR-gamma activation and increased lipid metabolism due to PPAR-alpha activation. The compound also exerted antioxidant effects via activation of Nrf2. These results suggest that AK belongs to the class of selective peroxisome proliferator-activated receptor modulators (SPPARMs), which are associated with a good safety profile when used in patients suffering from metabolic syndrome. Together with our studies to determine how AK production can be increased during Monascus fermentation, these data demonstrate the great potential of AK as a nutraceutical or therapeutic agent. | Monascus |
All tetrameric hemoglobins from Antarctic fish, including that from Trematomus bernacchii, HbTb form in the ferric state, promptly and distinctively from all the other tetrameric hemoglobins, a mixture of aquo-met at the alpha subunits and bis-histidyl adduct (hemichrome) at the beta subunits. The role of the tertiary and quaternary structure in the hemichrome formation is unknown. Here we report the cloning, expression, purification, spectroscopic and computational characterization of the beta-chain of HbTb (beta-HbTb). Similarly to the human beta-chains, beta-HbTb self-assembles to form the homotetramer beta(4)-HbTb; however, the latter quantitatively forms reversible ferric and ferrous bis-histidyl adducts, which are only partially present in the human tetramer (beta(4)-HbA). A molecular dynamics study of the isolated beta subunit of the two Hbs indicates that the ability to form hemichrome is an intrinsic feature of the chain; moreover, the greater propensity of beta-HbTb to form the bis-histidyl adduct is probably linked to the higher flexibility of the CD loop region. On the bases of these experimental and computational results on the isolated chain, the influence of the quaternary structure on the stability of the endogenous ferrous and ferric hexa-coordination is also discussed. | beta-Globins |
Currently, food allergies are an important health concern worldwide. The presence of undeclared allergenic ingredients or the presence of traces of allergens due to accidental contamination during food processing poses a great health risk to sensitized individuals. Therefore, reliable analytical methods are required to detect and identify allergenic ingredients in food products. Real-time PCR allowed a specific and accurate amplification of allergen sequences. Some processing methods could induce the fragmentation and/or degradation of genomic DNA and some studies have been performed to analyze the effect of processing on the detection of different targets, as thermal treatment, with and without applying pressure. In this review, we give an updated overview of the applications of real-time PCR for the detection of allergens of tree nut in processed food products. The different variables that contribute to the performance of PCR methodology for allergen detection are also review and discussed. | Allergens |
A Candida rugosa lipase immobilized on polypropylene powder was employed as the biocatalyst for the enantioselective hydrolysis of (R, S)-suprofen 2,2,2-trifluorothioester in cyclohexane, in which trioctylamine was added as the catalyst to perform in situ racemization of the remaining (R)-thioester. A hollow-fiber membrane was also integrated with the dynamic kinetic resolution process in order to continuously extract the desired (S)-suprofen into an aqueous solution containing NaOH. A kinetic model for the whole process (operating in batch and feed-batch modes) was developed, in which enzymatic hydrolysis and deactivation, lipase activation, racemization and non-enantioselective hydrolysis of the substrate by trioctylamine, and reactive extraction of (R)- and (S)-suprofen into the aqueous phase in the membrane were considered. Theoretical predictions from the model for the time-course variations of substrate and product concentrations in each phase were compared with experimental data. | Suprofen |
Venomous animals that are able to innoculate or inject venom and poisonous animals that cannot inject venom but are toxic when ingested belong to all zoological groups. They can be encountered worldwide in any ecosystem on land and at sea but they are more common and more dangerous in tropical areas. This first article of a series to appear in the next issues of Medecine Tropicale presents an overview of species involved in envenomations and poisonings. In addition to a brief reviewing geographic risks and circumstances in which bites, stings or ingestion occur, some information is provided about antivenim therapy, the only etiological treatment. | Animals, Poisonous |
PURPOSE OF REVIEW: The purpose of this paper is to review and discuss studies on soy allergy. RECENT FINDINGS: In Central Europe soy is a clinically relevant birch pollen-related allergenic food. Crossreaction is mediated by a Bet v 1 homologous protein, Gly m 4. Additionally, birch pollen allergic patients might acquire through Bet v 1 sensitization allergies to mungbean or peanut, in which Vig r 1 and Ara h 8 are the main cross-reactive allergens. Threshold doses in soy allergic individuals range from 10 mg to 50 g of soy and are more than one order of magnitude higher than in peanut allergy. No evidence was found for increased allergenicity of genetically modified soybeans. SUMMARY: In Europe, both primary and pollen-related food allergy exist. The diagnosis of legume allergy in birch pollen-sensitized patients should not be excluded on a negative IgE testing to legume extracts. Bet v 1 related allergens are often underrepresented in extracts. Gly m 4 from soy and Ara h 8 from peanut are nowadays commercially available and are recommended in birch pollen allergic patients with suspicion of soy or peanut allergy, but negative extract-based diagnostic tests to screen for IgE specific to these recombinant allergens. | Antigens, Plant |
BACKGROUND: Transoral thyroidectomy can be performed using nasal or oral intubation. Recently, we encountered two cases of vocal cord granuloma that were suspected to result from intraoperative compression by the oral endotracheal tube. CASES PRESENTATION: Two women underwent transoral endoscopic thyroidectomy with oral endotracheal tubes fixed at the mouth angle. Their initial postoperative recovery was uneventful, but they developed hoarseness 2 months after the surgery. Subsequent strobolaryngoscopy revealed vocal cord granulomas at the side of contact of the endotracheal tube. One patient received medication and voice therapy, and her granuloma shrank significantly one month later. The other patient underwent granuloma resection. Thereafter, the symptoms improved in both the patients. CONCLUSIONS: Oral intubation with tube placement at the mouth angle might result in the formation of vocal cord granulomas. Therefore, we suggest positioning the tube at the midline to avoid excessive irritation on one side of the vocal cord. | Granuloma, Laryngeal |
Five fungal endophytes (K4, K5, K6, K9, K14) producing Cajaninstilbene acid (CSA, 3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid) were isolated from the roots of pigeon pea [Cajanus cajan (L.) Millsp.]. CSA is responsible for the prominent pharmacological activities in pigeon pea. The amount of CSA in culture solution varied among the five fungal endophytes. K4 produced the highest levels of CSA (1037.13 microg/L) among the endophytes tested after incubation for five days. Both morphological characteristics and molecular methods were used for species identification of fungal endophytes. The five endophytic isolates were characterized by analyzing the internal transcribed spacer (ITS) rRNA and beta-tubulin genes. The K4, K5, K9 and K14 strains isolated from pigeon pea roots were found to be closely related to the species Fusarium oxysporum. K6 was identified as Neonectria macrodidym. The present study is the first report on the isolation and identification of fungal endophytes producing CSA in pigeon pea. The study also provides a scientific base for large scale production of CSA. | Cajanus |
State-level legislation was instrumental in achieving marriage equality and is similarly crucial in establishing protection from discrimination for LGBT employees. States that were early legalizers of same-gender marriage shared geographic, political, and demographic variables. An analysis of the characteristics of states that are early adopters of legislation prohibiting LGBT employment discrimination lacks in the literature. This study analyzed variables significant to the early state adoption of legislation prohibiting discrimination against LGBT employees using multinomial logistic regression. A state's region, the size of its urban population, college graduates, and the percentage of same-gender families were among nine variables significant to state adoption of anti-discrimination statutes protecting LGBT employees. Efforts to secure protection from discrimination for LGBT employees should focus on fair working conditions for all as opposed to specific rights based on sexual orientation and gender identity. Further, different LGBT rights issues may warrant different strategies for public support. | Right to Work |
A new series of N-3,3-diphenylpropyl-N-(p-X-benzyl)-N'-phenylureas (5a-g) and thioureas (6a-g) were synthesized by the reaction of secondary amines and phenyl isocyanate or isothiocyanate. The cytotoxic effects of the urea and thiourea derivatives were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. Moreover, the activity of compounds in the inhibition of DNA topoisomerases I and II-alpha was tested. The results indicated that the compounds presented important and promising antiproliferative action. | Thiourea |
More and more attention is paid to the radical nitric oxide which is now known to be part of the mammalian physiology and immune system. Nitric oxide is synthesized by one of the most complicated and fascinating enzyme families identified so far. Inducible nitric oxide synthesis after appropriate stimuli has regulatory, cytostatic and/or toxic consequences and may play an important role in the pathophysiology of several diseases." | Oxidoreductases Acting on CH-NH2 Group Donors |
Since its discovery in 2000, WW domain-containing oxidoreductase (WWOX, FOR or WOX1) has been considered as a tumor suppressor protein. Global research focus has been aimed mainly toward this direction. In this thematic issue, updated information has been collected regarding the structure, function and signaling of WWOX, along with its critical role as a tumor suppressor and participation in metabolism, neurodegeneration, ataxia, epilepsy, neural disorders, neuronal damages, and interactions with oncogenic viruses. WWOX is not a driver of cancer initiation. Chromosomal alterations in the WWOX gene enhance cancer progression. Importantly, a homozygous nonsense mutation of WWOX gene in humans leads to neural pathologies and early death, rather than spontaneous cancer development. These findings suggest new physiological functions of WWOX in metabolism and neural diseases, and these areas require further investigation." | WW Domain-Containing Oxidoreductase |
A growing number of weed species have evolved resistance to herbicides in recent years, which causes an immense financial burden to farmers. An increasingly popular method of weed control is the adoption of crops that are resistant to specific herbicides, which allows farmers to apply the herbicide during the growing season without harming the crop. If such crops are planted in the presence of closely related weed species, it is possible that resistance genes could transfer from the crop species to feral populations of the wild species via gene flow and become stably introgressed under ongoing selective pressure by the herbicide. We use a density-dependent matrix model to evaluate the effect of planting such crops on the evolution of herbicide resistance under a range of management scenarios. Our model expands on previous simulation studies by considering weed species with a more complex life cycle (perennial, rhizomatous weed species), studying the effect of environmental variation in herbicide effectiveness, and evaluating the role of common simplifying genetic assumptions on resistance evolution. Our model predictions are qualitatively similar to previous modeling studies using species with a simpler life cycle, which is, crop rotation in combination with rotation of herbicide site of action effectively controls weed populations and slows the evolution of herbicide resistance. We find that ignoring the effect of environmental variation can lead to an over- or under-prediction of the speed of resistance evolution. The effect of environmental variation in herbicide effectiveness depends on the resistance allele frequency in the weed population at the beginning of the simulation. Finally, we find that degree of dominance and ploidy level have a much larger effect on the predicted speed of resistance evolution compared to the rate of gene flow. | Herbicide Resistance |
Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level <29 IU/mL at week 48. No amino-acid substitutions associated with viral breakthrough were detected by deep sequencing, and no resistance to TAF was found through week 96. In addition, no difference in the frequency of HBeAg or hepatitis B surface antigen loss was observed. However, TAF was associated with a significantly higher ALT normalization rate than was TDF, based on the American Association for the Study of Liver Diseases criteria (male: ALT </=30 U/L and female: ALT </=19 U/L). An analysis of renal safety showed that patients treated with TAF had a significantly lower decrease in the estimated glomerular filtration rate level than did patients treated with TDF. Similarly, the declines of hip and spine bone mineral density were significantly less in the TAF group. These trends of efficacy and renal/bone safety continued through week 96. Longer term follow-up and real-world data will be required to determine if the differences in viral/biochemical response and renal/bone safety seen with TAF in comparison with TDF are clinically relevant. | Adenine |
We investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence. Expression of the pluripotency factor NANOG downregulates methionine adenosyltransferase 2 A, decreases ammonium, restores insulin sensitivity, increases glucose uptake, and enhances muscle regeneration post-injury. Similarly, selective inhibition of methionine adenosyltransferase 2 A activates Akt2 signaling, repairs pyruvate kinase, restores glycolysis, and enhances regeneration, which leads to significant enhancement of muscle strength in a mouse model of premature aging. Collectively, our investigation indicates that inhibiting methionine metabolism may restore age-associated impairments with significant gain in muscle function. | Racemethionine |
OBJECTIVE: The present study aims to translate into Turkish and investigate the validity and reliability of the Mental Health Recovery Measure (MHRM). METHOD: The sample consisted of 343 outpatients - and in-patients under treatment for a variety of psychiatric diagnoses at a state hospital and a university research hospital. The MHRM along with the Subjective Recovery Assessment Scale (SRAS), Psychological Well Being Scale (PWBS), Emotional Eating Scale (EES), and The Internalized Stigma of Mental Illness Scale (ISMI). RESULTS: The mean MHRM total score was estimated at 31.66 (sd=10.02). Exploratory factor analysis revealed one single robust factor explaining 64% of the variance of the total scores. Alpha internal consistency coefficient was calculated as 0.94 and corrected item-total correlation coefficients were entirely above 0.60. The MHRM scores showed positive and strong correlations with the PWBS (r=0.695; p<0.001) and SRAS (r=0.732; p<0.001), negative and strong correlation with the ISMI (r=-0.696; p<0.001) and no correlation with the EES scores (r=-0.021; p=0.703). CONCLUSION: Our data provides initial evidence supporting the validity and reliability of the Turkish MHRM in evaluating the tendency for recovery of mental health consumers for clinical and research purposes. Further studies addressing psychometric properties of the scale are warranted. | Mental Health Recovery |
Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with arsenic metabolites being implicated in the pathogenesis. In contrast, arsenic trioxide (As(2)O(3)) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAs(III)) to promyelocytic leukemia (PML) protein is the proposed initial step. These findings on the two-edged sword characteristics of arsenic suggest that after entry into cells, arsenic reaches the nucleus and triggers various nuclear events. Arsenic is reduced, conjugated with glutathione, and methylated in the cytosol. These biotransformations, including the production of reactive metabolic intermediates, appear to determine the intracellular dynamics, target organs, and biological functions of arsenic. | Arsenic Trioxide |
PURPOSE: Venous cerebral blood volume (CBV(v) ) is a major contributor to BOLD contrast, and therefore is an important parameter for understanding the underlying mechanism. Here, we propose a velocity-selective venous spin labeling (VS-VSL)-prepared 3D turbo spin echo pulse sequence for whole-brain baseline CBV(v) mapping. METHODS: Unlike previous CBV(v) measurement techniques that exploit the interrelationship between BOLD signals and CBV(v) , in the proposed VS-VSL technique both arterial blood and cerebrospinal fluid (CSF) signals were suppressed before the VS pulse train for exclusive labeling of venous blood, while a single-slab 3D turbo spin echo readout was used because of its relative immunity to magnetic field variations. Furthermore, two approximations were made to the VS-VSL signal model for simplified derivation of CBV(v) . In vivo studies were performed at 3T field strength in 8 healthy subjects. The performance of the proposed VS-VSL method in baseline CBV(v) estimation was first evaluated in comparison to the existing, hyperoxia-based method. Then, data were also acquired using VS-VSL under hypercapnic and hyperoxic gas breathing challenges for further validation of the technique. RESULTS: The proposed technique yielded physiologically plausible baseline CBV(v) values, and when compared with the hyperoxia-based method, showed no statistical difference. Furthermore, data acquired using VS-VSL yielded average CBV(v) of 2.89%/1.78%, 3.71%/2.29%, and 2.88%/1.76% for baseline, hypercapnia, and hyperoxia, respectively, in gray/white matter regions. As expected, hyperoxia had negligible effect (P > .8), whereas hypercapnia demonstrated vasodilation (P << .01). CONCLUSION: Upon further validation of the quantification model, the method is expected to have merit for 3D CBV(v) measurements across the entire brain. | Cerebral Blood Volume |
Bisphosphonates (BPs) are cornerstones in the treatment of patients with compromised skeletal integrity (either cancer related or not). However, a major indication for BPs use remains the treatment of patients with advanced cancer metastatic to the bone. Recently, several observations derived from clinical trials, primarily aimed at establishing the impact of BPs on the bone health of cancer patients, suggested a potential role for these agents as direct anti-tumor drugs. Consequently, a series of preclinical works were produced with the aim of clarifying the mechanism underlying this observed effect. However, the impact of such data is still under debate owing to the intrinsic weakness of observations from trials not adequately powered to support them. In conclusion, the entire matter remains one of the most intriguing in oncology, and data from ongoing and planned future studies will surely provide us with more information on the great potential of BPs in the adjuvant setting. | Diphosphonates |
With an increased focus on recycling, local authorities need to adapt their systems for curbside collection of household waste to accommodate an increased degree of sorting of waste types. Therefore, it is essential to study the transport aspects of waste collection. In this paper, we analyze the driving requirements for curbside collection of household waste for different systems in the context of Denmark. We consider a Collect, then sort system, as opposed to two Sort, then collect systems using single and multi-compartment vehicles, and compare the systems among themselves, and to the collection for incineration system. Our approach consists of solving the underlying capacitated arc routing problems of each system, and comparing the transport requirements in terms of driven distance and number of routes across systems. Our findings show that an increased degree of sorting is synonymous with a significant increase in the driven distance and the number of routes. Moreover, we find that the sort, then collect by multi-compartment vehicles system outperforms the others in terms of driven distance, and that the sort, then collect by single compartment vehicles system outperforms the others in terms of number of routes. We found that three cost drivers affect the overall results: the change in the size of the vehicle, the compression factor inside the vehicles' compartments, and the packing of the vehicles' compartments. | Sanitation |
The biochemical and biological effects of the combination of 5-aza-2'-deoxycytidine (5-aza-dCyd) and 3-deazauridine (3-DU) on L1210 leukemic cells and EMT6 tumor cells were investigated. The cytotoxic action of 5-aza-dCyd and 3-DU on both L1210 and EMT6 cells in vitro was synergistic when these agents were used in combination. The combination of 5-aza-dCyd and 3-DU produced a greater inhibition of in vitro growth of L1210 and EMT6 cells than did either agent alone. The in vivo antineoplastic activity of this combination was synergistic with respect to the increased survival time of BALB/c x DBA/2 F1 mice with L1210 leukemia. 3-DU, an agent that reduces the intracellular pool size of cytosine nucleotides, stimulated the incorporation of [3H]-5-aza-dCyd into DNA of both L1210 and EMT6 cells, suggesting that the synergistic action of this combination is related to the increased incorporation of 5-aza-dCyd in the presence of 3-DU. | 3-Deazauridine |
Bacterial meningitis is associated with high morbidity and mortality. Few cases of pneumococcal meningitis during pregnancy and the postpartum period have been reported. We describe a case of postpartum pneumococcal meningitis complicated by endocarditis. A 26-year-old para-2 woman who had had a normal vaginal delivery at 38 weeks at a maternity home was transported to our hospital with a 39.5 degrees C fever 11 days postpartum. Eight hours after her arrival, her state of consciousness deteriorated rapidly. Lumbar puncture revealed Gram-positive cocci consistent with Streptococcus pneumoniae. She was immediately treated with antibiotics and subsequently diagnosed with endocarditis. Final culture results from the blood and cerebrospinal fluid confirmed the presence of S. pneumoniae. She recovered completely with no evidence of neurological damage. Maintaining a high clinical suspicion and initiating appropriate diagnostic testing and therapeutic interventions promptly are essential to reducing the morbidity and mortality associated with bacterial meningitis. | Puerperal Infection |
Introduction: The development of novel complex biotherapeutics led to new challenges in biopharmaceutical industry. The potential of these particles has been demonstrated by the approval of several products, in the different fields of gene therapy, oncolytic therapy, and tumor vaccines. However, their manufacturing still presents challenges related to the high dosages and purity required.Areas covered: The main challenges that biopharmaceutical industry faces today and the most recent developments in the manufacturing of different biotherapeutic particles are reported here. Several unit operations and downstream trains to purify virus, virus-like particles and extracellular vesicles are described. Innovations on the different purification steps are also highlighted with an eye on the implementation of continuous and integrated processes.Expert opinion: Manufacturing platforms that consist of a low number of unit operations, with higher-yielding processes and reduced costs will be highly appreciated by the industry. The pipeline of complex therapeutic particles is expanding and there is a clear need for advanced tools and manufacturing capacity. The use of single-use technologies, as well as continuous integrated operations, are gaining ground in the biopharmaceutical industry and should be supported by more accurate and faster analytical methods. | Vaccines, Virus-Like Particle |
Sleep/wake timing shifts later in young humans during the second decade of life. In this review we describe sleep/wake patterns, changes in these patterns across adolescence, and evidence for the role of environmental, psychosocial, and biological factors underlying these changes. A two-process model incorporating circadian (Process C) and sleep/wake homeostatic (Process S) components is outlined. This model may help us to understand how developmental changes translate to shifted sleep/wake patterns. Delayed sleep phase syndrome (DSPS), which has a typical onset during the second decade of life, may be an extreme manifestation of homeostatic and circadian changes in adolescence. We describe symptoms, prevalence, and possible etiology of DSPS, as well as treatment approaches in adolescents." | Sleep Disorders, Circadian Rhythm |
The effect of an externally applied directional force on molecular friction is so far poorly understood. Here, we study the force-driven dissociation of the ligand-protein complex biotin-streptavidin and identify anisotropic friction as a not yet described type of molecular friction. Using AFM-based stereographic single molecule force spectroscopy and targeted molecular dynamics simulations, we find that the rupture force and friction for biotin-streptavidin vary with the pulling angle. This observation holds true for friction extracted from Kramers' rate expression and by dissipation-corrected targeted molecular dynamics simulations based on Jarzynski's identity. We rule out ligand solvation and protein-internal friction as sources of the angle-dependent friction. Instead, we observe a heterogeneity in free energy barriers along an experimentally uncontrolled orientation parameter, which increases the rupture force variance and therefore the overall friction. We anticipate that anisotropic friction needs to be accounted for in a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments. | Streptavidin |
BACKGROUND: Strongyloidiasis is an infectious disease that can be fatal in immunocompromised patients. Patients with end-stage renal failure who are on dialysis have a considerably weakened immune system, and organ transplantation is a major risk factor for severe strongyloidiasis. Knowledge of the local epidemiology in tropical and subtropical areas is an essential prerequisite for designing an appropriate strategy to prevent this potentially lethal complication. In this study, we aimed to estimate the prevalence and associated risk factors of S. stercoralis infection in patients on dialysis in Cochabamba, Bolivia. METHODS: A cross-sectional study was carried out among patients undergoing haemodialysis in Cochabamba (elevation 2,500 m, temperate climate), collecting information on socio-demographic, lifestyle, and clinical variables, and using one coproparasitological technique (the modified Baermann technique) and one serological (ELISA) test for S.stercoralis diagnosis. RESULTS: In total, 149 patients participated in the study (mean age = 51.4 years, 48.3% male). End-stage renal disease was predominantly (59%) of hypertensive and/or diabetic origin. The positive serological prevalence was 18.8% (95% CI: 13.3%-25.9%). Based on the sensitivity and specificity of the ELISA test, the estimate of the actual prevalence was 15.1% (95% CI: 9.4%-20.7%). Stool samples of 105 patients (70.5%) showed a coproparasitological prevalence of 1.9% (95% CI: 0.52%-6.68%). No potential risk factors were significantly associated with S. stercoralis infection. CONCLUSIONS: We found a high seroprevalence of S. stercoralis in Bolivian patients undergoing haemodialysis in Cochabamba. We recommend presumptive antiparasitic treatment at regular intervals to avoid the potentially fatal complications of severe strongyloidiasis. | Strongyloidiasis |
Aristolochic acids (AAs) are a family of structurally related nitrophenanthrene carboxylic acids that are present in medicinal herbs such as Aristolochia species. The organic anion transporters (OATs) of the solute carrier (SLC22) gene family located in the renal proximal tubules play a key role in the excretion of a variety of exogenous and endogenous compounds. However, it is unclear how AAs permeate into renal epithelial cells. In this regard, we investigated the role of rat OAT1 ([rOAT1] SLC22A6) in the cellular uptake of AAI in vitro and in vivo. A concentration- and time-dependent intracellular accumulation of AAI was observed in rOAT1-transfected human embryonic kidney 293 (HEK293) cells, which was 2- to 6-fold higher than the control cells. There was a significantly increased rate of cellular apoptosis in rOAT1-transfected HEK293 cells than control cells after AAI treatment. Para-aminohippuric acid (PAH) significantly reduced the intracellular accumulation of AAI in rOAT1-transfected HEK293 cells. Administration of AAI for 35 days in rats caused significantly reduced expression of OAT1 in basolateral membrane and declined renal clearance of PAH as well as renal proximal tubule injuries. These findings indicate that AAI is taken up by OAT1, which then exert its intracellular toxic effects on renal proximal tubule cells, which in turn damage functional OAT1 and may further disturb the transport of its substrates." | Organic Anion Transport Protein 1 |
Biobanks have been recognized as a key research infrastructure and how to approach ethical questions has been a topic of discussion for at least a decade by now. This article explores the characteristics of donors' participation in European biobanks as reflected in the consent documents of a selection of different biobanks from various European countries. The primary aim of this study is to understand how donors are informed about their participation in biobanking. Also the paper discusses what the most important thematic issues of information are to be given to the biobank participants and how this information should be presented in the consent documents. For these purposes, we analyse consent documents from 14 biobanks in 11 countries for six ethically relevant issues: (1) model of consent, (2) scope of future research, (3) access to medical data, (4) feedback to the participants, (5) consent withdrawal, and (6) role of research ethics committee. In order to compare different trends of informing donors of human biological material and medical data, we interpret the six analysed issues in the context of respect to donor's autonomy paradigm. Although the results of the paper reflect the heterogeneity of biobank consent document policies applied in different European countries, we uncovered some trends and suggested several examples of good practices to balance the interests of the donors with those of the researchers and future patients. | Consent Forms |
Despite medical and technical advancements stent thrombosis continued to poses a significant risk in patients after drug eluting stent (DES) implantation and clopidogrel resistance has been recognized as an important determinant of this risk. Novel antiplatelets such as prasugrel and ticagrelor can be used in cases of clopidogrel resistance however bleeding complications remain the Achilles' heel of antiplatelet therapy. Several genetic polymorphisms affect the clopidogrel absorption and bio-activation in the active form of the drug. CYP2C19 is responsible for most of the clopidogrel bio-transformation and loss of function as well as, gain of function polymorphisms of this enzyme has been recognized. Early studies have linked CYP2C19 genetic polymorphisms with clinical events, although, these findings were not confirmed by later studies. However, when the estimated thrombotic risk is high a combination of genetic information and functional platelet tests should be essential for clinicians to access clopidogrel effectiveness and to recommend alternative antiplatelet management. | Coronary Thrombosis |
The toxicities associated with 5-fluorouracil (5-FU), a potent broad-spectrum chemotherapeutic agent, can not only affect the morbidity and the efficacy of chemotherapy but also limit its clinical use. The objective of this study is to investigate the effects of a commercial anthocyanin-rich extract from bilberry (AREB) against 5-FU-induced myelotoxicity in vivo, and against chemosensitivity to 5-FU in vitro. A single injection of 5-FU at 200 mg/kg induced severe peripheral erythrocytopenia, thrombocytopenia and leucopenia as well as hypocellularity of the spleen and bone marrow in C57BL/6 mice. Oral administration of 500 mg/kg of AREB for 10 days significantly increased the number of red blood cells, neutrophils, and monocytes in peripheral blood to 1.2-fold, 9-fold, and 6-fold, respectively, compared with those seen after treatment with 5-FU alone (p< 0.05-0.001). The hypocellularity of the spleen and bone marrow caused by 5-FU was also distinctly alleviated in the AREB-treated group. Furthermore, AREB treatment with 50 and 100 microg/ml as a monomeric anthocyanin did not interfere with, but rather enhanced the chemotherapeutic efficacy of 5-FU in vitro. These results suggest that AREB may have protective potential against 5-FU-induced myelotoxiciy and/or the ability to enhance the chemotherapeutic effectiveness of 5-FU. | Vaccinium myrtillus |
PURPOSE OF REVIEW: Achalasia is one of the most commonly described primary esophageal motility disorders worldwide, but there is significant controversy regarding ideal management of end-stage disease. This article reviews the definition of end-stage achalasia and summarizes past and present surgical treatment. RECENT FINDINGS: Myotomy of the lower esophageal sphincter remains the mainstay of treatment of achalasia, even in advanced disease. Esophagectomy may have benefit as a primary treatment modality in end-stage achalasia with sigmoid esophagus, but international guidelines recommend consideration of laparoscopic or endoscopic approaches initially in most patients. Novel peroral esophageal plication techniques may provide alternative treatment options in patients with significant esophageal dilation that fail myotomy or esophagectomy. SUMMARY: End-stage achalasia is characterized by progressive tortuosity and dilation of the esophagus as a failure of primary peristalsis. Up to 20% of patients with achalasia will progress to end-stage disease. In most cases, laparoscopic or endoscopic myotomy is recommended as initial approach to surgical management. | Esophageal Sphincter, Lower |
The change in frequency of individual emissions in the European edible frog (Rana esculenta) when the temperature of the frog is modified, is part of a complex pattern of interaction between spontaneous otoacoustic emissions. At high temperatures (above 24 degrees C) two emissions are always detected (e.g., one near 800 Hz and one near 1200 Hz). The higher-frequency emission is lower in level and has a wider bandwidth than the lower-frequency emission. It is also often asymmetric and sometimes breaks into two emissions when an external suppressor tone is applied. When the temperature is decreased, these emissions are reduced in frequency at a rate of 0.04 octave/degree C. The higher-frequency emission becomes narrower and taller, and the lower-frequency emissions becomes broader and less intense. At approximately 18 degrees C the lowest of these emissions (now between 600 and 700 Hz) disappears and is replaced by a new emission approximately 100 Hz lower in frequency. When the temperature is carefully controlled the two emissions can exist simultaneously. The lowest-frequency emission changes 0.015 degree C/octave suggesting that the mechanisms controlling the frequency of this emission may be different than those determining the frequencies of the other emissions. All but the lowest-frequency emissions are maximal in level and have minimal bandwidth when the frequency is close to 700 Hz, which is interpreted as evidence that these emissions are filtered by a temperature-independent process. | Auditory Threshold |
Folate receptor alpha (FRalpha) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate-appended beta-CyD (Fol-c(1) -beta-CyD) was developed as an FRalpha-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c(1) -beta-CyD (PTX/Fol-c(1) -beta-CyD) in EOC-derived cell lines. We found that PTX/Fol-c(1) -beta-CyD killed not only FRalpha-expressing cells but also FRalpha-negative cells. In the FRalpha-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c(1) -beta-CyD, whereas knockdown of FRalpha did not. By contrast, knockdown of either FRalpha or proton-coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol-c(1) -beta-CyD in FRalpha-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c(1) -beta-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRalpha-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c(1) -beta-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c(1) -beta-CyD targets not only FRalpha but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity." | Proton-Coupled Folate Transporter |
New high-throughput culture-independent molecular tools are allowing the scientific community to characterize and understand the microbial communities underpinning environmental biotechnology processes in unprecedented ways. By creatively leveraging these new data sources, microbial ecology has the potential to transition from a purely descriptive to a predictive framework, in which ecological principles are integrated and exploited to engineer systems that are biologically optimized for the desired goal. But to achieve this goal, ecology, engineering and microbiology curricula need to be changed from the very root to better promote interdisciplinarity. | Food Chain |
Protein adsorption is the first and decisive step to define cell-biomaterial interaction. Guiding the adsorption of desired protein species may represent a viable approach to promote cell activities conducive to tissue regeneration. The aim of the present study was to investigate whether immobilized anti-Fibronectin aptamers could promote the attachment and growth of osteoblastic cells. Polyethyleneglycole diacrylate/thiolated Hyaluronic Acid hydrogels (PEGDA/tHA) were coated with anti-Fibronectin aptamers. Hydrogel loading and Fibronectin bonding were investigated, through spectrophotometry and Bradford assay. Subsequently, human osteoblasts (hOBs) were cultured on hydrogels for 10days in 2D and 3D cultures. Cells were monitored through microscopy and stained for focal adhesions, microfilaments and nuclei using fluorescence microscopy. Samples were also included in paraffin and stained with Hematoxylin-Eosin. Cell number on hydrogels was quantitated over time. Cell migration into the hydrogels was also studied through Calcein AM staining. Aptamers increased the number of adherent hOBs and their cytoplasm appeared more spread and richer in adhesion complexes than on control hydrogels. Viability assays confirmed that significantly more cells were present on hydrogels in the presence of aptamers, already after 48h of culture. When hOBs were encapsulated into hydrogels, cells were more numerous on aptamer-containing PEGDA-tHA. Cells migrated deeper in the gel in the presence of DNA aptamers, appearing on different focus planes. Our data demonstrate that anti-Fibronectin aptamers promote scaffold enrichment for this protein, thus improving cell adhesion and scaffold colonization. STATEMENT OF SIGNIFICANCE: We believe aptamer coating of biomaterials is a useful and viable approach to improve the performance of scaffold materials for both research and possibly clinical purposes, because different medical devices could be envisaged able to capture bioactive mediators from the patients' blood and concentrate them where they are needed, on the biomaterial itself. At the same time, this technology could be used to confer 3D cell culture scaffold with the ability to store proteins, such as Fibronectin, taking it from the medium and capture what is produced by cells. This is an improvement of traditional biomaterials that can be enriched with exogenous molecules but are not able to selectively capture a desired molecule. | Aptamers, Peptide |
It is known that malaria parasites are inhibited by sulfonamides and antifolate compounds, require 4-aminobenzoic acid for growth, and respond only partly to intact folic and folinic acids. Biochemical data obtained during the last decade on the synthesis of nucleic acid precursors and on folate enzymes in malaria support the hypothesis that malaria parasites are similar to microorganisms that synthesize folate cofactors de novo. Sulfa drugs inhibit plasmodial dihydropteroate synthase (EC 2.5.1.15). Pyrimethamine and many other antifolate compounds bind to tetrahydrofolate dehydrogenase (EC 1.5.1.3) of the parasite more tightly than to the host enzyme. However, the metabolic consequences of the depletion of folate cofactors as a result of drug inhibition are not yet known. Other areas to be studied are the origin of the pteridine moiety of folates, the addition of glutamate(s) in folate cofactor biosynthesis, the means by which intact, exogenous folates affect malarial growth, and demonstration of the enzymes and reactions involving N(5)-methyl tetrahydrofolate. | Dihydropteroate Synthase |
ETHNOPHARMACOLOGICAL RELEVANCE: A comprehensive ethnobotanical study was made in Turgutlu. This paper contains folk medicinal plants and ethnopharmacological information of this ethnobotanical study. AIM OF STUDY: The aim of this study is to collect and identify the plants used in therapy by the local people and to reveal information on traditional herbal medicine. MATERIALS AND METHODS: This study was made between 2010 and 2011 and its materials were the plants collected during the field work. The information was obtained through open and semi-structured interviews with the local people. In addition, informant consensus factor (FIC) and use value (UV) were calculated. RESULTS: 76 Folk medicinal plants belonging to 44 families were identified in this study. Among them, 68 species are wild and eight species are cultivated plants. The most common families are Asteraceae (11.8%), Rosaceae (9.2%), Lamiaceae (7.9%), Apiaceae (3.9%) and Malvaceae (3.9%); the most common preparations were infusion (37%) and decoction (18.5%). A total of 177 medicinal uses (remedies) was recorded. Digestive system disorders have the highest FIC (0.73). According to use value (UV) the most important plants were Rosa canina (0.75), Ficus carica subsp. carica (0.74), Tilia platyphyllos (0.71) and Vitex agnus-castus (0.70). CONCLUSION: In the research area the use of traditional folk medicine is still prevalent in the community especially in the villages. | Plants, Medicinal |
Thirty-one patients with biliary enteric fistula who were operated on over a 19-year period (1976-1994) with an incidence of 0.74% in all biliary tract operations were reviewed retrospectively to identify etiologic factors, types of fistulas, signs and symptoms, methods of diagnosis, management and prognosis of the cases. Most common symptoms were abdominal pain, nausea, vomiting and jaundice. Two patients had gallstone ileus. The majority of the patients had severe concomitant medical illnesses. The exact preoperative diagnosis of a biliary enteric fistula was established in only five (16%) patients. In 81% of the cases fistula was secondary to chronic calculous biliary tract disease. Postoperative complications included wound infection in six (19%), biliary fistula in two (6%) and erosive gastritis in one (3%) patient. Two patients died of intra-abdominal sepsis and two of cardiac failure, with an operative mortality of 13%. Early elective cholecystectomy is recommended to avoid complications of chronic calculous cholecystitis such as bilioenteric fistulas and their increased mortality and morbidity. | Biliary Fistula |
Objective: To evaluate how different physical activity (PA) interventions (traditional, exergaming, and teacher/parent education) impacted children's motor skills (object control, locomotor, and gross motor). Design: Systematic review and network meta-analysis. Data sources: PubMed, Medline, Scopus, Web of Science, EMBASE, and PsycINFO. Eligibility criteria: (1) Participants comprised 1708 children 3-12 years; (2) PA or exercise-based interventions were investigated; (3) only studies using a Test of Gross Motor Skills assessment were included; (4) RCT were chosen as the study design to assess the impact of PA interventions on children's motor skills; and (5) culture-based PA studies with English language only were included. Data were analyzed using a Bayesian network meta-analysis. Results: The results were reported as standardized mean differences (SMDs) with associated 95% credible intervals (CrIs). For object control, aerobic intervention (SMD 6.90, 95% Crl 1.39 to 13.50); for locomotor, exergaming intervention (SMD 12.50, 95% Crl 0.28 to 24.50); and for gross motor, aerobic intervention (SMD 7.49, 95% Crl 0.11 to 15.70) were the most effective treatments. Conclusion: Children's FMSs have been improved through different PA interventions. Among them, aerobic interventions seem to be the most effective intervention in enhancing object control skills and overall gross motor skills. | Network Meta-Analysis |
Primary intra-osseous carcinoma (PIOC) is a rare tumor, defined as squamous cell carcinoma that develops in the jaw bones, having no initial connection to adjacent skin or mucosa. It is locally aggressive, with metastases to regional lymph nodes, (28% of cases) and lung (5% of cases) at the time of diagnosis. Its origin may be di novo or from other odontogenic tumors. The maxillary bones have epithelial tissues; therefore this neoplasm is located exclusively on this site, predominantly in the jaw. PIOC diagnostic criteria are strict and include: squamous cell carcinoma histopathology, lack of commitment and sinus mucosa, ruling out the possibility of metastasis from a distant site with a thorough clinical study and complementary methods. The treatment is, whenever possible, oncologic resection, additional radio and / or chemotherapy. Reconstructive surgery with graft and / or prostheses for aesthetic and functional are also required. We report the case of a 72 years old man who consulted for sore jaw three months after molar extraction. Curettage biopsy was performed and then resected mandible with lymphadenectomy. Histopathological examination showed a poorly differentiated squamous cell carcinoma, infiltrating jawbone with morphological findings linking him to residual odontogenic cyst and metastatic lymph nodes in 15 of 48 isolates. Postoperative radiotherapy was performed, he died at 30 months of diagnosis by progressive deterioration. | Jaw Neoplasms |
The metabolism of 5-isopropyl-1-methyl-2-nitro-1H-[2-14C] imidazole in dogs has been investigated after oral administration of 50 mg/kg. Three main metabolites, still containing the nitro group and accounting for about 50% of the total radiocarbon, together with a small amount of the unchanged drug, were isolated from the urine within 48 hr. The structures were determined by mass, infrared, and nuclear magnetic resonance spectroscopy. The biotransformations giving rise to the metabolites isolated involve the isopropyl chain of the molecule, either at the tertiary carbon atom or at one of the two methyl groups, or both. Thus, the metabolic behavior of this 2-nitroimidazole derivative appears to be similar to that previously demonstrated for the class of the isomeric 5-nitroimidazoles. | Ipronidazole |
Erythrocytes from patients with chronic hemolytic variants of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have structural membrane protein abnormalities accompanied by decreased cell membrane deformability which we postulate represent the consequences of oxidant-induced membrane injury. To evaluate the pathophysiologic significance of oxidant-induced membrane injury, we studied the in vitro and in vivo effects of the thiol-oxidizing agent, diamide, on dog erythrocytes. In vitro incubation of dog erythrocytes with 0.4 mM diamide in Tris-buffered saline for 90 min at 37 degrees C resulted in depletion of GSH, formation of membrane polypeptide aggregates (440,000 and > 50,000,000 daltons) and decreased cell micropipette deformability, abnormalities similar to those observed in the erythrocytes of patients with chronic hemolytic variants of G-6-PD deficiency. In addition, diamide-incubated cells had increased viscosity and increased membrane specific gravity, but no change in ATP. Reinjection of 51Cr-labeled, diamide-incubated cells was followed by markedly shortened in vivo survival and splenic sequestration. Further incubation of diamide-incubated cells in 4 mM dithiothreitol reversed the membrane polypeptide aggregates, normalized micropipette deformability, decreased cell viscosity, prolonged in vivi survival, and decreased splenic sequestration. These studied demonstrate that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury. They suggest that oxidant-induced erythrocyte membrane injury plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants. | Diamide |
BACKGROUND: Protoilludene is a valuable sesquiterpene and serves as a precursor for several medicinal compounds and antimicrobial chemicals. It can be synthesized by heterologous expression of protoilludene synthase in Escherichia coli with overexpression of mevalonate (MVA) or methylerythritol-phosphate (MEP) pathway, and farnesyl diphosphate (FPP) synthase. Here, we present E. coli as a cell factory for protoilludene production. RESULTS: Protoilludene was successfully produced in E. coli by overexpression of a hybrid exogenous MVA pathway, endogenous FPP synthase (IspA), and protoilludene synthase (OMP7) of Omphalotus olearius. For improving protoilludene production, the MVA pathway was engineered to increase synthesis of building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) by sequential order permutation of the lower MVA portion (MvL), the alteration of promoters and copy numbers for the upper MVA portion (MvU), and the coordination of both portions, resulting in an efficient entire MVA pathway. To reduce the accumulation of mevalonate observed in the culture broth due to lower efficiency of the MvL than the MvU, the MvL was further engineered by homolog substitution with the corresponding genes from Staphylococcus aureus. Finally, the highest protoilludene production of 1199 mg/L was obtained from recombinant E. coli harboring the optimized hybrid MVA pathway in a test tube culture. CONCLUSIONS: This is the first report of microbial synthesis of protoilludene by using an engineered E. coli strain. The protoilludene production was increased by approx. Thousandfold from an initial titer of 1.14 mg/L. The strategies of both the sequential order permutation and homolog substitution could provide a new perspective of engineering MVA pathway, and be applied to optimization of other metabolic pathways. | Geranyltranstransferase |
Severe infections due to Candida species have become more frequent during the past two decades because of the increasing numbers of immunosuppressed patients being treated in our hospitals. Distinguishing colonization from invasive disease requires knowledge of the pathogenetic mechanisms leading to invasion. To assist the clinician in therapeutic decisions, clinical microbiologists should identify to species Candida organisms isolated from immunosuppressed patients. Quantitative or semiquantitative cultures of urine, burn tissues, intravascular catheter tips, and bronchoalveolar lavage specimens may provide useful information. Immunofluorescent staining of certain specimens can enhance diagnostic yield. The lysis-centrifugation blood culture technique offers some advantages over traditional broth techniques in detecting Candida fungemia. Antibody testing is of limited diagnostic value in highly immunosuppressed patients. Developing simple and reliable tests for detecting antigens or metabolites of Candida spp. in the sera of infected patients has proven difficult. Methods for typing Candida albicans are evolving. Typing should prove useful for studying the epidemiology of candidiasis in hospitalized patients. | Antibodies, Fungal |
Caregivers are often concerned with their child's gait, especially if it deviates from the development of other children. It is common that parents and grandparents have personal memories of brace wear or orthotic use to correct rotational or alignment difference as young children. Although perceived gait differences are a source of angst for families, many are of minimal functional concern and rarely need intervention. [Pediatr Ann. 2022;51(9):e340-e345.]. | Metatarsal Valgus |
Tryptase exacerbates intestinal ischemia-reperfusion injury, however, the direct role of tryptase in intestinal mucosal injury and the underlying mechanism remains largely unknown. Protease-activated receptor 2 (PARâÂÂ2), commonly activated by tryptase, interacts with various adaptor proteins, including betaâÂÂarrestinâÂÂ2. The present study aimed to determine whether tryptase is capable of inducing intestinal mucosal cell injury via PARâÂÂ2 activation and to define the role of betaâÂÂarrestinâÂÂ2 in the process of injury. The IECâÂÂ6 rat intestinal epithelial cell line was challenged by tryptase stimulation. Cell viability, lactate dehydrogenase (LDH) activity and apoptosis were analyzed to determine the severity of cell injury. Injury was also evaluated following treatments with specific PARâÂÂ2 and extracellular signalâÂÂrelated kinases (ERK) inhibitors, and knockdown of betaâÂÂarrestinâÂÂ2. PARâÂÂ2, ERK and betaâÂÂarrestinâÂÂ2 protein expression levels were evaluated. Tryptase treatment (100 and 1,000 ng/ml) resulted in IECâÂÂ6 cell injury, as demonstrated by significant reductions in cell viability, accompanied by concomitant increases in LDH activity and levels of cleaved caspaseâÂÂ3 protein expression. Furthermore, tryptase treatment led to a marked increase in PARâÂÂ2 and phosphorylatedâÂÂERK expression, and exposure to specific PARâÂÂ2 and ERK inhibitors eliminated the changes induced by tryptase. Knockdown of betaâÂÂarrestinâÂÂ2 blocked tryptaseâÂÂmediated cell injury, whereas tryptase exerted no influence on betaâÂÂarrestinâÂÂ2 expression in IECâÂÂ6 cells. These data indicate that tryptase may directly damage IECâÂÂ6 cells via PAR-2 and the downstream activation of ERK, and demonstrate that the signaling pathway requires beta-arrestin-2. | Receptor, PAR-2 |
T-cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8(+) T cells and CD11b(+) CD33(+) myeloid-derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression. To determine the underlying mechanism of TIM3 in immune response during HNSCC progression, we utilized the Tgfbr1/Pten 2cKO HNSCC mouse model with TIM3 overexpression. Treatment with anti-TIM3 monoclonal antibody effectively suppressed tumor growth through restoring effector T-cell function by targeting CD4(+) TIM3(+) cells and CD8(+) TIM3(+) cells and decreasing MDSCs. Our findings demonstrate TIM3 expression in patients with HNSCC and suggest anti-TIM3 immunotherapy as a novel therapeutic approach for effective treatment of HNSCC. | Mucin-3 |
Effectively planning conservation introductions involves assessing the suitability of both donor and recipient populations, including the landscape of disease risk. Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has caused extensive amphibian declines globally and may hamper reintroduction attempts. To determine Bd dynamics in potential source populations for conservation translocations of the threatened California red-legged frog (Rana draytonii) to Yosemite National Park, we conducted Bd sampling in two populations in the foothills of the Sierra Nevada Mountains, California, U.S.A. At one of two sites, we observed lethally high Bd loads in early post-metamorphic life stages and confirmed one chytridiomycosis-induced mortality, the first such report for this species. These results informed source population site selection for subsequent R. draytonii conservation translocations. Conservation efforts aimed at establishing new populations of R. draytonii in a landscape where Bd is ubiquitous can benefit from an improved understanding of risk through disease monitoring and ex situ infection studies. | Batrachochytrium |
The MAPK family is formed by extracellular signal-regulated kinases p38 kinase and stress-activated protein kinases (SAPK/JNK). There are three genes that encode for three JNK proteins. JNK3 is mainly expressed in the central nervous system and has been related to various processes in that tissue. Specifically, JNK3 plays a crucial role in neuronal death in several neurodegenerative diseases. The activation of this kinase has been described in epilepsy, Alzheimer's disease, Parkinson's disease and Huntington's disease. Different studies have shown that the lack of the Jnk3 gene confers neuroprotection. However, the specific mechanism involved in such neuroprotection has not yet been elucidated. Therefore, in the present study, we analyzed the neuroprotection in mice lacking Jnk3 against neuronal death induced by kainic acid. Moreover, we analyzed the activation of different MAPKs. The results revealed that neuronal death was attenuated and different activation/inactivation of p38 and extracellular signal-regulated kinases 1/2 was reported with respect to control. Therefore, the data indicate that the lack of the JNK3 protein modulates other MAPKs and these changes could also have a pivotal role in neuroprotection." | Mitogen-Activated Protein Kinase 10 |
Two fundamental properties of monomeric actin were examined in this study, ie its interaction with DNase-I, and the inhibition of endonuclease activity consecutive to the association of the two molecules. In particular, the topological independence between catalytic site of DNase-I and interface with actin, structural changes in actin monomer and the absence of conformational changes in DNase-I were described. We demonstrated a loss of flexibility of antigenic structures in actin subdomain I (ie epitopes 18-28 and 95-105) as well as modification in the exposure of Cys10 and Cys374 after DNase-I binding. Furthermore, the conformational changes induced by DNase-I into the actin molecule weakened the interaction of CapZ to its binding site located in the C-terminal region of actin monomer. These structural changes were time-dependent. When actin was cleaved in the DNase-I binding loop (sequence 38-52) at position 42 by E coli A2 strain protease, a tight DNase-I binding to split actin and the conformational changes were still observed, whereas the DNase-I inhibition activity was completely abolished. Finally, when we substitute Ca2+ by Mg2+ (ATP-Mg2+ monomeric actin) which induces a tighter conformation of actin and partially restores the inhibitory ability of split actin, long-range conformational effects of DNase-I are prevented and the ternary complex DNase-I-actin-CapZ is obtained. | CapZ Actin Capping Protein |
BACKGROUND: The sequelae of a central venous cutdown usually include venous deformity causing venous stenosis or stricture. However, the cellular mechanisms causing these deformities have not been elucidated. METHODS: Silicone 2.7-Fr catheters were placed via the right external jugular vein of 16 rats with the cutdown method. After fixation with formalin at scheduled intervals (1week, 2weeks, 4weeks, and 8weeks; 4 rats in each group), the vein segment with the catheter in situ was harvested. Histological changes in the vein wall were studied and serially compared with light microscopy; standard hematoxylin-eosin staining, Masson's trichrome staining, van Gieson's elastin stain, and immunohistochemical stain against alpha-actin. RESULTS: Pericatheter sleeve formation, circumferential smooth muscle cell proliferation and infiltration into the pericatheter sleeve by direct contact were noted in all 4 rats of 1-week model; this indicated the initiation of neointimal hyperplasia. The neointimal hyperplasia was located inside the elastin layer. At 2weeks, the SMCs stained faintly but the components of the vein wall were largely replaced by collagen. The proliferation and infiltration of SMCs stabilized at 4weeks and no SMCs were stained around the catheter. At 8weeks, luminal narrowing was noted and the venous wall was composed mainly of collagen. CONCLUSIONS: Circumferential neointimal hyperplasia occurred after surgical cutdown of the external jugular vein in a rat model and was caused by SMC activation, proliferation, and infiltration into the pericatheter sleeve. | Venous Cutdown |
Prox1 plays pivotal roles during embryonic lymphatic development and maintenance of adult lymphatic systems by modulating the expression of various lymphatic endothelial cell (LEC) markers, such as vascular endothelial growth factor receptor 3 (VEGFR3). However, the molecular mechanisms by which Prox1 transactivates its target genes remain largely unknown. Here, we identified Ets-2 as a candidate molecule that regulates the functions of Prox1. Whereas Ets-2 has been implicated in angiogenesis, its roles during lymphangiogenesis have not yet been elucidated. We found that endogenous Ets-2 interacts with Prox1 in LECs. Using an in vivo model of chronic aseptic peritonitis, we found that Ets-2 enhanced inflammatory lymphangiogenesis, whereas a dominant-negative mutant of Ets-1 suppressed it. Ets-2 also enhanced endothelial migration towards VEGF-C through induction of expression of VEGFR3 in collaboration with Prox1. Furthermore, we found that both Prox1 and Ets-2 bind to the VEGFR3 promoter in intact chromatin. These findings suggest that Ets family members function as transcriptional cofactors that enhance Prox1-induced lymphangiogenesis." | Proto-Oncogene Protein c-ets-2 |
We have investigated the sequences and the expression patterns of different members of the Xenopus laevis FoxP gene subfamily during embryogenesis. Low stringency hybridisation of a tadpole cDNA library with an xlFoxP2 fragment led to the isolation of several splice variants of xlFoxP1, xlFoxP2 and xlFoxP4. These variants do not only differ by utilisation of different leader exons, but also by alternative usage of coding exons thereby leading to functional alterations. For xlFoxP1b, we show that insertion of an additional exon disrupts binding to the co-repressor C-terminal binding protein1. Temporal and spatial expression patterns of xlFoxP2 and xlFoxP4 were analysed by RT-PCR and by whole mount in situ hybridisation. xlFoxP2 transcripts are detected from mid-gastrula to late tadpole stages and are found to be localised to pronephros, branchial arches and distinct structures of the hind-, mid- and forebrain, including the ciliary marginal zone of the retina. xlFoxP4 RNA is already present in early cleavage stage embryos and accumulates from midblastula until the end of embryogenesis. Localised expression is found within the anterior neural fold, in the mid- and hindbrain, in the branchial arches as well as in the pancreas. | Xenopus Proteins |
Mibefradil is a T-type and L-type calcium channel blocker (CCB) released in the United States in 1997 for management of hypertension and chronic stable angina. Postmarketing surveillance revealed a potential serious interaction between mibefradil and beta-blockers, digoxin, verapamil, and diltiazem, especially in elderly patients. The manufacturer voluntarily withdrew mibefradil on June 8, 1998. We describe 4 cases of cardiogenic shock in patients taking mibefradil and beta-blockers who began taking dihydropyridine CCBs. One case resulted in death; the other 3 survived episodes of cardiogenic shock with intensive support of heart rate and blood pressure. Physicians who are preparing to switch patients' medications from mibefradil to other antihypertensive agents should be aware of these potentially life-threatening drug-drug interactions. | Mibefradil |
The author described current system insuring victims of occupational accidents and patients with occupational diseases, with participation of all off-budget funds and health service budget, with consideration of work conditions and occupational morbidity in Rostov region. Analysis covered experience and efficiency of Obligatory Medical Insurance System (unique in this country, which participated in insuring occupational victims) in insuring victims of occupational accidents in the region. | Insurance, Accident |
Helminth parasites were collected from 14 raccoon dogs (Nyctereutes procyonoides viverrinus) and 2 Japanese weasels (Mustela itatsi sho) on Yakushima Island, Kagoshima Prefecture (Kyushu), Japan. In addition to trematodes and nematodes reported separately, everted cystacanths of 3 bird acanthocephalans (Mediorhynchus robustus in 5 animals, Porrorchis leibyi in 2 animals, and Sphaerirostris lanceoides in 1 animal) were collected from the raccoon dogs introduced recently on this World Natural Heritage Area. A cystacanth of P. leibyi was collected also from a weasel indigenous to this island that were killed by traffic accidents. Recovery of everted cystacanths of M. robustus from the intestine of raccoon dogs was remarkably frequent (36%), suggesting that this acanthocephalan should be highly prevalent in passerine hosts on Yakushima Island, and the animals might vigorously take insect hosts or paratenic hosts. Furthermore, the present report is the second on M. robustus after its first record in Japan (Aichi Prefecture, Honshu) as M. garruli from a Eurasian jay (Garrulus glandarius japonicus) by Yamaguti in 1939. Porrorchis leibyi has never been recorded in Japan. | Raccoon Dogs |
The anti-oestrogens, clomiphene citrate, tamoxifen and cyclofenil are commonly used in the treatment of female infertility. Their role in the management of anovulation is well established but there is continuing controversy about their relevance to other areas of management. We have studied the effects of each of these drugs on cervical mucus and sperm-cervical mucus interaction among 23 patients with unexplained infertility. Each patient received all three drugs in an alternative month treatment regime and in addition acted as her own control. The starting point in each patient was randomized. Luteinizing hormone (LH) and oestradiol were measured daily from day 10, and follicle scanning was also undertaken. Cervical mucus quality and sperm-cervical mucus interaction were studied on the day of onset of the LH surge. The use of clomiphene and tamoxifen resulted in a significant reduction in cervical mucus score and sperm-cervical mucus interaction as judged by the distance travelled by the vanguard spermatozoa. Cyclofenil had no effect on these parameters. | Cyclofenil |
Navigation technology and multimodality image fusion represent an important development in interventional radiology. It is a rapidly developing field with great promise for improving, optimizing, and refining our workflow, especially for performing complex and difficult biopsies and ablations. It can potentially reduce procedure time, radiation dose, and complications while enhancing procedure accuracy and effectiveness. Additionally, such techniques are likely to greatly benefit less experienced operators and shorten the long learning curve to mastery of conventional procedures. Here, we describe different aspects of currently available image-guided fusion devices including the types of clinically available technological platforms (electromagnetic vs optical fusion) used to fuse prior and real-time images; pretest planning software; and advantages and limitations reported in preclinical and emerging clinical studies. Much refinement and development still needs to be performed for both the tracking systems and preablation software predictability, but this is anticipated as substantial research within the framework of multiple academic industrial partnerships is ongoing. | Surgery, Computer-Assisted |
This study entailed conducting extensive qualitative interviews of mothers who had been invited to have their infants participate in the Kilimanjaro Intermittent Preventive Treatment of Malaria in Infants (Kili IPTi) trial, designed to assess the efficacy of intermittent preventive malaria chemoprophylaxis for infants. Our study sought to explore whether there was a relationship between the mothers' understanding of the research and the decision to enroll their infants or to decline. Such empirical data is necessary to address widely voiced concerns that limited understanding of research or exploitive inducement may undermine informed consent among clinical trial recruits in developing countries. The most striking result of the study was that, in general, those who declined to have their children participate in the trial had a better understanding of the trial than those who agreed to have their children participate. Decliners were more likely to understand the experimental nature of the trial and were less likely to confuse research with treatment, the conceptual error often labeled therapeutic misconception." Notably, in the context of the Kili IPTi trial, perception of clinical benefit may have been an accurate perception rather than therapeutic misconception because ancillary clinical benefits were provided to research participants. Neither participants nor decliners cited "altruistic" reasons for their decisions, despite presumptions among some scholars that such reasons are ethically the most appropriate motivations for participation in clinical research." | Therapeutic Misconception |
A number of bacterial and viral genes take part in the decision between lysis and lysogenization in temperate bacteriophages. In the lambda case, at least five viral genes (cI, cro, cII, N and cIII) and several bacterial genes are involved. Several attempts have been made to model this complex regulatory network. Our approach is based on a logical method described in the first paper of the series which formalizes the interactions between the elements of a regulatory network in terms of discrete variables, functions and parameters. In this paper two models are described and discussed, the first (two-variable model) focused on cI and cro interactions, the second (four-variable model) considering, in addition, genes cII and N. The treatment presented emphasizes the roles of positive and negative feedback loops and their interactions in the development of the phage. The role of the loops between cI and cro, and of cI on itself (which both have to be positive loops) was discovered earlier; this group's contribution to this aspect mainly deals with the possibility of treating these loops as parts of a more extended network. In contrast, the role of the negative loop of cro on itself had apparently remained unexplained. We realized that this loop buffers the expression of genes cro itself. cII, O and P against the inflation due to the rapid replication of the phage. More generally, negative auto-control of a gene appears an efficient way to render its expression insensitive (or less sensitive) to gene dosage, whereas a simple negative control would not provide this result. | Genes, Microbial |
Narcolepsy is a chronic disorder of EDS. All patients experience EDS. Other symptoms include cataplexy, sleep paralysis, hypnagogic hallucinations, and disrupted nocturnal sleep. Treatment, usually with stimulants and low-doses of antidepressant medications, can dramatically improve the patient's quality of life. Although only advanced practice nurses may be actively involved in the diagnosis and treatment of this disorder, all nurses can encourage their patients who complain of EDS to consult a specialist in sleep disorders medicine, provide emotional support after diagnosis, and educate patients and their families about narcolepsy and its treatment." | Disorders of Excessive Somnolence |
In the history of viral research, one of the important biological features of bacteriophage Mu is the ability to expand its host range. For extending the host range, the Mu phage encodes two alternate tail fibre genes. Classical amber mutation experiments and genome sequence analysis of Mu phage suggested that gene products (gp) of geneS (gpS = gp49) and gene S' (gpS' = gp52) are tail fibres and that gene products of geneU (gpU = gp50) and geneU' (gpU' = gp51) work for tail fibre assembly or tail fibre chaperones. Depending on the gene orientation, a pair of genes 49-50 or 52-51 is expressed for producing different tail fibres that enable Mu phage to recognize different host cell surface. Since several fibrous proteins including some phage tail fibres employ their specific chaperone to facilitate folding and prevent aggregation, we expected that gp50 or gp51 would be a specific chaperone for gp49 and gp52, respectively. However, heterologous overexpression results for gp49 or gp52 (tail fibre subunit) together with gp51 and gp50, respectively, were also effective in producing soluble Mu tail fibres. Moreover, we successfully purified non-native gp49-gp51 and gp52-gp50 complexes. These facts showed that gp50 and gp51 were fungible and functional for both gp49 and gp52 each other. | Bacteriophage mu |
Sixteen 50 day gestational ewes were fed lasalocid at the rate of 30 g t-1 and were orally inoculated with 100 infective Toxoplasma gondii oocysts 5 days after beginning feeding of lasalocid. Seventeen control ewes were similarly inoculated with T. gondii and were not fed lasalocid. The rate of abortion and neonatal mortality in both treated and untreated ewes was similar, indicating that feeding lasalocid was not effective in preventing T. gondii abortion in sheep. | Lasalocid |
The aim of this study was to investigate the segregation patterns of molar incisor hypomineralization (MIH) in families, given the evidence that its etiology is influenced by genetics. Clinically, MIH may be detected in parents and/or siblings of MIH-affected children. Our study included children with at least one first permanent molar affected by MIH (proband) and their first-degree relatives (parents and siblings). The participants were examined clinically to detect MIH, according to the European Academy of Paediatric Dentistry criteria (2003). A total of 101 nuclear families (391 individuals) were studied. Proband diagnosis was followed by MIH classification of the subject, his parents and siblings, as affected, unaffected, or unknown. Segregation analysis was performed using the multivariate logistic regression model of the Statistical Analysis for Genetic Epidemiology package, and segregation models (general transmission, environmental, major gene, dominant, codominant and recessive models). The Akaike information criterion (AIC) was used to evaluate the most parsimonious model. In all, 130 affected individuals, 165 unaffected individuals, and 96 unknown individuals were studied. Severe MIH was found in 50.7% of the cases. A segregation analysis performed for MIH revealed the following different models: environmental and dominance (p = 0.05), major gene (p = 0.04), codominant (p = 0.15) and recessive models (p = 0.03). According to the AIC values, the codominant model was the most parsimonious (AIC = 308.36). Our results suggest that the codominant model could be the most likely for inheriting MIH. This result strengthens the evidence that genetic factors, such as multifactorial complex defect, influence MIH." | Developmental Defects of Enamel |
Minimum inhibitory concentrations, minimum bactericidal concentrations, and killing curve assays were measured after Legionella pneumophila was grown in human lung fibroblasts. Results of susceptibility testing of organisms grown intracellularly are compared with results for organisms grown by standard tube dilution methods. | Cefamandole |
The aim of this work was to follow Prunus necrotic ringspot virus (PNRSV) infection in apricot reproductive tissues and transmission of the virus to the next generation. For this, an analysis of viral distribution in apricot reproductive organs was carried out at different developmental stages. PNRSV was detected in reproductive tissues during gametogenesis. The virus was always present in the nucellus and, in some cases, in the embryo sac. Studies within infected seeds at the embryo globular stage revealed that PNRSV infects all parts of the seed, including embryo, endosperm and testa. In the torpedo and bent cotyledon developmental stages, high concentrations of the virus were detected in the testa and endosperm. At seed maturity, PNRSV accumulated slightly more in the embryo than in the cotyledons. In situ hybridization showed the presence of PNRSV RNA in embryos obtained following hand-pollination of virus-free pistils with infected pollen. Interestingly, tissue-printing from fruits obtained from these pistils showed viral RNA in the periphery of the fruits, whereas crosses between infected pistils and infected pollen resulted in a total invasion of the fruits. Taken together, these results shed light on the vertical transmission of PNRSV from gametes to seedlings. | Ilarvirus |
Each year, one out of five women suffers the loss of a pregnancy. Such losses are more than statistics: to many mothers, they represent the death of a longed-for child. While increasing attention has been directed toward meeting the needs of these women, the services provided are often fragmented. The use of a comprehensive checklist for providing care facilitates continuity and consistency of care and offers structure and direction for the caregiver. In this manner, vital aspects of care are not omitted as the bereaved woman moves through the health-care delivery system. | Obstetric Nursing |
OBJECTIVE: Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas. STUDY DESIGN: Application of machine learning algorithms, including classification and regression trees and random forest models to observational data. SETTING: Single-tertiary referral center. PARTICIPANTS: Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021. INTERVENTIONS: Middle cranial fossa approach. MAIN OUTCOME AND MEASURES: Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model. RESULTS: Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction. CONCLUSION: Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data. | Cranial Fossa, Middle |
Comparing divergence in quantitative traits and neutral molecular markers, such as QST-FST comparisons, provides a means to distinguish between natural selection and genetic drift as causes of population differentiation in complex polygenic traits. Onithochiton neglectus (Rochebrune, 1881) is a morphologically variable chiton endemic to New Zealand, with populations distributed over a broad latitudinal environmental gradient. In this species, the morphological variants cluster into 2 geographically separated shell shape groups, and the phenotypic variation in shell shape has been hypothesized to be adaptive. Here, we assessed this hypothesis by comparing neutral genomic differentiation between populations (FST) with an index of phenotypic differentiation (PST). We used 7,562 putatively neutral single-nucleotide polymorphisms (SNPs) across 15 populations and 3 clades of O. neglectus throughout New Zealand to infer FST. PST was calculated from 18 shell shape traits and gave highly variable estimates across populations, clades, and shape groups. By systematically comparing PST with FST, we identified evidence of local adaptation in a number of the O. neglectus shell shape traits. This supports the hypothesis that shell shape could be an adaptive trait, potentially correlated with the ability to live and raft in kelp holdfasts. | Genetic Drift |
Athletic pubalgia (sportsman's hernia) is often repaired by surgery. The presence of pubic bone marrow edema (BME) in magnetic resonance imaging (MRI) may effect on the outcome of surgery. Surgical treatment of 30 patients with athletic pubalgia was performed by placement of totally extraperitoneal endoscopic mesh behind the painful groin area. The presence of pre-operative BME was graded from 0 to 3 using MRI and correlated to post-operative pain scores and recovery to sports activity 2 years after operation. The operated athletes participated in our previous prospective randomized study. The athletes with (n = 21) or without (n = 9) pubic BME had similar patients' characteristics and pain scores before surgery. Periostic and intraosseous edema at symphysis pubis was related to increase of post-operative pain scores only at 3 months after surgery (P = 0.03) but not to long-term recovery. Two years after surgery, three athletes in the BME group and three in the normal MRI group needed occasionally pain medication for chronic groin pain, and 87% were playing at the same level as before surgery. This study indicates that the presence of pubic BME had no remarkable long-term effect on recovery from endoscopic surgical treatment of athletic pubalgia. | Pubic Bone |
We report on two children with paratyphoid fever and rare cardiac complications (endocarditis and pericarditis) during an outbreak of Salmonella paratyphi A infection in Bangkok, Thailand, in 1996. Both of the patients had underlying congenital heart disease. Two cases in the literatures of endocarditis and five cases of pericarditis caused by Salmonella paratyphi were reviewed. These rare cardiac complications should be considered among persons who reside in an endemic area of enteric fever or during disease outbreaks, especially in children with underlying heart diseases. | Paratyphoid Fever |
BACKGROUND: Heterotopic pregnancy refers to the simultaneous coexistence of an intrauterine and extrauterine pregnancy. In natural conception it is very rare, with a rising incidence in patients undergoing assisted reproduction technologies. It presents a serious diagnostic problem which is often misdiagnosed. Currently, there are no standard protocols for the treatment and diagnosis of heterotopic pregnancy. METHODS: Two rare cases of spontaneous heterotopic pregnancy are presented. RESULT: The first patient had a complete abortion upon which an extrauterine pregnancy was detected. The second patient, after an extrauterine pregnancy removal, progressed with an intrauterine pregnancy until full term and it ended with the delivery of a healthy infant. CONCLUSION: Two demonstrated cases underscore that whenever abnormal adnexal findings are presented and the beta-hCG blood test is positive, the possibility of a heterotopic pregnancy should be suspected. | Pregnancy, Heterotopic |
Despite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT-protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours." | Protein-Arginine N-Methyltransferases |
Menaquinone-7 (MK-7) is the most potent subtype of vitamin K with extraordinarily high half-life in the circulatory system. Therefore, MK-7 plays a critical role in promoting human wellbeing today. Studies on MK-7 every year show more and more magnificent benefits of it in preventing cardiovascular diseases and osteoporosis to battling cancer cells, Alzheimer's and Parkinson's diseases. Thus, it needs to be supplemented to daily diet for accumulative and long-term benefits. Chemical synthesis of MK-7 produces a significant cis-isomer form of it, which has no biological activity. Fortunately, due to its key role in electron transfer in bacteria, trans-MK-7 is biosynthesized by especially Gram-positive strains mainly Bacillus genus. Concordantly, MK-7 could be produced via solid or liquid state fermentation strategies. In either regime, when static fermentation is applied in the absence of agitation and aeration, operational issues arise such as heat and mass transfer inefficiencies. Thus, scaling up the process becomes a challenge. On the other hand, studies have indicated that biofilm and pellicle formation that occur in static fermentations are key characteristics for extracellular MK-7 secretion. Therefore, this review covers the most recent discoveries of the therapeutic properties of MK-7 and optimization attempts at increasing its biosynthesis in different media compositions and effective growth parameters as well as the cutting-edge use of biofilm reactors where B. subtilis cells have the infrastructures to form mature biofilm formations on plastic composite supports. Biofilm reactors therefore can provide robust extracellular MK-7 secretion while simultaneously enduring high agitation and aeration rates, which then address the scale-up and operational issues associated with static fermentation strategies. | Vitamin K 2 |
Since its birth in the late 1980s, the field of microfluidics has continued to mature, with a growing number of companies pursuing diagnostic applications. In 2009 the worldwide in vitro diagnostics market was estimated at >$40 billion USD, and microfluidic diagnostics are poised to reap a significant part of this market across a range of areas including laboratory diagnostics, point-of-care diagnostics, cancer diagnostics, and others. The potential economic advantages of microfluidics are numerous and compelling: lower reagent and/or sample volumes, lower equipment costs, improved portability, increased automation, and increased measurement speed. All of these factors may help put more information in the hands of doctors and patients sooner, enabling earlier disease detection and more tailored, effective treatments. This chapter reviews the microfluidic diagnostics commercial landscape and discusses potential commercialization challenges and opportunities." | Diagnostic Techniques and Procedures |
In BriefThere has been a significant shift in treatment paradigms for both primary and metastatic spine tumors over the last several decades. This article highlights some of the more important treatment advances that practitioners should be made aware of. It is important to not only incorporate these changes into individual practice but also appreciate the treatment trends that herald a significantly different future for spine tumor treatment. | Spinal Neoplasms |
Hybridization of nanomaterials (NMs) with natural polymers is one of the best techniques to promote their exciting properties. In this way, the main objective of this work was to investigate the efficiency of decoration of the graphene oxide (GO) nano-sheets with tragacanth gum (TG) polysaccharide. To aim this, different approaches were used (with and without ultrasonic treatment) and various tests (XRD, FTIR, Raman, UV-Vis, DLS, Zeta potential, contact angle, AFM, FE-SEM, TEM, and MTT assay) were conducted. Test results indicated that the nano-hybrids were successfully synthesized. Furthermore, our findings represented that, the TG hybridized GO (TG-GO) appreciably enhanced the biocompatibility of GO. Moreover, it was demonstrated that the ultrasonic treatment of TG solution put a remarkable impact on the microstructure, wettability, and also surface charge characteristic of fabricated nano-hybrids and consequently improved the biocompatibility against L929-fibroblast cells. | Tragacanth |
The aim of this work was to test the potential use of plant-derived extracts and compounds to control Campylobacter jejuni in broiler chickens. Over a 7-wk feeding period, birds were fed a commercial diet with or without plant extracts (Acacia decurrens, Eremophila glabra), essential oil [lemon myrtle oil (LMO)], plant secondary compounds [terpinene-4-ol and alpha-tops (including alpha-terpineol, cineole, and terpinene-4-ol)], and the antibiotic virginiamycin. Traditional culture and real-time quantitative PCR techniques were used to enumerate the numbers of C. jejuni in chicken fecal and cecal samples. In addition, BW and feed intake were recorded weekly for the calculation of BW gain and feed conversion ratio. The mean log10 counts of C. jejuni were similar (P > 0.05) across treatments. However, significantly lower levels of fecal Campylobacter counts (P < 0.05) were recorded at d 41 for the alpha-tops treatment by culture methods. No differences (P > 0.05) in BW gain were obtained for dietary supplementation, except for the E. glabra extract, which had a negative impact (P < 0.001) on BW, resulting in sporadic death. Results from this study suggest that supplemental natural compounds used in the current study did not reduce the shedding of C. jejuni to desired levels. | Eremophila Plant |
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