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OBJECTIVES: The objective of this study was to confirm the validity of a short form of gross motor function measure for Fukuyama congenital muscular dystrophy (GMFM for FCMD). METHODS: This study is a case series and was conducted at the Tokyo Women's Medical University. Fifteen patients with FCMD were assessed using both the GMFM for FCMD with 68 items, which was created as a motor function measure for patients with FCMD on the basis of Rasch analysis, and the original GMFM with 88 items. The correlation between the GMFM for FCMD and the Ueda classification was assessed. Time required for each assessment was also evaluated. RESULTS: We found significant correlation between the GMFM for FCMD and the Ueda classification (r = 0.935); furthermore, the mean assessment time tended to decrease when using the GMFM for FCMD. CONCLUSIONS: GMFM for FCMD may be an appropriate motor function scale for patients with FCMD and might help decrease the assessment time. | Cobblestone Lissencephaly |
Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed." | Heart Diseases |
In birds, seasonal reproduction is regulated by day length, with long days in the spring activating the hypothalamic-pituitary-gonadal axis and reproductive behaviors. The photoreceptors mediating this process remain unknown, but recently, the premammillary nucleus (PMM) of the hypothalamus has been implicated as the site of photoperiodic signaling in turkeys. We performed electrolytic lesions of the PMM to elucidate its role in the photoactivation and maintenance of egg production in female turkeys. Our results show that ablation of the PMM does not alter the normal lay cycle. No differences were found between lesioned birds and sham controls in the latency to lay following photostimulation, nor in subsequent egg production over a period of 29 weeks. No differences in the incidence of gonadal regression were found, indicating that the PMM is not essential for the termination of breeding. We conclude that any role of the PMM in photoperiodic regulation, if it exists, is redundant with other components of the system. | Turkeys |
Six cases of acute puerperal inversion of the uterus are reported. In four of these, tocolytic agents were used to facilitate replacement of the inverted uterus; and in five, Prostin-15M was given after replacement. The use of tocolytics may obviate the need for general anesthesia for uterine replacement in some patients with uterine inversion. Prostin-15M serves to minimize bleeding and to maintain uterine position after replacement. | Carboprost |
Exposure to maternal mental health problems during pregnancy and the first year of life has been associated with the development of ADHD. One pathway through which maternal mental health may influence children's outcomes is via its effects on parenting. This study aimed to investigate the mediating role of parenting behavior in the pathway between maternal postnatal distress and later symptoms of ADHD in the child. Biological mothers living with their children participating in the Longitudinal Study of Australian Children with data available from waves 1 (child age 3-12 months) and 5 (child age 8-9 years) were included in the current study (n = 3456). Postnatal distress was assessed by parent report at wave 1. Parenting warmth, hostility and consistency were assessed by parent report at wave 5. ADHD status at wave 5 was ascertained by parent report of the child having a diagnosis of ADHD/ADD or by elevated ADHD symptoms by both parent and teacher report. There was evidence of an indirect pathway from maternal postnatal distress to child ADHD at age 8-9 years via parenting hostility, but not through parenting warmth or consistency, even after accounting for concurrent maternal mental health. Our findings highlight the importance of early identification and intervention for maternal postnatal distress, as treatment may prevent mothers from developing hostile parenting practices and also disrupt the pathway to ADHD in their offspring. | Maternal Health |
Pantalar arthrodesis creates a sensate prosthesis consisting of the ankle and rearfoot complex. Its primary purpose is to create a plantigrade stable rearfoot and ankle. Special attention must be placed on the technical aspects of this procedure, particularly the positioning of the ankle and subtalar complex. | Foot Joints |
A toxicologic and dermatologic review of l-borneol when used as a fragrance ingredient is presented. | Bicyclic Monoterpenes |
Plummer-Vinson Syndrome is a condition where iron deficiency is associated with difficulty swallowing due to the presence of an esophageal web. Deficiency of iron-dependent oxidative enzymes causes gradual degradation of the pharyngeal muscles which lead to mucosal atrophy and formation of webs. Although it is a very rare condition, an increased risk of esophageal squamous cell carcinoma makes its identification very important. Dilation of the esophageal web using a Savary dilator is a more effective and safer approach compared to conventional balloon dilation. | Plummer-Vinson Syndrome |
When it comes to microtubules, kinetochores leave nothing to chance. Recent studies have provided insight into an amazingly choreographed dance between the proteins in the kinetochore and their substrate and power source--the microtubule. | Kinetochores |
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor alpha-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate. In addition, FGF23 suppresses proximal tubular expression of 1alpha-hydroxylase, the key enzyme responsible for vitamin D hormone production. In distal renal tubules, FGF23 signaling activates with-no-lysine kinase 4, leading to increased renal tubular reabsorption of calcium and sodium. Therefore, FGF23 is not only a phosphaturic but also a calcium- and sodium-conserving hormone, a finding that may have important implications for the pathophysiology of chronic kidney disease. Besides these endocrine, Klotho-dependent functions of FGF23, FGF23 is also an auto-/paracrine suppressor of tissue-nonspecific alkaline phosphatase transcription via Klotho-independent FGFR3 signaling, leading to local inhibition of mineralization through accumulation of pyrophosphate. In addition, FGF23 may target the heart via an FGFR4-mediated Klotho-independent signaling cascade. Taken together, there is emerging evidence that FGF23 is a pleiotropic hormone, linking bone with several other organ systems." | Sodium-Phosphate Cotransporter Proteins, Type IIc |
Hsp90 is an abundant chaperone protein that assists the folding of specific proteins, such as steroid receptors, protein kinases, and so on, for their proper function. TP and RT domains of HBV polymerase have been also shown to be associated with Hsp90. Therefore, the identification of the binding sites within Hsp90, responsible for forming Hsp90/HBV Pol complex, is important for the understanding of HBV replication. In this study, cotransfection and immunoprecipitation experiments were performed to localize the binding sites of HBV pol to Hsp90. Our data show that HBV pol interact independently with both N-terminal and C-terminal fragments of Hsp90. Further analysis showed that N-terminal fragment (1-302) of Hsp90 interacts with both TP and RT domains of HBV pol, whereas C-terminal fragment (438-723) interacts with only RT domain. In conclusion, we showed that HBV pol independently interacts with N-terminal and C-terminal fragments, but not the middle fragment (327-438) of Hsp90. | Gene Products, pol |
Protection against infectious diseases can be obtained with vaccines generating immunogenic response through a combination of humoral and cellular immunity. In this study haematological and serum protein electrophoretic profiles of horses vaccinated against herpesvirus 1 (EHV-1) and 4 (EHV-4) were evaluated. Blood samples were collected from 16 horses before (T0), after 24h, 48h, 72h, 1st week, 2nd week and 3rd week (T1I, T2I, T3I, T7I, T14I and T21I) from the first EHV vaccine-dose administration as well as before (TPRE(II)), and after 24h, 48h, 72h, 1st week, 2nd week, 3rd week and 4th week (T1II, T2II, T3II, T7II, T14II, T21II and T28II) from the EHV vaccine-booster. Total leukocyte values increased at T1I, T1II, T3II and T28II compared to T0 (P < .01). Higher lymphocytes and lower neutrophils values were found after first vaccine-dose and vaccine-booster administration compared to the T0 (P < .01). Monocytes showed higher values at T14II than T0 (P < .01). Higher serum values of total proteins, alpha1-, alpha-2-, beta1-, beta2- and gamma-globulins were found in horses after first vaccine-dose and vaccine-booster administration (P < .01). Gathered results suggest that horses vaccinated against EHV1 and EHV-4 exhibited a dynamic change of WBC, lymphocytes, neutrophils and monocytes. Moreover, the analysis of serum electrophoresis pattern suggested that EHV vaccination induced the development of inflammation and antibody response in vaccinated horses as highlighted by the increase of alpha-, beta- and gamma-globulin fractions. These changes probably reflect the systemic immunological adaptation of animals to EHV vaccine. | Varicellovirus |
Nuclear factor YB (NF-YB) are plant-specific transcription factors that play a critical regulatory role in plant growth and development as well as in plant resistance against various stresses. In this study, a total of 49 NF-YB genes were identified from the genomes of Medicago truncatula and Medicago sativa. Multiple sequence alignment analysis showed that all of these NF-YB members contain DNA binding domain, NF-YA interaction domain and NF-YC interaction domain. Phylogenetic analysis suggested that these NF-YB proteins could be classified into five distinct clusters. We also analyzed the exon-intron organizations and conserved motifs of these NF-YB genes and their deduced proteins. We also found many stress-related cis-acting elements in their promoter region. In addition, analyses on genechip for M. truncatula and transcriptome data for M. sativa indicated that these NF-YB genes exhibited a distinct expression pattern in various tissues; many of these could be induced by drought and/or salt treatments. In particular, RT-qPCR analysis revealed that the expression levels of gene pairs MsNF-YB27/MtNF-YB15 and MsNF-YB28/MtNF-YB16 were significantly up-regulated under NaCl and mannitol treatments, indicating that they are most likely involved in salt and drought stress response. Taken together, our study on NF-YB family genes in Medicago is valuable for their functional characterization, as well as for the application of NF-YB genes in genetic breeding for high-yield and high-resistance alfalfa. | Medicago |
OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation. METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Biblioteca Virtual em Saude (BVS), Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute. RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate. CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject. | Smoking Cessation |
A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy." | Paraneoplastic Syndromes, Ocular |
In meiosis, a supramolecular protein structure, the synaptonemal complex (SC), assembles between homologous chromosomes to facilitate their recombination. Mammalian SC formation is thought to involve hierarchical zipper-like assembly of an SYCP1 protein lattice that recruits stabilizing central element (CE) proteins as it extends. Here we combine biochemical approaches with separation-of-function mutagenesis in mice to show that, rather than stabilizing the SYCP1 lattice, the CE protein SYCE3 actively remodels this structure during synapsis. We find that SYCP1 tetramers undergo conformational change into 2:1 heterotrimers on SYCE3 binding, removing their assembly interfaces and disrupting the SYCP1 lattice. SYCE3 then establishes a new lattice by its self-assembly mimicking the role of the disrupted interface in tethering together SYCP1 dimers. SYCE3 also interacts with CE complexes SYCE1-SIX6OS1 and SYCE2-TEX12, providing a mechanism for their recruitment. Thus, SYCE3 remodels the SYCP1 lattice into a CE-binding integrated SYCP1-SYCE3 lattice to achieve long-range synapsis by a mature SC. | Chromosome Pairing |
The reliable assessment of children's dental anxiety can have many benefits for the dental team, service providers and dental public health practitioners. This study aimed to identify and evaluate self-report measures, which are available to assess children's dental anxiety. Systematic searches of the literature between 1998 and 2011 were conducted to identify relevant studies. The properties of each measure (reliability and validity) were assessed, and measures were evaluated against a theoretical framework of dental anxiety. Executing the search strategy generated 498 articles and of these 60 studies met all of the inclusion criteria. Seven 'trait' and two 'state' measures of dental anxiety had been employed to assess children's dental anxiety over the past decade. Reliability and validity estimates for the most widely used measures were good; however, many questionnaires had a limited focus in the aspects of anxiety they assessed. The paper summarizes the measures of children's dental anxiety which may be most useful for a number of different purposes and populations. | Dental Anxiety |
In this study a palatal index (P.I.) was established for 121 randomly selected normal Australian children. Mean P.I. indices were compared in the primary, mixed and permanent dentitions. A subjective assessment of relative palatal height was also carried out by two independent examiners and an attempt was made to examine the reliability of the subjective assessment, and its validity compared with the P.I. Measurements were recorded on stone casts at Level 1 (distal to the primary second molars/second premolars) and Level 2 (between primary first and second molar/first and second premolars). At Level 1 the mean P.I. increased significantly from the primary to the mixed and permanent dentitions. At level 2 the P.I. remained stable. Findings indicate that subjective assessment of relative palatal height was fairly reliable: there was approximately 80% interexaminer and intraexaminer agreements. Subjective assessment of palatal height correlated reasonably well with the P.I. | Dentition, Mixed |
The paradigm producing recognition failure of recallable words was investigated in a series of three experiments. Results indicate that retrieval asymmetry: (a) exists in the recognition failure paradigm directly following list study, (b) increases significantly following a free-association task aimed at generation of the target words from the study list, and (c) can be used as a reasonably good predictor of the magnitude of recognition failure. Retrieval asymmetry and recognition failure are reliably related even when adjusted for the level of recognition probability, which has previously been shown by Tulving and Wiseman to be a good predictor of recognition failure. | Free Association |
Pneumatoceles are rare complications of pulmonary tuberculosis in children. We present 2 cases in infants of disseminated tuberculosis complicated by pneumatoceles with different evolution. This complication should be considered if worsening of respiratory symptoms occurs after initiating anti-tuberculous treatment. Treatment of pneumatoceles is usually conservative and surgical treatment should be used in patients with giant cysts which cause respiratory distress. | Tuberculosis, Miliary |
Osteoporosis and associated low-impact fractures are common. There is associated morbidity and mortality with low-impact fractures. It is critical to identify which patients would benefit from therapy. General treatment considerations are reviewed. Currently available treatment options are discussed. Certain patient populations pose challenges in the treatment of osteoporosis. An in-depth review of clinically challenging scenarios is presented: Treatment of patients with severe osteoporosis, Treatment of Premenopausal women with low bone density, Treatment of osteoporosis in patients with kidney disease, Treatment of Osteoporosis in patients on glucocorticoid therapy, Treatment of osteoporosis in patients with a fracture. | Osteoporosis |
BACKGROUND: The global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pain thresholds (PPTs), facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM). As traditional analgesics (acetaminophen and non-steroidal anti-inflammatory drugs) are not recommended for long-term use in OA, more fundamental knowledge related to other possible management regimes are needed. Duloxetine is a serotonin-noradrenalin reuptake inhibitor, and analgesic effects are documented in patients with OA although the underlying fundamental mechanisms remain unclear. The descending pain inhibitory control system is believed to be dependent on serotonin and noradrenalin. We hypothesized that the analgesic effect of duloxetine could act through these pathways and consequently indirectly reduce pain and sensitization. The aim of this mechanistic study is to investigate if PPTs, TSP, CPM, and clinical pain parameters are modulated by duloxetine. METHODS: This proof of concept study is a randomized, placebo-controlled, double-blinded, crossover trial, which compares PPTs, TSP, and CPM before and after 18 weeks of duloxetine and placebo in forty patients with knee OA. The intervention periods include a titration period (2 weeks), treatment period (60 mg daily for 14 weeks), and a discontinuation period (2 weeks). Intervention periods are separated by 2 weeks. DISCUSSION: Duloxetine is recommended for the treatment of chronic pain, but the underlying mechanisms of the analgesic effects are currently unknown. This study will investigate if duloxetine can modify central pain mechanisms and thereby provide insights into the underlying mechanisms of the analgesic effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT04224584 . Registered on January 6, 2020. EudraCT 2019-003437-42 . Registered on October 22, 2019. The North Denmark Region Committee on Health Research Ethics N-20190055. Registered on October 31, 2019. | Duloxetine Hydrochloride |
Mycotoxin is a class of poisonous secondary metabolites generated by filamentous fungi and found in agricultural commodities worldwide. Therefore, the current study aimed to investigate how aflatoxin B1 affected hepatic cellular architecture and Matrix metalloproteinase expression in particular (MMP1 and MMP7) in the livers of experimental mice (IHC). A total of sixteen mice (four groups) were studied after being given pure aflatoxin B1 (9mg/kg B.W., 6mg/kg B.W., and 3mg/kg B.W.) (produced from Aspergillus flavus) or a control group (not treated). MMP1 and MMP7 expressions were also measured using the MMP1 and MMP7 expression assays (IHC). The degree of liver damage is related to the AFB1 concentration and the duration of exposure. IHC reveals a considerable rise in MMP1 and MMP7 expression in the livers of mice given a maximum concentration of 90% ((9 mg/B.W.) pure AFB1), which approached the toxin's effect toxic dosage. MMP1 and MMP7 expression were also increased by AFB1 at dosages of 60 and 30% (6mg/BW and 3mg/B.W., respectively), although not to the same extent as 90%. MMP1 was significantly more expressed than MMP7 compared to control, and AFB1 at 90, 60, and 30% concentrations caused changes in hepatic cellular architecture, organization, and liver tissue damage and dramatically increased MMP1 and MMP7 production in hepatic tissue following treatment. Increased levels of pure aflatoxin B1 will harm liver tissue and MMP1 and MMP7 expression. MMP1 was more substantially expressed than MMP7." | Matrix Metalloproteinases, Secreted |
Ethylenediamine tetra-acetic acid disodium salt dihydrate was used as an impregnating reagent to resolve some cephalosporins. Both changes in the concentration of the impregnating reagent and in the composition of the mobile phase influenced the resolution. Three new solvent systems (I) propionic acid:2-propanol:water (6:3:3, v/v/v), (II) 2-prapanol:water:ethyl acetate (5:3:3, v/v/v) and (III) n-butanol:water:acetic acid (5:4:2, v/v/v) were found to be successful. | Cephalexin |
PURPOSE OF REVIEW: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, for which treatment guidelines are still evolving. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic modality for ALL, and this review describes the recent studies and current practice patterns concerning the who, when, and how of allo-HCT in the management of ALL. RECENT FINDINGS: Allogeneic stem cell transplantation is the treatment of choice for patients with ALL after first relapse and is also recommended for high-risk patients in first complete remission (CR1). Minimal residual disease evaluation and monitoring is developing as an important prognostic factor and could guide physicians in determining which patients, especially those with standard risk, might require transplant. Tyrosine kinase inhibitor (TKI) therapy allows a much higher proportion of Philadelphia-chromosome-positive ALL patients to attain remission and proceed to transplant with improved results; posttransplant TKI maintenance therapy may also provide survival benefit. Reduced-intensity conditioning regimens are a reasonable alternative for patients who would otherwise be ineligible for transplant because of age or comorbidity. SUMMARY: For patients with high-risk features, there is general agreement that allo-HCT in CR1 is a potentially curative option; however, there is no consensus on early transplant for standard-risk patients. | Myeloablative Agonists |
Essential oils (EOs) of Eugenia dysenterica fruits from seven populations were assessed using GC/MS and chemometric analysis. Variations in EOs between populations and three operational chemical units (OCUs), combined with foliar Mn(2+) as an environmental variable, indicate that 86.8% of variation in oils was explained by these predictors. Variance partitioning shows that the largest pure contribution was attributed to foliar Mn(2+) (13.1%), followed by OCU (11.4%). Populational origin contributed with lowest variance (6.6%). | Eugenia |
BACKGROUND: The purpose of this descriptive study was to determine and compare the incidence of left-sided and rightsided breast cancer at Dr George Mukhari Academic Hospital from January 2000 to June 2016. It aimed to determine if there was a significant variation in laterality of breast cancer at our institution. METHOD: A retrospective study. Medical records of breast cancer (BC) patients who were newly diagnosed from January 2000 to June 2016 were reviewed. Emphasis was on biopsy results (histology and/or cytology) and/or history of chemotherapy, and breast cancer laterality. RESULTS: Out of 1482 patients, 1427 had unilateral BC and 55 (3.7%) bilateral cancer. A total of 789 (55.3%) patients had left-sided breast cancer (LSBC) and 638 (44.7%) had right BC. Left BC was 10.6% more common than right BC with a left to right laterality ratio (LRR) of 1.24. There was a statistically significant relationship between laterality and stage (p = 0.050), with the right breast having more advanced stage cancers (88.7%) compared to the left breast (85%). There was no statistically significant difference between age, site and histological type of BC and laterality (p = 0.740, p = 0.052, p = 0.394 respectively). CONCLUSION: Left to right BC excess does exist in patients that were newly diagnosed at Dr George Mukhari Academic Hospital, South Africa, from January 2000 to June 2016. | Unilateral Breast Neoplasms |
Cutaneous tuberculosis is a specific form of tuberculosis, with various clinical pictures and resulting from either endo- or exogenous way of infection, immunological mechanisms and unfavourable conditions for mycobacterium development. The atypical course and symptoms of the disease may cause difficulties in obtaining proper diagnosis and, in consequence, result in delayed onset of appropriate treatment. When diagnosing cutaneous tuberculosis, a broad spectrum of differential diagnoses should be applied, taking into account other diseases, such as, among others, leishmaniasis, actinomycosis, leprosy or deep mycoses. In this report, a case of lymph node tuberculosis and of colliquative tuberculosis of the skin, at first erroneously diagnosed as actinomycosis, complicated by multiform erythema. In the reported case, no tuberculous bacilli were identified in bacteriological evaluations of bioptates, collected from the skin changes. The final diagnosis of the disease was determined by the presence of specific granulation tissue in the last of performed histopathological studies, as well as by hypersensitivity to tuberculin and the presence of mycobacterial DNA in PCR evaluation. According to the authors, in case of clinically suspected cutaneous tuberculosis, repeated (several) histopathological studies of samples from observed changes seem to be fairly justified. The results of histopathological studies should be completed by one of the methods of oligomycobacterial material evaluation, e.g. by identification of mycobacterial genetic material by means of nucleic acid amplification in the PCR method. | Erythema Induratum |
The optic axis of birefringent samples indicates the direction of optical anisotropy, which should be described in three-dimensional (3-D) space. We present a method to quantify the complete 3-D optic axis orientation calculated from in-plane optic axis measurements from a polarization-sensitive optical coherence tomography system. The in-plane axis orientations with different illumination angles allow the calculation of the necessary polar angle. The method then provides the information to produce the actual birefringence. The method and results from a biological sample are presented. | Birefringence |
BACKGROUND: Sore throat frequently occurs in children aged between four and fifteen years and is often associated to inflammation of the upper respiratory tract mucosa. A reliable approach to limit the damage caused by inflammation and, therefore, to alleviate associated symptoms might be the protection of the mucosa. Aim of this study was to assess the efficacy and tolerability of a medical device, formulated as a gummy lozenge and containing a combination of natural functional components (Erysimum, aloe vera and Xilogel(R)) able to exert a barrier effect on the mucosa, as ancillary treatment in children with sore throat. METHODS: This was an observational, prospective, parallel-group, multiple-dose trial of a medical device given in association to standard pharmacological prescribed therapy with an open label comparison vs. standard pharmacological prescribed therapy alone. The outcome measures of the study were assessed at baseline and after three days of treatment. RESULTS: One hundred and twelve school children with sore throat symptoms were recruited for this study and 69 were assigned to the group taking the study product. At the end of the treatment a statistically higher reduction in Sore Throat Pain Intensity Score and Pharyngitis Symptom Score was observed in the group taking the medical device. Moreover, the treatment with the medical device is associated to a statistically significant higher improvement of Child's General Conditions. The pediatrician assessed the efficacy and tolerability of the product under study as good/very good in 91% and 94%, respectively, of treated children. The consumer satisfaction questionnaire revealed that most of the children taking the lozenge rated it very positively in regard to its flavor and easiness of administration. CONCLUSIONS: The medical device used in this study may represent a valid choice as an adjuvant treatment in children with sore throat associated to upper respiratory tract infection. | Erysimum |
Vascularization is critical for skull development, maintenance, and healing. Yet, there remains a significant knowledge gap in the relationship of blood vessels to cranial skeletal progenitors during these processes. Here, we introduce a quantitative 3D imaging platform to enable the visualization and analysis of high-resolution data sets (>100 GB) throughout the entire murine calvarium. Using this technique, we provide single-cell resolution 3D maps of vessel phenotypes and skeletal progenitors in the frontoparietal cranial bones. Through these high-resolution data sets, we demonstrate that CD31(hi)Emcn(hi) vessels are spatially correlated with both Osterix+ and Gli1+ skeletal progenitors during postnatal growth, healing, and stimulated remodeling, and are concentrated at transcortical canals and osteogenic fronts. Interestingly, we find that this relationship is weakened in mice with a conditional knockout of PDGF-BB in TRAP+ osteoclasts, suggesting a potential role for osteoclasts in maintaining the native cranial microvascular environment. Our findings provide a foundational framework for understanding how blood vessels and skeletal progenitors spatially interact in cranial bone, and will enable more targeted studies into the mechanisms of skull disease pathologies and treatments. Additionally, our technique can be readily adapted to study numerous cell types and investigate other elusive phenomena in cranial bone biology. | Becaplermin |
OBJECTIVE: to develop the concept ambience for labor and normal institutionalized delivery, identifying in the literature its antecedent, defining attributes and the consequent. METHOD: the method used was the analysis of literature, corresponding to the first stage of the qualitative method of concept analysis. The theoretical operation was performed in the databases CINAHL COCHRANE, LILACS, PsycINFO, and PubMed. RESULTS: aspects of the parturient woman and the qualification of the physical and social space are presented as the antecedent. The defining attributes outline the assistance interaction process with Non-Invasive Technologies. As the consequent, we highlight the outcome for normal delivery, pain relief and comfort, woman satisfaction and well-being. FINAL CONSIDERATIONS: the analysis of the antecedent, defining attributes and the consequent allowed the elaboration of an unprecedent theoretical proposition of this concept. | Institutionalization |
Opioids, and more specifically mu-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest. It has been shown that allosteric modulators play key roles in influencing receptor function such as its tolerance to a ligand and affect downstream pathways. There has been a high variance of chemical structures that provide allosteric modulation at a given receptor, but recent studies and reviews tend to focus on the altered cellular mechanisms instead of providing a more rigorous description of the allosteric ligand's structure-function relationship. In this review, we aim to explore recent developments in the structural motifs that potentiate orthosteric binding and their influences on cellular pathways in an effort to present novel approaches to opioid therapeutic design. | Allosteric Site |
Heat shock protein genes, hsp90, hsc70, and hsp19.5, were cloned and sequenced from the diamondback moth, Plutella xylostella (L.) by RT-PCR and RACE method. The cDNA sequence analysis of hsp90 and hsp19.5 revealed open reading frames (ORFs) of 2,151 and 522 bp in length, which encode proteins with calculated molecular weights of 82.4 and 19.5 kDa, respectively. Analysis of cDNA from hsc70 revealed an ORF of 1,878 bp coding a protein with a calculated molecular weight of 69.3 kDa. Furthermore, the analysis of genomic DNA from hsc70 confirmed the presence of introns while no introns were apparent in hsp90 and hsp19.5. Southern blot analysis suggested the presence of multiple copies of each gene family in the DBM genome. Detectable expression of hsp19.5 was observed at the pupal stage while expression of hsp90 and hsc70 was detected at both pupal and adult stages. At adult stage, females showed a higher expression of hsp90 and hsc70 than males. An increased expression was observed in all three genes after exposure to a high temperature in both sexes. These results suggest that in addition to a heat shock response, these HSP genes might be involved in other functions during the course of development in DBM. | HSC70 Heat-Shock Proteins |
PURPOSE: The aim of this study was to investigate the oncologic efficacy of combining docetaxel with androgen deprivation therapy (ADT) versus nonsteroidal antiandrogen (NSAA) with ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with focus on the effect of sequential therapy in a real-world clinical practice setting. METHODS: The records of 382 patients who harbored high-volume mHSPC, based on the CHAARTED criteria, and had received ADT with either docetaxel (n = 92) or NSAA (bicalutamide) (n = 290) were retrospectively analyzed. The cohorts were matched by one-to-one propensity scores based on patient demographics. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), and time to second-line progression (PFS2) were compared. 2nd-line PFS defined as the time from CRPC diagnosis to progression after second-line therapy was also compared. RESULTS: After matching, a total of 170 patients were retained: 85 patients treated with docetaxel + ADT and 85 patients treated with NSAA + ADT. The median OS and CSS for docetaxel + ADT versus NSAA + ADT were not reached (NR) vs. 49 months (p = 0.02) and NR vs. 55 months (p = 0.02), respectively. Median time to CRPC and PFS2 in patients treated with docetaxel + ADT was significantly longer compared to those treated with NSAA (22 vs. 12 months; p = 0.003 and, NR vs. 28 months; p < 0.001, respectively). There was no significant difference in 2nd-line PFS between the two groups. CONCLUSIONS: Our analysis suggested that ADT with docetaxel significantly prolonged OS and CSS owing to a better time to CRPC and PFS2 in comparison to NSAA + ADT in high-volume mHSPC. | Nonsteroidal Anti-Androgens |
This paper reports on an exploratory study which aims to improve our understanding of how the Chief Executive Officers of Victorian health services monitor strategic and operational performance in their organisations. As a component of a large scale human resource management study, we surveyed 130 Chief Executive Officers (CEOs) of Victorian health sector agencies. Our findings suggest that performance monitoring was more advanced among the larger Victorian health sector organisations, and that there were areas for improvement throughout the system. Overall, the CEOs reported limited use of performance indicators related to service and clinical perspectives, with financial and volume indicators most widely used. There was little evidence that these organisations had processes in place (such as benchmarking and linking required outcomes to staff performance management) to understand the implications of the performance information and translate them into management action. The findings suggest that the sector requires technical expertise and support in data reporting, benchmarking and quality improvement in order to improve performance monitoring and ensure its relevance to strategic control, but further study is required." | Quality Indicators, Health Care |
Upon receptor activator of NF-kappaB ligand (RANKL) binding, RANK promotes osteoclast formation through the recruitment of tumor necrosis factor (TNF) receptor-associated factors (TRAFs). In vitro assays identified two RANK intracellular motifs that bind TRAFs: PVQEET(560-565) (Motif 2) and PVQEQG(604-609) (Motif 3), which potently mediate osteoclast formation in vitro. To validate the in vitro findings, we have generated knock-in (KI) mice harboring inactivating mutations in RANK Motifs 2 and 3. Homozygous KI (RANK(KI/KI) ) mice are born at the predicted Mendelian frequency and normal in tooth eruption. However, RANK(KI/KI) mice exhibit significantly more trabecular bone mass than age- and sex-matched heterozygous KI (RANK(+/KI) ) and wild-type (RANK(+/+) ) counterparts. Bone marrow macrophages (BMMs) from RANK(KI/KI) mice do not form osteoclasts when they are stimulated with macrophage colony-stimulating factor (M-CSF) and RANKL in vitro. RANKL is able to activate the NF-kappaB, ERK, p38, and JNK pathways in RANK(KI/KI) BMMs, but it cannot stimulate c-Fos or NFATc1 in the RANK(KI/KI) cells. Previously, we showed that RANK signaling plays an important role in Porphyromonas gingivalis (Pg)-mediated osteoclast formation by committing BMMs into the osteoclast lineage. Here, we show that RANKL-primed RANK(KI/KI) BMMs are unable to differentiate into osteoclasts in response to Pg stimulation, indicating that the two RANK motifs are required for Pg-induced osteoclastogenesis. Mechanistically, RANK Motifs 2 and 3 facilitate Pg-induced osteoclastogenesis by stimulating c-Fos and NFATc1 expression during the RANKL pretreatment phase as well as rendering c-Fos and NFATc1 genes responsive to subsequent Pg stimulation. Cell-penetrating peptides (CPPs) conjugated with RANK segments containing Motif 2 or 3 block RANKL- and Pg-mediated osteoclastogenesis. The CPP conjugates abrogate RANKL-stimulated c-Fos and NFATc1 expression but do not affect RANKL-induced activation of NF-kappaB, ERK, p38, JNK, or Akt signaling pathway. Taken together, our current findings demonstrate that RANK Motifs 2 and 3 play pivotal roles in osteoclast formation in vivo and mediate Pg-induced osteoclastogenesis in vitro. | Bacteroidaceae Infections |
PURPOSE: Otoendoscopy represents the initial non-invasive diagnostic cornerstone for external and middle ear disorders. Recently, new techniques of enhanced imaging such as narrow-band imaging (NBI) have been introduced but their role as a potential aid in otological practice remains unproven. In this pictorial review, we want to present the potential application of this endoscopic method, highlight its limitations, and give some hints regarding its future implementation. METHODS: Representative cases of external and/or middle ear pathologies were selected to illustrate the role of NBI in this regard. RESULTS: NBI may represent a useful aid in the otological work-up, in the differential diagnosis of ear tumor-like masses, and, possibly, in the prognosis of tympanic perforations. For other ear disorders, instead, this technique does not seem to add anything to the standard clinical practice. CONCLUSIONS: NBI might prove useful in the assessment of selected external and middle ear disorders but its role must be prospectively validated. | Narrow Band Imaging |
BACKGROUND: Sarcoma care is highly litigated in medical malpractice claims. Understanding the reasons for litigation and legal outcomes in sarcoma care may help physicians deliver more effective and satisfying care to patients while limiting their legal exposure. However, few studies have described malpractice litigation in sarcoma care. QUESTIONS/PURPOSES: (1) What percentage of sarcoma malpractice cases result in a defendant verdict? (2) What is the median indemnity payment for cases that result in a plaintiff verdict or settlement? (3) What are the most common reasons for litigation, injuries sustained, and medical specialties of the defendant physicians? (4) What are the factors associated with plaintiff verdicts or settlements and higher indemnity payments? METHODS: The national medicolegal database Westlaw was queried for medical malpractice cases pertaining to sarcomas that reached verdicts or settlements. Cases from 1982 to 2018 in the United States were included in the study to evaluate for trends in sarcoma litigation. Demographic and clinical data, tumor characteristics, reasons for litigation, injuries, and legal outcomes were recorded for each case. A univariate analysis was performed to identify factors associated with plaintiff verdicts or settlements and higher indemnity payments, such as tumor characteristics, defendant's medical or surgical specialty, reason for litigation, and injuries sustained. A total of 92 cases related to sarcomas were included in the study, of which 40 were related to bone sarcomas and 52 were related to soft-tissue sarcomas. Eighty-five percent (78 of 92) of cases involved adult patients (mean age +/- SD: 40 +/- 15 years) while 15% (14 of 92) of cases involved pediatric patients (mean age +/- SD: 12.5 +/- 5 years). RESULTS: Thirty-eight percent (35 of 92) of the included cases resulted in a defendant verdict, 30% (28 of 92) resulted in a plaintiff verdict, and 32% (29 of 92) resulted in a settlement. The median (interquartile range [IQR]) indemnity payment for plaintiff verdicts and settlements was USD 1.9 million (USD 0.5 to USD 3.5 million). Median (IQR) indemnity payments were higher for cases resulting in a plaintiff verdict than for cases that resulted in a settlement (USD 3.3 million [1.1 to 5.7 million] versus USD 1.2 million [0.4 to 2.4 million]; difference of medians = USD 2.2 million; p = 0.008). The most common reason for litigation was delayed diagnosis of sarcoma (91%; 84 of 92) while the most common injuries cited were progression to metastatic disease (51%; 47 of 92) and wrongful death (41%; 38 of 92). Malpractice claims were most commonly filed against primary care physicians (26%; 28 of 109 defendants), nononcology-trained orthopaedic surgeons (23%; 25 of 109), and radiologists (15%; 16 of 109). Cases were more likely to result in a ruling in favor of the plaintiff or settlement if a delay in diagnosis occurred despite suspicious findings on imaging or pathologic findings (80% versus 51%; odds ratio 3.84 [95% CI 1.34 to 11.03]; p = 0.02). There were no differences in indemnity payments with the numbers available in terms of tumor type, tumor location, defendant specialty, reason for litigation, and resulting injuries. CONCLUSIONS: Many lawsuits were made against primary care physicians, nononcology-trained orthopaedic surgeons, or radiologists for a delayed diagnosis of sarcoma despite the presence of imaging or histologic findings suspicious for malignancy. Although previous studies of bone and soft-tissue sarcomas have not shown a consistent association between time to diagnosis and decreased survival, our study suggests that physicians are still likely to lose these lawsuits because of the perceived benefits of an early diagnosis. CLINICAL RELEVANCE: Physicians can mitigate their malpractice risk while reducing delays in diagnosis of sarcomas by carefully reviewing all existing diagnostic studies, establishing closed-loop communication protocols to communicate critical findings from diagnostic studies, and developing policies to facilitate second-opinion consultation, particularly for imaging studies, with an experienced sarcoma specialist. Musculoskeletal oncologists may be able to help further reduce the rates of malpractice litigation in sarcoma care by helping patients understand that delays in diagnosis do not necessarily constitute medical malpractice. | Delayed Diagnosis |
Inhaled anesthetics are inhaled via the lungs. They subsequently pass through the alveolocapillary membrane and diffuse into the blood to finally target the central nervous system and induce anesthesia. This principle of anesthesia induction was first described for diethylether in 1847. Nevertheless, the use of diethylether for anesthesia is obsolete and even the use of nitrous oxide (introduced for anesthesia in 1847) is declining in Germany. Almost all modern volatile anesthetics are halogenated methylethylethers in which fluorine is used as a halogen. All of these anesthetics depress myocardial contractility and induce hypotension. Depression of CO2 and hypoxia-induced respiration are other serious side effects. Further side effects are liver and kidney related but they are rare and not induced by anesthetics per se but preferentially by toxic metobolites. Another promising inhalative anesthetic is xenon which fulfils many aspects of an ideal inhalative anesthetic. | Anesthetics, Inhalation |
Background: Decentralization of the sympathetic nervous system in persons with spinal cord injury (SCI) results in impaired vasomotor and sudomotor activity and, subsequently, impaired thermoregulatory capacity during exercise in the heat. Hyperthermia can be life-threatening and, as such, cooling interventions are needed to prevent this sequela. Objectives: To measure change in core temperature (DeltaT(C)) over time during exercise in normothermic and high ambient heat conditions to compare thermoregulatory capacity in persons with varying degrees of intact vasomotor and sudomotor activity and to determine the efficacy of three cooling interventions in mitigating T(C) rise. Methods: Three persons participated: a 51-year-old with complete (AIS A) tetraplegia (TP), a 32-year-old with AIS A paraplegia (PP), and a 40-year-old without SCI (AB). Each exercised for 30 minutes on a wheelchair treadmill propelled at 30 revolutions per minute under five different conditions: (1) cool (C) = 75 degrees F without cooling, (2) hot (H) = 90 degrees F without cooling, (3) 90 degrees F with cooling vest (CV), (4) 90 degrees F with water spray (WS), and (5) 90 degrees F with ice slurry ingestion (IS). DeltaT(C) was compared for all conditions in all participants. Results: DeltaT(C) in the C and H conditions was proportional to the neurological level of injury, with Tc rising highest in the TP followed by the PP then AB. WS was most efficacious at mitigating rise in T(C) followed by IS and CV in TP and PP. None of the cooling interventions provided an added T(C) cooling effect in AB. Conclusion: WS was most efficacious at mitigating rise in T(C) in TP>PP during exercise in the heat and should be studied in a larger SCI population. | Cool-Down Exercise |
Mycobacterium ulcerans, a decaying Mycobacterium marinum derivative is responsible for Buruli ulcer, a notifiable non-contagious disabling infection highly prevalent in some West African countries. Aquatic environments are suspected to host M. ulcerans, however, the exact reservoirs remain unknown. While M. marinum was found to resist amoebal microbicidal activities, this remains unknown for M. ulcerans. In this study M. ulcerans was co-cultured with the moderately halophile Acanthamoeba griffini at 30 degrees C to probe this tropical amoeba as a potential reservoir for M. ulcerans. In triplicate experiments, we observed engulfment of M. ulcerans by A. griffini trophozoites, followed by an unexpected significant difference of 98.4% (day 1), 99.5% (day 2), 99.5% (day 3) and 99.9% (day 7) between the number of intra-amoebal mycobacteria detected by PCR and the number of viable intra-amoebal mycobacteria measured by 10-week culture. Further encystment revealed only one Mycobacterium organism for 150 A. griffini cysts observed by electron microscopy and the culture of excysted amoebae remained sterile. In conclusion, these data install M. ulcerans as susceptible to A. griffini microbicidal activities rendering this amoeba species an unlikely host of M. ulcerans in natural environments. | Mycobacterium ulcerans |
Metamifop has been used to control gramineous weeds in paddy fields and may form residues in rice. In this study, the residue analysis method for metamifop and the metabolites was set up based on high-performance liquid chromatography-mass spectrometry and the chiral analysis method was also developed. The enantioselective degradation and residue of metamifop in rice processing were studied, and the major metabolites were monitored. The removal rate of metamifop by washing could reach 60.03%, while the loss in rice and porridge cooking was less than 16%. No decrease was found in fermentation into fermented grains, but metamifop was degraded in the process of rice wine fermentation with half-lives of around 9.5â¯days. N-(2-fluorophenyl)-2-(4-hydroxyphenoxy)-N-methylpropionamide and 6-chlorobenzo [d] oxazole-2 (3H)-one were found to be the major metabolites. This study reveals the enantioselective residue of metamifop in rice processing, which helps understand the potential risk in food consumption. | Benzoxazoles |
PURPOSE OF REVIEW: Calcinosis is a common complication of systemic sclerosis with no known effective pharmacologic therapy. We reviewed the literature regarding systemic sclerosis-related calcinosis as well as other disorders of biomineralization in order to identify targets of future study for calcinosis. RECENT FINDINGS: Patients with systemic sclerosis-related calcinosis demonstrate systemic abnormalities in mineralization pathways, including decreased levels of the mineralization inhibitor inorganic pyrophosphate. Insights from other mineralization disorders suggest that local and systemic phosphate metabolism pathways involving the ABCC6, ENPP1, and NT5E genes play a critical role in regulation of ectopic calcification. Knockout models of these genes may lead to an appropriate murine model for study of calcinosis. Poly(ADP-ribose) polymerase (PARP) enzymes may also play a critical role in hydroxyapatite nucleation and warrant future study in systemic sclerosis. Study of local and systemic mineralization pathways, particularly phosphate metabolism pathways and PARP enzymes, should provide greater insight into the pathogenesis of systemic sclerosis-related calcinosis. | Calcium Metabolism Disorders |
Distamycin and Hoechst 33258 have long served as the model compounds for biochemical, biophysical, and clinical studies of the drugs that bind in the DNA minor groove. However, the results presented in this investigation clearly show that 4,6-diamidino-2 phenylindole (DAPI) is superior to both of these drugs at negating the effects of intrinsic DNA curvature and anisotropic bendability as measured by electrophoretic and ligation analysis. In addition, DAPI was more effective than distamycin and Hoechst 33258 at inhibiting the assembly of nucleosomes onto synthetic and natural sequences that have multiple closely spaced oligo-AT sequences that serve as drug binding sites. Since these effects may be related to the biological action of the drugs, it was of interest to determine the mechanism that was responsible for the enhanced action of DAPI. The possibility that the differential drug potencies resulted from differential overall affinities of the ligands for A-tract molecules was considered, but drug binding studies suggested that this was not the case. It is also unlikely that the differential drug effects resulted from the binding of the drugs to different DNA sites since the oligo A/T binding sites for DAPI and Hoechst were centered on the same nucleotide positions as revealed by footprinting studies using exonuclease III, DNase I, and hydroxyl radical. However, the footprinting studies with DNase I did uncover a potentially important difference between the drugs. DAPI protected only the AT bp in the binding sites, while distamycin and Hoechst protected these bp as well as flanking Gs and Cs. These results permitted us to advance a preliminary model for the enhanced action DAPI. According to the model, the short length of DAPI and its absolute specificity for A/T bps with narrow minor grooves ensures that only particularly minor grooves that give rise to curvature and anisotropic bendability are occupied by the drug. Consequently, each helical deflection induced by an A-tract in the absence of the drug is countered by an opposite deflection induced by DAPI binding, thus effectively neutralizing intrinsic curvature and bending into the minor groove. | Bisbenzimidazole |
The extraction of nickel (Ni) from ultramafic soils by phytomining can be achieved using Alyssum murale cultures. This study presents a new process for the valorization of Ni accumulated by this plant through the production of a Ni ammonium disulfate salt (Ni(NH(4))(2)(SO(4))(2).6H(2)O). The process comprises an initial leaching of the ashes of A. murale with a sulphuric acid solution (1.9 M H(2)SO(4), T=95 degrees C, t=240 min, TS=150 g ash L(-1)), producing a leachate rich in Ni (10.2 g Ni L(-1); 96% Ni solubilisation), Mg, P, K, Fe, Ca and Al. The pH of the acid leachate is increased to 5.0 with NaOH (5M), followed by an evaporation step which produced a purified solution rich in Ni (21.3 g NiL(-1)) and an iron hydroxide precipitate. The cold crystallization (T=2 degrees C, t=6h) of this solution by the stoichiometric addition (x 1.2) of ammonium sulfate generates a Ni ammonium disulfate salt, containing 13.2% Ni, that is potentially valuable to industry. | Sulfuric Acids |
The variety of results of crystallographic studies of the serine proteases complexed with isocoumarin inhibitors presents a challenging problem to modeling methods and molecular energetics. Therefore, the thermodynamic cycle-perturbation technique has been used to study a model system of elastase and two peptidic inhibitors. Using the program AMBER, the technique correctly predicts changes of the binding constants for the trifluoroacetyl dipeptide inhibitors in comparison with available experimental (kinetic and crystallographic) data. However, the absolute values obtained are shown to be sensitive to the specific electrostatic interaction potential parameters used in the simulations. The reader and user are cautioned that thermodynamic cycle-perturbation results may be too optimistic by underestimating the accuracy of free energy values. This is especially a matter of concern for those cases where a direct comparison with experimental values is not possible, viz., (1) the stimulation of binding of novel compounds, (2) structurally uncertain binding sites, or (3) structurally different binding modes. With our best 4-31G* ESP (electrostatic potential) charges we were able to reproduce experimentally determined free energy differences (delta delta A) with an accuracy of about 1.5 kcal/mol. Dynamically induced structural changes in the binding site of elastase, and particularly changes in hydrogen-bond patterns of the binding site, are also reported. | Pancreatic Elastase |
The imaging technique of gamma scintigraphy has been used to quantify the total amount of drug deposited in the lungs and the pattern of regional lung deposition, for formulations of Berodual (Boehringer Ingelheim GmbH) delivered from pressurized metered dose inhalers formulated with chlorofluorocarbons, and with hydrofluoroalkane-134a or -227. Data were expressed as the mass of fenoterol deposited in the lungs from the Berodual formulations. All the formulations tested gave a whole lung deposition less than 20% of the metered (exvalve) dose. The mass of fenoterol deposited in the lungs for a solution formulation containing hydrofluoroalkane-134a was inversely proportional to the actuator nozzle diameter. The data suggest that the total and regional lung deposition of hydrofluoroalkane-based pressurized aerosol formulations is highly product-specific and that changes in bioavailability can be brought about by varying both the constituents of the formulation and the design of the actuator. | Fenoterol |
AIM: The aim of this study is to evaluate and compare the amount of radicular peroxide penetration when various concentrations of carbamide peroxide (CP) bleaching gels (10, 15, and 35%) and a mixture of 30% hydrogen peroxide (HP) with sodium perborate are used for intracoronal bleaching. MATERIALS AND METHODS: Fifty extracted single-rooted premolars from young adults were used. The specimens were then divided into five groups such that teeth with varying sizes were equally distributed in all groups. Group I-distilled water (control group), group II-10% CP, group III-15% CP, group IV-35% CP, and group V-30% HP with sodium perborate. Intermediate restorative material (IRM) was used to seal access cavities and left for a week at 37 degrees C in an incubator. Following the bleaching process, suspended teeth from plastic tubes containing distilled water were removed and the water was used to determine the amount of peroxide levels. A UV-visible spectrophotometer at a wavelength of 480 nm was used to determine the quantity of peroxide based on the optical density. RESULTS: Results showed the highest peroxide leakage in group V, followed by group IV, and then group III, whereas the least peroxide penetration was found in group II, and the control group or group I showed no penetration. The Kruskal-Wallis test showed a significant difference between the various groups tested. The Mann-Whitney test was done to find in which pair of groups there exists a significant difference. It was found that all the groups when compared among themselves showed a significant difference. CONCLUSION: The present study concluded that lower concentrations of CP 10 and 15% produced lower peroxide leakage. Hence, it could be tried as an alternate to traditional agents in cases with compromised tooth which shows cervical tooth defects where the risk of external root resorption is higher. CLINICAL SIGNIFICANCE: The management of discolored teeth involves different techniques; among various techniques, bleaching is considered to be a safe, effective, and relatively noninvasive technique to lighten discolored teeth and it also conserves dental hard tissue. | Carbamide Peroxide |
BACKGROUND: Endolymphatic sac is an established source of low-grade neoplasms, posing a difficult problem in local tumor control. CASE DESCRIPTION: Two cases of endolymphatic sac tumors are described in detail with regard to their clinical presentation and radiological findings. Both cases had diametrically opposite clinical outcomes in spite of repeated surgical interventions. A case with severe paraneoplastic syndrome and death after cancer cachexia" is described. CONCLUSIONS: Although endolymphatic tumors are known for their low-grade aggressiveness, in occasional cases, they may behave in a highly malignant behavior. The present communication highlights the contrast in clinical outcome and makes the clinician cautious of this special subgroup of tumors with a highly aggressive nature." | Ear Neoplasms |
Immunochemical detection of xenobiotics covalently bound to cellular proteins can provide information about toxic mechanism and is more specific than the alternative radiochemical studies. Both immunoblotting and immunohistochemical methods are used to pinpoint the target protein(s) and to identify the tissue targets. Also included in this unit are protocols for synthesizing artificial antigens, immunizing suitable host species, and using noncompetitive and competitive ELISA assays to characterize the antibodies produced. | Haptens |
The present paper reports the occurrence of the seventh species in the genus Amphiorchis (Digenea: Spirorchiidae) collected from the heart of a green turtle found in Florida, USA. A taxonomic key to the species of Amphiorchis and a literature review for the genus are presented. | Schistosomatidae |
53 samples of FD & C Yellow No. 5 (tartrazine; Colour Index No. 19140) were examined for combined benzidine. These samples, which represent separate lots from 12 dye distributors, were submitted to the US FDA for certification between 28 February 1990 and 27 June 1991. A method was developed to reduce the dye matrix with dithionite so that combined benzidine present in the form of azo or disazo dyes would be converted to free benzidine. Reduction was followed by extraction, diazotization and coupling with pyrazolone T, and the total benzidine present was quantitated as benzidine-pyrazolone T disazo dye (BZPT) by HPLC with detection at 500 nm. The limit of quantitation for benzidine in FD & C Yellow No. 5 by this method is 5 ng/g. 25 samples of FD & C Yellow No. 5 were found to contain 7-83 ng/g of combined benzidine that was released by dithionite reduction. 23 of these samples were from the same manufacturer. The identify of the BZPT from two FD & C Yellow No. 5 samples was confirmed by spectral analysis using HPLC with a photodiode array detector. | Benzidines |
Pogostemon Desf. includes a wide range of taxa found in subtropical and tropical areas. Few works, however, have studied microanatomical characteristics of Pogostemon species and as yet identified features of Pogostemon auricularius (L.) Hassk. Thus, in this paper, we examined the taxonomic implications of root, stem and leaf morphology for species P. auricularius collected from Quang Tri Province. Light microscopy was mainly used in our study. Qualitative characters like stem quadrangular, hirsute; leaves opposite, ovate, margin serrulate; calyx campanulate; corolla small with separate equal lobes have been found in P. auricularius. Epidermal anatomy on the aerial parts of the species like epidermal cell shape, anticlinal walls, trichomes types, stomata types and calcium oxalate crystals types were examined as well. Quantitative characters like the length and width of leaf blade and inflorescence; the size of oil droplet, stomata and calcium oxalate crystals measured provided taxonomic significance. Based on identifying morphological characteristics of P. auricularius, we aimed to contribute to the taxonomic investigation into the genus Pogostemon and give relative morphological and microanatomical features compared with other taxa. | Pogostemon |
Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here, we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca(2+) channels, while LTD required uniquely activation of L-type Ca(2+) channels. Notably, the voltage dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.SIGNIFICANCE STATEMENT This article shows for the first time a novel form of Ca(2+) channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with long-term depression (LTD) and long-term potentiation (LTP) being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-type and L-type voltage-gated Ca(2+) channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory. | Cerebellar Golgi Cells |
The design of stimuli-responsive self-assembled molecular systems capable of undergoing mechanical work is one of the most important challenges in synthetic chemistry and materials science. Here we report that foldectures, that is, self-assembled molecular architectures of beta-peptide foldamers, uniformly align with respect to an applied static magnetic field, and also show instantaneous orientational motion in a dynamic magnetic field. This response is explained by the amplified anisotropy of the diamagnetic susceptibilities as a result of the well-ordered molecular packing of the foldectures. In addition, the motions of foldectures at the microscale can be translated into magnetotactic behaviour at the macroscopic scale in a way reminiscent to that of magnetosomes in magnetotactic bacteria. This study will provide significant inspiration for designing the next generation of biocompatible peptide-based molecular machines with applications in biological systems. | Magnetosomes |
The highly virulent rabbit hemorrhagic disease virus (RHDV) has been widely used in Australia and New Zealand since the mid-1990s to control wild rabbits, an invasive vertebrate pest in these countries. In January 2014, an exotic RHDV was detected in Australia, and 8 additional outbreaks were reported in both domestic and wild rabbits in the 15 months following its detection. Full-length genomic analysis revealed that this virus is a recombinant containing an RHDVa capsid gene and nonstructural genes most closely related to nonpathogenic rabbit caliciviruses. Nationwide monitoring efforts need to be expanded to assess if the increasing number of different RHDV variants circulating in the Australian environment will affect biological control of rabbits. At the same time, updated vaccines and vaccination protocols are urgently needed to protect pet and farmed rabbits from these novel rabbit caliciviruses." | Hemorrhagic Disease Virus, Rabbit |
INTRODUCTION: Vitiligo pathogenesis is complicated, and several possibilities were suggested. However, it is well-known that the metabolism of pigments plays a significant role in the pathogenicity of the disease. OBJECTIVES: We explored the role of amino acids in vitiligo using targeted metabolomics. METHODS: The amino acid profile was studied in plasma using liquid chromatography. First, 22 amino acids were derivatized and precisely determined. Next, the concentrations of the amino acids and the molar ratios were calculated in 31 patients and 34 healthy individuals. RESULTS: The differential concentrations of amino acids were analyzed and eight amino acids, i.e., cysteine, arginine, lysine, ornithine, proline, glutamic acid, histidine, and glycine were observed differentially. The ratios of cysteine, glutamic acid, and proline increased significantly in Vitiligo patients, whereas arginine, lysine, ornithine, glycine, and histidine decreased significantly compared to healthy individuals. Considering the percentage of skin area, we also showed that glutamic acid significantly has a higher amount in patients with less than 25% involvement compared to others. Finally, cysteine and lysine are considered promising candidates for diagnosing and developing the disorder with high accuracy (0.96). CONCLUSION: The findings are consistent with the previously illustrated mechanism of Vitiligo, such as production deficiency in melanin and an increase in immune activity and oxidative stress. Furthermore, new evidence was provided by using amino acids profile toward the pathogenicity of the disorder. | Amino Acids, Diamino |
This is a report of a paratubal adult granulosa cell tumor (GCT) located within the right broad ligament in a 62-year-old woman. These are rare tumors with only 8 cases reported so far. Because of an overlap of topographic, morphologic, and immunohistochemical features, it is not always possible to differentiate between the broad ligament GCT and female adnexal tumor of probable Wolffian origin (FATWO). Although nuclear grooving is not an exclusive feature of GCT and can be seen in a variety of other neoplasms, in the context of the differential diagnosis between broad ligament GCT and FATWO, the presence of this feature may be very useful in establishing the diagnosis of broad ligament GCT. | Broad Ligament |
The total synthesis of tricyclic marine alkaloid fasicularin (1b) has been accomplished from a novel sterically well-defined alpha-aminonitrile 7, featuring a novel double consecutive epimerization process and Ir-catalyzed reductive functionalization of a tertiary gamma-lactam. The required configuration is obtained through the thermodynamically stereoselectively driven isomerization of a readily available 8a-cyanodecahydroquinoline framework. The strategy allows us to achieve the tricyclic core structures efficiently from affordable starting materials through simple operations. | Thiocyanates |
Nowadays, the ovarian reserve (OR) is considered more important than chronological age to estimate female reproductive capability. We conducted a retrospective, observational, and cohort study in order to detect the best predictor marker of OR, ovarian response, chances to obtain high-quality embryos, and pregnancy after in vitro fertilization (IVF) cycle in elderly women. For all eligible patients (aged between 40 and 50 and admitted to their first IVF cycle for primary infertility), we investigated the biochemical parameters and ultrasound aspects of ovaries and how they affected IVF outcomes. Age, basal follicle-stimulating hormone, basal luteinizing hormone, and basal-17beta-estradiol are better related to the dose of gonadotropin used during a controlled ovarian stimulation cycle. Basal anti-Mullerian hormone (AMH), antral follicular count (AFC), and maximum serum level of 17beta-estradiol before pickup resulted the best predictors of chances to retrieve at least 6 oocytes (at least 3 in metaphase II) and to have at least 1 to 3 embryos. The basal AMH, AFC and maximum serum level of 17beta-estradiol before pickup continue to show higher correlation to pregnancy rate. The maximum endometrial thickness at pickup resulted important to predict the pregnancy rate and the chances to detect ongoing pregnancy. It seems mandatory to well define the ovarian biological age rather than the chronological one in women older than 40 years of age in order to give the best counseling and to choose the most appropriate IVF protocols. | Ovarian Function Tests |
A powerful pH-free multicomponent NMR titration method can measure relative acidities, even of closely related compounds, with excellent accuracy. The history of the method is presented, along with details of its implementation and a comparison with earlier NMR titrations using a pH electrode. Many of its areas of applicability are described, especially equilibrium isotope effects. The advantages of the method, some practical considerations, and potential pitfalls are considered." | Magnetic Resonance Spectroscopy |
Pleasure and motivation are important factors for goal-directed behavior and well-being in both animals and humans. Intact hedonic capacity requires an undisturbed interplay between a number of different brain regions and transmitter systems. Concordantly, dysfunction of networks encoding for reward have been shown in depression and other psychiatric disorders. The development of technological possibilities to investigate connectivity on a functional level in humans and to directly influence networks in animals using optogenetics among other techniques has provided new important insights in this field of research.In this review, we aim to provide an overview on the neurobiological substrates of anhedonia on a network level. For this purpose, definition of anhedonia and the involved reward components are described first, then current data on reward networks in healthy individuals and in depressed patients are summarized, and the roles of different neurotransmitter systems involved in reward processing are specified. Based on this information, the impact of different therapeutic approaches on reward processing is described with a particular focus on deep brain stimulation (DBS) as a possibility for a direct modulation of human brain structures in vivo.Overall, results of current studies emphasize the importance of anhedonia in psychiatric disorders and the relevance of targeting this phenotype for a successful psychiatric treatment. However, more data incorporating these results for the refinement of methodological approaches are needed to be able to develop individually tailored therapeutic concepts based on both clinical and neurobiological profiles of patients. | Depressive Disorder, Major |
We describe the first virus-like particle of a hyperthermophilic euryarchaeote which was discovered in a strain of Pyrococcus abyssi" previously characterized in our laboratory. This particle, named PAV1, is lemon-shaped (120 nm x 80 nm), with a short tail terminated by fibers, and resembles the virus SSV1, the type member of the Fuselloviridae, isolated from Sulfolobus shibatae. Sensitivity of the virus-like particle to organic solvents and detergents suggested that the envelope of PAV1 may contain lipids in addition to proteins. It contains a double-stranded circular DNA of 18 kb which is also present in high copy number in a free form in the host cytoplasm. No integrated form of the PAV1 genome could be detected in the host chromosome. Under standard growth conditions, the host cells continuously release PAV1 particles into the culture supernatant without spontaneous lysis, with a maximum reached in the late stationary phase. UV, gamma irradiation, treatment with mitomycin C, and various physiological stresses had no effect on PAV1 production. Screening of a large number of Thermococcales isolates did not permit to find a sensitive host. These results suggest that PAV1 persists in the host strain in a stable carrier state rather than a prophage." | Fuselloviridae |
The bacteriophage T7 RNA polymerase gene was integrated into the fowlpox virus genome under the control of the vaccinia virus early/late promoter, P7.5. The recombinant fowlpox virus, fpEFLT7pol, stably expressed T7 RNA polymerase in avian and mammalian cells, allowing transient expression of transfected genes under the control of the T7 promoter. The recombinant fowlpox virus expressing T7 RNA polymerase offers an alternative to the widely used vaccinia virus vTF7-3, or the recently developed modified vaccinia virus Ankara (MVA) T7 RNA polymerase recombinant, a highly attenuated strain with restricted host-range. Recombinant fowlpox viruses have the advantage that as no infectious virus are produced from mammalian cells they do not have to be used under stringent microbiological safety conditions. | Avipoxvirus |
The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is usually straightforward, but atypical presentations can represent a significant diagnostic challenge. This review highlights the clinical and electrophysiological 'red flags' that should make one consider an alternative diagnosis." | Polyradiculoneuropathy, Chronic Inflammatory Demyelinating |
Non-polar solvents like hexane allow ionization of insoluble drugs, peptides, nucleotides and phospholipids as solids from paper. Ambient ionization is achieved simply by application of a high voltage to the wet paper. Transport and ionization mechanisms are discussed, including the possibility of field desorption from dendritic structures formed on the paper. | Hexanes |
Food toxicology (FT) is an old science whose origins may go back to primitive humans. However, due to major environmental damage, daily market launches of new food products, and the analytical ability to detect ever small quantities of toxicants in foods, FT is also an ever-growing science with an enormous task ahead. With respect to trace elements, current research trends can be encompassed under the headings of detection, control, and toxicological evaluation. Under the heading detection, quality, sensitivity, speed, automation, and specificity for each food type are the characteristics currently sought when developing new methodologies. Under control, there is a great need for constant monitoring, on an international level, of the levels of trace elements present in foods; and for development and application of new methodologies to guarantee product and process safety. Under toxicological evaluation, information about the bioavailability of trace elements and consequently studies of the chemical species present in foods have top priority. The work still outstanding in the study of trace element FT is immense, because it is necessary to achieve a profound understanding of the toxicological characteristics of food products in relation to trace elements; to give information to food manufacturers that they can use to adapt their production so that it meets the requirements of international legislation and demands for quality and innocuousness on the part of the market and consumers; and to develop standards regulating the maximum content of trace elements, according to the content of the various species. | Trace Elements |
Neuropil is a fundamental form of tissue organization within the brain(1), in which densely packed neurons synaptically interconnect into precise circuit architecture(2,3). However, the structural and developmental principles that govern this nanoscale precision remain largely unknown(4,5). Here we use an iterative data coarse-graining algorithm termed 'diffusion condensation'(6) to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy(7,8) coupled with lineage-tracing and cell-tracking algorithms(9,10) to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth-based on pioneer neurons-that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain. | Neuropil |
In this work, a sensitive and convenient protease-based fluorimetric high-throughput screening (HTS) assay for determining peptidyl-prolyl cis-trans isomerase activity was developed. The assay was based on a new intramolecularly quenched substrate, whose fluorescence and structural properties were examined together with kinetic constants and the effects of solvents on its isomerization process. Pilot screens performed using the Library of Pharmacologically Active Compounds (LOPAC) and cyclophilin A (CypA), as isomerase model enzyme, indicated that the assay was robust for HTS, and that comparable results were obtained with a CypA inhibitor tested both manually and automatically. Moreover, a new compound that inhibits CypA activity with an IC50 in the low micromolar range was identified. Molecular docking studies revealed that the molecule shows a notable shape complementarity with the catalytic pocket confirming the experimental observations. Due to its simplicity and precision in the determination of extent of inhibition and reaction rates required for kinetic analysis, this assay offers many advantages over other commonly used assays. | cis-trans-Isomerases |
Incursions of the coconut rhinoceros beetle (CRB), Oryctes rhinoceros, into different islands in the South Pacific have been detected in recent years. It has been suggested that this range expansion is related to an O. rhinoceros haplotype reported to show reduced susceptibility to the well-established classical biocontrol agent, Oryctes rhinoceros nudivirus (OrNV). Our understanding of the genetic characteristics which distinguish the population of O. rhinoceros that has recently established in Solomon Islands from other well-established populations across the region is very limited. Here, we hypothesized that the recently established O. rhinoceros population should have greater innate immune responses when challenged by OrNV than those of well-established and native O. rhinoceros populations. We used the RNA sequencing (RNA-Seq) approach to generate gene expression profiles of midgut tissue from OrNV-infected and noninfected individuals collected in the Solomon Islands (recent incursion), Papua New Guinea and Fiji (previously established), and the Philippines (within the native range). The collections included individuals from each of the three major mitochondrial lineages (CRB-G, CRB-PNG, and CRB-S) known to the region, allowing us to explore the specific responses of each haplotype to infection. Although insects from the Philippines and Solomon Islands that were tested belong to the same mitochondrial lineage (CRB-G), their overall responses to infection were different. The number of differentially expressed genes between OrNV-infected and noninfected wild-caught individuals from the four different locations varied from 148 to 252. Persistent OrNV infection caused a high level of induced antimicrobial activity and immune responses in O. rhinoceros, but the direction and magnitude of the responses were population specific. The insects tested from the Solomon Islands displayed extremely high expression of genes which are known to be involved in immune responses (e.g. coleoptericin, cecropin, and serpin). These variations in the host immune system among insects from different geographical regions might be driven by variations in the virulence of OrNV isolates, and this requires further investigation. Overall, our current findings support the importance of immunity in insect pest incursion and an expansion of the pest's geographic range. IMPORTANCE Oryctes rhinoceros nudivirus (OrNV) is a double-stranded DNA (dsDNA) virus which has been used as a biocontrol agent to suppress coconut rhinoceros beetle (CRB) in the Pacific Islands. Recently a new wave of CRB incursions in Oceania is thought to be related to the presence of low-virulence isolates of OrNV or virus-tolerant haplotypes of beetles (CRB-G). Our comparative analysis of OrNV-infected and noninfected CRBs revealed that specific sets of genes were induced by viral infection in the beetles. This induction was much stronger in beetles collected from the Solomon Islands, a newly invaded country, than in individuals collected from within the beetle's native range (the Philippines) or from longer-established populations in its exotic range (Fiji and Papua New Guinea [PNG]). Beetles from the Philippines and the Solomon Islands that were tested in this study all belonged to the CRB-G haplotype, but the country-specific responses of the beetles to OrNV infection were different. | Nudiviridae |
We examined neuronal responses of hypothalamic melanin-concentrating hormone (MCH) and corticotropin-releasing hormone (CRH) to background color in the self-fertilizing fish, Kryptolebias marmoratus. Fish were individually reared in lidless white or black cylindrical plastic containers for 15 days. The number of MCH-immunoreactive (ir) cell bodies in the nucleus lateralis tuberis (NLT) of the hypothalamus was significantly greater in the white-acclimated fish, while no significant differences were observed in the nucleus anterior tuberis (NAT) of the hypothalamus. Significant differences were not seen in the number of CRH-ir cell bodies in the NLT between the groups. The body of the white- and black-acclimated fish appeared lighter and darker, respectively, compared with the baseline color. In the black-acclimated fish, feeding activity was significantly greater with a tendency toward higher specific growth rate compared with the observations in white-acclimated fish. No significant inter-group cortisol level differences were observed. These results indicate that background color affects MCH neuronal activity in the NLT as well as body color adaptation but does not affect CRH neuronal activity in K. marmoratus. | Hypothalamic Hormones |
A 76-year-old patient was admitted with right-sided lower abdominal pain. CT scan of the abdomen demonstrated a fatty mass arising around the bowel in the left iliac fossa causing local distortion of the vasculature. His clinical condition rapidly deteriorated with worsening abdominal signs necessitating an exploratory laparotomy. A segment of perforated small bowel associated with mesenteric mass was excised and the patient died 3 days later. The histology demonstrated a well-differentiated liposarcoma. Liposarcomas are the most common soft tissue sarcomas in adults but occurrence in the gastrointestinal tract is extremely rare. The clinical presentation of these tumours is frequently non-specific and commonest symptoms are generalised, intermittent abdominal pain. Surgical resection with clear margins is the treatment of choice for primary liposarcomas. They are moderately radiosensitive and chemotherapy is non-effective. Although gastrointestinal liposarcomas have been previously reported, this is the first reported case of a primary liposarcoma associated with a small bowel perforation. | Ileal Neoplasms |
N-Methylquipazine (2-[1-(4-methyl)-piperazinyl)quinoline)) was labelled with carbon-11 by reacting [11C]methyl iodide with the nor-compound, quipazine. Radiochemical conversions were 79 +/- 7%, based on the alkylating agent. The total synthesis time including purification was 40 to 45 min. N-[Methyl-11C]methylquipazine thus synthesized was >99% radiochemically pure, and the specific activity ranged between 12-37 GBq/mumol. Dynamic imaging with PET was used to examine in vivo its distribution in rat and monkey. In rat the organ uptake at intermediate times was: liver > heart > whole brain > or = lung > extracerebral tissue. Brain uptake and wash-out were rapid: A maximum was reached in 2 to 3 min with subsequent decrease to approximately equal to 50% the peak value by 13 min. In monkey the tracer uptake was heterogeneous and high in regions known to contain 5-HT3 receptors but also in regions devoid of these receptors. Tissue kinetics were similar for all regions (initial rapid accumulation with tmax < or = 7 min, followed by slow decrease with all regions approaching the level of the cerebellum at 30 to 35 min). Pretreating with quipazine significantly decreased only the ratio of uptake in the medulla oblongata compared to the cerebellum. Although the nonspecificity of its binding limits the usefulness of N-[methyl-11C]methylquipazine, both its kinetic behavior and the blocking results indicate that a more selective arylpiperazine might prove to be a more attractive tracer for PET studies of 5-HT3 receptors. | Quipazine |
AIMS: This report presents a case wherein severe gagging during dental treatment was linked to hiatus hernia. METHODS AND RESULTS: A 22-year-old man with a severe gagging problem presented with a chief complaint of pain localized to the lower molars. Oral examination revealed inadequate plaque control, demineralization of the enamel surface on buccal-gingival margins of all teeth, and inflamed gingival tissue surrounding the coronal portion of both mandibular third molars; panoramic radiography revealed that they were horizontally impacted. As the patient reported experiencing vomiting and heartburn for the past two months, he was referred to the internal medicine department before scheduling surgical tooth extraction. Hiatus hernia and reflux esophagitis were diagnosed, and the severity of gagging was significantly reduced by modifying the patient's eating behavior and administering a proton pump inhibitor. Although intravenous sedation was still required for surgical extraction of the impacted third molars, preventive treatments, such as tooth cleaning and fluoride application, could be performed without the need for pharmacological intervention. CONCLUSION: While gagging is often attributed to conditioning responses and iatrogenic factors, interdisciplinary consultation for successful management may facilitate the elucidation of local anatomical and systemic causes. | Gagging |
The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has been characterized by mutagenesis and molecular modeling and is different from the antagonist binding site. The function and physiological regulation of the OT system is strongly steroid dependent. However, this is, unexpectedly, only partially reflected by the promoter sequences in the OT receptor gene. The classical actions of OT are stimulation of uterine smooth muscle contraction during labor and milk ejection during lactation. While the essential role of OT for the milk let-down reflex has been confirmed in OT-deficient mice, OT's role in parturition is obviously more complex. Before the onset of labor, uterine sensitivity to OT markedly increases concomitant with a strong upregulation of OT receptors in the myometrium and, to a lesser extent, in the decidua where OT stimulates the release of PGF(2 alpha). Experiments with transgenic mice suggest that OT acts as a luteotrophic hormone opposing the luteolytic action of PGF(2 alpha). Thus, to initiate labor, it might be essential to generate sufficient PGF(2 alpha) to overcome the luteotrophic action of OT in late gestation. OT also plays an important role in many other reproduction-related functions, such as control of the estrous cycle length, follicle luteinization in the ovary, and ovarian steroidogenesis. In the male, OT is a potent stimulator of spontaneous erections in rats and is involved in ejaculation. OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes. For example, in the rat, OT is a cardiovascular hormone acting in concert with atrial natriuretic peptide to induce natriuresis and kaliuresis. The central actions of OT range from the modulation of the neuroendocrine reflexes to the establishment of complex social and bonding behaviors related to the reproduction and care of the offspring. OT exerts potent antistress effects that may facilitate pair bonds. Overall, the regulation by gonadal and adrenal steroids is one of the most remarkable features of the OT system and is, unfortunately, the least understood. One has to conclude that the physiological regulation of the OT system will remain puzzling as long as the molecular mechanisms of genomic and nongenomic actions of steroids have not been clarified. | Receptors, Oxytocin |
Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit. | Influenza, Human |
Hypochondriasis may be conceptualized as a disorder of perception and cognition, in which somatic sensation is experienced as abnormally intense and is then incorrectly attributed to serious medical disease. We describe a therapy to modulate the hypochondriacal patient's somatic sensations, and to alter his or her cognitive appraisal of them, which focuses on four factors that amplify somatic symptoms: (1) attention and expectation; (2) symptom attribution and appraisal; (3) the context used for interpreting the symptoms; and (4) disturbing affect and dependency needs. This therapy, or selected portions of it, can be employed in clinical work with patients individually and in groups, in consultation work, and in more traditional psychotherapeutic settings. | Hypochondriasis |
Enzyme-instructed self-assembly is an increasingly attractive topic owing to its broad applications in biomaterials and biomedicine. In this work, we report an approach to construct enzyme-responsive aqueous surfactant two-phase (ASTP) systems serving as enzyme substrates by using a cationic surfactant (myristoylcholine chloride) and a series of anionic surfactants. Driven by the hydrophobic interaction and electrostatic attraction, self-assemblies of cationic-anionic surfactant mixtures result in biphasic systems containing condensed lamellar structures and coexisting dilute solutions, which turn into homogeneous aqueous phases in the presence of hydrolase (cholinesterase). The enzyme-sensitive ASTP systems reported in this work highlight potential applications in the active control of biomolecular enrichment/release and visual detection of cholinesterase. | Ions |
Sugar-based polyesters derived from sorbitol and isohexides were obtained via solvent-free enzymatic catalysis. Pendant hydroxyl groups, coming from the sorbitol units, were present along the polyester backbone, whereas the two isohexides, namely, isomannide and isoidide dimethyl ester monomers, were selected to introduce rigidity into the polyester chains. The feasibility of incorporating isomannide as a diol compared to the isoidide dimethyl ester as acyl-donor via lipase-catalyzed polycondensation was investigated. The presence of bicyclic units resulted in enhanced T(g) with respect to the parent sorbitol-containing polyester lacking isohexides. The different capability of the two isohexides to boost the thermal properties confirmed the more flexible character provided by the isoidide diester derivative. Solvent-borne coatings were prepared by cross-linking the sugar-based polyester polyols with polyisocyanates. The increased rigidity of the obtained sugar-based polyester polyols led to an enhancement in hardness of the resulting coatings. | Sorbitol |
Cognitive deficits (chemobrain) and peripheral neuropathy occur in approximately 75% of patients treated for cancer with chemotherapy and persist long-term in >30% of survivors. Without preventive or curative interventions and with increasing survivorship rates, the population debilitated by these neurotoxicities is rising. Platinum-based chemotherapeutics, including cisplatin, induce neuronal mitochondrial defects leading to chemobrain and neuropathic pain. This study investigates the capacity of nasally administered mesenchymal stem cell-derived mitochondria coated with dextran-triphenylphosphonium polymer (coated mitochondria) to reverse these neurotoxicities. Nasally administered coated mitochondria are rapidly detectable in macrophages in the brain meninges but do not reach the brain parenchyma. The coated mitochondria change expression of >2400 genes regulating immune, neuronal, endocrine and vascular pathways in the meninges of mice treated with cisplatin. Nasal administration of coated mitochondria reverses cisplatin-induced cognitive deficits and resolves neuropathic pain at a >55-times lower dose compared to uncoated mitochondria. Reversal of these neuropathologies is associated with resolution of cisplatin-induced deficits in myelination, synaptosomal mitochondrial integrity and neurogenesis. These findings demonstrate that nasally administered coated mitochondria promote resolution of chemobrain and peripheral neuropathy, thereby identifying a novel facile strategy for clinical application of mitochondrial donation and treating central and peripheral nervous system pathologies by targeting the brain meninges." | Chemotherapy-Related Cognitive Impairment |
Since the late 1970s glycine has been considered an important inhibitory neurotransmitter in brain stem and medulla. The description of its involvement in the mechanism of action of the potent neurotoxin strychnine pushed further the concept of inhibitory transmitter. The significant concentrations of glycine in forebrain motivated investigators to evaluate different aspects of glycinergic transmission under the ontogenetic, physiologic and pathologic standpoints. This review encompasses a few of these aspects as the role of the different glycine receptors (GlyRs) in intracellular chloride balance, glycine transporters, GABA/Glycine co-release, glycine/NMDA receptor interaction, glycine receptors in acute alcohol effects and advocates a more relevant role for glycine as a stimulatory transmitter in forebrain areas. Finally, the possible co-release of glycine and GABA is considered as an important process to understand the role of glycine in forebrain neural transmission. | Prosencephalon |
We report the case of a patient who acquired cutaneous leishmaniasis in Israel, with multiple lesions on the face and wrists. The diagnosis was made several months after the onset of disease. We observed large multiple ulcers, which at first responded to sodium stibogluconate (600 mg daily for 2 weeks). After initially decreasing in size, the lesions remained unchanged. Several weeks later clinical exacerbation of the cutaneous leishmaniasis was observed. Fearing late complications on the upper eyelid, we administered two 2-week courses of ketoconazole, 800 mg daily. The early and rapid improvement achieved indicates that ketoconazole was successful in this case of cutaneous leishmaniasis. | Gluconates |
Mercurochrome strongly inhibits aspartate transaminase and 2,3-dicarboxyethylated aspartate transaminase. The native enzyme exhibits a biphasic time-course of inactivation by mercurochrome with second-order rate constants 1.62 x 10(4) M-1 - min-1 and 2.15 x 10(3) M-1 - min-1, whereas the modified enzyme is inactivated more slowly (second-order rate constant 6.1 x 10(2) M-1 - min-1) under the same conditions. The inhibitor inactivates native and modified enzyme in the absence as well as in the presence of substrates. Mercurochrome-transaminase interaction is accompanied by a red shift in the absorption maximum of the fluorochrome of about 10 nm. Difference spectra of the mercurochrome-enzyme system versus mercurochrome, compared with analogous spectra of mercurochrome-ethanol, revealed that the spectral shifts recorded during mercurochrome-transaminase interaction are similar to those that occur when mercurochrome is dissolved in non-polar solvents. Studies of mercurochrome complexes with native or modified transaminase, isolated by chromatography on Sephadex G-25, revealed that native transaminase is able to conjugate with four mercurochrome molecules per molecule, but the modified enzyme is able to conjugate with only two mercurochrome molecules per molecule. | Merbromin |
Polycystic liver disease, a hereditary pathology, usually manifests as autosomal dominant polycystic kidney disease. The many cysts in the liver cause massive hepatomegaly, majorly affecting the patient's quality of life. In cases of refractory symptoms, liver transplantation is the only treatment choice. A 43-year-old woman was followed up as a hepatology outpatient in August 2020, with a progressive increase in abdominal volume, lower limb edema, and cachexia. The patient was diagnosed with polycystic renal and liver disease with massive hepatomegaly in March 2021, a combined kidney-liver transplant. Liver size represented 13% of the patient's corporal composition, weighing 8.6kg. The patient was discharged on the 7th postoperative day with no complications. Only 10-20% of patients with polycystic liver disease have clinical manifestations, most of which result from hepatomegaly. An increase in liver volume deteriorates liver function until the condition becomes end-stage liver disease, as kidney function is already compromised; liver-kidney transplantation remains the only treatment choice. The case described drew significant attention to the massive hepatomegaly presented in the patient, with the liver representing over 10% of the patient's body weight, approximately five to six times larger than a normal-sized liver. | Hepatomegaly |
Synthetic cathinones are derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant Catha edulis. Cathinone is the beta-keto analog of amphetamine, and all synthetic cathinones display a beta-keto moiety in their structure. Several synthetic cathinones are widely prescribed medications (e.g., bupropion, Wellbutrin((R))), while others are problematic drugs of abuse (e.g., 4-methylmethcathinone, mephedrone). Similar to amphetamines, synthetic cathinones are psychomotor stimulants that exert their effects by impairing the normal function of plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and 5-HT (SERT). Ring-substituted cathinones like mephedrone are transporter substrates that evoke neurotransmitter release by reversing the normal direction of transporter flux (i.e., releasers), whereas pyrrolidine-containing cathinones like 3,4-methylenedioxypyrovalerone (MDPV) are potent transporter inhibitors that block neurotransmitter uptake (i.e., blockers). Regardless of molecular mechanism, all synthetic cathinones increase extracellular monoamine concentrations in the brain, thereby enhancing cell-to-cell monoamine signaling. Here, we briefly review the mechanisms of action, structure-activity relationships, and in vivo pharmacology of synthetic cathinones. Overall, the findings show that certain synthetic cathinones are powerful drugs of abuse that could pose significant risk to users." | Catecholamine Plasma Membrane Transport Proteins |
Fumarate permeation in isolated rat liver mitochondria was demonstrated by measuring malate and phosphate efflux caused by fumarate added externally to the mitochondrial suspension. The existence of two specific fumarate translocators, fumarate/malate and fumarate/phosphate, is shown here. These carriers are distinguished in the light of different kinetic parameters (Km values are 50 microM and 150 microM, and Vmax values are 17 and 40 nmoles/min X mg mitochondrial protein, respectively) and of differing sensitivity to non-penetrant compounds. Fumarate was found to cause oxaloacetate efflux from mitochondria by means of an indirect process which involves the cooperation of both fumarate/malate and malate/oxaloacetate translocators. Results are discussed in the light of the physiological role played by fumarate translocation in both ureogenesis and aminoacid metabolism. | Mersalyl |
Spinal cord injury (SCI) results in loss of neurons, oligodendrocytes and myelin sheaths, all of which are not efficiently restored. The scarcity of oligodendrocytes in the lesion site impairs re-myelination of spared fibres, which leaves axons denuded, impedes signal transduction and contributes to permanent functional deficits. In contrast to mammals, zebrafish can functionally regenerate the spinal cord. Yet, little is known about oligodendroglial lineage biology and re-myelination capacity after SCI in a regeneration-permissive context. Here, we report that, in adult zebrafish, SCI results in axonal, oligodendrocyte and myelin sheath loss. We find that OPCs, the oligodendrocyte progenitor cells, survive the injury, enter a reactive state, proliferate and differentiate into oligodendrocytes. Concomitantly, the oligodendrocyte population is re-established to pre-injury levels within 2 weeks. Transcriptional profiling revealed that reactive OPCs upregulate the expression of several myelination-related genes. Interestingly, global reduction of axonal tracts and partial re-myelination, relative to pre-injury levels, persist at later stages of regeneration, yet are sufficient for functional recovery. Taken together, these findings imply that, in the zebrafish spinal cord, OPCs replace lost oligodendrocytes and, thus, re-establish myelination during regeneration." | Oligodendrocyte Precursor Cells |
Phosfolan, chlorpyrifos, and stirophos when applied to white mice at sublethal doses did not induce any delayed neurotoxic effect. On the other hand, Leptophos and EPN when administered orally at sublethal or lethal levels clearly produced a delayed neurotoxic ataxia in treated mice. The five tested organophosphorus insecticides were compared for their ability to inhibit cholinesterase, neurotoxic esterases and monoamine oxidase. I50 values were estimated for each case. The results revealed that all five compounds were inhibitors of cholinesterase, but only Leptophos and EPN were shown to be potent inhibitors for both neurotoxic esterase and monoamine oxidase in the mouse brain. Additional particular properties of both Leptophos and EPN were found in their ability to cause delayed neurotoxic ataxia in chickens and sheep fed once on sublethal doses of these compounds. It is believed that the phosphonate ester configuration of EPN and Leptophos has a specific mode of toxic action which is mainly located at the central nervous system. It is also postulated that these delayed neurotoxic agents might inhibit postganglionic sympathetic neurons, thus resulting in chronic paralytic effects. | Organothiophosphonates |
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality and atherosclerosis is the common root to most of the CVD. Oxidative stress is one of the most important factors driving atherosclerosis and its complications. Thus, strategies for the prevention and treatment of cardiovascular events had oxidative changes as a potential target. Natural vitamin E consists of a family of eight different compounds, four tocopherols and four tocotrienols. All tocopherols and tocotrienols are potent antioxidants with lipoperoxyl radical-scavenging activities. In addition, alpha-tocopherol possesses also anti-inflammatory as well as anti-atherothrombotic effects by modulating platelet and clotting system. Experimental and in vitro studies described molecular and cellular signalling pathways regulated by vitamin E antithrombotic and antioxidant properties. While observational studies demonstrated an inverse association between vitamin E serum levels and CVD, interventional trials with vitamin supplements provided negative results. This review focus on the impact of vitamin E in the atherothrombotic process and describes the results of experimental and clinical studies with the caveats related to the interventional trials with vitamin E to prevent CVD. | Tocotrienols |
The integrase (Int) proteins of coliphages HK022 and lambda, are phosphorylated in one or more of their tyrosine residues. In Int of HK022 the phosphorylated residue(s) belong to its core-binding/catalytic domains. Wzc, a protein tyrosine kinase of Escherichia coli, is not required for Int phosphorylation in vivo, however, it can transphosphorylate the conserved Tyr(342) catalytic residue of Int in vitro. Int purified from cells that overexpress Wzc has a reduced activity in vitro. In vivo, the lysogenization of wild type HK022 as well as of lambda is not affected by the overexpression of Wzc. However, the nin5 mutant of lambda, which lacks a protein-tyrosine phosphatase gene, shows a significantly reduced lysogenization. It is suggested that phosphorylation of Int by Wzc down regulates the activity of Int. | Bacteriophage HK022 |
PURPOSE: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors comprising various breast cancers simply defined by the absence of estrogen receptor, progesterone receptor and overexpression of human epidermal growth factor receptor 2 gene. In this review, we discuss the epidemiology, risk factors, clinical characteristics and prognostic variables of TNBC, and present the summary of recommended treatment strategies and all other available treatment options. METHODS: We performed a systematic literature search using Medline and selected those articles which seemed relevant for this review. In addition, the ClinicalTrials.gov was also scanned for ongoing trials. RESULTS: TNBC accounts for 10-20 % of all invasive breast cancers and has been found to be associated with African-American race, younger age, higher grade and mitotic index, and more advanced stage at diagnosis. Locoregional treatment is similar to other invasive breast cancer subtypes and involves surgery-mastectomy with or without adjuvant radiotherapy or breast conservation followed by adjuvant radiotherapy. Due to lack of drug-targetable receptors, chemotherapy is the only recommended systemic treatment to improve disease outcome. TNBC is sensitive to chemotherapy as demonstrated by high pathological complete response rates achieved after neoadjuvant chemotherapy, and this approach also allows for breast-conserving surgery. The peak risk of relapse is at 3 years after surgery, thereafter recurrence risk rapidly decreases. Survival after metastatic relapse is shorter as compared to other breast cancer subtypes, treatment options are few and response rates are poor and lack durability. Important molecular characteristics have now been identified that can subdivide this group of breast cancers further and can provide alternative systemic therapies. CONCLUSIONS: To improve therapeutic outcome of TNBC, reliable predictive biomarkers and newer drugs against the known molecular pathways are required." | Triple Negative Breast Neoplasms |
A 10.6 year old Turkish girl developed + the signs of a polyglandular autoimmune syndrome (PGA) type I since her first year of age. Apart from the endocrine and non-endocrine symptoms of PGA, she suffered from an acute state of illness with therapy-resistant fever and multiform exanthemas in the early course of disease. All included the criteria of Wissler-Fanconi syndrome became clear which has not yet been reported in association with PGA. Although this syndrome generally is considered an equivalent of Still's syndrome, rheumatoid symptoms could not be ascertained during the following 9-year-course of PGA. | Wissler's Syndrome |
N-Nitrosodimethylamine (NDMA) and two of its metabolites, monomethylhydrazine (MMH) and 1,1-dimethylhydrazine (UDMH) were metabolized to carbon dioxide by rat liver slices. Under these conditions, NDMA and MMH, but not UDMH, produced reactive metabolites that bound covalently to nucleic acids. Rat liver microsomes or 9000 X g supernatants were able to transform NDMA, MMH and UDMH to formaldehyde. In the case of MMH and UDMH, enzymatic and non-enzymatic pathways of formaldehyde formation were present in both liver microsomes and 9000 X g supernatants. NDMA, MMH and UDMH led to covalent binding in incubation mixtures containing either microsomes or 9000 X g supernatants. In the case of NDMA, the process was enzymatic and required NADPH in both cellular fractions. In the case of MMH, the process was enzymatic in microsomes, and required NADPH and oxygen when using UDMH or MMH and 9000 X g supernatants; interactions of a non-enzymatic nature leading to covalent binding to proteins were dominant. These results suggest that part of the carbon dioxide produced during NDMA metabolism might derive from UDMH and MMH. Similarly, a significant part of the covalent binding of NDMA metabolites to proteins in incubation mixtures containing microsomes or 9000 X g supernatants might derive from enzymatic and non-enzymatic reactions of UDMH or MMH. Also, a minor part of the covalent binding of NDMA reactive metabolites to nucleic acids might be due to further biotransformation of MMH to reactive metabolites. It may be concluded from the present results that biotransformation of NDMA to UDMH and MMH might not be a detoxication process, as previously thought, but one related to some of the toxic effects of NDMA. | Methylhydrazines |
A 16-year-old Korean male patient presented with macrodactyly, hemihypertrophy of the face and extremities, plantar cerebriform hyperplasia, a subcutaneous mass of the left chest, macrocephaly and verrucous epidermal nevi. These findings are consistent with Proteus Syndrome. The clinical features, etiology, management, natural course and differential diagnosis of this case are discussed. | Proteus Syndrome |
The objective of this paper is to provide a comprehensive review of explosive detection by chemiluminescence (CL) through a summary of the relevant literature in the last 5 years and a synopsis of current research topics and developments. The literature reviewed is specially addressed for the detection of a group of high explosives, containing nitrogen compounds. Most explosives compounds contain either nitro or nitrate groups which make possible their detection and quantification using detection systems based on chemiluminescent reactions. Practical considerations and experimental requirements are indicated, and the possibilities and limitations are evaluated. | Explosions |
Perineal infections are a common presenting complaint in women attending acutely to a gynaecology department. Specifically, Bartholin's abscesses can occur in approximately 2% of women. Conservative versus surgical approaches to manage these infections aims to reduce the need for hospital admission. We summarise the literature on the diagnosis and management of Bartholin's and other types of perineal infections and abscesses specific to gynaecology. | Bartholin's Glands |
The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure (CHF) and dilated cardiomyopathy in adults and in children. The prevention of anthracycline-induced cardiotoxicity is particularly important in children who can be expected to survive for decades after being cured of their malignancy. Attempts to reduce anthracycline cardiotoxicity have been directed towards: (i) decreasing myocardial concentrations of anthracyclines and their metabolites by dose limitation and schedule modification; (ii) developing less cardio-toxic analogs; and (iii) concurrently administering cardioprotective agents to attenuate the effects of anthracyclines on the heart. As regards schedule modification, avoidance of anthracycline peak levels may reduce the pathologic and clinical cardiotoxicity, although this has not always been observed. The analogs of doxorubicin, such as idarubicin and epirubicin, have similar cardiotoxicity to that of doxorubicin when given in amounts of equivalent myelotoxicity. Liposomal anthracyclines are a new class of agents that may permit more specific organ targeting, thereby producing less systemic and cardiac toxicity, but more studies are required to assess the advantages, if any, of these preparations over classical anthracyclines. The cardioprotective agent, dexrazoxane, an iron chelator, is highly effective and provides short-term cardioprotection to most patients receiving even the most intensive doxorubicin-containing regimens. Its long-term benefits remain to be determined. In addition, data remain insufficient to make specific recommendations regarding current use of dexrazoxane in children. It is thought that subtle abnormalities, related to anthracycline treatment in childhood, can develop into more permanent myocardial disease resulting in cardiomyopathy, which may progress to CHF. As regards the therapy of patients with anthracycline cardiotoxicity, two different situations have, therefore, to be considered: (i) if the patient presents with cardiac abnormalities, such as a reduction in fractional shortening at echocardiogram, without cardiac symptoms; and (ii) if the patient has CHF. In the presence of CHF, recovery with digitalis-diuretic therapy alone seldom occurs, and in patients who have refractory hemodynamic decompensation, heart transplantation is indicated. In patients with CHF, therapy with ACE inhibitors induces improvement in left ventricular structure and function, but this improvement is transient. Randomized clinical trials are, therefore, necessary to determine the effects of ACE inhibitors in mild-to-moderate left ventricular dysfunction. The beneficial effects of beta-adrenoceptor antagonists (beta-blockers) on cardiac function in heart failure due to anthracyclines seem comparable with those observed in other forms of heart failure with systolic dysfunction. Many drugs are available to treat children with CHF due to anthracycline treatment, but they are only palliative. | Anthracyclines |
BACKGROUND: Geobacter species grow by transferring electrons out of the cell--either to Fe(III)-oxides or to man-made substances like energy-harvesting electrodes. Study of Geobacter sulfurreducens has shown that TCA cycle enzymes, inner-membrane respiratory enzymes, and periplasmic and outer-membrane cytochromes are required. Here we present comparative analysis of six Geobacter genomes, including species from the clade that predominates in the subsurface. Conservation of proteins across the genomes was determined to better understand the evolution of Geobacter species and to create a metabolic model applicable to subsurface environments. RESULTS: The results showed that enzymes for acetate transport and oxidation, and for proton transport across the inner membrane were well conserved. An NADH dehydrogenase, the ATP synthase, and several TCA cycle enzymes were among the best conserved in the genomes. However, most of the cytochromes required for Fe(III)-reduction were not, including many of the outer-membrane cytochromes. While conservation of cytochromes was poor, an abundance and diversity of cytochromes were found in every genome, with duplications apparent in several species. CONCLUSIONS: These results indicate there is a common pathway for acetate oxidation and energy generation across the family and in the last common ancestor. They also suggest that while cytochromes are important for extracellular electron transport, the path of electrons across the periplasm and outer membrane is variable. This combination of abundant cytochromes with weak sequence conservation suggests they may not be specific terminal reductases, but rather may be important in their heme-bearing capacity, as sinks for electrons between the inner-membrane electron transport chain and the extracellular acceptor." | Bacterial Proton-Translocating ATPases |
Natural carbasugars are an important class of biologically active compounds. Due to their conformational freedom and the subtle difference in spectral characteristics between isomers, often their NMR-based structural assignments are erroneous. It is thus important to validate their structural identity through chemical synthesis. We report the first total syntheses and structural validation of five natural carbasugars, namely, lincitol A, lincitol B, uvacalol I, uvacalol J, and uvacalol K in their racemic forms, from a myo-inositol-derived common intermediate. This intermediate was synthesized by the vinylogous ring opening of myo-inositol orthoester cage under mild acidic conditions in six steps from myo-inositol. From this intermediate, we achieved the syntheses of (+/-)-lincitol A in six steps, (+/-)-lincitol B in seven steps, (+/-)-uvacalol I in five steps, (+/-)-uvacalol J in five steps, and (+/-)-uvacalol K in seven steps. The structure and relative stereochemistry of these natural products were confirmed by comparing the (1)H and (13)C NMR spectra of synthesised natural products with the reported data. These syntheses involved several unprecedented protecting-group manipulations and unexpected reactivities. | Carbasugars |
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