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The synthesis and relevant properties of some cationic polyelectrolytes of the [x,y]-ionene type (i.e., molecules consisting of dimethylammonium charge centers interconnected by alternating alkyl chain segments containing x and y methylene groups) are described. Such hydrophobic ionenes can form intramolecular aggregates and function as micelle-mimetic agents since they mimic the key properties of traditional surfactant micelles (such as hexadecyltrimethylammonium bromide) in many respects. However, the ionenes possess certain important advantages over surfactant micelles. For example, aqueous ionene-containing solutions exhibit much less foaming and analyte molecules can be extracted and recovered from their solutions by use of organic solvents. In this work, some applications of the ionenes in analytical chemistry, such as their use as mobile phase additives for thin-layer chromatographic and capillary electrophoretic separations, as fluorescence enhancement agents, and as a means to catalyze slow spectroscopic derivatization reactions are demonstrated. In addition, other potential advantages concerning the utilization of the micelle-mimetic ionenes in chemical analysis applications are mentioned. | Dimethylamines |
OBJECTIVE: To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death. DESIGN: Descriptive. SETTING: All delivery wards in Stockholm. POPULATION: Stillbirths from 22 completed weeks in Stockholm, Sweden. METHODS: Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated. MAIN OUTCOME MEASURE: The classification and the results of the validation are presented. RESULT: The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa=0.70). CONCLUSIONS: The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death." | Female Urogenital Diseases and Pregnancy Complications |
The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting. To define the role of autophagy in human disease, we analyzed the muscle biopsies of DD patients and monitored autophagy and several autophagy regulators like transcription factor EB (TFEB), a master player in lysosomal biogenesis, and vacuolar protein sorting 15 (VPS15), a critical factor for autophagosome and endosome biogenesis and trafficking. Furthermore, to clarify whether the mechanisms involved are shared by other AVMs, we extended our mechanistic study to a group of adult GSDII patients. Our data show that, similar to GSDII, DD patients display an autophagy block that correlates with the severity of the disease. Both DD and GSDII show accumulation and altered localization of VPS15 in autophagy-incompetent fibers. However, TFEB displays a different pattern between these two lysosomal storage diseases. Although in DD TFEB and downstream targets are activated, in GSDII patients TFEB is inhibited. These findings suggest that these regulatory factors may have an active role in the pathogenesis of these diseases. Therapeutic approaches targeted to normalize these factors and restore the autophagic flux in these patients should therefore be considered." | Vacuolar Sorting Protein VPS15 |
Meiosis and syngamy generate an alternation between two ploidy stages, but the timing of these two processes varies widely across taxa, thereby generating life cycle diversity. One hypothesis suggests that life cycles with long-lived haploid stages are correlated with selfing, asexual reproduction, or both. Though mostly studied in angiosperms, selfing and asexual reproduction are often associated with marginal habitats. Yet, in haploid-diploid macroalgae, these two reproductive modes have subtle but unique consequences whereby predictions from angiosperms may not apply. Along the western Antarctic Peninsula, there is a thriving macroalgal community, providing an opportunity to explore reproductive system variation in haploid-diploid macroalgae at high latitudes where endemism is common. Plocamium sp. is a widespread and abundant red macroalga observed within this ecosystem. We sampled 12 sites during the 2017 and 2018 field seasons and used 10 microsatellite loci to describe the reproductive system. Overall genotypic richness and evenness were high, suggesting sexual reproduction. Eight sites were dominated by tetrasporophytes, but there was strong heterozygote deficiency, suggesting intergametophytic selfing. We observed slight differences in the prevailing reproductive mode among sites, possibly due to local conditions (e.g., disturbance) that may contribute to site-specific variation. It remains to be determined whether high levels of selfing are characteristic of macroalgae more generally at high latitudes, due to the haploid-diploid life cycle, or both. Further investigations of algal life cycles will likely reveal the processes underlying the maintenance of sexual reproduction more broadly across eukaryotes, but more studies of natural populations are required. | Plocamium |
We present evidence that lichen aureus results from extravasation of red blood cells into the dermis caused by incompetence of an underlying perforator vein. The sudden appearance of the lesion suggests a blow out" of the microvasculature of the lower dermis caused by failure of the valves in the perforator vein. This incompetence of the perforator vein induces a permanent reversal in normal blood flow. The consequent continuous high pressure in the cutaneous microvasculature is responsible for long-term leakage of red blood cells. Digestion of the extravasated red cells by macrophages leaves an "auto-tattoo" of insoluble hemosiderin granules, which produce the distinctive golden or burnt orange color of lichen aureus." | Hemosiderin |
The mandibular buccal bifurcation cyst is a cystic lesion occurring on the buccal surface of the permanent mandibular first molar in 6- to 8-year-old children. The purpose of this article was to present a case report of an 8-year-old with a radiolucent area on the permanent mandibular left first molar, with clinical, radiological, and histological characteristics compatible with the pathological entity mentioned. The treatment adopted in this case was enucleation without extraction. The patient is still under observation without any sign of recurrence. | Jaw Diseases |
Birds combat ectoparasites with many defences but the first line of defence is grooming behaviour, which includes preening with the bill and scratching with the feet. Preening has been shown to be very effective against ectoparasites. However, most tests have been with feather lice, which are relatively slow moving. Less is known about the effectiveness of preening as a defence against more mobile and evasive ectoparasites such as hippoboscid flies. Hippoboscids, which feed on blood, have direct effects on the host such asanaemia, as well as indirect effects as vectors of pathogens. Hence, effective defence against hippoboscid flies is important. We used captive Rock Pigeons (Columba livia) to test whether preening behaviour helps to control pigeon flies (Pseudolynchia canariensis). We found that pigeons responded to fly infestation by preening twice as much as pigeons without flies. Preening birds killed twice as many flies over the course of our week-long experiment as birds with impaired preening; however, preening did not kill all of the flies. We also tested the role of the bill overhang, which is critical for effective preening against feather lice, by experimentally removing the overhang and re-measuring the effectiveness of preening against flies. Birds without overhangs were as effective at controlling flies as were birds with overhangs. Overall, we found that preening is effective against mobile hippoboscid flies, yet it does not eliminate them. We discuss the potential impact of preening on the transmission dynamics of blood parasites vectored by hippoboscid flies. | Ectoparasitic Infestations |
Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by alpha-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR. | 1-Naphthylisothiocyanate |
NF-kappaB is a transcription factor that regulates numerous physiological functions, and that is involved in the pathogenesis of various diseases. In the nervous system there is evidence supporting a dual role of NF-kappaB in neurodegenerative diseases; activation of NF-kappaB in neurons promotes their survival, whereas activation in glial and immune cells mediates pathological inflammatory processes. The reason for such a dichotomy lies in the complexity of the NF-kappaB system. Emerging research has begun to dissect the pathways leading to the activation of the different NF-kappaB proteins, and the gene targets of NF-kappaB, in cells of the nervous system. In this article the authors discuss recent findings concerning the roles of NF-kappaB in the pathogenesis of several neurodegenerative disorders, and its potential as a pharmaceutical target for these disorders. | NF-kappa B |
Multiple sclerosis may present an increased risk for venous thromboembolism. Ophthalmological symptoms include loss of vision, visual field loss, changes in color vision, diplopia and nystagmus. First-line treatments for multiple sclerosis are beta-interferon, glatiramer acetate, dimethyl fumarate and teriflunomide. To the best of our knowledge, no ophthalmologic side effects have been reported with glatiramer acetate. We present a woman with multiple sclerosis on glatiramer acetate therapy with a central retinal vein occlusion in the absence of other risk factors. | Retinal Vein Occlusion |
The proper use and economic impact of carboxymaltose iron were evaluated for patients hospitalized in the geriatric wards of a French university hospital from November 2019 to April 2020. Martial supplementation was recommended for 75.7% of the 173 patients who received carboxymaltose iron: 43.4% had a real indication for carboxymaltose iron, while 14.4% could have received sucrose iron and 17.9% could have received per os iron. Compliance with the recommendations would have generated savings of 10,345.80 euros (32.1%). | Glucaric Acid |
We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important." | Familial Primary Pulmonary Hypertension |
The Angiopoietin (Ang)-Tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) axis is an endothelial cell-specific ligand-receptor signaling pathway necessary for vascular and lymphatic development. The Ang-Tie axis is involved in regulating angiogenesis, vascular remodeling, vascular permeability, and inflammation to maintain vascular quiescence. Disruptions in the Ang-Tie axis are involved in many vascular and lymphatic diseases and play an important role in physiological and pathological vascular processes. Given recent advances in the Ang-Tie axis in the vascular and lymphatic systems, this review focuses on the multiple functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, atherosclerosis, ocular angiogenesis, tumor angiogenesis, and metastasis. A summary of relevant therapeutic approaches to the Ang-Tie axis, including therapeutic antibodies, recombinant proteins and small molecule drugs are also discussed. The purpose of this review is to provide new hypotheses and identify potential therapeutic strategies based on the Ang-Tie signaling axis for the treatment of vascular and lymphatic-related diseases. | Angiopoietins |
Ninety-two patients with American Burkitt's lymphoma were studied retrospectively to elucidate the role of surgery in the complications of treatment of Burkitt's lymphoma. All of the patients reviewed had been treated with at least one chemotherapeutic agent. Seventy-five percent of the patients had predominantly abdominal disease that required a laparotomy for diagnosis and treatment when possible. The postoperative complications, such as infections, were not more frequent when compared with other elective surgical procedures. Ten percent of all the patients had episodes of significant gastrointestinal bleeding secondary to disease or to the chemotherapy. One patient was treated surgically, and two patients had fatal hemorrhages. Further abdominal complications that required surgery included intussusception, cholelithiasis, small bowel obstruction, and bowel perforation. The incidence of renal failure because of electrolyte imbalance from tumor lysis syndrome was 30%. One third of these patients required access for dialysis. Ten percent of patients developed hemorrhagic cystitis, but none required surgery. Surgery was necessary in five patients with life-threatening pericardial effusion. Other surgical treatments are also reviewed. It is concluded that Burkitt's lymphoma has a significant cure rate with the appropriate medical and surgical therapies, and that the surgical approach to the disease and its complication should be optimistic and appropriately aggressive. | Burkitt Lymphoma |
BACKGROUND: Research on selenium nanoparticles (SeNPs) in chemical defense and chemotherapy of plants has developed rapidly owing to their high microbial toxicity, environmental safety, and degradability. Pine wilt disease (PWD) threatens pine forests worldwide; however, it is difficult to kill the nematodes (Bursaphelenchus xylophilus) inside the tree that cause PWD using traditional pesticide formulations. SeNPs could be the key to controlling PWD. RESULTS: In this study, approximately 50 nm SeNPs were prepared using a simple and green method, and chitosan was used to increase their biocompatibility and stability. The preparation and characterization results showed that the prepared SeNPs coated with chitosan (SeNPs@CS) were spherical and evenly dispersed. The bioassay results showed that SeNPs@CS had an LC(50) of 15.627 mg L(-1) against B. xylophilus. In addition, the killing mechanism of SeNPs@CS against B. xylophilus was studied. Confocal microscopy and transmission electron microscopy demonstrated that B. xylophilus were killed by reactive oxygen species, and the penetration of nano-form materials to B. xylophilus was higher than that of non-nano-form materials. To verify the effective penetration of SeNPs in pine tissues, Cy5-labeled SeNPs@CS was observed inside pine needles and branches using frozen sections and confocal microscopy. In addition, the cytotoxicity of SeO(2) and SeNPs@CS was tested, and the results showed that the cytotoxicity of SeNPs@CS to MC3T3-E1 cells was reduced. CONCLUSION: These results show that SeNPs are expected to be used as a new strategy for the control of PWD with oxidative damage and high penetration to B. xylophilus and effective target penetration and biosafety. (c) 2022 Society of Chemical Industry. | Xylophilus |
Hard water and elevated ammonia are problems for many United States groundwater drinking water utilities, and some utilities, particularly those in the Midwest, face both challenges. Ion (cation) exchange (IX) is a common treatment technique for hardness reduction (i.e., softening) and may be used to remove ammonia as well, but these constituents may compete in IX and impact overall treatment performance. Few data have been reported on the impact on ammonia concentrations when using IX for softening in full-scale systems. This study investigated four full-scale groundwater treatment plants in Illinois that practice IX for softening (raw water hardness > 220 mg/L as CaCO(3)) and have elevated groundwater ammonia concentrations (> 2 mg N/L). Sampling throughout the year revealed consistent finished water hardness levels but variable ammonia concentrations. Ammonia removal varied and depended on how much water had been treated since the last regeneration. High ammonia removal (sometimes > 90%) occurred in the first half of the IX service cycle, while effluent ammonia concentrations increased compared to the influent (sometimes > 200%) towards the end of the IX cycle (total length 50,000-92,000 gallons [190-350 m(3)]). Ammonia removal efficiency varied among the plants, but the overall trends were similar. Because variable ammonia concentrations may make it difficult to produce a consistent total chlorine residual, they can negatively impact disinfection and water quality in the distribution system. Ammonia concentrations should be considered when designing softening systems to determine regeneration frequency, develop blending strategies, or include an alternative ammonia treatment process before IX softening to produce a more stable and consistent finished water. | Water Softening |
As alternatives to traditional brominated flame retardants, organophosphate flame retardants (OPFRs), especially for organophosphate esters (OPEs) -- the most widely used and investigated OPFRs, have raised people's concern on their environmental and health-related risks over the years. Considering their extensive environmental occurrence and potential adverse effects, precise estimation on the human body burden of OPEs will be conducive to the restrictions on the usage of these compounds scientifically. Biomonitoring research can provide precise information on human exposure to OPEs as it reveals the degree of external exposure from all exposure routes. Knowledge on biotransformation and metabolism of OPEs in the biosystems is of great significance for our understanding of the internal exposure to these compounds. In this study, the biological metabolic processes of nine OPEs prevalent in the environment, involving tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tripropyl phosphate (TPrP), tri-n-butyl phosphate (TnBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPhP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP), are comprehensively reviewed. Specifically, the metabolic pathway, kinetics and mechanism of OPEs are depicted in detail. Under this context, the advances and limitations on biomonitoring of OPE metabolites in human urine are summarized. The requirements of specificity, quantitative stability, high detection frequency/concentration are needed for OPE metabolites to be considered and validated as biomarkers. Thus far, deeper elucidations on the metabolic processes and identification of biomarkers of OPEs are urgently required, given that some OPEs have no suitable biomarkers in human biomonitoring. For better assessment of the body burden of OPEs in humans, reliable and effective methodologies for urine sampling and estimation on internal exposure to OPEs need to be further developed in the future. | Flame Retardants |
The radiation-induced mortality together with the loss of body-weight and development of radiation sickness was studied in young adult Swiss albino mice after exposure to 1500 R of 60Co gamma-radiation in the presence and absence of 2-mercaptopropionyl-glycine (MGP), and results from both the groups were compared. It was found that the time of onset of radiation sickness was delayed in the drug-treated group, the mean survival time was also increased to 6 days as compared to 4.5 days in the untreated control group. These changes showed a direct correlation with the body-weight changes as the loss of weight in the drug-treated group was less marked and more gradual than in the untreated controls. | Tiopronin |
We have identified a homologue of 4-deoxygadusol (core of mycosporine-like amino acids) synthesizing gene (ZP_05036788) from Synechococcus sp. PCC 7335 that was found to have additional functionally unknown N-terminal domain similar to homologues from dinoflagellates based on the ClustalW analysis. Phylogenetic analysis revealed that Synechococcus sp. (ZP_05036788) makes a clade together with dinoflagellates and was closest to the Oxyrrhis marina. This study shows for the first time that N-terminal additional sequences that possess upstream plastid targeting sequence in Heterocapsa triquetra and Karlodinium micrum were already evolved in cyanobacteria, and plastid targeting sequence were evolved later in dinoflagellates after divergence from chloroplast lacking Oxyrrhis marina. Thus, MAAs synthesizing genes were transferred from cyanobacteria to dinoflagellates and possibly Synechococcus sp. PCC 7335 acted as a donor during lateral gene transfer event. In addition, we also tried to mutate 4-deoxygadusol synthesizing gene (YP_324358) of Anabaena variabilis PCC 7937 by homologous recombination, however, all approaches to get complete segregation of the mutants from the wild-type were unsuccessful, showing the essentiality of YP_324358 for A. variabilis PCC 7937. | Anabaena variabilis |
BACKGROUND: Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil, a widely used immunosuppressant. Numerous studies have developed limited sampling strategies (LSSs) to predict MPA AUC in solid organ transplant recipients. OBJECTIVES: To systematically review and assess quality of literature pertaining to MPA LSSs, evaluate clinical implications and provide suggestions for future research. METHODS: Literature searches of MEDLINE (1966 - May 2009) and EMBASE (1980 - May 2009) for English articles in solid organ transplantation, along with manual review of article references were conducted. Included articles were categorized according to criteria adapted from levels of evidence of the US Preventative Services Task Force. RESULTS: Of a total of 29 studies identified, 20 were in kidney, 4 in heart, 4 in liver and 1 in lung transplantation and 7 were in pediatrics. A total of 14 studies were deemed to be Level I evidence studies, 3 were Level II-1, 1 was Level II-2 and 11 were Level III. CONCLUSIONS: Although various LSSs that are well correlated to MPA AUC while being relatively unbiased and precise to predict MPA AUC have been developed, further research is needed to determine validity of these LSSs in a variety of patient populations and to determine if these LSSs improve patient outcomes. | Mycophenolic Acid |
A new method for intratypic antigenic differentiation of poliovirus strains has been developed. The method is based on the use of cross-absorbed sera in neutralization tests where virus is titrated by the cytopathic effect. Qualitative differences between the antigenic structure of vaccine and wild" strains as well as between some "wild" strains of the same serologic type have been found. The method may be used in practical laboratories." | Cytopathogenic Effect, Viral |
The beneficial effects of ultraviolet (UV) radiation on atopic dermatitis has been appreciated for many years. While broadband UVB and psoralen UVA have been the mainstay of phototherapy for some time, the past 5 years have seen the introduction of phototherapeutic modalities, including UVA-1 and 311nm UVB. The best modality and mode of usage is dependent on the type of atopic dermatitis, severity and body site. T lymphocytes play an important role in disease pathogenesis and UV radiation has profound effects on skin and systemic immune responses. | PUVA Therapy |
Studies have investigated the association between social vulnerability and SARS-CoV-2 incidence. However, few studies have examined small geographic units such as census tracts, examined geographic regions with large numbers of Hispanic and Black populations, controlled for testing rates, and incorporated stay-at-home measures into their analyses. Understanding the relationship between social vulnerability and SARS-CoV-2 incidence is critical to understanding the interplay between social determinants and implementing risk mitigation guidelines to curtail the spread of infectious diseases. The objective of this study was to examine the relationship between CDC's Social Vulnerability Index (SVI) and SARS-CoV-2 incidence while controlling for testing rates and the proportion of those who stayed completely at home among 783 Harris County, Texas census tracts. SARS-CoV-2 incidence data were collected between May 15 and October 1, 2020. The SVI and its themes were the primary exposures. Median percent time at home was used as a covariate to measure the effect of staying at home on the association between social vulnerability and SARS-CoV-2 incidence. Data were analyzed using Kruskal Wallis and negative binomial regressions (NBR) controlling for testing rates and staying at home. Results showed that a unit increase in the SVI score and the SVI themes were associated with significant increases in SARS-CoV-2 incidence. The incidence risk ratio (IRR) was 1.090 (95% CI, 1.082, 1.098) for the overall SVI; 1.107 (95% CI, 1.098, 1.115) for minority status/language; 1.090 (95% CI, 1.083, 1.098) for socioeconomic; 1.060 (95% CI, 1.050, 1.071) for household composition/disability, and 1.057 (95% CI, 1.047, 1.066) for housing type/transportation. When controlling for stay-at-home, the association between SVI themes and SARS-CoV-2 incidence remained significant. In the NBR model that included all four SVI themes, only the socioeconomic and minority status/language themes remained significantly associated with SARS-CoV-2 incidence. Community-level infections were not explained by a communities' inability to stay at home. These findings suggest that community-level social vulnerability, such as socioeconomic status, language barriers, use of public transportation, and housing density may play a role in the risk of SARS-CoV-2 infection regardless of the ability of some communities to stay at home because of the need to work or other reasons. | Census Tract |
OBJECTIVES: To investigate whether serum amylase can predict the recovery of salivary volume and determine the correlation of the level of cytokines, including epidermal growth factor, hepatocyte growth factor and keratinocyte growth factor, with oral mucositis during chemoradiotherapy for oral cancer. SUBJECTS AND METHODS: This study included 84 patients treated with preoperative chemoradiotherapy followed by curative surgery, following a phase II study protocol. We measured and analysed the correlation of the stimulated saliva volume, serum amylase and cytokines in resting saliva at baseline and 1 month after chemoradiotherapy with oral mucositis levels. RESULTS: We observed a negative correlation between the serum amylase level at the beginning of chemoradiotherapy and the stimulated saliva volume at 1 month after chemoradiotherapy (p = .03). Epidermal growth factor in resting saliva was significantly reduced after chemoradiotherapy (p < .01). The incidence of severe oral mucositis during chemoradiotherapy was significantly higher and negatively associated with the epidermal growth factor and keratinocyte growth factor levels (p = .04, p = .05). CONCLUSIONS: The serum amylase level at the beginning of chemoradiotherapy may be a predictor of the recovery of the saliva volume. Furthermore, cytokines such as epidermal growth factor and keratinocyte growth factor in resting saliva affect the development of oral mucositis during chemoradiotherapy. | Chemoradiotherapy |
To achieve a structural context for the analysis of G-protein coupled receptor (GPCR) oligomers, molecular modeling must be used to predict the corresponding interaction interfaces. The task is complicated by the paucity of detailed structural data at atomic resolution, and the large number of possible modes in which the bundles of seven transmembrane (TM) segments of the interacting GPCR monomers can be packed together into dimers and/or higher-order oligomers. Approaches and tools offered by bioinformatics can be used to reduce the complexity of this task and, combined with computational modeling, can serve to yield testable predictions for the structural properties of oligomers. Most of the bioinformatics methods take advantage of the evolutionary relation that exists among GPCRs, as expressed in their sequences and measurable in the common elements of their structural and functional features. These common elements are responsible for the presence of detectable patterns of motifs and correlated mutations evident from the alignment of the sequences of these complex biological systems. The decoding of these patterns in terms of structural and functional determinants can provide indications about the most likely interfaces of dimerization/oligomerization of GPCRs. We review here the main approaches from bioinformatics, enhanced by computational molecular modeling, that have been used to predict likely interfaces of dimerization/oligomerization of GPCRs, and compare results from their application to rhodopsin-like GPCRs. A compilation of the most frequently predicted GPCR oligomerization interfaces points to specific regions of TMs 4-6. | Receptors, G-Protein-Coupled |
Acquisition of a behavioral response motivated by shock was enhanced in rats chronically treated with yeast ribonucleic acid, and resistance to extinction was greater in rats so treated than in controls. This extends the role of ribonucleic acid to include a behavioral effect in laboratory mammals treated with a purified preparation from yeast. | Conditioning, Psychological |
Autism is a behaviorally defined neurodevelopmental disease characterized by social communication and social interaction deficits, as well as repetitive behaviors and restricted interests. Although the causes of autism are extremely complex, involving genes, environments and gene-environment interactions, genetic mutations are the important risk factors. For this reason, preclinical research is now shifting into focusing on generating transgenic and knockout models, especially using macaques, which are the closest relatives to humans. In spite of unique advantages of macaques over rodents in both functionally specialized brain structures and highly sophisticated social behaviors, the limited availability of phenotype screening tools restricts their translational utility. Here, this review focuses specially on behavioral phenotyping assays for macaque models of autism. In the first part, the existing behavioral tests are discussed, and the second part is devoted to some few, in our view, very promising tests of new developments. In years to come, we should develop macaque models with high construct validity, improve face validity by designing more specialized behavioral screening tools, strengthen collaborative efforts between rodent and macaque models, and ultimately translate the results from animal models into human clinical trials. | Behavior Rating Scale |
Fructooligosaccharides (FOS) are prebiotic substances found in several vegetable or natural foods. The main commercial production of FOS comes from enzymatic transformation of sucrose by the microbial enzyme fructosyltransferase. The development of more efficient enzymes, with high activity and stability, is required and this has attracted the interest of biotechnologists and microbiologists with production by several microorganisms being studied. This article reviews and discusses FOS chemical structure, enzyme characteristics, the nomenclature, producer microorganisms and enzyme production both in solid state fermentation and submerged cultivation. | Aspergillus |
Reactive oxygen species (ROS) generated in aerobic metabolism and oxidative stress lead to macromolecules damage, such as to proteins, lipids, and DNA, which can be eliminated by the redox buffer mycothiol (AcCys-GlcN-Ins, MSH). Myo-inositol-phosphate synthase (Ino-1) catalyzes the first committed step in the synthesis of MSH, thus playing a critical role in the growth of the organism. Although Ino-1s have been systematically studied in eukaryotes, their physiological and biochemical functions remain largely unknown in bacteria. In this study, we report that Ino-1 plays an important role in oxidative stress resistance in the gram-positive Actinobacteria Corynebacterium glutamicum. Deletion of the ino-1 gene resulted in a decrease in cell viability, an increase in ROS production, and the aggravation of protein carbonylation levels under various stress conditions. The physiological roles of Ino-1 in the resistance to oxidative stresses were corroborated by the absence of MSH in the Deltaino-1 mutant. In addition, we found that the homologous expression of Ino-1 in C. glutamicum yielded a functionally active protein, while when expressed in Escherichia coliBL21(DE3), it lacked measurable activity. An examination of the molecular mass (Mr) suggested that Ino-1 expressed in E. coliBL21(DE3) was not folded in a catalytically competent conformation. Together, the results unequivocally showed that Ino-1 was important for the mediation of oxidative resistance by C. glutamicum." | Myo-Inositol-1-Phosphate Synthase |
Four mitochondrial proteins have been identified that immunoprecipitate with the mammalian inhibitor of apoptosis (IAP) protein XIAP. Each of them interacts via a processed amino terminus that resembles those of the insect pro-apoptotic IAP binding proteins Grim, HID, Reaper, and Sickle. Two, Diablo/Smac and HrtA2/Omi, have been extensively characterized. Both Diablo and HtrA2 can bind to IAPs and promote apoptosis when over-expressed in transfected cells, but unlike the insect IAP antagonists, to date there is scant evidence that they are important regulators of apoptosis in more physiological circumstances." | High-Temperature Requirement A Serine Peptidase 2 |
Midline granuloma includes diverse clinicopathological entities, such as Wegener granulomatosis, polymorphic reticulosis, lethal midline granuloma and conventional malignant lymphoma of the nose usually of B-cell origin. The authors describe five patients with LMG clinically and pathologically typical. Using an extensive panel of monoclonal antibodies, they demonstrate an activate" T-cell phenotype observed on the initial lesion of the face in one patient, similar to that found in two patients with LMG but studied after dissemination in peripheral T-cell lymphoma. Furthermore, many atypical cells were found in LMG, and stained with the Ki-67 monoclonal antibody, a marker of proliferating cells. These findings support the view that LMG is closely related to T-cell malignancies. Two of them were treated with recombinant Interferon alpha 2a followed by a response rapidly objective. Immunohistologic studies are very important for confirming the T-cell origin of such a disease and for selecting patients to be treated with Interferon alpha." | Granuloma, Lethal Midline |
Inherited diseases of renal phosphate handling lead to urinary phosphate wasting and depletion of total body phosphorus stores. Clinical sequelae of inherited disorders that are associated with increased urinary phosphate excretion are deleterious and can lead to abnormal skeletal growth and deformities. This Review describes hereditary disorders of renal phosphate wasting taking into account developments in our understanding of renal phosphate handling from the last decade. The cloning of genes involved in these disorders and further studies on their pathophysiological mechanisms have given important insights in to how phosphatonins, such as FGF-23, regulate renal phosphate reabsorption in health and disease. X-linked dominant hypophosphatemic rickets results from mutation of a metalloprotease (PHEX) that has an unidentified role in FGF-23 degradation. Mutation of an RXXR proteolytic cleavage site in FGF-23 prevents degradation and increases circulating levels of FGF-23 in autosomal dominant hypophosphatemic rickets. FGF-23 acts to remove sodium phosphate co-transporters from the luminal membrane of proximal tubular cells with resultant renal phosphate wasting. Loss of function mutations in genes encoding the transporters NaPi-IIc and NaPi-IIa also result in renal phosphate wasting and rickets." | Familial Hypophosphatemic Rickets |
Granzyme A (GzmA) was first identified as a cytotoxic T lymphocyte protease protein with limited tissue expression. A number of cellular proteins are known to be cleaved by GzmA, and its function is to induce apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates during apoptotic cell death. Here, we demonstrated that histone H4 was cleaved by GzmA during staurosporine-induced cell death; however, in the presence of caspase inhibitors, staurosporine-treated Raji cells underwent necroptosis instead of apoptosis. Furthermore, histone H4 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. These results suggest that histone H4 is a novel substrate for GzmA in staurosporine-induced cells. [BMB Reports 2016; 49(10): 560-565]. | Staurosporine |
A properly operated death investigation system (DIS) serves multiple stakeholders. Law enforcement, public health departments and members of the public, benefit in various ways from the information that it provides. This information must be collected systematically and efficiently. The system must also be flexible enough to respond to pressures on its resources such as occurs during mass disasters. These obligations on a DIS require an investment of public money. However even in affluent Western countries the recent world economic crisis has led to a cut in spending on public services that affect both the healthcare system and services associated with death investigation. Although pathologists and other stake holders (judiciary, police, families) would like to see death investigations conducted to international standards, the fact is that policy makers in resource limited countries face additional population health and sociopolitical pressures which generally result in very little funding for the service. The purpose of this paper is to review some of the challenges that impede the proper functioning of a death investigation system in resource limited countries in Sub-Saharan Africa and the Caribbean. Possible solutions are discussed. | Morgue |
Mitochondria are metabolic hubs within mammalian cells and demonstrate significant metabolic plasticity. In oxygenated environments with ample carbohydrate, amino acid, and lipid sources, they are able to use the tricarboxylic acid cycle for the production of anabolic metabolites and ATP. However, in conditions where oxygen becomes limiting for oxidative phosphorylation, they can rapidly signal to increase cytosolic glycolytic ATP production, while awaiting hypoxia-induced changes in the proteome mediated by the activity of transcription factors such as hypoxia-inducible factor 1. Hypoxia is a well-described phenotype of most cancers, driving many aspects of malignancy. Improving our understanding of how mitochondria change their metabolism in response to this stimulus may therefore elicit the design of new selective therapies. Many of the recent advances in our understanding of mitochondrial metabolic plasticity have been acquired through investigations of cancer-associated mutations in metabolic enzymes, including succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. This review will describe how metabolic perturbations induced by hypoxia and mutations in these enzymes have informed our knowledge in the control of mitochondrial metabolism, and will examine what this may mean for the biology of the cancers in which these mutations are observed. WIREs Syst Biol Med 2016, 8:272-285. doi: 10.1002/wsbm.1334 For further resources related to this article, please visit the WIREs website. | Fumarate Hydratase |
The optimal workforce model for surgery has been much debated historically; in particular, whether there should be a recognised role for those successfully completing training employed as non-Consultant grade specialists. This role has been termed the 'sub-consultant' grade. This paper discusses historical and future career structures in surgery, draws international comparisons, and presents the results of a national trainee survey examining the post-Certificate of Completion of Training (CCT) non-consultant specialist grade. Junior doctors in surgical training (i.e. pre-CCT) were invited to participate in an electronic, 38-item, self-administered national training survey. Of 1710 questionnaires submitted, 1365 were appropriately completed and included in the analysis. Regarding the question 'Do you feel that there is a role in the surgical workforce for a post-CCT non-consultant specialist (sub-consultant") grade in surgery?', 56.0% felt there was no role, 31.1% felt there was a role and 12.8% were uncertain. Only 12.6% of respondents would consider applying for such a post, while 72.4% would not and 15.0% were uncertain. Paediatric (23.3%), general (15.7%) and neurosurgery (11.6%) were the specialties with the highest proportions of trainees prepared to consider applying for such a role. For both questions, there was a significant gender difference in responses (p < 0.0001, Chi-square test) with female trainees more likely to consider applying. Overall 50.8% of respondents felt that the introduction of a post-CCT non-consultant specialist grade would impact positively upon service provision, however, only 21.6% felt it would have a positive impact on patient care, 13.9% a positive impact on surgical training, 11.1% a positive impact on the surgical profession and just 7.9% a positive impact on their surgical career. This survey indicates that the introduction of a 'sub-consultant' grade for surgeons who have completed training would be unpopular, with the majority believing it would be to the detriment of both patient care and surgical training. Changes to surgical career structures must be made in the interests of patient safety and quality, and on this basis ASiT supports the continued provision of primarily Consultant-delivered care." | General Surgery |
PURPOSE OF REVIEW: Since its approval in November 2018, venetoclax with a hypomethylating agent backbone has shown promising efficacy for older, newly diagnosed acute myeloid leukemia (AML) patients who are unfit for standard intensive induction chemotherapy. This regimen is well tolerated, allows for deep and durable responses and may be increasing the prevalence of the disease. Although there is justifiable excitement, it remains to be seen to what extent venetoclax-based regimens, as they are currently administered, will have a long-term impact on the treatment of AML. This review aims to evaluate the strengths of the regimen that deserve enthusiasm as well as its shortcomings, which should be viewed as opportunities for improvement. RECENT FINDINGS: The clinical efficacy as well as the novel mechanism of venetoclax with hypomethylating agents will be described here. SUMMARY: Venetoclax with hypomethylating agents do not represent the holy grail for AML, but this regimen is a promising step in the right direction, and proof of principle that a low-intensity therapy can have a major impact on this disease." | Bridged Bicyclo Compounds, Heterocyclic |
Over the past three years the Worcester Youth Guidance Center has developed a series of mental health programs directed to the Hispanic community of Worcester, Massachusetts. The model for these programs has been that of strategic intervention. This approach was based upon knowledge gained from the literature and extensive exploratory contacts with key Hispanic leaders. The Center's Hispanic Program consists of five components: (1) community education and training. (2) clinical consultation, (3) program consultation, (4) research, and (5) clinical intervention and case management. This article describes these components in detail and presents a rationale for strategic intervention. | Child Guidance Clinics |
Vitamin-K-dependent protein S is an anticoagulant plasma protein which functions as cofactor to activated protein C (APC) in the degradation of coagulation factors Va and VIIIa. In addition, it interacts with C4b-binding protein (C4BP), a regulator of the complement system. Using a human protein S cDNA clone as probe, cDNA clones for rabbit protein S were isolated from a rabbit liver cDNA library. The cDNA sequence encoded the mature protein S and 12 residues of the leader sequence. The amino acid sequence of the single-chain 634-amino-acid-residue-long rabbit protein S molecule was 82% and 81% identical to those of human and bovine protein S, respectively. Northern blotting demonstrated protein S mRNA not only in liver but also in reproductive organs (testis, ovary and uterus), in lung and brain. Recombinant rabbit protein S was expressed in eucaryotic cells and found to be post-translationally modified, i.e. it had the correct amino terminus, contained N-linked carbohydrate side chains, gamma-carboxyglutamic acid residues and beta-hydroxylated aspartic acid and asparagine residues. Recombinant rabbit protein S bound calcium like its human counterpart, as judged by its migration in the presence of calcium on agarose-gel electrophoresis. Rabbit protein S has been reported to be species specific with respect to its interaction with APC and not to function with bovine APC. However, we found it to act as cofactor to both human and bovine APC, albeit it was somewhat more efficient with human than with bovine APC. Rabbit protein S, like its human and bovine counterparts, bound human C4BP in a reaction which was associated with the loss of its APC-cofactor activity. However, unlike human plasma, rabbit plasma appeared to contain only the free form of protein S as a radiolabeled rabbit protein S tracer added to rabbit plasma migrated as free protein S on agarose-gel electrophoresis. Addition of human C4BP to rabbit plasma resulted in the formation of a C4BP-protein-S complex, suggesting an explanation for the absence of complexed protein S in rabbit plasma to be sought for in the structure of rabbit C4BP. | Protein S |
Immune homeostasis is maintained by a precise balance between effector immune cells and regulatory immune cells. Chronic deviations from immune homeostasis, driven by a greater ratio of effector to regulatory cues, can promote the development and propagation of inflammatory diseases/conditions (i.e., autoimmune diseases, transplant rejection, etc.). Current methods to treat chronic inflammation rely upon systemic administration of non-specific small molecules, resulting in broad immunosuppression with unwanted side effects. Consequently, recent studies have developed more localized and specific immunomodulatory approaches to treat inflammation through the use of local biomaterial-based delivery systems. In particular, this review focuses on (1) local biomaterial-based delivery systems, (2) common materials used for polymeric-delivery systems and (3) emerging immunomodulatory trends used to treat inflammation with increased specificity. | Immunomodulation |
Four flavonoids including (2S)-3',4'-methylenedioxy-5,7-dimethoxyflavan and hispidulin 7-(6-E-p-coumaroyl-beta-D-glucopyranoside), and one tocopherol were isolated from the capitulum of Eriocaulon buergerianum KOERN. Their structures were established by spectral and chemical evidence. | Eriocaulaceae |
With recent rapid advances in mapping of the human genome, including highly polymorphic and closely linked markers, studies of marker associations with disease are increasingly relevant for mapping disease genes. The use of nuclear-family data in association studies was initially developed to avoid possible ethnic mismatching between patients and randomly ascertained controls. The parental marker alleles not transmitted to an affected child or never transmitted to an affected sib pair form the so-called AFBAC (affected family-based controls) population. In this paper, the theoretical foundation of the AFBAC method is proved for any single-locus model of disease and for any nuclear family-based ascertainment scheme. In a random-mating population, when there is a marker association with disease, the AFBAC population provides an unbiased estimate of the overall population (control) marker alleles when the recombination fraction (theta) between the marker and disease genes is sufficiently small that it can be taken as zero (theta = 0). With population stratification, only marker associations present in the subpopulations will be detected with family-based analyses. Of more importance, however, is the fact that, when theta not equal to 0, differences between transmitted parental (patient) marker allele frequencies and non- or never-transmitted parental marker allele frequencies (implying a marker association with disease) can only be observed for marker genes linked to a disease gene (theta < 1/2). Thus, associations of unlinked marker loci with disease at the population level, caused by population stratification, migration, or admixture, are eliminated. This validates the use of family-based association tests as an appropriate strategy for mapping disease genes. | Genetic Linkage |
Verrucous psoriasis is characterized clinically by symmetric hypertrophic verrucous plaques on an erythematous base and histologically by overlapping features of both verrucae and psoriasis with negative human papilloma virus (HPV) studies. A 46-year-old African-American male presented with an 8-year history of extensive malodorous, symmetric, verrucous plaques manifesting as erythroderma. Biopsies showed epidermal hyperplasia and papillomatosis, parakeratosis with neutrophils, and dilated vessels in the dermal papillae. The polymerase chain reaction of lesional skin was negative for HPV DNA, and T-cell gene rearrangement was negative. The patient was diagnosed with erythrodermic verrucous psoriasis. Verrucous psoriasis is a rare presentation of psoriasis and has only been reported as a localized variant. To the authors' knowledge, erythrodermic verrucous psoriasis has not been reported. This presentation was a diagnostic and therapeutic challenge and serves to heighten the awareness of a unique variant of psoriasis. | Dermatitis, Exfoliative |
The Heerfordt syndrome is characterized by fever, uveitis, swelling of parotid gland and facial nerve palsy, and 53 cases have been reported in Japan until 2000. In the present review, we mainly focused on those clinical cases reported. Most patients were between 20 and 40 years of age, and females appeared to have greater risk than males. The definite diagnosis of this syndrome is established histologically according to sarcoidosis. In addition 67 gallium scan is helpful for diagnosis, and it shows increased uptake of Ga to the ophthal lesion, parotid glands and hilar lesions. Therapeutic trial with prednisolone is sometimes required especially for facial palsy. | Uveoparotid Fever |
The goal of this study is to supplement the composition and nature of sphingophosphonolipids diversity from edible mollusks (Mytilus galloprovincialis, Eobania vermiculata) and from jellyfish Pelagia noctiluca, organisms rich in phosphonolipids. M. galloprovincialis contained a major ceramide 2-aminoethylphosphonate (CAEP-IM) and a minor ceramide that was detected chromatographically as the methyl analog (CAEP-IIM). In CAEP-IM, saturated fatty acids (FA) of 14, 16 and 18 carbons amounted to 68.8%; also 52.5% dihydroxy bases were detected. On thin layer chromatography, the Rf for CAEP-IIM was smaller than the Rf for CAEP-IM because of an increase of 22.0% in 2OH-16:0 FA, plus 29.2% trihydroxy bases (phytosphingosine). Similarly, a ceramide 2-methylaminoethylphosphonate (CAEP-IIE, 1.5% of phospholipids) was quantitated in Eobania (apart from the previously reported major CAEP, 7.6%). In CAEP-IIE, saturated and hydroxy FA of 14, 16 and 18 carbons amounted to 37.0 and 37.8%; 29.1% dihydroxy and 23.0% trihydroxy bases were detected in the same molecule. Eobania's unsaturated FA percentages (total lipids: 66.3, polar: 47.5, neutral: 59.0) were similar to those previously found for other land snails. A suite of two minor CAEP (CAEP-IIP, CAEP-IIIP) was quantitated in Pelagia at 2.0 and 1.3% of phospholipids (apart from the previously reported major CAEP, 21.0%) identified chromatographically as methyl analogs. In CAEP-IIP, saturated FA of 14, 16, 18 and 19 carbons amounted to 56.0%; 12.6% dihydroxy and 34.1% trihydroxy bases were also detected in CAEP-IIP. The Rf CAEP-IIIP<Rf CAEP-IIP owing to an increase of +8.5% of hydroxy FA and +12.3% of trihydroxy bases. The compositions of CAEP-IIM and CAEP-IIE appear to be specific of each organism, while the composition of molluscan or jellyfish major sphingophosphonolipids appears not specific. | Aminoethylphosphonic Acid |
Usher syndrome (USH) is the most common form of deaf-blindness, with an estimated prevalence of 4.4 to 16.6 per 100,000 people worldwide. The most common form of USH is type IIA (USH2A), which is caused by homozygous or compound heterozygous mutations in the USH2A gene and accounts for around half of all USH cases. USH2A patients show moderate to severe hearing loss from birth, with diagnosis of retinitis pigmentosa in the second decade of life and variable vestibular involvement. Although hearing aids or cochlear implants can provide some mitigation of hearing deficits, there are currently no treatments aimed at preventing or restoring vision loss in USH2A patients. In this review, we first provide an overview of the molecular biology of the USH2A gene and its protein isoforms, which include a transmembrane protein (TM usherin) and an extracellular protein (EC usherin). The role of these proteins in the inner ear and retina and their impact on the pathogenesis of USH2A is discussed. We review animal cell-derived and patient cell-derived models currently used in USH2A research and conclude with an overview of potential treatment strategies currently in preclinical development and clinical trials. | Usher Syndromes |
The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn't code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets. | Ubiquitination |
BACKGROUND AND PURPOSE: Vascular 'denervation' hyper-reactivity has generally been investigated 1-2 weeks after administration of chemicals that temporarily prevent transmitter release, but do not necessarily inactivate the neuronal noradrenaline transporters (NETs). We have investigated the reactivity of rat tail arteries over longer periods after removing the terminals by surgical denervation. EXPERIMENTAL APPROACH: Two and 7 weeks after denervation, myography was used to assess contractions of isolated arterial segments to phenylephrine, methoxamine, clonidine, vasopressin and angiotensin II (AII). Denervation was confirmed by lack of tyrosine hydroxylase immunoreactive nerve terminals. KEY RESULTS: The NET inhibitor, desmethylimipramine, increased the pEC(50) for phenylephrine in control, but not denervated arteries after both 2 and 7 weeks. Relative to controls, pEC(50)s for phenylephrine (with desmethylimipramine), methoxamine, clonidine and vasopressin were increased at 2 but not 7 weeks after denervation. The pEC(50) for phenylephrine in the absence of desmethylimipramine was greater than control after both 2 and 7 weeks' denervation. The maximum contraction to vasopressin was larger than in controls at 2 but not 7 weeks after denervation, whereas contractions to AII were markedly enhanced at both time points. CONCLUSIONS AND IMPLICATIONS: Increased vascular reactivity to alpha(1)- and alpha(2)-adrenoceptor agonists, and vasopressin is transient following denervation. After 7 weeks, increased reactivity to phenylephrine can be entirely accounted for by the loss of NETs. Maintained supersensitivity to AII indicates that denervation differentially and selectively affects vascular reactivity to circulating vasoconstrictor agents. This might explain persistent vasoconstriction in denervated skin of humans after nerve injuries." | Adrenergic alpha-1 Receptor Agonists |
The effect of milk extract of Semecarpus anacardium Linn. nut milk extract (SA) was studied to gain some insight into this intriguing disease with reference to collagen metabolism. Arthritis was induced in rats by injecting Freund's complete adjuvant containing 10mg of heat killed mycobacterium tuberculosis in 1 ml paraffin oil (0.1 ml) into the left hind paw of the rat intradermally. After 14 days of induction, SA (150 mg/kg body weight/day) was administered orally by gastric intubations for 14 days. Decreased levels of collagen and glycosaminoglycans (GAGS) components (chondroitin sulphate, heparan sulphate, hyaluronic acid) and increase in the levels of connective tissue degrading lysosomal glycohydrolases such as acid phosphatase, beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin-D observed in arthritic animals were reverted back to near normal levels upon treatment with SA. The drug effectively regulated the uriniray markers of collagen metabolism namely hexosamine, hexuronic acid, hydroxyproline and total GAGS. Electron microscopic studies also revealed the protective effect of SA. Hence, it can be suggested that SA very effectively regulate the collagen metabolism that derange during arthritic condition. | Semecarpus |
Chelation and removal of cadmium from rats which were exposed to cadmium by multiple injections were studied in vivo after injection of two different compounds, 2,3-dimercaptopropanol (BAL) and diethylenetriamine pentaacetic acid (DTPA). Rats were injected i.p. with 1 mg of Cd/kg as 109CdCl2 daily for 4 days and 3 days after the last injection, they were treated with the chelating agents alone or in combination 5 days in a week for 2 weeks. BAL (50 mg/kg) alone or in combination with DTPA (50 mg/kg) was effective in removing cadmium from the body without increasing the level of cadmium in the kidney, the critical organ in cadmium toxicity. After treatment with BAL alone and BAL-DTPA, cadmium was excreted mainly in the feces with marked decrease in hepatic and renal concentrations of both cadmium and metallothionein. Injection of DTPA alone increased the urinary excretion of cadmium without any significant change in tissue cadmium. Although the urinary excretion of zinc was increased after injection of DTPA and also BAL-DTPA, there was no change in the tissue levels of zinc and copper. The results of this study suggest the potential use of BAL or BAL-DTPA combination as a mode of chelation of cadmium from the body under proper experimental conditions in chronic cadmium poisoning. It may be possible to prevent tubular damage in the kidney, the critical organ in cadmium toxicity by this treatment. | Cadmium Poisoning |
It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule. | Pregnenediones |
Diamond-Blackfan anemia (DBA) is a congenital anemia and a broad spectrum of developmental abnormalities that presents soon after birth. The anemia is due to a failure of erythropoiesis with normal platelet and myeloid lineages. Approximately 10-20% of DBA cases are inherited. Genetic studies have identified heterozygous mutations in at least one of eight ribosomal protein genes in up to 50% of cases. Mutations in RPL5 and RPL11 are at a high risk for developing malformation. Especially, mutations in RPL5 are associated with multiple physical abnormalities, including cleft lip/plate and thumb and heart anomalies. Recently, the 5q- syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation, is caused by a somatically acquired deletion of chromosome 5q, which results in haploinsufficiency of RPS14. These data indicate that abnormalities in ribosome function are broadly implicated in both congenital and acquired bone marrow failure syndrome in humans." | Anemia, Hypoplastic, Congenital |
RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of TNF receptor-associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor, osteoprotegerin (OPG), but also has additional more complex levels of regulation. It is crucial for the differentiation of bone-resorbing osteoclasts and is deregulated in disease processes such as osteoporosis and cancer bone metastasis. Cells expressing RANK and RANKL are commonly found in the tumor environment. In many tumor types, the RANK/RANKL pathway is overexpressed, and this is in most cases correlated with poor prognosis. RANK signaling plays an important role in the innate and adaptive immune response, generates regulatory T (Treg) cells, and increases the production of cytokines. It is also involved in chemo resistance in vitro. Recent evidence suggests that RANKL blockade improves the efficacy of anti-CTLA-4 antibodies against solid tumors and experimental metastasis. Therefore, there is increasing interest to use RANKL inhibition as an immunomodulatory strategy in an attempt to make immune-resistant tumor responsive to immune therapy." | Receptor Activator of Nuclear Factor-kappa B |
Vascular endothelial growth factor A (VEGF-A) is a promoter of neovascularization and thus a popular therapeutic target for diseases involving excessive growth of blood vessels. In this study, we explored the potential of the disaccharide sucrose octasulfate (SOS) to alter VEGF165 diffusion through Descemet's membrane. Descemet's membranes were isolated from bovine eyes and used as a barrier between two chambers of a diffusion apparatus to measure VEGF transport. Diffusion studies revealed a dramatic increase in VEGF165 transport in the presence of SOS, with little diffusion of VEGF165 across the membrane over a 10-h time course in the absence of SOS. Diffusion studies with VEGF121, a non-heparin binding variant of VEGF, showed robust diffusion with or without SOS. To determine a possible mechanism, we measured the ability of SOS to inhibit VEGF interactions with extracellular matrix (ECM), using cell-free and cell surface binding assays. Binding studies showed SOS had no effect on VEGF165 binding to either heparin-coated plates or endothelial cell surfaces at less than mg/ml concentrations. In contrast, we show that SOS inhibited VEGF165 binding to fibronectin in a dose dependent manner and dramatically accelerated the rate of release of VEGF165 from fibronectin. SOS also inhibited the binding of VEGF165 to fibronectin-rich ECM deposited by vascular smooth muscle cells. These results suggest that fibronectin-rich extracellular matrices serve as barriers to VEGF165 diffusion by providing a network of binding sites that can trap and sequester the protein. Since the content of Descemet's membrane is typical of many basement membranes it is possible that they serve throughout the body as formidable barriers to VEGF165 diffusion and tightly regulate its bioavailability and distribution within tissues. | Facilitated Diffusion |
Overconfidence has been identified as a source of suboptimal decision making in many real-life domains, with often far-reaching consequences. This study identifies a mechanism that can cause overconfidence and demonstrates a simple, effective countermeasure in an incentive-compatible experimental study. We observed that joy induced overconfidence if the reason for joy (an unexpected gift) was unrelated to the judgment task and if participants were not made specifically aware of this mood manipulation. In contrast, we observed well-calibrated judgments among participants in a control group who were in their resting mood. Furthermore, we found well-calibrated judgments among participants who received the joyful mood induction together with questions that forced them to reflect on their current mood and the (ir)relevance of its cause to our judgment tasks. Our findings suggest that being aware of one's positive mood and the reason for that mood may effectively reduce overconfidence for a short period. | Happiness |
Faith in paranormal cures has always been the last hope of many sufferers from chronic or incurable diseases. Magico-religious rituals of healing are still around, but some have been replaced by pseudo-scientific systems, thinly disguising old superstitions in new obscurantism, more appealing to the half-educated. In medical quackery, inventiveness seems to be limitless, and only the main paranormal healing systems can be reviewed here. The increasing popularity of 'alternative' healing indicates the extent of dissatisfaction with dehumanising aspects of modern, technological medicine and its preoccupation with curing the curable at the expense of caring for the incurable. This leaves the sufferers, and also healthy people labelled with non-existent diseases, bleeding prey for the sharks roving the seas of medical ignorance. | Radiesthesia |
Rhodotorula mucilaginosa produces the siderophore rhodotorulic acid (RA) when grown in iron-limited conditions. R. mucilaginosa grew at rates between 0.10 and 0.19 h(-1) in iron-restricted conditions, depending on the carbon source, and at 0.23 h(-1) in iron-sufficient conditions. In bioreactors inoculated with iron-starved pre-cultures, initial specific growth rates in batch culture were dependent on the iron concentration. The critical dilution rate (Dcrit, at which steady state cultures cannot be sustained) in continuous cultures was also dependent on the iron concentration and was lower than mu(max) in batch culture. Sucrose was the best carbon source for RA production [287+/-11 micromol (g biomass)(-1)] and production could be further increased by supplementing the medium with the precursors acetate [460+/-13 micromol (g biomass)(-1)], ornithine [376+/-6 micromol (g biomass)(-1)], or both [539+/-15 micromol (g biomass)(-1)]. Citric acid was an effective suppresser of RA production. RA was produced in a growth rate dependent manner and was optimally produced at pH 6.5. | Rhodotorula |
Bioethics education is a central element in the biotechnology curriculum. Re-imagining distance learning, virtual reality (VR) is taking student involvement to the next level of interaction, offering a real classroom experience and a new way to gain ethical reasoning skills. Here, we explore a new paradigm for bioethics education that involves VR. | Bioethics |
The specific activities of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) have been determined in the brain of rats by HPLC using electrochemical detection. The method allows, from a single sample, the simultaneous measurement of all three compounds and collection of each peak for radioactivity determinations. Five male Wistar rats were injected i.v. with 2.0 mCi/kg of DL-5-hydroxy-[G-3H]tryptophan (2.6 Ci/mmol) and 30 min later the animals were killed by near freezing. Whole brains were removed and homogenized in an acid medium. The content of 5-HTP, 5-HT, and 5-HIAA were determined by HPLC. Each peak of interest was immediately collected after detection in scintillation vials by use of a small dead space detector (TL-9A, Bioanalytical Systems, Inc.). The amounts of radioactivity were determined and specific activities calculated from the results. A second chromatography system (TLC) was used to check the authenticity and purity of compounds separated by the HPLC. | Hydroxyindoleacetic Acid |
Non-human primates (NHPs) often live in inaccessible areas, have cryptic behaviors, and are difficult to follow in the wild. Here, we present a study on the spread of the simian T-lymphotropic Virus Type 1 (STLV-1), the simian counterpart of the human T-lymphotropic virus type 1 (HTLV-1) in a semi-captive mandrill colony. This study combines 28 years of longitudinal monitoring, including behavioral data, with a dynamic mathematical model and Bayesian inference. Three transmission modes were suspected: aggressive, sexual and familial. Our results show that among males, STLV-1 transmission occurs preferentially via aggression. Because of their impressive aggressive behavior male mandrills can easily transmit the virus during fights. On the contrary, sexual activity seems to have little effect. Thus transmission appears to occur primarily via male-male and female-female contact. In addition, for young mandrills, familial transmission appears to play an important role in virus spread. | Mandrillus |
Melittin is a major active peptide component of bee venom that has been demonstrated to show anti-tumor effects. Osteosarcoma is a type of bone tumor with a high degree of malignancy, and metastasis is the main challenge of osteosarcoma therapy. This study aimed to investigate the role of melittin in the lung metastasis of osteosarcoma. 143 B cells were treated with different concentrations of melittin in vitro. Wound-healing and transwell assays were performed to determine the cell migration and invasion potential. Quantitative real-time PCR and Western blot experiments were performed to evaluate the expression levels of Wnt/beta-catenin signaling pathway-related factors after treatment with melittin. The orthotopic implantation model and hematoxylin-eosin staining were used to investigate the effect of melittin treatment on tumor formation and lung metastasis. Immunohistochemical staining and Western blot experiments were performed to indicate the melittin-mediated expression changes in Wnt/beta-catenin signaling pathway-related factors. The cell migration and invasion potential were observed to be inhibited in a dose-dependent manner upon treatment with melittin. Treatment with medium and high concentrations of melittin attenuated the mRNA and protein expression of LRP5, beta-catenin, MMP-2, cyclin D, c-Myc, survivin, MMP-9, and VEGF genes in vitro. Melittin significantly inhibited the growth of tibia xenografts in nude mice and decreased the number of lung metastatic nodules. Consistent with the results observed in vitro, treatment with melittin at medium and high concentrations attenuated the expression of Wnt/beta-catenin signaling pathway-related factors in vivo. In vitro, Wnt/beta-catenin signaling pathway was involved in Melittin-mediated -migration and invasion potential of 143 B cells. Similarly, as observed in the in vivo experiments, Wnt/beta-catenin signaling pathway was also associated with the role of melittin on lung metastasis of osteosarcomas. | Melitten |
Cisatracurium, (1R, 1'R, 2R, 2'R)-2,2-[1,5-pentanediylbis-[oxy(3-oxo- 3,1-propanediyl]]bis[1-[(3,4-dimethoxyphenyl)-methyl]-1,2,3,4- tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzenesulphonate (51W89), is an intermediate-acting neuromuscular blocking agent. 51W89 is one of ten isomers contained in Tracrium (atracurium besylate) and represents approximately 15 percent of the atracurium mixture. Clinical studies have indicated that 51W89 is more potent and is significantly weaker as a histamine releaser than atracurium. In vitro studies in human plasma have shown that, like atracurium, 51W89 spontaneously degrades at physiological pH by Hoffmann elimination to form laudanosine and the quaternary monoacrylate. Subsequent ester hydrolysis of the monoacrylate generates the monoquaternary alcohol. In rat plasma, 51W89 is also metabolized by non-specific carboxylesterases to the monoquaternary alcohol and the monoquaternary acid, the former being rapidly hydrolysed further to the more stable acid. It has been reported that laudanosine can be further metabolized via N-dimethylation to yield tetrahydropapaverine. The rate-limiting step in the degradation of 51W89 in human plasma is Hofmann elimination, whilst in rat plasma, the action of non-specific carboxylesterases is rate limiting. As part of the development of 51W89, the disposition of 14C-51W89 following a single intravenous bolus dose was studied in various animal species and humans. In the present work, we describe the identification of 51W89 metabolites in urine and bile from these studies by high performance liquid chromatography/mass spectrometry using pneumatically-assisted electrospray ionization coupled to an on-line radioactivity monitor.(ABSTRACT TRUNCATED AT 250 WORDS) | Neuromuscular Blocking Agents |
Salmonella enterica is a human pathogen with over 2,500 serovars characterized. S. enterica serovars Choleraesuis and Paratyphi C are two globally distributed serovars. We have developed a rapid molecular-typing method to detect serovars Choleraesuis and Paratyphi C in food samples by using a comparative-genomics approach to identify regions unique to each serovar from the sequenced genomes. A Salmonella-specific primer pair based on oriC was designed as an internal control to establish accuracy, sensitivity, and reproducibility. Serovar-specific primer sets based on regions of difference between serovars Choleraesuis and Paratyphi C were designed for real-time PCR assays. Three primer sets were used to screen a collection of over 100 Salmonella strains, and both serovars Choleraesuis and Paratyphi C gave unique amplification patterns. To develop the technique for practical use, its sensitivity for detection of Salmonella spp. in a food matrix was determined by spiking experiments. The technique was also adapted for a real-time PCR rapid-detection assay for both serovars Choleraesuis and Paratyphi C that complements the current procedures for Salmonella sp. isolation and serotyping. | Salmonella paratyphi C |
There has been increasing prevalence in the community of chronic kidney disease and an increased demand for nephrology trained nursing staff. We explored how nephrology trained nurses are impacted by daily caseload pressure, organisational support and workplace education. A co-designed 57-item questionnaire developed by the research team and clinical nephrology nurses hosted on Qualtrics was distributed to nephrology nurses in Australia and New Zealand. The 370 respondents described a strong professional identity as a nephrology nurse. 70% described pressure to work overtime and only 2% were adequately staffed. 40% felt at times that their patients clinical care was 'unsafe' and one-third described the erosion of work-based educational opportunities. However, team collegiality was high, a strength of the nursing profession. The nephrology nursing workforce will face important challenges over the next decade and there must be an organisational response to prevent continued staff shortages. | Nephrology Nursing |
Paracetamol and its four main metabolites, the sulphate (S), glucuronide (G), cysteine (C) and mercapturic acid (M) conjugates, are readily separated in a synthetic mixture using slightly acidic aqueous alcoholic eluents (e.g. water-methanol-formic acid, 85:15:0.15, v/v/v) on either octadecyl silica (ODS silica) or octadecyl silica which has been further silanized to remove residual hydroxyl groups (ODS/TMS silica). The dependences of k' upon alcohol, acid and added salt concentrations are reported for both materials. The latter material gives the higher plate efficiencies and is much superior when applied to analysis of urines taken after therapeutic doses and overdoses of paracetamol. At least four additional metabolites are reported in overdose urines. Mass spectrometric analysis (high and low resolution) has confirmed the identity of M and identified one of the additional metabolites as methoxyparacetamol. Mass spectra of the remaining additional metabolites enable major structural features to be deduced. One of these metabolites may be associated with liver damage. | Acetaminophen |
BACKGROUND: Few studies in the literature address the surgical management of patients with breast carcinoma who present with associated nipple discharge. The purpose of the current study was to determine the feasibility of breast-conserving surgery (BCS) for these patients. METHODS: The medical records of patients who presented with pathologic nipple discharge and underwent diagnostic or curative surgery between January 1990 and December 2002 were retrospectively reviewed. RESULTS: A total of 188 patients presented with nipple discharge during the study period. Of those, 47 had breast carcinoma. One patient had metachronous bilateral nipple discharge associated with malignant disease. Therefore, medical records associated with a total of 48 cases were reviewed. The median patient age was 52 years (range, 29-87 years), and the median follow-up duration was 45 months (range, 6-109 months). Twenty-nine patients had ductal carcinoma in situ (DCIS), 14 had Stage I disease, 3 had Stage II disease, and 2 had Stage III disease. Twenty-four patients were ultimately treated with mastectomy. For 16 of these patients, mastectomy was required because extensive disease was found in reexcisional segmental mastectomy specimens. Among patients with Stage 0 or I disease, the incidence of occult nipple-areola complex (NAC) involvement was 16% (3 of 19 patients). Twenty-four patients were ultimately treated with BCS with (n = 13) or without (n = 11) adjuvant radiotherapy. Local disease recurrence was noted at 14, 28, and 40 months, respectively, in 3 patients who declined adjuvant radiotherapy after BCS for DCIS. Among patients treated with BCS, comedonecrosis, multifocality, and the absence of adjuvant radiotherapy were associated with decreased local recurrence-free survival (P = 0.0005, P = 0.045, and P = 0.013, respectively). However, disease-free survival (mean +/- standard error) was similar for patients who underwent mastectomy and patients who underwent BCS (90 +/- 6 months; 95% confidence interval [CI], 78-101 months vs. 82 +/- 6 months; 95% CI, 69-94 months; P = 0.528). One patient with Stage I disease died of distant metastases at 99 months. CONCLUSIONS: Patients with breast carcinoma accompanied by nipple discharge presented primarily with early-stage breast carcinoma associated with DCIS. Occult NAC involvement was not an uncommon finding in patients with early-stage breast carcinoma. Nonetheless, BCS can be performed safely if negative margins are achieved and if appropriate adjuvant radiotherapy or systemic therapy is administered. | Paget's Disease, Mammary |
Pyruvate decarboxylase (PDC) uses thiamine diphosphate as an essential cofactor to catalyze the formation of acetaldehyde on the pathway of ethanol synthesis. Here we report the crystallographic image of a prereaction intermediate of a bacterial pyruvate decarboxylase prepared by cocrystallizing the enzyme with pyruvate and a stable analogue of the cofactor's activated ylid form. A second crystal structure of PDC in complex with fluoride shows that the ion organizes a water molecule that occludes the pyruvate binding site, accounting for the inhibitory effect of the halide. Also reported is a structure of the cofactor-free apo form, which when compared to the structure of the holo form indicates how thiamine diphosphate organizes the active site pocket of pyruvate decarboxylase to support catalysis. Guided by the structural and enzymatic data, we propose roles for several key residues in the catalytic mechanism. | Pyruvate Decarboxylase |
Novexel is developing the novel, orally active, semisynthetic streptogramin NXL-103, which has potential therapeutic application in the treatment of community-acquired pneumonia, community- or hospital-acquired MRSA, vancomycin-resistant enterococcus, and acute bacterial skin and soft tissue infections. NXL-103 is a combination of streptogramin A:streptogramin B components, initially developed in a 70:30 dose ratio. In multiple in vitro studies, NXL-103 demonstrated potent activity against different types of bacteria, such as Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, Haemophilus influenzae and Haemophilus parainfluenzae. NXL-103 was not affected by the resistance profiles of bacteria against other commonly used antibiotics. In phase I clinical trials, NXL-103 achieved bactericidal levels in plasma and was generally well tolerated, with side effects primarily on the gastrointestinal system. The first phase II trial conducted to evaluate the efficacy of NXL-103 against community-acquired pneumonia revealed that the compound was comparable with amoxicillin. NXL-103 has promise to become an important agent in the treatment of community-acquired pneumonia and complex skin and soft tissue infections, pending further development. | Streptogramin Group A |
Serotonin (5-hydroxytryptamine; 5-HT) is able to activate the hypothalamo-pituitary-adrenal axis via multiple actions at different levels. In the human adrenal gland, 5-HT, released by subcapsular mast cells, stimulates corticosteroid production through a paracrine mode of communication which involves 5-HT receptor type 4 (5-HT4) primarily located in zona glomerulosa. As a result, 5-HT is much more efficient to stimulate aldosterone secretion than cortisol release in vitro and administration of 5-HT4 receptor agonists to healthy individuals is followed by an increase in plasma aldosterone levels without any change in plasma cortisol concentrations. Interestingly, adrenocortical hyperplasias and tumors responsible for corticosteroid hypersecretion exhibit various cellular and molecular defects which tend to reinforce the intraadrenal serotonergic tone. These pathophysiological mechanisms, which are summarized in the present review, include an increase in adrenal 5-HT production and overexpression of 5-HT receptors in adrenal neoplastic tissues. Altogether, these data support the concept of adrenal serotonergic paracrinopathy and suggest that 5-HT and its receptors may constitute valuable targets for pharmacological treatments of primary adrenal diseases. | Serotonin |
PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental anomaly in which the normal regression of the primary vitreous and hyaloid vasculature does not occur. In the literature, there are a few cases of PHPV in adulthood. We report the novel presentation of phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with PHPV. We discuss the best management of this condition with a review of the literature on this topic. METHODS: Case report and literature review. RESULTS: Medical management was unsuccessful in this case and vitrectomy and fragmatome lensectomy improved vision from PL to counting fingers. CONCLUSION: This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome." | Persistent Hyperplastic Primary Vitreous |
Seventeen hospitalized patients (age 39-66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d. The 12-h plasma concentration at steady-state varied between 40-637 nmol/l for imipramine, 49-1148 nmol/l for desipramine and 89-1603 nmol/l for imipramine + desipramine. Guided by plasma level monitoring, a final therapeutic plasma level between 548-910 nmol/l for imipramine + desipramine was achieved (therapeutic dose range: 50-400 mg/day). Mean time to reach the therapeutic level was 19 days. The mean 2-OH-imipramine/imipramine ratio was 0.24 and mean 2-OH-desipramine/desipramine ratio was 0.56. There was a significant intrapatient correlation between the two ratios, both during 100 mg imipramine/d and at the therapeutic dose level. A low ratio was associated with high imipramine and particularly with a high desipramine level. Well defined steady state levels were established at two different dose levels in 12 patients and at three dose levels in 5 patients. With increasing dose there was a marked and disproportionate rise in the desipramine level and to some extent in the imipramine level. Saturation of imipramine and desipramine hydroxylation appeared to be responsible for the dose-dependent kinetics. Concomitant treatment with levomepromazine and perphenazine in one patient resulted in a significant rise both in imipramine and desipramine concentration, apparently due to inhibition of the hydroxylation. Eleven out of twelve endogenously depressed patients responded completely to treatment, whereas the response was poor in the non-endogenously depressed patients despite optimal drug levels. | Imipramine |
Genome-wide association scans in type 2 diabetes (T2D) have identified a risk variant, rs13266634 (Arg325Trp), in SLC30A8 on chromosome 8. SLC30A8 encodes a beta-cell specific zinc-ion transporter and rs13266634 has been shown to affect insulin secretion. Recently, autoantibodies for Slc30A8 with high predictive value were demonstrated in individuals with type 1 diabetes (T1D), making this gene an interesting T1D candidate gene. We genotyped rs13266634 in 3008 cases and controls and 246 families from Denmark. Association to T1D could not be demonstrated. | Zinc Transporter 8 |
Autologous stem cell transplantation is used widely after high-dose chemotherapy for treating hematological and other malignancies. Bone marrow harvested for autologous bone marrow transplantation may contain residual malignant cells even when the cancer is judged to be in remission. Attempts to purge marrow of its putative residual malignant cells may delay hemopoietic reconstitution and are of uncertain efficacy. In this report, we demonstrate the possibility of applying hypothermia to autologous stem cell purging. Using clonogenic assay, we compared the surviving fraction of human leukemia (HL60, K562) and human small cell lung cancer (H69) cell lines with that of normal human bone marrow CFU-GM and BFU-E cells after incubation at 4 +/- 0.1 degrees C for 24 and 48 h. Hypothermia decreased the surviving fraction of HL60, H69, and K562 cells. In contrast, the surviving fractions of stem cells were not affected by the temperature shift. The surviving fraction of HL60 cells at 4 degrees C cooling was significantly lower than that at 22 degrees C cooling. These findings suggest that in vitro hypothermia may selectively purge residual malignant cells in stored remission bone marrow and may be applicable before autologous bone marrow transplantation. In addition, the method is very simple and cost effective. | Tumor Stem Cell Assay |
Paediatric chronic fatigue syndrome or myalgic encephalomyelitis affects at least 1% of secondary school children in the UK and is very disabling. Treatment is effective but few children get a diagnosis or access treatment. This paper summarises what we currently know about diagnosing and treating this important illness in childhood. | Fatigue Syndrome, Chronic |
SkinEthic Laboratories is a France-based biotechnology company recognised as the world leader in tissue engineering. SkinEthic is devoted to develop and produce reliable and robust in vitro alternative methods to animal use in cosmetic, chemical and pharmaceutical industries. SkinEthic models provide relevant tools for efficacy and safety screening tests in order to support an integrated decision-making during research and development phases. Some screening tests are referenced and validated as alternatives to animal use (Episkin), others are in the process of validation under ECVAM and OECD guidelines. SkinEthic laboratories provide a unique and joined experience of more than 20 years from Episkin SNC and SkinEthic SA. Their unique cell culture process allows in vitro reconstructed human tissues with well characterized histology, functionality and ultrastructure features to be mass produced. Our product line includes skin models: a reconstructed human epidermis with a collagen layer, Episkin, reconstructed human epidermis without or with melanocytes (with a tanning degree from phototype II to VI) and a reconstructed human epithelium, i.e. cornea, and other mucosa, i.e. oral, gingival, oesophageal and vaginal. Our philosophy is based on 3 main commitments: to support our customers by providing robust and reliable models, to ensure training and education in using validated protocols, allowing a large array of raw materials, active ingredients and finished products in solid, liquid, powder, cream or gel form to be screened, and, to provide a dedicated service to our partners. | Animal Testing Alternatives |
A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-[(2-(dimethylamino)pyrimidin-5-yl]methylenechroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 = 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent. | Chromans |
The present study examined the involvement of GABA(A) and GABA(B) receptors in the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Rats were trained to discriminate either 300 or 700 mg/kg GHB IG from water using a T-maze, food-reinforced drug-discrimination procedure. The direct GABA(B) agonist, baclofen, substituted completely for both training doses of GHB; its potency to substitute for GHB increased moderately as the training dose of GHB was increased. The positive GABA(A) modulator, diazepam, substituted partially for 300 mg/kg GHB, but failed to elicit GHB-appropriate responding in rats trained with the higher GHB dose. Finally, the GABA(B) antagonist, CGP 35348, completely blocked the discriminative stimulus effects of the high training dose of GHB, but only partially antagonized the effects of the low training dose. These results suggest that (a) GHB produces a compound stimulus, and (b) both GABA(B)- and GABA(A)-mediated cues are prominent components of this compound stimulus; the contribution of each component, however, appears to vary as the training dose of GHB is increased. | GABA-B Receptor Antagonists |
Bonded retainers may play an important role in reducing unwanted tooth movements following orthodontic treatment, with an open-ended perspective on retention now established. The importance of planning for bonded retention is emphasised, with key principles in minimising failure rates as well as wire and adhesive options discussed. Approaches to preparation of the wire and the teeth, the bonding process, as well as variations in retainer design, and means of preventing problems and undertaking repairs in order to achieve predictable fixed retention in the long term are also outlined. | Orthodontic Appliance Design |
Hyaluronan (HA) is a critical component of cancer microenvironment that is known to increase tumor progression and aggressiveness. The synthesis of HA starts from the cytosolic precursors UDP-N-acetylglucosamine and UDP-glucuronic acid. These two sugar nucleotides have several functions in addition to glycoconjugate synthesis and glucuronidation reactions, each of which can have a critical role in cancer. HA is synthesized by a family of three HA synthase (HAS) enzymes and, in this review, we described the main posttranslational modifications that are known to regulate HA metabolism. In particular, as the main HAS in adult tissues is HAS2, we focused on the role of AMPK-mediated phosphorylation and glycosylation by O-linked N-acetylglucosamine (O-GlcNAcylation) of HAS2 which mediate HAS2 inactivation and activation, respectively. HA catabolism, furnishing glucuronic acid and N-acetylglucosamine, can represent for a cancer cell a valid source of substrates to sustain complex tumor metabolism, and we highlight a presumable metabolic fate of such sugars in tumor cells." | Uridine Diphosphate Glucose Dehydrogenase |
There is growing interest in the irradiation of food and agricultural products for insect disinfestation, sprout inhibition, delayed ripening and the reduction of microbiological loads. Extensive research has been done on this process, and irradiation to a maximum dose of 10 kGy is recognized as safe by national and international regulatory agencies. The question has been raised, however, whether irradiation of pesticide residues might produce radiation products that were more toxic or less toxic than the original pesticide. To address this question, we observed the effects of 10 kGy of gamma-radiation on malathion as measured by sister-chromatid exchange (SCE), micronuclei formation, cell survival, growth rate and polyploid formation. We found no significant differences between the effects of irradiated and unirradiated malathion on any of these end-points. Polyploid formation was the most dramatic effect of both irradiated and control malathion on V79 Chinese hamster cells. Cell survival, polyploid formation and growth rate were slightly better in cells treated with irradiated malathion. In Molt-4 human lymphocyte cells, micronuclei formation was not affected by irradiated or unirradiated malathion. Compared to malathion alone, the lack of such biological effects indicates that none of the presumed radiation-induced breakdown products increased or decreased the endpoints studied. The number of SCE was consistently, but not significantly, higher in the cells treated with irradiated malathion. There were no significant differences in cell survival or micronucleus formation in the human lymphocyte cell line Molt-4 treated with irradiated or control malathion. Thus, the irradiation of the pesticide malathion to 10 kGy, a recommended upper dose for most food irradiations, does not significantly alter its toxicity in these in vitro systems. | Sister Chromatid Exchange |
Turner's painting of a dental surgeon's rooms, discussed in the first of these two papers,(1) is a very satisfying work of art, successful in its relaying of a domestic drama, and also fulfilling Payne Knight's commission to produce a work to equal that of the older masters. It cannot, though, be relied upon to show us what a late Georgian dentist's rooms actually looked like. For this we are very fortunate to have Turner's sketchbook, with its preparatory drawings for the painting. | Dental Facilities |
Food is our daily companion, performing numerous beneficial functions for our bodies. Many of them can help to alleviate or prevent ailments and diseases. In this review, an extensive bibliographic search is conducted in various databases to update information on unprocessed foods with anti-inflammatory and antioxidant properties that can aid in treating diseases such as cancer. The current state of knowledge on inflammatory processes involving some interleukins and tumor necrosis factor-alpha (TNF-alpha) is reviewed. As well as unprocessed foods, which may help reduce inflammation and oxidative stress, both of which are important factors in cancer development. Many studies are still needed to take full advantage of the food products we use daily. | Antioxidants |
The molecular and cellular mechanisms which up-regulate IgE synthesis in most atopic patients are only incompletely understood. There is no doubt that T cells play a prominent role in the B cell immunoglobulin switch to IgE. T-cell-derived interleukin (IL)-4 is a specific inducer of IgE synthesis which activates B cells to proliferate and, furthermore, induces other cells to release cytokines which enhance IgE synthesis. Additional costimulatory signals are required, however, for B cell activation and the consequent immunoglobulin switch to IgE. Besides physical B/T cell interaction, direct B cell activation through anti-CD40 provides such a signal. IL-4-induced B cell activation is amplified by other cytokines such as IL-5, IL-6, IL-3, probably IL-9, and tumor necrosis factor-alpha, whereas interferon (IFN)-gamma, IFN-alpha, transforming growth factor-beta and IL-12 are able to inhibit IL-4-induced IgE synthesis. These different IgE-synthesis-modulating lymphokines are secreted by different T cell subsets, TH1 and TH2. While IgE synthesis is activated by TH2-derived lymphokines, TH1 cell clones exhibit cytolytic activity. The detection of allergen-specific T cells in peripheral blood mononuclear cells (PBMNCs) of atopic patients, with a lymphokine profile similar to TH2, and the predominance of TH2 cells in PBMNCs of these patients might be one explanation for increased serum IgE concentrations in atopic individuals. It is not known, however, which stimulus leads to a predominant expression of TH2 cells over TH1 cells in atopic patients with consequently increased IgE synthesis. | Lymphocyte Cooperation |
Cytochrome P450 aromatase (AROM) catalyzes the biosynthesis of estrogen from androgen. Previously crystal structures of human AROM in complex with the substrate androstenedione, and inhibitors exemestane, as well as the newly designed steroidal compounds, have been reported. Here we report the first crystal structure of testosterone complex of human placental AROM. Testosterone binds at the androgen-specific heme distal pocket. The polar and hydrophobic interactions with the surrounding residues resemble the interactions observed for other ligands. The heme proximal region comprises the intermolecular interface in AROM, and also the putative interaction surface of its redox partner cytochrome P450 reductase. Unreported previously, the proximal region is characterized by a large surface cavity, unlike most known P450's. Using five best X-ray data sets from androstenedione and testosterone complexes of AROM, we now unequivocally show the presence of an unexplained ligand electron density inside the proximal cavity. The density is interpreted as ordered five ethylene glycol units of polyethylene glycols used as a solvent for steroids and also in crystallization. Interestingly, polyethylene glycol exhibits weak inhibition of AROM enzyme activity in a time dependent manner. Besides its critical role in the redox partner coupling and electron transfer process, the proximal cavity possibly serves as the interaction site for other molecules that may have regulatory effects on AROM activity. In addition, the new data also reveal a previously unidentified water channel linking the active site to the lipid interface. The channel could be the predicted passage for water molecules involved in catalysis. | Cytochrome P450 Family 19 |
The first examples of intramolecular Zr-catalyzed electrophilic alkylation of aryl olefins are disclosed. Substituted carbo- and heterocycles are prepared efficiently and diastereoselectively. | Alkylating Agents |
Clinical nurse educators in a BSN program developed the SIM-PLE (Simulation-Positive Learning Evaluation) rubric to evaluate student performance in simulation. A pilot study was conducted over two semesters with junior level medical-surgical classes made up of approximately 110-130 students each semester, and the tool was revised and re-evaluated. Inter-rater reliability testing utilized 69 SIM-PLE rubric student evaluations (N = 69). Inter-rater reliability was assessed with comparison of lead faculty with three other instructors utilizing two raters for each simulation experience. The intraclass correlation coefficient (ICC) suggested high inter-rater reliability. The t-test difference was not significant. One-way analysis of variance (ANOVA) showed a significant difference in the Collaboration subcategory score. Univariate ANOVA indicated both raters scored consistently with each other overall and that they both scored JR1 differently than JR2. The pilot study and testing of interrater reliability of the rubric revealed positive findings. The role of the rubric in providing formative feedback during debrief sessions empowered students to analyze their own performance and/or experience to self-correct or improve their future practice based on these experiences. | Medical-Surgical Nursing |
Certain proteases from the circulation, mast cells and elsewhere signal directly to cells by cleaving protease-activated receptors (PARs), members of a new subfamily of G-protein-coupled receptor. Cleavage exposes a tethered ligand domain that binds to and activates the cleaved receptors. Advances in the past year have improved our understanding of the molecular mechanisms of this signaling and how it is switched off. It is now recognized that PARs play important roles in 'emergency situations' - such as trauma, when there is generation or release of proteases - and are involved in coagulation, inflammation, pain, healing and protection. Selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases. | Receptors, Thrombin |
The evolution of high virulence bacterial strains has necessitated the development of novel therapeutic agents to treat resistant infections. Metal-based therapeutics represent a promising avenue for advancement, given their structural variability and unique modes of action relative to classical organic molecules. One strategy that has seen marked success is the incorporation of ferrocene into the framework of established antibacterial agents, while ruthenium-based complexes have also shown promise as bioactive compounds. This work focused on the preparation of novel ruthenium(II)-arene complexes containing Schiff base ligands with an attached ferrocene, and evaluation of their antibacterial activity. Structure-activity relationships identified the importance of having a phenyl group between the Schiff base imine and the appended ferrocene. This complex, C2, showed prominent activity against several clinically relevant bacterial strains, including a minimum inhibitory concentration of 16 mug mL(-1) for methicillin-resistant Staphylococcus aureus (MSRA). Overall, the results of this study represent a promising new lead for future development of novel antibacterial agents. | Ruthenium |
INTRODUCTION: Ureteric injuries are rarely associated with spinal trauma with an incidence of less than 1%. Missed injuries can lead to urinoma collection, urosepsis and even death. MATERIALS AND METHODS: A 75-year-old man presented 1 month following fall with high-grade fever and severe back pain mimicking spondylodiscitis clinically. Plain radiograph showed features of ankylosing spondylitis with a suspicious trans-discal injury at L3-L4. Hyper-intense fluid within L3/L4 disk space communicating to a large psoas collection measuring 13 x 6 cms mimicking spondylodiscitis with abscess formation was observed in magnetic resonance imaging (MRI). MRI with contrast enhancement demonstrated a leak through left ureter into the psoas muscle raising suspicion of a ureteric injury. Plain computerized tomography revealed a three-column fracture at L4, and a ureteric leak into the psoas collection with proximal hydronephrosis was seen after contrast administration, establishing the presence of a ureteric fistula resulting in urinoma. RESULTS: Following initial symptomatic improvement after ureteric stenting, the patient succumbed to urosepsis at 3 months. CONCLUSION: We report for the first time a post-traumatic urinoma secondary to ureteric injury clinically mimicking spondylodiscitis. Clinicians need to be aware of the possibility of ureteric injury in hyperextension lumbar fractures occurring in ankylosing spondylitis and treat them early to avoid urological complications. | Urinoma |
The Bardet-Biedl syndrome is a rare autosomal recessive disorder characterized by pigmentary retinopathy, obesity, polydactyly, hypogonadism, and mental retardation. Renal abnormalities, hypertension, acquired heart disease, and hepatic fibrosis also occur in homozygotes. Two adult Bardet-Biedl sibs, a man with hypertension and cardiomegaly and a woman with biliary cirrhosis, and 75 relatives in 5 generations of the extended family were identified. Hospital records for major illnesses, death certificates, and autopsy reports were examined. The frequent observation of obesity, hypertension, diabetes mellitus, and renal disease in first-degree relatives, obligate gene carriers, and other blood relatives raise the possibility that Bardet-Biedl heterozygotes are also predisposed to these disorders. | Laurence-Moon Syndrome |
Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7-63 were isolated from the rhizomes of Smilax glabra. Their structures were elucidated on the basis of extensive spectroscopic analyses, as well as by comparison with literature data. Twenty-seven of these compounds were obtained from and identified in the genus Smilax for the first time. The absolute configuration of (2S)-1,2-O-di-trans-p-coumaroylglycerol (43) was determined for the first time using the exciton-coupled circular dichroism (ECCD) method. Thirty isolated compounds were evaluated for their antimicrobial activity against three Gram-negative bacteria, three Gram-positive bacteria and one fungus, and the corresponding structure-activity relationships were also discussed. Eighteen compounds were found to be antimicrobial against the microorganisms tested and the minimum inhibitory concentrations (MIC) were in the range of 0.0794-3.09 mM. Among them, compound 1 showed antimicrobial activity against Canidia albicans with MIC value of 0.146 mM, which was stronger than cinchonain Ia with an MIC of 0.332 mM. Compounds 3 and 4 exhibited inhibitory activity against Staphylococcus aureus with MIC values of 0.303 and 0.205 mM, respectively. The results indicated that these antimicrobial constituents of this crude drug might be responsible for its clinical antimicrobial effect. | Benzoates |
Infections by VZV, the virus that causes chickenpox and herpes zoster, usually are diagnosed by the classic clinical presentations. In immunocompromised patients, however, the atypical presentation can make the diagnosis more challenging. Although varicella typically follows an uncomplicated course in children, adults and immunocompromised patients can develop complications involving several organs; some complications may be fatal. Prevention of disease with the vaccine is ideal. When varicella or zoster infection does occur, proper treatment should be initiated, depending on the age and immune status of the patient. | Chickenpox |
Endotetraploidy with 4-chromatid chromosomes divides by a bipolar, 2-step meiotic-like division back to diploidy (subcells), which is chiefly achieved by co-segregation of whole genomes uncoupled from spindle participation. This study shows diploid subcell inheritance of endopolyploid-division traits: perpendicular division relative to the cytoskeleton axis, dysfunctional centromere/kinetochore regions and whole genomic separations from co-segregation. The assimilation of these traits into the innate mitotic machinery of the subcells resulted in diploid mitotic divisions that tolerated mild disturbances in cycling progression and in chromosomal distributions. The data were interpreted as demonstrating a blending together of endopolyploid and mitotic division traits with result of an endo-modified mitosis in subcell propagation. Additionally, chromosomal stickiness caused breakage in anaphase/telophase. The observations are discussed in regard to a potential for slowly developing aneuploidy with increasing genomic complexity, which is widely accepted to be the basic route in tumorigenesis. | Cell Nucleus Division |
Atrophic rhinitis is a chronic inflammatory disease of the nose, which is more common in India. Chronic dacryocystitis is its rare complication. The authors found four cases of chronic dacryocystitis from March 2002 to October 2003 due to atrophic rhinitis. It was diagnosed clinically by the regurgitation test and lacrimal syringing. These cases were treated conservatively for a period of six weeks to make the nasal mucosa healthier and were then subjected to endoscopic dacryocystorhinostomy (end-DCR) under local anaesthesia. The procedure was found to be more difficult due to bleeding and the healing time was prolonged as compared to other cases of end-DCR. After one to one and half years of follow-up the primary success rate was 75 per cent but after revision surgery in one case, all cases were successful. Hence it was concluded that atrophic rhinitis is no more a contraindication for end-DCR. However, meticulous initial preparation and post-operative follow-up is necessary to improve the result. | Dacryocystitis |
The present investigation aimed at defining the localization of apolipoproteins (apo) A-I, A-IV, B-48, and B-100 along the crypt-villus axis of the human fetal colon, their biogenesis during gestation, and their hormonal regulation. Using immunofluorescence, the distribution of apo A-I and A-IV appeared as a gradient, increasing from the developing crypt to the tip of the villus. On the other hand, apo B-100 staining was found in the crypt and the lower mid-villus region with varying intensities in the upper villus cells, while the 2D8 antibody which recognizes both apo B-100 and B-48, revealed uniform staining along the crypt-villus axis. Apolipoprotein synthesis, determined by [35S] methionine labeling, immunoprecipitation, and SDS-PAGE showed a predominance of apo A-IV (53%), followed by apo A-I (23.9%), apo B-48 (13.4%), and apo B-100 (9.7%). The synthesis of each apolipoprotein was significantly modulated by hydrocortisone, insulin and epidermal growth factor (EGF). Apart from a decrease in apo B-100 exerted by EGF and a reduction in apo A-I resulting from the addition of insulin, the other apolipoproteins were all enhanced. Our data confirm that the fetal colon has the capacity to synthesize apolipoprotein A-I, A-IV, B-48, and B-100 and establish that their synthesis are modulated by hormonal and growth factors known to be involved in the regulatory mechanism of the functional development of human jejunum. | Apolipoproteins |
A double-blind, parallel investigation was undertaken to evaluate the efficacy of transdermally delivered scopolamine hydrobromide in acute vertigo as compared to meclizine hydrochloride and placebo. Statistical analysis of subjective patient responses and clinical observations suggested that both scopolamine and meclizine are more effective than placebo. Both have significant, but different, side effects. | Meclizine |
A facile patterning method for the functionalization of vertically aligned carbon nanotubes is described. Modification of the surface of nanotube forests with hydrophilic, hydrophobic, or polymerizable small molecules was achieved via UV-triggered attachment of perfluoroarylazides. Multiple functionalizations of the tube surface can be achieved. Macro- and micropatterning of forest substrates were demonstrated. Superhydrophobic surfaces containing superhydrophilic regions were prepared. | Nanotubes, Carbon |
During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A beta cell-specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the beta cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent beta cell compensation, may be a factor in the development of GDM in humans. | Receptors, Kisspeptin-1 |
Munchausen syndrome by proxy is a subtle and difficult to diagnose form of child abuse in which the carer (usually the mother) simulates, manipulates or produces symptoms of illness in the victim. In most cases the detrimental effect is caused by applying foreign substances or by airway obstruction. In the presented case a 20-month-old girl developed a spreading soft-tissue infection resistant to treatment on the left upper arm after vaccination, which required a number of surgical interventions. Repeatedly, microorganisms from the intestinal flora were isolated from the wound secretion. After the girl suffered respiratory and circulatory arrest, which required resuscitation measures, chemical toxicological tests revealed not medically prescribed benzodiazepines in serum and urine. When the mother, a trained nurse, was confronted with the allegation to have manipulated the symptoms of the illness she committed suicide. The forensic autopsy of the suicide produced numerous hints suggesting chronic self-damaging behaviour described as Munchausen syndrome. This case shows a number of manipulation forms with the maintenance of a chronic skin and soft tissue infection belonging to the rarer forms of inflicting damage to the child. It also illustrates that confrontation with the allegation of Munchausen syndrome by proxy creates a very stressful emotional situation that may lead to a suicidal act. | Munchausen Syndrome by Proxy |
BACKGROUND: After outpatient oculoplastic surgical procedures, to report the feasibility of a policy of planning the first post-operative control not at one day after surgery but at the time of suture removal or lacrimal drainage system irrigation. PATIENTS AND METHODS: A retrospective case-series chart review analysis in a tertiary referral center of hundred and five consecutive outpatients was performed. Surgical procedures: eyelid (75/105), transpunctal endoscopic lacrimal drainage (11/105), both eyelid and transpunctal endoscopic lacrimal drainage (15/105), orbita soft tissue (4/105). MAIN OUTCOME: number of patients who had a first post-operative control for a different purpose than the one planned by the policy and whether it led to additional interventions. RESULTS: Out of 105 patients, 95 had their first control 12 +/- 4 days (mean +/- SD) after surgery according to the established policy. In 10 patients the first control occurred earlier (3 +/- 1 days) without leading to additional medico-surgical interventions. CONCLUSION: After outpatient oculoplastic surgical procedures, it is possible, with apparently no major consequences, to plan the first post-operative control not on the first day after surgery but later at time of suture removal or lacrimal drainage system irrigation. | Postoperative Care |
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