Assessment of the insecticidal potential of Eucalyptus urograndis essential oil against Rhodnius neglectus Lent (Hemiptera: Reduviidae).
The resistance of triatomines to pyrethroids has been reported in several Latin American countries, including Brazil, indicating the need for the development of new approaches for the control of vectors of the Chagas disease. In here, we evaluated the insecticidal potential of the essential oil of Eucalyptus urograndis (Myrtaceae) against unsexed third and fourth instars of Rhodnius neglectus Lent (Hemiptera: Reduviidae) in topical application, fumigation, surface contact, and repellency . The insecticidal activity of the essential oil tested was detected by topical application (LD50 = 0.1731 μL/insect and LD99 = 0.2948 μL/insect for 24 h), fumigation (LC50 = 0.021 mL/mL air and LC99 = 0.1525 mL/mL air for 24 h) and surface contact (LC50 = 0.7073 μL/cm(2) and LC99 = 4.59 μL/cm(2) for 24 h). Mortality observed after 48-72-h exposure was very high and did not allow for any adjustment of the mortality curve. In the repellency assay, an effect was observed on 80% of tested nymphs. However, no repellency was observed after 24 h of exposure. Eucalyptus urograndis essential oil has a high insecticidal and repellent potential for R. neglectus nymphs, whether serving as a molecular model for new substances or as an alternative for the control of these insects.


Ascending uretero-pyelography in renal failure.
Ascending uretero-pyelography has been carried out over a period of 13 years in 97 consecutive patients with undiagnosed renal failure. Sixty-nine were in a non-obstructive uropathy group while 26 had ureteric obstructions. There were two failures. Over 60% of examinations were performed under local anaesthesia, each examination taking an average of 20 min. There has been no mortality and two anaesthetic complications have been the only significant morbidity. Ureteric injury, urinary infection and renal function have all been investigated and recorded. Five per cent of patients developed urinary infection following AUP but without any major consequences. No significant ureteric injury occurred and no late sequelae were noted. Neither any reaction to contrast medium nor any further deterioration in renal function was observed; AUP was diagnostic in 46% of patients. In the remainder it ruled out obstructive uropathy and gave useful information about the kidneys, ureters and bladder. In experienced hands and with proper facilities AUP is safe and can be helpful in the diagnosis and management of patients in renal failure.


The effects of corticotropin-releasing hormone on peptidergic neurons in the rat forebrain.
Our previous study showed that intracerebroventricular (ICV) administration of corticotropin-releasing hormone (CRH) produced a significant increase in locomotor activity at a dose of 1 microgram and slow stereotypy with prominent grooming at a dose of 10 micrograms. In addition, the ICV administration of CRH caused a significant increase in dopamine (DA) and norepinephrine turnover (NE) in various forebrain regions. The present study was designed to investigate the effects of the ICV administration of CRH on cholecystokinin (CCK), neuropeptide Y (NPY), somatostatin (SOM) and gamma-amino butyric acid (GABA) in the rat forebrain. The ICV administration of 1 and 10 micrograms CRH caused a marked reduction in CCK-like immunoreactivity (CCK-LI), NPY-LI and SOM-LI in the medial frontal cortex (MFC) and anterior cingulate cortex (Ant.CC), whereas it induced an increment of NPY-LI in the nucleus accumbens (NAc) and striatum. Increased SOM-LI and decreased NPY-LI were observed in the hippocampus following the ICV administration of CRH at both doses. The ICV administration of CRH caused a significant decrease in the BAGA content in the MFC, ant.CC, NAc and striatum. Taken together with our previous findings, these results indicate that the ICV administration of CRH induced classical neurotransmitter and neuropeptide abnormalities in the central nervous system which resulted increased emotionality, especially anxiety, in rats.


[Prediabetes as a therapeutic challenge in internal medicine].
The term prediabetes describes a fasting blood glucose level that is elevated but not yet in the diabetic range, a blood glucose level that is elevated after 120 min in a standard 75‑g oral glucose tolerance test, or both. The American Diabetes Association definition also includes glycated hemoglobin A (HbA1c). The incidence of prediabetes is rapidly increasing. Progression from normal glucose tolerance to diabetes is a continuous process. Insulin resistance and insulin secretory dysfunction, the simultaneous presence of which characterizes manifest diabetes, are already present in the prediabetic stage. Prediabetes is associated with an increased risk of diabetes; however, by no means all people with prediabetes go on to develop diabetes. Nevertheless, the identification of an increased risk of diabetes is still relevant insofar as it requires the adoption of diabetes prevention measures. Structured lifestyle intervention has been shown to be the most effective strategy for treating prediabetes. To increase its efficiency, it should, as far as possible, be made exclusively available to those people on whom it is most likely to confer a benefit. This would make it necessary to stratify people with prediabetes according to their risk profile. In a population of people at increased risk of diabetes (Tübingen Diabetes Family Study), a cluster analysis was performed, resulting in six clusters/subgroups. Within these, three high-risk subgroups were identified: Two of these risk groups show predominant insulin secretory dysfunction or predominant insulin resistance and high diabetes and cardiovascular risk. The third group shows a high risk of nephropathy and high mortality, but a comparatively lower diabetes risk. In general, prediabetes cannot yet be treated in a targeted pathophysiologically oriented manner. The new classification of prediabetes-based on pathophysiology-is now opening up new avenues for diabetes prevention. Current and future studies should confirm the assumption that the effectiveness of established, or not yet established, preventive measures depends on the respective subgroup.


Prevotella Copri and Microbiota in Rheumatoid Arthritis: Fully Convincing Evidence?
: Gut microbiota regulates the host's immune system. Microorganisms and their compounds can co-exist peacefully with the immune system and coordinate its function and regulation. Some microbial clusters may be harmful and others helpful in the respective negative or positive balance of the immune network. These insights have revealed important mechanisms for understanding and treating autoimmune and inflammatory diseases. This Editorial aims to clarify the role of specific genus of gut microbiota, such as Prevotella, in influencing the pathogenesis of Rheumatoid Arthritis (RA).


Clinical results of nonsurgical treatment for spinal metastases.
In contrast with many analyses of surgical treatment for spinal metastases, there have been only a few recent well-documented publications assessing nonsurgical treatment. This paper is a study of the outcome of nonsurgical therapy for metastatic tumors of the spine. One hundred and one patients with spinal metastases were treated with radiation therapy and/or chemotherapy without surgical intervention between 1990 and 1995, in prospective analysis, and had follow-up for more than 24 months. This study included 59 men and 42 women with a mean age of 61 years (range: 14 to 81). Mean follow-up periods were 11 months for patients dying of the disease and 53 months for the survivors. Neurological status, pain relief, functional improvement, and cumulative survival rate were assessed. Of the total treated, 67 patients (66%) were evaluated as being neurologically stable or improved after treatment. Pain relief was achieved in 67%, and 64% showed functional improvement. Primary lesion responsiveness to nonsurgical therapy influenced the survival, neurological recovery, pain control, and function. Neurological findings before therapy were useful in predicting ambulatory status after treatment. Nonsurgical treatment was often successful when primary tumors had responsiveness to radiation therapy and/or chemotherapy. We found this to be evident even when neurological deficits were found, particularly in lumbar spines. Spinal metastases of tumors with less responsiveness, unless patients were neurologically intact, responded poorly to therapy. Most of the patients who were successfully treated enjoyed relief lasting nearly until death. Their functional ability was limited by general debility, rather than by local tumor regeneration.


A simplified colorimetric micromethod for determination of serum cholesterol.
A simple and rapid micromethod is described for quantitation of cholesterol in 5-10 microliter of serum using uranyl acetate to deproteinize the serum and o-phthalaldehyde reagent to develop color. Independent analyses of serum samples by the present method and by two reference methods, Abell-Kendall and automated colorimetric method, indicated accuracy of the micromethod (r = 0.99). Use of capillary blood specimens makes this procedure applicable for screening infants and small children.


Absolute configuration of the hydroxyfarnesylethyl group of haem A, determined by X-ray structural analysis of bovine heart cytochrome c oxidase using methods applicable at 2.8 Angstrom resolution.
The absolute configuration of haem A, the prosthetic group of cytochrome c oxidase, was determined to be S by analysis of the bond angles surrounding the chiral centre of haem A after refinement with X-PLOR starting from respective initial structures with R and S configurations under absolute configuration constraints at 1.8 Angstrom resolution. The same result was obtained by refinement at 1.8 Angstrom resolution without the absolute configuration constraints. Both of these methods were applicable down to a resolution of about 2.8 Angstrom. The constrained refinement converges more quickly than the unconstrained refinement.


[Medial AV-nodular rhythm observed during an endolaryngeal micro-surgical intervention (author's transl)].
A case of therapy resistant junctional nodal rhythm in the course of a microsurgical laryngeal operation is reported. The interaction of possible reflex mechanisms is discussed. Attempts to reverse the electrocardioscopic findings with drugs were unsuccessful. Diminuation of the mechanical irritation caused by the operation-laryngoscope resulted in immediate return to sinusrhythm.


Abnormal visual processing and increased seizure susceptibility result from developmental exposure to the biocide methylisothiazolinone.
Methylisothiazolinone (MIT) is a commonly used biocide known to be neurotoxic in vitro. Brief exposure of cortical neurons in culture to MIT results in increased neurodegeneration, whereas chronic exposure of developing neurons in culture to low concentrations of MIT has been shown to interfere with normal neurite outgrowth. However, the effects of chronic MIT exposure on the developing nervous system have not been tested in vivo. Here we expose Xenopus laevis tadpoles to sub-lethal concentrations of MIT during a critical period in neural development. We find that MIT exposure results in deficits in visually mediated avoidance behavior and increased susceptibility to seizures, as well electrophysiological abnormalities in optic tectal function, without any effects on overall morphology, gross anatomy of the visual projections, overall visual function, and swimming ability. These effects indicate that chronic exposure to low levels of MIT results in neural circuit-level deficits that result in abnormal neurological function without causing increased mortality or even gross anatomical defects. Our findings, combined with the fact that the long-term neurological impacts of environmental exposure to MIT have not been determined, suggest a need for a closer evaluation of the safety of MIT in commercial and industrial products.


A cell-culture system for long-term maintenance of elevated hydrostatic pressure with the option of additional tension.
In cell stress research, there is still a need to apply long-term hydrostatic pressure without changing any other environmental condition. We present here a new, open, pressurized chamber system allowing long-term sustained and dynamic application of hydrostatic pressure with the option of additional tension. Based on the computer-controlled Flexcell Strain Unit, we designed a pressurized chamber with a dynamic airflow and a defined membrane extension, which can be regulated by spacers. During operation up to 26.6kPa, O(2) partial pressures and pH in the cell-culture medium do not change compared to control cultures kept at normal atmosphere.


Proteomic analysis of the EhV-86 virion.
Emiliania huxleyi virus 86 (EhV-86) is the type species of the genus Coccolithovirus within the family Phycodnaviridae. The fully sequenced 407,339 bp genome is predicted to encode 473 protein coding sequences (CDSs) and is the largest Phycodnaviridae sequenced to date. The majority of EhV-86 CDSs exhibit no similarity to proteins in the public databases. Proteomic analysis by 1-DE and then LC-MS/MS determined that the virion of EhV-86 is composed of at least 28 proteins, 23 of which are predicted to be membrane proteins. Besides the major capsid protein, putative function can be assigned to 4 other components of the virion: two lectin proteins, a thioredoxin and a serine/threonine protein kinase. This study represents the first steps toward the identification of the protein components that make up the EhV-86 virion. Aside from the major capsid protein, whose function in the virion is well known and defined, the nature of the other proteins suggest roles involved with viral budding, caspase activation, signalling, anti-oxidation, virus adsorption and host range determination.


Ultrasound in the evaluation of normal and induced ovulation.
In the past several years sonography has become an invaluable research tool for the investigation of spontaneous and induced ovulation and has added to the understanding of folliculogenesis and reproductive endocrinology. In practical terms, in ovulation induction sonography assists in the evaluation of the number and distribution of follicles, necessary for adequate interpretation of estrogen levels. Although there is no ideal size when it can be assumed that a follicle is mature, estimation of follicle size is of value and is a good guide to the timing of hCG administration. If the follicles are extremely small or there is evidence of hyperstimulation, these observations, together with the E2 levels, may be used to decide whether a further ultrasonic examination is warranted for the assessment of follicular growth or whether the treatment cycle should be abandoned. Provided follicular size is within normal limits, the diameter of the largest follicle may also be used in IVF programs to determine when the patient should be admitted to the hospital for more intensive monitoring of follicular development and the administration of hCG. Ultrasound is also valuable in patients with only one ovary accessible to laparoscopy. Even if the largest follicle is in the inaccessible ovary, the treatment cycle does not have to be abandoned, provided that several follicles are developing in the contralateral ovary. If neither ovary is accessible laparoscopically, percutaneous oocyte aspiration offers the patient the opportunity of IVF and embryo transfer.


Minimal residual disease detection using flow cytometry: Applications in acute leukemia.
Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia.


Survivin degradation by bergenin overcomes pemetrexed resistance.
Chemoresistance is a primary factor for treatment failure and tumor recurrence in non-small cell lung cancer (NSCLC) patients. The oncoprotein survivin is commonly upregulated in human malignancies and is associated with poor prognosis, but its effect on carcinogenesis and chemoresistance in NSCLC is not yet evident, and to explore an effective inhibitor targeting survivin expression is urgently needed. The protumor characteristics of survivin and antitumor activities of bergenin in NSCLC cells were examined by MTS, colony formation assays, immunoblot, immunohistochemistry, and in vivo xenograft development. Survivin was upregulated in non-small cell lung cancer (NSCLC) tissues, while its depletion inhibited NSCLC tumorigenesis. The current study focused on bergenin, identifying its effective antitumor effect on NSCLC cells both in vivo and in vitro. The results showed that bergenin could inhibit cell proliferation and induce the intrinsic pathway of apoptosis via downregulating survivin. Mechanistically, bergenin reduced the phosphorylation of survivin via inhibiting the Akt/Wee1/CDK1 signaling pathway, thus resulting in enhanced interaction between survivin and E3 ligase Fbxl7 to promote survivin ubiquitination and degradation. Furthermore, bergenin promoted chemoresistance in NSCLC cells re-sensitized to pemetrexed treatment. Survivin overexpression is required for maintaining multiple malignant phenotypes of NSCLC cells. Bergenin exerts a potent antitumor effect on NSCLC via targeting survivin, rendering it a promising agent for the treatment of NSCLC.


Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome.
Alterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) have not been well studied, partially because of a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with post-thrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of the disease and clinical outcomes of interventions. In the present study, we investigated the feasibility and diagnostic value of preintervention indirect lymphography in patients with CVO and their pre- and postintervention Villalta scores. A total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared between the legs with CVO and healthy legs. Moreover, the correlation between the lymphatic changes and clinical severity of PTS was evaluated using the Villalta score and CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. The mean patient age was 44 ± 12 years, and 10 patients (59%) were women. The patients had undergone treatment at a mean of 25 ± 6 months after their first episode of deep vein thrombosis. Five patients (29%) had had recurrent deep vein thrombosis. The mean pre- and postinterventional Villalta score was 10.5 ± 1.46 and 9.27 ± 1.12, respectively (P = .0096). Using the CEAP classification, four legs were class 5, seven were class 4, and three each were class 3 and 2. The primary and secondary patency rate was 70.5% and 82.5% after a mean follow-up of 18 months, respectively. Indirect lymphography of the superficial and deep lymphatic systems was completed before intervention in both legs for all 17 patients (21 legs). According to the qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis revealed abnormal function of the deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. Indirect lymphography is a feasible diagnostic tool to use for the evaluation of the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all our patients with moderate to severe PTS. The clinical significance of these lymphatic changes is not clear; however, an association between clinical severity and outcomes is possible.


Dopaminergic regulation of prolactin and growth hormone synthesis in rat pituitary tumor cells.
The dopaminergic regulation of prolactin (PRL) and growth hormone (GH) synthesis were studied in monolayer cultures of rat pituitary tumor (GH3) cells. PRL synthesis could not be inhibited by dopamine at concentrations ranging from 10(-9) to 10(-5) M. Bromocriptine inhibited PRL synthesis only at the very high concentration of 10(-5) M, and this effect was not reversible by metoclopramide. GH synthesis was inhibited by 10(-6) and 10(-5) M dopamine but not by bromocriptine, and the dopamine effect was blocked by metoclopramide. These results suggest the existence of a defective dopaminergic regulation of PRL and GH synthesis in GH3 cells.


The role of endothelin and RAS/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications.
Systemic sclerosis (SSc) is a disease of connective tissue with high rate of morbidity and mortality highlighted by extreme fibrosis affecting various organs such as the dermis, lungs, and heart. Until now, there is no specific cure for the fibrosis occurred in SSc disease. The SSc pathogenesis is yet unknown, but transforming growth factor beta (TGF-β), endothelin-1 (ET-1), and Ras-ERK1/2 cascade are the main factors contributing to the tissue fibrosis through extracellular matrix (ECM) accumulation. Several studies have hallmarked the association of ET-1 with or without TGF-β and Ras-ERK1/2 signaling in the development of SSc disease, vasculopathy, and fibrosis of the dermis, lungs, and several organs. Accordingly, different clinical and experimental studies have indicated the potential therapeutic role of ET-1 and Ras antagonists in these situations in SSc. In addition, ET-1 and connective tissue growth factor (CTGF) as a cofactor of the TGF-β cascade play a substantial initiative role in inducing fibrosis. Once initiated, TGF-β alone or in combination with ET-1 and CTGF can activate several kinase proteins such as the Ras-ERK1/2 pathway that serve as the fundamental factor for developing fibrosis. Furthermore, Salirasib is a synthetic small molecule that is able to inhibit all Ras forms. Therefore, it can be used as a potent therapeutic factor for fibrotic disorders. So, this review discusses the role of TGF-β/ET-1/Ras signaling and their involvement in SSc pathogenesis, particularly in its fibrotic situation.


Are factor V and prothrombin mutations associated with increased risk of oral cancer?
Methylenetetrahydrofolate reductase is associated with pathogenesis of both thrombosis and oral cancer. Therefore, a search for a similar association of other thrombosis-related factors with oral cancer is justified. In order to investigate whether the coagulation factor V Leiden and prothrombin G20210A mutations increase the risk of oral cancer, we searched for these mutant alleles by RFLP analysis in DNA samples of 102 patients with oral cancer and 120 healthy controls. Neither the Leiden nor the G20210A alleles were found in statistically different frequencies in the two groups. In addition, no statistical difference was observed in parameters such as sex, age and positive family history for cancer. Nevertheless, a significant difference was observed for Leiden in patients with a positive history for thrombophilia (p < 0.001). There seems to be no association of prothrombin, and possibly a minor contribution of factor V, in oncogenesis in the oral region.


Rate and determinants of 10-year persistence with antihypertensive drugs.
To assess the proportion of patients starting with antihypertensive drug treatment who continued treatment for at least 10 years. A retrospective cohort study. The PHARMO record linkage system containing drug dispensing records from community pharmacies and linked hospital discharge records of approximately 950 000 subjects. Patients who started using antihypertensive drugs (two or more prescriptions) in 1992 and did not receive a prescription for any antihypertensive drug in the 365 days preceding the first prescription. Persistence with antihypertensive drugs until 10 years. Among a total of 2325 patients who started using antihypertensive drugs, 39% used continuously during the 10 years of follow-up. Approximately 22% temporarily discontinued and restarted treatment, whereas 39% of patients discontinued permanently. Older patients were more persistent than younger patients [20-39 years: odds ratio (OR) 2.08; 95% confidence interval (CI) 1.52-2.84; 40-59 years: (reference), > or = 60 years: OR 0.69; 95% CI 0.54-0.89]. More patients who started with diuretics (reference) and beta blockers (OR 1.15; 95% CI 0.87-1.52) discontinued compared with those who started with dihydropyridine calcium antagonists (OR 0.54; 95% CI 0.34-0.84), and angiotensin-converting enzyme (ACE) inhibitors (OR 0.38; 95% CI 0.27-0.55). Patients who started with combination therapy (OR 0.29; 95% CI 0.14-0.54 compared with diuretics) or patients who were initially treated by a cardiologist (OR 0.82; 95% CI 0.61-0.97) or internist (OR 0.80; 95% CI 0.62-0.98 compared with general practitioners) also showed higher persistence. Long-term persistence in daily practice is low compared with persistence observed in randomized clinical trials and should be considered in the choice of a first-line antihypertensive agent.


Intradural jugular tuberclectomy in a case of inadequate extradural removal.
The jugular tubercles are paired protuberances that arise from the inferolateral margins of the clivus and project posterosuperiorly over the hypoglossal canal. These bony structures sometimes obscure and hinder surgical manipulation of lesions situated in the lateral and premedullary cisterns during extended far lateral suboccipital approaches. The application of intradural jugular tuberclectomy is described to remove this bony eminence. A case of ruptured dissecting aneurysm in the vertebral artery was treated through the transcondylar approach. Extradural removal of the posterior portion of the jugular tubercle was performed. The dura over the jugular tubercle was then removed, and the anterior part of the jugular tubercle was drilled away between the intradural hypoglossal canal foramen and jugular foramen under the lower cranial nerves. Great care was required during the intradural drilling procedure to prevent damage to the lower cranial nerves, brain stem, and jugular bulb. Intradural jugular tuberclectomy provided an adequate microscopic view of the midline anterior lower clival region. Intradural jugular tuberclectomy is a useful technique to remove the anterior part of this bony eminence after the transcondylar approach.


ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma.
ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts. Isogenic astrocytoma cells (+/-IDH1R132H/+/-ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/-ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells. Adding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition. ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.


[Cerebral convulsion following peridural anesthesia with bupivacaine in cesarean section].
Maternal convulsions and severe fetal bradycardia resulted from the accidental intravascular injection of 0.5% bupivacaine for epidural anesthesia in preparation for caesarean section. Ventilation with oxygen, application of anticonvulsive drugs, relaxation and intubation was promptly performed followed by immediate caesarean section. The newborn was depressed at birth, recovered quickly and showed no neurologic deficits neither in the immediate postnatal period nor in neurobehaviour tests at the age of three months.


[Inflammatory factors promote the expression of PD-L1 in Tca8113].
To investigate the mechanism of immunologic escape in the tumor microenvironment, study the expression of programmed death 1 ligand-1 (PD-L1) in Tca8113 with treatment of inflammatory factors. The expression of PD-L1 treated with inflammatory factors (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) was detected by flow cytometry (FCM). The expression of PD-L1 in Tca8113 was up-regulated conspicuously with treatment of inflammatory factors (P < 0.05), including: IL-1beta, IL-6, TNF-alpha, IFN-y. And the factors played the role in synergistic effects, most significantly in the groups of IL-1beta + IFN-gamma, TNF-alpha + IFN-gamma and IL-1beta + IL-6 + IFN-gamma + TNF-alpha. But the influence of IL-2 on the expression of PD-L1 was not significant (P > 0.05). With the up-regulated expression of PD-L1, the tumor would be escaped more easily from the immunoreactions, while there were an abundance of inflammatory factors in the tumor microenvironment.


In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence.
There is a paucity of research on reducing dressing adherence. This is partly due to lack of an in vitro model, recreating the clinical variability of wounds. Previously we described an in vitro gelatin model to evaluate adherence in a standardized manner. We present evaluation of strategies to reduce adherence in six dressings. Dressing materials used were: PET (Control), fine mesh gauze coated in bismuth and petroleum jelly (BIS), nanocrystalline silver (NS), wide mesh polyester coated in polysporin ointment (WM), fine mesh cellulose acetate coated in polysporin ointment (FM), and soft silicone mesh (SIL). The dressing material was applied to gelatin and incubated for 24h. Adherence was tested using an Instron 5965 force-measurement device. Testing was repeated with various adherence reducing agents: water, surfactant, and mineral oil. Adherence from least to greatest was: SIL, NS, BIS, WM, FM, PET. Water reduced adherence in all dressings; the effect increasing with exposure time. Surfactant reduced adherence of NS. Mineral oil effectively decreased adherence of BIS, and WM. This model allows for reproducible measurement of dressing adherence. Different interventions affect various dressings. No single intervention optimally decreases adherence for all dressings.


Promoting patient safety using electronic medical records in nursing/midwifery undergraduate curricula: Discussion paper.
This discussion paper highlights the importance of Australian nursing and midwifery students' lack of exposure to electronic medical records during their undergraduate programs. There is pressure on universities offering nursing and midwifery programs to provide students with opportunities to learn to use patient electronic medical records. This will provide authentic rehearsal with the digital technology prior to clinical placements and increase graduate work readiness. Informed by contemporary literature, we describe the benefits of implementing electronic medical records (eMR) in health organisations and identify the challenges and barriers to implementing and integrating the education of electronic records into undergraduate nursing and midwifery programs. Undergraduate students who had not experienced eMR as part of on-campus learning felt unprepared and lacked confidence when commencing clinical practice. Some international nursing and midwifery programs have found that student's skills improve in decision-making and documenting patient observations when eMR is integrated into their university education program. Successful integration of an eMR program should consider academic/teaching staff skills and confidence in technology use, initial and ongoing costs and technical support required to deliver the program. In conclusion, Australian universities need to embed eMR learning experiences into the nursing and midwifery undergraduate curricula to increase students work-readiness with a focus on patient safety.


Combination of linear and nonlinear multivariate approaches effectively uncover responses of phytoplankton communities to environmental changes at regional scale.
The response of a community to environmental changes is either linear or non-linear, so that they can be investigated approximately by linear or nonlinear models. At community level, redundancy analysis (RDA) and canonical correspondence analysis (CCA), and Mantel test and Generalized Dissimilarity Modelling (GDM) are two pairs of fundamental multivariate approaches. Thus, it is necessary to determine how they are used for a given group of communities or a metacommunity. In the present study, we explored the applications of the two pairs of commonly used multivariate methods for the analysis of tropical phytoplankton communities. Phytoplankton were collected from 60 tropical reservoirs in southern China at two distinct regions and two hydrological seasons. Because of a short environmental gradient, response of phytoplankton communities to the environmental gradients was first explored with linear models: distance-based redundancy analysis (db-RDA) and Mantel test. Then, CCA and GDM were further applied to recognize the nonlinear relationship between phytoplankton community variation and environmental changes, and to detect the significant environmental and/or spatial variables. Our results strongly suggest that the combination of db-RDA and GDM provides a highly effective tool to uncover the linearity and nonlinearity in community responses and the important associated environmental and spatial variables, which were significantly different between flooding and dry seasons.


Design and synthesis of (4E)-4-(4-substitutedbenzylideneamino)-3-substituted-2,3-dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists.
Novel 2-thioxothiazole derivatives (6-19) as potential adenosine A2A receptor (A2AR) antagonists were synthesized. The strong interaction of the compounds (6-19) with A2AR in docking study was confirmed by high binding affinity with human A2AR expressed in HEK293T cells using radioligand-binding assay. The compound 19 demonstrated very high selectivity for A2AR as compared to standard A2AR antagonist SCH58261. Decrease in A2AR-coupled release of endogenous cAMP in treated HEK293T cells demonstrated in vitro A2AR antagonist potential of the compound 19. Attenuation in haloperidol-induced impairment (catalepsy) in Swiss albino male mice pre-treated with compound 19 is evocative to explore its prospective in therapy of PD.


Sexual differences in over-winter torpor patterns of Richardson's ground squirrels in natural hibernacula.
Over-winter torpor patterns of Richardson's ground squirrels hibernating in southern Alberta were monitored with temperature-sensitive radiocollars to determine if these patterns differed between males and females in a manner related to the greater costs of mating effort by males than females. The hibernation season (from immergence to emergence) was composed of three periods: post-immergence euthermy, heterothermy, and pre-emergence euthermy. The hibernation season was shorter for juveniles than adults both among males (< 150 versus 234 days) and females (185 versus 231 days), a reflection of the later immergence into hibernation by juveniles. However, regardless of the absolute duration of hibernation, heterothermy accounted for a smaller proportion of the hibernation season of males (93±5%) than females (98±1%) and, within the heterothermal period, males had shorter torpor bouts and longer inter-torpor arousals. Overall, males spent a smaller proportion of the hibernation season in torpor (85±6%) than females (92±1%). This sexual difference was largely attributable to the longer duration of preemergence euthermy for males than females. Males terminated torpor in January and February, when hibernacula were at their coldest, then remained euthermic for 8.8 days (range 0.5-25.0 days) before emergence. In contrast, females terminated torpor in March, when hibernaculum temperatures were increasing, then remained euthermic for only 1.1 days (range 0.5-2.0 days) before emergence. Males lost less mass per euthermic day during hibernation than females (7.0 versus 9.3 g/day). Males and females hibernated at similar depths (56 cm), but males had larger chambers than females (18 versus 16 cm3/g). Many males, but no females, cached seeds in the hibernaculum. Males met the costs of thermogenesis and euthermy from a combination of fat reserves and food caches, whereas females relied solely on fat. Access to food caches permitted males to terminate torpor several weeks in advance of emergence, during which time they recouped mass and developed sperm in preparation for the forthcoming mating season.


Multidomain STS/TULA proteins are novel cellular regulators.
Proteins of the STS/TULA family recently emerged as important regulators of cellular functions. They exhibit a unique domain architecture, featuring at least three interactive/functional domains. Despite a significant degree of homology between the two members of this family, there are considerable functional differences between them. Thus, one of them is ubiquitously expressed in mammalian tissues and exhibits high phosphatase activity, whereas the other one is expressed in lymphocytes only and exhibits very low phosphatase activity, but is capable of promoting apoptosis, an activity unique for this family member. Among several functions reported for STS/TULA proteins, the most characterized one is the regulation of protein tyrosine kinase-mediated signaling. Interestingly, gene deletion of neither family member results in a discernible phenotype, whereas simultaneous deletion of both members causes hyperreactivity of T cells. Despite their apparent importance, the physiological role and the molecular basis of the effects of STS/TULA proteins remain poorly understood. This brief review summarizes what is currently known about the STS/TULA family and outlines the unresolved questions in this area.


Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67.
The monoclonal antibody Ki-67, which reacts with cells in the active part of the cell cycle, was used to evaluate immunocytochemically the growth fraction in 22 primary brain neoplasms. The percentage of labelled cells reflected the histological grade of malignancy of each neoplasms. High percentage of Ki-67-positive cells were observed in one choroid plexus carcinoma (60%), one primary melanoma of meninges (40%), three medulloblastomas (40%-50%), one anaplastic astrocytoma and six glioblastomas (10%-40%). One ependymoma had 7% positive cells. Rare positive cells (1%) were present in one pilocytic astrocytoma and one ganglioglioma. Except one negative case, the meningiomas (five cases) had values of positivity ranging from 1% to 6%. Two acoustic schwannomas were negative. These results suggest that immunocytochemical staining with the Ki-67 may be a useful method for measuring the growth fraction in brain neoplasms.


Development and application of an enzyme-linked immunosorbent assay for the analysis of hydrolyzed fumonisins.
Polyclonal antibodies against hydrolyzed fumonisin B1 (HFB1) were prepared by immunization of rabbits with a keyhole limpet hemocyanin conjugate coupled by glutaraldehyde. Sensitivity and specificity of these antibodies were tested in a direct competitive enzyme-linked immunosorbent assay (ELISA), in which a HFB1-horseradish peroxidase conjugate prepared by reductive alkylation served as the labeled antigen. A direct competitive ELISA for the quantitative determination of HFB1 in corn-based food samples was developed with this antibody. The 50% inhibition level was used for the determination of cross-reactivity. The cross-reactivities of the antibodies for HFB2 and HFB3 were 4.3% and 14.4%, respectively, whereas the parent compound fumonisin B1 (FB1) showed no cross reactivity. The detection limit of the EIA calculated from the HFB1-concentration given a 30% binding inhibition was 0.25 ng/ml for the standard solutions and 10 ng/g for the analyzed food samples e.g. tortilla chips, nachos and cornflakes. Mean recoveries of HFB1 for artificially contaminated food samples were in the range of 96 to 98%. This test offers a rapid and economic opportunity for the HFB1-screening of food samples.


Thermal properties and pyrolysis kinetics of phosphate-rock acid-insoluble residues.
In the phosphorous-sulphur two-step process for the clean production of phosphoric acid, a phosphate-rock acid-insoluble residue (PAIR) is a solid filter residue obtained via the phosphoric acid acidolysis of phosphate rock (PR). PAIR combined with other raw materials can be used to prepare cement, ceramics and glasses, opening a potential avenue for large-scale PAIR utilisation. However, the preparation of such materials requires high-temperatures calcination. Understanding the high-temperature thermal properties of PAIR can enable its more targeted comprehensive utilisation or disposal. In this study, the thermal properties and pyrolysis kinetics of PAIR were systematically studied using a multiple heating rate method based on thermogravimetric analysis and a kinetic model. Results showed that from room temperature to 1200 °C, the main changes in the PAIR were the complete removal of fluorine and sulphur, partial removal of phosphorus and conversion of quartz to cristobalite. Moreover, during these processes, H2O(g), NH3, N2, CO2, SO2, P2O5(g), CO, CF3+ and organic gases were volatilised. Herein, the pyrolysis kinetics of PAIR is divided into five stages. Stage 1 (conversion rate ɑ: 0.05-0.2) conforms to the random nucleation and growth as well as the Avrami-Erofeev (n = 2/3) mechanism; the corresponding mechanism function is F(ɑ) = [-Ln(1 - ɑ)]2/3. Stage 2 (ɑ: 0.2-0.4) conforms to the first-order chemical reaction mechanism; the corresponding mechanism function is F(ɑ) = -Ln(1 - ɑ). Stage 3 (ɑ: 0.4-0.6) conforms to the phase boundary-controlled reaction and one-dimensional movement mechanism; the corresponding mechanism function is F(ɑ) = ɑ. Stage 4 (ɑ: 0.6-0.8) conforms to the three-dimensional diffusion process (Jander model); the corresponding mechanism function is F(ɑ) = [1 - (1 - ɑ)1/3]2. Stage 5 (ɑ: 0.6-0.95) conforms to the one-dimensional diffusion process; the corresponding mechanism function is F(ɑ) = ɑ2.


Superiority of clinical American Joint Committee on Cancer T classification for perihilar cholangiocarcinoma.
Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma. Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell's concordance index (C-index). Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P < .001); the AJCC system had the greatest discriminability for resectability (area under the curve 0.721). Overall survival at 5 years was 69.9% for AJCC cT1, 45.8% for cT2, 31.8% for cT3, and 15.3% for cT4 tumors (cT1 vs cT2; P = .002, cT2 vs cT3; P = .008 and cT3 vs cT4; P < .001). The AJCC system had the largest C-index of 0.627. The AJCC T system was the optimal classification system for predicting resectability and survival in perihilar cholangiocarcinoma.


Salvage Transoral Robotic Surgery for Recurrent or Residual Head and Neck Squamous Cell Carcinoma: A Single Institution Experience.
The present study was conducted to evaluate the technical feasibility, safety and adequacy of surgical margins with salvage transoral robotic surgery (TORS) for recurrent or residual head and neck squamous cell carcinoma patients. Thirty patients who underwent salvage TORS using the 'DaVinci' robot were enrolled in the study and data related to their surgical time, complications and functional outcome were recorded. The feasibility of salvage TORS in our study was observed to be 100%. Positive margins were encountered in only 6.7% of patients. Mean blood loss was 23.3 ml with no patient requiring blood transfusion. Postoperative complications in the form of primary haemorrhage requiring active surgical intervention occurred in 13.3%. Oral feeding could be started as early as the 3rd postoperative day in a few patients, with nasogastric tubes being removed on the 12th postoperative day. Long term gastrostomy tube dependency was seen in 10% cases. Median survival of patients was 19 months. Salvage TORS is a safe, effective and feasible option in the management of treatment failure cases. It offers an alternative surgical approach with unexpected benefits in terms of tracheostomy tube use, Ryle's tube and gastrostomy dependence.


Microdialysis calibration using retrodialysis and zero-net flux: application to a study of the distribution of zidovudine to rabbit cerebrospinal fluid and thalamus.
A retrodialysis (RD) method for the real-time calibration of on-line microdialysis (MD) procedures was investigated in vitro and in vivo. Calibration by retrodialysis was simultaneously validated through the use of a zero-net flux (ZNF) method, which assumes directional independence of diffusion of the solute. In RD, a calibrator with dialysance (PeA; effective permeability-surface area product) similar to that of the compound of interest is introduced into the perfusate. If the calibrator is suitable, its loss from the perfusate during RD is identical to the recovery of the solute of interest determined simultaneously by normal MD. Two antiviral nucleosides (AZT and AZdU) which differ structurally by only a methylene group were utilized as solute and calibrator, respectively. Both nucleosides exhibited similar recovery and loss at flow rates of 0.5 to 5 microL/min in vitro, indicating a similar PeA product in this flow domain. Furthermore, both compounds showed similar loss into the lateral ventricle or thalamus of rabbits (n = 4) during RD at a flow rate of 1 microL/min for 6 hr. The relative loss decreased rapidly within the first hour, reaching a relatively stable value after 2 hr. The significant reduction in the loss of AZdU and AZT in vivo compared with that in vitro likely results from a lower diffusion coefficient in tissue. The distribution of AZT between plasma and cerebrospinal fluid (CSF) in the ventricle and extracellular fluid (ECF) in thalamus was determined at steady state using calibration by RD and ZNF simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)


The survival rate of tuberculosis patients in HIV-treated cohort of 2008-2018 in Almaty, Kazakhstan.
HIV/TB comorbidity is responsible for 1.6 million deaths worldwide. HIV/TB control and patients' survival are still among priorities of the national HIV and TB programs. We aimed to evaluate the HIV/TB survival in connection with TB treatment outcomes and factors influencing life duration of the cohort 2008-2018 in Almaty, Kazakhstan. This retrospective cohort study extracted data for all HIV and pulmonary TB adults coinfected during 2008-2018 in Almaty from national registries to apply descriptive, Kaplan-Meier estimation, and Cox proportional hazards regression model. Survival function for the TB treatment outcomes and factors predicting the probability of survival were tested and described. The cohort population (n = 521) mean age was 37.4 years with 405 (77.7%) males and 210 (40.3%) marrieds. More than one TB treatment had 181 (34.7%) patients, 291 (55.9%) were smear-positive (SS+), and 423 (81.2%) were on antiretroviral therapy with mean CD4 count 254.22cells/µL. Probability to live longer was higher (128 versus 37 months, p = 0.003; 95% confidence interval (CI) 71.65, 184.35) for those who succeeded in TB treatment compared to "lost to follow-up" and "failed" treatment outcomes. Adjusted Cox regression model death hazard showed association with missing ART treatment (HR: 1.699, 95%CI 1.164, 2.481, p = 0.006) and having CD4 count < 499 (HR 2.398, 95%CI 1.191, 4.830, p < 0.014). TB treatment outcomes, ART treatment, and the CD4 count of HIV/TB coinfected population substantially influence their life duration. The medical decision- and policy-makers should take this into consideration when implementing targeted improvements in the national HIV and TB programs.


Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions.
Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 μM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (△Ψm), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions.


Effects of excess methionine on collagen metabolism: a study on newborn rat skin.
We studied the biochemical effects of excess methionine intake on the skin of newborn rats. Group 1 pups were intubated with methionine dissolved in 0.1 ml physiological saline solution in the amount of 0.1 g/100 body wt as a control using a gastric needle. Group 2 pups were given 0.2 g/100 g in the same manner as group 1 as an experimental group. They were intubated every other day from day 3 to 13. On Day 15, [14C]proline was injected intraperitoneally into pups and their skin was removed. 14C total and hydroxyproline uptake was examined in the tissue as well as in the sequential extracts. Although excess methionine intake by the pups did not alter the collagen content of their skin, it caused an increase in the content of type III collagen and a decrease in crosslinked collagen. In addition, newly synthesized collagen in the neutral salt extract increased in the excess methionine group, indicating that crosslinked collagen decreases as excess methionine was intubated. The present study demonstrated that excess methionine in the early lactational period altered the nature of the skin collagen of suckling newborn rat pups.


Intraabdominal pyloromyotomy through the umbilical route: a technical improvement.
Performing a pyloromyotomy through a supraumbilical skin fold incision will leave an almost invisible scar and therefore has definitive cosmetic advantages. This alternative approach may be related to technical difficulties in delivering a large pyloric tumor when compared with the conventional pyloromyotomy through a right upper quadrant incision. However, in situ (intraabdominal) myotomy can help overcome this inconvenience. Of 122 cases of infantile hypertrophic pyloric stenosis operated on between January 1990 and August 1996, 29 underwent a pyloromyotomy performed intraabdominally through the umbilical route. The medical records of these babies were reviewed. Twenty-three boys and six girls (median age, 30 days; range, 17 to 70 days) underwent surgery. The median hospital stay was 2.5 days. There were two intraoperative technical complications (small mucosal perforation) and one postoperative wound complication (abcess formation) requiring local drainage. In situ pyloromyotomy through the umbilical route is an elegant alternative in cases of a large pyloric tumor.


Clinical and molecular epidemiology of vancomycin-resistant Enterococcus faecium bacteremia from an Indian tertiary hospital.
We determined the clinical and molecular epidemiology of emerging nosocomial vancomycin-resistant Enterococcus faecium (VREfm)-causing serious bloodstream infections (BSIs) and the correlations between antibiotic resistance and virulence determinants among isolates. All isolates were confirmed by molecular methods (16SrRNA and E. faecium ddl genes) and tested for disk diffusion. PCR was used to detect aac(6')-aph(2″), vanA and vanB resistance genes, and asa1, cylA, ace, esp, gelE and hyl virulence genes. VREfm and high-level gentamicin-resistant (HLGR) representative isolates were selected to characterize by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Of 173 isolates, 73 (42.2%), 146 (84.4%), and 0 (0.0%) were vanA-containing VREfm, aac(6')-aph(2″)-positive HLGR, and vanB-positive. Independent predictors of VREfm infection were hematological malignancies (P = 0.001) and previous hospitalizations (P = 0.007). Observed mortality rate was 34.7%. Independent predictors of BSI-related mortality were endotracheal intubations (P < 0.001), gastrointestinal diseases (P = 0.002), and pulmonary disease (P < 0.001). All VREfm were resistant to vancomycin, teicoplanin, ciprofloxacin, and erythromycin. The esp, hyl, ace, asa1, cylA, and gelE genes were detected at 55.9, 22.5, 2.9, 2.3, 1.7, and 1.2%, respectively. The esp gene was significantly associated with VREfm compared to VSEfm (P = 0.001). PFGE analysis revealed 23 clones, with 7 major clones. The MLST analysis revealed the following five sequence types: ST80, ST17, ST117, ST132, and ST280, all belonging to CC17. The emergence and expansion of VREfm CC17 with limited antibiotic options in our hospital present a serious public health menace and represent challenges to infection control.


Effect of the biocontrol bacterium Bacillus amyloliquefaciens on the rhizosphere in ginseng plantings.
Panax ginseng is an important medicinal herb due to its ability to strengthen the human immune system. However, due to the increasing needs of ginseng in medicine, the continuous cropping of ginseng has become more common and has resulted in increased problems with fungal decay. Thus, chemical fungicides are commonly used in ginseng plantings, which have caused fungicide residue problems. As an alternative control measure, biocontrol bacteria can be used to manage fungal pathogens. Additionally, these bacteria are environmentally friendly and can also improve stress tolerance in plants. In this study, an antifungal bacterial strain, TB6, that possesses ACC deaminase activity was isolated from the rhizosphere of ginseng plants. This strain was identified as Bacillus amyloliquefaciens. TB6 was applied to 2-year-old ginseng seedlings for a 2-year period, and its impact on the soil rhizosphere was evaluated. The results revealed that strain TB6 decreased fungal abundance and diversity; improved urease, catalase, and phosphatase activities; and decreased the cellulase activity of the rhizosphere soil. In addition, strain TB6 also promoted root growth and increased the fresh weight of ginseng roots, in addition to increasing polyphenol oxidase and catalase activities. These results may have practical implications for the use of biocontrol bacteria in ginseng plantings.


Personal strivings and marijuana use initiation, frequency, and problems.
This study examined relations between perceived conflict/utility of marijuana use in achieving valued personal goals and marijuana use initiation, marijuana use frequency, and marijuana-related problems. Personal strivings are higher order goals that may influence marijuana use to the extent that they are congruent or incongruent with use. Participants were 592 young adults who generated lists of personal strivings independent of the substance use assessment. They then evaluated their 10 most important strivings with regard to the perceived conflict/utility of several levels of marijuana use in achieving their most important strivings. Less marijuana use-striving conflict was positively associated with use initiation and frequency. A significant gender interaction emerged in the prediction of use frequency; marijuana use-striving conflict was more strongly associated with use frequency for men than women. The relationship between use-striving conflict and marijuana-related problems was mediated fully by use frequency.


Novel ATP-binding heat-inducible protein of Mr = 37,000 that is sensitive to transformation in BALB/3T3 cells.
Using affinity chromatography on ATP-agarose, we have identified a major ATP-binding protein in Nonidet P-40 extracts of avian and mammalian cells labeled with [35S]methionine. After washing ATP-agarose beads with high-ionic-strength buffer (0.4 M NaCl), the 37-kD protein was shown to be one of the major ATP-binding proteins while p72 and grp78, which are members of the hsp70 family, also bound to ATP-agarose. This protein consisted of several spots on two-dimensional gel electrophoresis. The isoelectric point of the most basic spot was approximately 9.2 in chick embryo fibroblasts, whereas it was about 8.8 in mouse 3T3 cells. The identities of these proteins in mouse and chick cells were confirmed by peptide mapping. After heat-shock treatment of BALB/3T3 cells, the major heat-shock protein, hsp70, was shown to be induced very rapidly after heat shock and was recovered in the ATP-binding fraction. Besides hsp70, a 37-kD protein was also found to be induced by heat shock. This protein was drastically induced by treating the cells with alpha,alpha'-dipyridyl, an iron chelating reagent, but not with sodium arsenite, calcium ionophore, or tunicamycin. The synthesis and the total amount of this ATP-binding protein increased in mouse 3T3 cells transformed by simian virus 40, methylcholanthrene, or activated c-Ha-ras oncogene compared to their normal counterparts. The incorporation of [32P]orthophosphate was not detected in either normal or transformed cells. These studies established that a major ATP-binding protein of Mr = 37,000 is a heat-inducible protein and that the synthesis of this protein is regulated by malignant transformation.


Synthesis and characterization of agar-based silver nanoparticles and nanocomposite film with antibacterial applications.
This study describes the synthesis and characterization of silver nanoparticles and nanocomposite material using agar extracted from the red alga Gracilaria dura. Characterization of silver nanoparticles was carried out based on UV-Vis spectroscopy (421 nm), transmission electron microscopy, EDX, SAED and XRD analysis. The thermal stability of agar/silver nanocomposite film determined by TGA and DSC analysis showed distinct patterns when compared with their raw material (agar and AgNO(3)). The TEM findings revealed that the silver nanoparticles synthesized were spherical in shape, 6 nm in size with uniform dispersal. The synthesized nanoparticles had the great bactericidal activity with reduction of 99.9% of bacteria over the control value. The time required for synthesis of silver nanoparticles was found to be temperature dependent and higher the temperature less the time for nanoparticles formation. DSC and XRD showed approximately the same crystalline index (CI(DSC) 0.73).


A deoxyribonucleic acid ligase from nuclei of rat liver. Purification and properties.
A DNA ligase has been extensively purified from nuclei of rat livers. The ligase seals single strand nicks in DNA with any of the four usual bases on either the 3 or 5 sides. It requires ATP and a divalent cation (Mg-2plus or Mn-2plus) for activity. At low Mg-2plus concentrations the activity is greatly stimulated by a variety of monovalent cations. Relatively small excesses of either monovalent or divalent cation above the amounts which give maximal activity lead to inhibition of activity. Poly(G) and poly(I) inhibit ligase activity; several other polyribonucleotides are not inhibitory. Low concentrations of inorganic pyrophosphate are inhibitory. The molecular weight of the ligase is estimated from gel filtration to be about 10 times 10-4.


Pituitary metastasis masquerading as non-functioning pituitary adenoma in a woman with adenocarcinoma lung.
Incidental detection of pituitary metastasis in patients with primary breast carcinoma is not uncommon. However, pituitary metastasis manifesting as bitemporal hemianopia as a presenting manifestation in a patient with silent adenocarcinoma of the lung, that too in a women, is quite uncommon. We report such a case.


High frequency jet ventilation in the management of intra-operative tracheal injury.
A patient undergoing pharyngo-oesphagectomy with gastric transposition sustained a large tracheal tear during the blind oesophageal dissection. High frequency jet ventilation was successfully employed in the acute airway management and continued postoperatively.


Nuclear factor erythroid-2-related factor 2 (Nrf2) is a potential prognostic factor in patients with gastric adenocarcinoma.
Gastric cancer is one of the leading causes of cancer-related death, and many researchers are focused on the discovery and use of different biomarkers in prognosis prediction. The use of Nrf2 as a prognostic marker in patients with gastric cancer remains controversial. In this study, we evaluated the expression of Nrf2 protein in gastric adenocarcinoma. A total of 86 patients who underwent gastric resection and D2 lymph node dissection due to gastric adenocarcinoma were included. Clinicopathological characteristics, such as age, gender, gastrectomy type, pathologic T (pT) and N (pN) stages, tumor grade, tumor type per Lauren's classification, presence of lymphovascular invasion, and Nrf2 expression were evaluated. While pT, pN, and Nrf-2 expression were found to be negative prognostic predictors for overall survival in one-way analysis of variance, Nrf-2 expression was the only significant negative prognostic predictor in multivariance analysis. pT, pN, diffuse type, high tumor grade, and Nrf-2 expression significantly affected overall survival in Kaplan-Meier survival analyses (p = 0.02, p = 0.03, p < 0.01, p = 0.027, and p = 0.001, respectively). Our findings support that Nrf2 is a prognostic marker in patients with gastric adenocarcinoma. Anti-Nrf2 therapy options should be investigated to improve prognosis in gastric cancer patients.


Giardia lamblia produces alanine anaerobically but not in the presence of oxygen.
Proton nuclear magnetic resonance was used to follow glucose metabolism in Giardia lamblia. Under strictly anaerobic conditions this organism produces equimolar ethanol and alanine as well as CO2 and some acetate. Aerobically the production of both alanine and ethanol are inhibited and more acetate and CO2 are formed. These changes in the balance of products are reversible over the range 0-46 microM O2. In the presence of 46 microM O2, alanine was not detectable. The O2-sensitivity of alanine production may highlight the necessity for redox-balancing reactions in an organism exposed in situ to fluctuating concentrations of O2.


Comparison of conventional continuous positive airway pressure to continuous positive airway pressure titration performed with sleep endoscopy.
To evaluate the effect and obtain a pressure value of continuous positive airway pressure (CPAP) under direct visualization using drug-induced sleep endoscopy (DISE) and compare the pressure values with values obtained using conventional CPAP. Prospective, double-blinded, cohort study. Sixteen patients with obstructive sleep apnea syndrome (OSAS) were included in the study. Each patient underwent polysomnographic evaluation. After diagnosis of OSAS, patients underwent conventional CPAP titration. Patients were then taken to the operating theatre and put under sedation, where CPAP titration with nasendoscopy was performed (DISE CPAP). There were no statistically significant differences between the two techniques regarding pressure levels that decreased apneas in conventional CPAP and provided sufficient opening during DISE CPAP. Results with conventional CPAP titration and endoscopy-assisted CPAP titration showed no statistically significant difference. Endoscopy-assisted CPAP is a cheaper and less time consuming alternative to conventional CPAP and has similar results.


Making proteins into drugs: assisted delivery of proteins and peptides into living neurons.
The introduction of exogenous proteins and peptides into cells is a valuable experimental approach. However, exogenous proteins are not internalized by living cells readily. This limitation has been overcome by the development of peptide-based methods that assist in the delivery of exogenous proteins into the cytoplasm and nucleus. These methods may facilitate the in vivo delivery of reagents in therapies aimed at neurodegenerative disorders and recovery from nervous system injury.


Chromogenic platform based on recombinant Drosophila melanogaster acetylcholinesterase for visible unidirectional assay of organophosphate and carbamate insecticide residues.
In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC(50) values against the tested six insecticides (0.06 μg mL(-1) of carbofuran, 0.28 μg mL(-1) of methomyl, 0.03 μg mL(-1) of dichlorvos, 31.6 μg mL(-1) of methamidophos, 2.0 μg mL(-1) of monocrotophos, 6.3 μg mL(-1) of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10(-3) to 10(1) μg g(-1). Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.


Improved outcome for peripheral blood stem cell transplantation for advanced primary myelodysplastic syndrome.
Stem cell transplantation for myelodysplastic syndrome (MDS) is characterized by high transplant-related mortality (TRM), especially in older patients and those with more advanced disease. Outcome after peripheral blood stem cell transplantation (PBSCT) may be superior to earlier results with bone marrow transplantation. Forty-three patients (aged 12-73 years; median, 49 years) received an HLA-identical sibling donor PBSCT. Twenty three patients aged < or =55 years without prohibitive comorbidity received myeloablative total body irradiation-based conditioning, followed by a T cell-depleted PBSCT and delayed add-back of donor lymphocytes. Older patients or those with comorbidities (n = 20) received reduced-intensity conditioning and an unmanipulated PBSCT. Thirty-seven (86%) had advanced disease (refractory anemia with excess blasts [n = 9], refractory anemia with excess blasts in transformation [n = 6], acute myelogenous leukemia [n = 13], or treatment-related MDS [n = 9]); 6 had low-risk MDS (refractory anemia or refractory anemia with ringed sideroblasts). The median follow-up was 18 months (range, 5-89 months). Actuarial probabilities of 3-year overall survival (OS), disease-free survival, relapse, and TRM were 64%, 59%, 26%, and 23%, respectively, for 34 primary MDS patients. The best results were in 19 patients younger than 50 years of age undergoing myeloablative PBSCT (actuarial probabilities of OS, disease-free survival, relapse, and TRM were 81%, 72%, 22%, and 7%, respectively). Although outcomes for all stages of primary MDS were improved, that for therapy-related MDS remained dismal, with 11% OS, because of a high relapse rate (89%).


Quantifying contributions of natural variability and anthropogenic forcings on increased fire weather risk over the western United States.
Previous studies have identified a recent increase in wildfire activity in the western United States (WUS). However, the extent to which this trend is due to weather pattern changes dominated by natural variability versus anthropogenic warming has been unclear. Using an ensemble constructed flow analogue approach, we have employed observations to estimate vapor pressure deficit (VPD), the leading meteorological variable that controls wildfires, associated with different atmospheric circulation patterns. Our results show that for the period 1979 to 2020, variation in the atmospheric circulation explains, on average, only 32% of the observed VPD trend of 0.48 ± 0.25 hPa/decade (95% CI) over the WUS during the warm season (May to September). The remaining 68% of the upward VPD trend is likely due to anthropogenic warming. The ensemble simulations of climate models participating in the sixth phase of the Coupled Model Intercomparison Project suggest that anthropogenic forcing explains an even larger fraction of the observed VPD trend (88%) for the same period and region. These models and observational estimates likely provide a lower and an upper bound on the true impact of anthropogenic warming on the VPD trend over the WUS. During August 2020, when the August Complex "Gigafire" occurred in the WUS, anthropogenic warming likely explains 50% of the unprecedented high VPD anomalies.


Protein-encapsulated bio-nanocapsules production with ER membrane localization sequences.
Bio-nanocapsules (BNCs) are hollow nanoparticles composed of the L protein of hepatitis B virus (HBV) surface antigen (HBsAg), which can specifically introduce genes and drugs into various kinds of target cells. Although the classic electroporation method has typically been used to introduce highly charged molecules such as DNA, it is rarely adopted for proteins due to its very low efficiency. In this study, a novel approach to the preparation of BNC was established whereby a target protein was pre-encapsulated during the course of nanoparticle formation. Briefly, because of the process of BNC formation in a budding manner on the endoplasmic reticulum (ER) membrane, the association of target proteins to the ER membrane with lipidation sequences (ER membrane localization sequences) could directly generate protein-encapsulating BNC in collaboration with co-expression of the L proteins. Since the membrane-localized proteins are automatically enveloped into BNCs during the budding event, this method can be protect the proteins and BNCs from damage caused by electroporation and obviate the need for laborious consideration to study the optimal conditions for protein encapsulation. This approach would be a useful method for encapsulating therapeutic candidate proteins into BNCs.


Frontostriatal circuits are necessary for visuomotor transformation: mental rotation in Parkinson's disease.
The mental rotation of objects requires visuospatial functions mediated by the parietal lobes, whereas the mental rotation of hands also engages frontal motor-system processes. Nondemented patients with Parkinson's disease (PD), a frontostriatal disorder, were predicted to be impaired on mentally rotating hands. Side of PD motor symptom onset was investigated because the left motor cortices likely have a causal role in hand mental rotation. The prediction was that patients with right-side onset (RPD, greater left-hemisphere dysfunction) would commit more errors rotating hands than patients with left-side onset (LPD). Fifteen LPD, 12 RPD, and 13 normal control adults (NC) made same/different judgments about pairs of rotated objects or hands. There were no group differences with objects. When rotating hands, RPD, but not LPD, made more errors than the NC group. A control experiment evaluated whether visual field of presentation explained differences between PD subgroups. In the first experiment (1A), the hand to be mentally rotated was presented in the right visual field, but here (1B) it was presented in the left visual field. Only the LPD group made more errors than the NC group. The evidence suggests a double dissociation for the RPD and LPD groups between tasks differing in visual-field presentation. The findings indicate that hemifield location of a to-be-rotated hand stimulus can cause the hemispheric frontoparietal networks to be differentially engaged. Moreover, frontostriatal motor systems and the parietal lobes play a necessary role during the mental rotation of hands, which requires integrating visuospatial cognition with motor imagery.


Palladium-catalyzed carboboration of alkynes using chloroborane and organozirconium reagents.
Three-component coupling of bis(dialkylamino)chloroborane, alkynes and organozirconium reagents proceeded in the presence of palladium catalysts, leading to the formation of stereo-defined alkenylborane derivatives via cis-carboboration of carbon-carbon triple bonds.


Insights into the mechanisms of aqueous Cd(II) reduction and adsorption by nanoscale zerovalent iron under different atmosphere conditions.
Nanoscale zero-valent iron (NZVI) can effectively remove and recover Cd(II) from aqueous solutions. However, the oxygen effects on Cd(II) removal by NZVI have been overlooked and not well studied. In this research, the Cd MNN auger lines obtained by X-ray photoelectron spectroscopy (XPS) revealed that Cd(II) adsorbed on the NZVI surface could be reduced to Cd(0) by the Fe(0) core under anaerobic conditions. With coexisting oxygen, the Cd(II) removal efficiency declined significantly, and Cd(II) reduction was inhibited by the thickened surface γ-FeOOH layer. Furthermore, the post-oxygen intrusion corroded the generated Cd(0) and led to the dramatic leaching of Cd(II) ions. According to the density functional theory (DFT) simulation, the adsorbed Cd(II) was preferably coordinated via a monodentate model on the surface of Fe3O4 and γ-FeOOH, which are the dominant surface species of NZVI under anaerobic and aerobic conditions, respectively. Thus, γ-FeOOH with doubly coordinated hydroxyl groups provided fewer adsorption sites than Fe3O4 for Cd(II) ions. Overall, the atmospheric conditions of subsurface remediation and wastewater treatment should be considered when applying NZVI for Cd(II) removal. Favorable atmospheric conditions would improve the efficiency and cost-effectiveness of NZVI-based technologies for the practical remediation of Cd(II) pollution.


Experimental design for multi-drug combination studies using signaling networks.
Combinations of multiple drugs are an important approach to maximize the chance for therapeutic success by inhibiting multiple pathways/targets. Analytic methods for studying drug combinations have received increasing attention because major advances in biomedical research have made available large number of potential agents for testing. The preclinical experiment on multi-drug combinations plays a key role in (especially cancer) drug development because of the complex nature of the disease, the need to reduce development time and costs. Despite recent progresses in statistical methods for assessing drug interaction, there is an acute lack of methods for designing experiments on multi-drug combinations. The number of combinations grows exponentially with the number of drugs and dose-levels and it quickly precludes laboratory testing. Utilizing experimental dose-response data of single drugs and a few combinations along with pathway/network information to obtain an estimate of the functional structure of the dose-response relationship in silico, we propose an optimal design that allows exploration of the dose-effect surface with the smallest possible sample size in this article. The simulation studies show our proposed methods perform well.


Clinical experience with Genotropin worldwide: an update March 1987.
The efficacy and safety of Genotropin (recombinant somatropin, KabiVitrum AB, Sweden) was analysed in 199 children with hGH deficiency, comprising a combined series of four current multicentre trials. Stimulation of linear growth from pretreatment height velocities of 3-4 cm/year to about 10 cm/year was observed after 6 and 9 months of treatment. Statistical analysis revealed significantly greater height velocities (by 2-3 cm/year) when the weekly dose of the hormone was given in 6-7 injections rather than in 3 injections. Immunogenicity seems to be very low, with only about 2% of the children having detectable antibodies during treatment.


miR-125a-5p promotes gastric cancer growth and invasion by regulating the Hippo pathway.
This study was carried out to explore the potential involvement of miR-125a-5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression. In vitro transfection of miR-125a-5p mimics or inhibitors, qRT-PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR-125a-5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR-125a-5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT-PCR, and immunoblotting were performed to explore the role of miR-125a-5p in the epithelial-mesenchymal transition (EMT) and association among miR-125a-5p, EphA2, TAZ, and TEAD2 in GC cells. MiR-125a-5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR-125a-5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR-125a-5p reversed EMT in vitro. miR-125a-5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR-125a-5p was overexpressed in late-stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2. miR-125a-5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.


Innovative approaches in CNS clinical drug development: Quantitative systems pharmacology.
Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed. Quantitative systems pharmacology (QSP) uses mathematical computerized models to characterize biological systems, disease processes and CNS drug pharmacology. Integrated experimental medicine should increase the probability and predictability of success while controlling clinical trials costs. Finally, the societal perspective and patient empowerment also offer additional approaches to demonstrate the benefit of a new drug in the CNS field.


Attentional and emotional mechanisms related to pain as predictors of chronic postoperative pain: a comparison with other psychological and physiological predictors.
The present prospective longitudinal study on chronic postoperative pain was conducted to assess the predictive power of attentional and emotional variables specifically assumed to augment pain, such as pain hypervigilance, pain-related anxiety, pain catastrophizing and attentional biases to pain. Their relevance was determined in comparison with other psychological and physiological predictors (depression, anxiety, somatization, cortisol reactivity, pain sensitivity). In 84 young male patients the predictor variables were assessed one day before surgery (correction of chest malformation). Postoperative outcome (subjective pain intensity and pain-related disability) was assessed three (N=84) and six months (N=78) after surgery. Patients were classified into good and poor outcome groups. Patients with high pain intensity three (25%) or six months (14%) after surgery, differed significantly from those low in pain with regard to their preoperative performance in the dot-probe task (high attentional bias towards positive words). A sizeable portion (54%) of patients still felt disabled due to pain after three months and a few patients after six months (13%). These patients were those with high preoperative ratings in the Pain Vigilance and Awareness Questionnaire. The few subjectively disabled patients after six months could be identified in addition by low pressure pain and high cold pain thresholds before surgery. An attentional bias towards positive stimuli prior to surgery may indicate a maladaptive coping style, which avoids necessary confrontation with pain and predisposes patients to chronic postoperative pain. Lasting subjectively felt pain-related disability occurs predominantly in patients with high levels of pain hypervigilance before surgery.


Predictors of recurrence following laparoscopic minor hepatectomy for hepatocellular carcinoma in the UK.
Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.


Enhanced plasmon resonance light scattering signals of colloidal gold resulted from its interactions with organic small molecules using captopril as an example.
Gold nanoparticles are known for their plasmon resonance absorption (PRA) depending on their size. Our this investigation shows that plasma resonance light scattering (PRLS) signals in the corresponding PRA region could be measured using a common spectrofluorometer, and be enhanced when aggregation of gold nanoparticles occurs due to their interaction with organic small molecules (OSMs). Using captopril (Cap) as an example, we investigated the interactions of gold nanoparticles with OSMs in order to propose a general method of OSMs such as typical clinic organic drugs. In aqueous medium of pH 2.09, there are about 2.2 x 10(3) Cap molecules covalently binding to the surface of a 10-nm diameter gold nanoparticle through the thiol functional group of Cap, and thus forms a core-shell assembly of [(Au)(31000)]@[(Cap)(2200)], displaying strong enhanced PRLS signals in the PRA region of gold colloid. The PRLS intensities characterized at 553.0 nm were found to be proportional to the concentration of Cap over the range of 0.1-1.7 mg L(-1) with the determination limit (3sigma) of 32.0 microg L(-1). With that, Cap in pharmaceutical preparations could be determined with the recovery of 97.0-104.5% and R.S.D. of less than 2.4%.


Hierarchically structured catalysts for cascade and selective steam reforming/hydrodeoxygenation reactions.
We report a hierarchically structured catalyst with steam reforming and hydrodeoxygenation functionalities being deposited in the micropores and macropores, respectively. The catalyst is highly efficient to upgrade the pyrolysis vapors of pine forest product residual, resulting in a dramatically decreased acid content and increased hydrocarbon yield without external H2 supply.


Drugging the human methylome: an emerging modality for reversible control of aberrant gene transcription.
Protein and DNA methylation have emerged as critical mechanisms for the control of regulated gene transcription. In humans, the addition, recognition and removal of methyl groups are orchestrated by at least 344 proteins that we collectively refer to as the 'methylome'. The large size of the methylome likely reflects the importance of precise control over this small covalent modification. An increasing number of reports implicating the misregulation of methylation in disease make the proteins governing this modification attractive target for small molecule drug discovery. In light of the emerging opportunities for the development of therapeutics that modulate methylation-dependent pathways, this review examines the protein families that constitute the methylome, with emphasis on the methylation of arginine and lysine residues of proteins. Genetic aberrations that give rise to disease are highlighted, in addition to recent proof-of-concept successes in the development of small molecule modulators of methylome constituents.


Release and interconversion of P2 receptor agonists by human osteoblast-like cells.
Nucleotides, acting as agonists at P2 receptors, are important extracellular signaling molecules in many tissues. In bone they affect both bone-forming osteoblast and bone-resorbing osteoclast cell activity. The presence of nucleotides in the extracellular microenvironment is largely determined by their release from cells and metabolism by ecto-enzymes, both of which have scarcely been studied in bone. We have investigated adenosine 5'-triphosphate (ATP) release from SaOS-2 osteoblastic cells and the activities of cell surface ecto-enzymes on ATP metabolism. ATP, but not LDH, was detected in SaOS-2 cell conditioned medium, suggesting these cells were actively releasing ATP. Introduction of ADP resulted in increased ATP concentrations in the medium, which was found not to be receptor mediated. Nucleotide inhibition and substrate specificity studies revealed an ecto-nucleoside diphosphokinase (ecto-NDPK) was responsible for the ADP-->ATP conversion; PCR and immunocytochemistry confirmed its presence. Analysis of ATP metabolism over time demonstrated overall ATP degradation was increased by inhibiting ecto-NDPK activity; confirming that the combined action of multiple osteoblast-expressed ecto-enzymes affected extracellular nucleotide concentration. The data establish the coexistence of ATP-consuming, and for the first time, ATP-generating activities on the osteoblast cell surface, the discovery of which has significant implications for studies involving P2 receptor subtypes in bone.


Take two orthogonals and call me in the morning.
Analysis of variance (ANOVA) is used to prevent inflated type I error when hypothesis testing involves comparing more than two groups. If an ANOVA result indicates a statistically significant difference exists somewhere within, the next task is to discover exactly which combination or combinations of those groups account for the significant difference. Among many methods available for that exploration, orthogonal contrasts and relatively simple graphs are noteworthy.


[Massive infection of odontogenic origin (author's transl)].
2565 patients with infections of odontogenic origin are reported. In only 34,8% of the cases the correct diagnosis was established. Purulent inflammations of the submaxillar area mostly occurred (49,9%) followed by the pharyngeal area (19,9%). Early signs of the spreading of the inflammation must be the indication to send the patient to the hospital to avoid complications.


NSP4 as adjuvant for immunogenicity and design of effective therapeutic HPV16 E6/E7/L1 DNA vaccine in tumor-bearing and healthy C57BL/6 mice.
In humans, approximately 5% of all cancers are attributable to HPV infection. Prophylactic vaccines can inhibit viral migration and persistence. However, further studies are still required to develop such treatments. To achieve this goal, we designed a therapeutic HPV DNA vaccine encoding a construct of E6/E7/L1 and used NSP4 antigen as an adjuvant to assess the efficiency of this construct in generating antigen-specific antitumor immune responses. Sixty female C57BL/6 mice (6-8 weeks old) were purchased from the Institute Pasteur of Iran. Through a subcutaneous (s.c) injection of a suspension of 100 µl PBS containing 106 TC-1 cells/mouse in the back side, 30 of them became cancerous, while 30 of them were healthy control mice. To amplify E6/E7/L1-pcDNA3 and NSP4-pcDNA3, the competent cells of DH5α and to generate a tumor, TC-1 cell line was used. Mice were then immunized with the HPV DNA vaccine. Cell proliferation was assessed by MTT assay. Finally, cytokine responses (IL-4, IL-12, IFN- γ) were measured in the supernatant of mice spleen cells. Mice receiving the NSP4/E6-E7-L1 vaccine had the highest stimulatory index compared to other groups, although it was not statistically significant. Interleukin 4/12 and IFN-γ production were significantly higher in E6-E7-L1 / NSP4 group and E6-E7-L1 group compared to other groups (P < 0.05). Among different groups, E6/E7/L1 + NSP4 group was able to slow down the tumor growth process, but it was not significant (p > 0.05). Among the aforementioned cytokines, IFN-γ and IL-12 are among the cytokines that stimulate the Th1 pathway and IL-4 cytokine stimulates the Th2 pathway and B lymphocytes. Our data revealed that the present vaccine can reduce tumor size, and cytokine measurement showed that it stimulates innate and acquired immune responses, thus it can be a therapeutic vaccine in the tumor-bearing mice model.


Male adolescents with Interleukin 10 rs1800872 AA genotype had higher prevalence and slower recoveries of post-traumatic stress disorder at late stage of a follow-up.
Pathophysiological mechanisms of post-traumatic stress disorder (PTSD) are elusive and heterogeneous relationships have been reported among PTSD, Interleukin 10 (IL-10), and other factors after stresses. The present study aimed to longitudinally investigate associations of PTSD with environmental factors and genetic variation of rs1800872 at IL-10 gene. Symptoms of PTSD were measured by PTSD Checklist-Civilian Version (PCL-C) in 462 high school students at 6, 12, and 18 months after Wenchuan earthquake in China. Genotypes of IL-10 rs1800872 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and verified by DNA sequencing. AA homozygotes had higher PTSD prevalence than C allele carriers only at 18 months in male, but not female subjects. PTSD prevalence at 18 months was lowered in all subjects except male AA homozygotes when compared to that at 6 months, and only in female C allele carriers when compared to that at 12 months. PCL-C scores at 18 months were decreased in all students but not in male AA homozygotes when compared to those at 6 months. IL-10 rs1800872 was associated with PTSD at 18 months. Patterns of predictors of PCL-C scores were different between AA homozygotes and C allele carriers at different times during the follow-up. There were different reciprocal actions of IL-10 rs1800872 with other potential factors or predictors on PTSD in a time-course and gender-dependent manner. Male students with IL-10 rs1800872 AA genotype had higher prevalence and slower recoveries of PTSD at late stage of the follow-up, suggesting requirements of special psychiatric care or drug supplementation at this stage.


Increased suicidality in depression: group or subgroup characteristic?
A lifetime history of depressive episodes and suicide attempts was ascertained from 172 depressed patients admitted to a psychiatric inpatient service. Fifty-five of these patients had made at least one suicide attempt. The correlation of depressive episodes and the total number of suicide attempts for this group was close to zero. However, when the data were converted into rate measures (number of episodes or attempts per year), the correlations were very high and significant. It appears that approximately one-third of severely depressed, hospitalized patients have a history of suicide attempts and, once a suicide attempt has occurred, the patient is at high risk for more suicide attempts if future depressions occur. Within the group of depressives with a history of suicide attempt, the risk of suicidal behavior is evenly distributed. No evidence in favor of a "hypervulnerable" subgroup was found.


Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.
We present the unusual case of a 33-year-old woman who presented with a 2 year history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later, the lesion had enlarged by 5mm, with associated enhancement of the dura of the planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis associated with immunoglobulin G4.


Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation.
Up to 50% of systemic lupus erythematosus (SLE) patients world-wide develop lupus nephritis (LN). In low to middle income countries and in particular in sub-Saharan Africa, where SLE is prevalent with a more aggressive course, LN and end stage renal disease is a major cause of mortality. While developed countries have the funding to invest in SLE and LN research, patients of African descent are often underrepresented in clinical trials. Thus, the complex influence of ethnicity and genetic background on outcome of LN and SLE as a whole, is not fully understood. Several pathophysiological mechanisms including major role players driving LN have been identified. A large body of literature suggest that prevention of fibrosis-which contributes to chronicity of LN-may significantly improve long-term prognosis. Bone morphogenetic protein-7 (BMP-7) was first identified as a therapeutic option in this context decades ago and evidence of its benefit in various conditions, including LN, is ever-increasing. Despite these facts, BMP-7 is not being implemented as therapy in the context of renal disease. With this review, we briefly summarise current understanding of LN pathology and discuss the evidence in support of therapeutic potential of BMP-7 in this context. Lastly, we address the obstacles that need to be overcome, before BMP-7 may become available as LN treatment.