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Poria cocos is a well-known medicinal plant widely used in China and other East Asian countries owing to its various therapeutic effects. However, the bioactive constituents responsible for the pharmacological effects of Poria cocos and their metabolites in vivo are still unclear to date. The aim of the present study was to develop a practical method based on the combined use of the liquid chromatography coupled with electrospray ionization multistage tandem mass spectrometry (LC-ESI-MS(n) ) for the comprehensive and systematic separation and characterization of the bioactive constituents of Poria cocos extract and their metabolites in rats. Based on the proposed strategy, a total of 34 compounds were characterized from the extract of Poria cocos. Among them, eight were unambiguously identified by comparing their retention times and mass spectra with those of reference standards, and 26 were tentatively identified on the basis of their MS(n) fragmentation behaviors and molecular weight information from literatures. In vivo, seven compounds were successfully detected in rat urine whereas one was found in rat plasma. This study proposed a series of potential bioactive components and provided helpful chemical information for further research on the action mechanism of traditional Chinese medicine. | Poria |
TIM proteins are known to promote viral entry into host cells. Unexpectedly, a recent study has shown that TIM proteins also inhibit HIV-1 release from the host cell by directly binding to phosphatidylserine exposed on the virus surface, providing details on a new role of TIM proteins in HIV replication. | Receptors, Virus |
Tolerance to prolonged water deficit occurs along a continuum in plants, with dehydration tolerance (DhT) and desiccation tolerance (DT) representing some of the most extreme adaptations to water scarcity. Although DhT and DT presumably vary among individuals of a single species, this variability remains largely unstudied. Here, we characterized expression dynamics throughout a dehydration-rehydration time-course in six diverse genotypes of the dioecious liverwort Marchantia inflexa. We identified classical signatures of stress response in M. inflexa, including major changes in transcripts related to metabolism, expression of LEA and ELIP genes, and evidence of cell wall remodeling. However, we detected very little temporal synchronization of these responses across different genotypes of M. inflexa, which may be related to genotypic variation among samples, constitutive expression of dehydration-associated transcripts, the sequestration of mRNAs in ribonucleoprotein partials prior to drying, or the lower tolerance of M. inflexa relative to most bryophytes studied to date. Our characterization of intraspecific variation in expression dynamics suggests that differences in the timing of transcriptional adjustments contribute to variation among genotypes, and that developmental differences impact the relative tolerance of meristematic and differentiated tissues. This work highlights the complexity and variability of water stress tolerance, and underscores the need for comparative studies that seek to characterize variation in DT and DhT." | Gene Expression Regulation, Plant |
A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. | Fox-Fordyce Disease |
The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non-motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11-year-old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy. A homozygous variant, c.870_871del, was identified in the CDK10 gene, predicted to cause a frameshift, p.Trp291Alafs*18, in the cyclin-dependent kinase 10 protein. CDK10 mRNAs were detected in patient cells and do not seem to undergo non-sense mediated decay. CDK10 is the binding partner of Cyclin M (CycM) and CDK10/CycM protein kinase regulates ciliogenesis and primary cilium elongation. Notably, CycM gene is mutated in patients with STAR syndrome. Following incubation, the patient cells appeared less elongated and more densely populated than the control cells suggesting that the CDK10 mutation affects the cytoskeleton. Upon starvation and staining with acetylated-tubulin, gamma-tubulin, and Arl13b, the patient cells exhibited fewer and shorter cilia than control cells. These findings underscore the importance of CDK10 for the regulation of ciliogenesis. CDK10 defect is likely associated with a new form of ciliopathy phenotype; additional patients may further validate this association. | Agenesis of Corpus Callosum |
Echidnas (Tachyglossus aculeatus) are amongst the largest deep hibernators, but it is difficult to get them to hibernate normally under laboratory conditions. We measured body temperature (Tb) in 14 free-ranging echidnas using implanted data-loggers. Cooling during entry into hibernation bouts followed a Newtonian cooling curve, and conductances calculated from cooling curves were identical to those observed in cold exposed euthermic echidnas. Comparison with a reference soil temperature demonstrated that echidnas showed behavioural thermoregulation during hibernation; early in the hibernation season echidnas preferred to hibernate in cool areas, while during the coldest months they moved to warmer hibernacula, giving a preferred Tb in the range 8-10 degrees C. Thermal buffering against excessive variation in Tb may be as important as maintaining a low Tb. | Tachyglossidae |
Mycoplasma bovis is a common pathogenic microorganism of cattle and represents an important hazard on the cattle industry. Adherence to host cells is a significant component of mycoplasma-pathogenesis research. Fibronectin (Fn), an extracellular matrix protein, is a common host cell factor that can interact with the adhesions of pathogens. The aims of this study were to investigate the Fn-binding properties of M. bovis fructose-1,6-bisphosphate aldolase (FBA) and evaluate its role as a cell adhesion factor during mycoplasma colonization. The fba (MBOV_RS00435) gene of M. bovis was cloned and expressed, with the resulting recombinant protein used to prepare rabbit polyclonal antibodies. The purified recombinant FBA (rFBA) was shown to have fructose bisphosphate aldolase activity. Western blot indicated that FBA was an antigenically conserved protein in several M. bovis strains. Western blot combined with immunofluorescent assay (IFA) revealed that FBA was dual-localized to both cytoplasm and membrane in M. bovis. IFA showed that rFBA was able to adhere to embryonic bovine lung (EBL) cells. Meanwhile, an adhesion inhibition assay demonstrated that anti-rFBA antibodies could significantly block the adhesion of M. bovis to EBL cells. Moreover, a dose-dependent binding of rFBA to Fn was found by dot blotting and enzyme-linked immunosorbent assays. Together these results provided evidence that FBA is a surface-localized and antigenic protein of M. bovis, suggesting that it may function as a virulence determinant through interacting with host Fn. | Mycoplasma bovis |
Glycated albumin (GA) is a candidate for glycemic indicator to control prediabetes, the half-life of which is about 2 weeks, which is neither too long nor too short, considering that there is no longer any need for daily fingerstick sampling but glucose levels can be controlled in a relatively short term. Its usefulness as a glycemic indicator must be widely recognized by developing a simple and miniaturized GA sensor for point-of-care testing (POCT) devices. In this study, we propose an aptamer-based capacitive electrode for electrochemical capacitance spectroscopy (ECS) to specifically detect GA in an enzyme-/antibody-free manner. As a component of the bioelectrical interface between the sample solution and the electrode, a densely packed capacitive polyaryl film coated on a gold electrode contributes to the detection of GA by the ECS method. In addition, the GA aptamer tethered onto the polyaryl-film-coated gold electrode is useful for not only specifically capturing GA but also inducing changes in the concentration of cations released from the cation/GA aptamer complexes by GA/GA aptamer binding. Also, hydrophilic poly(ethylene glycol) (PEG) coated on the polyaryl film electrode in parallel with the GA aptamer prevents interfering proteins such as human serum albumin (HSA) and immunoglobulin G (IgG) from nonspecifically absorbing on the polyaryl film electrode. Such a GA aptamer-based capacitive electrode produces significant signals of GA against HSA and IgG with the change in GA concentration (0.1, 1, and 10 mg/mL) detected by the ECS method. This indicates that the ECS method contributes to the evaluation of the GA level, which is based on the rate of glycation of albumin. Thus, a platform based on ECS measurement using the aptamer-based capacitive electrode is useful for protein analysis in an enzyme-/antibody-free manner. | Glycated Serum Albumin |
Although lung adenocarcinoma patients have benefited from the development of targeted therapy, patients with lung squamous cell carcinoma (SqCC) have no effective treatment due to the complexity and heterogeneity of the disease. Therefore, basing on the genetic analysis of mutations in lung squamous cell carcinoma to design multi-target inhibitors represents a potential strategy for the medical treatment. In this study, through screening an in-house focused library, we identified an interesting indazole scaffold. And following with binding analysis, we elaborated the structure-activity relationship of this hit compound by optimizing four parts guided by the DDR2 enzymatic assay, which resulted in a potent lead compound 10a. We conducted further optimization of dual enzymatic inhibitions towards FGFR1 and DDR2, two important kinases in lung squamous cell carcinoma. Finally, from the cellular antiproliferative activity tests and in vivo pharmacokinetic test, 3-substituted indazole derivative 11k was found to be a promising candidate and subjected to in vivo pharmacology study with the mouse xenograft models, demonstrating profound anti-tumor efficacy. Additional in vitro druglike assessment reinforced that compound 11k could be valuable for SqCC drug development. | Discoidin Domain Receptor 2 |
Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure-activity relationship of harmine derivatives has been summarized. | Peganum |
Nairobi sheep disease was seen principally upon movement of susceptible animals into the enzootic areas. This occurred most frequently for marketing purposes near the main centres of population. Other outbreaks followed local breakdowns in tick control measures. The disease did not occur in epizootic form during the period under consideration. Nairobi sheep disease was isolated from pools of Rhipicephalus appendiculatus but not from many pools of other tick species. No virus was isolated from the blood or tissues of a range of wild ruminants and rodents. | Nairobi Sheep Disease |
AIM: To assess the observed volume of filled C-shaped root canals from different CBCT and micro-CT having nano-CT as a reference. MATERIALS AND METHODS: Twelve extracted mandibular molars with C-shaped root canals were endodontically treated using Reciproc Blue R25 (VDW GMBH, Munich, Germany) in a reciprocating system and filled with gutta-percha (Dentsply Maillefer) and AH Plus sealer (Dentsply DeTrey, Konstanz, Germany). CBCT scans were performed using 3 units-3D Accuitomo 170 (J. Morita, Kyoto, Japan), ProMax 3D Max (Planmeca, Helsinki, Finland), and NewTom VGi EVO (Cefla QR, Verona, Italy)-at two resolution modes: standard and high. Micro-CT and nano-CT scans were also obtained. The volume of all filled C-shaped root canals was obtained using CTAn software (Bruker, Kontich, Belgium), and the blooming artifact, in relation to nano-CT volume, was calculated. The data were evaluated by the Bland-Altman plots and ANOVA two-way for repeated measures (alpha = 0.05). RESULTS: All CBCT units and micro-CT showed significantly larger observed volume of root canal filling when compared to nano-CT. The blooming artifact of root canal filling in standard resolution was significantly larger than that in high resolution (p < 0.05) in all CBCT units. CONCLUSIONS: Endodontic filling material with AH Plus sealer causes blooming artifacts in CBCT units and micro-CT. CLINICAL RELEVANCE: Considering the anatomical complexity of C-shaped root canals and the challenges associated with endodontic treatment, CBCT is frequently recommended for follow-up evaluations. However, the presence of endodontic filling material can result in blooming artifacts that may potentially impact the accurate diagnosis of endodontic complications. | Root Canal Filling Materials |
This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice were fed a standard diet or a Western diet high in fat and fructose, supplemented or not with B. uniformis CECT 7771 for 14 weeks. B. uniformis CECT 7771 reduced body weight gain, plasma cholesterol, triglyceride, glucose, and leptin levels; and improved oral glucose tolerance in obese mice. Moreover, B. uniformis CECT 7771 modulated the gut microbiota and immune alterations associated with obesity, increasing Tregs and reducing B cells, total macrophages and the M1/M2 ratio in both the gut and epididymal adipose tissue (EAT) of obese mice. B. uniformis CECT 7771 also increased the concentration of the anti-inflammatory cytokine IL-10 in the gut, EAT and peripheral blood, and protective cytokines TSLP and IL-33, involved in Treg induction and type 2 innate lymphoid cells activation, in the EAT. It also restored the obesity-reduced TLR5 expression in the ileum and EAT. The findings indicate that the administration of a human intestinal bacterium with immunoregulatory properties on the intestinal mucosa helps reverse the immuno-metabolic dysfunction caused by a Western diet acting over the gut-adipose tissue axis. | Bacteroides Infections |
The pulmonary vascular bed is both a source of and target for a number of vasoactive factors. Among the most important for pulmonary vascular homeostasis are factors that utilise cyclic guanosine monophosphate (cGMP) as an intracellular second messenger. These include nitric oxide and the natriuretic peptide family (atrial, brain and C-type natriuretic peptides). In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. One PDE5 inhibitor, sildenafil, has been shown to improve pulmonary haemodynamics and exercise capacity in patients with PAH and is now an approved treatment. Others are under investigation. An interesting, although still tentative, observation is the potential of sildenafil to reduce pulmonary vascular resistance without adversely affecting ventilation-perfusion matching. Another is the expression of phosphodiesterase type 5 in the hypertrophied right ventricle. These data suggest that phosphodiesterase type 5 inhibitors may have effects that distinguish them from other treatments for pulmonary hypertension and merit further study." | Cyclic Nucleotide Phosphodiesterases, Type 5 |
This is a brief response to 'Do not despair about severity-yet' by Barra et al It argues that they have no serious criticisms of Daniel Hausman's essay, 'The Significance of Severity' and that indeed their work lends further support to his view that there is no justification for prioritising severity. As policy-akers, Barra and his coauthors are more constrained by popular attitudes, which apparently favour prioritising severity." | Hope |
Lomustine (CCNU) microcapsules was prepared by improved recoacervation method, then mixed microcapsules with 0.7% collagen swelling solution to prepare the emulsion, spreaded the emulsion on the plate to form membrane and cross-linked it, the membrane would be planted into body and was expected to release at steady speed. The concentration of CCNU and the CCNU content of microcapsules were measured by ultraviolet spectrophotometry to observe the release of CCNU be slow and constant, approach to 0-class release approximately. | Lomustine |
Congenic MRL-lpr mice homozygous and heterozygous for the IFN-gamma gene disruption were created to assess the role of this pleotropic cytokine on the lymphoaccumulation and lupus-like disease of Fas-defective mice. Early death was prevented, and glomerulonephritis severely reduced in IFN-gamma-/- mice. Hypergammaglobulinemia was maintained with a switch from IgG2a to IgG1 predominance, but the dramatic decrease in levels of the dominant IgG2a anti-dsDNA autoantibodies was not associated with a compensatory increase in TH2-associated IgG subclasses. Remarkably, early death and glomerulonephritis were also prevented in IFN-gamma+/- mice, although autoantibody levels and glomerular immune deposits were equivalent to IFN-gamma+/+ lpr mice, indicating the importance of additional locally-exerted disease-promoting effects of IFN-gamma. IFN-gamma-/- mice exhibited reduced lymphadenopathy concomitant to a decrease in DN B220(+) T cells. In vivo BrdU labeling showed reduced proliferation of DN B220(+) cells in IFN-gamma-/- vs. IFN-gamma+/+ lpr mice, while enhanced proliferation of all other T cell subsets was unaffected. Macrophages of IFN-gamma-/-lpr mice expressed markedly decreased levels of MHC class I and II molecules compared with controls. Moreover, the heightened expression of MHC class II molecules on proximal tubules of IFN-gamma+/+ lpr mice was significantly reduced in both IFN-gamma-/- and IFN-gamma+/- mice. The data indicate that IFN-gamma hyperproduction is required for lupus development, presumably by increasing MHC expression and autoantigen presentation to otherwise quiescent nontolerant anti-self T cells, and also by promoting local immune and inflammatory processes. | Lupus Vulgaris |
Over the past four decades, the patch clamp technique and nicotinic ACh (nACh) receptors have established an enduring partnership. Like all good partnerships, each partner has proven significant in its own right, while their union has spurred innumerable advances in life science research. A member and prototype of the superfamily of pentameric ligand-gated ion channels, the nACh receptor is a chemo-electric transducer, binding ACh released from nerves and rapidly opening its channel to cation flow to elicit cellular excitation. A subject of a Nobel Prize in Physiology or Medicine, the patch clamp technique provides unprecedented resolution of currents through single ion channels in their native cellular environments. Here, focusing on muscle and alpha7 nACh receptors, we describe the extraordinary contribution of the patch clamp technique towards understanding how they activate in response to neurotransmitter, how subtle structural and mechanistic differences among nACh receptor subtypes translate into significant physiological differences, and how nACh receptors are being exploited as therapeutic drug targets. LINKED ARTICLES: This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc/. | Nicotinic Antagonists |
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient presented with persistent fever and severe headache. Medical imaging examinations revealed multiple abnormal intracranial lesions. The patient had previously been misdiagnosed with encephalitis and acute disseminated encephalomyelitis" after visiting numerous hospitals. Eventually, by combing the characteristics of the case and genetic testing results, the patient was diagnosed with TSC accompanied by Mycoplasma pneumoniae infection. The purpose of this case report and literature review is to improve understanding of the clinical diagnosis and treatment of TSC so as to avoid misdiagnosis, missed diagnosis, and overtreatment." | Tuberous Sclerosis |
Non-gestational choriocarcinoma (NGCO) is a rare primary ovarian cancer with poor prognosis. It is important to distinguish it from gestational ovarian choriocarcinoma (GCO), because there are different treatment options. However, it is difficult to distinguish the two types by routine histologic, ultrastructural, or immunohistochemical examination. The authors present NGCO in a 41-year-old woman, which was confirmed by DNA polymorphism analysis. All tested microsatellite markers had identical DNA profiles with the same allelic sizes between tumor and normal myometrium of the patient, indicating that both tissues originated from the same person. The results confirmed that the tumor was non-gestational in origin. Although the tumor was large, the authors performed hand- assisted laparoscopic surgical (HALS) staging. After three cycles of combination chemotherapy and surgery, the patient has not had any evidence of disease 48 months after treatment. This case demonstrates the usefulness of HALS staging and DNA polymorphism analysis in NGCO." | Choriocarcinoma, Non-gestational |
BACKGROUND: Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis-nephrocalcinosis, progressive chronic kidney disease (CKD) and kidney failure (KF). Current management is symptomatic and does not prevent disease progression. Here we describe the contemporary DD1 picture across Europe to highlight its unmet needs. METHODS: A physician-based anonymous international e-survey supported by several European nephrology networks/societies was conducted. Questions focused on DD1 clinical features, diagnostic procedure and mutation spectra. RESULTS: A total of 207 DD1 male patients were reported; clinical data were available for 163 with confirmed CLCN5 mutations. Proteinuria was the most common manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithiasis. After 5.5 years, approximately 50% of patients presented with renal dysfunction, 20.7% developed CKD stage >/=3 and 11.1% developed KF. At the last visit, hypercalciuria was more frequent in paediatric patients than in adults (73.4% versus 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation, decreased glomerular filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared with those with early-stop mutations. CONCLUSIONS: Results from this large DD1 cohort confirm previous findings and provide new insights regarding age and genotype impact on CKD progression. Our data strongly support that DD1 should be considered in male patients with CKD, nephrocalcinosis/hypercalciuria and non-nephrotic proteinuria and provide additional support for new research opportunities. | Dent Disease |
The addition of prostaglandin (PG) D2 contracted helical strips of dog cerebral, coronary, renal and femoral arteries; the contraction was greatest in cerebral arteries. The contractile response of cerebral arteries was potentiated by aspirin and attenuated by polyphloretin phosphate. In the arterial strips contracted with PGF2 alpha, PGD2 elicited a concentration-related relaxation; the relaxation was greatest in mesenteric arteries. In mesenteric arterial strips contracted with norepinephrine, a lesser degree of relaxation was induced, and in the K+-contracted arteries, only a contraction was induced. Treatment with PGD2 attenuated the contractile response of cerebral and mesenteric arteries to PGF2 alpha or PGE2; this inhibitory effect was approximately 10 times greater in mesenteric arteries. However, the response to serotonin (for cerebral arteries) or norepinephrine (for mesenteric) was unaffected. It may be concluded that the heterogeneity of responses to PGD2 of a variety of dog arteries is due to different contributions of vasoconstrictor and vasodilator mechanisms. PGD2 appears to share the mechanism underlying arterial contraction with PGF2 alpha and PGE2, and interferes with the effect of these PG's possibly on receptor sites. | Polyphloretin Phosphate |
Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk variants. We reviewed the published literature from April 2020 to November 2022 searching for non-African American (non-AA) patients with FSGS associated with COVID-19 (eight White patients, six Hispanic patients, three Asian patients, one Indian patient, and one Asian Indian patient). The following histologic patterns were found: collapsing (n=11), not otherwise specified (n=5), tip (n=2), and perihilar (n=1). Fifteen of the 19 patients had AKI. The APOL1 genotype was reported in only six of the 19 non-AA patients. Three of them (two Hispanic patients and one White patient) with collapsing FSGS had high-risk APOL1 variants. The other three patients (two White patients and one Hispanic patient with the collapsing variant, tip variant, and not otherwise specified) had low-risk APOL1 variants. Among 53 African American patients with collapsing FSGS associated with COVID-19, 48 had high-risk APOL1 variants and five had low-risk APOL1 variants. We conclude that in non-AA patients, FSGS is a rare complication of COVID-19. FSGS associated with COVID-19 can occur rarely with low-risk APOL1 variants in non-AA and AA patients. Non-AA patients reported to be associated with high-risk APOL1 variants possibly reflect inaccuracy of self-reported race with AA admixture because of unknown ancestry. Given the importance of APOL1 in the pathogenesis of FSGS associated with viral infection and to avoid racial bias, it seems appropriate that APOL1 testing be considered in patients with FSGS associated with COVID-19, regardless of self-reported race. | Apolipoprotein L1 |
Upon HIV attachment, fusion and entry into the host cell cytoplasm, the viral core undergoes rearrangement to become the mature reverse transcription complex (RTC). Reduced infectivity of viral deletion mutants of the core proteins, capsid and negative factor (Nef), can be complemented by vesicular stomatitis virus (VSV) pseudotyping suggesting a role for these viral proteins in a common event immediately post-entry. This event may be necessary for correct trafficking of the early complex. Enzymatic activation of the complex occurs either before or during RTC maturation, and may be dependent on the presence of deoxynucleotides in the host cell. The RTC initially becomes enlarged immediately after entry, which is followed by a decrease in its sedimentation rate consistent with core uncoating. Several HIV proteins associated with the RTC and recently identified host-cell proteins are important for reverse transcription while genome-wide siRNA knockdown studies have identified additional host cell factors that may be required for reverse transcription. Determining precisely how these proteins assist the RTC function needs to be addressed. | Reverse Transcription |
Influenza virus infection was associated with development of oxidative stress in liver of mice, viz. increase in amount of lipid peroxidation products, decrease in cytochrome P-450 and NADP. H-cytochrome c-reductase activity, and inhibition of liver monooxygenases (aniline hydroxylase, ethylmorphine-N-demethylase, amidopyrine-N-demethylase and analgin-N-demethylase). These effects were most pronounced on the 7th day after virus inoculation as compared to the 5th one. Supplementation of mice with vitamin E before virus inoculation leads to liver protection against oxidative stress and toxicosis. A marked decrease of lipid peroxidation products and an increase of cytochrome P-450 and activities of monooxygenases was established. The stabilizing effect of vitamin E was dose-dependent and was most pronounced on the 5th day after virus inoculation as compared to the 7th one. | Aminopyrine N-Demethylase |
OBJECTIVE: To determine the management of patients with 1st trimester nausea and vomiting and hyperemesis gravidarum. METHODS: A panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. RESULTS: Hyperemesis gravidarum is distinguished from nausea and vomiting during pregnancy by weight loss>/=5 % or signs of dehydration or a PUQE score>/=7. Hospitalization is proposed when there is, at least, one of the following criteria: weight loss>/=10%, one or more clinical signs of dehydration, PUQE (Pregnancy Unique Quantification of Emesis and nausea) score>/=13, hypokalemia<3.0mmol/L, hyponatremia<120mmol/L, elevated serum creatinine>100mumol/L or resistance to treatment. Prenatal vitamins and iron supplementation should be stopped without stopping folic acid supplementation. Diet and lifestyle should be adjusted according to symptoms. Aromatherapy is not to be used. If the PUQE score is<6, even in the absence of proof of their benefit, ginger, pyridoxine (B6 vitamin), acupuncture or electrostimulation can be used, even in the absence of proof of benefit. It is proposed that drugs or combinations of drugs associated with the least severe and least frequent side effects should always be chosen for uses in 1st, 2nd or 3rd intention, taking into account the absence of superiority of a class over another to reduce the symptoms of nausea and vomiting of pregnancy and hypermesis gravidarum. To prevent Gayet Wernicke encephalopathy, Vitamin B1 must systematically be administered for hyperemesis gravidarum needing parenteral rehydration. Patients hospitalized for hyperemesis gravidarum should not be placed in isolation (put in the dark, confiscation of the mobile phone or ban on visits, etc.). Psychological support should be offered to all patients with hyperemesis gravidarum as well as information on patient' associations involved in supporting these women and their families. When returning home after hospitalization, care will be organized around a referring doctor. CONCLUSION: This work should contribute to improving the care of women with hyperemesis gravidarum. However, given the paucity in number and quality of the literature, researchers must invest in the field of nausea and vomiting in pregnancy, and HG to identify strategies to improve the quality of life of women with nausea and vomiting in pregnancy or hyperemesis gravidarum. | Obstetricians |
The ability of indoprofen or sodium indoprofen to inhibit phenylquinone-writhing and renal prostaglandin synthesis was determined in mice following a single oral dose of either drug. Male mice (4/group) were treated with 1.5 mg/kg indoprofen or sodium indoprofen. Inhibition of phenylquinone-writhing was determined at 2, 4, 8, 16 and 32 hr post treatment. Animals were sacrificed and blood collected for determination of plasma indoprofen concentration. Kidneys were removed and prepared for determination of renal prostaglandin synthesis by an in vitro technique. Phenylquinone-writhing was significantly depressed by both preparations at 2 and 4 hr post treatment. Sodium indoprofen also significantly depressed writhing at 8 hr post treatment. Renal prostaglandin synthesis, like phenylquinone-writhing, was significantly depressed at 2 and 4 hr after drug treatment. Plasma indoprofen concentration was correlated with both inhibition of phenylquinone-wrighing and inhibition of renal prostaglandin synthesis. When writhes were plotted versus prostaglandin synthesis, a positive correlation was observed suggesting a temporal relationship between inhibition of phenylquinone-writhing and inhibition of renal prostaglandin synthesis. | Indoprofen |
Sodium cyanide (NaCN) is a commonly and widely used industrial and laboratory chemical reagent that is highly toxic. Its availability and rapid harmful/lethal effects combine to make cyanide a potential foodborne/waterborne intentional-poisoning hazard. Thus, laboratory studies are needed to understand the dose-dependent progression of toxicity/lethality following ingestion of cyanide-poisoned foods/liquids. We developed an oral-dosing method in which a standard pipette was used to dispense a sodium cyanide solution into the cheek, and the rat then swallowed the solution. Following poisoning (4-128 mg/kg), overt toxic signs were recorded and survival was evaluated periodically up to 30 hours thereafter. Toxic signs for NaCN doses higher than 16 mg/kg progressed quickly from head burial and mastication, to lethargy, convulsions, gasping/respiratory distress, and death. In a follow-on study, trained operant-behavioral performance was assessed immediately following cyanide exposure (4-64 mg/kg) continuously for 5 h and again the following day. Onset of behavioral intoxication (i.e., behavioral suppression) occurred more rapidly and lasted longer as the NaCN dose increased. This oral-consumption method with concomitant operantbehavioral assessment allowed for accurate dosing and quantification of intoxication onset, severity, and recovery, and will also be valuable in characterizing similar outcomes following varying medical countermeasure drugs and doses. | Sodium Cyanide |
Red-green color discrimination is compromised in anomalous trichromacy, the most common inherited color vision deficiency. This computational analysis tested whether three commercial optical filters with medium-to-long-wavelength stop bands increased information about colored surfaces. The surfaces were sampled from 50 hyperspectral images of outdoor scenes. At best, potential gains in the effective number of surfaces discriminable solely by color reached 9% in protanomaly and 15% in deuteranomaly, much less than with normal trichromacy. Gains were still less with lower scene illumination and more severe color vision deficiency. Stop-band filters may offer little improvement in objective real-world color discrimination. | Color Perception Tests |
The first known case of trisomy 20 mosaicism is described. As in other cases of (partial) trisomy 20, the patient showed scarce physical malformations. It is suggested that trisomies for chromosomes of the F group are rare not because they are lethal but as a result of the morphology of the chromosomes involved. | Chromosome Duplication |
We describe here the identification, purification, and characterization of a semialdehyde dehydrogenase with a novel fatty acid binding function. The coenzyme A derivative of an 125I-labeled long chain saturated fatty acid (13-iodo-tridecanoate) was used to tag proteins which bind myristoyl-CoA. A prominent 57 kDa band was identified, which was isolated from bovine liver by a high salt extraction followed by ammonium sulfate precipitation. Sequential chromatographic separation using phenyl-Sepharose, hydroxyapatite, DEAE-Sepharose, Mono Q, and Fast Flow S resins resulted in a purified protein that migrated as a single band of 57 kDa on denaturing gels. Sephacryl-200 gel filtration provided a native molecular mass estimation of 118 kDa suggesting that this protein exists as a dimer. Two-dimensional gel analysis resolved three isoform variants with pI values of 7.4, 7.7, and 7.9, respectively, and established that the pI = 7.9 form has the highest propensity for fatty acid binding. We proceeded to generate tryptic peptides from the purified protein and subjected several peptides to microchemical sequencing. Degenerate oligonucleotide probes were designed and polymerase chain reaction was used to generate a unique nucleotide sequence. Subsequent screening of a bovine liver cDNA library yielded a 1.7-kilobase clone which encodes a protein of 537 amino acids (58 kDa) with 95% identity to mammalian methylmalonate semialdehyde dehydrogenase (MMSDH). In vitro assays confirmed that the purified 57-kDa protein exhibited MMSDH activity, and that preincubation of the enzyme with fatty acyl-CoA inhibited its dehydrogenase activity. The myristyl-CoA analog therefore serves as an affinity label for MMSDH. We propose that fatty acyl CoAs may have the potential to function as enzyme regulators in vivo." | Methylmalonate-Semialdehyde Dehydrogenase (Acylating) |
The authors report a case of a 4-year-old child who developed hallucinations after hypospadias repair. He was brought to the emergency department the morning after outpatient surgery where the diagnosis of central anticholinergic syndrome was made. We review oxybutynin overdose and the importance of providing clear instruction to parents and caregivers about the administration of medications. | Muscarinic Antagonists |
Management of patients with aneurysmal subarachnoid hemorrhage focuses on prevention of rebleeding by early treatment of the aneurysm, as well as detection and management of neurologic and medical complications. Early detection of delayed cerebral ischemia and management of modifiable contributing causes such as vasospasm take a central role, with the goal of preventing irreversible cerebral injury. In efforts to prevent delayed cerebral ischemia, multimodality monitoring has emerged as a promising tool in detecting subclinical physiologic changes before infarction occurs. However, there has been much variability in the utilization of this technology. Recent consensus guidelines discuss the role of multimodality monitoring in acute brain injury. In this review, we evaluate these guidelines and the utility of each modality of multimodality monitoring in aneurysmal subarachnoid hemorrhage. | Brain Ischemia |
This article reviews possible clinical applications of positron emission tomography (PET) in brain tumor patients. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry. It therefore provides different information about tumors when compared to histological or neuroradiological methods. Common clinical indications for PET comprise tumor delineation and identification of the metabolically most active tumor regions (target for biopsy, differentiation of viable tumor from necrosis). Further, the spatial relation between brain activated e.g., by speech, and the tumor bulk can be explored by activation studies. PET could also aid in the prediction of treatment response by measurement of tumor perfusion or hypoxia. Moreover, PET tracers could identify treatment targets e.g., gene products. The latter topic has not been systematically evaluated in human patients. | Tomography, Emission-Computed |
Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMV or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV. | Arenavirus |
This paper describes a fully spike-based neural network for optical flow estimation from dynamic vision sensor data. A low power embedded implementation of the method, which combines the asynchronous time-based image sensor with IBM's TrueNorth Neurosynaptic System, is presented. The sensor generates spikes with submillisecond resolution in response to scene illumination changes. These spike are processed by a spiking neural network running on TrueNorth with a 1-ms resolution to accurately determine the order and time difference of spikes from neighbouring pixels, and therefore infer the velocity. The spiking neural network is a variant of the Barlow Levick method for optical flow estimation. The system is evaluated on two recordings for which ground truth motion is available, and achieves an average endpoint error of 11% at an estimated power budget of under 80 mW for the sensor and computation. | Models, Neurological |
A 7-year-old neutered male Jack Russell terrier-cross was presented for signs of recurrent paraphimosis, despite previous surgical enlargement of the preputial ostium. Revision surgery was performed using a combination of preputial advancement and phallopexy, which resulted in complete and permanent coverage of the glans penis by the prepuce, and at 1 year postoperatively, no recurrence of paraphimosis had been observed. The combined techniques allow preservation of the normal penile anatomy, are relatively simple to perform and provide a cosmetic result. We recommend this combination for the treatment of paraphimosis in the dog, particularly when other techniques have failed. | Paraphimosis |
BACKGROUND: Increases in pneumococcal meningitis were reported from Ghanaian regions that lie in the meningitis belt in 2016-2017, despite introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose schedule (6, 10, and 14 weeks). We describe pneumococcal meningitis epidemiology in the Ghanaian Northern and Upper West regions across two meningitis seasons. METHODS: Suspected meningitis cases were identified using World Health Organization standard definitions. Pneumococcal meningitis was confirmed if pneumococcus was the sole pathogen detected by polymerase chain reaction, culture, or latex agglutination in cerebrospinal fluid collected from a person with suspected meningitis during December 2015-March 2017. Pneumococcal serotyping was done using PCR. Annual age-specific pneumococcal meningitis incidence (cases per 100,000 population) was calculated, adjusting for suspected meningitis cases lacking confirmatory testing. FINDINGS: Among 153 pneumococcal meningitis cases, 137 (89.5%) were serotyped; 100 (73.0%) were PCV13-type, including 85 (62.0%) that were serotype 1, a PCV13-targeted serotype. Persons aged >/=5 years accounted for 96.7% (148/153) of cases. Comparing 2015-2016 and 2016-2017 seasons, the proportion of non-serotype 1 PCV13-type cases decreased from 20.0% (9/45) to 4.1% (3/74) (p = 0.008), whereas the proportion that was serotype 1 was stable (71.1% (32/45) vs. 58.1% (43/74); p = 0.16). Estimated adjusted pneumococcal meningitis incidence was 1.8 in children aged <5 years and ranged from 6.8-10.5 in older children and adults. CONCLUSIONS: High pneumococcal meningitis incidence with a large proportion of serotype 1 disease in older children and adults suggests infant PCV13 vaccination has not induced herd protection with this schedule in this high-transmission setting. | Meningitis, Pneumococcal |
Feral raccoons (Procyon lotor) have been growing in number in Japan, and they are becoming a problematic invasive species. Consequently, they are commonly captured and killed in pest control programs. For effective population control of feral raccoons, it is necessary to understand their reproductive physiology and ecology. Although the reproductive traits of female raccoons are well known, those of the males are not well understood because specialized knowledge and facilities are required to study them. In this study, we first used a simple evaluation method to assess spermatogenesis and presence of spermatozoa in the tail of the epididymis of feral male raccoons by histologically examining the testis and epididymis. We then evaluated the possibility of using 7 variables-body weight, body length, body mass index, testicular weight, epididymal weight, testicular size and gonadosomatic index (GSI)-to estimate spermatogenesis and presence of spermatozoa in the tail of the epididymis. GSI and body weight were chosen as criteria for spermatogenesis, and GSI was chosen as the criterion for presence of spermatozoa in the tail of the epididymis. Because GSI is calculated from body weight and testicular weight, this model should be able to be used to estimate the reproductive state of male raccoons regardless of season and age when just these two parameters are known. In this study, GSI was demonstrated to be an index of reproductive state in male raccoons. To our knowledge, this is the first report of such a use for GSI in a member of the Carnivora. | Raccoons |
Non-surgical management of posterolateral corner (PLC) knee injuries is reserved for specific isolated mild to moderate injuries. There has been a relative scarcity of studies discussing non-surgical management existing secondary to the relative rarity of isolated PCL injuries. In these specific cases, a few studies have shown non-surgical management to result in satisfactory outcomes. This review of the literature outlines the outcomes and treatment options for posterolateral corner (PLC) knee injuries, which is based on the grade of the injury. However, no matter what the grade of injury, it is crucial to rule out other associated deficiencies before undertaking a nonoperative approach in the management of the posterolateral corner of the knee. | Knee Injuries |
The mammalian paraoxonases (PONs) have been linked to protection against oxidative stress. However, the physiological roles of members in this family (PON1, PON2, and PON3) are still being characterized. PON2 and PON3 are expressed in the aldosterone-sensitive distal nephron of the kidney and have been shown to negatively regulate expression of the epithelial sodium channel (ENaC), a trimeric ion channel that orchestrates salt and water homeostasis. To date, the nature of this phenomenon has not been explored. Therefore, to investigate the mechanism by which PON2 regulates ENaC, we expressed PON2 along with the ENaC subunits in fisher rat thyroid (FRT) cells, a system that is amenable to biochemical analyses of ENaC assembly and trafficking. We found that PON2 primarily resides in the endoplasmic reticulum (ER) in FRT cells, and its expression reduces the abundance of each ENaC subunit, reflecting enhanced subunit turnover. In contrast, no effect on the levels of mRNAs encoding the ENaC subunits was evident. Inhibition of lysosome function with chloroquine or NH4Cl did not alter the inhibitory effect of PON2 on ENaC expression. In contrast, PON2 accelerates ENaC degradation in a proteasome-dependent manner and acts before ENaC subunit ubiquitination. As a result of enhanced ENaC subunit ubiquitination and degradation, both channel surface expression and ENaC-mediated Na+ transport in FRT cells were reduced by PON2. Together, our data suggest that PON2 functions as an ER chaperone to monitor ENaC biogenesis and redirects the channel for ER-associated degradation. | Aryldialkylphosphatase |
Isoliquiritigenin (ISL), a flavonoid chalcone that is present in licorice, shallot, and bean sprouts, is known to have antitumorigenic activities. The present study examined whether ISL alters prostate cancer cell cycle progression. DU145 human and MatLyLu (MLL) rat prostate cancer cells were cultured with various concentrations of ISL. In both DU145 and MLL cells treated with ISL, the percentage of cells in the G1 phase increased, and the incorporation of [(3)H]thymidine decreased. ISL decreased the protein levels of cyclin D1, cyclin E, and cyclin-dependent kinase (CDK) 4, whereas cyclin A and CDK2 expressions were unaltered in cells treated with ISL. The expression of the CDK inhibitor p27(KIP1) was increased in cells treated with 20 micromol/L ISL. In addition, treatment of cells with 20 micromol/L ISL for 24 hours led to G2/M cell cycle arrest. Cell division control (CDC) 2 protein levels remained unchanged. The protein levels of phospho-CDC2 (Tyr15) and cyclin B1 were increased, and the CDC25C level was decreased by ISL dose-dependently. We demonstrate that ISL promotes cell cycle arrest in DU145 and MLL cells, thereby providing insights into the mechanisms underlying its antitumorigenic activities. | Shallots |
BACKGROUND: Introgression of mitochondrial DNA (mtDNA) is among the most frequently described cases of reticulate evolution. The tendency of mtDNA to cross interspecific barriers is somewhat counter-intuitive considering the key function of enzymes that it encodes in the oxidative-phosphorylation process, which could give rise to hybrid dysfunction. How mtDNA reticulation affects the evolution of metabolic functions is, however, uncertain. Here we investigated how morpho-physiological traits vary in natural populations of a common rodent (the bank vole, Myodes glareolus) and whether this variation could be associated with mtDNA introgression. First, we confirmed that M. glareolus harbour mtDNA introgressed from M. rutilus by analyzing mtDNA (cytochrome b, 954 bp) and nuclear DNA (four markers; 2333 bp in total) sequence variation and reconstructing loci phylogenies among six natural populations in Finland. We then studied geographic variation in body size and basal metabolic rate (BMR) among the populations of M. glareolus and tested its relationship with mtDNA type. RESULTS: Myodes glareolus and its arctic neighbour, M. rutilus, are reciprocally monophyletic at the analyzed nuclear DNA loci. In contrast, the two northernmost populations of M. glareolus have a fixed mitotype that is shared with M. rutilus, likely due to introgressive hybridization. The analyses of phenotypic traits revealed that the body mass and whole-body, but not mass corrected, BMR are significantly reduced in M. glareolus females from northern Finland that also have the introgressed mitotype. Restricting the analysis to the single population where the mitotypes coexist, the association of mtDNA type with whole-body BMR remained but those with mass corrected BMR and body mass did not. Mitochondrial sequence variation in the introgressed haplotypes is compatible with demographic growth of the populations, but may also be a result of positive selection. CONCLUSION: Our results show that the phenotypic traits vary markedly along the north-south axis of populations of M. glareolus. This variation may be related to adaptation to local environments and coincides with the gradient of genome reticulation between M. glareolus and M. rutilus, which was assessed by mtDNA introgression. Introgression of mtDNA may have affected morpho-physiological traits but do not show strong effects on either body mass or basal metabolic rate alone. We discuss the causes and biological meaning of our results and the means to clarify these questions in future research. | Arvicolinae |
Post marketing data offer rich information and cost-effective resources for physicians and policy-makers to address some critical scientific questions in clinical practice. However, the complex confounding structures (e.g., nonlinear and nonadditive interactions) embedded in these observational data often pose major analytical challenges for proper analysis to draw valid conclusions. Furthermore, often made available as electronic health records (EHRs), these data are usually massive with hundreds of thousands observational records, which introduce additional computational challenges. In this paper, for comparative effectiveness analysis, we propose a statistically robust yet computationally efficient propensity score (PS) approach to adjust for the complex confounding structures. Specifically, we propose a kernel-based machine learning method for flexibly and robustly PS modeling to obtain valid PS estimation from observational data with complex confounding structures. The estimated propensity score is then used in the second stage analysis to obtain the consistent average treatment effect estimate. An empirical variance estimator based on the bootstrap is adopted. A split-and-merge algorithm is further developed to reduce the computational workload of the proposed method for big data, and to obtain a valid variance estimator of the average treatment effect estimate as a by-product. As shown by extensive numerical studies and an application to postoperative pain EHR data comparative effectiveness analysis, the proposed approach consistently outperforms other competing methods, demonstrating its practical utility. | Propensity Score |
Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of COVID-19 were identified on March 9, 2020 and since then 33,567 confirmed cases and 230 deaths were documented. In this study, viral whole genome sequencing was performed on 133 SARS-CoV-2 positive samples collected between March 2020 and January 2021. Phylogenetic analysis was conducted to evaluate the genomic diversity of circulating SARS-CoV-2 lineages in Cyprus. 15 different lineages were identified that clustered into three groups associated with the spring, summer and autumn/winter wave of SARS-CoV-2 incidence in Cyprus, respectively. The majority of the Cypriot samples belonged to the B.1.258 lineage first detected in September that spread rapidly and largely dominated the autumn/winter wave with a peak prevalence of 86% during the months of November and December. The B.1.1.7 UK variant (VOC-202012/01) was identified for the first time at the end of December and spread rapidly reaching 37% prevalence within one month. Overall, we describe the changing pattern of circulating SARS-CoV-2 lineages in Cyprus since the beginning of the pandemic until the end of January 2021. These findings highlight the role of importation of new variants through travel towards the emergence of successive waves of incidence in Cyprus and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures. | SARS-CoV-2 |
Addition of dihydroxyacetone phosphate (2.5 mM) or 3-phosphoglycerate (2.5 mM) to a suspension of isolated intact chloroplasts, which contains Pi only in low concentrations (0.2 mM) leads to a competitive inhibition of Pi uptake in the light. In consequence, the ATP/ADP ratio is strongly decreased. The rate of O2 evolution is also reduced under these conditions, but the degree of inhibition is much higher after addition of dihydroxyacetone phosphate than after addition of 3-phosphoglycerate. Therefore, besides the competitive inhibition of Pi uptake, additional effects of dihydroxyacetone phosphate and 3-phosphoglycerate on O2 evolution and CO2 fixation of isolated intact chloroplasts must occur, which are discussed. | Dihydroxyacetone Phosphate |
Adult male Sprague-Dawley rats were treated with the anabolic androgenic steroid nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) during 14 days. The effect on the densities of the neurokinin NK1 receptor in brain was examined with autoradiography. An overall tendency of attenuation of NK1 receptor density was observed after completed treatment with nandrolone decanoate. The density of the NK1 receptor was found to be significantly lower compared to control animals in the nucleus accumbens core (37% density reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region, no structures exhibited any significant reduction of NK1 receptor density. This result provides additional support to the hypothesis that substance P and the NK1 receptor may be involved as important components that participate in mediating physiological responses including the adverse behaviors often associated with chronically administrated anabolic androgenic steroids in human. | Nandrolone |
The in vitro activity of rifampin alone and in combination with oxacillin was determined for 75 Staphylococcus aureus strains (64 susceptible and 11 resistant to oxacillin). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by broth microdilution; antibiotic combinations were evaluated by microdilution checkerboard and time-kill studies. The 90% MIC of rifampin was less than or equal to 0.015 micrograms/ml after both 24 and 48 h of incubation. The 90% MBC of rifampin was less than or equal to 2.0 micrograms/ml on subculture at 24 h of incubation and less than or equal to 0.5 micrograms/ml on subculture at 48 h. MIC checkerboards with oxacillin-susceptible strains revealed an additive or indifferent effect in 35 strains (55%) and antagonism in 29 strains (45%). MBC checkerboards performed by subculture at 24 h demonstrated antagonism for all but one of the oxacillin-susceptible strains, with sub-MBCs of rifampin impairing the bactericidal activity of oxacillin. MBC checkerboards performed by 48-h subculture revealed antagonism with 37 strains (58%); in 26 additional strains (40%), a synergistic, additive, or indifferent effect was observed at low antibiotic concentrations, but antagonism was seen at higher concentrations. Time-kill studies tended to show indifference rather than antagonism with oxacillin plus rifampin. In checkerboards performed with oxacillin-resistant strains, the addition of rifampin did not improve oxacillin inhibitory or bactericidal activity to a clinically significant extent; however, the addition of oxacillin improved the bactericidal activity of rifampin at easily achievable serum concentrations. | Oxacillin |
The first workshop on endodontics, in 1978, pointed out that the standard of endodontics in the United Kingdom was poor. The British Endodontic Society has subsequently attempted to improve the remuneration in the NHS by conducting and publishing a survey, and also establishing guidelines for minimum acceptable standards. Despite this, in the author's opinion, there has been no improvement. However, four ways of raising the standards of endodontics are proposed. | Endodontics |
INTRODUCTION: Ischemia in ovarian torsion and subsequent reperfusion has significant effects on fertility in the long term. The most important reason for these changes is thought to be a reperfusion injury rather than ischemia. We aimed to evaluate whether the reperfusion injury following ovarian detorsion could be reduced by hypothermia and intermittent reperfusion. MATERIALS AND METHODS: Forty adult female rats were divided into five groups as follows: Sham (Sh) (nâ¯=â¯8), torsion detorsion (control TD) (nâ¯=â¯8), progressive reperfusion gradual detorsion" (GD) (nâ¯=â¯8), hypothermia (H) (nâ¯=â¯8) and the progressive reperfusion + hypothermia (GDâ¯+â¯H) (nâ¯=â¯8). In all rats, except for the Sh group, the left ovary was rotated counter clockwise 1080 degrees and fixed to the abdominal wall by three 5-0 non-absorbable sutures followed by the closure of the laparotomy. After 30â¯h, reperfusion was achieved following the detorsion of the ovaries. In both the control TD and H groups, the torsed ovaries were detorsed. H group, however, was subjected to hypothermia with ice packs 30â¯min before and during the detorsion. Tissue temperature was kept constant at 4⯠degrees C, controlled by a digital thermometer. In the GD group, the torsed ovary and pedicle were detorsed by 360 degrees , followed by a 5 min pause. This procedure was repeated twice until a complete detorsion was achieved. GDâ¯+â¯H group underwent hypothermia with ice packs 30â¯min before the procedure and the torsed ovary and pedicle were detorsed by 360 degrees . After a 5 min pause, we repeated this process twice to provide full detorsion. The tissue temperature was constantly held at 4⯠degrees C. In the hypothermia groups, we applied hypothermia for an additional 30â¯min after detorsion and then left the rats at normal body temperature during reperfusion. We followed the rats in all groups for 60â¯days. Then we excised the left ovaries of all rats through laparotomy and spared some of the ovaries for biochemical and pathological examination. Intracardiac blood was taken at the end of the procedure and it was sent to the biochemical laboratory to assess oxidative stress markers. Finally, all the animals were sacrificed with high-dose of anesthesia. RESULTS: Evaluation of the results revealed that oxidative stress markers were significantly lower, and antioxidant parameters were higher in the experimental groups compared with the control TD group (pâ¯<â¯0.05). Histopathologically, we found that tissues were preserved in GD, H, GDâ¯+â¯H groups (pâ¯<â¯0.05). When we compared the groups among each other, both biochemical and histopathological values in GDâ¯+â¯H group showed that the tissue was preserved from oxidative damage, albeit the difference did not reach a level of significance. DISCUSSION: Several studies have shown that both hypothermia and intermittent reperfusion protect tissue from IR damage in the early period. However, as far as we know there is no study on long-term outcomes of both practices. Our study showed that both hypothermia and intermittent reperfusion alone protect tissue from IR damage in the long term. However, it did not show the superiority of the combination of both methods compared to that of individual application. The advantages of these methods lie in their easy application and cost-effectiveness. We believe that our study will serve as a base for future studies on the subject." | Ovarian Torsion |
Analysis of glycogen debranching enzyme (debrancher) cDNA from a patient with glycogen storage disease type III revealed a deletion of 124 base pairs. A donor splice site mutation (IVS G+1 to T) was identified in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated enzyme due to premature termination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis of the patient's genomic DNA showed an additional, unique EcoRI fragment of 5.8 kb, which was inherited from the mother. These results suggested that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, and had a genetic defect relating to an aberrant 5.8-kb EcoRI fragment." | Glycogen Debranching Enzyme System |
1. During comparison of different test systems for examination on salmonellae the routine method revealed only 2 of 35 fishmeal consignments as positive. In second streaks after 48 hours on selective media 5 more consignments were discovered to contain samonellae. Using pre-enrichment culture gave evidence for 11 positive consignments altogether. 2. The pre-enrichment method led to about 20 times higher yields in isolating enterobacteriaceae than the usual enrichment method. 3. Neither salmonellae nor enterobacteriaceae statistically showed uniform distribution in fishmeal. In addition, with the aid of the variance test of homogenity, an extremely heterogeneous ratio of the both germ types to each other was proved. Consequently, assaying the enterobacteriaceae contents is not suitable to draw any reliable conclusions upon the salmonellae contents of fishmeal. 4. Assuming a constant contamination rate of 400.000 salmonella units in consignments of 100 tons and testing them by the required 47 random samples, it can be deduced from probability calculus that only about 1 per cent of a larger number of consignments will fail to be recognized as positive. This risk of acceptance increases progressively with diminishing rate of salmonella contamination. Thus about 80 per cent of consignments containing even as much as 20.000 salmonella units will be accepted as false negatives". 5. Because of the usually low contamination rates of fishmeal it is an erroneous idea to increase the efficiency of assay by modifying the sample sizes in relation to the shipping weight. For this reason the orders for fishmeal examination in the Federal Republic of Germany should be revised. It is suggested to take at least the number of samples required hitherto for consignments of 100 tons. By this without doubt the risk of accepting "false negatives" can be reduced significantly, but it remains still impossible to recognite every contaminated fishmeal consignment and to stop its acceptance by bacteriological examination. 6. From practical examinations and theoretical considerations it is derivable that one has either to tolerate a low degree of salmonella contamination which hygienically may be without any importance or to treat every imported fishmeal by irradiation or heat pelleting." | Fish Flour |
To define the epidemiology, pathogenesis, pathology, presentation, and management of tuberculous mycotic aneurysm of the aorta (TBAA) in the therapeutic era, we reviewed all of the cases reported in the English language literature from 1945 to the present. To the 39 cases in the published literature, we add two cases of our own. Although it is exceedingly rare, the prevalence of this lesion has remained relatively constant. In 75% of the cases, TBAA appeared to result from erosion of the aortic wall by a contiguous focus; 25% from direct seeding of the aortic intima or of the adventitia or media (via the vasa vasorum). Most of the aneurysms were saccular (90%) and false (88%). The thoracic and abdominal aortas were affected with equal frequency. The mean (+/- SD) age of the patients was 50+/-16 years. Twenty-two were men, and 19 were women. In 63% of the cases, tuberculosis (TB) was diagnosed at presentation. Disseminated TB was present in 46% of the cases. One or more of three clinical scenarios suggested TBAA: persistent pain, major bleeding, and a palpable or radiographically visible para-aortic mass, especially if it is expanding or pulsatile. In turn, each of these findings suggested a complication of TBAA that may be an indication for surgical intervention. Among the patients who were offered both medical and surgical treatment, 20 of 23 (87%) survived. Among those who were offered only one form of treatment or were offered no treatment at all there were no survivors. Both in situ reconstruction with a prosthetic graft, and extra-anatomic bypass appeared to offer excellent results, provided that an effective regimen of antituberculous drugs was delivered postoperatively. We offer our conclusions: (1) symptomatic TBAA is a rare but uniformly fatal lesion if not diagnosed promptly, (2) in the context of active TB, and especially miliary TB, TBAA should be suspected whenever one or more of the three clinical scenarios are present, and (3) combined medical and surgical therapy appears to offer the best chance of a cure. | Aneurysm, Infected |
Based on the features of molecular pharmacognosy subjects, this paper analyzed and induced three features of the curriculum, basic contents and learning methods of it for the need of under-graduate or post-graduate students study. The future development of the molecular pharmacognosy was also introduced in this paper. It was aimed to make the students clear about the subject of molecular pharmacognosy on the whole and spread it in teaching. | Pharmacognosy |
The sterols 7 alpha-hydroxycholest-4-en-3-one (I) and 5 alpha-cholestane-3 alpha,7 alpha-diol (II) are competitive inhibitors for rabbit hepatic microsomal preparations of steroid 12 alpha-hydroxylase with apparent Ki values of 56 and 93 microM, respectively. To ascertain the optimum structure for a substrate with maximal enzymic activity, nine sterols or steroidal acids containing the 7 alpha-hydroxy-4-en-3-one or 3 alpha,7 alpha-dihydroxy-5 alpha configuration were prepared and studied as inhibitors with enzyme preparations in the presence of NADPH, oxygen and appropriate cofactors. Although each of these compounds exhibited competitive inhibition, the best inhibitor for sterol (I) was 7 alpha,25-dihydroxycholest-4-en-3-one (IV) (Ki 36 microM). Steroidal acids (3-oxo-7 alpha-hydroxychol-4-enoic acid and 3-oxo-7 alpha-hydroxy-4-cholene-24-carboxylic acid) were poor inhibitors (Ki 1080 and 654 microM, respectively). For sterol (II) the best inhibitors were sterol (IV) (Ki 35 microM) and 5 alpha-cholestane-3 alpha,7 alpha,25-triol (VIII) (Ki 45 microM). The 12 alpha-hydroxylated products of sterols (I) and (IV) were less tightly bound to the enzyme (Ki 88 and 98 microM, respectively) in the presence of sterol (II). Allochenodeoxycholic acid (Ki 495 microM) was not a good inhibitor for sterol (II). 12 alpha-Hydroxylated products of sterols (IV) and (VIII) were isolated from larger scale incubations, separated by HPLC and identified by mass spectrometry. | Steroid 12-alpha-Hydroxylase |
The need of highly viable cells dissociated from Schmidtea mediterranea is constantly growing. In this chapter, we describe a cell dissociation method based on papain (papaya peptidase I). This enzyme, often used to dissociate cells with complex morphology, is a cysteine protease with a broad specificity and increases both the yield and the viability of the dissociated cell suspension. The papain dissociation is preceded by a pretreatment for mucus removal, as this was shown to greatly improve the yield of cell dissociation, regardless of the method used. Papain-dissociated cells are suitable for a variety of downstream applications, like live immunostaining, flow cytometry, cell sorting, transcriptomics, and cell transplantation, also at the single-cell level. | Mediterranea |
Arabidopsis thaliana glucuronokinase (AtGlcAK) was cloned and shown to be able to use various uronic acids as substrates to produce the corresponding uronic acid-1-phosphates. AtGlcAK or Bifidobacterium infantis galactokinase (BiGalK) was used with a UDP-sugar pyrophosphorylase, an inorganic pyrophosphatase, with or without a glycosyltransferase for highly efficient synthesis of UDP-uronic acids and glucuronides. These improved cost-effective one-pot multienzyme (OPME) systems avoid the use of nicotinamide adenine dinucleotide (NAD(+))-cofactor in dehydrogenase-dependent UDP-glucuronic acid production processes and can be broadly applied for synthesizing various glucuronic acid-containing molecules. | Uronic Acids |
Effects of dopaminergic drugs (L-dopa plus benserazide, or nomifensine) on human visual function have been tested in healthy volunteers by measuring the psychophysical contrast sensitivity for sinusoidal gratings of various spatial frequencies. After drug administration the contrast sensitivity improved in all subjects over a limited range of medium to high spatial frequencies. | Benserazide |
BACKGROUND: Most nursing facilities (NFs) lack methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) surveillance programs due to limited resources and high costs. We investigated the utility of environmental screening of high-touch surfaces in patient rooms as a way to circumvent these challenges. METHODS: We compared MRSA and VRE culture data from high-touch surfaces in patients' rooms (14450 samples from 6 NFs) and ranked each site's performance in predicting patient colonization (7413 samples). The best-performing sites were included in a MRSA- and a VRE-specific panel that functioned as a proxy for patient colonization. Molecular typing was performed to confirm available concordant patient-environment pairs. RESULTS: We identified and validated a MRSA panel that consisted of the bed controls, nurse call button, bed rail, and TV remote control. The VRE panel included the toilet seat, bed controls, bed rail, TV remote control, and top of the side table. Panel colonization data tracked patient colonization. Negative predictive values were 89%-92% for MRSA and 82%-84% for VRE. Molecular typing confirmed a strong clonal type relationship in available concordant patient-environment pairs (98% for MRSA, 91% for VRE), pointing to common epidemiological patterns for environmental and patient isolates. CONCLUSIONS: Environmental panels used as a proxy for patient colonization and incorporated into facility surveillance protocols can guide decolonization strategies, improve awareness of MRSA and VRE burden, and inform efforts to reduce transmission. Targeted environmental screening may be a viable surveillance strategy for MRSA and VRE detection in NFs. | Bathroom Equipment |
Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-alpha production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-kappaB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-alpha production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis. | Endotoxin Tolerance |
Treatment with flutamide has been associated with clinical hepatotoxicty. The toxicity, metabolism,and transport of flutamide were investigated using cultured human hepatocytes. Flutamide and its major metabolite, 2-hydroxyflutamide, caused an inhibition of taurocholate efflux in human hepatocytes with an IC50=75 microM and 110 microM, respectively. Treatment of hepatocytes with flutamide or 2-hydroxyflutamide for 24 h resulted in time- and concentration-dependent toxicity as assessed by inhibition of protein synthesis. Toxicity was greater after 1 h than after 24 h of treatment. Recovery in inhibition of protein synthesis by 24 h was attributed to the decreased presence of flutamide due to its metabolism. Flutamide was metabolized by hepatocytes to several metabolites, and formation of reactive intermediates of flutamide, as evidenced by the presence of glutathione-related adducts, was observed. Inhibition of flutamide metabolism by 1-aminobenzotriazole (ABT) resulted in enhancement of flutamide toxicity, which was associated with sustained levels of nonmetabolized drug. ABT also prevented the formation of reactive intermediates of flutamide. There was an additive toxicity when cells were treated with a combination of flutamide and 2-hydroxyflutamide. Simultaneous treatment with flutamide and acetaminophen (APAP) resulted in additive to synergistic toxic effects. Flutamide and APAP were found to have significant effects on each other's metabolism. Flutamide inhibited glucuronidation and sulfation of APAP, resulting in greater amounts of APAP available for bioactivation. APAP inhibited the hydroxylation of flutamide, and subsequent sulfation and acetylation of 4-nitro-3-(trifluoromethyl) aniline, a metabolite of flutamide. In summary, we suggest that inhibition of bile acid efflux by flutamide and its 2-hydroxy metabolite may play a role in flutamide-induced liver injury. Both flutamide and 2-hydroxyflutamide are responsible for cytotoxicity if not metabolized. The data also suggest a possible drug-drug interaction between flutamide and APAP, resulting in inhibition of flutamide metabolism and increased APAP bioactivation and toxicity. | Flutamide |
Pancreas divisum (PD) is a common anatomic variant of the pancreatic duct. Causal association between PD and pancreatitis has been debated for many years. Minor papilla sphincterotomy (miES) is offered in clinical practice to patients with idiopathic acute recurrent pancreatitis (iRAP) and PD. However, available data originate mainly from observational studies with many limitations. An ongoing international, multicenter, sham-controlled trial is evaluating the efficacy of miES in iRAP and PD. Endoscopic therapy for pain relief has limited to no benefit in patients with chronic abdominal pain or chronic pancreatitis who have PD and is not recommended. | Pancreas Divisum |
The 1st International Reference Reagents (IRR) of Diphtheria and Tetanus Toxoids for Flocculation Test (DIFT and TEFT) were established by the WHO in 1988. These reagents are essential for the standardization of assays used to calculate Lf units of toxoids. Candidate replacement materials were provided by several European vaccine manufacturers and were formulated and freeze-dried at NIBSC. This paper provides a summary of the results of an international collaborative study including 18 laboratories from 16 countries, which examined the candidate replacement materials in a variety of methods. Materials 02/176 and 04/150 were proposed and adopted by the Expert Committee on Biological Standardization of WHO in October 2007 as 2nd WHO International Standards of Diphtheria and Tetanus Toxoid for use in Flocculation Test. The replacement standards were assigned the value of 1100 and 690Lf/ampoule, respectively, based on results of flocculation tests carried out using provided reagents. Material coded 02/176 fully complied with the WHO specifications for stability, residual moisture content, precision of fill and sterility. Stability of material coded 04/150 was slightly lower than expected but predictions were based only on 2-year data and were to be further monitored, post-adoption. | Toxoids |
During the period 1923 to 1972, 62 women with theca-cell tumors were treated at Radiumhemmet. The mean age at diagnosis was 59.5 years. Concomitant endometrial carcinoma was found in 13 patients. At 1978, after a mean observation time of 15.5 years, 30 patients were alive. No patient died from thecoma. Malignant disease caused death in 7 women. No difference in survival was found between 20 patients and 40 controls matched by age and place of residence. | Thecoma |
The paper examines the first twenty verb-forms recorded for six Hebrew-speaking children aged between 1;2 and 2;1, and how they evolve into fully inflected verbs for three of these children. Discussion focuses first on what word-forms children initially select for the verbs they produce, what role these forms play in children's emergent grammar, and how emergent grammar is reflected in the acquisition of fully inflected forms of verbs. Children's early verb repertoire indicates that they possess a strong basis for moving into the expression of a variety of semantic roles and the syntax of a range of different verb-argument structures. On the other hand, children's initial use of verbs demonstrates that they still need to acquire considerable language-particular grammatical knowledge in order to encode such relations explicitly. This language-particular knowledge demonstrates a clear pattern of acquisition, in which aspect precedes inflectional marking for gender, followed by tense, and then by person. | Human Development |
In this work, the potential of Methylocystis hirsuta to simultaneously use methane and volatile fatty acids mixtures for triggering PHBV accumulation was assessed for the first time batchwise. Biotic controls carried out with CH(4) alone confirmed the inability of Methylocystis hirsuta to produce PHBV and achieved 71.2 +/- 7 g m(-3)d(-1) of PHB. Pure valeric acid and two synthetic mixtures simulating VFAs effluents from the anaerobic digestion of food waste at 35 degrees C (M(1)) and 55 degrees C (M(2)) were supplied to promote 3-HV inclusion. Results showed that pure valeric acid supported the highest polymer yields of 105.8 +/- 9 g m(-3)d(-1) (3-HB:3-HV=70:30). M(1) mixtures led to a maximum of 103 +/- 4 g m(-3)d(-1) of PHBV (3-HB:3-HV=85:15), while M(2) mixtures, which did not include valeric acid, showed no PHV synthesis. This suggested that the synthesis of PHBV from VFAs effluents depends on the composition of the mixtures, which can be tuned during the anaerobic digestion process. | Polyhydroxybutyrates |
Neonatal infections are responsible for 20% of neonatal deaths yearly. In this review, we focused on the origins of the commoner neonatal infections, and we define the role of obstetricians. Regarding group B Streptococcus, a key measure for the prevention of neonatal infection is the vaginal-rectal culture screening at term pregnancy. Intravenous penicillin is the first-line prophylaxis at the start of labor, with intravenous ampicillin as an alternative. First-generation cephalosporins or clindamycin are recommended in case of penicillin allergy. Concerning urinary tract infections (UTIs), guidelines recommend complete urinalysis and urine culture in the first trimester of pregnancy for the screening of asymptomatic bacteriuria. For lower UTIs, guidelines recommend nitrofurantoin as first-choice antibiotic. Amoxicillin or cefalexin are second-line antibiotics. For upper UTIs, guidelines recommend cephalexin per os as first line. Candida spp. colonization affects 20% of pregnant women; however, congenital fetal candidosis and Candida amnionitis are rare. First-line treatment in case of symptomatic vaginitis during pregnancy or asymptomatic colonization during the third trimester is vaginal clotrimazole. Fluconazole is not approved in pregnancy, especially during the first trimester. Genital mycoplasmas colonization during pregnancy is usually asymptomatic and associated with bacterial vaginosis. Colonization is related to neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pneumonia, chorioamnionitis, and sepsis. Macrolides are the first-line treatment along with lactobacillus supplementation. In cases of preterm premature rupture of membranes or preterm labor, ceftriaxone, clarithromycin, and metronidazole are required to prevent intra-amniotic infection. Intra-amniotic infection affects 1 to 5% of deliveries at term and one-third of preterm ones and is associated with perinatal death, early-onset neonatal sepsis, RDS, BPD, pneumonia, meningitis, and prematurity-related diseases. Guidelines recommend a combination of ampicillin and gentamicin, and in case of caesarean section, an additional dose of clindamycin or metronidazole is required. In conclusion, obstetricians should be aware that the treatment of maternal infection during pregnancy can prevent potentially lethal infections in the newborn. KEY POINTS: . Part of neonatal infections starts from maternal infections that must be treated during pregnancy.. . Streptococcus group B and asymptomatic bacteriuria should be investigated in pregnancy and treated.. . Mycoplasma and ureaplasma vaginal colonization during pregnancy is related to negative neonatal outcomes.. | Gynecologists |
Eph receptor tyrosine kinases play a key role in cell-cell communication. Lack of structural information on the entire multi-domain intracellular region of any Eph receptor has hindered understanding of their signaling mechanisms. Here, we use integrative structural biology to investigate the structure and dynamics of the EphA2 intracellular region. EphA2 promotes cancer malignancy through a poorly understood non-canonical form of signaling involving serine/threonine phosphorylation of the linker connecting its kinase and SAM domains. We show that accumulation of multiple linker negative charges, mimicking phosphorylation, induces cooperative changes in the EphA2 intracellular region from more closed to more extended conformations and perturbs the EphA2 juxtamembrane segment and kinase domain. In cells, linker negative charges promote EphA2 oligomerization. We also identify multiple kinases catalyzing linker phosphorylation. Our findings suggest multiple effects of linker phosphorylation on EphA2 signaling and imply that coordination of different kinases is necessary to promote EphA2 non-canonical signaling. | Receptor, EphA2 |
Urologic emergencies can involve the kidneys, ureters, bladder, urethra, penis, scrotum, or testicles. History and physical examination are essential to diagnosis, whereas imaging is increasingly used to confirm diagnoses. Acute urinary retention should be relieved with Foley placement. Penile emergencies include paraphimosis, which can be treated by foreskin reduction, whereas penile fracture and priapism require urologic intervention. Fournier gangrene and testicular torsion are scrotal emergencies requiring emergent surgery. Nephrolithiasis, although painful, is not an emergency unless there is concern for concomitant urinary tract infection, both ureters are obstructed by stones, or there is an obstructing stone in a solitary kidney. | Male Urogenital Diseases |
Infections of the vertebra and neighboring disc create the characteristic lesions of vertebral osteomyelitis. The incidence has been estimated to range from 0.3 to 6.5 cases/100,000 persons. The hematogenous route of infection is predominant while direct inoculation through iatrogenic procedures and contiguous spread from adjacent tissue are rare. Most patients with hematogenous vertebral osteomyelitis exhibit predisposing factors, such as advanced age and diabetes mellitus. Diagnosis is often delayed due to the nonspecific nature of back pain, the main symptom. Furthermore, fever is frequently absent. Staphylococcus aureus is the most prevalent pathogen of pyogenic vertebral osteomyelitis in Europe. Magnetic resonance imaging (MRI) is the method of choice for the radiological diagnosis and blood cultures belong to the standard procedures. In cases of negative blood cultures a biopsy is generally warranted for microbiological diagnosis, either by computed tomography (CT)-guided needle biopsy or open surgery. Randomized trials that have addressed different antibiotic regimens are lacking. The recommended duration of treatment ranges from 6 weeks to 3 months. Patients with abscesses and implant devices in particular should be treated for 3 months. | Bone Diseases, Infectious |
Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation (AF), there is a clinical need to test newer agents. One hundred patients with AF who had unsuccessful therapy with 1.9 +/- 1.0 type IA antiarrhythmic agents were randomized to receive either propafenone (n = 50) or sotalol (n = 50). Patients were stratified into 4 groups based on AF pattern (chronic vs paroxysmal) and left atrial size (large [> or = 4.5 cm] vs small [< 4.5]). The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method. For patients randomized to propafenone, 46 +/- 8%, 41 +/- 8% and 30 +/- 8% remained in sinus rhythm at 3, 6 and 12 months, respectively, after cardioversion. A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up (49 +/- 7%, 46 +/- 8% and 37 +/- 8% at 3, 6 and 12 months, respectively; p = NS). The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension. Except for constipation that occurred more frequently in patients treated with propafenone, adverse side effects were equally distributed between the 2 therapies. Two patients receiving sotalol died during follow-up. Propafenone and sotalol, 2 new antiarrhythmic agents, were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF. Response rates were not affected by arrhythmia pattern, left atrial size or unsuccessful prior drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) | Propafenone |
Hospitals should evaluate four approaches to providing high-quality, cost-effective care for Medicaid patients: Continue to focus on strengthening primary care and improving cost efficiency in the current Medicaid market. Develop value-based, risk-sharing contracts with existing Medicaid managed care organizations. Partner with existing Medicaid managed care organizations to develop new products for targeted market segments. Own a health plan targeting the Medicaid market segment. | Medicaid |
Cervical chondrocutaneous branchial remnants are rare congenital choristomas. These lesions contain a cartilage core surrounded by skin with adnexal structures and subcutaneous fat. Correspondingly, on ultrasound there is a tubular hypoechoic core surrounded by hyperechoic, while on CT there is central intermediate attenuation surrounded by fat attenuation tissues. These features are exemplified in this sine qua non radiology-pathology correlation article. Management includes complete surgical resection and evaluating for potential associated anomalies, such as other branchial apparatus anomalies, as well as cardiac anomalies. | Choristoma |
Objective: To study the effect of various laser-activated irrigation protocols on endodontic sealer penetration into the dentinal tubules. Background data: Laser-activated irrigation is helpful for smear layer removal and thus might increase the penetration of endodontic sealer into the dentinal tubules. Methods: Forty-eight mandibular premolars with straight canals were instrumented and divided into four groups: C-I group, conventional needle irrigation with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA); Er:YAG-I, Er,Cr:YSGG-I, and Nd:YAP-I groups, NaOCl and EDTA irrigations activated by erbium:yttrium-aluminum-garnet (Er:YAG), erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG), and neodymium:yttrium-aluminum-perovskite (Nd:YAP) lasers, respectively. The cleanness of the treated canals was evaluated by scanning electron microscopy (SEM). Then, canals were obturated with AH-Plus sealer labeled with rhodamine B (0.1%) and combined with gutta-percha. After setting, canals were sectioned at 2, 5, and 8 mm short from the root apex, and the penetration area of the AH-Plus into the dentinal tubules was observed using confocal laser scanning microscopy (CLSM). Results: SEM results indicated that the Er:YAG-I and Er,Cr:YSGG-I lasers were more effective than the Nd:YAP-I and C-I in removing the smear layer. CLSM results indicated that the average AH-Plus penetration areas among the tested groups were in ascending order: C-I < Nd:YAP-I < Er:YAG-I, Er,Cr:YSGG-I (p < 0.05). Conclusions: Laser-activated irrigations significantly increased the penetration of the endodontic sealer into the dentinal tubules, among which Er:YAG-I and Er,Cr:YSGG-I lasers were the most effective and may be considered routine protocols for endodontic treatment. | Sodium Hypochlorite |
The prevalence of the use of herbal medicines is on the rise across the world, especially amongst pregnant women. A fact that draws attention is that many species commonly used by pregnant women, including the Tropaeolum majus L. (Tropaeolaceae), also present inhibitory activity on the angiotensin-converting enzyme (ACE). Herein, we have investigated the effects of T. majus extract (HETM) on fetal development, evaluating its relationship with possible ACE inhibitory activity. Pregnant Wistar rats were treated with different HETM doses (3, 30 and 300 mg/kg/day) from gestational days 8-20. Rats were sacrificed on the day 20 of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights, maternal ACE activity and aldosterone levels, live fetuses mean; dead fetuses percentage, fetus weight, and fetal malformation. All pregnant rats treated with high HETM doses showed significant reduction in plasma ACE activity accompanied by a decrease in serum aldosterone levels. Moreover, significant changes in fetal development were observed, including growth retardation and renal damage after 20 days of gestation. Thus, data presented demonstrate the significant effects of the use of HETM on fetal development during pregnancy. | Tropaeolum |
The role of Brachyury and other T-box genes in the differentiation of mesoderm and endoderm of vertebrates is well established. Recently, homologues of Brachyury have been isolated from an increasing number of diverse organisms ranging from Cnidaria to vertebrates and insects. Comparative expression and function analysis allows the origin of the mesoderm and the evolution of the developmental role of Brachyury gene family in metazoans to be traced. The data suggest that an ancestral function of Brachyury was to designate a blastoporal region that had distinct properties in induction and axis elongation. A subset of blastoporal cells expressing Brachyury and other genes that convey specific mesodermal functions may have segregated as a distinct cell population from this region in the course of mesoderm evolution. | T-Box Domain Proteins |
Thirty-nine cases of pulmonary paragonimiasis due to Paragonimus westermani were identified in Manipur, India. Recurrent haemoptysis, often increased on exertion, was the most common symptom. The clinical features and radiological appearances simulated pulmonary tuberculosis and 23 cases were treated for tuberculosis for varying periods before the final diagnosis. Young males aged 11 to 30 years comprised two-thirds of the cases. The disease was acquired by eating raw or improperly cooked crabs (Potamon deham). Intradermal tests (IDT) employing a saline extract of adult Paragonimus were a simple and reliable method of detecting present or past infection. Erythema of large size even without wheal and pseudopodia may indicate a positive IDT. Charcot-Leyden crystals (CLC) were detected in all sputum samples positive for Paragonimus ova. In patients (four) presenting with pleural effusion, Paragonimus ova were not present in the sputum, stool or pleural fluid. Bithionol (2,2'-thiobis [4,6-dichlorophenol]) orally, 40 mg/kg body-weight/day, 10 to 25 doses, cured all cases and, except in one, side effects were minimal. Relapse in one patient after six months' treatment was apparently cured by a second course of Bithionol. | Bithionol |
Pretreatment with multiple methamphetamine injections prior to a high-dose methamphetamine challenge administration can attenuate long-term deficits in striatal and hippocampal serotonin content caused by the stimulant. The present data extend previous findings by demonstrating that rats pretreated with escalating doses methamphetamine did not exhibit dopamine deficits in the striatum, nor serotonin deficits in striatal, frontal cortical, or hippocampal tissues, 7 days after a challenge methamphetamine administration. This protection was not due to attenuation of methamphetamine-induced hyperthermia or altered brain methamphetamine concentrations. These data differ from previous findings thereby highlighting that different mechanisms contribute to the tolerance of the neurotoxic effects. | Drug Tolerance |
Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients(1). Both the number of transferred T cells and their differentiation state are critical determinants of effective responses(2,3). T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells(4,5) and lower therapeutic efficacy(6), whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial(7). Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8(+) T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8(+) T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential. | T Cell Transcription Factor 1 |
The great apes (orangutans, gorillas, chimpanzees, bonobos and humans) descended from a common ancestor around 13 million years ago, and since then their sex chromosomes have followed very different evolutionary paths. While great-ape X chromosomes are highly conserved, their Y chromosomes, reflecting the general lability and degeneration of this male-specific part of the genome since its early mammalian origin, have evolved rapidly both between and within species. Understanding great-ape Y chromosome structure, gene content and diversity would provide a valuable evolutionary context for the human Y, and would also illuminate sex-biased behaviours, and the effects of the evolutionary pressures exerted by different mating strategies on this male-specific part of the genome. High-quality Y-chromosome sequences are available for human and chimpanzee (and low-quality for gorilla). The chromosomes differ in size, sequence organisation and content, and while retaining a relatively stable set of ancestral single-copy genes, show considerable variation in content and copy number of ampliconic multi-copy genes. Studies of Y-chromosome diversity in other great apes are relatively undeveloped compared to those in humans, but have nevertheless provided insights into speciation, dispersal, and mating patterns. Future studies, including data from larger sample sizes of wild-born and geographically well-defined individuals, and full Y-chromosome sequences from bonobos, gorillas and orangutans, promise to further our understanding of population histories, male-biased behaviours, mutation processes, and the functions of Y-chromosomal genes. | Y Chromosome |
Fibrillar collagens, the most abundant proteins in the vertebrate body, are involved in a plethora of biological interactions. Plasma protein von Willebrand factor (VWF) mediates adhesion of blood platelets to fibrillar collagen types I, II, and III, which is essential for normal haemostasis. High affinity VWF-binding sequences have been identified in the homotrimeric collagen types II and III, however, it is unclear how VWF recognizes the heterotrimeric collagen type I, the superstructure of which is unknown. Here we present the crystal structure of VWF domain A3 bound to a collagen type III-derived homotrimeric peptide. Our structure reveals that VWF-A3 interacts with all three collagen chains and binds through conformational selection to a sequence that is one triplet longer than was previously appreciated from platelet and VWF binding studies. The VWF-binding site overlaps those of SPARC (also known as osteonectin) and discodin domain receptor 2, but is more extended and shifted toward the collagen amino terminus. The observed collagen-binding mode of VWF-A3 provides direct structural constraints on collagen I chain registry. A VWF-binding site can be generated from the sequences RGQAGVMF, present in the two alpha1(I) chains, and RGEOGNIGF, in the unique alpha2(I) chain, provided that alpha2(I) is in the middle or trailing position. Combining these data with previous structural data on integrin binding to collagen yields strong support for the trailing position of the alpha2(I) chain, shedding light on the fundamental and long-standing question of the collagen I chain registry. | Collagen Type I |
Ivermectin is a macrocyclic lactone (fermentation) product and actinomycete (Streptomyces avermitilis) that possesses an unusually broad spectrum of potent activity against several species of nematodes, arachnids, and insects that parasitize domestic animals. From clinical trials in humans it has been found to be microfilaricidal, killing microfilariae of Onchocerca volvulus (the parasite causing onchocerciasis), and interrupting its transmission by the black fly vector. Dermal microfilariae density in patients are reduced to near zero levels for 6-12 months after a single oral dose of ivermectin 0.15-0.2 mg/kg. Its precise mechanism of action is unknown. It has a time to maximum concentration of 2.7-4.3 h, and an elimination half-life of 28 +/- 10 h. When compared with an oral solution the tablet dosage form has a relative bioavailability of approximately 60 percent. Not much is known about its metabolism in humans, and the unchanged drug is not detected in the urine. Controlled clinical trials have shown ivermectin to be associated with milder side effects than diethylcarbamazine, the current drug of choice for onchocerciasis therapy. It does not cause the severe Mazzoti-type (anaphylactoid) reactions that are associated with diethylcarbamazine use. Ivermectin is effective, safer, and more tolerable than diethylcarbamazine. It should, therefore, replace diethylcarbamazine as the drug of choice for onchocerciasis therapy. | Ivermectin |
The seemingly simple structure of the actin filament belies the elaborate signaling pathways that regulate its assembly and disassembly in eukaryotic cells. In retrospect, this signaling complexity should not be surprising. Actin regulates many dynamic cellular processes, including protein and organelle trafficking, establishment of cell polarity, directional migration, cellular traction, and the efficiency of endocytosis. Signaling events that coordinately control actin turnover during these processes must display a high degree of sophistication. Emerging data on an important regulator of actin dynamics, the actin-related protein 2 and 3 (Arp2/3) complex, suggest a model of how this may occur." | Actin-Related Protein 2-3 Complex |
An editorial about the use of usual and customary charges for out-of-network benefit determinations. | Insurance Coverage |
Gallbladder stones are common, but most persons with stones are asymptomatic. The symptoms of gallbladder stones are usually characteristic. They are often associated with other types of abdominal symptoms, which are not affected by cholecystectomy. Day surgery laparoscopic cholecystectomy is increasingly popular. The operation may be associated with serious complications, but the risk is low. 85-90% of patients operated with cholecystectomy are asymptomatic after the operation. | Cholecystectomy, Laparoscopic |
An ionic liquid (IL) was introduced into the organic-silica hybrid monolithic column as the stationary phase for capillary electrochromatography (CEC). The monolithic silica matrix containing chloropropyl functional group was prepared by the in situ co-condensation of tetramethoxysilane and (3-chloropropyl)-trimethoxysilane via a sol-gel process and chemical modification with N-methylimidazole. The electroosmotic flow of the IL-modified hybrid monolithic column was reversed at acidic pH and the morphology of the column was characterized by scanning electron microscope. Four aromatic hydrocarbons were completely separated with 40% acetonitrile phosphate buffer as the mobile phase and seven inorganic ions were efficiently separated with the phosphate buffer on the column in CEC. Reproducibilities of migration time for four aromatic hydrocarbons (benzene, naphthalene, anthracene, chrysene) were acceptable on IL-modified hybrid monolithic columns. Relative standard deviations of run-to-run (n=5), peak area-to-peak area (n=5), day-to-day (n=3) and column-to-column (n=3) were in the range of 0.72-0.88, 1.47-5.40, 2.44-4.99 and 3.01-8.11%, respectively." | Capillary Electrochromatography |
Ubiquitin is a 76-amino acid protein that is highly conserved among higher and lower eukaryotes. The polyubiquitin gene UBI4 encodes a unique precursor protein that contains five ubiquitin repeats organized in a head-to-tail arrangement. Although the involvement of the yeast polyubiquitin gene UBI4 in the stress response was reported long ago, there are no reports regarding the underlying mechanism of this involvement. In this study, we used UBI4-deletion and UBI4-overexpressing yeast strains as models to explore the potential mechanism by which UBI4 protects yeast cells against paraquat-induced oxidative stress. Here, we show that ubi4Delta cells exhibit oxidative stress, an apoptotic phenotype, and a decreased replicative lifespan. Additionally, the reduced resistance of ubi4Delta cells to paraquat that was observed in this study was rescued by overexpression of either the catalase or the mitochondrial superoxide dismutase SOD2. We also demonstrated that only SOD2 overexpression restored the replicative lifespan of ubi4Delta cells. In contrast to the case of ubi4Delta cells, UBI4 overexpression in wild-type yeast increases the yeast's resistance to paraquat, and this overexpression is associated with large pools of expressed ubiquitin and increased levels of ubiquitinated proteins. Collectively, these findings highlight the role of the polyubiquitin gene UBI4 in apoptosis and implicate UBI4 as a modulator of the replicative lifespan. | Ubiquitin C |
Bacteria can utilize signal molecules to coordinate their behavior to survive in dynamic multispecies communities. Indole is widespread in the natural environment, as a variety of both Gram-positive and Gram-negative bacteria (to date, 85 species) produce large quantities of indole. Although it has been known for over 100 years that many bacteria produce indole, the real biological roles of this molecule are only now beginning to be unveiled. As an intercellular signal molecule, indole controls diverse aspects of bacterial physiology, such as spore formation, plasmid stability, drug resistance, biofilm formation, and virulence in indole-producing bacteria. In contrast, many non-indole-producing bacteria, plants and animals produce diverse oxygenases which may interfere with indole signaling. It appears indole plays an important role in bacterial physiology, ecological balance, and possibly human health. Here we discuss our current knowledge and perspectives on indole signaling. | Microbiological Phenomena |
Job satisfaction surveys among physicians, a recent phenomenon, are a very important managerial tool to determine the work motivation needs of physician-employees. The first MD Job Survey was done in 1984 by Lichtenstein on physicians employed by prisons. The largest survey of salaried physicians to date has been the 1987 Health Services Research Center of Chapel Hill survey of physicians employed in group practices. Currently, individual group practices are surveying their staffs with job satisfaction questions in order to enhance the work environment. | Medical Staff |
The pKa of the catalytic base was lowered and its distance to the general acid catalyst, Glu179, was increased in the glucoamylase from Aspergillus awamori by replacing the catalytic base Glu400 with cysteine followed by oxidation to cysteinesulfinic acid [Fierobe, H.-P., Mirgorodskaya, E., McGuire, K. A., Roepstorff, P., Svensson, B. and Clarke, A. J. (1998) Biochemistry 37, 3743-3752. 1H NMR spectroscopy demonstrated that the oxidized mutant Glu400-->Cys-SO2H glucoamylase, like the wild-type, catalyzed hydrolysis with inversion of the anomeric configuration of the product. Relative to the catalytic base mutant Glu400-->Cys, the Cys400-SO2H glucoamylase had 700 times higher kcat toward maltose, while K(m) was unchanged. Compared to wild-type glucoamylase, the Cys400-SO2H derivative had kcat values of 150-190% and 85-320% on malto- and isomaltooligosaccharides, respectively, while K(m) values were similar to those of wild-type with the two disaccharides and 3.5-5.5- and 1.8-2.5-fold higher for the longer malto- and isomaltooligosaccharides substrates, respectively. The pH-activity dependence at saturating concentration of maltose indicated that the pKa of the catalytic base Cys400-SO2H was about 0.5 pH unit lower than that of wild-type Glu400. The Ki of Cys400-SO2H glucoamylase for the pseudotetrasaccharide and potent inhibitor acarbose increased more than 10(4)-fold, but Ki values of the mono- and disaccharide analogues 1-deoxynojirimycin and beta-O-methylacarviosinide were unchanged, suggesting perturbation at binding subsites beyond the catalytic center. A distinct property of Cys400-SO2H glucoamylase was the catalysis of the condensation of beta-D-glucopyranosyl fluoride and subsequent hydrolysis of the product to beta-glucose, under conditions where this was not detected for the wild-type enzyme. | Isomaltose |
Matrikines, peptides originating from the fragmentation of extracellular matrix proteins are identified to play important role in both health and disease. They possess biological activities, much different from their parent protein. Identification of such bioactive cryptic regions in the extracellular matrix proteins has attracted the researchers all over the world in the recent decade. These bioactive peptides could find use in preparation of biomaterials and tissue engineering applications. Matrikines identified in major extracellular matrix (ECM) proteins like collagen, elastin, fibronectin, and laminin are being extensively studied for use in tissue engineering and regenerative medicine. They are identified to modulate cellular activity like cell growth, proliferation, migration and may induce apoptosis. RGD, a well-known peptide identified in fibronectin with cell adhesive property is being investigated in designing biomaterials. Collagen hexapeptide GFOGER was found to promote cell adhesion and differentiation. Laminin also possesses regions with strong cell adhesion property. Recently, cell-penetrating peptides from elastin are used as a targeted delivery system for therapeutic drugs. The continued search for cryptic sequences in the extracellular matrix proteins along with advanced peptide coupling chemistries would lead to biomaterials with improved surface properties. This review article outlines the peptides derived from extracellular matrix and some of the possible applications of these peptides in therapeutics and tissue engineering applications. | Scleroproteins |
The role of prophylactic antibiotics in radical hysterectomy patients was studied in a double-blind randomized prospective study of mezlocillin (Mezlin, Miles Pharmaceuticals), a broad-spectrum semisynthetic penicillin, compared to placebo. Thirty evaluable patients received 4 g mezlocillin or saline placebo intravenously one-half hour before surgery, a second dose four to six hours later, and a final dose six hours after that. The rate of wound infection, postoperative use of additional antibiotics, fever index, and the incidence of standard febrile morbidity were all significantly lower in the mezlocillin group. Short-term perioperative prophylactic antibiotics are indicated in patients undergoing radical hysterectomy. | Mezlocillin |
An asymmetric approach for the synthesis of substituted delta-sultams with multiple synthetic handles is described. This study demonstrates the facile construction of a stereochemically diverse array of substituted delta-sultams, more specifically substituted 3,4,5,6-dihydro 1,2-thiazine 1,1-dioxides. A pivotal Mitsunobu alkylation/RCM sequence is used to assemble key allyl sultam building blocks possessing a C3 stereogenic handle. All subsequent reactions are achieved with high levels of diastereoselectivity to afford enantiopure delta-sultams in good yields. | Sulfonamides |
Bacterial infections of the central nervous system (CNS) continue to be an important cause of morbidity and mortality in children. The spectrum of bacterial infection of CNS includes; focal or multifocal infections like brain abscesses or subdural empyema; or more generalized or diffuse infections like pyogenic meningitis or ventriculitis. Focal and generalized infections may co-exist in an individual patient. Prompt and adequate antibiotic therapy and occasionally neurosurgical interventions are the cornerstone of effective management. The recent emergence of several multidrug-resistant bacteria poses a threat to the effective management of bacterial CNS infections. Several adjunctive anti-inflammatory and neuroprotective therapies are being tried, however; none has made a remarkable impact on the outcome. Consequently, bacterial CNS infections in children still remain a challenge to manage. In this review, authors discuss the current updates on the diagnostic and therapeutic aspects of bacterial infections of the CNS in children (post-neonatal age group). | Empyema, Subdural |
Here we announce the complete genome sequence of the symbiotic and nitrogen-fixing bacterium Sinorhizobium fredii USDA257. The genome shares a high degree of sequence similarity with the closely related broad-host-range strains S. fredii NGR234 and HH103. Most strikingly, the USDA257 genome encodes a wealth of secretory systems. | Sinorhizobium |
Fusion inhibitors can be an effective salvage therapy in HIV-patients with multiple resistances. However, the management and maintenance of the therapy, which requires percutaneous self-administration, can be a difficult task for patients. Preparation and administration are time-consuming and may force patients to alter their daily routine. Therefore, appropriate counselling and training is important. Evidence-based guidelines can help health care professionals to provide continuing high quality care. The department of Clinical Nursing Science at the University Hospital Basel have developed a nursing guideline, which formulates patient-management from decision-making up to the support needed in long-time treatment maintenance. The main focus of this article lies on the theoretical framework of this guideline and a description of its key elements. These are important aspects of managing the treatment of chronic illness in general. Therefore, this article addresses all health care providers supporting chronically ill patients in their medication management. | Enfuvirtide |
The classic view of representation in the cerebellum assumes two homunculi, one in the anterior lobe and one in the posterior lobe. Functional imaging has confirmed this somatotopy in the human anterior lobe but not, so far, in the posterior lobe. Using fMRI, we found separate peaks of activation for finger and toe in three ipsilateral cerebellar regions. In both the anterior and posterior lobe, the toe representation was semicircular around the finger area, with peaks of activation aligned in accord with the classic homunculi. Also, segregated peaks of activation were found in the pyramis vermis. These results confirm the existence of a second homunculus in the posterior lobe of the human cerebellum and suggest a third one. | Toes |
The present study investigated the effects of the SSRI fluoxetine and the serotonin synthesis blocker--parachlorophenylalanine (PCPA) on morphine self-administration and startle reactivity in rats subjected to social isolation during adulthood. Adult Wistar rats were housed individually or in pairs for 21days. They were treated with fluoxetine, PCPA, or vehicle and tested for their startle response and intake of a morphine solution (0.5mg/ml). Socially restricted rats consumed significantly more morphine solution (but not water) than rats living in pairs, in both one-bottle and in two-bottle tests. They also showed significantly higher startle response amplitude. Daily fluoxetine treatment (5mg/kg i.p.) counteracted these behavioral alterations induced by isolation housing while PCPA treatment (200mg/kg for 3 consecutive days) further exacerbated it. Social isolation may increase morphine self-administration and emotional reactivity in the startle box by affecting serotonin. Antidepressants (such as fluoxetine) may normalize or stabilize serotonin function and restore the behavioral changes produced by isolation. | Reflex, Startle |
Pearl oyster aquaculture is a major activity in French Polynesia atoll lagoons. After the economic decline that characterized the last decade, concerns recently rose about discarded installations and materials that supported aquaculture practices and by facilities abandoned after they had to close their activities. In May 2013, a first inventory of the type and amount of pearl farms derelict gear (PFDG) was achieved on 47 sites in Ahe lagoon. Surveys were conducted within and outside the boundaries of aquaculture concessions. Twenty types of PFDG littered the lagoon floor and the water column. The most impacted areas were near abandoned grafting houses with up to nine types of PFDG. Forty-five percent of the sites were impacted, including outside concessions. While management authorities are fully aware of the problem, this first assessment is a wake-up call to stimulate the cleaning of lagoons, enhance awareness among farmers, and identify potential ecological consequences on lagoon ecosystems. | Waste Products |
Caprine parain fl uenza virus type 3 (CPIV3) was first identified in goats named JS2013 in China. In 2019, a sheep herd broke a disease with respiratory disease in Hebei province, China. In order to confirm the pathogen of the disease, the nasal swabs, stool swabs and blood samples were collected from the sheep. Virus isolation was performed on MDBK cells and identification was conducted by RT-PCR. The complete genome of the isolate was sequenced and phylogenetic analyzed. In order to evaluate the pathogenicity of the virus, five seronegative sheep were experimental infected with the virus suspension. The phylogenetic analyses based on the complete genome and the M gene indicated that the isolate strain was distinguished distinct from previously reported CPIV3 lineage of JS2013. The virus-inoculated sheep displayed the syndrome with depression, cough, and fever. Virus shedding were detected by RT-PCR from nasal swabs. All infected showed virus shedding during 2 - 21dpi and viremia could be detected in serum samples. Gross pathological assessment of sheep in infected group showed gross lesion in the lungs. Histopathological observation results indicated that lungs had mild to moderate interstitial pneumonia, with thickened alveolar walls, decreased alveolar space, and increased amounts of inflammatory cells infiltration. This is the first report of pathogenicity of the novel lineage of sheep-derived CPIV3. The results would be helpful for further studies on the prevention and control strategies for CPIV3 infections in goat and sheep. | Parainfluenza Virus 3, Human |
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