Robotic beyond total mesorectal excision surgery for primary and recurrent pelvic malignancy: Feasibility and short-term outcomes.
To explore the feasibility and safety of robotic beyond total mesorectal excision (TME) surgery for primary and recurrent pelvic malignancy. Patients undergoing robotic beyond TME resections for primary or recurrent pelvic malignancy between July 2015 and July 2021 in a public quaternary and a private tertiary centre were included. Demographic and clinical data were recorded and outcomes analysed. Twenty-four patients (50% males) were included, with a median age of 58 (45-70.8) years, and a BMI of 26 (24.3-28.1) kg/m2 . Indication for surgery was rectal adenocarcinoma in nineteen, leiomyosarcoma in two, anal squamous cell carcinoma in one and combined rectal and prostatic adenocarcinoma in two patients. All patients required resection of at least one adjacent pelvic organ including genitourinary structures (n = 23), internal iliac vessels (n = 3) and/or bone (n = 2). Eleven patients had a restorative procedure. Of the 13 nonrestorative cases, nine needed perineal reconstruction with a flap. There was one conversion due to bleeding. The mean operating time was 370 (285-424) min, and the median blood loss was 400 (200-2,000) ml. The median length of stay was 16 (9.3-23.8) days. Fourteen patients (58.3%) had postoperative complications; eight of them (33.3%) were Clavien-Dindo III or more complication. Twenty-three (95.8%) patients had an R0 resection. During a median follow-up of 10 (7-23.5) months, five patients (20.8%) had systemic recurrences. No local recurrences were identified during the study period. Implementation of robotic beyond TME surgery for primary and recurrent pelvic malignancy is feasible within a highly specialised setting.


Quinolinic acid neurotoxicity: protection by intracerebral phenylisopropyladenosine (PIA) and potentiation by hypotension.
In the present study we have used the purine agonist R-phenylisopropyladenosine (PIA) which suppresses excitatory amino acid release to assess its effect on quinolinate toxicity. Quinolinic acid was injected into the rat hippocampus alone or with PIA and the animals allowed to recover. After 4 days the brain was removed for histological examination. The extent of neuronal degeneration was assessed blind by an independent observer on a scale of 0 (no damage) to 10 (complete degeneration). Co-administration of PIA protected against the toxicity, and this protective action of PIA was blocked by a xanthine adenosine receptor antagonist. However, systemic injections of PIA or the non-purine ganglion blocking drug trimetaphan, both of which caused significant depression of blood pressure, potentiated quinolinate toxicity. The results may indicate an interaction between endogenous excitotoxins and episodes of hypotension which may be critical in determining cell death in the CNS.


Clinical chemical indexes and severity of coronary atherosclerosis.
The present study measured triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C), LDL and LDL/HDL-C, TC/HDL-C and HDL-C/TC. 100 ratios in 261 men and women undergoing coronary arteriography. The results show that TG, TC, HDL-C and LDL levels are not related to the severity of coronary artery disease (CAD). The LDL/HDL-C, TC/HDL-C and HDL/TC.100 ratios are statistically related to the severity of CAD. The LDL/HDL-C ratio appeared to be the most sensitive index for reflecting CAD of mild severity with a predictive value of 83.3% at 76.6% specificity and at 77.7% sensitivity (cut-off: 3.20). Average values of LDL and HDL-C alone are not reliable indices of mild severity CAD.


Brevicomin: principal sex attractant in the frass of the female western pine beetle.
The principal component of the sex attractant produced by the female western pine beetle (Dendrotonus brevicomis) is exo-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane; the trivial name brevicomin is suggested.


Bronchoalveolar lavage and the immunology of lung cancer.
Current concepts on the application of bronchoalveolar lavage (BAL) for the investigation of tumor markers and antitumor activities exerted by effector cells in the lung parenchyma are summarized. The evaluation of BAL cellular and humoral constituents might provide new insights into the pathogenic mechanisms taking place in lung cancer.


Genotoxicity of nano- and micron-sized manganese oxide in rats after acute oral treatment.
The use of nanotechnology has led to rapid growth in various areas. Manganese oxide (MnO2) nanomaterials (NMs) are typically used for biomedical applications. However, characterizing the potential human health effects of MnO2 NMs is required before fully exploiting these materials. The aim of this study was to investigate the acute oral toxicity of MnO2 NMs and MnO2-bulk particles in female albino Wistar rats. The genotoxic effects were examined using comet, micronucleus and chromosomal aberration assays. Nanosized MnO2 (45nm) significantly (p<0.01) increased DNA damage in peripheral blood leukocytes and micronuclei and enhanced chromosomal aberrations in the bone marrow cells at 1000mg/kg bw. These findings showed that the neurotoxicity of MnO2-45nm in the brain and red blood cells, as determined through acetylcholinesterase activity, was significantly (p<0.01) inhibited at 1000 and 500mg/kg bw doses. MnO2-45nm disrupted the physicochemical state and neurological system of the animals through alterations in ATPases via the total Na(+)-K(+), Mg(2+) and Ca(2+) levels in the brain P2 fraction. In addition, 500 and 1000mg/kg bw doses of MnO2-45nm caused significant changes in AST, ALT and LDH levels in the liver, kidney and serum of treated rats. Significant tissue distribution was found in all tissues in a dose- and time-dependent manner. MnO2-45nm exhibited much higher absorptivity and tissue distribution compared with MnO2-bulk. A large fraction of MnO2-45nm was cleared in the urine and feces. The histopathological analysis revealed that MnO2-45nm caused alterations in the liver, spleen and brain. These findings will provide fundamental information regarding the potential toxicities and biodistribution of nano and bulk MnO2 generated through acute oral treatment.


Acid phosphatase of the rat epididymis. III. Histochemical and biochemical responses in experimental conditions.
The specific activities of three acid phosphatases were followed in the epididymis of growing rats. All activities were constantly rising but revealed two steeper parts probably corresponding to the increase of androgen secretion and the arrival of spermatozoa in the epididymis. Simultaneously an increase in the histochemical staining was obtained in all epididymal segments. Both biochemical and histochemical studies showed that castration reduced the activity of all acid phosphatases and this could be restored with testosterone-estradiol treatment. Estradiol had no effect on the activities in the castrated animal, but in the normal animal it caused an elevation of Enzyme I activity. In the histochemical study estradiol seemed to restore the acid phosphatase activity. Enzyme I reacted slower than the others to both castration and hormone treatment. Increased elimination caused by ligation of the epididymis caused a reduction in the activity of all enzymes within four days. It was greatest in the area of the corpus. This study, however, rendered no further elucidation for the assumption that acid phosphatases participate in the elimination of excessive and defective spermatozoa.


Role of hot singlet excited states in charge generation at the black dye/TiO2 interface.
Photoinduced electron transfer at low-band-gap ruthenium-based dye/TiO2 has been investigated by means of ultrafast transient absorption and DFT/TDDFT calculations. We demonstrate that although the charge generation mechanism is triplet mediated upon band gap excitation, as already proven in high band gap dyes such as the well-known N3 and N719, when excess energy is provided which allows to reach high energy singlet states still in the visible spectral range, ultrafast electron transfer takes place. No intersystem crossing process is observed and charge generation happens only from the singlet excited state.


Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU).
This study was initiated to explore the effect of recombinant rat Crry linked to the Fc portion of rat IgG2a (Crry-Ig) on the induction of experimental autoimmune anterior uveitis (EAAU) and on established disease. EAAU was induced in Lewis rats by immunization with bovine melanin-associated antigen (MAA). MAA sensitized animals received Crry-Ig, rat IgG2a (isotype control) or PBS separately before the onset of EAAU or after the onset of clinical disease. Administration of Crry-Ig suppressed the induction of EAAU while all animals injected with IgG2a or PBS developed the normal course of EAAU. Treatment with Crry-Ig resulted in the suppression of ocular complement activation as well as the functional activity of complement in the peripheral blood. At the peak of EAAU, levels of IFN-γ, IP-10, ICAM-1 and LECAM-1 were significantly reduced within the eyes of Crry-Ig treated Lewis rats. Importantly, administration of Crry-Ig even after the onset of EAAU resulted in a sharp decline in the disease activity and early resolution of EAAU. Collectively, the evidence presented here demonstrate that inhibition of complement by Crry-Ig results in low levels of inflammatory molecules-C3 activation products, MAC, cytokines, chemokines and adhesion molecules in the eye. Down-regulation of these molecules affects the infiltration and recruitment of inflammatory cells to the eye resulting in the inhibition of EAAU.


Oral squamous cell carcinoma cells modulate osteoclast function by RANKL-dependent and -independent mechanisms.
Oral squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and bone invasion is a common clinical problem. Recent studies have revealed that bone resorption by osteoclasts is an important step in the progress of bone invasion by oral SCCs. We previously reported that oral SCC cells induce osteoclastogenesis by suppressing osteoprotegerin (OPG) in host cells. In the present study, we examined the effects of oral SCCs on osteoclast function. Both BHY cells, a human oral SCC cell line, and its conditioned medium (BHY-CM) stimulated osteoclast survival by suppressing Bim, a pro-apoptotic protein, depending on extracellular signal-regulated kinase (ERK) and multinucleation. Adding BHY cells but not BHY-CM induced pit-forming activity by osteoclasts and adding OPG abrogated the activity. Thus, oral SCC cells regulate not only osteoclastogenesis but also its function.


Retracted: An Efficient Stacked Deep Transfer Learning Model for Automated Diagnosis of Lyme Disease.
[This retracts the article DOI: 10.1155/2022/2933015.].


MALDI-TOF MS identification of Cimex lectularius and Cimex hemipterus bedbugs.
Bedbugs (Cimex lectularius and C. hemipterus) have reemerged as a major public health problem around the world. Their bites cause various skin lesions as well as discomfort and anxiety. Their role as potential vectors of various infectious agents is discussed. Accordingly, all suspected cases of bedbug infestations need to be documented thoroughly, with an unequivocal identification of the arthropods involved, if any are present. Although morphological identification is easily and quickly performed by entomologists or professionals, it can be challenging otherwise. Also, distinguishing Cimex lectularius and C. hemipterus requires entomological expertise. MALDI-TOF mass spectrometry has been recently presented as an additional tool for arthropod identification. In this study, we assess the use of MALDI-TOF MS for the identification of laboratory and wild strains of C. lectularius and C. hemipterus. Several body parts of laboratory reared C. lectularius specimens were used to develop a MALDI-TOF MS protocol for bedbug identification, which was later validated using five other laboratory and wild populations of C. hemipterus and C. lectularius. A total of 167C. lectularius and C. hemipterus bedbug specimens (98 laboratory specimens and 69 wild specimens) were submitted to MALDI-TOF MS analysis. 143/167 (85.63%) provided high quality MS spectra. The in-lab database was then upgraded with a total of 20 reference spectra from all bedbug populations and the rest of the MS spectra (123 bedbugs) were blind tested. All specimens were properly identified to the species level using MALDI-TOF MS and 86,25% (69/80) were aptly identified according to their origin with LSVs ranging from 1.867 to 2.861. MALDI-TOF MS appears as a reliable additional tool for the identification of these two anthropophilic species.


Immune measures in alcohol-dependent persons with minor health abnormalities.
Altered immunity is commonly associated with alcoholism. However, few studies have contrasted alcoholism per se with effects of the medical sequelae or comorbidities of alcoholism on the immune system. We previously found few differences in lymphocyte subsets, mitogen response, granulocytic phagocytosis, or natural killer cell activity when we compared healthy urban alcohol-dependent individuals with community control subjects. To begin to explore the role of medical factors, 11 alcohol-dependent persons derived from the same clinical population but showing mild medical abnormalities (AMMAs), primarily abnormal liver function test results, were compared with the previously described 44 alcohol-dependent persons without medical dysfunctions and 34 nonabusing community persons. The AMMAs had lower numbers of CD45RA + inducer-suppressor/naive cells (P <.02) and HLA-DR+-activated T cells (P <.04) compared with findings for nonabusers and higher percentages of circulating CD56 + natural killer cells (P <.03). Mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen; natural killer cell activity; and granulocyte functions did not differ across groups. The AMMAs reported higher alcohol consumption than that reported by the other groups. The findings seem to indicate that mild medical conditions, or conditions linked to abnormal liver function test results, are associated with some of the immune alterations reported in alcohol-dependent persons. Immune changes, even among chronically alcohol-dependent persons, may occur along a continuum associated with total alcohol exposure and intercurrent physiologic abnormalities. Clinical studies may need to control for such mild abnormalities when investigating alcohol-immune relationships, and clinical interventions may be especially important for alcohol-dependent individuals who show early signs of compromised health.


Corrigendum: A novel ferroptosis-related LncRNA pair prognostic signature predicts immune landscapes and treatment responses for gastric cancer patients.
[This corrects the article DOI: 10.3389/fgene.2022.899419.].


Consumer Wearable Sleep Trackers: Are They Ready for Clinical Use?
As the importance of good sleep continues to gain public recognition, the market for sleep-monitoring devices continues to grow. Modern technology has shifted from simple sleep tracking to a more granular sleep health assessment. We examine the available functionalities of consumer wearable sleep trackers (CWSTs) and how they perform in healthy individuals and disease states. Additionally, the continuum of sleep technology from consumer-grade to medical-grade is detailed. As this trend invariably grows, we urge professional societies to develop guidelines encompassing the practical clinical use of CWSTs and how best to incorporate them into patient care plans.


[Association between polymorphism in DVWA and IL-1beta and Kashin-Beck disease].
To investigate the association between IL-1beta and DVWA gene and Kashin-Beck disease (KBD). Peripheral genomic DNA were extracted from 105 patients with KBD and 98 healthy controls. PCR-RFLP were performed to detect SNP loci of IL-1beta gene and DVWA gene. The patients with KBD had significantly higher frequency of rs16944 (IL-1beta) locus (chi2 = 24.28, P < 0.001) and single allele frequency of rs16944 (chi2 = 5.683, P = 0.0171) than the healthy controls. There were no significant differences in genotype frequencies,single allele frequencies and haplotypes in rs4685241 and rs1143627 between the patients with KBD and the healthy controls. rs16944 (IL-1beta) is associated with KBD.


Robotic assisted laparoscopic partial nephrectomy using contrast-enhanced ultrasound scan to map renal blood flow.
The paper describes novel real-time 'in situ mapping' and 'sequential occlusion angiography' to facilitate selective ischaemia robotic partial nephrectomy (RPN) using intraoperative contrast enhanced ultrasound scan (CEUS). Data were collected and assessed for 60 patients (61 tumours) between 2009 and 2013. 31 (50.8%) tumours underwent 'Global Ischaemia', 27 (44.3%) underwent 'Selective Ischaemia' and 3 (4.9%) were removed 'Off Clamp Zero Ischaemia'. Demographics, operative variables, complications, renal pathology and outcomes were assessed. Median PADUA score was 9 (range 7-10). The mean warm ischaemia time in selective ischaemia was less and statistically significant than in global ischaemia (17.1 and 21.4, respectively). Mean operative time was 163 min. Postoperative complications (n = 10) included three (5%) Clavien grade 3 or above. Malignancy was demonstrated in 47 (77%) with negative margin in 43 (91.5%) and positive margin in four (8.5%). Long-term decrease in eGFR post selective ischaemia robotic partial nephrectomy was less compared with global ischaemia (four and eight, respectively) but not statistically significant. This technique is safe, feasible and cost-effective with comparable perioperative outcomes. The technical aspects elucidate the role of intraoperative CEUS to facilitate and ascertain selective ischaemia. Further work is required to demonstrate long-term oncological outcomes. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd.


FITC-Dextrans as tracers for macromolecular movements in the nervous system. A freeze-drying method for dextrans of various molecular sizes injected into normal animals.
A freeze-drying method has been developed by which fluorescein thiocarbamoyl dextrans (FITC-dextrans) can be localized in thin sections from nervous tissue and muscles. Labelled dextrans with molecular weights of 3,000, 20,000, 70,000 and 150,000 were injected intravenously (i.v.) into golden hamsters and samples from brain, trigeminal ganglia and sciatic nerves were examined 30 min or 4 h later. For comparison experiments were also carried out in mice and some other tracers were tested as well. The dextrans did not pass out of blood vessels in cerebral cortex and white matter. The blood vessels in the trigeminus ganglion were permeable to all of the tested compounds, i.e. even the FITC-dextran with mol.wt. 150,000. Little, if any, i.v. injected dextran could be detected in the endoneurium of sciatic nerve fascicles. Even very high concentrations of dextrans (mol.wt. 3,000 and 150,000) injected around the sciatic nerves did not penetrate the perineurium of the sciatic nerve. As compared with other tracers dextrans have the advantage that they can be obtained in a wide range of molecular sizes. With the proposed technique presented at the end of this article they can be used for studies on vascular permeability in deep tissue like brain, ganglia and peripheral nerve. The use of these tracers will probably be particularly advantageous in investigations concerning the etiology of edematous conditions.


Cloning and characterization of a soluble acid invertase-encoding gene from muskmelon.
Soluble acid invertase (S-AIV; EC 188.8.131.52) is thought to play a critical role in sucrose hydrolysis in muskmelon (Cucumis melo L.) fruit. A full-length cDNA clone encoding S-AIV was isolated from muskmelon by RT-PCR and RACE. The clone, designated as CmS-AIV1, contains 2178 nucleotides with an open reading frame of 1908 nucleotides. The deduced 636 amino acid sequence showed high identities with other plant soluble acid invertases. Northern blot analysis indicated that CmS-AIV1 was expressed in flowers and fruit, but was not detected in roots, stems or leaves. Moreover, the mRNA accumulation of CmS-AIV1 showed its maximum level at 10 days after pollination (DAP) and decreased gradually during fruit development until its minimum level at mature fruit. Interestingly, the sucrose content was very low in fruit before 20 DAP but increased dramatically between 20 and 30 DAP during fruit development. In contrast to sucrose content, the activities of S-AIV was very high in fruit before 20 DAP and decreased apparently between 20 and 30 DAP, suggesting that sucrose metabolism may be linked to the CmS-AIV1 transcript level in muskmelon fruit.


The Protective Role of Celastrol in Renal Ischemia-Reperfusion Injury by Activating Nrf2/HO-1, PI3K/AKT Signaling Pathways, Modulating NF-κb Signaling Pathways, and Inhibiting ERK Phosphorylation.
Celastrol, a natural triterpenoid derived from Tripterygium wilfordii, possesses numerous biological effects. We investigated celastrol's antioxidant potential through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) and its effect on phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling, nuclear factor-kappa B (NF-κB) pathways, and extracellular signal-regulated kinase (ERK) activation in kidney ischemia-reperfusion injury (IRI) rat model. Rats were given celastrol 2 mg/kg orally for 1 week before subjection to renal ischemia-reperfusion surgery. Kidney functions, renal MDA, and reduced glutathione were determined; also, renal levels of ERK1/2, HO-1, PI3K, IL-6, TNF-α, IκBα, NF-κB/p65, and cleaved caspase-3 were measured. In addition, gene expression of kidney injury molecule-1 (KIM-1), Nrf-2, and AKT were determined. Celastrol pretreatment attenuated oxidative stress and increased Nrf2 gene expression and HO-1 level. Also, it activated the PI3K/AKT signaling pathway and decreased the p-ERK:t- ERK ratio and NFκBp65 level, with a remarkable decrease in inflammatory cytokines and cleaved caspase-3 levels compared with those in renal IRI rats. Conclusively, celastrol showed a reno-protective potential against renal IRI by suppressing oxidative stress through enhancing the Nrf2/HO-1 pathway, augmenting cell survival PI3K/AKT signaling pathways, and reducing inflammation by inhibiting NF-κB activation.


A rare case of primary angiosarcoma of the anterior mediastinum.
A 32-year-old male patient was initially diagnosed with fibrosing mediastinitis. The patient subsequently developed severe dyspnea and was further diagnosed with constrictive pericarditis due to the extent of fibrosing mediastinitis around the heart. Therefore, the patient underwent surgical resection of the fibrotic tissue in the anterior mediastinum including the pericardium and the pleura. Postoperative histological and immunohistochemical analyses revealed angiosarcoma. Seven years after the diagnosis, he is still alive. Herein, we report a case of atypical primary angiosarcoma of the anterior mediastinum causing constrictive pericarditis and restrictive pulmonary dysfunction.


[Evaluation of normal submandibular gland function by sialo-scintigraphy].
To study the normal glandular function of the submandibular gland as a background for evaluation of changes in submandibular gland diseases. The backgrounds of both submandibular area and temporal area were analyzed comparatively with Emission Computerized Tomography in eleven pairs of normal submandibular gland. About 2.18 times of the temporal background equals to submandibular area background; the Concentrate Index of normal submandibular gland was 1.42 +/- 0.89; the Secretory Index was (109.4 +/- 39.8)%, the Secretory Index Ratio and the Concentrate Index Ratio were (77.2 +/- 17.2)% and 71.0 +/- 15.2% respectively; and the Function Index was (89.9 +/- 7.4)%. The use of submandibular area background and functional index to represent submandibular gland function is more accurate and more sensitive. Normal functional index can provide the basis for researching submandibular gland disease.


Fruit form Influences Postprandial Glycemic Response in Elderly and Young Adults.
This study compared the effects of consuming different forms (bite size, puree) and two fruit types (guava, papaya) on glycemic response (GR) in elderly and young adults. This study was conducted using a randomized, crossover design. Nineteen healthy participants (9 elderly, 10 young adults) were recruited from the general public in Singapore. Participants consumed glucose (reference food) on three occasions and test fruits (guava bites, guava puree, papaya bites, and papaya puree) on one occasion each. Blood glucose was analyzed prior to consuming the test food, at 15, 30, 45, 60, 90 and 120 minutes after food consumption. The incremental area under the blood glucose response curve (iAUC) over 120 minutes for all the treatments was significantly lower than glucose (all P < 0.001). All fruit forms and types studied were low glycemic index (GI) (guava bites: 29; papaya bites: 38; papaya puree: 42; guava puree: 47), albeit a significant difference in GI between the treatments was found (P = 0.003). Elderly exhibited significantly greater GR than young participants (P = 0.019). Although fruit form influences GR in the elderly and young adults, all fruit types and forms studied were found to be low GI. This study indicates that fruits are a valuable source of nutrient irrespective of the form of delivery in elderly and young adults. This study was registered at www.anzctr.org.au as ACTRN12614000655640.


Pseudo-hyperscanning shows common neural activity during face-to-face communication of affect to be associated with shared affective feelings but not with mere emotion recognition.
Current theories in cognitive neuroscience assume that internal simulation, i.e., the reproduction of brain activity underlying another person's inner state and behaviour in the perceiver's brain, plays an important role in understanding others. Here we test the prediction that common neural activity during facial communication of affect leads to interpersonal understanding. Six female senders and 30 male observers (six of which were the senders romantic partners and 24 unknown others) underwent pseudo-hyperscanning fMRI (functional magnetic resonance imaging). Senders were asked to submerge themselves into emotional situations and to facially express their emotional feelings as they arose to the observer. Observers were uninformed about the sender's task and were asked to watch and feel with the sender. Using between-brain spatial correlation analysis we found that mere emotion recognition was not closely related to the degree to which an observer reproduced the sender's spatial pattern of neural activity in his own brain. However, in runs in which the observer had correctly identified the communicated emotion, between-brain similarity of spatial patterns of neural activity predicted the degree to which the observer experienced a similar emotional feeling as the sender. This effect remained significant when differences between romantic partners and unknown others and sender effects were removed. These findings are in line with previous studies that suggest that facial emotion recognition, at least at a coarse level, might be supported by neural processes that do not rely on internal simulation. Shared affective experiences, on the other hand, might arise from common neural activity between the sender's and the observer's brain, leading to a "shared space of affect" which might be critical for the flow of more subtle affective information between brains.


Enhanced Production of Astaxanthin without Decrease of DHA Content in Aurantiochytrium limacinum by Overexpressing Multifunctional Carotenoid Synthase Gene.
Aurantiochytrium limacinum produces both docosahexaenoic acid (DHA) and astaxanthin, respectively. Organisms that produce these industrially important materials more efficiently than microalgae are currently needed. In this study, we overexpressed a putative homolog of CarS, which is involved in synthesizing the astaxanthin precursor, β-carotene, in A. limacinum to increase carotenoid synthesis with the goal of obtaining strains that produce large amounts of both DHA and carotenoids. AlCarS transformants #1 and #18 produced significantly increased amounts of astaxanthin as assessed according to culture (up to 5.8-fold) and optical density (up to 9.3-fold). The improved astaxanthin production of these strains did not affect their DHA productivity. Additionally, their CarS expression levels were higher than those of the wild-type strain, suggesting that CarS overexpression enhanced β-carotene production, which in turn improved astaxanthin productivity. Although cell yields were slightly decreased, these features will be valuable in health food, medical care, and animal feed fields.


Retracted: Ecological Adaptability and Application of Traditional Historical Buildings under the Background of Environmental Protection.
[This retracts the article DOI: 10.1155/2022/5107325.].


[Organization of care for tuberculosis children who had contact with maternal hospital worker suffering from bacillar tuberculosis].
While contacting a patient with bacillar tuberculosis, neonates and their mother are at risk for the disease, which makes it necessary to make up a programme that involves emergency antituberculosis measures. Among them primary specific drug therapy in all children in contacts, which may prevent tuberculosis in them, is highly effective.


Endoscopic ultrasound-guided fine-needle aspiration cytology of peripheral nerve-sheath tumors.
Endoscopic ultrasound (EUS) has allowed for the fine-needle aspiration and diagnosis of many different gastrointestinal neoplasms, including mesenchymal tumors. Although most mesenchymal tumors of the gastrointestinal tract are gastrointestinal stromal tumors (GISTs), other mesenchymal tumors, including neural tumors, do occur. Proper diagnosis and differentiation of these tumors from GISTs are important because of their different prognoses and treatment regimens. We encountered three peripheral nerve-sheath tumors of the gastrointestinal tract aspirated by EUS (two schwannomas and a granular-cell tumor). We report on the endoscopic ultrasound, cytologic, histologic, and immunohistochemical findings of these cases.


Non-infectious factors associated with stillbirth in pigs: a review.
The main objective of this review is to provide current information regarding non-infectious risk factors associated with stillborn piglets. These factors can be roughly categorized as genetic, maternal, piglet and environmental factors, but also interactions exist between several factors. An understanding of this multifactorial problem should help practitioners and farmers implementing a more effective farrowing management to obtain a high reproductive efficiency. From the papers studied in this review, it can be concluded that litter size, parity, sow's body condition and farrowing supervision/birth assistance seems to be the most relevant risk factors associated with stillborn piglets.


Primary biliary cirrhosis: new thoughts on pathophysiology and treatment.
Primary biliary cirrhosis (PBC) is an idiopathic inflammatory hepatic disorder characterized by granulomatous destruction of small bile ducts and formation of antimitochondrial antibodies. Having found that most patients with PBC have antibody reactivity to retroviral proteins, we recently cloned a retroviral sequence directly from biliary epithelium extracted from PBC livers. Further evidence for an infectious etiology of PBC has been derived from an in vitro model using normal biliary epithelial cells in culture with lymph node extracts from patients with chronic liver disease. In this model, biliary epithelial cells cocultivated with PBC lymph nodes developed a specific phenotype of PBC with immunohistochemical evidence of antimitochondrial antibody reactivity. This model has been used to show that patients with PBC harbor a transmissible agent that may be related to the cloned retrovirus. Pilot studies using antiretroviral treatment for patients with PBC have also supported the involvement of a retrovirus in the disease process. Because the antiretroviral therapy was tolerated without undue adverse events, a multicenter controlled trial is being established to determine whether patients with PBC derive significant benefit from this new line of investigation and management.


Peripheral group II and III metabotropic glutamate receptors in the knee joint attenuate carrageenan-induced nociceptive behavior in rats.
This study sought to evaluate whether peripheral group II and III metabotropic glutamate receptors (mGluRs) in the knee joint have inhibitory effects on carrageenan-induced nociceptive behavior. To this end, changes in weight load and hind paw withdrawal threshold were measured in rats following the administration of specific peripheral group II and III mGluR agonists 30min before (induction phase) and 4h after (maintenance phase) the injection of carrageenan (1%, 50μl). During the induction phase of arthritic pain, a significant recovery of reduced weight load occurred after the administration of 500μM APDC ((2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate; group II agonist) and 100 and 500μM L-AP4 (l-2-amino-4-phosphonobutylate; group III agonist). Similarly, 100 and 500μM APDC and 500μM L-AP4 significantly reduced mechanical hyperalgesia during the induction phase. In the maintenance phase, APDC at all doses (10, 100 and 500μM) and 100 and 500μM L-AP4 significantly counteracted the reduction in weight load, and APDC and L-AP4 at all doses (10, 100 and 500μM) inhibited mechanical hyperalgesia. The current study suggests that peripheral group II and III mGluRs in the knee joint negatively modulates nociceptive behavior during both the induction and maintenance phases of carrageenan-induced arthritic pain.


Dispersion of overdamped diffusing particles in channel flows coupled to transverse acoustophoretic potentials: transport regimes and scaling anomalies.
We address the dispersion properties of overdamped Brownian particles migrating in a two-dimensional acoustophoretic microchannel, where a pressure-driven axial Stokes flow coexists with a transverse acoustophoretic potential. Depending on the number and symmetries of the stable nodal points of the acoustophoretic force with respect to the axial velocity profile, different convection-enhanced dispersion regimes can be observed. Among these regimes, an anomalous scaling, for which the axial dispersion increases exponentially with the particle Peclét number, is observed whenever two or more stable acoustophoretic nodes are associated with different axial velocities. A theoretical explanation of this regime is derived, based on exact moment homogenization. Attention is also focused on transient dispersion, which can exhibit superballistic behavior 〈(x-〈x〉)^{2}〉∼t^{3},x being the axial coordinate.


Predictive criteria for failed sphincterotomy in spinal cord injury patients.
Nine patients with chronic high spinal cord injury who failed sphincterotomy secondary to detrusor hypocontractility underwent neurourological evaluation. Testing revealed an abnormality involving the sensory limb of the somatic sacral reflex arc (abnormal R wave) or at the level of the spinal interneuron pool (abnormal or absent S wave). This study strongly suggests that the sensory input from the bladder to the spinal cord, together with alteration in the sensory motor integration that occurs at the level of the interneuron pool, is important in influencing the characteristics of the detrusor contraction following high spinal cord injury. Predictive criteria for failed sphincterotomy are a slow increase to maximum intravesical pressure before voiding and abnormal lumbosacral sensory evoked potentials.


Physiological and biochemical characteristic of Miscanthus × giganteus grown in heavy metal - oil sludge co-contaminated soil.
The effect of oil sludge and zinc, present in soil both separately and as a mixture on the physiological and biochemical parameters of Miscanthus × giganteus plant was examined in a pot experiment. The opposite effect of pollutants on the accumulation of plant biomass was established: in comparison with uncontaminated control the oil sludge increased, and Zn reduced the root and shoot biomass. Oil sludge had an inhibitory effect on the plant photosynthetic apparatus, which intensified in the presence of Zn. The specific antioxidant response of M. × giganteus to the presence of both pollutants was a marked increase in the activity of superoxide dismutase (mostly owing to oil sludge) and glutathione-S-transferase (mostly owing to zinc) in the shoots. The participation of glutathione-S-transferase in the detoxification of both the organic and the inorganic pollutants was assumed. Zn inhibited the activity of laccase-like oxidase, whereas oil sludge promoted laccase and ascorbate oxidase activities. This finding suggests that these enzymes play a part in the oxidative detoxification of the organic pollutаnt. With both pollutants used jointly, Zn accumulation in the roots increased 6-fold, leading to increase in the efficiency of soil clean-up from the metal. In turn, Zn did not significantly affect the soil clean-up from oil sludge. This study shows for the first time the effect of co-contamination of soil with oil sludge and Zn on the physiological and biochemical characteristics of the bioenergetic plant M. × giganteus. The data obtained are important for understanding the mechanisms of phytoremediation with this plant.


Diagnosis of annular pancreas with endoscopic retrograde cholangiopancreatography.
Two patients with annular pancreas are described. The diagnosis was established unequivocally with endoscopic retrograde cholangiopancreatography before operation. In both patients there was pancreatitis of the annular pancreas. The first patient also had congenital absence of the ventral pancreas and pancreatic insufficiency. The second patient subsequently developed gastric outlet obstruction. The literature is reviewed.


Gingival metastasis from primary hepatocellular carcinoma. Report of a case.
A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver.


Purification of phosphoenolpyruvate carboxykinase from Saccharomyces cerevisiae and its use for bicarbonate assay.
Electrophoretically homogeneous phosphoenolpyruvate carboxykinase (EC 188.8.131.52) from Saccharomyces cerevisiae was obtained in high yields by means of a two-step purification procedure consisting of ion-exchange chromatography and affinity chromatography on adenosine 5'-monophosphate-Sepharose 4B. In the latter step the binding of the enzyme to the resin specifically required the presence of Mn2+. The enzyme was eluted when Mn2+ was removed by addition of ethylenediaminetetraacetate to the elution buffer. Homogeneity, molecular weight, and subunit composition of phosphoenolpyruvate carboxykinase were checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. A factor which caused an underestimation of the enzyme activity in crude extracts was identified as adenylate kinase. Finally, a method is proposed for the enzymatic assay of bicarbonate using a purified phosphoenolpyruvate carboxykinase preparation.


Trauma score versus revised trauma score in TRISS to predict outcome in children with blunt trauma.
We analyzed the accuracy of TRISS and a revised TRISS to predict survival outcome in a group of 1,562 consecutive children less than 15 years old admitted with blunt trauma to a pediatric trauma center. TRISS is an index that computes a probability of survival for each patient based on Trauma Score, Injury Severity Score, and age. R-TRISS uses the Revised Trauma Score instead of the Trauma Score. We used a statistical method based on TRISS and R-TRISS to compare patient outcomes from the pediatric study group with those of an adult baseline control group from the Major Trauma Outcome Study. Both TRISS and R-TRISS have the capability to accurately quantify survival outcome for children with blunt trauma; there was no statistical difference between the two methods to do so.


Toward a psychology of deafness?
A large scale study comparing Yugoslavian and American adolescents with normal hearing and with early profound deafness suggests that a relative tendency to impulsivity is a notable characteristic of the deaf group. Despite the conclusiveness of the study overall, there was little intercorrelation among individual subjects on the several test measures employed. A stereotype should be avoided therefore, and the tests viewed as perhaps tapping different personality aspects or avenues of development for what clinically becomes a final common pathway. Comparable and comparative studies of deaf children of deaf parents and of children whose hearing parents have learned manual language early may define how much the tendency is based on qualities of parental discomfort with a deaf child, on the unavailability of language, or on the absence of sound alone.


The effect of carboxylesterase inhibition on interspecies differences in soman toxicity.
Subcutaneous administration of 2 mg/kg cresylbenzodioxaphosphorin oxide (CBDP) produced complete inhibition of carboxylesterase activity in plasma and lung of mice, rats, guinea pigs and rabbits, without inhibition of acetylcholinesterase activity in either brain or diaphragm. This CBDP treatment also reduced the subcutaneous soman LD50 in these species by 48-90% in comparison to the soman LD50 in control animals. The interspecies differences in the soman LD50 values that were seen in control animals were absent in CBDP-treated animals. The soman LD50 values in control animals were 125 micrograms/kg (mouse), 116 micrograms/kg (rat), 32.3 micrograms/kg (guinea pig) and 22.8 micrograms/kg (rabbit), whereas the soman LD50 values in CBDP-treated animals from these species were clustered in a narrow dose range (11.8-15.6 micrograms/kg) and were not significantly different. This suggests that the amount of CBDP-sensitive carboxylesterase available for detoxification of soman in each species may be an important determinant of interspecies differences in soman toxicity.


Effects of intrabronchial foreign body retention.
Unrecognized bronchial foreign bodies (Fbs) cause irreversible changes in the airways. However, the exact course of these changes is not well-known. We developed an animal model of bronchial obstruction to radiologically and histopathologically assess the development of postobstructive pulmonary changes. A piece of peanut was placed in the airways of 21 rabbits through a 2.5-mm rigid bronchoscope. Animals were divided into three groups (groups I-III) that were sacrificed on day 3,10, and 30 after Fb placement, respectively. Prior to sacrifice, since there were no differences between the groups prior to Fb placement, computerized tomography (CT) of the lung was taken, and the lungs were harvested for histologic analysis under light microscope. In group I, leukocyte infiltration around the bronchial wall (P = 0.0003) and edema (P = 0.0384) around the alveolar septa were the predominant histological findings. The CT scan was normal. In group II and group III, increased amounts of mononuclear cells and macrophage infiltration around the bronchial wall were observed (P = 0.0008, P = 0.0409, respectively). There were no differences in presence of granuloma formation, emphysema, atelectasis, or thickness of alveolar septa among the three groups. The CT scan of group II showed consolidations plus minimal bronchial dilatation in the involved lung of the rabbits (P not significant). Bronchial cartilage destruction was seen in 4 out of 7 rabbits in group III (P = 0.0071). We conclude that 30-day retention of intrabronchial peanut caused bronchial cartilage destruction and fibrosis that were attributed as bronchiectatic changes in the airways of the lung parenchyma. Therefore, any case with suspected foreign body aspiration should be treated immediately to prevent possible irreversible changes of the lungs.


Mapping of pgi and gpd genes involved in C-1 assimilation in the obligate methylotroph Methylobacillus flagellatum.
Homologous matings with plasmids R68.45 and pULB113, and also with Hfr type donor were employed for mapping pgi and gpd genes involved in C-1 metabolism in the obligate methylotroph Methylobacillus flagellatum. A preliminary map of the late chromosomal region was constructed on the basis of these experimental results. The C-1 markers were linked to methionine and leucine auxotrophy and nalidixic acid resistance markers. The phenomenon of retrotransfer, or shuttle transfer of chromosomal markers by Inc P1 plasmids, revealed earlier, was demonstrated for M. flagellatum.


Peripapillary atrophy in unilateral capsular glaucoma.
Pairwise comparisons of peripapillary crescents and haloes were performed for 56 eyes of 28 patients with early or moderate unilateral capsular glaucoma and no signs of exfoliation in the contralateral eye. The eyes differed highly significantly in rim area, rim/disc area ratio, cup area, and cup volume. They did not differ in disc areas, scleral ring areas, or size of peripapillary crescents. In the nonglaucomatous and glaucomatous eyes a significant correlation existed between the intraocular pressure (IOP) and the area of peripapillary atrophy. The area of peripapillary atrophy was significantly correlated with the damage to the glaucomatous optic nerve head. We concluded that the area of peripapillary atrophy is largely an inborn feature, and that nerve fiber loss can occur without differences in the peripapillary tissues. Nevertheless, an IOP-induced change in the retinal pigment epithelium cannot be ruled out.


Treatment of patients with malignant lymphomas with monoclonal antibodies.
Malignant lymphomas represent a heterogenous group of B and T cell-derived malignancies. Most lymphomas are sensitive to chemo- and radiotherapy, however many patients will eventually relapse. Immunotherapeutic approaches including monoclonal antibodies, cytokines or vaccination approaches may offer an alternative treatment of chemotherapy-resistant residual cells especially in cases with low tumor burden or residual disease following chemo- or radiotherapy. Monoclonal antibodies have been successfully applied in their native form, or coupled with radioisotopes or toxins to selectively destroy lymphoma cells and promising results in early clinical trials have been obtained. Alternatively, bispecific antibodies and idiotypic vaccination strategies are used to target autologous T cells to eliminate lymphoma cells. A humanized anti-CD20 antibody showed excellent results in chemotherapy refractory lymphomas and has recently been approved for clinical application in CD20 positive B cell lymphomas.


Sonographic assessment of the normal limits and percentile curves of liver, spleen, and kidney dimensions in healthy school-aged children.
The purpose of this study was to determine the normal standards of liver, spleen, and kidney dimensions and the relationship of each with sex, age, body weight, height, body mass index, and body surface area in healthy school-aged children. Seven hundred twelve healthy school-aged children (7-15 years) in 2 neighboring cities, including rural areas and city centers, were evaluated prospectively. Sex, age, weight, height, body mass index, and body surface area were determined for each case. Organ dimensions were measured 3 times, and the mean values were recorded. All measured organs had a normal position, shape, and echo texture. The children were separated into 5 groups according to body weight. There were no significant differences in organ dimensions with respect to sex (P > .05). The mean right kidney length was shorter than the left kidney length, and the difference was significant (P = .009). Body weight showed the best correlation with liver, spleen, and kidney dimensions. The results were also supported by the variance and covariance of the correlation coefficients. The normal limits of the liver, spleen, and kidneys are important parameters during a sonographic examination. This study revealed that organ dimensions showed the best correlation with body weight. To our knowledge, in clinical practice there are no pediatric organ dimension percentile graphs for interpretation of sonographic examinations. We hope this study contributes to daily practice in radiology clinics.


How sustainable are biopolymers? Findings from a life cycle assessment of polyhydroxyalkanoate production from rapeseed-oil derivatives.
The main purpose of the article was to compare different scenarios of biopolymer production and their impacts on the environment using Life Cycle Assessment. Three alternative polyhydroxyalkanoates (PHA: amorphous PHA and poly(3-hydroxybutyrate), P(3HB)) production scenarios were considered to assess its environmental impact: Scenario A - Production of mcl-PHA/P(3HB) from crude vegetable oil; Scenario B - Production of P(3HB) with biodiesel by-product; Scenario C - Production of mcl-PHA/P(3HB) from used vegetable oil. Subject to the scenario considered, it was shown that the environmental efficiency of PHA production is highly dependent on carbon sources used, and it is strongly supporting production of mcl-PHA instead of P(3HB). As LCA study shows, due to low yield of P(3HB) in comparison to mcl-PHA production in considered processes, all the P(3HB) production scenarios have higher impacts than the production of mcl-PHA. Production processes based on bacterial fermentation had its impacts related mostly to the raw materials used and to its separation phase. Additionally, using secondary materials instead of raw ones, namely used oil instead of virgin oil, gives significant improvement with regard to environmental impact. The resource efficiency is also the identified as the key factor with sensitivity analysis that indicates the possible increase of biopolymer yield as the most beneficial factor. Biobased polymers have big environmental potential but still need significant improvement with regard to their manufacturing processes in order to become more economically benign. Preferably production of these microbial polymers should be integrated into biorefinery blocks, where such waste stream arises (e.g. biodiesel production plant).


Immunogenicity of experimental live attenuated Japanese encephalitis vaccine viruses and comparison with wild-type strains using monoclonal and polyclonal antibodies.
A total of 105 hybridomas secreting anti-Japanese encephalitis (JE) virus monoclonal antibodies (mAbs) were generated from six fusions against four strains of JE virus: wild-type strains SA14 and G8924 and live attenuated vaccines SA14-5-3 and SA14-14-2 (PDK-9). Most of the mAbs (87%) elicited haemagglutination inhibition activity while only a minority (24%) elicited neutralization. None of the mAbs prepared against SA14-5-3, parent of SA14-14-2, elicited neutralization while the only mAbs prepared against SA14-14-2 that elicited neutralization recognized flavivirus cross-reactive epitopes. In comparison, mAbs raised against wild-type strains showed that a spectrum of epitopes with different specificities, including JE type-specific epitopes, elicited neutralizing activity. Two mAbs, prepared against SA14-5-3 virus, were found to be vaccine-specific and five, prepared against strains SA14 and G8924, were wild-type-specific.


Alteration of Mitochondrial Function in Oxidative Stress in Parkinsonian Neurodegeneration: A Cross-Sectional Study.
Appropriate mitochondrial function and oxidative balance are critical to neuronal survival. Accumulation of reactive oxygen species leads to oxidative stress that can cause free radical damage to biomolecules of the cell components and the molecules in the cellular milieu that eventually lead to a variety of chronic diseases including neurodegenerative disorders. Mitochondrial dysfunction initiates neuronal apoptosis thereby leading to neurodegenerative diseases including Parkinson's disease (PD). To evaluate oxidative stress vis-a-vis mitochondrial function (Cytochrome C oxidase activity) in PD patients, Parkinson plus syndrome (PPS) patients in comparison with healthy controls (HCs). Cross-sectional Study. We assessed oxidative stress by chemiluminescence using luminol, and cytochrome c oxidase activity (CCO) by CCO kit using spectrophotometry in PD patients (n = 80), PPS patients (n = 40), and HCs (n = 40). Data were presented as number (%) or mean ± SD/median as approximate. Quantitative baseline variables were compared among the groups using one-way ANOVA and qualitative variables were compared using Chi-square test. The difference in median was compared using Kruskal-Wallis test followed by Post-hoc Bonferronni correction. Compared to HCs (Median 7.53 ± 15.58 RLU/sec/cell), ROS level in PD (14.13 ± 29.5), and PPS (17.43 ± 15.91) patients was significantly higher (P = 0.0029: HC vs, PD & P = 0.0500: HC vs. PPS). Also, ROS in PD patients (14.13 ± 29.5) was higher that PPS patients (17. 43 ± 15.91) but the difference was not statistically significant (P = 0.84). The CCO activity was found to be diminished in PD (Median: 0.025 ± 0.013 units/ml) and PPS patients (0.027 ± 0.008) in comparison to HCs (0.117 ± 0.049). Mitochondrial dysfunction and oxidative stress is associated with PD and PPS and may play an important role in etiopathogenesis. Though the cause-effect conundrum has not been comprehensively probed but addressing oxidative stress and mitochondrial damage may serve as an adjunctive therapy for PD and PPS. Iron metabolism as reflected in the red cell indices may aid in differentiating PD from PPS.


Antigenic variants of rabies virus.
The authors studied nineteen street virus isolates from different regions of Canada using either anti-nucleocapsid and anti-glycoprotein monoclonal antibodies or cross-protection tests. This study only allowed us to recognize three groups of viruses with different nucleocapsid patterns, and no difference, as far as protection with a Pitmann-Moore vaccine is concerned, between four of these strains.


Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: a perspective.
Structure and dynamics of G proteins and their cognate receptors, both alone and in complex, are becoming increasingly accessible to experimental techniques. Understanding the conformational changes and timelines that govern these changes can lead to new insights into the processes of ligand binding and associated G protein activation. Experimental systems may involve the use of, or otherwise stabilize, non-native environments. This can complicate our understanding of structural and dynamic features of processes such as the ionic lock, tryptophan toggle, and G protein flexibility. While elements in the receptor's transmembrane helices and the C-terminal α5 helix of Gα undergo well-defined structural changes, regions subject to conformational flexibility may be important in fine-tuning the interactions between activated receptors and G proteins. The pairing of computational and experimental approaches will continue to provide powerful tools to probe the conformation and dynamics of receptor-mediated G protein activation.


Age-related differences and circadian and seasonal variations of myelopoietic progenitor cell (CFU-GM) numbers in mice.
The effect of aging on the myelopoietic progenitor cell (CFU-GM) numbers in mice was studied with special emphasis on biological rhythms in hemopoiesis. Female C3H mice, 16-, 21- and 26-month-old, were investigated versus 3-month-old controls every 3 hours during the 24-h period at three different times of the year. Strong circadian rhythms were observed in both CFU-GM concentration and content in the femur of all age-groups. The amplitudes and the 24-h mean values were declining in mice aged 21 and 26 months. From 16 months of age, a significant advance of circadian peak phases was observed. The overlapping was variable during the 24-h period. The present results may explain previous inconsistencies regarding myelopoietic progenitor cell numbers in aging mice. Some seasonal differences in rhythmicity patterns were also observed. Fitting of original data to single sinus functions was highly significant, although important details sometimes were obscured.


Quilty indicates increased risk for microvasculopathy and poor survival after heart transplantation.
The impact of Quilty (sub-endocardial infiltration of lymphocytes) on the development of stenotic microvasculopathy and outcome after heart transplantation has not yet been evaluated. Biopsies (n = 9,713) obtained within the first post-transplant year from 873 patients (722 men, age 49.3 +/- 0.3 years) were evaluated by light microscopy (hematoxylin-eosin) for Quilty and cellular rejection (ISHLT), stenotic microvasculopathy (luminal radius:medial thickness ratio <1) and endothelial disease (core diameter:cell diameter ratio < or =1). Risk factors for stenotic microvasculopathy were analyzed by logistic regression. Overall survival and freedom from graft failure (cardiac re-transplantation, myocardial infarction and sudden cardiac death) were estimated by the Kaplan-Meier method and tested using a Cox proportional hazard model. We found 1,830 (19%) Quilty-positive biopsies in 481 (55%) Quilty-formers and stenotic microvasculopathy in 866 (9%) biopsies of 379 (43%) patients. Evidence of Quilty (odds ratio [OR] 1.77; 95% confidence interval [CI] 1.26 to 2.57) and endothelial disease (OR 4.98; 95% 95% CI 3.31 to 7.49) indicated higher risk, whereas post-transplant statin therapy was associated with lower risk for stenotic microvasculopathy (OR 0.68; 95% CI 0.48 to 0.97). Freedom from graft failure was lower in Quilty-formers (p = 0.0060) and even worse if patients suffered from both Quilty and stenotic microvasculopathy (p = 0.0017). Both factors were confirmed in multivariate regression analysis (stenotic microvasculopathy risk ratio [RR] 1.90, 95% CI 1.23 to 2.95; Quilty RR 1.77, 95% CI 1.11 to 2.82, p = 0.0430). Presence of Quilty indicates increased risk for stenotic microvasculopathy in biopsy early after heart transplantation. Both are associated with poor outcome due to graft failure.


Selective binding by Helicobacter pylori of leucocyte gangliosides with 3-linked sialic acid, as identified by a new approach of linkage analysis.
The human gastric pathogen Helicobacter pylori has been shown to bind to glycoconjugates of human leucocytes in a sialic acid-dependent way. In order to improve the identification of the binding epitope, a new technique was developed to analyze the ketosidic linkage position between a terminal sialic acid and the consecutive monosaccharide. Permethylation and reduction with LiAlH4 followed by trifluoroacetolysis in 1000:1 trifluoroacetic anhydride:trifluoroacetic acid (24 h, 100 degrees C) results in the cleavage of glycosidic but not ketosidic bonds. The disaccharide products were analyzed by gas chromatography-mass spectrometry and sialyl-3 or -6 position and NeuAc or NeuGc are identified by their separate retention times and mass spectra. The method was worked out on model saccharides and applied on five-sugar gangliosides (sialylparaglobosides) of human leucocytes. Radiolabeled Helicobacter pylori was shown to bind to the upper part, but not to the lower part, of the five-sugar interval of a mixture of gangliosides separated on a thin-layer chromatogram. Using a membrane blotting procedure the active and inactive bands were isolated and shown to be NeuAcalpha2-3- and NeuAcalpha2-6-paraglobosides, respectively.


The creation and development of an instrument to determine fitness to stand trial.
A research team, consisting of a jurist and a psychologist, created and developed an instrument which could be used to effectively assess the fitness to stand trial of an accused person. A questionnaire was compiled and sent out to 736 members of both the legal and mental health professions. The information received from the response group was used to compile the fitness instrument. This instrument was applied to 100 observandi, committed to Oranje Hospital in terms of the Criminal Procedure Act, by way of a semi-structured interview. The same 100 observandi were evaluated by a multi-disciplinary team of the hospital and the results of the two groups were compared. This comparison showed a significant resemblance and it was concluded that the instrument could successfully be used as a single method of evaluating triability.


The association of venous thromboembolism with blood transfusion in kidney transplant patients.
Red blood cell transfusion (RBCT) is common after kidney transplantation and could have pro-thrombotic effects predisposing to venous thromboembolism (VTE). The risks for developing of VTE after RBCT in kidney transplant patients are unknown. This was a retrospective cohort study of adult kidney transplant recipients from 2002 to 2018. The exposure of interest was receipt of RBCT after transplant. Cox proportional hazards models were used to calculate hazard ratios (HR) for the outcomes of venous thromboembolism [VTE] (deep venous thrombosis [DVT] or pulmonary embolism [PE]) using RBCT as a time-varying, cumulative exposure. Out of 1258 kidney transplants recipients, 468 (37%) were transfused during the study period. Seventy-nine study participants (6.3%) developed VTE, 72 DVT (5.7%), and 22 PE (1.8%). For the receipt of 1, 2, 3-5, and >5 RBCT, compared to individuals never transfused, the number of events and adjusted HR (95%CI) for VTE were 6 (6.2%) HR 1.57 (0.69-3.58), 9 (7.6%) HR 2.54 (1.30-4.96), 15 (11.9%) HR 2.73 (1.38-5.41), and 23 (18.1%) HR 5.77 (2.99-11.14) respectively; for DVT, it was 6 (6.2%) HR 1.94 (0.84-4.48), 9 (7.6%) HR 2.92 (1.44-5.94), 14 (11.1%) HR 3.29 (1.63-6.65), and 21 (16.5%) HR 6.97 (3.53-13.76), respectively. For PE, among transfused individuals, there were 14 events (3.0%) and the HR was 2.40 (1.02-5.61). The risks for developing VTE, DVT, and PE were significantly increased in kidney transplant patients receiving RBCT after transplant. Receipt of RBCT should prompt considerations for judicious monitoring and assessment for thrombosis.


Television viewing associates with delayed language development.
To identify impact of television viewing on language development. The case-control study included 56 new patients with language delay and 110 normal children, aged 15-48 months. Language delay was diagnosed by reviewing language milestones and Denver-II. Television viewing variables and child/parental characteristics between both groups were interviewed. The data were analyzed by ANOVA and chi-square test. Adjusted odds ratios and 95% confidence intervals were calculated from multivariate logistic regression model. Forty-six boys and 10 girls; mean [+/-SD] age, 2.11+/-0.47 years of the case group and 59 boys and 51 girls; mean [+/-SD] age, 2.23+/-0.80 years of the control group were enrolled. Children who had language delay usually started watching television earlier at age 7.22+/-5.52 months vs. 11.92+/-5.86 months, p-value<0.001 and also spent more time watching television than normal children (3.05+/-1.90 h/day vs. 1.85+/-1.18 h/day; p-value<0.001). Children who started watching television at<12 months of age and watched television>2 h/day were approximately six times more likely to have language delays. There is a relationship between early onset and high frequency of TV viewing and language delay.


Usefulness of new and traditional serum biomarkers in children with suspected appendicitis.
The objective of the study is to evaluate the usefulness of the leukocyte (white blood count [WBC]) and neutrophil (absolute neutrophil count [ANC]) counts; the values of C-reactive protein (CRP), procalcitonin, and calprotectin (CP); and the APPY1 Test panel of biomarkers, to identify children with abdominal pain at low risk for appendicitis. Children 2 to 14 years of age with abdominal pain suggesting acute appendicitis (AA) were prospectively included. Procalcitonin, calprotectin, C-reactive protein, white blood count, ANC, and the new plasma APPY1 Test were performed. The final diagnosis was determined by histopathology in cases of AA and telephone follow-up in children discharged without AA. Between February 2012 and June 2013, 185 children were enrolled with an average age of 9.32±2.7 years. Eighty-nine (48.1%) were finally diagnosed with AA. The APPY1 Test panel showed the highest discriminatory power, sensitivity of 97.8 (95% confidence interval [CI], 92.2-99.4), negative predictive value of 95.1 (95% CI, 83.9-98.7), negative likelihood ratio of 0.06 (95% CI, 0.01-0.22), and specificity of 40.6 (95% CI, 31.3-50.5). A negative APPY1 Test and ANC less than 7500 per milliliter provided a sensitivity of 100 (95% CI, 95.9-100), negative predictive value of 100 (95% CI, 89.8-100), and specificity of 35.4 (95% CI, 26.6-45.4). In the multivariate analysis, only the APPY1 Test and ANC greater than 7500 per milliliter were significant risk factors for AA (odds ratio, 13.76; 95% CI, 3.02-62.57, and odds ratio, 6.37; 95% CI, 2.89-14.28, respectively). The APPY1 Test panel with ANC could be useful in identifying children with abdominal pain suggestive of AA who are at low risk for this disease.


One injection to profile the chemical composition and dual-antioxidation activities of Rosa chinensis Jacq.
An on-line high-performance liquid chromatography-diode-array-detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-total antioxidant capacity detection (HPLC-DAD-ESI-IT-TOF-MS-TACD) system was applied for the identification and evaluation of antioxidants in Rosa chinensis Jacq., an edible flower in food industry and a widely used traditional Chinese medicine. With the help of this platform, the HPLC fingerprint, mass fragmentations, and sample activity profiles against 1,1-diphenylpicryl-2-hydrazyl radical (DPPH•) and ferric reducing antioxidant power (FRAP) were recorded after one injection. Using this technique, 80 compounds were separated and identified by their LC/MS behaviors with the assistance of standard compounds. In addition, 11 different Rosa chinensis Jacq. samples were profiled and then quantified for their DPPH• and FRAP activities. Interestingly, a total of 52 compounds showed antioxidative effects against DPPH• and 61 were active against FRAP. The results demonstrated that the on-line system is a powerful technique for antioxidant discovery in Rosa chinensis Jacq. and other food resources.


Comparison of primers for the detection of pathogenic Escherichia coli using real-time PCR.
To evaluate PCR primers for the detection of pathogenic Escherichia coli in a real-time PCR assay and determine their utility in produce irrigation water testing. Three previously published PCR primer sets and one set designed for this study were tested for their ability to produce amplification products for several pathogenic E. coli serotypes from whole cells as template. Two of the previously published primer sets were chosen for real-time PCR detection limit determination. The coneaeA and PEH detection limit of E. coli O157:H7 was 10(0) and 10(1) CFU rxn(-1) in sterile water respectively. To detect E. coli O157:H7 in sprout irrigation water, the water required dilution due to PCR inhibitors. The detection limit of the coneaeA and PEH was 10(1) and between 10(2) and 10(3) CFU rxn(-1) in diluted sprout irrigation water respectively. The primer set coneaeA was able to produce an amplification product from each E. coli serotype, except O128:H7 and most sensitive for real-time PCR detection of pathogenic E. coli in diluted sprout irrigation water. The necessity of a dissociation analysis to distinguish positive samples from those with fluorescence of random dsDNA generation for real-time PCR in a complex background was established.


Deficiency of S100 calcium binding protein A9 attenuates vascular dysfunction in aged mice.
S100 calcium-binding protein A9 (S100A9) is a danger-associated molecular pattern molecule that mediates the inflammatory response. Inflammation is essential in aging-related cardiovascular diseases. However, less is known regarding the role of S100A9 in vascular aging. S100A9 null mice were used to investigate the role of S100A9 in aging-related pathologies. Artery rings were used to measure the functional characteristics of vascular with a pressurized myograph. Telomere length, Sirtuin activity, oxidative stress, and endothelial nitric oxide synthetase (eNOS) activity were used to elevate vascular senescence. Intraperitoneal glucose tolerance (IPGTT) and insulin sensitivity test (IST) were employed to investigate the effects of S100A9 on insulin resistance. Inflammation response was reflected by the concentration of inflammatory cytokines. The Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) inhibitors were used to identify the downstream molecular mechanisms of S100A9 in aging-induced senescence in endothelial cells. S100A9 expression in vascular increased with aging in mice and humans. Deficiency of S100A9 alleviated vascular senescence in aged mice, as evidenced by increased telomere length, Sirtuin activity, and eNOS activity. Meanwhile, S100A9 knockout improved endothelium-dependent vasodilatation and endothelial continuity in aged mice. Moreover, the increased insulin resistance, oxidative stress, and inflammation were mitigated by S100A9 deletion in aged mice. In vitro, S100A9 induced senescence in endothelial cells, and that effect was blunted by TLR4 but not RAGE inhibitors. The present study suggested that S100A9 may contribute to aging-related pathologies and endothelial dysfunction via the TLR4 pathway. Therefore, targeting S100A9/TLR4 signaling pathway may represent a crucial therapeutic strategy to prevent age-related cardiovascular diseases.


[Buerger's disease starting in the upper extremity. A favorable response to nifedipine treatment combined with stopping tobacco use].
A case of a 38-year-old smoker male who had vasoconstriction and instep claudication of the right hand, is presented. After a year of evolution, he experienced the same alteration on the left foot. He was diagnosed as suffering from thromboangiitis obliterans, by means of angiography. After oral nifedipine treatment, combined with cessation of smoking, all symptoms and trophics regressed.


Impact of school operating scenarios on COVID-19 transmission under vaccination in the U.S.: an agent-based simulation model.
At the height of the COVID-19 pandemic, K-12 schools struggled to safely operate under the fast-changing pandemic situation. However, little is known about the impact of different school operating scenarios considering the ongoing efforts of vaccination. In this study, we deployed an agent-based simulation model to mimic disease transmission in a mid-sized community consisting of 10,000 households. A total of eight school operating scenarios were simulated, in decreasing order of restrictiveness regarding COVID-19 mitigation measures. When masks were worn at school, work, and community environments, increasing in-person education from 50% to 100% would result in only 1% increase in cumulative infections. When there were no masks nor contact tracing while schools were 100% in person, the cumulative infection increased by 86% compared to the scenario when both masking and contact tracing were in place. In the sensitivity analysis for vaccination efficacy, we found that higher vaccination efficacy was essential in reducing overall infections. Our findings showed that full in-person education was safe, especially when contact tracing, masking, and widespread vaccination were in place. If no masking nor contact tracing was practiced, the transmission would rose dramatically but eventually slow down due to herd immunity.


Calpastatin participates in the regulation of cell migration in BAP1-deficient uveal melanoma cells.
To detect how BRCA-associated protein 1 (BAP1) regulates cell migration in uveal melanoma (UM) cells. Wound healing and transwell assays were performed to detect UM cell migration abilities. Protein chip, immunoprecipitations and surface plasmon resonance analyses were applied to identify BAP1 protein partners. Western blot and calpain activity assays were used to test the expression and function of calpastatin (CAST). CAST protein was confirmed as a new BAP1 protein partner, and loss of BAP1 reduced the expression and function of CAST in UM cells. The overexpression of CAST rescued the cell migration phenotype caused by BAP1 loss. BAP1 interacts with CAST in UM cells, and CAST and its subsequent calpain pathway may mediate BAP1-related cell migration regulation.


Pleiotropy in the presence of allelic heterogeneity: alternative genetic models for the influence of APOE on serum LDL, CSF amyloid-β42, and dementia.
The two genetic polymorphisms, rs7412 and rs429358, that collectively form the e2, e3, and e4 alleles of apolipoprotein E (APOE) are among the most widely studied sequence variants in the genome. The predominant model for testing APOE involves the haplotype combinations of e2, e3, and e4 and has been basis of associations with dementia, atherosclerosis, and serum lipid levels. Here, we demonstrate the functional independence of these two component sites, with rs7412 contributing to the majority of variance in serum LDL (p=10-20), whereas rs429358 alone influences variance in CSF amyloid-ß42 (Aß42) (p=10(-17)). This latter relationship is also reflected in the association of APOE with dementia, where rs429358 strongly influences disease (p=10(-67)), but rs7412 does not. Models based upon e2, e3, and e4 explained less variance for both dementia risk and CSF Aß42 than did rs429358 alone. When adjusted for CSF Aß42, the association of rs429358 with dementia is greatly reduced but remains significant indicating that APOE polymorphism influences disease by additional mechanisms distinct from Aß42 metabolism. We reach four principal conclusion from this study: 1) rs429358 alone is responsible for the association of APOE with dementia; 2) The association of APOE with dementia is substantially mediated by its effect on CNS Aß42 levels; 3) The association of APOE with dementia is not mediated by its impact on peripheral lipid metabolism; and 4) The dichotomy of effects of rs429358 and rs7412 represents one of the best examples of genetic pleiotropy for complex traits known and illustrates the importance of allelic heterogeneity in APOE.


Public health priority setting on a national scale: The Scottish experience.
Scotland has the lowest life expectancy in Western Europe and significant health inequalities. A national review of public health in 2015 found that there was a lack of coherent action across organisational boundaries, inhibiting progress. This paper describes a rapid (four-month) systematic approach to prioritisation of Scotland's public health challenges, which was evidence-based, transparent and made use of significant stakeholder engagement. Cross-sectional survey of stakeholders in deliberative meetings. An independent Expert Advisory Group (EAG) was formed to develop a typology of public health priorities, a long-list of potential priorities and ranking criteria. Deliberative stakeholder events were held at which the criteria were refined and priorities scored by participants from a wide range of stakeholder organisations. The proposed typology identified three types of public health priorities: risk factors, social factors and system factors; medically defined disease entities were not used deliberately, to facilitate broad stakeholder participation. Fifteen criteria were identified to help identify priority issues, based on the scope of their burden, amenability to change, and multi-stakeholder preferences. Six public health priorities were selected by the EAG based on stakeholder scoring of a long-list against these criteria. Prioritisation is important in modern public health but it is challenging due to limited data availability, lack of agreed evidence on effectiveness and efficiency of interventions, and divergent stakeholder views. The Scottish experience nevertheless shows that useful public health priorities can be agreed upon by a wide range of stakeholders through a transparent, participatory and logical process.


LAMC2 promotes EGFR cell membrane localization and acts as a novel biomarker for tyrosine kinase inhibitors (TKIs) sensitivity in lung cancer.
The epidermal growth factor receptor (EGFR) is one of the first and most prominent driver genes known to promote malignant lung cancer. Investigating regulatory mechanisms beyond ligand-receptor binding, phosphorylation, and receptor kinase activation as means of EGFR signaling activation is important for improving EGFR-targeted therapy. Here, we report that Laminin-5γ-2 (LAMC2) retained high oncogenic capacity in lung cancer, silencing LAMC2 inhibited EGFR-induced cell proliferation and tumor growth in vivo. Deletion mutation experiments showed that both the EGF-Lam and LamB regions of LAMC2 are necessary for EGFR receptor binding, and that LAMC2 and EGFR were found to co-localize at the endoplasmic reticulum (ER) membrane. In addition, LAMC2 overexpression enhanced EGFR membrane deposition and promoted EGFR transport from the ER. Moreover, LAMC2 was necessary for preventing EGFR protein degradation via ubiquitination. Lastly, our study showed that high LAMC2 expression is positively associated with response to gefitinib (EGFR tyrosine kinase inhibitor) treatment. Overall, our study revealed a new regulatory mechanism of LAMC2 in promoting EGFR protein expression and stability by facilitating ER transport and preventing protein degradation via ubiquitination. Moreover, LAMC2 may serve as a stratifying biomarker for patients suitable for EGFR-TKI treatment.


Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response.
Human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), a rapidly progressing, clonal malignancy of CD4+ T lymphocytes. Fewer than one in 20 infected individuals typically develop ATL and the onset of this cancer occurs after decades of relatively symptom-free infection. Leukemic cells from ATL patients display extensive and varied forms of chromosomal abnormalities and this genomic instability is thought to be a major contributor to the development of ATL. HTLV-I encodes a regulatory protein, Tax, which is necessary and sufficient to transform cells and is therefore considered to be the viral oncoprotein. Tax interacts with numerous cellular proteins to reprogram cellular processes including, but not limited to, transcription, cell cycle regulation, DNA repair, and apoptosis. This review presents an overview of the impact of HTLV-I infection in general, and Tax expression in particular, on cell cycle progression and the repair of DNA damage. The contribution of these activities to genome instability and cellular transformation will be discussed.


Th17 cytokines regulate osteoclastogenesis in rheumatoid arthritis.
This study determined the effect of type 17 helper T-cell (Th17) cytokines on osteoclastogenesis in rheumatoid arthritis (RA). The expression of IL-17 and receptor activator of NF-κB ligand (RANKL) was determined in synovial tissue, fibroblast-like synoviocytes (FLSs), and synovial fluids of RA patients using immunostaining and enzyme-linked immunosorbent assay. Th17 cytokine-induced RANKL expression was studied in RA FLS by using real-time PCR, luciferase activity assays, and Western blot analysis. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and Th17 cytokines, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-17-prestimulated FLS. There was significant correlation between RANKL and IL-17 levels in RA synovial fluid. IL-17, IL-21, and IL-22 increased the expression of Rankl mRNA in RA FLS, and the IL-17-induced RANKL expression decreased by the inhibition of Act1, tumor necrosis factor receptor-associated factor 6, NF-κB, and activator protein-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of exogenous RANKL. The osteoclastic effect was reduced by inhibition of tumor necrosis factor-α. Th17 cytokines have a dual effect on osteoclastogenesis in RA: direct induction of osteoclastogenesis from monocytes and up-regulation of RANKL production in RA FLS. This Th17 cytokine/RANKL axis could be a potential therapeutic target for bone destruction in RA.


Signature pedagogies: An integrative review of an emerging concept in nursing education.
The aim of this paper is to provide an integrative review of the literature associated with signature pedagogies and to discover what lessons have been learned about unearthing, articulating and applying signature pedagogies across a variety of disciplines, but particularly with respect to nursing. A systematic search of databases using key terms was utilised with a particular focus to papers emerging from nursing disciplines. The databases MEDLINE, CINAHL, ERIC, Web of Science and Google Scholar were searched for literature from 2005 to 2018 inclusive. An initial examination of titles and abstracts by the authors resulted in the retrieval of 45 papers and following the application of exclusion criteria, 25 papers were included. Signature pedagogy literature is a developing area and scholars both in nursing disciplines and beyond, often fail to develop on Lee Shulman's framework in their identification of signature pedagogies, resulting in poorly adapted conceptions. Ways forward include closer linking with the original signature pedagogy framework in research, the development of robust evidence-based signature pedagogy identification processes in disciplines and a reconsideration of the esteem of scholars performing signature pedagogies within disciplines.


A comparison of gambling behavior, problem gambling indices, and reasons for gambling among smokers and nonsmokers who gamble: evidence from a provincial gambling prevalence study.
Numerous epidemiological and clinical studies have found that tobacco use and gambling frequently cooccur. Despite high rates of smoking among regular gamblers, the extent to which tobacco potentially influences gambling behavior and vice versa is poorly understood. The current study aimed to provide more insight into this relationship by directly comparing nonsmoking and smoking gamblers on gambling behavior, problem gambling indices, and reasons for gambling. The data for this study came from the 2005 Newfoundland and Labrador Gambling Prevalence Study. Gamblers identified as nonsmokers (N = 997) were compared with gamblers who smoke (N = 622) on numerous gambling-related variables. Chi-square analyses were used to compare groups on demographic variables. Associations between smoking status and gambling criteria were assessed with a series of binary logistic regressions. The regression analyses revealed several significant associations between smoking status and past 12-month gambling. Higher problem gambling severity scores, use of alcohol/drugs while gambling, amount of money spent gambling, use of video lottery terminals, and reasons for gambling which focused on positive reinforcement/reward and negative reinforcement/relief were all associated with smoking. The findings suggest an association between smoking and potentially problematic gambling in a population-based sample. More research focused on the potential reinforcing properties of tobacco on the development and treatment of problematic gambling is needed.


WITHDRAWN: World Apheresis Association Newsletter: April 1, 2016.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries.
Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.


Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.
To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.


Mutations in both the structured domain and N-terminus of histone H2B bypass the requirement for Swi-Snf in yeast.
The chromatin elements targeted by the ATPdependent, Swi-Snf nucleosome-remodeling complex are unknown. To address this question, we generated mutations in yeast histone H2B that suppress phenotypes associated with the absence of Swi-Snf. Sin- (Swi-Snf-independent) mutations occur in residues involved in H2A-H2B dimer formation, dimer- tetramer association, and in the H2B N-terminus. The strongest and most pleiotropic Sin- mutation removed 20 amino acid residues from the H2B N-terminus. This mutation allowed active chromatin to be formed at the SUC2 locus in a snf5Delta mutant and resulted in hyperactivated levels of SUC2 mRNA under inducing conditions. Thus, the H2B N-terminus may be an important target of Swi-Snf in vivo. The GCN5 gene product, the catalytic subunit of several nuclear histone acetytransferase complexes that modify histone N-termini, was also found to act in conjunction with Swi-Snf. The phenotypes of double gcn5Deltasnf5Delta mutants suggest that histone acetylation may play both positive and negative roles in the activity of the Swi-Snf-remodeling factor.


Expression of chemokine receptors in normal and inflamed human intestine, tonsil, and liver--an immunohistochemical analysis with new monoclonal antibodies from the 8th international workshop and conference on human leucocyte differentiation antigens.
Chemokines are important mediators involved in the recruitment of leucocytes to lymphoid tissues and to sites of inflammation. To identify suitable monoclonal antibodies for immunohistochemistry, we tested a panel of new reagents provided by the cytokine/chemokine receptor section of the 8th HLDA workshop on cryostat sections of normal human gut, tonsil, and liver. In addition, inflamed intestinal tissues from individuals with Crohn's disease and ulcerative colitis were analysed. Our results reveal an upregulated expression of chemokine receptors like CCR6, CCR7, CCR9, CXCR1, and CXCR3 in inflamed gut. Enhanced expression of such molecules likely contributes to the maintenance of inflammation in chronic inflammatory bowel disease.


The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study.
A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads in non-diabetic offspring of type 2 diabetic patients. We genotyped SLC30A8 rs13266634 in 846 non-diabetic offspring of type 2 diabetic patients from five different white populations: Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and measurements of insulin sensitivity. Homozygous carriers of the major type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/- 2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found no significant genotype effect on insulin release measured during the OGTT or on estimates of insulin sensitivity. Of European non-diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2 diabetes. These diabetes-prone offspring are characterised by a 19% decrease in first-phase insulin release following an intravenous glucose load, suggesting a role for this variant in the pathogenesis of pancreatic beta cell dysfunction.


Are we wasting our time with the sentinel technique? Fifteen reasons to stop axilla dissection.
Originally, surgery for breast cancer involved removing the pectoral muscles and the regional lymph nodes. This drastic technique was based on Halsted's paradigm of continuous tumour spread via the lymph nodes. In the last century, the amount of surgery has gradually decreased as breast cancer has been recognised as a primary systemic, or partially systemic, disease. Nowadays, breast-conserving therapy is widely used, but axillary lymph node dissection (ALND) and the sentinel technique are still common. Can the patient also be spared such axillary surgery? We have assembled convincing arguments against ALND (and therefore also against the sentinel technique) based on the probability that positive lymph nodes are unlikely to metastasise and that removing them is redundant. At least a discussion of this topic is more than overdue, even if it may be too early to change behaviour.


Plasma concentrations of epidural bupivacaine in mother and newborn: 0.125% versus 0.375%.
Central venous plasma concentrations of bupivacaine were determined in two groups of 15 parturients each who were given epidural analgesia for labor and vaginal delivery. One group received 10 ml of 0.125% bupivacaine plus epinephrine 1:800,000, the other group received 7 ml of 0.375% bupivacaine plus epinephrine 1:800,000. Plasma concentrations of bupivacaine in the umbilical venous (UV) and the umbilical arterial (UA) blood of their babies were also determined. The mean UA, UV, and maternal central venous (MV) plasma concentrations of bupivacaine differed significantly between the two groups: in patients given 0.375% bupivacaine UA values were 63% higher (P less than 0.01), UV values were 57% higher (P less than 0.01), and the MV values were 34% higher (P less than 0.05) than in patients given 0.125% bupivacaine. The measured plasma concentrations speak in favor of the less concentrated solution of bupivacaine in epidural analgesia for obstetrics. Seven milliliters of bupivacaine 0.375% is suitable for epidural analgesia in obstetrics but a low concentration-low dose technique, using 10 ml of bupivacaine 0.125% plus epinephrine 1:800,000 is safer. It provides good analgesia with minimal or no motor block and is associated with low maternal and neonatal plasma concentrations of bupivacaine, well below toxic levels and, to our knowledge, lower than in any other study.


Effect of diazepam on anxiety, sexual motivation, and blood testosterone in anxious male mice.
The effects of diazepam on anxious behavior, sexual motivation, and blood level of testosterone in the presence of a female were studied in male mice with elevated anxiety. Diazepam produced an anxiolytic effect in novel environment, but was ineffective during social contacts. The drug potentiated the primary sexual interest, but failed to correct exhaustion of sexual motivation. The drug produced no effect on blood testosterone.


[Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites].
It is well-known that fumonisin B1 (FB1) stimulates apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been investigated. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB1, fumonisin B2 (FB2), hydrolyzed fumonisin B1 (HFB1) and N-palmitoyl-hydrolyzed fumonisin B1 (N-Pal-HFB1) and investigated caspase 3 activation and DNA fragmentation. Only exposure to 10 μmol/L FB1 for 24h led to a significantly increased activity of caspase 3 and to DNA fragmentation. All other compounds tested did not show any significant activation of caspase 3 activity. Further we examined wether a sphinganine accumulation is correlated with the induction of apoptosis in IHKE cells. Therefore we developed a liquid chromato-graphy/electrospray ionization-tandem-mass spectrometry(HPLC-MS/MS)-method using phytosphingosine as an internal standard to determine sphinganine- and sphingosine concentrations in incubated IHKE cells. Whereas a significant increase of sphinganine was observed with all substrates, sphingosine levels remained unchanged. This shows that FB1 exposure leads to apoptosis in a sphinganine-independent mechanism.


Burst nucleation by hot injection for size controlled synthesis of ε-cobalt nanoparticles.
Reproducible growth of narrow size distributed ε-Co nanoparticles with a specific size requires full understanding and identification of the role of essential synthesis parameters for the applied synthesis method. For the hot injection methodology, a significant discrepancy with respect to obtained sizes and applied reaction conditions is reported. Currently, a systematic investigation controlling key synthesis parameters as injection-temperature and time, metal to surfactant ratio and reaction holding time in terms of their impact on mean ([Formula: see text]mean) and median ([Formula: see text]median) particle diameter using dichlorobenzene (DCB), Co2(CO)8 and oleic acid (OA) as the reactant matrix is lacking. A series of solution-based ε-Co nanoparticles were synthesized using the hot injection method. Suspensions and obtained particles were analyzed by DLS, ICP-OES, (synchrotron)XRD and TEM. Rietveld refinements were used for structural analysis. Mean ([Formula: see text]mean) and median ([Formula: see text]median) particle diameters were calculated with basis in measurements of 250-500 particles for each synthesis. 95 % bias corrected confidence intervals using bootstrapping were calculated for syntheses with three or four replicas. ε-Co NPs in the size range ~4-10 nm with a narrow size distribution are obtained via the hot injection method, using OA as the sole surfactant. Typically the synthesis yield is ~75 %, and the particles form stable colloidal solutions when redispersed in hexane. Reproducibility of the adopted synthesis procedure on replicate syntheses was confirmed. We describe in detail the effects of essential synthesis parameters, such as injection-temperature and time, metal to surfactant ratio and reaction holding time in terms of their impact on mean ([Formula: see text]mean) and median ([Formula: see text]median) particle diameter. The described synthesis procedure towards ε-Co nanoparticles (NPs) is concluded to be robust when controlling key synthesis parameters, giving targeted particle diameters with a narrow size distribution. We have identified two major synthesis parameters which control particle size, i.e., the metal to surfactant molar ratio and the injection temperature of the hot OA-DCB solution into which the cobalt precursor is injected. By increasing the metal to surfactant molar ratio, the mean particle diameter of the ε-Co NPs has been found to increase. Furthermore, an increase in the injection temperature of the hot OA-DCB solution into which the cobalt precursor is injected, results in a decrease in the mean particle diameter of the ε-Co NPs, when the metal to surfactant molar ratio [Formula: see text] is fixed at ~12.9.


Regioselective enzymatic acylation of ribavirin to give potential multifunctional derivatives.
Lipase-catalyzed synthesis of potential multifunctional ribavirin derivatives was performed in acetone. Divinyl dicarboxylates with different chain lengths (C4, C6, C9, C10) were used as acyl donors and the reactions were catalyzed by lipase immobilized on acrylic resin from Candida antarctica (CAL-B). Ribavirin was regioselectivly acylated at the primary hydroxyl groups and the corresponding vinyl esters (C4, C6, C9, C10) were prepared in respective yields of 48%, 65%, 54%, 55%.