Association of serum cardiac troponin I and severity of coronary stenosis in patients with varied renal functions: a retrospective cohort study.
Recent studies showed cardiac troponin I (cTnI) might be a non-invasive biomarker to estimate the severity of coronary stenosis. However, serum cTnI is also found associated with renal function. The study objective is to analyse the association of serum cTnI and severity of coronary stenosis in patients with varied renal functions. A retrospective cohort study. The First Affiliated Hospital, College of Medicine, Zhejiang University in Hangzhou, China. A total of 6487 subjects who underwent elective coronary angiography between January 2017 to June 2020 were involved in this study. Severity of coronary stenosis was divided into three degrees based on Gensini score, mild coronary stenosis, moderate coronary stenosis and severe coronary stenosis. By using ordinal logistic regression, serum cTnI was associated with severity of coronary stenosis (OR=1.14, p<0.05). By construction and comparison of two models for predicting severity of coronary stenosis, the addition of cTnI significantly improved the predictive ability of the model. Differences between areas under the curves were 0.03, 0.03, 0.03, 0.12 (all p<0.05). Net reclassification improvements were 0.08, 0.05, 0.05, 0.35, respectively, in varied renal functions. Compared with the participants with normal renal function and without hypertroponinaemia, groups of participants with hypertroponinaemia showed higher ORs. ORs were 3.52, 4.20, 4.45, 6.00, respectively, as renal function decreased (all p<0.05). In this cohort of patients with stable coronary artery disease and varied renal functions, cTnI was intensely associated with severity of coronary stenosis which based on Gensini score. The presentation of hypertroponinaemia in patients with impaired renal function always indicates a higher risk of severe coronary stenosis.


Antiplasmodial, antitrypanosomal, and cytotoxic activities of prenylated flavonoids isolated from the stem bark of Artocarpus styracifolius.
In continuation of our efforts to find new antimalarial drugs, a systematic IN VITRO evaluation using a chloroquine resistant strain of PLASMODIUM FALCIPARUM (FcB1) was undertaken on extracts prepared from various parts of Vietnamese plants. The ethyl acetate extract obtained from the stem bark of ARTOCARPUS STYRACIFOLIUS (Moraceae) exhibited strong antiplasmodial activity (87 % at 10 µg/mL) whereas weak cytotoxicity was observed in a human fibroblast cell line (MRC-5). Phytochemical investigation of this extract led to isolation of two new prenylated flavonoids, styracifolins A and B ( 1 and 2), as well as the known artoheterophyllin A ( 3) and B ( 4), artonins A ( 5), B ( 6), and F ( 7), and heterophyllin ( 8). Structures of 1 and 2 were elucidated by spectroscopic methods and through comparison with data reported in the literature. Compounds 1- 8 exhibited antiplasmodial activities with IC (50) values ranging from 1.1 µM to 13.7 µM, and compounds 1, 2, 6, and 8 showed significant antitrypanosomal activities.


[Hemangioendothelioma of the brain presenting with intracerebral hemorrhage: a case report].
Hemangioendothelioma (HE) is an uncommon vascular tumor that is intermediate in histological appearance between a hemangioma and an angiosarcoma. Presently, it is regarded as endothelial tumors of low-grade or intermediate malignancy. It has been reported in the liver, lung, heart, mediastinum, lymph nodes, extremity, and bone. The occurrence in the brain is extremely rare; only 16 cases have so far been reported. We report a 51-year-old woman who presented with transient visual disturbance and weakness of the left upper limb on April 12th 2003. Computed tomography (CT) revealed a high density mass in the right parietal lobe. In magnetic resonance imaging (MRI), the lesion is hyperintense on TIWI, isointense on T2WI, and no enhancement with gadopentetate dimegliumine. Intratumoral hemorrhage was indicated and preoperative diagnosis was cavernous angioma. The tumor was excised completely on April 28th 2003. Pathologically, the tumor cells resembled endothelial cells, positive immunoreactivity for Factor VIII, and grew in small nests or cords. Postoperative MRI showed complete removal of the tumor. There has been no recurrence for 8 months after the surgery, but we have to follow MRI up for a long time. We discussed intracerebral HE clinically and neuroradiologically.


Clinical features of severe wasp sting patients with dominantly toxic reaction: analysis of 1091 cases.
Massive wasp stings have been greatly underestimated and have not been systematically studied. The aim of this study was to identify the clinical features and treatment strategies of severe wasp stings. A multicenter retrospective study was undertaken in 35 hospitals and medical centers including 12 tertiary care hospitals and 23 secondary care hospitals in the Hubei Province, China. The detailed clinical data of 1091 hospitalized wasp sting patients were investigated. Over three-fourths (76.9%) of the cases had 10 or more stings and the in-hospital mortality of patients was 5.1%. Forty-eight patients died of organ injury following toxic reactions to the stings, whereas six died from anaphylactic shock. The in-hospital mortality in patients with >10 stings was higher than that of ≤10 stings (5.2% vs. 1.0%, p = 0.02). Acute kidney injury (AKI) was seen in 21.0% patients and most patients required blood purification therapy. Rhabdomyolysis was seen in 24.1% patients, hemolysis in 19.2% patients, liver injury in 30.1% patients, and coagulopathy in 22.5% patients. Regression analysis revealed that high creatinine level, shock, oliguria, and anemia were risk factors for death. Blood purification therapy was beneficial for patients with ≥20 stings and delayed hospital admission of patients (≥4 hours after sting). In China, most patients with multiple wasp stings presented with toxic reactions and multiple organ dysfunction caused by the venom rather than an anaphylactic reaction. AKI is the prominent clinical manifestation of wasp stings with toxic reaction. High creatinine levels, shock, oliguria, and anemia were risk factors for death.


Recommendations for Use of Affirmative Psychotherapy With LGBT Older Adults.
Affirmative therapy is a type of psychotherapy used to validate and advocate for the needs of sexual and gender minority clients. Therapists use verbal and nonverbal means to demonstrate an affirming stance toward lesbian, gay, bisexual, and transgender (LGBT) clients. Although this therapeutic approach can be used with LGBT individuals across the lifespan, the case presented in this paper highlights the benefit of using this approach with older LGBT individuals. Discussion of the unique challenges faced by older LGBT people will be followed with an illustrative case that shows ways that affirmative therapy can help individuals achieve greater self-actualization. The case formulation and conclusion will highlight specific ways that therapists can convey an affirmative stance and help clients feel welcome and accepted in the therapeutic setting. Recommendations for environmental cues, intake questions, and treatment skills will be offered at the conclusion.


Formation of three N-acetyl-L-cysteine monoadducts and one diadduct by the reaction of S-(1,2-dichlorovinyl)-L-cysteine sulfoxide with N-acetyl-L-cysteine at physiological conditions: chemical mechanisms and toxicological implications.
Previously, our laboratory has shown that S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS), a Michael acceptor produced by a flavin-containing monooxygenase 3 (FMO3)-mediated oxidation of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), is a more potent nephrotoxicant than DCVC. In the present study, we characterized reactions of DCVCS with nucleophilic amino acids. DCVCS incubations with N-acetyl-L-cysteine (NAC) at pH 7.4 and 37 degrees C for 1 h resulted in the formation of three monoadducts and one diadduct characterized by LC/MS, 1H NMR, and 1H-detected heteronuclear single quantum correlation. The formation of all adducts (with relative ratios of 29, 31, 24, and 12%, respectively) was rapid and time-dependent; the half-lives of the two DCVCS diastereomers in the presence of NAC were 13.8 (diastereomer I) and 9.4 min (diastereomer II). Adducts 1 and 2 were determined to be diastereomers of S-[1-chloro-2-(N-acetyl-L-cystein- S-yl)vinyl]-L-cysteine sulfoxide formed by Michael addition of NAC to the terminal vinylic carbon of DCVCS followed by loss of HCl. Adduct 4 was determined to be S-[2-chloro-2-(N-acetyl-L-cystein- S-yl)vinyl]-L-cysteine sulfoxide formed from the initial Michael addition product followed by a less favorable loss of HCl and/or by a rearrangement of adduct 2 through the formation of a cyclic chloronium ion. The addition of another molecule of NAC to monoadducts 1, 2, or 4 resulted in the formation of the novel diadduct, S-[2,2-( N-acetyl-L-cystein-S-yl)vinyl]-L-cysteine sulfoxide (adduct 3), whose detection in relatively large amount suggests that DCVCS could act as a cross-linking agent. DCVCS was not reactive with N-acetyl-L-lysine or L-valinamide at similar incubation conditions. Collectively, the results suggest selective reactivity of DCVCS toward protein sulfhydryl groups. Furthermore, the cross-linking properties of DCVCS may in part explain its high nephrotoxic potency.


Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands: A Clinicopathologic Study With Correlation Between MYB Fusion and Protein Expression.
Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%. The following features were identified as adverse prognostic factors of RFS on univariate analysis: large tumor size, solid growth pattern, increased mitoses, positive margin, American Joint Committee on Cancer clinical staging, high-grade transformation, vascular invasion, nuclear atypia, open chromatin, prominent nucleoli, and tumor necrosis. However, on multivariate analysis, only increased mitoses (≥5/10 high-power fields), any solid growth pattern, and advanced American Joint Committee on Cancer TNM staging were independent adverse predictors for RFS. MYB immunoexpression and MYB-NFIB translocation were common findings in ACC, occurring in 72% and 59% of the tested ACCs, respectively. The sensitivity and specificity of MYB immunohistochemistry in detecting MYB-NFIB fusion was relatively low at 78% sensitivity and 50% specificity. The high prevalence of alterations leading to high expression of the MYB transcription factor family suggests that targeted approaches developed to suppress the expression of these oncogenic transcription factors and/or the transcriptional activity of these proteins would be a rational therapeutic approach to investigate in ACC.


Effect of diabetes on alteration of metabolism in cardiac myocytes: therapeutic implications.
Diabetic cardiomyopathy is a distinct entity in humans. It leads to ventricular dysfunction independent of and additive to coronary artery disease and hypertension. Clinical and experimental studies have pointed to the role of metabolic derangements in the development of diabetic cardiomyopathy. Altered insulin signaling in diabetes leads to decreased myocyte glucose uptake and utilization, associated with an increased concentration of free fatty acids. This results in decreased glucose oxidation and increased fatty acid oxidation. Fatty acids increase mitochondrial oxygen consumption for ATP production and stimulate the uncoupling proteins in mitochondria. These proteins decrease the mitochondrial protein gradient, leading to fall in ATP production. The resultant defect in myocardial energy production impairs myocyte contraction and diastolic function. This is the hallmark of diabetic cardiomyopathy at earlier stages. In later stages diabetes impairs the myocyte ischemic defense mechanism, leading to increased cardiovascular morbidity and mortality. Other factors contributing toward causation of diabetic cardiomyopathy are collagen accumulation leading to reduced myocardial compliance, accumulation of advanced glycation end product-modified extracellular matrix proteins with subsequent inelasticity of vessel walls and myocytes, abnormal myocardial calcium handling leading to altered mechanics, endothelial dysfunction, cardiac autonomic neuropathy, and impairment of ischemic preconditioning. Trimetazidine acts a metabolic switch, favoring glucose over free fatty acids as the substrate for metabolism in cardiac myocytes.


Two new α-pyrone derivatives from an endolichenic fungus Tolypocladium sp.
Two new α-pyrone derivatives, tolypocladones A (1) and B (2), together with five known compounds were isolated from an endolichenic fungus Tolypocladium sp. (4259a). The structures of all the compounds were determined by analysis of their MS and NMR data. Among them, compound 1 was an enantiomeric mixture and the configuration was established by single-crystal X-ray diffraction analysis using Cu-Kα radiation. Also, this is the first report of the presence of compound 3 (glycine, N-(2,3-dihydroxybenzoyl)-methyl ester) and compound 4 (2H-pyran-2-one, 4-methoxy-6-(1,3-pentadienyl)) as natural products.


Early life response to infection.
Sepsis is a serious complication in preterm and term infants, yet our understanding of how neonates respond to infection remains poorly defined. We describe our current clinical, cellular and molecular understanding of the neonatal host systemic response to infection. We find that host resilience essentially relies on innate immune mechanisms despite there being a complete repertoire of cellular components of the adaptive immune arm. The functional interplay between metabolism, immunity and microbiome further suggests that neonatal vulnerability to infection is not simply due to immaturity of the immune system but how immune homeostasis is regulated. Further research is required for exploring regulatory homeostatic mechanisms between innate and adaptive responses and microbiome colonization at birth, but which can impart an adverse trajectory to infection. The vulnerability and resilience against infection in neonates, including extreme preterm infants, still remains poorly understood. We advance the view that greater consideration should be given to understanding the set point in the regulation of homeostatic control of innate and adaptive immunity and its interplay with metabolism and the newly acquired microbiome.


[Biomechanical properties study of aorta in β-aminopropionitrile-induced rat model].
To investigate thoracic aortic longitudinal elastic strength in β-aminopropionitrile (BAPN) treated rat model of aortic dissection (AD). Twenty-nine young rats (Sprague-Dawley) were divided into tow groups, control group (n = 12) and BAPN group (n = 17). Seventeen rats were treated with 0.25% BAPN mixed in feed for 6 weeks. All the rats were sacrificed in the end of experiment and aorta was harvested for biomechanical and pathological study. Longitudinal elastic strength and stress were detected and analyzed by material testing machine. Elasticity modulus as well as maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility was calculated according to the analysis with thickness and area of aortic media. Nine BAPN-treated rats died of aortic dissecting aneurysm rupture during the experiment. The diameter of the aneurysms was (6.33 ± 1.17) mm and the length was (9 ± 5) mm. The maximum diameter significantly increased in BAPN-induced rats with AD (group B2) compared with without AD (group B1) and control group ((6.49 ± 1.20) mm vs. (1.45 ± 0.11), (1.25 ± 0.26); F = 165.257, P = 0.001 and 0.000, respectively), but there was no significance between group B1 and control group (P = 0.108). Thickness and area of aortic media in BAPN-induced rats significantly increased compared with control group (F = 27.277 and 27.153, P = 0.000 and 0.000, respectively), but there was no significance of area between group B1 and B2 (P = 0.540). Maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus were significantly decreased from group B2, group B1 to control group (P < 0.01, respectively). This study built a successful model of AD. Biomechanical analysis and the decrease of maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus may explain the formation of AD partly.


Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice.
The role of resident renal mononuclear phagocytes in acute kidney injury is controversial with experimental data suggesting both deleterious and protective functions. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most marked in diphtheria toxin-treated mice. Despite this, diphtheria toxin treatment did not protect from renal ischemia. In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations. Abolition of the protected phenotype by administration of diphtheria toxin to clodronate-treated mice suggested that the protective effect of clodronate resulted from the presence of a cytoprotective intrarenal population of mononuclear phagocytes sensitive to diphtheria toxin-mediated ablation.


Chemotherapy and radiotherapy of malignant hepatic tumours.
Cure of primary liver tumours remains possible only by surgery and early diagnosis will therefore continue to be important; the value of regular screening of cirrhotic patients for development of HCC by ultrasound scanning and estimation of AFP is now established. Prognosis of irresectable HCC depends largely on the general condition of the patient at the time of diagnosis and is better in the absence of cirrhosis. Radiotherapy has little role in the management of patients with HCC, but benefit with acceptable morbidity may be obtained from parenteral chemotherapy, with doxorubicin or its derivatives used as single agents, or with a combination of 5-FU and methyl-CCNU. There may be advantage from regional therapy given via the hepatic artery and early results from the combination of embolization with arterial doxorubicin are encouraging. The use of radiolabelled antibodies to tumour-related determinants of hormonal manipulation show promise. Worthwhile results from the non-surgical management of peripheral (intrahepatic) cholangiocarcinoma and primary hepatic sarcoma remain scarce. Isolated hepatic metastases from colorectal primaries may be resectable; for those that are not, results from regional chemotherapy with 5-FU or FUDR are encouraging, but cost and high morbidity currently limit more general application.


N-acetylcysteine amide augments the therapeutic effect of neural stem cell-based antiglioma oncolytic virotherapy.
Current research has evaluated the intrinsic tumor-tropic properties of stem cell carriers for targeted anticancer therapy. Our laboratory has been extensively studying in the preclinical setting, the role of neural stem cells (NSCs) as delivery vehicles of CRAd-S-pk7, a gliomatropic oncolytic adenovirus (OV). However, the mediated toxicity of therapeutic payloads, such as oncolytic adenoviruses, toward cell carriers has significantly limited this targeted delivery approach. Following this rationale, in this study, we assessed the role of a novel antioxidant thiol, N-acetylcysteine amide (NACA), to prevent OV-mediated toxicity toward NSC carriers in an orthotropic glioma xenograft mouse model. Our results show that the combination of NACA and CRAd-S-pk7 not only increases the viability of these cell carriers by preventing reactive oxygen species (ROS)-induced apoptosis of NSCs, but also improves the production of viral progeny in HB1.F3.CD NSCs. In an intracranial xenograft mouse model, the combination treatment of NACA and NSCs loaded with CRAd-S-pk7 showed enhanced CRAd-S-pk7 production and distribution in malignant tissues, which improves the therapeutic efficacy of NSC-based targeted antiglioma oncolytic virotherapy. These data demonstrate that the combination of NACA and NSCs loaded with CRAd-S-pk7 may be a desirable strategy to improve the therapeutic efficacy of antiglioma oncolytic virotherapy.


Are HMO enrollees healthier than others? Results from the community tracking study.
This analysis addresses the question of biased selection into health maintenance organizations (HMOs) by using recent, nationally representative data from the Community Tracking Study (CTS) to compare the health status of nonelderly privately insured persons enrolled in HMO and non-HMO plans. Contrary to the conventional view that HMOs receive favorable selection, we find among the privately insured that HMO enrollees are not healthier and may be slightly less healthy. To help understand that result, we present evidence suggesting that other factors, including cost considerations, may be more important than health when people are deciding whether to enroll in an HMO.


Asymmetric total synthesis of dibenzocyclooctadiene lignan natural products.
[structure: see text] Full details of the asymmetric total syntheses of the dibenzocyclooctadiene lignans interiotherin A, angeloylgomisin R, gomisin O, and gomisin E (epigomisin O) are presented. The syntheses were based on a unified synthetic strategy involving a novel crotylation using the Leighton auxiliary that occurred with excellent asymmetric induction (>98:2 enantiomeric ratio), a diastereoselective hydroboration/Suzuki-Miyaura coupling reaction sequence, and an atropdiastereoselective biarylcuprate coupling, both of which occurred with total (>20:1) stereocontrol. The syntheses were achieved in six to eight steps from simple aromatic precursors.


[Metabolic syndrome in dialyzed patients. Diagnosis and insulin resistance].
The criteria for diagnosis of metabolic syndrome (MeS) in patients treated with intermittent hemodialysis or peritoneal dialysis are presented in the paper. Metabolic syndrome is diagnosed in more than 60% of dialyzed patients, but components of MeS, especially hypertension, are much more frequently, also in patients in whom there is no basis for the diagnosis. Increased insulin resistance is a symptom, that in dialysis patients is associated with loss of muscle mass. This is one of the causes of protein malnutrition, despite the concomitant determined abdominal obesity.


Non-Hodgkin's Lymphoma of the Central Nervous System with N-Methyl-D-Aspartate Receptor Antibody Positivity - A Case Report.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, among the paraneoplastic syndromes, is a recently characterized autoimmune encephalitis most commonly associated with antibodies against subunits of the NMDAR in the central nervous system. As a paraneoplastic syndrome, anti-NMDAR encephalitis is commonly associated with ovarian teratomas, small cell lung carcinomas and testicular germ cell tumors. To our knowledge, there have been no cases with primary central nervous system lymphoma (PCNSL), a rare type of extranodal non-Hodgkin's lymphoma, without lymph node involvement associated with anti-NMDAR encephalitis. A 58-year-old right-handed male patient with complaints of instability in walking for two months, progressively smaller handwriting, hallucinations when falling asleep or waking up, decreased memory, inability to maintain attention was admitted to our hospital for further diagnosis and treatment. Lumbar puncture was performed with the diagnosis of possible encephalitis after many further examinations and CSF studies revealed NMDAR antibody positivity, leading to the initial diagnosis of anti - NMDAR encephalitis. He was treated with high dose methylprednisolone and intravenous immunoglobulin. Due to the continuation of the patient's presenting symptoms and cranial magnetic resonance imaging findings, a stereotactic brain biopsy was performed from the area with contrast enhancement and the diagnosis was revised as PCNSL associated with NMDAR antibody positivity. This report emphasizes the importance of anti-NMDAR encephalitis as a paraneoplastic syndrome in previously undiagnosed PCNSL. Therefore, it is crucial to be aware of anti-NMDAR encephalitis as a paraneoplastic neurological syndrome that can present with non-Hodgkin's lymphoma. It is necessary to continually observe the evolution of the disease and perform further diagnostic tests for early identification.


Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells.
IL-6 is an inflammatory cytokine that has been linked to aggressive prostate cancer (PCa). Previous studies have demonstrated that IL-6 can enhance the differentiation of PCa cells toward a neuroendocrine (NE) phenotype, a possible indicator of hormone-refractory disease. In this report, we present evidence that the mechanism of IL-6-stimulated NE differentiation employs a detergent-resistant (lipid raft) membrane compartment for signal transduction in LNCaP PCa cells. Signal transducer and activator of transcription (STAT)3, a mediator of IL-6 signaling, was rapidly phosphorylated and translocated to the nucleus in LNCaP cells treated with IL-6. Both processes were inhibited by filipin, a cholesterol-binding compound that disrupts plasma membrane lipid rafts. Isolation of Triton X-100-insoluble raft fractions from LNCaP cells by discontinuous sucrose gradient centrifugation demonstrated that the 80-kDa IL-6 receptor localized almost exclusively to the raft compartment. Although STAT3 was located predominantly in the Triton X-100-soluble subcellular fraction in exponentially growing cells, abundant phosphorylated STAT3 was detected in the raft fraction after stimulation with IL-6. Increases in expression of the NE marker, neuron-specific enolase, and neuron-specific enolase promoter activity after IL-6 treatment were reduced after membrane rafts were disrupted by filipin treatment. LNCaP cells expressed the raft-resident proteins flotillin-2 and G(ialpha2), but notably not caveolins, the predominant structural protein present in caveolar membrane rafts in many tissues and tumor cells. These results are the first to define a role for lipid raft membrane microdomains in signal transduction mechanisms capable of promoting the NE phenotype in PCa cells, and they demonstrate that the raft compartment is capable of mediating such signals in the absence of caveolins. Our results also suggest a mechanistic role for membrane cholesterol in cell signaling events relevant to PCa progression.


[Anaphylactic shock following intravenous hydrocortisone succinate administration].
Glucocorticoids are frequently used in clinical anaesthesiology and intensive care because of their antiallergic, antiinflammatory and antioedematous properties and anaphylactic reactions are rare. We report on a 62-year-old asthmatic patient with evidence of aspirin sensitivity. We administered 100 mg of hydrocortisone-21-hemisuccinate (Pharmacia & Upjohn, Erlangen, Germany) dissolved in 100 ml 0.9% sodium chloride solution for perioperative corticoid substitution. The patient immediately developed severe bronchospasm and anaphylactic shock requiring intubation and mechanical ventilation. He received adrenaline, isoflurane, ketamine and inhalational fenoterol. He then developed atrioventricular block type III for which we transcutaneously paced the patient. Subsequently he was tested via skin prick tests, intracutaneous tests and i.v.-challenges resulting in the patient having positive reactions to hydrocortisone-21-hemisuccinate. Thus when allergic-like reactions result from glucocorticoid therapy one should consider corticoid allergy as a differential diagnosis.


Neural basis of the visual working memory deficit in schizophrenia: Merging evidence from fMRI and EEG.
Although people with schizophrenia (PSZ) exhibit robust and reliable deficits in working memory (WM) capacity, the neural processes that give rise to this impairment remain poorly understood. One reason for this lack of clarity is that most studies employ a single neural recording modality-each with strengths and weaknesses-with few examples of integrating results across modalities. To address this gap, we conducted a secondary analysis that combined data from an overlapping set of subjects in previously published electroencephalographic and functional magnetic resonance imaging studies that used nearly identical working memory tasks (visual change detection). The prior studies found similar patterns of results for both posterior parietal BOLD activation and suppression of the alpha frequency band within the EEG. Specifically, both signals exhibited abnormally shallow modulation as a function of the amount of information being stored in WM in PSZ. In the present study, both alpha suppression and posterior parietal BOLD activity increased as the number of items stored in WM increased. The magnitude of alpha suppression modulation was correlated with the magnitude of BOLD signal modulation in PSZ, but not in HCS. This finding suggests that the same illness-related biological processes constrain both alpha suppression and BOLD signal modulation as a function of WM storage in PSZ. The complementary strengths of these two techniques may thus combine to advance the identification of the processes underlying WM deficits in PSZ.


Measured proton sensitivities of bubble detectors.
The neutron dose equivalent in aircraft is measured using commercial bubble detectors, but at high altitudes there are not only neutrons but also protons. Bubble detectors have been used because they are considered not to be sensitive to protons, but this has been the subject of only a few studies. In this study, by irradiating bubble detectors with energetic protons, the detectors' responses to protons were observed. Bubbles were clearly formed by protons, but the proton sensitivities were one order of magnitude smaller than the neutron sensitivities. Thus, counts of protons can be ignored in neutron measurements in aircraft.


[Secular trends in food intakes among the elderly aged 60 and older in nine provinces in China from 1991 to 2015].
To analysis the status and trend of food intake of elderly aged 60 and older years old in nine provinces of China. The data of China Health and Nutrition Survey from 1991 to 2015 were used, which elderly ≥60 years old were selected as the subjects. The dietary survey used compared. The 3-consecutive day-24-hour dietary recall was used to collect information on food intake, the condiment intake was collected by weighting and bookkeeping method. The intakes of cereals and tubers and vegetables among the elderly were 363.3 g/d and 249.1 g/d, respectively in 2015, decreased by 65.4 g/d and 17.6 g/d as compared with those in 1991. The intakes of meat, egg, and edible oil were 56.7 g/d, 19.2 g/d and 27.5 g/d respectively and increased by 7.5 g/d, 19.2 g/d and 2.5 g/d as compared to those with 1991. The intakes of eggs, soybeans and nuts were higher among the elderly people having high income or living in urban areas. In 2015, the proportion of elderly in nine provinces of China whose intake of vegetables, fruits, soybeans, milk and dairy products was lower than the recommended amount was relatively high. The proportion of meat higher than the recommended value is higher than that of aquatic products and eggs. Oil, salt and other limited flavoring intake of less than and above the limit was nearly 50 percent of the population. There are three problems in the diet of the elderly in nine provinces in China: the structure of diet is not rational; low intake of the food rich in high quality protein and low fat such as aquatic products, eggs, dairy products and so on; the problem of excessive oil and salt in food.


How parents of teens store and monitor prescription drugs in the home.
Qualitative interviews were conducted with parents of teens to explore how parents store and monitor prescription drugs in the home. Most parents had prescription drugs in the house, but took few precautions against teens accessing these drugs. Strategies for monitoring included moving the drugs to different locations, remembering how many pills were left, and how medication containers were positioned. Reasons given for not securing drugs were that parents did not think that their teens would be interested in their prescription drugs and did not believe that they could be used to get high. This study highlights the need for parents to be educated about securing prescription drugs, the dangers of non-medical prescription drug use by teens, and which drugs might be used for non-medical purposes.


Hyaluronic acid-modified multiwalled carbon nanotubes for targeted delivery of doxorubicin into cancer cells.
Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.


A randomised trial to assess the safety and efficacy of artemether-lumefantrine (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda.
Coartem is a fixed-dose combination of artemether-lumefantrine that, given in six doses, provides effective treatment for children with uncomplicated Plasmodium falciparum infection in areas with highly endemic and multidrug-resistant malaria. In Rwanda since 2001, amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) has been the first-line treatment, but resistance to this combination has rapidly emerged and spread. Coartem was considered as a possible alternative, and a randomised, open-label, clinical trial to test its safety, tolerability and efficacy was carried out in 2004-2005. Five hundred children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to AQ+SP or Coartem. Patients were followed up until day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Adequate clinical and parasitological response (ACPR) was significantly higher in children treated with Coartem than in those treated with AQ+SP: the PCR-adjusted 28-day ACPR was 96.68% for Coartem and 79.35% for AQ+SP. Both treatments rapidly cleared parasitaemia and fever, although parasite clearance was significantly faster in children treated with Coartem. Mean packed cell volume increased in all patients, with no significant differences between treatments. Coartem proved to be more efficacious than AQ+SP, with a good safety and tolerability profile.


RNxQuest: An Extension to the xQuest Pipeline Enabling Analysis of Protein-RNA Cross-Linking/Mass Spectrometry Data.
Cross-linking and mass spectrometry (XL-MS) workflows are increasingly popular techniques for generating low-resolution structural information about interacting biomolecules. xQuest is an established software package for analysis of protein-protein XL-MS data, supporting stable isotope-labeled cross-linking reagents. Resultant paired peaks in mass spectra aid sensitivity and specificity of data analysis. The recently developed cross-linking of isotope-labeled RNA and mass spectrometry (CLIR-MS) approach extends the XL-MS concept to protein-RNA interactions, also employing isotope-labeled cross-link (XL) species to facilitate data analysis. Data from CLIR-MS experiments are broadly compatible with core xQuest functionality, but the required analysis approach for this novel data type presents several technical challenges not optimally served by the original xQuest package. Here we introduce RNxQuest, a Python package extension for xQuest, which automates the analysis approach required for CLIR-MS data, providing bespoke, state-of-the-art processing and visualization functionality for this novel data type. Using functions included with RNxQuest, we evaluate three false discovery rate control approaches for CLIR-MS data. We demonstrate the versatility of the RNxQuest-enabled data analysis pipeline by also reanalyzing published protein-RNA XL-MS data sets that lack isotope-labeled RNA. This study demonstrates that RNxQuest provides a sensitive and specific data analysis pipeline for detection of isotope-labeled XLs in protein-RNA XL-MS experiments.


The effect of two models of supervision on selected outcomes.
To evaluate the effect of training in two different supervisory models on the supervision itself, the quality of care, and job satisfaction of nurses in different service settings in a district health service (DHS) in South Africa. As part of a larger health systems study, the results of supervision training were evaluated. The quantitative study was done in three health districts in South Africa. The modified matrix (MM) model of supervision was taught and implemented in District A, the Centre for Health and Social Studies (CHESS) model in District B, and the control was District C. Checklists based on direct observation and record reviews were used to measure quality of care (quality of hand-over between shifts, nursing records, management of chronic diseases, and implementation of universal precautions). Questionnaires were used to measure perception of supervision and patient satisfaction. Chi-square analysis was done. Supervision ratings before and after the interventions differed significantly in the total sample, but not by district. In the district with the MM model, care for people with chronic diseases improved significantly, but other measures did not. The supervision training had some influence, but more measures of effectiveness of supervision training are needed.


Annexin A5 multitasking: a potentially novel antiatherothrombotic agent?
Atherothrombosis, formed on an underlying atherosclerotic plaque, is the key pathogenic mechanism behind the majority of clinically evident cardiovascular ischemic diseases including acute coronary artery disease, cerebrovascular and peripheral arterial occlusion. Annexin A5 (ANXA5; previously annexin V), a member of the annexin superfamily, is a protein with potent and unique antithrombotic properties. The antithrombotic effect exerted by ANXA5 is thought to be mediated mainly by mechanical shielding of phospholipids, phosphatidylserine in particular, thereby reducing their availability for coagulation reactions. However, other intriguing properties of ANXA5 potentially contributing to its antithrombotic function, especially downregulation of surface expressed tissue factor, or interaction with additional ligands involved in hemostasis such as sulfatide and heparin, as well as upregulation of urokinase-type plasminogen activator were reported. The biological significance of ANXA5 as a member of endogenous antithrombotic system in vivo has been suggested recently for the large vasculature and for placental microcirculation. Antiatherothrombotic potential of ANXA5 deserves further attention and careful studies in order to determine its true physiological impact as well as its possible therapeutic applications.


Total synthesis of (+)-przewalskin B.
An efficient strategy for the total synthesis of (+)-przewalskin B is reported. The key steps feature an intermolecular S(N)2' substitution of iodoallylic phosphate with organocupper reagent, a diastereoselective organocatalytic aldol cyclization, as well as a Rh(2)(OAc)(4)-mediated intramolecular carbene insertion to the tertiary C-H bond.


Effects of OM-853, a novel indolonaphthyridine derivative, on behavioral responses in the forced swim test in rats.
Effects of OM-853 on behavioral responses in the forced swim test were studied. OM-853 significantly reduced the duration of immobility without any change in the exploratory activity. Imipramine also reduced the duration of immobility, but idebenone did not. On the other hand, vinpocetine enhanced the duration with a suppressive effect on ambulation. The anti-immobility effect of OM-853 was reversed by pretreatment with haloperidol. These results demonstrate that the effect of OM-853 on the swim test is different from that of idebenone and vinpocetine. Furthermore, the present results suggest that OM-853 may exert its anti-immobility activity through facilitated transmission of the dopaminergic and/or adrenergic systems.


Severity and form of temporomandibular disorder symptoms: Functional, physical, and psychosocial impacts.
The associations between the presence of differing severity/form of temporomandibular disorder (TMD) symptoms and oral health-related quality of life (OHRQoL) were explored. The severity and form of TMDs in young adults were categorized based on the Fonseca Anamnestic Index (FAI) and Diagnostic Criteria for TMDs (DC/TMD), and OHRQoL was assessed with the Oral Health Impact Profile-14 (OHIP-14). Data were analyzed using non-parametric statistics (α = 0.05). The study cohort consisted of 501 young adults (mean age 19.7 ± 1.3 years; 75.2% women). Participants with severe/moderate TMDs had significantly higher OHIP severity scores than those with mild/no TMDs. Moreover, participants with combined/pain-related symptoms exhibited significantly higher severity scores compared to those without symptoms. The physical pain and psychological discomfort domains were typically more impaired regardless of severity/form of TMD symptoms. More severe and painful symptoms were related to greater impairments in OHRQoL, especially in the physical and psychological domains.


An investigation of the auditory perception of western lowland gorillas in an enrichment study.
Previous research has highlighted the varied effects of auditory enrichment on different captive animals. This study investigated how manipulating musical components can influence the behavior of a group of captive western lowland gorillas (Gorilla gorilla gorilla) at Bristol Zoo. The gorillas were observed during exposure to classical music, rock-and-roll music, and rainforest sounds. The two music conditions were modified to create five further conditions: unmanipulated, decreased pitch, increased pitch, decreased tempo, and increased tempo. We compared the prevalence of activity, anxiety, and social behaviors between the standard conditions. We also compared the prevalence of each of these behaviors across the manipulated conditions of each type of music independently and collectively. Control observations with no sound exposure were regularly scheduled between the observations of the 12 auditory conditions. The results suggest that naturalistic rainforest sounds had no influence on the anxiety of captive gorillas, contrary to past research. The tempo of music appears to be significantly associated with activity levels among this group, and social behavior may be affected by pitch. Low tempo music also may be effective at reducing anxiety behavior in captive gorillas. Regulated auditory enrichment may provide effective means of calming gorillas, or for facilitating active behavior. Zoo Biol. 35:398-408, 2016. © 2016 Wiley Periodicals, Inc.


A positive feedback loop between glycogen synthase kinase 3beta and protein phosphatase 1 after stimulation of NR2B NMDA receptors in forebrain neurons.
N-methyl-D-aspartate receptors (NMDARs) are critical for neuronal plasticity and survival, whereas their excessive activation produces excitotoxicity and may accelerate neurodegeneration. Here, we report that stimulation of NMDARs in cultured rat hippocampal or cortical neurons and in the adult mouse brain in vivo disinhibited glycogen synthase kinase 3beta (GSK3beta) by protein phosphatase 1(PP1)-mediated dephosphorylation of GSK3beta at the serine 9 residue. NMDA-triggered GSK3beta activation was mediated by NMDAR that contained the NR2B subunit. Interestingly, GSK3beta inhibition reduced inhibitory phosphorylation of the PP1 inhibitor 2 (I2) and attenuated serine 9 dephosphorylation by PP1. These data suggest existence of a feedback loop between GSK3beta and PP1 that results in amplification of PP1 activation by GSK3beta. In addition, GSK3beta inhibition decreased PP1-mediated dephosphorylation of the cAMP-response element-binding protein (CREB) at the serine 133 residue in NMDA-stimulated neurons. Conversely, overexpression of GSK3beta abolished non-NR2B-mediated activation of CRE-driven transcription. These data suggest that cross-talk between GSK3beta and PP1 contributes to NR2B NMDAR-induced inhibition of CREB signaling by non-NR2B NMDAR. The excessive activation of NR2B-PP1-GSK3beta-PP1 circuitry may contribute to the deficits of CREB-dependent neuronal plasticity in neurodegenerative diseases.


BMN 250, a fusion of lysosomal alpha-N-acetylglucosaminidase with IGF2, exhibits different patterns of cellular uptake into critical cell types of Sanfilippo syndrome B disease pathogenesis.
Sanfilippo syndrome type B (Sanfilippo B; Mucopolysaccharidosis type IIIB) occurs due to genetic deficiency of lysosomal alpha-N-acetylglucosaminidase (NAGLU) and subsequent lysosomal accumulation of heparan sulfate (HS), which coincides with devastating neurodegenerative disease. Because NAGLU expressed in Chinese hamster ovary cells is not mannose-6-phosphorylated, we developed an insulin-like growth factor 2 (IGF2)-tagged NAGLU molecule (BMN 250; tralesinidase alfa) that binds avidly to the IGF2 / cation-independent mannose 6-phosphate receptor (CI-MPR) for glycosylation independent lysosomal targeting. BMN 250 is currently being developed as an investigational enzyme replacement therapy for Sanfilippo B. Here we distinguish two cellular uptake mechanisms by which BMN 250 is targeted to lysosomes. In normal rodent-derived neurons and astrocytes, the majority of BMN250 uptake over 24 hours reaches saturation, which can be competitively inhibited with IGF2, suggestive of CI-MPR-mediated uptake. Kuptake, defined as the concentration of enzyme at half-maximal uptake, is 5 nM and 3 nM in neurons and astrocytes, with a maximal uptake capacity (Vmax) corresponding to 764 nmol/hr/mg and 5380 nmol/hr/mg, respectively. Similar to neurons and astrocytes, BMN 250 uptake in Sanfilippo B patient fibroblasts is predominantly CI-MPR-mediated, resulting in augmentation of NAGLU activity with doses of enzyme that fall well below the Kuptake (5 nM), which are sufficient to prevent HS accumulation. In contrast, uptake of the untagged recombinant human NAGLU (rhNAGLU) enzyme in neurons, astrocytes and fibroblasts is negligible at the same doses tested. In microglia, receptor-independent uptake, defined as enzyme uptake resistant to competition with excess IGF2, results in appreciable lysosomal delivery of BMN 250 and rhNAGLU (Vmax = 12,336 nmol/hr/mg and 5469 nmol/hr/mg, respectively). These results suggest that while receptor-independent mechanisms exist for lysosomal targeting of rhNAGLU in microglia, BMN 250, by its IGF2 tag moiety, confers increased CI-MPR-mediated lysosomal targeting to neurons and astrocytes, two additional critical cell types of Sanfilippo B disease pathogenesis.


Effects of fatigue, rumination thinking, and sleep quality on hopelessness in family caregivers of cancer patients.
The heavy care burden, long-term dependence of caring for cancer patients, and changing social roles put family caregivers at high risk of mental disorders and hopelessness. This explored the relationship between fatigue, sleep quality, rumination, and hopelessness, and provides suggestions to maintain caregivers' mental health. We investigated 536 family caregivers of cancer patients in three grade A hospitals in Liaoning Province who met the inclusion criteria on the Beck Hopelessness Scale (BHS), Fatigue Scale-14 (FS-14), Nolen-Hoeksema Ruminative Responses Scale (RRS), and Pittsburgh Sleep Quality Index (PSQI). Data were analyzed with SPSS 26.0, and Amos 22.0 was used to fit the structural equation model. The family caregivers had a higher degree of hopelessness and fatigue, while sleep quality and rumination were positively correlated with hopelessness (r = 0.483-0.906; P < 0.05). Fatigue and sleep quality can indirectly affect hopelessness through rumination thinking, while hopelessness has a direct effect on sleep. There are multiple action paths between fatigue and sleep quality, rumination thinking, and hopelessness. Family caregivers' physical and mental health can be maintained and hopelessness avoided by improving sleep quality, alleviating fatigue, and psychological counseling.


[Medial patellofemoral ligament reconstruction with gracilis autograft for patellar instability].
We describe a technique for patellar stabilization by reconstruction of the medial patellofemoral ligament with the gracilis tendon. The tendon is anchored posteriorly on the soft tissue of the medial femoral epicondyle and anteriorly on the medial border of the patella. The plasty is completed by suture of the medial patellar wing. Inferior or medial transposition of the tibial tubercle may be associated. We have used this technique since 1995 for 145 knees with patellar instability. The small incisions have the advantages of minimally invasive surgery, particularly for the postoperative period and the cosmetic effect.


Prevalence and survival of Listeria monocytogenes in Danish aquatic and fish-processing environments.
Listeria monocytogenes contamination of ready-to-eat food products such as cold-smoked fish is often caused by pathogen subtypes persisting in food-processing environments. The purpose of the present study was to determine whether these L. monocytogenes subtypes can be found in the outside environment, i.e., outside food processing plants, and whether they survive better in the aquatic environment than do other strains. A total of 400 samples were collected from the outside environment, fish slaughterhouses, fish farms, and a smokehouse. L. monocytogenes was not detected in a freshwater stream, but prevalence increased with the degree of human activity: 2% in seawater fish farms, 10% in freshwater fish farms, 16% in fish slaughterhouses, and 68% in a fish smokehouse. The fish farms and slaughterhouses processed Danish rainbow trout, whereas the smokehouse was used for farm-raised Norwegian salmon. No variation with season was observed. Inside the processing plants, the pattern of randomly amplified polymorphic DNA (RAPD) types was homogeneous, but greater diversity existed among isolates from the outside environments. The RAPD type dominating the inside of the fish smokehouse was found only sporadically in outside environments. To examine survival in different environments, L. monocytogenes or Listeria innocua strains were inoculated into freshwater and saltwater microcosms. Pathogen counts decreased over time in Instant Ocean and remained constant in phosphate-buffered saline. In contrast, counts decreased rapidly in natural seawater and fresh water. The count reduction was much slower when the natural waters were autoclaved or filtered (0.2-microm pore size), indicating that the pathogen reduction in natural waters was attributable to a biological mechanism, e.g., protozoan grazing. A low prevalence of L. monocytogenes was found in the outside environment, and the bacteria did not survive well in natural environments. Therefore, L. monocytogenes in the outer environment associated with Danish fish processing is probably of minor importance to the environment inside a fish production plant.


Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO).
The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH.


Underground friends or enemies: model plants help to unravel direct and indirect effects of arbuscular mycorrhizal fungi on plant competition.
*We studied the effects of two arbuscular mycorrhizal (AM) fungi, singly or together, on the outcome of competition between a host (tomato cultivar, wild-type (WT)) and a surrogate nonhost (rmc, a mycorrhiza-defective mutant of WT) as influenced by the contributions of the direct and AM phosphorus (P) uptake pathways to plant P. *We grew plants singly or in pairs of the same or different genotypes (inoculated or not) in pots containing a small compartment with (32)P-labelled soil accessible to AM fungal hyphae and determined expression of orthophosphate (P(i)) transporter genes involved in both AM and direct P uptake. *Gigaspora margarita increased WT competitive effects on rmc. WT and rmc inoculated with Glomus intraradices both showed growth depressions, which were mitigated when G. margarita was present. Orthophosphate transporter gene expression and (32)P transfer showed that the AM pathway operated in single inoculated WT, but not in rmc. *Effects of AM fungi on plant competition depended on the relative contributions of AM and direct pathways of P uptake. Glomus intraradices reduced the efficiency of direct uptake in both WT and rmc. The two-fungus combination showed that interactions between fungi are important in determining outcomes of plant competition.


Unilateral adrenal hematoma with associated giant mass: a report of two cases.
Background: Adrenal hematoma is a rare yet potentially life-threatening event that occurs both in traumatic conditions and in a variety of nontraumatic conditions. In the present study, we report the two cases with idiopathic unilateral adrenal hematoma. Case presentation: Case 1 involved a 72-year-old man who was complaining of upper abdominal pain. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a giant mixed density tumor in the right retroperitoneal space. To remove the tumor, we carried out an adrenalectomy on the right adrenal gland, resecting a specimen measuring 15 × 13.5 cm. The histopathological findings of the specimen revealed a hematoma with normal adrenal tissue. Case 2 involved a 53-year-old woman who complained of an uncomfortable feeling in her left upper abdomen. A retroperitoneal tumor had formed a multicystic lesion and resected because the left renal vein had become compressed. The resected specimen was 10.5 × 10 cm in size and revealed an adrenal hematoma. In the absence of any obvious etiology, the diagnoses in both cases were idiopathic adrenal hematoma. Conclusion: An accurate diagnosis of idiopathic adrenal hematoma is quite difficult to make prior to surgery. Some imaging modalities are useful in generating a differential diagnosis.


Excitonic effects in the optical spectra of graphene nanoribbons.
We present a first-principles calculation of the optical properties of armchair-edged graphene nanoribbons (AGNRs) with many-electron effects included. The reduced dimensionality of the AGNRs gives rise to an enhanced electron-hole binding energy for both bright and dark exciton states (0.8-1.4 eV for GNRs with width approximately 1.2 nm) and dramatically changes the optical spectra owing to a near complete transfer of oscillator strength to the exciton states from the continuum transitions. The characteristics of the excitons of the three distinct families of AGNRs are compared and discussed. The enhanced excitonic effects found here are expected to be of importance in optoelectronic applications of graphene-based nanostructures.


Whole blood microRNA expression may not be useful for screening non-small cell lung cancer.
At least seven studies have suggested that microRNA levels in whole blood can be diagnostic for lung cancer. We conducted a large bi-institutional study to validate this. Qiagen® PAXgene™ Blood miRNA System was used to collect blood and extract RNA from it for 85 pathologic stage I-IV non-small cell lung cancer (NSCLC) cases and 76 clinically-relevant controls who had a benign pulmonary mass, or a high risk of developing lung cancer because of a history of cigarette smoking or age >60 years. Cases and controls were similar for age, gender, race, and blood hemoglobin and leukocyte but not platelet levels (0.23 and 0.26 million/μl, respectively; t test P = 0.01). Exiqon® MiRCURY™ microarrays were used to quantify microRNAs in RNA isolates. Quantification was also performed using Taqman™ microRNA reverse transcription (RT)-PCR assays for five microRNAs whose lung cancer-diagnostic potential had been suggested in seven published studies. Of the 1,941 human mature microRNAs detectable with the microarray platform, 598 (31%) were identified as expressed and reliably quantified among the study's subjects. However, none of the microRNAs was differentially expressed between cases and controls (P >0.05 at false discovery rate <5% in test using empirical Bayes-moderated t statistics). In classification analyses with leave-one-out internal cross-validation, cases and controls could be identified by microRNA expression with 47% and 50% accuracy with support vector machines and top-scoring pair methods, respectively. Cases and controls did not differ for RT-PCR-based measurements of any of the five microRNAs whose biomarker potential had been suggested by seven previous studies. Additionally, no difference for microRNA expression was noticed in microarray-based microRNA profiles of whole blood of 12 stage IA-IIIB NSCLC cases before and three-four weeks after tumor resection. These findings show that whole blood microRNA expression profiles lack diagnostic value for high-risk screening of NSCLC, though such value may exist for selective sub-groups of NSCLC and control populations.


Synergistic regulation of human megakaryocyte development.
Little information exists concerning differing levels of regulation occurring during human megakaryocyte development. We hypothesize that megakaryocytic proliferation and maturation is controlled by two, synergistic regulatory factors. One, megakaryocyte colony-stimulating activity, is an obligate requirement for colony formation and drives the development of relatively immature cells. Megakaryocyte colony-stimulating activity is a functional component of the human recombinant proteins, interleukin 3 or GM-CSF. Human recombinant growth factors, interleukin 1, interleukin 6, or crythropoietin, do not effect megakaryocyte development either alone or in combination with interleukin 3. Full maturation requires a second synergistic activity which increases megakaryocyte number, size, and cytoplasmic and antigenic content. In culture, this synergistic regulator augments maturation by increasing the number of colonies, colony cellularity, and size. In suspension cultures, this cofactor increases megakaryocyte cytoplasmic and antigenic content, and shifts the morphological distribution from immature to mature megakaryocytes. Finally, this activity also increases the number of antigen positive megakaryocytes, either by stimulating proliferation or conversion of antigen-negative to antigen-positive cells. Comparative studies of megakaryocytic regulation suggests that this in vitro regulator mimicks some of the known effects of thrombopoietin in vivo.


The presence of extreme feather peckers in groups of laying hens.
Feather pecking is a serious economic and welfare problem in laying hens. Feather damage occurs mainly through severe feather pecking (SFP). Selection experiments have proved that this behavior is heritable and lines have been divergently selected for high (HFP) and low feather pecking (LFP). The number of bouts of SFP per hen follows a Poisson distribution with a maximum nearby 0. A few studies indicate that the distribution within flocks is not homogenous but contains sub-groups of birds showing extremely high levels of feather pecking (EFP). It was the aim of the current study to re-analyze data on SFP of lines selected for HFP/LFP and their F2 cross so as to uncover hidden sub-populations of EFP birds. Data of seven selection generations of HFP and LFP selection lines as well as their F2 cross have been used. We fitted a two-component mixture of Poisson distributions in order to separate the sub-group of EFP from the remaining birds. HFP and LFP lines differed mainly in mean bouts per bird. The proportion of EFP was only marginal in the LFP as compared with the HFP and the F2 population. Selection for LFP did not result in total elimination of EFP. The presence of even small proportions of EFP may play an important role in initiating outbreaks of feather pecking in large flocks. Further studies on feather pecking should pay special attention to the occurrence of EFP sub-groups.


Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice.
This article reviews pharmacokinetic (PK) and pharmacodynamic (PD) concepts relating to the pharmacology of basal insulin analogs. Understanding the pharmacology of currently available long-acting basal insulins and the techniques used to assess PK and PD parameters (e.g. the euglycemic clamp method) is important when considering the efficacy and safety of these agents, and can help in understanding the rationale for specific dosing strategies when tailoring therapy for a specific patient. Basal insulins such as insulin glargine 100 units (U)/mL and insulin detemir show improved PK/PD characteristics compared with the intermediate-acting NPH insulin, with a longer duration of action, a more consistent glucose-lowering effect and less prominent concentration peaks. However, more recently developed basal insulins (insulin glargine 300 U/mL, and insulin degludec 100 U/mL and 200 U/mL) have PK/PD profiles closer to the physiologic profile of endogenous basal insulin owing to a more evenly distributed, predictable and prolonged time-action profile that exceeds 24 hours and improved within-patient variability in glucose-lowering effect. The clinical implications and relevance of these PK/PD profiles is explored, including the potential effect of PK/PD parameters on glycemic control and hypoglycemia, and the timing of dosing. The improved PK/PD properties of newer longer-acting basal insulins may translate into clinical benefits for patients with type 1 and type 2 diabetes, such as more consistent insulin levels in the blood over 24 hours, lower intra-patient variability, a reduced risk of nocturnal hypoglycemia, and more flexibility in dosing time, all of which are important to consider when choosing a basal insulin regimen.


Semi-Automated Neurofeedback Therapy for Persistent Postconcussive Symptoms in a Military Clinical Setting: A Feasibility Study.
Neurofeedback therapy (NFT) has demonstrated effectiveness for reducing persistent symptoms following traumatic brain injury (TBI); however, its reliance on NFT experts for administration and high number of treatment sessions limits its use in military medicine. Here, we assess the feasibility of live Z-score training (LZT)-a variant of NFT that requires fewer treatment sessions and can be administered by nonexperts-for use in a military clinical setting. A single group design feasibility study was conducted to assess acceptability, tolerance, treatment satisfaction, and change in symptoms after a 6-week LZT intervention in 38 Service Members (SMs) with persistent symptoms comorbid with or secondary to mild TBI. Acceptance and feasibility were assessed using treatment completion and patients' satisfaction with treatment. To evaluate changes in symptom status, a battery of self-report questionnaires was administered at baseline, posttreatment, and 3-month follow-up to evaluate changes in psychological, neurobehavioral, sleep, pain, and headache symptoms, as well as self-efficacy in symptom management and life satisfaction. Participants tolerated the treatment well and reported a positive experience. Symptom improvement was observed, including depressive, neurobehavioral, and pain-related symptoms, with effects sustained at 3-month follow-up. LZT treatment appears to be a feasible, non-pharmacological therapy amenable to SMs. Results from this pilot study promote further investigation of LZT as an intervention for SMs with persistent symptoms following TBI.


Parametric study of ion acceleration in a one-dimensional plasma expansion using the particle-in-cell simulation.
The one-dimensional expansion of a plasma off a planar wall into a vacuum is studied using particle-in-cell computer simulation. Particular emphasis is put on the acceleration of ions in the plasma. Energy transfer from the electronic to the ionic subsystem, the energy spectra of the ions, and the center-of-mass motion of the ion cloud are monitored. Various parameters that influence the acceleration process are studied: the presence of several ion charge states, of neutrals, the effects of a binary mixture of ions, and of a thermal nonequilibrium between ions and electrons.


A new syndrome: multiple dislocations of distal interphalangeal joints associated with interstitial pneumonia, Sjögren's syndrome, and positive autoantibodies.
Abstract A 54-year-old woman and a 64-year-old man consulted our clinic for dislocation of the distal interphalangeal (DIP) joints. They both had been diagnosed as having Sjögren's syndrome. In addition, interstitial pneumonia had been detected several years earlier in both cases. Antibodies to SSA/Ro (52 kDa) and Jo-1 were detected in their sera, but serum CK and aldolase levels were normal. There were no eruptions, and muscle strength was normal in both patients. The combination of the following six conditions, i.e., (1) multiple dislocations of DIP joints, (2) interstitial pneumonia, (3) Sjögren's syndrome, (4) positive anti-SSA antibodies (52 kDa), (5) positive anti-Jo-1 autoantibodies, and (6) children with hypermobile joints is quite rare and not observed frequently. Existence of the above six conditions in two patients is even rarer. Therefore, the probability that all six conditions would coincidentally coexist in each of the two separate subjects is virtually zero. In this article, we propose a novel clinical complex - multiple dislocations of DIP joints, interstitial pneumonia associated with Sjögren's syndrome, and positive anti-SSA and anti-Jo-1 antibodies (DIPSSJ) - as a new syndrome of which clinicians should be aware. Because the children of both patients had hypermobile joints, the syndrome may be partially genetic.


[Early identification value of quick sequential organ failure assessment score in patients with sepsis of different ages].
To investigate the value of quick sequential organ failure assessment (qSOFA) score in early identification for sepsis patients of different ages. A retrospective study was conducted. The clinical data of 1 529 patients with suspected infection in emergency department of Changshu No.2 People's Hospital from September 2017 to March 2020 were collected. All patients were assessed for qSOFA score, and the diagnosis and treatment were recorded. Sepsis-3 was defined as the diagnostic criteria for sepsis. All the patients were divided into five groups according to age, youth group (< 45 years old), middle-aged group (45-59 years old), presenile group (60-74 years old), elderly group (75-89 years old), and longevity group (≥ 90 years old). The patients' examination results, diagnosis and treatment status were collected. The distribution of different scores of qSOFA was analyzed to calculate the sensitivity, specificity, positive predictive value and negative predictive value of different qSOFA scores for the diagnosis of sepsis in patients with suspected infection of different ages. The receiver operator characteristic curve (ROC curve) was drawn to analyze the diagnostic value of qSOFA score for sepsis in patients with suspected infection at different ages. Of 1 529 suspected infection patients, there were 67 patients in youth group, 129 patients in middle-aged group, 465 patients in presenile group, 778 patients in elderly group and 90 patients in longevity group. There were significant differences in lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), qSOFA score and the increased value of SOFA score compared with the basic value (ΔSOFA) among the suspected infection patients at different ages. Among suspected infection patients at different ages, the patients with qSOFA score ≥ 1 were the most, and the proportion of sepsis patients was larger. Further analysis showed that qSOFA score ≥ 1 had a high diagnostic sensitivity in patients with suspected infection at different ages. In the youth group, the sensitivity was 84.4%, and the specificity was the highest (74.3%). Although qSOFA score ≥ 2 had a high specificity in the diagnosis of sepsis (all > 97%), its sensitivity was very low (all < 44%). In this study, all patients with a qSOFA score of 3 were sepsis, and the positive predictive value of the diagnosis of sepsis in each group was 100%. ROC curve analysis showed that the area under ROC curve (AUC) of qSOFA score for the diagnosis of sepsis in all suspected infection patients was 0.771 [95% confidence interval (95%CI) was 0.747-0.794], when the best cut-off value was 0.5, the sensitivity was 93.4% and the specificity was 45.6%. Among suspected infection patients of all ages, the accuracy of qSOFA score in the diagnosis of sepsis in the youth group and the longevity group was relatively high, with AUC (95%CI) of 0.825 (0.724-0.927) and 0.837 (0.756-0.917), respectively; when the best cut-off value was 0.5, the sensitivity was 84.4% or 92.2%, and the specificity was 74.3% or 56.4%, respectively. qSOFA score has an early diagnosis value for sepsis, especially in the patients aged < 45 years old or ≥ 90 years old. Using qSOFA score ≥ 2 to screen patients with suspected infection is likely to cause missed diagnosis.


[The tongue as a factor in craniofacial growth. 4. Results of animal experiments].
Post-natal craniofacial growth in the miniature pig MIN-LEWE is influenced by the tongue in various ways. Periodic and locally differentiated intensive craniofacial growth explains why the tongue has a measurable effect on jaw growth only at certain times. This is the situation in animals glossectomized at an age of 12 weeks. Shortening of the tongue in miniature pigs aged six weeks resulted in no measurable changes in the jaw after a prolonged post-surgical interval (23 weeks), which indicates that the capacity of the orofacial system during post-natal development is considerable.


Influence of alpha-fetoprotein on the in vitro and in vivo immune response to acetylcholine receptor.
Alpha-fetoprotein (AFP) derived from amniotic fluid and both maternal and umbilical cord sera but not from hepatoma, blocks the binding of serum acetylcholine receptor (AChR) antibody from patients with myasthenia gravis (MG) and animals with experimental autoimmune MG (EAMG) to AChR preparations as measured by a radioimmunoassay. AFP also inhibits the AChR and mitogen induced in vitro proliferative response of lymphocytes obtained from animals with EAMG. Laboratory animals repeatedly injected with AFP fail to develop EAMG in response to sensitization with AChR. Animals with established EAMG show clinical improvement in response to AFP treatment. AChR antibodies are suppressed in such AFP-treated animals. AFP is present in increased amounts during pregnancy and thus could contribute to remissions during the second half of pregnancy in patients with MG. The rapid decrease in levels of AFP during the post-partum period may also be partly responsible for relapses seen during this period. AFP may also be responsible for the appearance of transitory neonatal MG only sometime after birth and in only a minority of cases.


Effects of insulin on free amino acids in plasma and the role of the amino acid metabolism in the etiology of diabetic microangiopathy.
To investigate if alterations of the amino acid metabolism may play a more important role in the etiology of diabetic microangiopathy than hitherto recognized, free amino acids in plasma were measured by means of high-performance liquid chromatography (HPLC) in healthy individuals (REF) and patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Isoleucine and leucine in IDDM were within normal limits, whereas they were significantly higher in NIDDM (P < 0.01 and P < 0.001, respectively). This was not due to age differences. In order to evaluate the impact of insulin on amino acid metabolism, amino acids were also measured in pregnant women (PREG) undergoing glucose tolerance tests as a screening for pregnancy diabetes and in patients with polycystic ovary syndrome (PCO) undergoing euglycemic insulin clamp tests. Insulin considerably reduced the amino acid concentration. Isoleucine and leucine were particularly depressed. On the whole there was strong covariance between the three branched-chain amino acids, isoleucine, leucine, and valine (P < 0.0001). There was no covariance between amino acid and glucose or HbA1c concentrations. A protein meal strongly stimulated insulin production (+55 mIU/liter), whereas a galactose meal revealed only a minor increase in insulin response (+12 mIU/liter) in contrast to a tolerance test with the same amount of glucose (+67 mIU/liter). It is concluded that disturbed amino acid metabolism may be a more important causative factor in the etiology of diabetic microangiopathy than hitherto recognized and, in addition, that this may affect the therapeutic approach in both IDDM and NIDDM patients.


Lead Poisoning in Children.
Asymptomatic lead poisoning has become more common in children. Blood lead levels of less than 5 µg per dL are associated with impairments in neurocognitive and behavioral development that are irreversible. Risk factors for lead poisoning include age younger than five years, low socioeconomic status, living in housing built before 1978, and use of imported food, medicines, and pottery. The U.S. Preventive Services Task Force released a recommendation in 2019 citing insufficient evidence to assess the balance of benefits and harms of universal screening for elevated blood lead levels in asymptomatic children and pregnant women. Local risk factors can be substantial, and the Centers for Disease Control and Prevention (CDC) recommends that states and cities formulate their own targeted screening guidelines. In the absence of local guidance, the CDC recommends screening all Medicaid-eligible children at 12 months and again at 24 months, or at least once between 36 and 72 months if not previously screened. The CDC also recommends universal screening in areas where more than 27% of the housing was built before 1950, or where at least 12% of children 12 to 36 months of age have blood lead levels greater than 10 µg per dL. Life-threatening lead levels are treated with chelation therapy, and lower levels should prompt case management and environmental investigations to identify and remove the source of exposure. Primary prevention strategies are essential to eliminate the harmful effects of lead on child development.


The Synthesis of YNU-5 Zeolite and Its Application to the Catalysis in the Dimethyl Ether-to-Olefin Reaction.
During prior investigations of the synthesis of the novel zeolite YNU-5 (YFI), it was found that a very slight amount of an impurity phase contaminated the desired zeolitic phase. This impurity was very often ZSM-5 (MFI). The phase composition was determined to be sensitive to the water in the synthesis mixture, and it was possible to obtain a pure phase and also to intentionally generate a specific impurity phase. In the present work, trials based on the dimethyl ether-to-olefin (DTO) reaction using a fixed-bed downflow reactor were performed to assess the effect of the purity of YNU-5 on its catalytic performance. Dealuminated pure YNU-5 exhibited rapid deactivation due to coking at time on stream (TOS) values exceeding 5 min. Surprisingly, this deactivation was greatly suppressed when the material contained a trace amount of ZSM-5 consisting of nano-sized particles. The formation of ZSM-5 nanoparticles evidently improved the performance of the catalytic system during the DTO reaction. The product distributions obtained from this reaction using highly dealuminated and very pure YNU-5 resembled those generated by 12-ring rather than 8-ring zeolite catalysts. The high selectivity for desirable C3 and C4 olefins during the DTO reaction over YNU-5 is beneficial.


Discrepancies of Notch 1 receptor during development of chronic seizures.
The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer's disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.


[Influence of Confucian's doctrine of the mean on formulae of traditional Chinese medicine].
The doctrine of the mean is an important and integral part of the thought of Confucianism, which occupied a dominant position for a long time in Chinese history since the Western Han dynasty and exerted a great influence for the development of cultural thought in later ages, including the principle of conduct and behave, the construction of social structure etc. Here the influence of the doctrine of the mean on formulae of traditional Chinese medicine is discussed in order to illuminate that specific historical and cultural background of China were the root of traditional Chinese medicine, whose theory and clinical practice all were affected by these in varying degrees, offering some clue for clinical prescriptions.


Disposal of blood [1-13C]lactate in humans during rest and exercise.
Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1-13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.


Histo-proteomic profiling of formalin-fixed, paraffin-embedded tissue.
In the functional proteome era, the proteomic profiling of clinicopathologic-annotated tissues is an essential step for mining and evaluating candidate biomarkers for disease. For many diseases, but especially cancer, the development of predictive biomarkers requires performing assays directly on the diseased tissue. The last decade has seen the explosion of both prognostic and predictive biomarkers in the research setting but few of these biomarkers have entered widespread clinical use. Previously, application of routine proteomic methodologies to clinical formalin-fixed and paraffin-embedded tissue specimens has provided unsatisfactory results. In this paper, we will discuss recent advancements in proteomic profiling technology for clinical applications. These approaches focus on the retention of histomorphologic information as an element of the proteomic analysis.


Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing.
The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has been hypothesized to be broadly activated by aversive stimuli. However, this encoding pattern has only been demonstrated for a limited number of stimuli, and the RMTg influence on ventral tegmental (VTA) responses to aversive stimuli is untested. Here, we found that RMTg neurons are broadly excited by aversive stimuli of different sensory modalities and inhibited by reward-related stimuli. These stimuli include visual, auditory, somatosensory and chemical aversive stimuli, as well as "opponent" motivational states induced by removal of sustained rewarding or aversive stimuli. These patterns are consistent with broad encoding of negative valence in a subset of RMTg neurons. We further found that valence-encoding RMTg neurons preferentially project to the DA-rich VTA versus other targets, and excitotoxic RMTg lesions greatly reduce aversive stimulus-induced inhibitions in VTA neurons, particularly putative DA neurons, while also impairing conditioned place aversion to multiple aversive stimuli. Together, our findings indicate a broad RMTg role in encoding aversion and driving VTA responses and behavior.


[Induced differentiation of stem cells into androgen-secreting cells].
Leydig cells are the major source of androgens in males. Stem cells can be induced to differentiate into androgen-secreting Leydig like cells, whose functions are regulated by the hypothalamus and pituitary, so that they precisely secret the necessary hormones to maintain physiological function. Therefore, the establishment of an effective protocol to induce the differentiation of stem cells into androgen-secreting cells is very helpful for the treatment of hypogonadism caused by abnormalities of Leydig cells. This review outlines the recent findings concerning the differentiation of stem cells into androgen-secreting cells.


Dual infection in chronic hepatitis C patients.
Hepatitis C and B virus(HCV, HBV) dual infection may occur and even persist in the same patient. Different results have been found in clinical and laboratory studies of dually infected patients. In our study, we aimed to investigate the effect of previous or present hepatitis B virus infection to clinical course and antiviral therapy in patients with chronic hepatitis C. Hundredthirty consecutive patients with hepatitis C, who were referred to our gastroenterology unit, were studied retrospectively. Patients who were exposed to HBV infection were named as group 1, and patients who had pure hepatitis C infection were named as group 2. Fifty patients in group 1 were compared with 80 patients in group 2. HBs Ag was positive in 12, and HBV antibodies were positive in the other 38 patients of group 1. Age, sex, follow-up duration, transaminase levels, liver synthesis functions, histopathological findings, Child-Pugh stages and presence of complications were not statistically different in groups 1 and 2. HBV-DNA by PCR assay was negative in all 12 HBs Ag positive patients. Hepatocelluler carcinoma(HCC) was found totally in 8 cases, 2 in group 1 and 6 in group 2, while none in HBs Ag positive patients. Antiviral therapy was administired to 39 patients, 15 in group 1 and 24 in group 2. There was no difference in regard to treatment duration and response to treatment between both groups. In our study, we have found previous or present HBV infections were observed frequently in chronic hepatitis C patients, although it's effect to clinical course and antiviral therapy is not significant.


Malignant müllerian mixed tumor (carcinosarcoma) of the fallopian tube: an immunohistochemical study of neoplastic cells.
The patient was a 65-year-old woman who complained of lower abdominal pain. Salpingo-oophorectomy and hysterectomy were performed due to suspicion of ovarian cancer. At surgery a polypoid mass was observed in the fimbria of the left fallopian tube. Histologically, proliferation of undifferentiated neoplastic cells with marked cytological atypia predominated in the tumor. Proliferation of rhabdomyoblastic cells or spindle cells, as well as adenocarcinoma arising from the mucosa of the fallopian tube, was observed. A diagnosis of malignant müllerian mixed tumor (MMMT) was made. CD10 was expressed in adenocarcinoma, undifferentiated, spindle and rhabdomyoblastic cells. Furthermore, rhabdomyoblastic cells were positive for desmin and myoglobin. Undifferentiated and spindle neoplastic cells were focally positive for ASMA and negative for h-caldesmon. Finally, our preliminary report suggests that MMMT of the fallopian tube may contain immature smooth muscle cells or cells with the myofibroblast-like immunohistochemical phenotype in the undifferentiated component.


Factors that influence abusive interactions between aging women and their caregivers.
Research findings suggest that one or more factors-personality and/or drug or financial dependency, cognitive and personality impairments, contextual factors, or severe stress-render elders vulnerable to caregiver maltreatment (i.e., either abuse or neglect), but may also make them more prone to abusing their caregivers. However, it is often the interaction between elders and caregivers that determines whether maltreatment will actually occur. Maltreatment of elders is less likely when caregivers (1) are free of mental impairments and of drug and personality dependency, (2) are trained to cope with the stress of caregiving and of highly provocative and/or abusive elders, (3) and are adequately reimbursed and socially supported.


Genomic instability in Buccal mucosal cells of children living in abnormal conditions from Santos-Sao Vicente Estuary.
The aim of this study was to evaluate genomic instability and cytotoxicity in buccal mucosa cells of children living in abnormal conditions from Santos Sao Vicente estuary. The study area is located between coordinates 23°58'11.8"S and 46°24'26.3"W, in the southwestern zone of the Sao Paulo State, Brazil. A total of 40 children was distributed into two groups: exposed and non-exposed groups. The frequency of micronuclei increased to buccal mucosa cells of children living in Santos Sao Vicente estuary when compared to the non-exposed group (p < 0.05). No remarkable differences on buccal cells were found inpyknosis, karyorrhexis and karyolysi between groups. Taken together, our results suggest that children living in contaminated areas comprise a high group for genomic instability on buccal mucosa cells. Given that the current investigation is a preliminary study, further analysis with a larger sample of children is interesting as a future perspective.


[Development of multi-channels cardiac electrophysiological polygraph with LabVIEW as software platform and its clinical application].
Polygraph has become a necessary instrument in interventional cardiology and fundamental research of medicine up to the present. In this study, a LabView development system (DS) (developed by NI in U.S.) used as software platform, a DAQ data acquisition module and universal computer used as hardware platform, were creatively coupled with our self-made low noise multi-channels preamplifier to develop Multi-channels electrocardiograph. The device possessed the functions such as real time display of physiological process, digit highpass and lowpass, 50Hz filtered and gain adjustment, instant storing, random playback and printing, and process control stimulation. Besides, it was small-sized, economically practical and easy to operate. It could advance the spread of cardiac intervention treatment in hospitals.


Factors Associated with Hospitalization among Emergency Department Patients Referred for Quick Investigation of Iron-Deficiency Anemia.
Although patients with anemia are frequently seen in emergency departments (EDs), studies on patients presenting there with symptomatic chronic anemia--usually iron-deficiency anemia (IDA) caused by occult gastrointestinal bleeding--are lacking. Awareness of predictors of hospitalization could direct the ED triage to the appropriate diagnostic setting. Based on initial observations that some patients with IDA were hospitalized after ED referral and initial evaluation at a quick diagnosis unit (QDU), a new cost-effective alternative to hospitalization for diagnostic workup, this study aimed to determine the patient factors associated with hospitalization after the first QDU visit. An 8-year prospective cohort study of patients with IDA referred from the ED to the QDU of a third-level university hospital was conducted. Patients with a baseline hemoglobin level of <9 g/dL in the ED, proven iron deficiency, and no overt bleeding were included. The primary outcome was hospitalization after the initial QDU assessment. Two hundred eighty-four (7.7%) of 3692 patients were hospitalized. Inter-rater agreement of appropriateness of admissions was 90.6% (κ = 0.82). Overall, 90% of study patients presented to the ED with symptomatic anemia, and 87% were transfused there. On multivariate analysis, age ≥ 65 years, living alone, a post-transfusion hemoglobin level of <9 g/dL, higher age-adjusted overall comorbidity, heart failure, and poor physical health-related quality of life at first QDU visit independently predicted hospitalization. While these predictors do not necessarily reflect the need for hospitalization, they are easily evaluated during the initial ED visit and can guide the triage of similar IDA patients to the suitable setting for timely investigation.


[The presence of morphine as heroin metabolites in placental tissue and fetus: case report].
Females who have developed addiction to heroin also abuse it during pregnancy. Heroin can be detected in the fetal blood-flow already an hour after maternal i.v. injection. Heroin metabolites enter the fetal blood-flow through the placental barrier by passive transport. We present a 27-year-old female in the 5th month of pregnancy that had a miscarriage. Chemo-toxicological analysis (gas chromatography with mass spectrometry--GC/MS), showed the presence of morphine in the fetal liver (31.92 ng/g), placenta (27.94 ng/g) and meconium (136.33 ng/g). The analysis did not show the presence of 6-monoacetylmorphine. In all cases when the autopsy of fetus or newborn is performed, with mother suspected as i.v. heroin abuser, chemo- toxicological placental analysis, placenta and meconium should be also done.


Genotoxicity of polycyclic musk fragrances in the sister-chromatid exchange test.
The synthetic polycyclic musk fragrance compounds Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclo-penta-(g)-2-++ +benzopyrane, Tonalide (7-acetyl-1,1,3,4,4,6-hexamerthyltetraline), Celestolide (4-acetyl-1,1-dimethyl-6-tert, butylindane), Phantolide (6-acetyl-1,1,2,3,3,5-hexamethylindane), Cashmeran (6,7-dihydro-1,1,2,3,3-pentamethyl-4-(5H) indanone) and Traseolide (5-acetyl-1,1,2,6-tetramethyl-3-isopropylindane) are widely used as fragrance ingredients in perfumes, lotions and detergents; as food additives in cigarettes and fish baits. Several studies identified polycyclic musk fragrances in aquatic environment samples, human milk and human adipose tissue as highly lipophil with human lymphocytes.


Visible-light-absorbing C-N cross-coupling for the synthesis of hydrazones involving C(sp2)-H/C(sp3)-H functionalization.
An efficient C-N cross-coupling approach for the synthesis of hydrazones was developed through C(sp2)-H and C(sp3)-H functionalization of indole and methylarene under visible light irradiation using photocatalyst eosin Y, ethanol:water as a green solvent and atmospheric air as an oxidant. With the aid of eosin Y, the C-H bonds of indole and methylarenes were activated followed by coupling with arylhydrazines. The procedure was applied to a wide variety of substrates with good functional group compatibility, offering a creative way to make hydrazones from inexpensive and easily accessible raw materials. The absence of metals, low cost, environmental friendliness, green solvent, non-toxicity, ease of handling, and utilization of renewable energy sources like visible light are some of this method's primary advantages.


Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves.
The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3-week-old) and ruminating (6-month-old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high-pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration-time profile of the central compartment was best described by a two-compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age-related differences in plasma concentration-time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.