Neonatal Pain Response to Various Heel Prick Devices: A Randomized Controlled Trial.
Heel prick is a commonly performed painful intervention in neonates. Though different devices are available, there is a need to compare the procedural pain response elicited by them. To compare the neonatal pain response to three different heel prick devices; automatic lancet, manual lancet, and 26-gauge (G) hypodermic needle. Parallel-group three-arm randomized controlled trial. Clinically stable neonates of gestational age >28 weeks and birth weight >800 g undergoing heel prick for estimation of random blood sugar. One hundred and eighty neonates were randomized to automatic lancet (n=59), manual lancet (n=59), or needle (n=62) groups between March, 2021 and August, 2022. The primary outcome was the premature infant pain profile-revised (PIPP-R) score. Secondary outcomes were post-intervention cerebral regional oxygen saturation (CrSO2), changes in CrSO2 (DCrSO2), the time for CrSO2 normalization using near-infrared spectroscopy, duration of audible cry, and the number of squeezes and pricks needed. Intention-to-treat analysis was done. Median (IQR) of PIPP-R scores were comparable in the automatic lancet [6 (4, 7.5)], manual lancet [5.5 (3.5, 8)], and needle [6 (3-9.6)] groups; P=0.59. No difference was observed in post-intervention CrSO2, DCrSO2, and the number of pricks. However, the time required for CrSO2 normalization and the number of squeezes were significantly higher with the needle. All three devices induced similar pain responses to heel prick in neonates; though, the number of squeezes needed was higher with the needle.


Effect on intimal hyperplasia of dexamethasone released from coated metal stents compared with non-coated stents in canine femoral arteries.
Polymer-coated, dexamethasone (DXM)-releasing stents were tested in order to assess the efficacy of DXM released locally for the prevention of stent restenosis due to intimal hyperplasia. Strecker stents coated with a biodegradable membrane containing DXM were implanted percutaneously into the femoral artery in 14 dogs. The contralateral artery received a conventional non-coated stent serving as control. The drugs are eluted by degradation of the carrier membrane. Follow-up intraarterial digital subtraction angiography (DSA) was obtained at 3, 6, 9, 12, and 24 weeks with subsequent autopsy. Specimens for gross and microscopic pathology were obtained and histomorphometry was performed. Four of 14 DXM-coated stents showed thrombotic occlusion within the first 3 weeks; ten DXM-coated stents remained patent. At follow-up DSA, DXM-coated stents showed a significantly wider lumen than the non-coated stents. At morphometry there was less intimal hyperplasia over DXM-coated stents than over non-coated stents (p < 0.05). DXM-coated stents reduce neointimal hyperplasia in dogs when compared with non-coated stents.


Evidence for proximal cysteine and lysine residues present at the nucleotide domain of rabbit muscle creatine kinase.
Inactivation of rabbit muscle creatine kinase by o-phthalaldehyde was investigated. The loss of enzyme activity was concomitant with the increase in fluorescence intensity at 410 nm. The modified enzyme showed a characteristic absorption peak at 336 nm. These evidences suggested that the mechanisms of inhibition of creatine kinase by o-phthalaldehyde involves binding of the thiol and the epsilon-amino group of enzyme leading to the formation of isoindole derivative. None of the substrates, except Mg-ATP, provided protection against o-phthalaldehyde inhibition. This was corroborated by fluorescence studies. Double inhibition experiments showed that p-chloromercuricphenyl sulphonic acid, a thiol-specific reagent, binds to the same cysteine which is also involved in the o-phthalaldehyde reaction. Stoichiometric results indicated that 2 mol of o-phthalaldehyde were incorporated per mole of enzyme molecule upon complete inactivation. Denaturation of creatine kinase by urea or heat treatment prior to o-phthalaldehyde addition resulted in the decrease of fluorescence intensity indicating that native conformation of the enzyme is essential for isoindole derivative formation.


Temporal bone pathology in congenital anomalies of the oval window and the facial nerve.
Temporal bones of six infants with congenital ear anomalies were examined for abnormalities of the oval window and facial nerve. These temporal bones were classified into two groups according to the degree of malformation: group A, those with atresia or absence of the oval window; and, group B, those with hypoplasia of the stapes and annular ligament. Group A, consisting of five ears, were associated with severe middle ear anomalies such as the abnormal course of the facial nerve and absence of the stapes. In group B, consisting of seven ears, the stapes were present and the facial nerve presented minor anomalies such as obtuse angulation at the first genu, central migration of the geniculate ganglion cells, ectopic muscles and a wide bony dehiscence of the facial canal around the oval window. Probable origin of the anomalies in group A could mainly be due to maldevelopment of the facial nerve during an earlier embryonal period while that of group B could have developed after the ninth week of the fetal period and are mostly localized along the second branchial arch.


Assessment of suturing in the vertical plane shows the efficacy of the multi-degree-of-freedom needle driver for neonatal laparoscopy.
We have developed a thin needle driver with multiple degrees-of-freedom (DOFs) for neonatal laparoscopic surgery. The tip of this needle driver has three DOFs for grasp, deflection and rotation. Our aim was to evaluate the performance of the multi-DOF needle driver in vertical plane suturing. Six pediatric surgeons performed four directional suturing tasks in the vertical plane using the multi-DOF needle driver and a conventional one. Assessed parameters were the accuracy of insertion and exit, the depth of suture, the inclination angle of the needle and the force applied on the model. In left and right direction sutures, the inclination angle of the needle with the multi-DOF needle driver was significantly smaller than that with the conventional one (p = 0.014, 0.042, respectively). In left and right direction sutures, the force for pulling the model with the multi-DOF needle driver was smaller than that with the conventional one (p = 0.036, 0.010, respectively). This study showed that multi-directional suturing on a vertical plane using the multi-DOF needle driver had better needle trajectories and was less invasive as compared to a conventional needle driver.


Fearful apes or nervous goats? Another look at functions of dispositions or traits.
In his article, Grossmann argues that, in the context of human cooperative caregiving, heightened fearfulness in children and human sensitivity to fear in others are adaptive traits. I offer and briefly defend a rival hypothesis: Heightened fearfulness among infants and young children is a maladaptive trait that did not get deselected in the process of evolution because human sensitivity to fear in others mitigates its disadvantageous effects to a sufficient extent.


Preparation and characterization of subcellular fractions from the liver of C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase activities.
The present study was designed to prepare and characterize subcellular fractions from the liver of male C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase isozymes. The effects of different washing and pelleting procedures on the mitochondrial, microsomal and cytosolic fractions were studied. It was found that 133,000 gav for 60 min (i.e. more extensive force than the usual 105,000 gav for 60 min) was necessary to obtain a membrane-free cytosolic fraction, while one wash for microsomes and two washes for mitochondria yielded reasonably pure fractions. The purity of the different fractions obtained by differential centrifugation was then determined using established enzyme markers and morphological examination with the electron microscope. Several enzymes involved in drug metabolism were also measured in these fractions. The subcellular distributions obtained here for marker enzymes closely resemble those reported for rat liver. Starvation had no significant effect on the epoxide hydrolase activities nor did the addition of mouse bile or rat liver cytosol, which might contain inhibitors. The change in epoxide hydrolase activities with time after preparation of the subcellular fractions was studied, as well as the effect of freeze-thawing. The subfractions prepared here are suitable for the further characterization of the different forms of epoxide hydrolase present in mouse liver, as well as for other studies requiring well-characterized subfractions.


Histogenesis of cholangiomas and cholangiocarcinomas in thioacetamide fed rats.
A sequential, histologic analysis of the livers of male albino rats chronically fed the hepatocarcinogen thioacetamide (TAA) is performed after one, two, three, four, eight and twelve months of treatment. Liver cell alterations present after one, two and three months consist of centrolobular liver cell degeneration and oval cell proliferation. After 8 months of TAA treatment, a variety of benign tumors (cystadenomas, angiomas, cholangiomas) is observed. From the 12th month all experimental animals develop cholangiocarcinomas. Pulmonary metastases are discovered after 15 months. The role of the oval cells in relation to the later appearing cholangiocarcinoma is discussed. A review of literature is given.


Pore formation in tablets compressed from binary mixtures as a result of deformation and relaxation of particles.
This paper describes the internal structure of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch. The minimum particle diameter of pregelatinised starch inside tablets compressed from mixtures was calculated from the difference between the initial pore size distribution and the pore size distribution after removal of the starch particles by burning. Subsequently, the tablets were carefully crushed. These powders, consisting of almost only sodium chloride particles, were measured by laser diffraction. It was found that the diameter of the sodium chloride particles hardly changed, whereas the minimum diameter of starch particles strongly decreased during the compaction process. As an effect of the difference in yield pressure, the harder sodium chloride particles cause deformation of the softer starch particles, resulting in a change in particle shape. The pore size distribution of tablets compressed from mixtures of sodium chloride and starch is typically that of viscoelastic materials; the larger pores (>5 microm) change, while the small pores stay constant in number and size. The median pore diameter in tablets compressed from the mixtures is higher than the median pore diameter in tablets compressed from the pure materials. This paper shows that the formation of large pores was the result of the extra porosity expansion of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch.


Comparative Analysis of Rural-Urban Definitions in Predicting Surgeon Workforce Supply.
There are multiple different systems that define a rural area in health services research, but few studies compare their ability to measure access to health resources. Our objective was to compare various definitions of rurality to determine which system best measures local surgeon supply. In this retrospective observational study, we used the 2019 Area Health Resource File to obtain the 2017 county-level supply of general surgeons, surgical subspecialists, and total physicians for all counties in the United States. Physicians per 100,000 population were calculated for each physician measure and were the primary outcomes. The rural-urban measurements included were the Office of Management and Budget 2017 definition, Urban Influence Codes (UIC), Rural-Urban Commuting Codes (RUCCs), and Census urban population within the county. We also developed and tested a measure combining the RUCCs and Census urban population. Linear regression was used to compare performance of these definitions for each outcome using adjusted R2 values. In 3138 counties included in the study, dichotomous measures of rural-urban using the UIC/RUCC had the lowest adjusted R2 values across all outcomes. Quartiles using the Census urban population and the RUCC/Census urban population combined measure had the highest adjusted R2 values for all outcomes. The Census urban population had the best performance in measuring geographic access to surgical care. This study can inform surgical health services researchers who want to include measures of rurality in their analysis.


A review of factors affecting biosynthesis of carotenoids by the order Mucorales.
This is a review of factors affecting carotenogenesis by the order Mucorales which includes Phycomyces blakesleeanus, Choanephora cucurbitarum and Blakeslea trispora. The Mucorales have opposite sex types and when mated, beta-carotene production is increased 15 to 20 times. Trisporic acids are the substances produced upon mating which stimulate carotenogenesis. Structural analogs have been shown to mimic the actions of the trisporic acids. The common denominator of the stimulators is the ionone ring and the hydrocarbon side chain. Secondary metabolism is discussed as well as the use of food byproducts to stimulate, specifically, the production of beta-carotene by B. trispora.


Butyrate alleviates PTZ-induced mitochondrial dysfunction, oxidative stress and neuron apoptosis in mice via Keap1/Nrf2/HO-1 pathway.
This study aims to evaluate the neuroprotective effect of sodium butyrate against the pentylenetetrazol (PTZ)-induced kindling epilepsy. Sodium butyrate (SB) (5, 10 and 20 mg/kg) and sodium valproate for 40 days and PTZ (37 mg/kg) injection every day were conducted for Kunming mice, to investigate seizure intensity and latency, oxidative stress parameters, mitochondrial structure and function, histopathology, and Keap1/Nrf2/HO-1 expressions. It is shown that seizure latency was effectively increased and the intensity of seizures decreased by treatment with sodium butyrate. It was also found to reverse the structural disruption of the mitochondria, reduce the ROS level and improve the levels of NAD + and ATP in the brains of epileptic mice. Furthermore, pretreatment with SB led to an increase in antioxidant enzyme activity (CAT, SOD and GSH-PX) in the brain as well as conferred a neuroprotective effect against neuron loss and apoptosis. The activation of Keap1/Nrf2/HO-1 signals was also identified, in which the antiepileptic effect of SB may be partially due to its anti-mitochondrial injury and neuroprotective activities. Accordingly, the results of a series of functional tests indicate a significant improvement of neurological function following SB treatment. In a mouse model of seizures, brain injury and neurological deficits can be attenuated by treatment with butyrate through the activation of Nrf2 pathway and the improvement of mitochondrial function.


Crystals of Lumbricus erythrocruorin.
Lumbricus terrestris erythrocruorin, a 3.9 X 10(6) Mr respiratory protein, has been crystallized in four different forms. Despite the high molecular symmetry apparent from images in electron micrographs, only one crystal form expresses any molecular symmetry as crystallographic symmetry. The lattice parameters provide upper limits on the molecular dimensions of 267 A X 308 A X 172 A (1 A = 0.1 nm), which agree well with dimensions obtained from electron micrographs of negatively stained molecules. We have collected diffraction data to 5.5 A from type III crystals and have begun a structural analysis.


Suppression of radiation damping in high-resolution NMR.
The radiation damping field induced by an intense NMR line can be counterbalanced by a DANTE sequence of small flip angle pulses of opposite phase applied during the free induction decay. The transient NMR signal is acquired, one complex data point at a time, in the intervals between these DANTE pulses. As the intense signal decays, reducing the radiation damping field, the flip angles of the DANTE pulses are reduced at a matching rate. An experimental test on an aqueous solution of d-glucose demonstrates a reduction in linewidth at half height from 13.5 to 0.8 Hz, revealing a weak doublet response previously hidden under the broad water line.


The influence of the opioid pentapeptide methionine-enkephalin on seasonal and FSH-induced ovarian recrudescence in the gecko Hemidactylus frenatus.
Although methionine-enkephalin (M-ENK) is implicated in the regulation of reproductive functions in vertebrates, its function in reptiles is little understood. This study aims to elucidate the role of M-ENK on seasonal and follicle stimulating hormone (FSH)-induced ovarian recrudescence in the gecko Hemidactylus frenatus. In the first experiment, administration of 5 µg M-ENK did not affect germinal bed activity or follicular developmental stages I, II, and III (previtellogenic) and IV (vitellogenic), but there were no stage V (vitellogenic) follicles in the ovary. However, there was a significant decrease in the mean numbers of oogonia and primary oocytes in the germinal bed associated with the complete absence of stage IV and V follicles in 25 µg M-ENK-treated lizards in contrast to experimental controls. Furthermore, there was a significant decrease in gonadotropin-releasing hormone - immunoreactive (GnRH-ir) content in the median eminence (ME) and pars distalis (PD) of the pituitary gland and sparse labelling of hypothalamic GnRH-ir neurons in 25 µg M-ENK-treated lizards. In the second experiment, treatment with FSH during the regression phase of the ovarian cycle resulted in the appearance of stage IV and V follicles, in contrast to their absence in the initial controls and treatment controls. However, treatment with 25 µg M-ENK + FSH did not result in the appearance of these follicles, indicating the inhibitory effect of M-ENK on FSH-induced ovarian recrudescence. These findings suggest that M-ENK inhibits the germinal bed and vitellogenic follicular growth in a dose-dependent manner, possibly mediated through the suppression of GnRH release in the ME and PD. In addition, M-ENK may also act at the level of the ovary in the gecko.


Influence of the Building Unit on Covalent Organic Frameworks in Mediating Photo-induced Energy-Transfer Reversible Complexation-Mediated Radical Polymerization (PET-RCMP).
Two imine-based covalent organic framework photocatalysts with different building units, TPB-DMTA-COF and TAT-DMTA-COF, for photo-induced energy transfer reversible complexation-mediated radical polymerization (PET-RCMP) were developed and investigated, producing ideal polymers with accurate molecular weight and moderate dispersity under visible light irradiation. The chain extension and spatiotemporal control experiments revealed the high chain-end fidelity of polymers and the compatibility of RCMP processes in both bulk and aqueous system. Moreover, density functional theory (DFT) calculations verified that heteroatom-doped TAT-DMTA-COF exhibits higher activities for weakening C-I bond energy barrier, which promotes PET-RCMP polymerization performance. This work demonstrates that rational adjustment of building block for constructing COF heterogeneous photocatalyst can enhance the catalytic performance of PET-RCMP, providing a design methodology for the development of polymeric organic photoelectric semiconductor catalysts to mediate RCMP.


Time course of development of changes in the structure and reactivity of small veins from portal hypertensive rabbits.
1. Myographic and histological techniques were used to study the mechanical and morphological properties of oesophageal and mesenteric veins from rabbits subjected to 0, 4, 14 and 90 days of partial portal vein stenosis. 2. The stenosis caused an immediate increase in portal pressure from 10.5 mmHg (1.4 kPa) to 20.5 mmHg (2.7 kPa); the pressure returned to the control level by 90 days. 3. The lumen diameter of oesophageal veins was increased by 76% after 4 days and by 147% after 90 days, while that of the mesenteric veins was unchanged. The media thickness in both veins increased rapidly, reaching a maximum at 14 days (82%, oesophageal; 56%, mesenteric) and thereafter decreasing. 4. The contractility of oesophageal veins was transiently decreased (at 4 days), while that of the mesenteric veins was transiently increased (at 14 days). 5. In further experiments, sclerosing of the oesophagus, which is believed to restrict flow without reducing pressure, restricted the increase in lumen diameter of oesophageal veins caudal to the sclerosing site, but did not affect the media thickness. 6. The results suggest that, in oesophageal and mesenteric veins, portal pressure is a primary determinant of media thickness but not of lumen diameter.


[General review of rhinolithiases].
The aim of this study was to analyze the clinical presentation and characteristics of rhinolithiasis, a rare and forgotten entity. Between 1990 and 2007, 20 cases of rhinolithiasis presented for consultation. The clinical course noted chronic nasal discharge associated with nasal obstruction. The protocol was the same for all patients: history of disease, meticulous endonasal endoscopy and plain radiography (+/-CT scan). Rhinolithiasis was found in adults (55%), females, patients living in rural areas (66%) with unfavorable socioeconomic conditions. The diagnosis delay varied between six months and eight years. The examination showed the rhinolith in the form of a grey concretion, primarily unilateral and on the right-hand side in 60% of the patients. Only one bilateral case presented following destruction of the posterior nasal septum. The rhinolith measured between 5 and 50mm in diameter with only three associated foreign bodies (15%). The rhinolith was extracted through the natural pathways under local anesthesia in 60% of the cases. Complications were rare (epistaxis 10%) and favorable progression without recurrence was generally observed after a mean 16 months of follow-up (range, six months to 11 years). Chronic nasal discharge without a history of rhinologic disease requires an endonasal examination under good conditions after retraction. Rhinolithiasis is easily recognized, in particular on imaging studies. Treatment is simple and curative in the majority of cases.


Polyethylene fibre reinforced poly(methylmethacrylate)--water sorption and dimensional changes during immersion.
The reinforcement of acrylic denture base resin with high performance polyethylene fibre in chopped, woven and continuous parallel forms resulted in significant reductions in water sorption and dimensional changes during immersion. The dimensional changes during immersion mainly occur during the non-steady state of the diffusion process.


Prognostic relevance of autophagy-related markers p62, LC3, and Beclin1 in ovarian cancer.
To analyze the expression of autophagy markers p62, LC3, and Beclin1 in ovarian cancer tissue and evaluate the prognostic potential of these markers. The study enrolled 328 patients: 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. The expression of p62, LC3, and Beclin1 was analyzed in central and invasive tumor segments with immunohistochemistry combined with tissue microarray. The expression levels of the analyzed markers were correlated with relevant histopathology parameters. The expression of all analyzed markers was most remarkable in epithelial ovarian carcinoma. There was a strong positive correlation between the expressions of p62 and LC3, while these two markers negatively correlated with Beclin1. High-grade serous carcinoma had higher p62 and LC3 levels, and lower Beclin1 levels than other tumor types. This expression profile was also observed in more advanced tumor stages. Prominent p62 and LC3 expression in combination with weak Beclin1 expression in high-grade serous carcinoma indicates potential for the application of autophagy inhibitors in patients with this tumor subtype.


The Conundrum of Online Prescription Drug Promotion Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".
This commentary discusses pertinent issues from Hyosun Kim's paper on online prescription drug promotion. The study is well-designed and the findings highlight some of the consequences of the Food and Drug Administration's (FDA's) decision to deregulate online advertising of prescription drugs. While Kim's findings confirm some of the early concerns, they also provide a perspective of implementation challenges in the ever-changing technological environment.


Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (Il10ra) and its association with the autoimmune phenotype.
Several studies suggest that interleukin (IL)-10 pathway is involved in murine lupus, while no linkage of IL-10 gene polymorphism to disease susceptibility has been reported in studies with lupus-prone mice. Since IL-10 functions through the specific IL-10 receptor alpha (IL-10RA) chain and the IL-10RA gene (Il10ra) is linked to the susceptibility loci of atopic dermatitis and Crohn's disease identified using mouse models, we supposed that IL-10RA might be involved in murine lupus. By flow cytometry analysis, we found that NZW mice, one of the parental strains of lupus-prone (NZBxNZW) F1 mice, express extremely low levels of IL-10RA compared with NZB mice, the other parental strain, and the healthy BALB/c and C57BL/6 mice. Sequence analyses of Il10ra cDNA of NZW mice showed multiple nucleotide mutations compared with that of NZB and C57BL/6 strains, some of which would result in amino acid substitutions in the IL-10RA protein. Lupus-prone MRL mice shared the same polymorphism with NZW. Analyses using (NZBxNZW) F1xNZB backcross mice showed that high serum levels of IgG antichromatin antibodies were regulated by a combinatorial effect of the NZW Il10ra allele and a heterozygous genotype for Tnfa microsatellite locus. Our data suggest that the polymorphic NZW-type Il10ra may be involved in the pathologic production of antichromatin antibodies and, if so, may contribute in part to the development of systemic lupus erythematosus as one susceptibility allele.


PCR-based subtraction analyses for upregulated gene transcription in cadmium-exposed rat lung type 2 epithelial cells.
The aim of this study was to gain insight into early events in the lung epithelial cells following acute Cd exposure. We adopted the polymerase chain reaction (PCR)-based subtraction technique and found several genes that were upregulated in immortalized rat lung type 2 epithelial cells (SV40T2). The upregulation of those genes was confirmed by Northern blot analysis and categorized into three groups (highly, moderately, and weakly inducible genes). Heme oxygenase-1 (HO-1), HSP 72, hepatic steroid hydroxylase/CYPIIA2, and Cd-inducible gene 1 (cdig1, a new gene, Accession Nos. AB086233 and AB086234) were highly inducible genes, testosterone-repressed prostate message 2 mRNA was moderately inducible, and collagen-binding protein and cdig2 (another new gene, Accession No. AB086193) mRNAs were weakly inducible. The expression of cdig1 increased linearly with time up to 9h, while that of HO-1 reached the maximum value at 4h in response to 10 microM Cd.


Crystals of SctV from different species reveal variable symmetry for the cytosolic domain of the type III secretion system export gate.
Type III secretion systems (T3SSs) are proteinaceous devices employed by Gram-negative bacteria to directly transport proteins into a host cell. Substrate recognition and secretion are strictly regulated by the export apparatus of the so-called injectisome. The export gate SctV engages chaperone-bound substrates of the T3SS in its nonameric cytoplasmic domain. Here, the purification and crystallization of the cytoplasmic domains of SctV from Photorhabdus luminescens (LscVC) and Aeromonas hydrophila (AscVC) are reported. Self-rotation functions revealed that LscVC forms oligomers with either eightfold or ninefold symmetry in two different crystal forms. Similarly, AscVC was found to exhibit tenfold rotational symmetry. These are the first instances of SctV proteins forming non-nonameric oligomers.


Frequency-dependent shear viscosity, sound velocity, and sound attenuation near the critical point in liquids. III. The shear viscosity.
We compare theoretical results for the shear viscosity calculated in one-loop order within the field-theoretical method of the renormalization-group theory with experiments. Our expressions describe the nonasymptotic crossover in both temperature and density, and allow us to consider effects of finite gravitation and finite frequency at which the experiments are performed. In doing so we treat the critical exponent x(eta) of the shear viscosity as an independent parameter, keeping the one-loop value of the Kawasaki amplitude fixed. Within our model we also consider the temperature and density dependence of the thermal diffusion including gravitational effects.


Helminths and allergy: the example of tropomyosin.
Parasitic worms contain potent allergens, but epidemiological and experimental studies suggest that infections with certain helminths are negatively associated with the prevalence of allergic diseases. This seeming contradiction can be addressed by using filarial tropomyosin as an example. This protein shares structural features and crossreacting B-cell epitopes with other highly allergenic invertebrate tropomyosins. Nevertheless, it usually does not provoke allergic disease in infected individuals. In addition, it is one of the most prominent candidates for an anti-nematode vaccine. Recent data suggest mechanisms that might prevent hosts from developing allergic reactions against allergens of their parasites, such as filarial tropomyosin.


Alterations of acidic phospholipids in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis.
We analyzed phospholipids, especially the acidic phospholipids, i.e. phosphatidylglycerol (PG) and phosphatidylinositol (PI), of bronchoalveolar lavage (BAL) fluids from patients with pulmonary alveolar proteinosis. A significant decrease in PG and a concomitant increase in PI were found in the phospholipid of the patient's BAL fluids compared to that of normal subjects. Thus, the PG to PI ratio was significantly decreased in pulmonary alveolar proteinosis. These changes in the acidic phospholipids in BAL fluids of patients with pulmonary alveolar proteinosis appear to indicate that a switch-over in the synthesis of both acidic phospholipids from a same precursor CDP-diacylglycerol (CDP-DG) in alveolar Type II cells occurs in a such diseased state. However, since the molecular species profiles of PG and PI in the patient's BAL fluids were distinctly different from each other, the PG and PI present in the alveoli of the patients appeared to be derived from different pools of CDP-DG in alveolar Type II cells.


Utilization trends of cervical artificial disc replacement during the FDA investigational device exemption clinical trials compared to anterior cervical fusion.
While anterior cervical discectomy and fusion (ACDF) is the gold standard surgical treatment for cervical disc disease, concerns regarding adjacent segment degeneration lead to the development of cervical disc arthroplasty (CDA). This study compares the utilization trends of CDA versus ACDF during the period of the Food and Drug Administration Investigational Device Exemption clinical trials from 2004 to 2007. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the USA between 2004 and 2007. The prevalence of CDA and ACDF procedures was estimated and stratified by age, sex, diagnosis, census region, payor class, and hospital characteristics. The average length of hospital stay, total charges, and costs were also estimated. The number of CDA surgeries significantly increased annually from 2004 to 2007 and mostly took place at urban non-teaching hospitals. There were no regional differences between CDA and ACDF utilization. There was no difference between sex or admission type between CDA and ACDF patients. ACDF patients were older and had more diabetes, hypertension, and chronic obstructive pulmonary disease. CDA patients were more likely to be discharged home and had shorter hospital stays but had a higher rate of deep venous thrombosis than ACDF patients. Significantly more CDA patients had private insurance while more ACDF patients had Medicare. The average cost was higher for ACDF than CDA. While ACDF dominated surgical intervention for cervical disc disease during the trial period, CDA utilization increased at a significantly greater rate suggesting rapid early adoption.


Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia.
Apoptosis of cardiomyocytes, under ischemic conditions, has been identified as an essential process in the progression of heart failure. Under hypoxic conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). As ROS appear to have a critical role in heart failure, there has been considerable interest in identifying the candidate proteins involved and in developing strategies to reduce oxidative stress. Lon protease (Lon) is a multifunctional protein that mediates protein quality control and stress response in mitochondria. However, comprehensive and detailed studies, on the role of Lon in hypoxia-induced cardiomyocyte apoptosis, have yet to be carried out. In the present study, we demonstrated that hypoxia induced ROS-dependent cardiomyocyte apoptosis. Lon was upregulated in hypoxia-induced cardiomyocytes. Lon downregulation attenuated hypoxia-induced cardiomyocyte apoptosis through a reduction of ROS level. Moreover, overexpression of Lon stimulated ROS production and induced apoptosis under normoxic conditions in cardiomyocytes. Our results identify Lon as a novel regulator of cardiomyocyte fate and offers exciting new insights into the therapeutic potential of hypoxia-induced cardiomyocyte apoptosis.


Frames and counter-frames giving meaning to dementia: a framing analysis of media content.
Media tend to reinforce the stigmatization of dementia as one of the most dreaded diseases in western society, which may have repercussions on the quality of life of those with the illness. The persons with dementia, but also those around them become imbued with the idea that life comes to an end as soon as the diagnosis is pronounced. The aim of this paper is to understand the dominant images related to dementia by means of an inductive framing analysis. The sample is composed of newspaper articles from six Belgian newspapers (2008-2010) and a convenience sample of popular images of the condition in movies, documentaries, literature and health care communications. The results demonstrate that the most dominant frame postulates that a human being is composed of two distinct parts: a material body and an immaterial mind. If this frame is used, the person with dementia ends up with no identity, which is in opposition to the Western ideals of personal self-fulfilment and individualism. For each dominant frame an alternative counter-frame is defined. It is concluded that the relative absence of counter-frames confirms the negative image of dementia. The inventory might be a help for caregivers and other professionals who want to evaluate their communication strategy. It is discussed that a more resolute use of counter-frames in communication about dementia might mitigate the stigma that surrounds dementia.


Lipopolysaccharide structures of Helicobacter pylori wild-type strain 26695 and 26695 HP0826::Kan mutant devoid of the O-chain polysaccharide component.
We describe a re-investigation of the structure of the lipopolysaccharide (LPS) from Helicobacter pylori genomic strain 26695 and its corresponding HP0826::Kan mutant lacking the O-chain component based on the in-depth NMR analysis of the oligosaccharide products obtained through the use of various degradation procedures performed on the purified LPS from both strains, as well as CE-MS data. New structural evidence indicates the presence of the linear arrangement of glucan and heptan portions of the LPS attached through -6-α-DDHep-3-α-L-Fuc-3-β-GlcNAc- fragment to the inner core DD-heptose residue. This structure differs from previously reported structures of the H. pylori 26695 LPS in several aspects.


A catalytic role for proangiogenic marrow-derived cells in tumor neovascularization.
Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing different tumor angiogenesis models, both find that activated MMP-9 delivered by BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The changes in microvascular anatomy induced by MMP-9-expressing BMDCs are strikingly different between the preirradiated tumor vascular bed model employed by Ahn and Brown and the invasive glioblastoma model utilized by Du et al., likely mirroring the complexity of the real tumor microenvironment and the intricacy of roles of different BMDC populations in mediating tumor neoangiogenesis.


Non-invasive measurement of circadian clock activity in the turquoise killifish.
Non-invasive measurement of circadian rhythms is important for longitudinal assays of the rhythmic swimming behavior of the turquoise killifish (Nothobranchius furzeri). Here, we introduce a custom-built, video-based system for non-invasive circadian rhythm measurement. We describe imaging tank setup, video recording and editing, and fish movement tracking. We then detail circadian rhythm analysis. This protocol can be used for repetitive and longitudinal analysis of circadian rhythms in the same fish with minimal stress and can be applied to other fish species. For complete details on the use and execution of this protocol, please refer to Lee et al..1.


Dental erosions and other extra-oesophageal symptoms of gastro-oesophageal reflux disease: Evidence, treatment response and areas of uncertainty.
Extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD) are often studied, but remain a subject of debate. It has been clearly shown that there is a relationship between the extra-oesophageal symptoms chronic cough, asthma, laryngitis and dental erosion and GORD. Literature is abundant concerning reflux-related cough and reflux-related asthma, but much less is known about reflux-related dental erosions. The prevalence of dental erosion in GORD and vice versa, the prevalence of GORD in patients with dental erosion is high but the exact mechanism of reflux-induced tooth wear erosion is still under review.


Endocrine disrupting compounds in municipal and industrial wastewater treatment plants in Northern Greece.
The occurrence and fate of endocrine disrupting compounds (EDCs) in a sewage treatment plant and two industrial wastewater treatment plants from textile and tannery factories were investigated. EDCs of interest are 4-nonylphenol, 4-octylphenol, their ethoxylate oligomers (mono- and di-ethoxylates of nonylphenol and octylphenol), bisphenol A, triclosan and steroid estrogens. Target compounds were determined in dissolved fraction, total suspended solids and sludge by employing solid phase extraction and ultrasonication followed by gas chromatography-mass spectrometry. Nonylphenols and oligomers with one or two ethoxy groups were the most abundant compounds in raw wastewater as well as in effluents from all the treatment stages of sewage treatment plant, followed by triclosan and bisphenol A. Steroids were found at very low concentrations. Almost all phenolic EDCs compounds were predominantly associated to suspended solids in influents whereas the dissolved fraction dominated the treated effluents. High removal rates, ranging from 86% to 99%, were observed throughout the whole treatment process. Biodegradation was the main removal pathway of EDCs. Tannery wastewaters exhibited high concentrations of nonylphenolic compounds. This type of wastewaters could pose a significant risk to the aquatic and terrestrial environment.


A high-throughput SNP discovery strategy for RNA-seq data.
Single nucleotide polymorphisms (SNP) have been applied as important molecular markers in genetics and breeding studies. The rapid advance of next generation sequencing (NGS) provides a high-throughput means of SNP discovery. However, SNP development is limited by the availability of reliable SNP discovery methods. Especially, the optimum assembler and SNP caller for accurate SNP prediction from next generation sequencing data are not known. Herein we performed SNP prediction based on RNA-seq data of peach and mandarin peel tissue under a comprehensive comparison of two paired-end read lengths (125 bp and 150 bp), five assemblers (Trinity, IDBA, oases, SOAPdenovo, Trans-abyss) and two SNP callers (GATK and GBS). The predicted SNPs were compared with the authentic SNPs identified via PCR amplification followed by gene cloning and sequencing procedures. A total of 40 and 240 authentic SNPs were presented in five anthocyanin biosynthesis related genes in peach and in nine carotenogenic genes in mandarin. Putative SNPs predicted from the same RNA-seq data with different strategies led to quite divergent results. The rate of false positive SNPs was significantly lower when the paired-end read length was 150 bp compared with 125 bp. Trinity was superior to the other four assemblers and GATK was substantially superior to GBS due to a low rate of missing authentic SNPs. The combination of assembler Trinity, SNP caller GATK, and the paired-end read length 150 bp had the best performance in SNP discovery with 100% accuracy both in peach and in mandarin cases. This strategy was applied to the characterization of SNPs in peach and mandarin transcriptomes. Through comparison of authentic SNPs obtained by PCR cloning strategy and putative SNPs predicted from different combinations of five assemblers, two SNP callers, and two paired-end read lengths, we provided a reliable and efficient strategy, Trinity-GATK with 150 bp paired-end read length, for SNP discovery from RNA-seq data. This strategy discovered SNP at 100% accuracy in peach and mandarin cases and might be applicable to a wide range of plants and other organisms.


An extensive polymerase chain reaction-allele-specific polymorphism strategy for clinical ABO blood group genotyping that avoids potential errors caused by null, subgroup, and hybrid alleles.
ABO genotyping is complicated by the remarkable diversity at the ABO locus. Recombination or gene conversion between common alleles may lead to hybrids resulting in unexpected ABO phenotypes. Furthermore, numerous mutations associated with weak subgroups and nondeletional null alleles should be considered. All known ABO genotyping methods, however, risk incorrect phenotype predictions if any such alleles are present. An extensive set of allele-specific primers was designed to accomplish hybrid-proof multiplex polymerase chain reaction (PCR) amplification of DNA fragments for detection of ABO alleles. Results were compared with serologic findings and ABO genotypes defined by previously published PCR-restriction fragment length polymorphism/PCR-allele-specific polymorphism (ASP) methods or DNA sequencing. Phenotypically well-characterized samples from blood donors with common blood groups and rare-subgroup families were analyzed. In addition to the commonly encountered alleles (A1, A1(467C>T), A2, B, O1, O1v, and O2), the new method can detect hybrid alleles thanks to long-range amplification across intron 6. Four of 12 PCR-ASP procedures are used to screen for multiple infrequent subgroup and null alleles. This concept allows for a low-resolution typing format in which the presence of, for example, a weak subgroup or cis-AB/B(A) is indicated but not further defined. In an optional high-resolution step, more detailed genotype information is obtained. A new genotyping approach has been developed and evaluated that can correctly identify ABO alleles including nondeletional null alleles, subgroups, and hybrids resulting from recombinational crossing-over events between exons 6 and 7. This approach is clinically applicable and decreases the risk for erroneous ABO phenotype prediction compared to previously published methods.


Interaction of cholesterol with saturated phospholipids: role of the C(17) side chain.
Cholesterol and 5-androsten-3 beta-ol differ structurally only in the presence of an eight carbon side chain at the C(17) position in the former sterol. Both molecules decrease the main transition enthalpy change (delta H) in a series of phosphatidylcholines and phosphatidylethanolamines, of acyl chain length n, with the reduction being a linear function of sterol concentration (c). The sterol concentrations at which delta H = 0 bear a straight line relationship to n and are equivalent for both cholesterol and 5-androsten-3 beta-ol. In addition, both sterols give identical delta H versus c slopes. These results underscore the importance of acyl chain length in the cholesterol/phospholipid interaction and also indicate that the cholesterol C(17) side group is not an essential requirement for the capacity of the sterol to decrease the enthalpy change of the main transition.


The impact of sarcopenia on outcomes in patients with inflammatory bowel disease undergoing colorectal surgery.
Sarcopenia is an independent predictor of poor post-operative outcomes following major surgery. Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC), which are chronic inflammatory conditions involving the gastrointestinal system. Evidence demonstrates that up to 60% of patients with IBD have sarcopenia. Despite advances in medical management, more than 15% of patients with UC and 80% with CD eventually require surgical intervention. The primary aim of the study was to assess the impact of sarcopenia on post-operative anastomotic leak rates. A retrospective cohort study of patients at Royal Perth Hospital who underwent major abdominal surgery for management of IBD between January 2010 and December 2020 was performed. Sarcopenia was assessed according to the skeletal muscle index at the level of the third lumbar vertebrae using the cut off 52.4 and 38.5 cm2 /m2 for men and women, respectively. A total of 147 patients were included. The prevalence of sarcopenia within the study population was 36.1%. Patients with sarcopenia were significantly taller (P = 0.025) and were more likely to be on pre-operative steroid medications (P = 0.045). There was no difference in the remaining baseline characteristics between sarcopenic and non-sarcopenic patients. Patients with sarcopenia were more likely to develop a post-operative anastomotic leak (OR:11.303, 95% CI, 1.53-83.51, P = 0.017), grade IV complications (OR:6.79, 95%CI:1.1-43.6, P = 0.044) and require total parenteral nutrition (TPN) (OR:3.212, 95% CI:1.3-8.1, P = 0.013). Sarcopenia significantly increases the risk of major post-operative complications for patients with IBD undergoing colorectal surgery.


Lab at home: a promising prospect for on-site chemical and biological analysis.
The continuing pursuit for a healthy life has led to the urgent need for on-site analysis. In response to the urgent needs of on-site analysis, we propose a novel concept, called lab at home (LAH), for building automated and integrated total analysis systems to perform chemical and biological testing at home. It represents an emerging research area with broad prospects that has not yet attracted sufficient attention. In this paper, we discuss the urgent need, challenges, and future prospects of this area, and the possible roadmap for achieving the goal of LAH has also been proposed.


Lymphoid antigenic determinants of the chicken: ontogeny of bursa-dependent lymphoid tissue.
The ontogenic development of the bursa-dependent lymphoid tissue in the chicken has been studied using rabbit antisera specific for B lymphocyte sub-populations and two elements of the bursal microenvironment. The antigens investigated were: the chicken B lymphocyte antigen ( CBLA ); mature B lymphocyte antigen ( CMBLA ); a foetal-associated antigen ( CFAA ) present on embryonic haemopoietic cells and adult bone marrow and bursa cells; immunoglobulin (Ig) and IgG; a bursa-specific cortical reticulin fibre antigen ( CBRFA ); a gut-associated mucin antigen ( CGAMA ) present on bursal medullary reticular epithelial (REp) cells. The development of suspected precursor cells was examined using a rabbit antiserum specific for foetal spleen cells. The major finding was the interrelationship between developing B cells and the bursal microenvironment. The first CBLA - and CFAA -positive cells were detected in the bursa at day 8 of incubation but their precise localization was difficult to assess. In 12-15 day embryos, both these cells were found predominantly in the tunica-propria in close proximity to cells bearing the reticulin fibre antigen CBRFA . This close association between CBLA -, CFAA - and CBRFA determinants represents the earliest stages of B cell differentiation and mimics that found in the adult bursa cortex. By day 18, the majority of bursa cells expressed CBLA and Ig and were localized in the developing medullary follicles, the REp cells of which were CGAMA -positive, demonstrating a very early interaction between intestinal tract contents, bursal REp cells and B cell maturation. Around hatching some bursa cells showed a marked increase in the membrane expression of CBLA and Ig, and the simultaneous expression of CMBLA and IgG. These cells were present in medullary follicles; CBRFA was present on cortical reticulin fibres which provided a supporting framework for the more immature CFAA -positive cells.


Rectal v. intravenous administration of indomethacin in the treatment of renal colic.
Rectal administration of 100 mg indomethacin in solution had as good, and almost as rapid, an effect on renal colic as 50 mg given intravenously. Side effects were significantly fewer with the rectal than with the intravenous route.


Choosing a CEO: the necessity of shared Christian values.
The CEO candidate and the Catholic health care facility must clarify expectations and determine if the candidate's values can be expressed administratively to mesh with the organization's philosophy.


In Situ AFM Imaging of Microstructural Changes Associated with The Spin Transition in [Fe(Htrz)₂(Trz)](Bf₄) Nanoparticles.
Topographic images of [Fe(Htrz)₂(trz)](BF₄) nanoparticles were acquired across the first-order spin transition using variable-temperature atomic force microscopy (AFM) in amplitude modulation mode. These studies revealed a complex morphology of the particles consisting of aggregates of small nanocrystals, which expand, separate and re-aggregate due to the mechanical stress during the spin-state switching events. Both reversible (prompt or slow recovery) and irreversible effects (fatigue) on the particle morphology were evidenced and correlated with the spin crossover properties.


The effect of the microtubule inhibitor tubulozole-C on the tegument of triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica.
The benzimidazole derivative, triclabendazole is the main drug used against Fasciola hepatica, although its precise mode of action remains to be fully determined. Previous studies have suggested that triclabendazole acts as a microtubule inhibitor in the same manner as tubulozole-C. Consequently, flukes from triclabendazole-susceptible and triclabendazole-resistant isolates were treated with tubulozole-C (1x10(-6 )M) in vitro and changes in tegumental morphology and tubulin distribution within the tegument were monitored by scanning and transmission electron microscopy, together with tubulin immunocytochemistry. Tubulozole-C caused severe disruption within the tegument of triclabendazole-susceptible flukes. Tubulin immunoreactivity diminished within the tegumental syncytium of the triclabendazole-susceptible flukes following treatment with tubulozole-C. In contrast, tubulozole-C caused only minor disruption of the tegument in triclabendazole-resistant F. hepatica and did not significantly alter the pattern of tubulin immunostaining within the tegumental syncytium. The results of the present study indicate that tubulozole-C and triclabendazole share the same target molecule and that triclabendazole-resistant flukes are also cross-resistant to tubulozole-C.


Effect of section thickness on cone beam computed tomography-based measurements of intrabony defects compared with clinical measurements.
It is unknown whether cone beam computed tomography (CBCT) image reconstruction characteristics, including section thickness, may affect linear bone measurements of periodontal intrabony defects. The aim of this study was to compare intrasurgical and CBCT-based linear measurements of intrabony defects focusing on CBCT section thickness. Sixty-six intrabony defects were assessed in 21 patients with chronic generalized severe periodontitis. Linear measurements of alveolar bone (radiographic bone level [rBL]), assessed in CBCT images at diverse section thicknesses: 0.25 mm (voxel size), 1 mm, and 3 mm, were compared with clinical bone level (cBL) measurements obtained intrasurgically. To provide identical reference points for rBL and cBL measurements, individually adjusted grooves on the reference stent were prepared for each periodontal defect site. CBCT measurements were performed in two rounds by two trained observers. Observer agreement was assessed by intraclass correlation coefficients (ICC). ANOVA assessed the difference among cBL and rBL at different section thicknesses. Intra- and inter-observer agreement was excellent (ICC >0.99) and highly significant independent of the observer, evaluation round, and CBCT section thickness. Mean rBL in the diverse CBCT section thicknesses was very close to that measured clinically (cBL). There was no statistically significant difference between cBL and rBL for any section thickness, neither for the overall evaluated sites, nor the maxilla or mandible separately. No statistically significant difference between clinical and radiographic bone level for 0.25-, 1-, and 3-mm CBCT section thicknesses were observed when assessing intrabony periodontal defects.


Myofunctional evaluation after surgery for tonsils hypertrophy and its correlation to breathing pattern: a 2-year-follow up.
To evaluate the myofunctional status in children submitted to adenoidectomy or adenotonsillectomy, correlating the pre and post-surgical patterns throughout a 24-month-period. To correlate the myofunctional alterations to the sort of surgery performed (adenoidectomy versus adenotonsillectomy) and to the predominant post-surgical breathing pattern (predominantly nasal versus allergic rhinitis). Forty children were assessed by the otorhinolaryngologist and speech therapist before and 1-24 months after surgery. In order to evaluate myofunctional status, a pre-structured protocol was designed, which included observations regarding facial posture, tonicity, mastication, deglutition and respiration. A score from 0 (normal pattern) to 12 (highly altered) was set. There was a partial, but progressive decrease of the score after surgery (p < 0.001). This decrease was markedly observed during the first 6 months following surgical procedure (p < 0.001), after which it was no longer significant. There was no correlation between the myofunctional progress and the sort of surgery performed. The myofunctional improvement was more accentuated in nasal breathers when compared to those with allergic rhinitis. Improvement of myofunctional status seems to be observed in children after surgery. In this study, the improvement was predominantly accomplished during the first 6 months following surgical procedure. Persistent pattern of mouth breathing due to allergic rhinitis may difficult recovery of the myofunctional status. The most adequate post-surgical moment for the otorhinolaryngologist to refer the patient to speech therapist for myofunctional therapy seems to be crucial, as well as the recognition by the speech therapist of the persistence of the obstructive symptoms, re-referring this patient to the physician.


Use of Raman spectroscopy to decrease time for identifying the species of Candida growth in cultures.
The objective of this study is to establish Raman signatures from pure cultures of different Candida species using Raman Spectroscopy (RS) and use these signatures for rapid identification of unknown Candida species. Pure cultures of five Candida species were evaluated using RS to build a limited signature library. 'Raman Processing' (RP) software was used for Principal Component Analysis (PCA) and Differential Functional Analysis (DFA). Eleven principal components described at least 95% variance in the spectra. Raman signatures from these known Candida species were able to identify the species of unknown Candida cultures with 100% accuracy. Raman spectroscopy can improve early identification of Candida species and may facilitate early optimal antifungal therapy.


Ustekinumab in bio-naïve and bio-failure Crohn's disease patients: Results from a « real-life » monocentric cohort.
The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients.


Cutaneous leukocytoclastic vasculitis with cervical tuberculous lymphadenitis: a case report and literature review.
Cutaneous leukocytoclastic vasculitis (CLV) is a small-vessel vasculitis localized to the skin. Many possible causes exist for this pathological condition, including drugs, infection, collagen vascular disease, and malignancy. However, Mycobacterium tuberculosis is rarely reported to be associated with CLV. Here, we report a 49-year-old male patient that presented with fever, myalgia, and multiple palpable purpura on both of his legs. The biopsy from the purpura yielded a histologic diagnosis of leukocytoclastic vasculitis. The patient had several enlarged lymph nodes on his right neck, and the biopsy revealed tuberculous lymphadenitis. There were no signs of vasculitis present in the internal organs. After anti-tuberculosis treatment, his fever declined and the skin purpura were completely resolved. Although incidence is rare, tuberculosis should be considered as a possible cause of CLV.


Carbon tetrachloride induced ultrastructural alterations in pancreatic acinar cells and in the hepatocytes. Similarities and differences.
We found that 14C from 14CCl4 gets covalently bound to rat pancreas and liver microsomal lipids. The intensity of this process in 320 times smaller in the former than in the latter organ. We did not detect any cytochrome P-450 (P-450) or ethylmorphine N-demethylase activity in pancreatic microsomes in contrast to the high content of those components occurring in liver. Similarly, CCl4 induced lipid peroxidation is observed in liver preparations but not in pancreas. There was no evidence for any histological alterations in pancreas 24 h after administration of a toxic dose causing marked cnetrolobular necrosis in liver. CCl4 causes profound ultrastructural alterations in the hepatocytes involving early the endoplasmic reticulum, the Golgi complex and the nuclear envelope and later the entire cell. In selected clones of pancreatic acinar cells we observed an intense dilatation in the rough endoplasmic reticulum and polysome detachment from their membranes, the appearance of myelin figures and occasionally of large autophagic vacuoles. No alterations in other organelles were detected but a slight increase in the number of lipid droplets was observed. CH2Cl2 did not behave similarly.


Polymerase chain reaction with insertion sequence-specific and -unrelated primers: a new tool for the identification of IS1548 insertion targets in Streptococcus agalactiae.
We developed a PCR method with outward insertion sequence-specific and -unrelated primers to identify IS1548 targets in the genome of unsequenced Streptococcus agalactiae strains. Our rapid and easy method allowed the identification of previously known but also of yet unnoticed integration sites in the three clinical isolates tested.


Hindsight in the relative abundance, metabolic potential and genome dynamics of uncultivated marine archaea from comparative metagenomic analyses of bathypelagic plankton of different oceanic regions.
Marine planktonic archaea are widespread and abundant in deep oceanic waters but, despite their obvious ecological importance, little is known about them. Metagenomic analyses of large genome fragments allow access to both gene content and genome structure from single individuals of these cultivation-reluctant organisms. We present the comparative analysis of 22 archaeal genomic clones containing 16S rRNA genes that were selected from four metagenomic libraries constructed from meso- and bathypelagic plankton of different oceanic regions (South Atlantic, Antarctic Polar Front, Adriatic and Ionian Sea; depths from 500 to 3000 m). We sequenced clones of the divergent archaeal lineages Group 1A (Crenarchaeota) and Group III (Euryarchaeota) as well as clones from the more frequent Group I Crenarchaeota and Group II Euryarchaeota. Whenever possible, we analysed clones that had identical or nearly identical 16S rRNA genes and that were retrieved from distant geographical locations, that is, that defined pan-oceanic operational taxonomic units (OTUs). We detected genes involved in nitrogen fixation in Group 1A Crenarchaeota, and genes involved in carbon fixation pathways and oligopeptide importers in Group I Crenarchaeota, which could confirm the idea that these are mixotrophic. A two-component system resembling that found in ammonia-oxidizing bacteria was found in Group III Euryarchaeota, while genes for anaerobic respiratory chains were detected in Group II Euryarchaeota. Whereas gene sequence conservation was high, and recombination and gene shuffling extensive within and between OTUs in Group I Crenarchaeota, gene sequence conservation was low and global synteny maintained in Group II Euryarchaeota. This implies remarkable differences in genome dynamics in Group I Crenarchaeota and Group II Euryarchaeota with recombination and mutation being, respectively, the dominant genome-shaping forces. These observations, along with variations in GC content, led us to hypothesize that the two groups of organisms have fundamentally different lifestyles.


Adsorption of Ni2+ and Cu2+ Ions from Wastewater by a Silanized Zeolite Produced with a 3-Mercaptopropyl Trimethoxysilane Modification.
Adsorption characteristics of a silanized zeolite for Ni2+ and Cu2+ ions in water solutions were analyzed by SEM, FTIR and XRD techniques. For ion removal, an optimum ratio of 1 g/L silanized zeolite was obtained for adsorbing a Ni2+ and Cu2+ solution. Equilibrium states at 220 and 108 min were reached for the adsorption of Ni2+ and Cu2+, respectively. In a pH range of 2-6, the modified zeolite demonstrated an excellent resistance to acids by exhibiting a high adsorption capacity, which increased with a larger pH.


Glomus tumour: an analysis of 43 patients and review of the literature.
Glomus tumours are hamartomas derived from the normal glomus body. A total of 43 glomus tumours have been seen over the past 18 years, and are reviewed. Their clinical presentations and pathology are analysed and the continuing difficulty in diagnosis is examined.


Anti-glioma effect of ginseng-derived exosomes-like nanoparticles by active blood-brain-barrier penetration and tumor microenvironment modulation.
Inhibition of tumor growth and normalization of immune responses in the tumor microenvironment (TME) are critical issues for improving cancer therapy. However, in the treatment of glioma, effective nanomedicine has limited access to the brain because of the blood-brain barrier (BBB). Previously, we demonstrated nano-sized ginseng-derived exosome-like nanoparticles (GENs) consisting of phospholipids including various bioactive components, and evaluated anti-tumor immune responses in T cells and Tregs to inhibit tumor progression. It was found that the enhanced targeting ability of GENs to the BBB and glioma induced a significant therapeutic effect and exhibited strong efficacy in recruiting M1 macrophage expression in the TME. GENs were demonstrated to be successful candidates in glioma therapeutics both in vitro and in vivo, suggesting excellent potential for inhibiting glioma progression and regulating tumor-associated macrophages (TAMs).


A comprehensive understanding about the pharmacological effect of diallyl disulfide other than its anti-carcinogenic activities.
Diallyl disulfide (DADS), an oil-soluble sulfur compound that is responsible for the biological effects of garlic, displays numerous biological activities, among which its anti-cancer activities are the most famous ones. In recent years, the pharmacological effects of DADS other than its anti-carcinogenic activities have attracted numerous attentions. For example, it has been reported that DADS can prevent the microglia-mediated neuroinflammatory response and depression-like behaviors in mice. In the cardiovascular system, DADS administration was found to ameliorate the isoproterenol- or streptozotocin-induced cardiac dysfunction via the activation of the nuclear factor E2-related factor 2 (Nrf2) and insulin-like growth factor (IGF)-phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling. DADS administration can also produce neuroprotective effects in animal models of Alzheimer's disease and protect the heart, endothelium, liver, lung, and kidney against cellular or tissue damages induced by various toxic factors, such as the oxidized-low density lipoprotein (ox-LDL), carbon tetrachloride (CCl4), ethanol, acetaminophen, Cis-Diammine Dichloroplatinum (CisPt), and gentamicin. The major mechanisms of action of DADS in disease prevention and/or treatment include inhibition of inflammation, oxidative stress, and cellular apoptosis. Mechanisms, including the activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase A (PKA), and cyclic adenosine monophosphate-response element binding protein (CREB) and the inhibition of histone deacetylases (HDACs), can also mediate the cellular protective effects of DADS in different tissues and organs. In this review, we summarize and discuss the pharmacological effects of DADS other than its anti-carcinogenic activities, aiming to reveal more possibilities for DADS in disease prevention and/or treatment.


Assessment of Osstell™ and Periotest® systems in measuring dental implant stability (in vitro study).
The objectives of this in vitro study were to investigate the sensitivity and reliability of the Osstell™ systems (Resonance Frequency Analysis - RFA) compared to the Periotest® system in implant bone simulated conditions. Three conditions were simulated: (1) the direct fixture-bone contact and fibrous tissue fixture contact, (2) The different levels of horizontal bone loss, and (3) The hardening implant-bone interface. Forty-nine dental implant fixtures were placed in the center of acrylic cubes. In Part I seven fixtures were placed in direct contact with acrylic and another seven were placed in contact with polyvinyl siloxane impression material as soft interface. Part II: four sets of 0, 2, 4 and 6 mm horizontally exposed fixture samples were made (seven fixtures in each set). Part III: seven fixtures were placed in contact with a thin mix of autopolymerizing resin. The stability of these fixtures was measured using Osstell™ and Periotest® systems. The mean Periotest® value(PTV) and Osstell™ measurements showed a significant difference between the direct contact and soft interface (P < 0.001). These values also showed statistically significant difference between the different levels of horizontally exposed fixture groups (P < 0.001). The level of horizontal fixture exposure was strongly correlated with the PTVS (r = 0.967) and strongly negatively correlated with Implant Stability Quotient (r = -0.946). A strong correlation was found between the Osstell™ readings and the change in the stiffness of the autopolymerizing resin fixture interface group (r = 0.986). Both Osstell™ and Periotest® systems proved to be sensitive in measuring dental implant stability in hard and in soft interfaces. Osstell™ also proved to be sensitive in detecting changes in the fixture interface stiffness. Osstell™ system proved to be more reliable compared to Periotest® system in measuring dental implant stability in hard and in soft interfaces.


Delayed in sensorimotor reflex ontogeny, slow physical growth, and impairments in behaviour as well as dopaminergic neuronal death in mice offspring following prenatally rotenone administration.
The environment is varying day by day with the introduction of chemicals such as pesticides, most of which have not been effectively studied for their influence on a susceptible group of population involving infants and pregnant females. Rotenone is an organic pesticide used to prepare Parkinson's disease models. A lot of literature is available on the toxicity of rotenone on the adult brain, but to the best of our knowledge, effect of rotenone on prenatally exposed mice has never been investigated yet. Therefore, the recent work aims to evaluate the toxic effect of rotenone on mice, exposed prenatally. We exposed female mice to rotenone at the dose of 5 mg/Kg b.w. throughout the gestational period with oral gavage. We then investigated the effects of rotenone on neonate's central nervous systems as well as on postnatal day (PD) 35 offspring. In the rotenone group, we observed slow physical growth, delays in physical milestones and sensorimotor reflex in neonates and induction of anxiety and impairment in cognitive performances of offspring at PD-35. Additionally, immunohistochemical analysis revealed a marked reduction in TH-positive neurons in substantia nigra. Histological examination of the cerebellum revealed a decrease in Purkinje neurons in the rotenone exposed group as compared to the control. The data from the study showed that prenatally exposure to rotenone affects growth, physical milestones, neuronal population and behaviour of mice when indirectly exposed to the offspring through their mother. This study could provide a great contribution to researchers to find out the molecular mechanism and participating signalling pathway behind these outcomes.


Anthropometric indicators of body fat as discriminators of low levels of cardiorespiratory fitness in adolescents.
To evaluate the discriminatory power of anthropometric indicators of body fat (BF) for identifying low levels of cardiorespiratory fitness, as well as the association between cutoff points and low levels of cardiorespiratory fitness in adolescents. This is a cross-sectional study involving 1132 students (age 14-19 years). The following anthropometric variables were measured according to international standards: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), triceps skinfold thickness (TR), subscapular skinfold (SS), suprailiac skinfold (SI), sum of triceps and subscapular skinfolds (∑TR + SS), and sum of triceps, subscapular and suprailiac skinfolds (∑TR + SS + SI). The BF percentage was calculated using the equations of Lohman (1986) (%FL), Slaughter et al. (1988) (%FS), and Boileau et al. (1985) (%FB). Except for TR, WC, WHtR and BMI, boys with values for the other anthropometric indicators (SS, SI, ∑TR + SS, ∑TR + SS + SI, %FL, %FS, %FB) above the cutoff point were more likely to have low levels of cardiorespiratory fitness. Girls with values for TR, ∑TR + SS, %FB and %FL above the cutoff points were more likely to have low levels of cardiorespiratory fitness. Anthropometric indicators had discriminatory power to identify low levels of cardiorespiratory fitness. The reported anthropometric indicators, indexes and equations can be used by healthcare professionals in clinical practice and by school teachers as a simple, fast and inexpensive alternative to identify low levels of cardiorespiratory fitness.


Transient Palatal Tremor and Action Induced Foot and Leg Dystonia due to Hypertrophic Olivary Degeneration: a Case Report.
Hypertrophic olivary degeneration (HOD) is a rare phenomenon that occurs after various insults to the Guillain-mollaret triangle (GMT). HOD is unique because the degeneration of inferior olivary nucleus becomes hypertrophic rather than atrophic. In this study, a 31-year-old woman developed HOD after pontine cavernoma surgery had been performed. The clinical manifestation was involuntary intorsion of right lower extremity during walking, which has not been reported in the literature. The woman also presented with palatal tremor, the most classic symptom of HOD. HOD's imaging trait include olive hypertrophy with increased T2 signal intensity on MRI, which are corresponding to the pathological findings. HOD is a self-limiting disease and excessive treatments are unnecessary.


[Left-helical (PPII-PPII) type of globular protein structure: the level of the left helical type of poly-L-proline II in Kunitz trypsin inhibitor is no less than 43%. Experimental Reper spectrum of the extended left helix].
There is established that the protein trypsin inhibitor Kunitz is a globular protein of (PPII-PPII)-type. The content of poly-L-proline helix is not smaller than 43%. It has been shown by CD method that the transition from an extended left-handed helical structure to alpha-helix arises on heating till the denaturation temperatures. On this assumption the CD spectrum of poly-L-proline II type has been calculated.


[Determination of the effectiveness of plasma exchange in kidney diseases by a biological test].
Plasma toxicity and plasma exchange efficacy were studied in two groups of patients: I gr.--8 patients with various degree of disturbed renal function who did not need hemodialysis treatment; II gr.--9 patients treated by periodic hemodialysis. A biologic toxicity test was used together with the clinical, immunologic and biochemical indices as a criterion for plasma exchange efficacy. The test gives direct information for the total plasma toxicity which is of great advantage and helps in the decision for another plasma exchange.


Empirical Evaluation of the Role of Vocal Fold Collision on Relative Fundamental Frequency in Voicing Offset.
Relative fundamental frequency (RFF) is an acoustic measure of changes in fundamental frequency during voicing transitions. The physiological mechanisms underlying RFF remain unclear. Recent modeling suggests that changes in RFF during voicing offset are due to decreases in overall system stiffness as a direct result of the cessation of vocal fold collision. To evaluate this finding empirically, here we examined whether variable timing between the end of vocal fold collision and the final voicing cycle used to calculate RFF explained the variability in RFF across individual voicing offset utterances. RFF during voicing offset was calculated from /ifi/ utterances produced by 35 participants under endoscopy, with and without vocal effort. RFF was calculated via two methods, in which utterances were aligned by (1) the end of vocal fold collision, or (2) the end of voicing. Analyses of variance were used to determine the effects of vocal effort and RFF method on the mean and standard deviation of RFF. Aligning by vocal fold collision resulted in statistically significantly lower standard deviations. RFF means were statistically higher using the collision method; however, the degree of vocal effort was statistically significant regardless of the method. These results provide empirical evidence to support that decreases in RFF during voicing offset are a result of decreases in system stiffness due to termination of vocal fold collision.


[First clinical experiences with a new cementless knee endoprosthesis for the dog].
This paper reports on the clinical application and first experiences of a newly developed cementless knee endoprosthesis for dogs. The GenuSys knee-endoprosthesis was implanted in 23 knees of 22 dogs with severe gonarthritis and a history of pain. Their body weight ranged from 28 to 55 kg, their age between 5 and 12 years. This knee implant for dogs is a cementless "mobile bearing prosthesis". An additional fixation with one screw is necessary in the femoral component. Currently, there are four standard sizes of the prosthesis available. At the end of the study, 16 of 22 controlled patients (72.7%) were fully weightbearing on the operated limb or only showed a discreet lameness. We observed no complications in 12 cases (54.5%). In 10 cases problems in the course of healing were detected and made or would have made reoperation necessary. The complications noted were subluxation (n = 6, 27.3%), wound infection (n = 3, 13.6%) and a serious decrease in the range of motion (n = 1, 4.5%). Four of these 10 patients (40%) were subsequently healed through surgery. The remaining six dogs (27.3%) were euthanized or underwent arthrodesis of the leg. Sixteen of 22 dogs (72.2%) showed much better weightbearing and an increased quality of life after endoprosthesis of the knee. Although the complication rate was high, we expect better results in the future due to improvements in the equipment and surgical procedure. A definitive conclusion can only be made based on the results of a long-term study.


Bridging the simulation-to-real gap for AI-based needle and target detection in robot-assisted ultrasound-guided interventions.
Artificial intelligence (AI)-powered, robot-assisted, and ultrasound (US)-guided interventional radiology has the potential to increase the efficacy and cost-efficiency of interventional procedures while improving postsurgical outcomes and reducing the burden for medical personnel. To overcome the lack of available clinical data needed to train state-of-the-art AI models, we propose a novel approach for generating synthetic ultrasound data from real, clinical preoperative three-dimensional (3D) data of different imaging modalities. With the synthetic data, we trained a deep learning-based detection algorithm for the localization of needle tip and target anatomy in US images. We validated our models on real, in vitro US data. The resulting models generalize well to unseen synthetic data and experimental in vitro data making the proposed approach a promising method to create AI-based models for applications of needle and target detection in minimally invasive US-guided procedures. Moreover, we show that by one-time calibration of the US and robot coordinate frames, our tracking algorithm can be used to accurately fine-position the robot in reach of the target based on 2D US images alone. The proposed data generation approach is sufficient to bridge the simulation-to-real gap and has the potential to overcome data paucity challenges in interventional radiology. The proposed AI-based detection algorithm shows very promising results in terms of accuracy and frame rate. This approach can facilitate the development of next-generation AI algorithms for patient anatomy detection and needle tracking in US and their application to robotics. • AI-based methods show promise for needle and target detection in US-guided interventions. • Publicly available, annotated datasets for training AI models are limited. • Synthetic, clinical-like US data can be generated from magnetic resonance or computed tomography data. • Models trained with synthetic US data generalize well to real in vitro US data. • Target detection with an AI model can be used for fine positioning of the robot.


Discovery of P2X3 selective antagonists for the treatment of chronic pain.
Purinergic receptor P2X3 has been linked to analgesia in a number of pre-clinical models of pain, and is expressed in the human pain perception pathway. Only few P2X3-selective antagonists have been reported to date. This Letter describes the SAR and in vivo analgesic profile of a novel scaffold of selective P2X3 antagonists.


Kinetics of Angiotensin I alteration of conformation on different hydrophobic interaction chromatographic surfaces.
In the present study, Angiotensin I (Ang I) will be used as model peptide to assess on-column alteration of conformation phenomena. Adsorptive behavior of Ang I on various commercial hydrophobic interaction surfaces (Butyl, Octyl and Phenyl - Sepharose), under different conditions, was investigated. In order to calculate the cis-trans isomerization rate constants of Ang I on the stationary phase's surface, the first and second moments of the proline peptide elution profiles were determined. The activation energies for the isomerization process on Phenyl and Butyl Sepharose were also calculated. Results suggest that the stationary phase catalyzes Ang I isomerization and that catalysis is dependent on hydrophobic interaction ligand nature.


Voriconazole and posaconazole therapy for experimental Candida lusitaniae infection.
The in vitro activity of posaconazole (PSC) and voriconazole (VRC) was tested by using time-kill studies against 3 strains of Candida lusitaniae. Both drugs showed fungistatic activity against all strains. The efficacy of those compounds was evaluated by reducing kidney fungal burden and by determining (1→3)-β-d-glucan serum levels in a murine model of invasive infection of C. lusitaniae. The therapies tested were VRC at 10, 25, or 40 mg/kg/day and PSC at 5, 12.5, or 20 mg/kg/twice a day. All the dosages showed efficacy in a dose-dependant manner being high doses of both antifungals able to sterilize some kidneys after 10 days. With the exception of the strain FMR 9474, against which PSC was more effective than VRC, no differences in reducing tissue burden were found between the treatments. All doses of both antifungals were able to significantly reduce (1→3)-β-d-glucan serum levels with no significant differences between treatments and between the same doses of both drugs.


Regioselective tandem dimethylsulfonium methylide addition-eliminative olefination of diendioates: a novel route to 1,3-butadien-2-ylmalonates.
The appropriate choice of dimethylsulfonium methylide generation conditions enables the highly regioselective tandem ylide addition-eliminative olefination to 1,3-dienedioates providing 1,3-butadien-2-ylmalonates, a novel class of 2-substituted 1,3-dienes suitable for quick assembly of precursors for type 2 intramolecular Diels-Alder reactions.


Comparative study of the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide or chlorpropamide.
This study was designed to compare the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide, chlorpropamide or biguanides in non-insulin-dependent diabetes. It is divided into two parts: a) in the retrospective study (473 subjects), glucose control of patients who were transferred from chlorpropamide, gliclazide, glibenclamide, glibenclamide + biguanide or metformin to the fixed combination glibenclamide-phenformin in the same tablet (2.5 mg and 25 mg, respectively) was monitored. A statistically significant decrease of blood glucose and glycosylated hemoglobin values was found under the combination of glibenclamide-phenformin contained in the same tablet in contrast to the values obtained with the treatment with glibenclamide, gliclazide, chlorpropamide, combination of glibenclamide and biguanides, metformin, and insulin. b) In the prospective study (57 subjects), the patients were transferred from chlorpropamide or gliclazide to glibenclamide for 3 months and then reallocated to the previous treatment for 3 additional months. It was found that under glibenclamide, glucose control was significantly better than under chlorpropamide or gliclazide. In conclusion, glibenclamide, a second generation sulfonylurea, and the fixed combination glibenclamide-phenformin in the same tablet are more effective compared to the other antidiabetic agents here studied and lead to a better control of type II diabetic patients. There was no increase in plasma lactic acid concentration in all patients studied before and after having received the fixed combination of glibenclamide-phenformin in the single tablet form.


Activation of CB1 cannabinoid receptors in the dorsolateral periaqueductal gray reduces the expression of contextual fear conditioning in rats.
Conditioned fear to context causes freezing and cardiovascular changes in rodents and has been used to measure anxiety. It also activates the dorsolateral column of the periaqueductal gray (dlPAG). Microinjections of cannabinoid agonists into the dlPAG produced anxiolytic-like effects in the elevated plus maze, but the effects of these treatments on fear conditioning remains unknown. The objective of this study was to verify if intra-dlPAG injection of the CB1 cannabinoid receptor agonist anandamide (AEA) or the anandamide transport inhibitor AM404 would attenuate behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats submitted to a contextual fear-conditioning paradigm. Male Wistar rats with cannulae aimed at the dlPAG were re-exposed to a chamber where they had received footshocks 48 h before. Fifteen minutes before the test, the animals received a first intra-dlPAG injection of vehicle or AM251, a CB1 receptor antagonist (100 pmol/200 nl), followed 5 min later by vehicle, AEA (5 pmol/200 nl) or AM404 (50 pmol/200 nl). Freezing and cardiovascular responses were recorded for 10 min. Freezing and cardiovascular responses were reduced by administration of either AEA or AM404 into the dlPAG before re-exposition to the aversively conditioned context. These effects were abolished when the animals were locally pretreated with AM251. The latter drug, even at a higher dose (300 pmol), was ineffective when administered alone into the dlPAG. The results suggest that facilitation of endocannabinoid-mediated neurotransmission in the dlPAG, through activation of local CB1 receptors, attenuates the expression of contextual fear responses.


A novel laboratory method for simulating pollinator exposure to agrochemical-laden particulate matter.
Environmental transport and deposition of particulate matter (PM) associated with toxic chemicals has begun to receive attention as a source of risk to pollinators. For example, dust arising from manipulations of insecticide-treated seed has potential to exert toxic effects among non-target insects. Similarly, synthetic steroid growth promoters, antibiotics and multiple insecticides and parasiticides detected in fugitive beef cattle feedyard PM may also negatively impact pollinators since many of these chemicals have been detected on wildflowers and pollinators collected near beef cattle feedyards. Therefore, there is a need to assess risk to pollinators posed by deposition of agrochemical-laden PM, both in the field and the laboratory. Unfortunately, established laboratory methods for simulating PM exposure or toxicity associated with contaminated PM are few and highly situation-specific. Herein we describe development and use of a PM circulation system that can be employed to evaluate toxicity of agrochemical-contaminated PM in the laboratory under controlled conditions. Two model organisms (honeybees (Apis mellifera) and mason bees (Osmia lignaria)) were exposed to agrochemical-free PM in the circulator system, and post-exposure mortality was compared with controls. No significant differences in mortality between exposed and control bees were observed. Next, honeybees and mason bees were exposed to PM spiked with an insecticide known to exert toxic effects to pollinators (thiamethoxam). Bees experienced significantly higher mortality when exposed to thiamethoxam-laden PM at environmentally relevant concentrations as compared to bees exposed to agrochemical-free PM. These results confirm the validity of these methods for use in controlled laboratory PM toxicity tests and offer a source of positive and negative control groups for laboratory and field experiments examining exposure of pollinators to potentially toxic agrochemical-laden PM. This method facilitates generation of more realistic toxicity data than standard contact toxicity tests when pollinator exposure scenarios involve particulate-based agrochemicals or other toxic chemicals.


Hyperactivity: glycogen synthase kinase-3 as a therapeutic target.
The diagnosis of hyperactivity-associated disorders has increased within the past few years. The prevalence of hyperactivity-associated disorders is indicative of the need to more fully understand the underlying causes and to develop improved therapeutic interventions. There is increasing evidence that glycogen synthase kinase-3 (GSK3) mediates locomotor hyperactivity in a number of animal models, and therefore may be a potential target for therapeutic intervention in hyperactivity-associated behaviors. In this review, we discuss 1) the effect of manipulations of GSK3 in the absence of drugs and disorders on locomotor activity, 2) the role of GSK3 in drug-induced hyperactivity in rodents, and 3) regulation of locomotor activity by GSK3 in transgenic mouse models related to specific disorders. These studies link GSK3 regulation and activity to hyperactivity-associated behaviors and disease pathologies.


Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial.
We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.


Mixing regime shapes the community assembly process, microbial interaction and proliferation of cyanobacterial species Planktothrix in a stratified lake.
Lake mixing influences aquatic chemical properties and microbial community composition, and thus, we hypothesized that it would alter microbial community assembly and interaction. To clarify this issue, we explored the community assembly processes and cooccurrence networks in four seasons at two depths (epilimnion and hypolimnion) in a mesotrophic and stratified lake (Chenghai Lake), which formed stratification in the summer and turnover in the winter. During the stratification period, the epilimnion and hypolimnion went through contrary assembly processes but converged to similar assembly patterns in the mixing period. In a highly homogeneous selection environment, species with low niche breadth were filtered, resulting in decreased species richness. Water mixing in the winter homogenized the environment, resulting in a simpler microbial cooccurrence network. Interestingly, we observed a high abundance of the cyanobacterial genus Planktothrix in the winter, probably due to nutrient redistribution and Planktothrix adaptivity to the winter environment in which mixing played important roles. Our study provides deeper fundamental insights into how environmental factors influence microbial community structure through community assembly processes.


Development of the olfactory and accessory lobes in the American lobster: an allometric analysis and its implications for the deutocerebral structure of decapods.
The allometric changes characterizing the growth of the deutocerebrum (midbrain) of the American lobster (Homarus americanus) are studied using computerized three-dimensional reconstructions of serial brain sections. During the embryogenesis of the midbrain, the paired accessory lobes (higher order processing areas) appear later than the paired olfactory lobes (primary olfactory centers), but the former grow faster from their emergence until metamorphosis. The accessory lobes, as they enlarge, shift progressively from a medial to a posterior position in the lateral deutocerebrum. In early juvenile stages the accessory lobes are one of the largest neuropils of the brain. However, these lobes stop growing in adult animals, whereas the brain and olfactory lobes continue to enlarge, albeit at a slow rate. The overall shape of the brain and the relative proportions and locations of the deutocerebral neuropils and associated cell clusters of various lobster ontogenetic stages are similar to those of selected adult decapods. In addition, the relation between deutocerebral organization and brain size seem parallel during lobster development and across crustacean species. Measurements of the brains of 13 species of decapods (illustrated in Sandeman et al. [1993] J. Exp. Zool. 265:112, plus Homarus) indicate the following trends: Small brains possess olfactory lobes but no accessory lobes, larger brains possess accessory lobes that are medial and small relative to the olfactory lobes, and the largest brains contain relatively voluminous posterior accessory lobes. These observations indicate that some differences in the organization of the deutocerebrum are related to absolute brain size in crustaceans and suggest that ontogenetic scaling of proportions may apply to the deutocerebral neuropils of decapods. Peramorphosis and paedomorphosis in the evolution of the decapod brain are considered.


Anticipating manic and depressive transitions in patients with bipolar disorder using early warning signals.
In bipolar disorder treatment, accurate episode prediction is paramount but remains difficult. A novel idiographic approach to prediction is to monitor generic early warning signals (EWS), which may manifest in symptom dynamics. EWS could thus form personalized alerts in clinical care. The present study investigated whether EWS can anticipate manic and depressive transitions in individual patients with bipolar disorder. Twenty bipolar type I/II patients (with ≥ 2 episodes in the previous year) participated in ecological momentary assessment (EMA), completing five questionnaires a day for four months (Mean = 491 observations per person). Transitions were determined by weekly completed questionnaires on depressive (Quick Inventory for Depressive Symptomatology Self-Report) and manic (Altman Self-Rating Mania Scale) symptoms. EWS (rises in autocorrelation at lag-1 and standard deviation) were calculated in moving windows over 17 affective and symptomatic EMA states. Positive and negative predictive values were calculated to determine clinical utility. Eleven patients reported 1-2 transitions. The presence of EWS increased the probability of impending depressive and manic transitions from 32-36% to 46-48% (autocorrelation) and 29-41% (standard deviation). However, the absence of EWS could not be taken as a sign that no transition would occur in the near future. The momentary states that indicated nearby transitions most accurately (predictive values: 65-100%) were full of ideas, worry, and agitation. Large individual differences in the utility of EWS were found. EWS show theoretical promise in anticipating manic and depressive transitions in bipolar disorder, but the level of false positives and negatives, as well as the heterogeneity within and between individuals and preprocessing methods currently limit clinical utility.