The Cytoplasmic domain of transferrin receptor 2 dictates its stability and response to holo-transferrin in Hep3B cells.
Transferrin receptor 2 (TfR2) is a homolog of transferrin receptor 1 (TfR1), the receptor responsible for the uptake of iron-loaded transferrin (holo-Tf) into cells. Unlike the ubiquitous TfR1, TfR2 is predominantly expressed in the liver. Mutations in TfR2 gene cause a rare autosomal recessive form of the iron overload disease, hereditary hemochromatosis. Previous studies demonstrated that holo-Tf increases TfR2 levels by stabilizing TfR2 at the protein level. In this study we constructed two chimeras, one of which had the cytoplasmic domain of TfR2 and the remaining portion of TfR1 and the other with the cytoplasmic and transmembrane domain of TfR1 joined to the ectodomain of TfR2. Similar to TfR2, the levels of the chimera containing only the cytoplasmic domain of TfR2 increased in a time- and dose-dependent manner after the addition of holo-Tf to the medium. The half-life of the chimera increased 2.7-fold in cells exposed to holo-Tf like the endogenous TfR2 in HepG2 cells. Like TfR2 and unlike TfR1, the levels of the chimera did not respond to intracellular iron content. These results suggest that although holo-Tf binding to the ectodomain is necessary, the cytoplasmic domain of TfR2 is largely responsible for its stabilization by holo-Tf.


Fibula osteotomy using a rib cutter.
We find the use of a rib cutter to be a useful alternative instrument in carrying out a fibular osteotomy.


Nucleotide sequence of the gene encoding the 11-kDa subunit of the ubiquinol-cytochrome-c oxidoreductase in Saccharomyces cerevisiae.
The nucleotide sequence of the gene encoding the 11-kDa subunit VIII of the ubiquinol-cytochrome-c oxidoreductase in Saccharomyces cerevisiae has been determined. The coding sequence has a length of 330 bp and is preceded at a distance of 361 bp by another reading frame, coding for a protein of as yet unknown function. The 11-kDa gene is transcribed independently of the URFx gene and transcription of both is sensitive to catabolite repression. Multiple 5' and 3' termini of transcripts of the gene for the 11-kDa subunit were identified by S1 nuclease protection analysis of DNA X RNA hybrids. The 5' termini map 52 +/- 2 and 60 +/- 2 nucleotides upstream of the initiation codon whereas the 3' termini map 336 +/- 2 and 350 +/- 2 nucleotides downstream of the stop codon. The subunit VIII reading frame encodes a protein with a molecular mass of 12.4 kDa and a polarity of 37.6%. It is predicted to contain a high content of beta-sheet segments, which may be capable of forming a barrel-like structure in a lipid bilayer. A comparison of the sequence with those of the small subunits of the beef heart complex reveals similarity with the 9.5-kDa subunit VII (core-linked protein) characterized by Borchart et al. (1986) FEBS Lett. 200, 81-86. The significance of this is discussed.


A Three-Year Observation of Corneal Backscatter After Small Incision Lenticule Extraction (SMILE).
To investigate changes in corneal backscatter after small incision lenticule extraction (SMILE). One eye was randomly selected from 34 patients who underwent SMILE procedures. Corneal backscatter was analyzed using Scheimpflug technology before surgery and at postoperative 1 day, 1 week, 1 month, 3, 6, and 12 months, and 3 years. Three different corneal depths (the anterior 120 µm, the center, and the posterior 60 µm) and three concentric radial zones (0 to 2, 2 to 6, and 6 to 10 mm) were analyzed. Another 40 eyes of 40 patients who underwent femtosecond laser-assisted LASIK (FS-LASIK) were examined before surgery and at postoperative 1 day and 3 years as the control group. At postoperative day 1, a significant increase in corneal backscatter was detected in the SMILE group compared to preoperative values in the central 0 to 6 mm zone of the anterior layer and the 0 to 2 mm zone of the central layer (all P < .01). This increase was higher than the increase in the FS-LASIK group in the central 0 to 6 mm zone of the anterior and central layers (all P < .01). No significant differences in corneal backscatter were detected between preoperative values and the 1-week, and 1-, 3-, 6-, and 12-month follow-up visits in the SMILE group (all P > .05). Moreover, a significant decrease in corneal backscatter was detected in the three zones of all three layers in the two groups at 3 years postoperatively compared to preoperative values (all P < .001) and no significant difference was found between the two groups (all P < .05). Corneal backscatter peaks and declines to the baseline in the early period after SMILE and corneal transparency achieves an improvement within 3 years postoperatively. [J Refract Surg. 2017;33(6):377-382.].


Capacity to improve fine motor skills in Williams syndrome.
Individuals with Williams syndrome (WS) are known to have difficulties in carrying out fine motor movements; however, a detailed behavioural profile of WS in this domain is still missing. It is also unknown how great the capacity to improve these skills with focused and extensive practice is. We studied initial performance and learning capacity in a sequential finger tapping (FT) task in WS and in typical development. Improvement in the FT task has been shown to be sleep dependent. WS subjects participating in the current study have also participated in earlier polysomnography studies, although not directly related to learning. WS participants presented with great individual variability. In addition to generally poor initial performance, learning capacity was also greatly limited in WS. We found indications that reduced sleep efficiency might contribute to this limitation. Estimating motor learning capacity and the depth of sleep disorder in a larger sample of WS individuals might reveal important relationships between sleep and learning, and contribute to efficient intervention methods improving skill acquisition in WS.


Neuroticism, depression and pain perception in migraine and tension-type headache.
People with migraine and tension-type headache (TTH) have psychiatric comorbidities. We aimed to test differences in mental health constructs by type and frequency of primary headache and associated pain sensitivity. Data on headache features, neuroticism (Eysenck Personality Questionnaire) and depression (Major Depression Inventory) were obtained from 547 individuals classified into chronic (≥15) or episodic (<15 headache days/month) and into pure migraine (n=43), pure tension type headache (TTH, n=97), migraine and TTH (n=83) and no headache diagnosis (controls, n=324) groups. A pericranial total tenderness score (TTS) and pressure pain thresholds (PPTs) were measured. Differences in mental health constructs were examined by headache frequency and type using generalized linear mixed models adjusting for sociodemographic covariates. Depression scores were highest among people with chronic headache, lower in those with episodic headache, and lowest in controls. The chronic and episodic headache groups had higher neuroticism scores than controls. Mental health construct scores were highest for the migraine and TTH group and lowest in the control group. TTS and cephalic PPTs were correlated with neuroticism and depression and were higher in the chronic headache group compared to the no headache group even when adjusted for neuroticism and depression. Neuroticism and depression scores are associated with headache frequency (chronic vs episodic) and are highest for migraine and TTH followed by pure TTH then migraine. Mental health constructs were correlated with but did not influence differences in TTS and PPTs between headache groups.


De novo food sensitization and eosinophilic gastrointestinal disease in children post-liver transplantation.
Children have increased prevalence of food allergy (FA) and eosinophilic gastrointestinal disease (EGID) following liver transplantation. The aim of this study was to identify related risk factors. Chart review of pediatric liver transplant (LT) recipients with de novo FA and/or EGID post-LT and non-allergic controls. We identified 30 (8.5%) children with FA and/or EGID among 352 pediatric LT recipients. Median age at transplant was 0.9 inter-quartile range (IQR 0.6-2.0) years. FA developed at a median 1.0 (IQR 0.5-8.2) yr post-LT and manifested with gastrointestinal symptoms (53%) or urticaria/angioedema (40%). Commonly avoided foods included milk (60%), egg (57%), and peanut (47%). Of the 15 children with FA who underwent endoscopy, 11 had eosinophilic infiltrates in multiple segments of the esophagus alone or in combination with other bowel segments. FA and EGID were linked to transplantation at a younger age (median, 0.9 vs. 5.5 yr), higher frequency of blood eosinophilia, and prior history of rhinitis and atopic dermatitis. Tacrolimus use and tacrolimus serum levels were similar between allergic subjects and controls. Findings suggest that exposure to tacrolimus alone post-LT is insufficient to initiate de novo allergic disease in LT recipients; rather, younger age and underlying predisposition to atopic disease may play larger roles.


Effect of DA-9701 on gastric emptying in a mouse model: assessment by ¹³C-octanoic acid breath test.
To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the ¹³C-octanoic acid breath test in a mouse model. Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g ¹³C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the ¹³C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments: DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week. Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the ¹³C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049]. The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed with repeated measurements in the same mouse using the ¹³C-octanoic acid breath test. Our findings suggest that DA-9701 has therapeutic potential for the treatment of functional dyspepsia.


[Community ecology of the metazoan parasites of five Scombrid species (Perciformes: Scombridae), from the coastal zone of the State of Rio de Janeiro, Brazil].
From June 2001 to March 2004, 171 marine scombrid fishes (Perciformes: Scombridae) from the coastal zone of the State of Rio de Janeiro, Brazil (21-23 degrees S, 41-45 degrees W) were necropsied to study their community metazoan parasites: 46 Euthynnus alleteratus (Rafinesque, 1810); 15 Katsuwonus pelamis (Linnaeus, 1758); 30 Sarda sarda (Bloch, 1793) ; 43 Scomber scombrus Linnaeus, 1758 and 37 Scomberomorus brasiliensis Collette, Russo & Zavala-Camim, 1978. All specimens of E. alleteratus, K. pelamis and S. brasiliensis were parasitized by one or more metazoan species. In S. sarda and S. scombrus 96.7% and 60.4% of specimens were parasitized, respectively. Forty-four different metazoan parasites species were collected: 22 in E. alleteratus, 13 in K. pelamis, 14 in S. sarda, three in S. scombrus and 12 in S. brasiliensis. Euthynnus alleteratus is a new host record for 12 metazoan parasite species, K. pelamis and S. scombrus for one species each, S. sarda for eighth species and S. brasiliensis for five species. Nine parasites species were new geographical record. Fifteen species were common in at least two communities. The digeneans were the majority of the parasite specimens collected in E. alleteratus and S. brasiliensis with 85.7% and 72.5%, respectively. In K. pelamis and S. sarda the majority of the parasite specimens collected were cestodes and copepods, 64.5% and 62.9%, respectively. Only larval stages of nematodes were collected in S. scombrus. The parasite of 5 host species showed the typical aggregate pattern of distribution. Four cases of positive correlation and three cases of negative correlation between host's length and prevalence and parasite abundance were found. The parasite community of K. pelamis showed the higher values of the mean parasite species richness and diversity. Only in S. scombrus the abundance and parasite species richness were correlates with the host's length. Euthynnus alleteratus was the species with the higher number of ectoparasites (11), adult endoparasites (5) and larval stage of endoparasites (6). The infracommunities of larval stage of endoparasites showed correlation with the host's length and abundance, parasite species richness, diversity and numerical dominance.


The role of peroxiredoxins in cancer.
Peroxiredoxins (PRDXs) are a ubiquitously expressed family of small (22-27 kDa) non-seleno peroxidases that catalyze the peroxide reduction of H2O2, organic hydroperoxides and peroxynitrite. They are highly involved in the control of various physiological functions, including cell growth, differentiation, apoptosis, embryonic development, lipid metabolism, the immune response, as well as cellular homeostasis. Although the protective role of PRDXs in cardiovascular and neurological diseases is well established, their role in cancer remains controversial. Increasing evidence suggests the involvement of PRDXs in carcinogenesis and in the development of drug resistance. Numerous types of cancer cells, in fact, are characterized by an increase in reactive oxygen species (ROS) production, and often exhibit an altered redox environment compared with normal cells. The present review focuses on the complex association between oxidant balance and cancer, and it provides a brief account of the involvement of PRDXs in tumorigenesis and in the development of chemoresistance.


[Pharmacology of Sinupret. Recent results on the rational for the Sinupret compound].
The herbal medicinal product Sinupret has been successfully used for the treatment of sinusitis for 70 years. In Germany the product is established as a standard in the therapy of sinusitis. The most recent pharmacodynamic findings resulted from close scientific cooperation with Pontus Stierna and co-workers from the Karolinska Institute in Stockholm: Mice were infected intranasally with Streptococcus pneumoniae to induce bacterial rhinosinusitis. Animals were randomized to treatment with ampicillin, dexamethasone, Sinupret, or sham treatment. All groups receiving active treatment showed a reduction in bacterial growth after 4 days and a significant reduction of bacterial growth after 8 days. Similar results were observed regarding histopathology. Initial findings in a sinusitis model in the New Zealand White rabbit confirmed the results observed in the aforementioned studies in mice. Understanding of the pharmacological profile of Sinupret supports the knowledge about the clinical efficacy of this herbal medicinal product.


Acetate ester production by Chinese yellow rice wine yeast overexpressing the alcohol acetyltransferase-encoding gene ATF2.
Acetate ester, which are produced by fermenting yeast cells in an enzyme-catalyzed intracellular reaction, are responsible for the fruity character of fermented alcoholic beverages such as Chinese yellow rice wine. Alcohol acetyltransferase (AATase) is currently believed to be the key enzyme responsible for the production of acetate ester. In order to determine the precise role of the ATF2 gene in acetate ester production, an ATF2 gene encoding a type of AATase was overexpressed and the ability of the mutant to form acetate esters (including ethyl acetate, isoamyl acetate, and isobutyl acetate) was investigated. The results showed that after 5 days of fermentation, the concentrations of ethyl acetate, isoamyl acetate, and isobutyl acetate in yellow rice wines fermented with EY2 (pUC-PIA2K) increased to 137.79 mg/L (an approximate 4.9-fold increase relative to the parent cell RY1), 26.68 mg/L, and 7.60 mg/L, respectively. This study confirms that the ATF2 gene plays an important role in the production of acetate ester production during Chinese yellow rice wine fermentation, thereby offering prospects for the development of yellow rice wine yeast starter strains with optimized ester-producing capabilities.


Design and construction of an open multistranded beta-sheet polypeptide stabilized by a disulfide bridge.
The design and characterization of an open eight-stranded beta-sheet in a synthetic, 2-fold symmetric 70-residue peptide is described. The design strategy involves the generation of a 35-residue four-stranded beta-sheet peptide in which successive hairpins are nucleated by appropriately positioned (D)Pro-Xxx sequences. Oxidative dimerization using a single Cys residue positioned at the center of the C-terminal strand results in a disulfide-bridged eight-stranded structure. Nuclear Overhauser effects firmly establish an eight-stranded beta-sheet in methanol. In water, the outer strands are frayed, but a well-defined four-stranded beta-sheet stabilized by a disulfide bridge and a hydrophobic cluster is determined from NMR data. Comparison of the precursor peptide with the disulfide-bridged dimer reveals considerable enhancement of beta-sheet content in the latter, suggesting that the disulfide cross-link is an effective strategy for the stabilization of beta-sheets.


Formulation, evaluation and bioactive potential of Xylaria primorskensis terpenoid nanoparticles from its major compound xylaranic acid.
In recent years, fungi have been shown to produce a plethora of new bioactive secondary metabolites of interest, as new lead structures for medicinal and other pharmacological applications. The present investigation was carried out to study the pharmacological properties of a potent and major bioactive compound: xylaranic acid, which was obtained from Xylaria primorskensis (X. primorskensis) terpenoids in terms of antibacterial activity, antioxidant potential against DPPH & H2O2 radicals and anticancer activity against human lung cancer cells. Due to terpenoid nature, low water solubility and wretched bioavailability, its pharmacological use is limited. To overcome these drawbacks, a novel xylaranic acid silver nanoparticle system (AgNPs) is developed. In addition to improving its solubility and bioavailability, other advantageous pharmacological properties has been evaluated. Furthermore, enhanced anticancer activity of xylaranic acid and its AgNPs due to induced apoptosis were also confirmed by determining the expression levels of apoptosis regulatory genes p53, bcl-2 and caspase-3 via qRT PCR method. This is the first study developing the novel xylaranic acid silver nanoparticle system and enlightening its therapeutic significance with its improved physico-chemical properties and augmented bioactive potential.


[The role of trans-rectal echography (TRE) in the evaluation and staging of bladder tumors: comparison with suprapubic echography and computerized axial tomography (CAT)].
TAU and CT are, after cystoscopy, the two most largely used methods in the diagnosis and the staging of the bladder tumors. TRUS is mostly used in the pathologies of the prostate and the seminal vesicles. 38 patients (34 M and 4 F) suffering from bladder cancer are included in this study in the period from July 1995 to January 1997. They are evaluated with TAU, TRUS and CT in order to evaluate the sensitivity and the specificity of TRUS in the diagnosis and the stadiation of bladder tumors. The patients included in this study are divided in two subgroups as patients having superficial and infiltrating tumors according to pathologic stage after TURB or radical cystoprostatectomy. Specificity and sensitivity values, overstaging and undestaging rates are calculated for each group. In the superficial tumors, TAU had a sensitivity and specificity of 72.2%, while with CT these values were respectively 70% and 75%; in the infiltrating tumors, TAU presented sensitivity of 65% and specificity of 70% while CT presented respectively 72.2% and 77.5%. With TRUS these values were 88.8% and 94.4% in the superficial tumors and 90% and 95% in the infiltrating tumors. The method with the highest overstaging rate was CT with 33.3% while the ones with the highest understaging rates were TAU and CT with 22.2%. The sensitivity with TRUS was 100% in a total of 29 infiltrating and superficial tumors of the trigone while it was only 55.5% in the tumors of the lateral walls and the dome. With TAU these values were respectively 82.7% and 22.2%, with CT respectively 79.3% and 44.4%. The specificity with TRUS was 100% for the tumors of the lateral walls and 77.7% of the dome; with TAU these values were respectively 75.8% and 55.5% with CT 75.8% and 77.7%. In conclusion, TRUS may be used with a high sensitivity and specificity in the diagnosis and the stadiation of infiltrating and superficial bladder tumors situated at the peritrigonal zone and in the diagnosis of tumors situated in other regions of the bladder.


Time-varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: an EEG-TMS study.
Motor evoked potentials (MEPs) elicited by a train of consecutive, individual transcranial magnetic stimuli demonstrate fluctuations in amplitude with respect to time when recorded from a relaxed muscle. The influence of time-varying, instantaneous modifications of the electroencephalography (EEG) properties immediately preceding the transcranial magnetic stimulation (TMS) has rarely been explored. The aim of this study was to investigate the influence of the pre-TMS motor cortex and related areas EEG profile on time variants of the MEPs amplitude. MRI-navigated TMS and multichannel TMS-compatible EEG devices were used. For each experimental subject, post-hoc analysis of the MEPs amplitude that was based on the 50th percentile of the MEPs amplitude distribution provided two subgroups corresponding to "high" (large amplitude) and "low" (small amplitude). The pre-stimulus EEG characteristics (coherence and spectral profile) from the motor cortex and related areas were analyzed separately for the "high" and "low" MEPs and were then compared. On the stimulated hemisphere, EEG coupling was observed more often in the high compared to the low MEP trials. Moreover, a paradigmatic pattern in which TMS was able to lead to significantly larger MEPs was found when the EEG of the stimulated motor cortex was coupled in the beta 2 band with the ipsilateral prefrontal cortex and in the delta band with the bilateral centro-parietal-occipital cortices. This data provide evidence for a statistically significant influence of time-varying and spatially patterned synchronization of EEG rhythms in determining cortical excitability, namely motor cortex excitability in response to TMS.


A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro.
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro. However, treatment with the Jak1/2 inhibitor, baricitinib, markedly inhibited osteoclastogenesis in the co-culture. On the other hand, baricitinib did not inhibit RANKL-induced osteoclast differentiation of bone marrow macrophages. These results indicated that baricitinib acted on osteoblasts, but not on bone marrow macrophages. Baricitinib suppressed 1,25D3 and PGE2-induced up-regulation of RANKL in osteoblasts, but not macrophage colony-stimulating factor expression. Moreover, the addition of recombinant RANKL to co-cultures completely rescued baricitinib-induced impairment of osteoclastogenesis. shRNA-mediated knockdown of Jak1 or Jak2 also suppressed RANKL expression in osteoblasts and inhibited osteoclastogenesis. Finally, cytokine array revealed that 1,25D3 and PGE2 stimulated secretion of interleukin-6 (IL-6), IL-11, and leukemia inhibitory factor in the co-culture. Hence, Jak1 and Jak2 represent novel therapeutic targets for osteoporosis as well as inflammatory bone diseases including rheumatoid arthritis.


Isolation and characterization of phellodendronoside A, a new isoquinoline alkaloid glycoside with anti-inflammatory activity from Phellodendron chinense Schneid.
Bark of Phellodendron chinense Schneid. (Rutaceae), called "Huang Bai" in China, is one of the 50 most used Chinese medicines in clinical practice. In this paper, a new isoquinoline alkaloid glycoside was isolated from P. chinense, and its structure was elucidated using spectroscopic method. The compound was eventually identified as (1S, 3"S)-1, 2, 3, 4-tetrahydro-7-hydroxy-1-[(4-hydroxybenzyl) methyl]-2-methyl-8-O-isoquinolinyl-[3-hydroxy-3-methylglutaryl]-β-D-glucopyranoside and named as Phellodendronoside A (PDA). The results of molecular docking showed that PDA could stably bind to an extracellular signal-regulated kinase (ERK), stress-activated protein kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) proteins that are closely related to inflammation. Further, the anti-inflammatory activity of PDA was evaluated using the lipopolysaccharide (LPS) induced RAW264.7 macrophage model. We observed that PDA can effectively reduce the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and decrease the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, we found that PDA inhibits the activation of ERK, JNK and p38MAPK proteins in the MAPK signaling pathway. Collectively, the present study demonstrates that PDA has excellent anti-inflammatory effect in vitro by inhibiting the overproduction of pro-inflammatory mediators, and its mechanism of action involves suppressing the activation of MAPK pathways, suggesting that PDA may be a potential agent for the treatment of inflammatory illness.


Salivary otorrhoea: a case report and a review of the literature.
This report presents an unusual case of spontaneous salivary otorrhoea in which advanced imaging was used to identify a developmental defect in the anterior wall of the bony external auditory meatus. This defect, the so-called foramen of Huschke, was subsequently found to be the source of the fistula. A review of the literature highlights the diagnostic dilemmas that such cases pose for the clinician.


Pleurotus mushrooms. Part II. Chemical composition, nutritional value, post-harvest physiology, preservation, and role as human food.
The fruit bodies of Pleurotus species as a class of "Edible Fungal Foods" have been discovered to have definite nutritive and medicinal values. They are a good source of nonstarchy carbohydrates, dietary fiber (that can help in reducing the plasma cholesterol), most of the essential amino acids, minerals and vitamins of B group, and folic acid (necessary to counteract pernicious anaemia) in particular. Considering the essential amino acid index, biological value, in vitro digestibility, nutritional index, and protein score, Pleurotus species fall between high grade vegetables and low grade meats. Fractions of water-soluble polysaccharides are reported to possess antitumor activity. The physiological processes such as changes in water content, respiratory rate, texture, color, and activities of enzymes like proteases and polyphenol oxidases during the after-harvest life are delineated. The problems and prospects of processing the fruit bodies by various methods are discussed. Potentialities for production and consumption of the fruit bodies in different parts of the world are brought out.


Salicylic acid treatment via the rooting medium interferes with stomatal response, CO2 fixation rate and carbohydrate metabolism in tomato, and decreases harmful effects of subsequent salt stress.
Salicylic acid (SA) applied at 10(-3) m in hydroponic culture decreased stomatal conductance (g(s)), maximal CO(2) fixation rate (A(max) ) and initial slopes of the CO(2) (A/C(i)) and light response (A/PPFD) curves, carboxylation efficiency of Rubisco (CE) and photosynthetic quantum efficiency (Q), resulting in the death of tomato plants. However, plants could acclimate to lower concentrations of SA (10(-7) -10(-4) m) and, after 3 weeks, returned to control levels of g(s), photosynthetic performance and soluble sugar content. In response to high salinity (100 mm NaCl), the pre-treated plants exhibited higher A(max) as a function of internal CO(2) concentration (C(i) ) or photosynthetic photon flux density (PPFD), and higher CE and Q values than salt-treated controls, suggesting more effective photosynthesis after SA treatment. Growth in 10(-7) or 10(-4) m SA-containing solution led to accumulation of soluble sugars in both leaf and root tissues, which remained higher in both plant parts during salt stress at 10(-4) m SA. The activity of hexokinase (HXK) with glucose, but not fructose, as substrate was reduced by SA treatment in leaf and root samples, leading to accumulation of glucose and fructose in leaf tissues. HXK activity decreased further under high salinity in both plant organs. The accumulation of soluble sugars and sucrose in roots of plants growing in the presence of 10(-4) m SA contributed to osmotic adjustment and improved tolerance to subsequent salt stress. Apart from its putative role in delaying senescence, decreased HXK activity may divert hexoses from catabolic reactions to osmotic adaptation.


Pharmacokinetics of tetracycline encapsulated in bovine carrier erythrocytes.
Tetracycline was encapsulated in erythrocytes with a dialysis technique. The effect of drug concentration (0.2 mg/ml of erythrocytes) on encapsulation of [14C]sucrose and [3H]tetracycline was reduction of the tetracycline encapsulation, but not [14C]sucrose. Carrier erythrocytes containing tetracycline reinjected in calves were studied for their pharmacokinetic constants. The drug half-life was 6.7 hours, with an overall elimination constant of 0.104 hour-1.


Short-term testing of antifouling surfaces: the importance of colour.
Data from short-term biofouling assays are frequently used to evaluate the performance of antifouling (AF) coatings. There are a large number of factors, however, that may influence community development. One such factor is colour. The hypothesis was that differences in colour may impact the short-term development of a biofouling community and therefore bias the results. An experiment was designed to investigate the effect of black and white substrata on settlement of fouling organisms in the field. Both Ulva sp. and Spirorbis sp. had significantly higher settlement on black surfaces. This result emphasises the importance of considering colour and other factors when undertaking short-term testing of AF coatings.


Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production.
The tightly regulated biosynthesis and catabolism of the glycosaminoglycan hyaluronan, as well as its role in organizing tissues and cell signaling, is crucial for the homeostasis of tissues. Overexpression of hyaluronan plays pivotal roles in inflammation and cancer, and markedly high serum and tissue levels of hyaluronan are noted under such pathological conditions. This review focuses on the complexity of the regulation at transcriptional and posttranslational level of hyaluronan synthetic enzymes, and the outcome of their aberrant expression and accumulation of hyaluronan in clinical conditions, such as systemic B-cell cancers, aggressive breast carcinomas, metabolic diseases and virus infection.


A Flexible Electrode Based on Iron Phosphide Nanotubes for Overall Water Splitting.
The design of cheap and efficient water splitting systems for sustainable hydrogen production has attracted increasing attention. A flexible electrode, based on carbon cloth substrate and iron phosphide nanotubes coated with an iron oxide/phosphate layer, is shown to catalyze overall water splitting. The as-prepared flexible electrode demonstrates remarkable electrocatalytic activity for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) at modest overpotentials. The surface iron oxide/phosphate, which is formed in situ, is proposed to improve the HER activity by facilitating the water-dissociation step and serves directly as the catalytically-active component for the OER process.


Heart preservation using continuous ex vivo perfusion improves viability and functional recovery.
Cold static storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent, so continuous perfusion (CP) during ex vivo transport may improve viability and function of heart grafts. Canine hearts underwent CP (n=9) or CS (n=9) for 6 h while intramyocardial pH was continuously monitored. Biopsies were assayed for ATP, caspase-3, malondialdehyde (MDA), and endothelin-1 (ET-1) levels at baseline, after preservation (t1), and after 1 h of blood reperfusion on a Langendorff model (t2). Functional recovery was determined at t2 by +dP/dt, -dP/dt, developed pressure, peak pressure and end-diastolic pressure. CP resulted in higher tissue pH and ATP stores and reduced caspase-3, MDA and ET-1 levels compared with CS at both t1 and t2. Post reperfusion recovery was significantly greater in CP vs CS for all myocardial functional parameters except end-diastolic pressure. Weight gain was significantly increased in CP vs CS at t1, but not at t2. Low-grade tissue acidosis and energy depletion occur during CS and are associated with oxidative injury and apoptosis during reperfusion. CP attenuates these biochemical and pathologic manifestations of tissue injury, together with improved myocardial recovery, despite mild, transient edema.


Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective agonists.
On the basis of docking studies carried out using the recently published cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, which presented p-fluorobenzyl and carboxycycloheptylamide substituents bound in the 1 and 3 positions of the 1,8-naphthyiridine-4-one nucleus, showed a high CB2 affinity with a Ki of 1.0 nM. The substitution of the naphthyridine-4-one nucleus with the quinoline-4-one system determined a general increase in CB2 affinity. In particular, the N-cyclohexyl-7-chloro-1-(2-morpholin-4-ylethyl)quinolin-4(1H)-on-3-carboxamide (40) possessed a remarkable affinity, with Ki of 3.3 nM, which was also accompanied by a high selectivity for the CB2 receptor (Ki(CB1)/Ki(CB2) ratio greater than 303). Moreover, the [35S]GTPgamma binding assay and functional studies on human basophils indicated that the 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives behaved as CB1 and CB2 receptor agonists.


Nanoemulsion-Based Transdermal Drug Delivery System for the Treatment of Tuberculosis.
The nanoemulsion based carriers are the most suitable delivery systems for poorly soluble drugs to improve the drugs solubility, permeation of drugs and ultimately increase bioavailability by transdermal therapeutic system. The nanoemulsion for poorly soluble drugs is admirable and offered several advantages over others drug delivery. For nanoemulsions formulation, they have to deliver the energetic element at the specific organ with nominal uneasiness. Because of the prevention of hepatic first pass uptake transdermal course excel usual crest and trough plasma shape that usually comfort the administration. The antitubercular drugs relate to the formulation of Poly DL-Lactide-Co-Glycolide nanoparticles having an active substance encapsulated within and that the encapsulated substances are stable with respect to each other. The present study aimed to explore the challenges and methods in order to increase the solubility of poorly aqueous soluble drug for improved bioavailability alongwith relative study of toxicity problems related to anti-tubercular drug.


A prospective, multicenter, randomized-controlled 5-year study of hybrid and fully etched implants for the incidence of peri-implantitis.
The dual acid-etched (DAE) implant was commercially introduced in 1996 with a hybrid design incorporating a machined surface in the coronal region from approximately the third thread to the seating surface. This design was intended to reduce the risks of peri-implantitis and other related soft tissue complications that were reported for implants with surface roughness in the coronal region. The objective of this prospective, randomized-controlled clinical trial was to determine the incidence of peri-implantitis for a fully etched implant with the DAE surface extending to the implant platform. Patients had implant sites randomly assigned to receive one hybrid control implant and at least one fully etched test implant in support of a short-span fixed restoration to ensure that variables (e.g., demographics, jaw locations, and bone density) were consistent between groups. Prostheses were inserted 2 months after implant placement with follow-up evaluations scheduled annually for 5 years to assess mucosal health based on bleeding on probing, suppuration, and probing depths. Evaluations also included radiographic and mobility assessments. One hundred twelve patients who were enrolled at seven centers received 139 control and 165 test implants (total: 304 implants). With >5 years of postloading evaluations, there was one declaration of peri-implantitis associated with a control implant that was successfully treated later. Clinical probing and radiographic assessments did not reveal differences between groups in mucosal health outcomes or other signs of peri-implantitis. Five-year results of this randomized-controlled study showed no increased risk of peri-implantitis for fully etched implants compared to hybrid-designed implants.


The effect of thymus cells on bone marrow transplants into sublethally irradiated mice. Lack of correlation between spleen colony formation and competitive repopulation of granulocytic system.
Bone marrow cells formed similar numbers of 10-day spleen colonies in sublethally (6 Gy) irradiated C57B1/6 mice in lethally (7.5 Gy) irradiated mice i.e. approximately 20 per 10(5) cells. Numbers of 10 day endogenous spleen colonies in sublethally irradiated mice (0.2 to 0.6 per spleen) did not differ significantly from the numbers in lethally irradiated mice. Yet, transplants of 10(7) coisogenic marrow cells into sublethally irradiated mice resulted in predominantly endogenous recovery of granulocyte system as evidenced by utilization of "beige" marker for transplanted cells. Nevertheless, transplanted cells engrafted into sublethally irradiated mice were present in their hemopoietic tissues throughout the observation period of 2 months never exceeding 5 to 10% of all cells. Thymus cells stimulated endogenous and exogenous spleen colony formation as well as endogenous granulopoietic recovery. Additionally, they increased both the frequency and absolute numbers of graft-derived granulocytic cells in hemopoietic organs of transplanted mice. They failed, however, to essentially change the quantitative relationships between endogenous and exogenous hemopoietic recovery. These results may suggest that spleen colony studies are not suitable for prediction of events following bone marrow transplant into sublethally irradiated mice. Simultaneously, they have strengthened the necessity for appropriate conditioning of recipients of marrow transplants.


Pyogenic sacroiliitis in Qatar.
We describe our experience in handling six cases of pyogenic sacroiliitis. Two were males and four were females with a mean age of 24.9 years. None had a history of i.v. drug abuse. Blood cultures were positive in half of the patients. The sacroiliac joint aspirate was positive in one additional patient. Staphylococcus aureus was recovered from three of four culture positive cases. Bone and CT scans revealed abnormalities in all patients. Response to antibiotic therapy was satisfactory in all except one patient who had an early relapse. Early diagnoses and proper treatment would result in improved outcomes.


[Adenosine metabolism in lymphocytes and neurochemical stressor reactions in mice with metastatic Lewis carcinoma after surgical removal of the tumor].
Surgical operation of metastatic Lewis carcinoma, carried out in male mice of C57B1 strain, which stimulated distinctly the metastases spreading, was accompanied by phase impairments in activities of adenosine deaminase and 5'-nucleotidase in immunocompetent cells correlating with neurochemical stressory reactions. Thus, excessive stressory alterations in activity of symptoadrenal and hypothalamic mediatory systems appear to be among the factors responsible for inhibition of metabolism in lymphoid cells and for stimulation of metastatic spreading.


High speed, high temperature electrical characterization of phase change materials: metastable phases, crystallization dynamics, and resistance drift.
During the fast switching in Ge2Sb2Te5 phase change memory devices, both the amorphous and fcc crystalline phases remain metastable beyond the fcc and hexagonal transition temperatures respectively. In this work, the metastable electrical properties together with crystallization times and resistance drift behaviour of GST are studied using a high-speed, device-level characterization technique in the temperature range of 300 K to 675 K.


[The performance of respirator alarms during simulated critical events in CMV/IPPV artificial respiration].
Alarm systems of ventilators enhance detection of possible critical events during artificial ventilation. Due to their significance, in some countries the alarm detection of ventilators is regulated by federal law. Up to now, no recommendations for the adjustment of alarm limits exist and only a few detailed investigations of the accuracy of alarm detection are available. METHODS. The response of four commercially available ventilators (Servoventilator 900C, Siemens, Inc.; Bennett 7200a, Hoyer, Inc.; Veolar, Hamilton, Inc.; EVITA, Dräger, Inc.) to critical events during artificial ventilation of a test lung were evaluated. We measured the alarm time (the time between event creation and alarm response) of ten different simulated critical events including disconnection, differentisized leaks, failure of the gas supply, and obstruction at different places in the artificial airway. DISCUSSION. All respirators were able to recognise severe critical situations such as hose disconnection, failure of gas supply, and total airway obstruction within a short time (< 15 s). The recognition of small airway leaks was more difficult for the ventilators even when the alarm thresholds were close. The alarm detection of the EVITA (software 10.0 or less) under conditions of partial airway obstruction may be a source of risk for the patient as the machine continued supplying inspiration with pressure-limited ventilation even when the pressure threshold was reached.


Research secures the future of osteopathic medicine: Part 2: Readdressing the function and structure of colleges of osteopathic medicine.
Many problems exist within the contemporary medical education process in general and the osteopathic medical profession in particular. Part 2 of this series suggests that the single greatest impediment to solving these problems is an institutional infrastructure that is not congruent with the institution's functions, as defined in its mission statement. (This mission statement generally entails two primary goals: education and research). Two major divisions within the core's infrastructure are suggested: medical education and medical research. By restructuring their infrastructure, colleges of osteopathic medicine can more effectively address and support their primary functions of education and research.


Some properties of two autolytic-defective mutants of Streptococcus faecalis ATCC 9790.
The isolation and some properties of two mutants of Streptococcus faecalis ATCC 9790 (S. faecium) which autolyze at a much slower rate than the wild type are described. Compared with the wild type, mutant E71 autolyzed more slowly, contained less active but more latent autolysin in the isolated wall fraction, and possessed a wall of very similar chemical composition and degree of cross-bridging. Ultrastructural studies of exponential phase cells showed that cells of E71 were on the average slightly longer and had slightly thickened walls compared to the wild type. Mutant E81 autolyzed much more slowly, grew exponentially in long chains (8 to 40 cells compared with mainly diplococci), contained much less active and latent autolysin in the wall, and possessed a wall of very similar chemical composition but with about twice the content of N-terminal groups. Mutant E81 walls were more susceptible to isolated autolysin but possessed an autolysin of the same specificity as the wild type. Ultrastructurally E81 cells were, on the average, significantly longer and had thicker walls than the wild type. Mutant E71 may be partially blocked at either transport of autolysin to the wall or in conversion of latent to active autolysin. The pleitropic effects noted in mutant E81 have been taken to suggest a possible membrane defect and to support the role of the autolysin in cell separation.


Examining hepatoprotective effects of astaxanthin against methotrexate-induced hepatotoxicity in rats through modulation of Nrf2/HO-1 pathway genes.
Methotrexate (MTX), as a folic acid antagonist, is an effective drug in treating a wide range of malignancies and autoimmune diseases. However, the clinical use of MTX has been limited due to its side effects, the most common of which is hepatotoxicity. In this study, rats were randomly divided into six groups: three treatment groups received methotrexate and different doses of astaxanthin (AX) for 14 days. At the end of the study, blood samples were collected to determine serum levels of ALT, AST, ALP, and LDH. Also, liver tissues were isolated to evaluate antioxidant enzymes and markers of oxidative stress, histopathological damage, and expression of NF-E2-related transcription factor (Nrf2) and Heme oxygenase-1 (HO-1) genes. The results showed that administration of MTX significantly increased the levels of ALT, AST, ALP, and LDH in the blood, markers of oxidative stress, and histopathological damage in liver tissue and significantly reduced the levels of antioxidant enzymes and the expression of Nrf2 and HO-1 genes. On the other hand, treatment with AX decreased blood levels of ALT, AST, ALP, and LDH and oxidative stress markers and remarkably raises the activity of antioxidant enzymes and expression of Nrf2 and HO-1 genes in liver tissue. In addition, histopathological lesions were improved with AX administration. The findings of this study indicated that AX may be useful for the prevention of MTX-induced hepatotoxicity by improving oxidative and inflammatory changes.


Gastrobiliary dysmotility in patients with chronic pancreatitis as assessed by a single noninvasive test.
We simultaneously assessed gastric emptying and gallbladder contraction after oral administration of a liquid meal by noninvasive ultrasonography in 17 patients with chronic pancreatitis (CP) and in 17 healthy controls. Gastrointestinal (GI) transit was also assessed by a noninvasive radioopaque marker method. Exocrine pancreatic function was evaluated by analyzing pure pancreatic juice and by analyzing the autonomic nervous system by cardiovascular reflex tests. Patients with CP showed impaired gallbladder contraction at 15 min and hastened gastric emptying. The cause of the former is unclear, whereas the latter was closely related with decreased pancreatic lipase output, but not with autonomic dysfunction. GI transit time did not differ between controls and patients with CP. In conclusion, we succeeded in clearly demonstrating impaired gallbladder contraction and hastened gastric emptying in patients with CP by a single noninvasive test, ultrasonography. We also revealed for the first time that hastened gastric emptying is associated with insufficient pancreatic lipase output.


Creutzfeldt-Jakob disease with features of obsessive-compulsive disorder and anorexia nervosa: the role of cortical-subcortical systems.
The authors examined the clinical and neuropathological characteristics of a patient who developed features of obsessive-compulsive disorder (OCD) and anorexia nervosa (AN) as the initial presentation of Creutzfeldt-Jakob disease. He had mild Parkinsonism and showed deficits in visual scanning, set shifting, graphomotor speed, sequencing, and verbal and nonverbal memory. Neuropathological study showed spongiosis and neuronal loss in cortical (e.g., frontal, temporal, parietal), and especially in subcortical structures (e.g., basal ganglia, thalamus). This study supports the hypothesis of abnormal frontal-striatal functioning in the cause of OCD, even in demented subjects. In addition, the authors discuss the role of frontal-temporal-subcortical dysfunction in the cause of acquired AN.


Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients.
Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is urgently needed for prognosticating clinical outcomes to preselect patients who would benefit the most from PPV. In this retrospective study, to detect a molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in castration-resistant prostate cancer (CRPC) patients before administration of PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase, haptoglobin, and neutrophil elastase was significantly associated with overall survival (OS) among vaccinated CRPC patients (adjusted P < 0.01). By promoter sequence analysis of these three genes, we found that rs5472 of haptoglobin (HP), an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated CRPC patients (P = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28-0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma of CRPC patients before administration of PPV exhibited rs5472 dependence (P < 0.001 for mRNA expression and P < 0.05 for protein level). Our findings suggest that rs5472 may play an important role in the immune response to PPV via regulation of HP. Thus, we concluded that rs5472 is a potential prognostic biomarker for PPV.


The UFM1 conjugation system in mammalian development.
Posttranslational modifications by ubiquitin and ubiquitin-like proteins are important in regulating cellular protein functions. UFM1 (ubiquitin-fold modifier 1), first identified almost two decades ago, is a member of the ubiquitin-like protein family. UFM1 is covalently conjugated to the target proteins in an enzymatic cascade consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. At the molecular level, modification by UFM1 (UFMylation) is an important mediator of the protein function. Dysregulation of the UFM1 system, e.g., the knockout of UFMylation components, disturbs proteome homeostasis and triggers endoplasmic reticulum stress. Such changes are linked to developmental disorders, tumorigenesis, tissue injury, inflammation, and several hereditary neurological syndromes. This review will focus on the role of the UFMylation in animal development and associated congenital disorders. We will cover the hematopoietic system, liver, central nervous system, intestine, heart, kidney, immune, and skeletal system to provide insight into disease pathogenesis and shed light on possible novel therapeutic methods.


Binding of fibrinogen to the pathogenic Aspergillus species.
The binding of human fibrinogen to the pathogenic aspergilli was investigated in vitro by different procedures using either fibrinogen in solution or fixed, insolubilized fibrinogen. Binding of fibrinogen was detected at the surface of hyphae and conidia by an immunofluorescence assay. Ultrastructural localization of the binding sites was visualized with fibrinogen-sensitized gold particles. The labelling was restricted to the outer cell wall layer of the 'smooth' walled conidia. Quantitative analysis of the binding carried out with 125I-labelled human fibrinogen on 33 species belonging to different groups (opportunistic fungi, strictly saprophytic or phytopathogenic fungi and dermatophytes or related species) clearly demonstrated that among all the fungi tested, only the pathogenic aspergilli significantly bound fibrinogen. The average amount of fibrinogen bound to individual conidia was also quantified. Binding was greater to Aspergillus niger (5-fold), Aspergillus fumigatus (2.5-fold) and Aspergillus flavus conidia (2.3-fold) than to Aspergillus terreus conidia. The results suggest that fibrinogen binding could contribute to the pathogenesis of aspergillosis.


The Protective Effect of Kaempferol Against Ischemia/Reperfusion Injury Through Activating SIRT3 to Inhibit Oxidative Stress.
The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms. H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo. After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function. Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.


Physiological integration plays key role in cranberry (Ericales: Ericaceae) for tolerance of damage by Dasineura oxycoccana (Diptera: Cecidomyiidae).
Understanding the mechanisms by which plants tolerate herbivory is important in the study of insect-plant interactions. In cranberry, current season growth has been identified as the main source of photosynthate for the developing fruits. Feeding injury by larvae of cranberry tipworm, Dasineura oxycoccana Johnson, disrupts the apical growth of cranberry shoots or uprights, but does not impact fruit output. To study the effects of experimentally depleting photosynthate available from sources other than the current season growth on fruit output, we girdled tipworm-injured uprights. This technique enabled us to estimate the contribution of current season growth in supplying photosynthate to developing fruits in tipworm-injured uprights. The mean fruit weight declined by >55% in those tipworm-injured uprights that were limited to photosynthate from only the current season growth (girdled uprights). The result was consistent between two phenologically different cultivars of cranberry, one a native selection from wild cranberry stands ('Howes') and the other a hybrid ('Stevens'). In addition, fruit weight was positively correlated to current season leaf area in the girdled uprights only. These results strongly suggest that physiological integration among the different sources of photosynthate plays a key role in the tolerance of tipworm feeding injury for fruit output in cranberry.


A higher score on the Aging Males' Symptoms scale is associated with insulin resistance in middle-aged men.
An age-associated androgen decrease and its pathological conditions are defined as late-onset hypogonadism (LOH). Among the various symptoms associated with LOH, a visceral fat increase is strongly associated with relatively low levels of testosterone. However, few studies have investigated the relationship between the Aging Males' Symptoms (AMS) scores and metabolic abnormalities. Thus, we aimed to clarify this relationship by investigating the relationship between AMS scores and various markers in blood. During routine health examinations in 241 middle-aged males (52.7±7.5 years of age, mean±SD), 150 males (62.2%) displayed higher AMS values than normal. No statistical association was observed between total AMS scores and any testosterone value. All mental, physical and sexual AMS subscales were significantly positively correlated with insulin levels and HOMA-IR. Only sexual subscale scores were significantly inversely associated with free or bioavailable testosterone level. Males with insulin resistance (HOMA-IR≥2.5) demonstrated significantly higher AMS scores than those with normal insulin sensitivity (HOMA-IR<2.5). AMS values were positively correlated with fasting blood glucose, insulin and HOMA-IR values. Interestingly, univariate and multivariate analyses revealed that HOMA-IR≥2.5 was a significant predictor for detection of moderately severe AMS values (AMS≥37), whereas AMS≥37 was not a predictor of metabolic syndrome by International Diabetes Federation (IDF) criterion. In conclusion, almost 60% of healthy male subjects displayed abnormal AMS scores. AMS values were not associated with testosterone values but rather were related to insulin resistance, particularly in subjects with moderately severe AMS values. Insulin resistance-related general unwellness might be reflected by AMS values.


Electrospun fixed dose formulations of amlodipine besylate and valsartan.
Increasing numbers of elderly people require multi-drug therapies. One route to improve adherence rates is to prepare fixed dose combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. Here, we report the use of electrospinning to prepare fast-dissolving oral FDCs containing amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment of hypertension. Electrospun fibers were prepared loaded with one or both drugs, using polyvinylpyrrolidone as the polymer matrix. The fibers were largely cylindrical in morphology and comprise amorphous solid dispersions except with the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment efficiencies of >85% of the theoretical dose. The mats have folding endurances and thicknesses suitable for use as oral films. The amlodipine besylate-loaded systems are fast-dissolving, with >90% release obtained within 120 s. In contrast, valsartan release from its single-drug formulations took longer, ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360 s was achieved when the loading was 5% w/w of each drug, but again the release time increased with drug loading. Electrospun fibers therefore have significant promise as FDCs, but the target drug and its loading need to be carefully considered.


The application of modern light-curing radiopaqie glass ionomer composites to the apical osteotomy.
The report reveals the application of modern light-curing radiopaque glass ionomer composites as a retrograde filling substance in the aplical osteotomy. The excellent results after 20 apical osteotomies which have been observed in the course of 3 years, prove the real possibility of using them in the dental surgery.


Neuro-Ophthalmology Annual Review.
The purpose of this review was to update the practicing ophthalmologist on the English language neuro-ophthalmology literature from the past year. A review of English language literature from August 1, 2013, to August 1, 2014, was conducted. The author searched PubMed from August 1, 2013, to August 1, 2014, limited to English language publications including original articles, review articles, and case reports and excluding letters to the editor, unpublished work, and abstracts. The following topics were searched: pupillary abnormalities, eye movement dysfunction, neuromuscular diseases, optic neuropathies, optic neuritis, demyelinating diseases including multiple sclerosis, lesions of the optic chiasm and posterior primary visual pathways, elevated intracranial pressure, tumors and aneurysms affecting the visual pathways, vascular diseases, higher visual function, and neuroimaging advances. The focus of this review is on clinically relevant literature in the past year for the practicing ophthalmologist. The aim was to highlight remarkable and interesting literature rather than exhaustively including all new neuro-ophthalmological publications of the year. Initially, more than 11,000 articles were identified. One hundred were selected that met criteria specified above. This review updates the comprehensive ophthalmologist on neuro-ophthalmic topics.


Explaining the visible and the invisible: Public knowledge of genetics, ancestry, physical appearance and race in Colombia.
Using data from focus groups conducted in Colombia, we explore how educated lay audiences faced with scenarios about ancestry and genetics draw on widespread and dominant notions of nation, race and belonging in Colombia to ascribe ancestry to collectivities and to themselves as individuals. People from a life sciences background tend to deploy idioms of race and genetics more readily than people from a humanities and race-critical background. When they considered individuals, people tempered or domesticated the more mechanistic explanations about racialized physical appearance, ancestry and genetics that were apparent at the collective level. Ideas of the latency and manifestation of invisible traits were an aspect of this domestication. People ceded ultimate authority to genetic science, but deployed it to work alongside what they already knew. Notions of genetic essentialism co-exist with the strategic use of genetic ancestry in ways that both fix and unfix race. Our data indicate the importance of attending to the different epistemological stances through which people define authoritative knowledge and to the importance of distinguishing the scale of resolution at which the question of diversity is being posed.


[Animal experimental models of breast cancer for therapeutic testing of hormones and antihormones].
Syngeneically and xenogeneically transplanted hormone-dependent mammary carcinomas were used for therapeutic in vivo estimation of the effect of hormones and antihormones. During the transplantation the majority of the tumors of the rat shows development from hormone dependence to hormone independence and, consequently, chemically induced (DMBA, NMU) mammary carcinomas have been the subject of considerable interest. Hormone-dependent mammary carcinomas of the mouse (MXT, estradiol- and progesterone-induced tumors and pregnancy-dependent mammary tumors of different mouse strains) are suitable for estimation of the effects of hormones. Xenogeneically transplanted hormone-dependent human tumors (B0 or T61, Br-10, SE, MCF-7, ZR75-1) are introduced in testing of hormones. During the transplantation of human mammary carcinomas in nude mice the hormone receptor status is preserved, and it is possible to perform endocrine treatments in models of human mammary carcinomas.


Dilemmas of spiritual assessment: considerations for nursing practice.
Interest in the spiritual dimension of nursing has resulted in a proliferation of published research internationally that is very prescriptive, suggesting that nurses should be providing spiritual care. However, little research has been published that provides nurses with a potential framework for the assessment and subsequent delivery of spiritual care. It would appear that there is a consensus of opinion that nurses can and should be able to undertake an assessment of their patients' spiritual needs. However, such assumptions may be unfounded, inaccurate, misguided and potentially detrimental to patient care. This article explores the area of spiritual assessment, drawing on the international literature, highlighting potential dilemmas in conducting a spiritual assessment. A review of some of the currently available spiritual assessment tools is also undertaken. A debate is presented based on the authors' experiences and opinions with regard to this aspect of care. The debate is informed by a review of the literature specifically addressing spiritual assessment. The authors use United Kingdom policy to illustrate drivers and provide a context for the debate. However the dilemmas presented and issues raised are of significance to a wider international audience. It is argued that the area of spiritual assessment needs careful consideration, both nationally and internationally, by those professionals involved in the provision of spiritual care so that potential dilemmas can be identified and reviewed. Such consideration may prevent the construction and subsequent use of inappropriate assessment tools within practice. The article incorporates some considerations for practice.


On the definition of gestational-age-specific mortality.
The "fetuses at risk" concept of gestational-age-specific mortality proposed by Yudkin et al. (Lancet 1987;1:1192-4) and extended by various researchers is becoming popular in perinatal and pediatric epidemiology. However, the definitions using this concept have led to a puzzling phenomenon in which mortality rates appear to increase monotonically with advancing gestational age. While proponents of this concept have highlighted the rationale for using as the denominator the number of fetuses at risk rather than that of fetuses delivered at a particular gestational week, many have not discussed how the numerator is derived. This article reviews various definitions of gestational-age-specific mortality rates. It points out that the definitions based on the concept of Yudkin et al. are indicators of short-term risk only. Furthermore, the seemingly monotonic positive association between mortality rates and gestational age is a misinterpretation. All of the definitions are valid when used and interpreted correctly. The choice of which definition to adopt depends on the specific issues one attempts to address. Calls for abandoning the conventional definitions are not justified.


Multi-dimension apportionment of clean air "parade blue" phenomenon in Beijing.
The mass concentration and major chemical components of fine particulate matter were measured before, during and after Beijing's massive parade commemorating 70th anniversary of the Chinese Victory in World War II on September 3, 2015. Regional emission inventory, positive matrix factorization (PMF), observations from space and backward air mass trajectories were jointly applied to identify the major pollution sources and their temporal and spatial variations. The contributions of emissions variations and the meteorological conditions related to the "parade blue" phenomenon in Beijing and its surrounding areas were investigated in detail. The main cause of the decreased PM2.5 mass concentration was attributed to the absolute reduction in emissions of primary air pollutants. The chemical composition of PM2.5 varied significantly before, during and after the parade. Fugitive dust particles were well controlled, the secondary formation of PM2.5 was reduced along with the controlled gaseous precursors' emissions from vehicles and industrial sources during the temporary intensified control period. During the parade period, the SO2 and NO2 column concentrations in Beijing and the surrounding areas decreased sharply, indicating that the coordinated reduction in primary emissions from the surrounding areas of Beijing played an important role in lowering the ambient concentration of SO2 and NO2 and accordingly lowered PM2.5 and improved the regional air quality. A comparison of the temperature, humidity, and wind speed and direction during the same periods in 2014 and 2015 showed that the meteorological conditions positively influenced the achievement of "parade blue".


Associations between mental health status and labor force transitions in China: A longitudinal study between agricultural and nonagricultural sectors.
No consensus has been reached on the relationship between retirement and mental health, and limited information is available on retirement and mental health in developing countries. This study investigated the associations between short-term changes in mental health status and labor force transitions (retirement and reemployment) in both the agricultural and nonagricultural sectors in China. This study used nationally representative panel data from three waves (2011, 2015, and 2018) of the China Health and Retirement Longitudinal Study on workers and retirees aged 40-70 years in China. The latent change score (LCS) model was employed. The transition from nonagricultural and agricultural sectors to retirement significantly increased the changes in the Center for Epidemiological Studies-Depression scale (CES-D-10) score. Reentering the nonagricultural sectors significantly decreased the changes in the CES-D-10 score, whereas reentering the agricultural sectors had no impact on the changes in the CES-D-10 score. Stronger associations were identified among male workers, while the associations were weaker and less significant for female workers. Findings are consistent with the resource-based dynamic theory and extends the work in developing country by showing the mental health status worsens after retirement transitions and improves after reentering the workforce, especially for nonagricultural male workers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The Challenges of Management of High-grade Gliomas in Nigeria.
High-grade gliomas (HGG) are among the most challenging brain tumors despite many research efforts worldwide. The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. Glioma was 60 (23.8%) of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks) of ≥70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.


Dynamic and static recordings of the comfortable zone.
A dynamic and a static method of assessing the comfortable zone by means of a screw jack were compared in 12 subjects. Recorded under dynamic conditions the average width of the comfortable zone was approximately 3.0 mm, and under static conditions approximately 5.0 mm (P less than 0.0001). It is suggested that in the dynamic experiments the larger output from receptors in the chewing system was responsible for the narrower zone, i.e. the more precise assessments of the comfortable zone.


Epidermal growth factor receptor expression during morphological differentiation of pheochromocytoma cells, induced by nerve growth factor or dibutyryl cyclic AMP.
Rat pheochromocytoma cells (clone PC12) possess functional surface receptors for both nerve growth factor (NGF) and epidermal growth factor (EGF). PC12 cells respond to NGF as well as to dibutyryl cyclic AMP (dbcAMP) by arrest of cell proliferation and initiation of morphological differentiation, while EGF acts as a mitogen. Exposure of PC12 cells to NGF for several days resulted in a complete loss of rapid EGF responses, such as membrane ruffling and activation of active K+ transport. EGF binding studies revealed that this loss of EGF responses was due to an almost complete reduction of the number of EGF binding sites. In contrast, exposure of PC12 cells to dbcAMP for 2 days did not affect the rapid EGF responses, despite the morphological differentiation. Moreover, EGF binding studies demonstrated a twofold increase in the number of high-affinity binding sites and a small increase in the number of low-affinity sites. In addition, exposure of the cells to dbcAMP caused a twofold increase of EGF-receptor phosphotyrosine kinase activity. These results indicate that neither EGF-binding or the presence of EGF receptors nor the rapid EGF responses are sufficient for persistent proliferation, on one hand, or sufficient to avoid morphological differentiation, on the other.


Transfer of 14C to prenatal and neonatal rats from their mothers exposed to 14C compounds by ingestion.
The transfer of 14C through placenta or milk was investigated and the radiation dose to fetal and newborn rats was estimated. Female rats at different gestational stages or after delivery were exposed to 14C in the form of sodium bicarbonate, thymidine and lysine by a single ingestion. Radioactivity in maternal tissues and conceptuses (placenta, fetal membrane and fetus) and in the newborn was determined at various times after ingestion. After exposure to these 14C compounds, there was no significant difference between the 14C concentration in the fetus and that in the maternal tissues, suggesting that the placenta has no effect in preventing or accelerating the placental transfer of 14C. The concentration and content of 14C in the fetus and newborn were, however, dependent on the chemical form of 14C and on the prenatal or neonatal stage at the time of ingestion. The result of the dose estimation showed that 14C-lysine gave significantly higher prenatal and neonatal doses than 14C-sodium bicarbonate or 14C-thymidine.


Molecular monitoring of the development of intestinal microbiota in Japanese infants.
The faecal microbiota of 166 healthy Japanese newborns was analysed periodically from day 1 after birth until the age of 3 years by using the reverse transcription-quantitative PCR. Faecal pH and the organic acid concentration were also examined. Colonisation by both facultative anaerobes and strict anaerobes was confirmed in 95% of the meconium tested. Bifidobacterium-predominant microbiota was established subsequently in most of the infants by 3 months after birth. Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium catenulatum group and Bifidobacterium bifidum were the species mainly detected. Intergroup correlation analysis revealed that the bifidobacterial population levels, but not other strict anaerobe groups, were found to be negatively correlated with those of the Enterobacteriaceae from 7 days until 3 months after birth. Faecal pH was maintained at about 6 until 6 months after birth and reached 6.6 at 3 years after birth. The initial concentration of faecal organic acids (19 μM/g of faeces) just after birth increased until 3 years after birth to the level of 111 μM/g of faeces. Early start of feeding formula milk promoted colonisation by obligate anaerobes such as the Clostridium coccoides group, the Clostridium leptum subgroup, Prevotella, and Atopobium cluster during the 3 months after birth. Population levels of the bifidobacteria until 1 month after birth and those of the Bacteroides fragilis group until 6 months after birth were lower in infants delivered by Caesarean section than in those delivered normally. The results suggested that both earlier start of feeding of formula milk and the mode of infant delivery were found to be important in the development of intestinal microbiota in early infancy.


Intraoperative magnetic resonance imaging in neurosurgery: the Brigham concept.
The resection of brain tumors is limited by the surgeon's ability to precisely define margins. To overcome this problem, various neuronavigational tools have been used. The development of image-guided navigation systems represents a substantial improvement in the microsurgical treatment of various intracranial lesions. However, a major drawback of this technology is that they use images acquired preoperatively, on which the surgical planning and intraoperative performance is based. As the intracranial anatomy dynamically changes during a neurosurgical procedure, only intraoperatively acquired images can provide the neurosurgeon with the information needed to perform real-time, image-guided surgery. Because magnetic resonance imaging best delineates the soft-tissue extent of most tumors, it currently remains the superior method for intraoperative image guidance. In this review, we outline the development as well as current and possible future applications of the intraoperative MRI (iMRI) unit at the Brigham and Women's Hospital, Boston, MA.


[Pneumocalorimetric assessment of functional state of the cardiorespiratory system in polyclinical practice].
Physical efficiency (PhE), maximal calorific capacity (MCC) and Pneumocalorimetric index which conditions the function of the respiratory apparatus can be described by the following equation: PhE = 59.9 . MCC + 33. An error of PhE calculated with the above mentioned technique doesn't exceed 12,5%. The use of pneumocalorimetric enables to assess the functional state of the cardiorespiratory system by determining PhE, labour-intensiveness of the method is 5.1 minutes per a test.


Hip arthroscopic surgery: patient evaluation, current indications, and outcomes.
Arthroscopic surgery in the hip joint has historically lagged behind its counterparts in the shoulder and knee. However, the management of hip injuries in the athletic population has rapidly evolved over the past decade with our improved understanding of mechanical hip pathology as well as the marked improvement in imaging modalities and arthroscopic techniques. Current indications for hip arthroscopic surgery may include symptomatic labral tears, femoroacetabular impingement (FAI), hip capsular laxity/instability, chondral lesions, disorders of the peritrochanteric or deep gluteal space, septic joint, loose bodies, and ligamentum teres injuries. Furthermore, hip arthroscopic surgery is developing an increasingly important role as an adjunct diagnostic and therapeutic tool in conjunction with open femoral and/or periacetabular osteotomy for complex hip deformities. Arthroscopic techniques have evolved to allow for effective and comprehensive treatment of various hip deformities. Techniques for extensile arthroscopic capsulotomies have allowed for improved central and peripheral compartment exposure and access for labral takedown, refixation, treatment of chondral injury, and osteochondroplasty of the femoral head-neck junction and acetabular rim. While favorable short-term and midterm clinical outcomes have been reported after arthroscopic treatment of prearthritic hip lesions, greater long-term follow-up is necessary to assess the efficacy of hip arthroscopic surgery in altering the natural history and progressive degenerative changes associated with FAI.


Palliative care for breathless patients in the community.
Breathlessness is one of the commonest symptoms experienced by people receiving palliative care. However, misunderstanding of the nature of palliative care may hinder assessment, management and evaluation of care and may contribute to the fear associated with living with breathlessness in the community. Knowledge of related anatomy and physiology of breathlessness is vital in informing nursing care and interventions. Pharmacological interventions have their place, but the focus of nursing care should be on systematic holistic assessment. Using this, nurses should adopt a proactive role in supporting and helping patients to adapt to change by maximizing coping strategies.


Evidence for a role of geranylgeranylation in renal angiomyolipoma and renal epithelioid angiomyolipoma.
Research on mevalonate kinase deficiency has revealed that it may lead to the development of renal angiomyolipomas (RAMLs). Thus, it was suspected that geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in the mevalonate pathway, may be involved in the development of RAMLs. In the present study, the expression of GGPPS in RAMLs and renal epithelioid angiomyolipomas (REAs) was assessed, and paraffin embedded specimens from 60 patients, including 9 cases with REA and 51 cases with RAML, were examined. Immunoreactivity was evaluated semi-quantitatively according to the intensity of staining and the percentage of positively stained cells. The results indicated that GGPPS was predominantly present in the cytoplasm, and REA tissues exhibited higher expression of GGPPS in the cytoplasm compared with RAML tissues. It was also identified that GGPPS was upregulated in TSC2-null cells, and inhibition of GGPPS could induce apoptosis of TSC2-null cells by autophagy. In conclusion, the increased expression of GGPPS in RAMLs and REAs indicated that mevalonate pathways may be involved in disease progression. GGPPS may serve as a potential therapeutic target and the current results may provide a novel therapeutic strategy for RAML and lymphangioleiomyomatosis.


Oxaloacetate Protects Rat Liver From Experimental Warm Ischemia/Reperfusion Injury by Improving Cellular Energy Metabolism.
Liver ischemia/reperfusion injury (IRI) is an important cause of liver damage especially early after liver transplantation, following liver resection, and in other clinical situations. Using rat experimental models, we identified oxaloacetate (OAA) as a key metabolite able to protect hepatocytes from hypoxia and IRI. In vitro screening of metabolic intermediates beneficial for hepatocyte survival under hypoxia was performed by measures of cell death and injury. In vivo, the effect of OAA was evaluated using the left portal vein ligation (LPVL) model of liver ischemia and a model of warm IRI. Liver injury was evaluated in vivo by serum transaminase levels, liver histology, and liver weight (edema). Levels and activity of caspase 3 were also measured. In vitro, the addition of OAA to hepatocytes kept in a hypoxic environment significantly improved cell viability (P < 0.01), decreased cell injury (P < 0.01), and improved energy metabolism (P < 0.01). Administration of OAA significantly reduced the extent of liver injury in the LPVL model with lower levels of alanine aminotransferase (ALT; P < 0.01), aspartate aminotransferase (AST; P < 0.01), and reduced liver necrosis (P < 0.05). When tested in a warm IRI model, OAA significantly decreased ALT (P < 0.001) and AST levels (P < 0.001), prevented liver edema (P < 0.001), significantly decreased caspase 3 expression (P < 0.01), as well as histological signs of cellular vesiculation and vacuolation (P < 0.05). This was associated with higher adenosine triphosphate (P < 0.05) and energy charge levels (P < 0.01). In conclusion, OAA can significantly improve survival of ischemic hepatocytes. The hepatoprotective effect of OAA was associated with increased levels of liver bioenergetics both in vitro and in vivo. These results suggest that it is possible to support mitochondrial activity despite the presence of ischemia and that OAA can effectively reduce ischemia-induced injury in the liver.


MUNC13-1 heterozygosity does not alter voluntary ethanol consumption or sensitivity in mice.
The role of the munc13-1 presynaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc13-1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitters in excitatory neurons. Ethanol binds munc13-1, which decreases its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and is associated with a resistance to sedation following ethanol exposure. The current study assessed the effects of munc13-1 heterozygosity on ethanol sensitivity and consumption in mice, as well as on learning and anxiety-like behaviors, which can influence alcohol intake. Wild-type and mutant mice underwent 6 cycles of drinking-in-the-dark (DID) as well as rotarod testing following ethanol injection, to probe for differences in ethanol consumption and sensitivity, respectively. We did not detect genotype-based differences in our measures of anxiety, spatial learning, ethanol consumption, or ethanol sensitivity. However, heterozygotes showed increased use of a spatial navigation strategy in a dual-solution water maze, as opposed to a stimulus-response strategy. To summarize, although reduction of Dunc13 in flies produces clear effects on ethanol consumption and sensitivity, heterozygosity for munc13-1 does not, potentially due to compensatory adaptation by other munc-13 isoforms.


168 million years old "marine lice" and the evolution of parasitism within isopods.
Isopods (woodlice, slaters and their relatives) are common crustaceans and abundant in numerous habitats. They employ a variety of lifestyles including free-living scavengers and predators but also obligate parasites. This modern-day variability of lifestyles is not reflected in isopod fossils so far, mostly as the life habits of many fossil isopods are still unclear. A rather common group of fossil isopods is Urda (190-100 million years). Although some of the specimens of different species of Urda are considered well preserved, crucial characters for the interpretation of their lifestyle (and also of their phylogenetic position), have so far not been accessible. Using up-to-date imaging methods, we here present morphological details of the mouthparts and the thoracopods of 168 million years old specimens of Urda rostrata. Mouthparts are of a sucking-piercing-type morphology, similar to the mouthparts of representatives of ectoparasitic isopods in groups such as Aegidae or Cymothoidae. The thoracopods bear strong, curved dactyli most likely for attaching to a host. Therefore, mouthpart and thoracopod morphology indicate a parasitic lifestyle of Urda rostrata. Based on morphological details, Urda seems deeply nested within the parasitic isopods of the group Cymothoida. Similarities to Aegidae and Cymothoidae are interpreted as ancestral characters; Urda is more closely related to Gnathiidae, which is therefore also interpreted as an ingroup of Cymothoida. With this position Urda provides crucial information for our understanding of the evolution of parasitism within isopods. Finally, the specimens reported herein represent the oldest parasitic isopods known to date.


Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function.
Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive reactive oxygen species (ROS) formation are a few of the suggested key mechanisms. Astaxanthin (AST), a carotenoid, is known to act as an antioxidant and protect neurons from excitotoxic injuries. However, the exact molecular mechanism of AST neuroprotection is not clear. Thus, in this study, we investigated the role of AST in neuroprotection in excitotoxicity. We utilized primary cortical neuronal culture and live cell fluorescence imaging for the study. Our results suggest that AST prevents neuronal death, reduces ROS formation and decreases the abnormal mitochondrial membrane depolarization induced by excitotoxic glutamate insult. Additionally, AST modulates intracellular calcium levels by inhibiting peak and irreversible secondary sustained calcium levels in neurons. Furthermore, AST regulates the ionotropic glutamate subtype receptors NMDA, AMPA, KA and mitochondrial calcium. Moreover, AST decreases NMDA and AMPA receptor protein expression levels, while KA remains unaffected. Overall, our results indicate that AST protects neurons from excitotoxic neuronal injury by regulating ionotropic glutamate receptors, cytosolic secondary calcium rise and mitochondrial calcium buffering. Hence, AST could be a promising therapeutic agent against excitotoxic insults in neurodegenerative diseases.


Nutrition, overnutrition, and obesity in the first year of line in Malmö, Sweden.
The feeding pattern, calorie intake, weight and height were studied at various ages during the first 12 months in 243 infants born in Sweden. The feeding pattern and calorie intake was close to that recommended. 0-6% in each age group were found to be obese (20-40% above the standard weight) and 15-23% overweight (10-20% above the standard weight). The mean calorie intake during the months before and when obesity and overweight were diagnosed exceeded the normal by 10% or less. When re-examined at age 2 plus or minus 1/2 years, 50% of those children obese up to 1 year remained so, and only 2 earlier overweight had become obese. 25% of the obese children had one obese parent, compared with 10% of the normal children and overweight ones. The low incidence of overnutrition and the low freqency of obese and overweight infants in this study compared with previous studies support the idea that high calorie intake is of importance in the development of obesity during infancy. Accordingly, overnutrition seems to be one factor, in the multifactorial aetiology of obesity, and reduction of overnutrition can reduce, but not abolish, infantile obesity. Whether the reduction of this will subsequently prevent adult obesity remains to be proved.


International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (rheumatoid arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome)?: The unmet needs and the clinical grey zone in autoimmune disease management.
Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity.


Principles of Cation-π Interactions for Engineering Mussel-Inspired Functional Materials.
Supramolecular assembly is commonly driven by noncovalent interactions (e.g., hydrogen bonding, electrostatic, hydrophobic, and aromatic interactions) and plays a predominant role in multidisciplinary research areas ranging from materials design to molecular biology. Understanding these noncovalent interactions at the molecular level is important for studying and designing supramolecular assemblies in chemical and biological systems. Cation-π interactions, initially found through their influence on protein structure, are generally formed between electron-rich π systems and cations (mainly alkali, alkaline-earth metals, and ammonium). Cation-π interactions play an essential role in many biological systems and processes, such as potassium channels, nicotinic acetylcholine receptors, biomolecular recognition and assembly, and the stabilization and function of biomacromolecular structures. Early fundamental studies on cation-π interactions primarily focused on computational calculations, protein crystal structures, and gas- and solid-phase experiments. With the more recent development of spectroscopic and nanomechanical techniques, cation-π interactions can be characterized directly in aqueous media, offering opportunities for the rational manipulation and incorporation of cation-π interactions into the design of supramolecular assemblies. In 2012, we reported the essential role of cation-π interactions in the strong underwater adhesion of Asian green mussel foot proteins deficient in l-3,4-dihydroxyphenylalanine (DOPA) via direct molecular force measurements. In another study in 2013, we reported the experimental quantification and nanomechanics of cation-π interactions of various cations and π electron systems in aqueous solutions using a surface forces apparatus (SFA).Over the past decade, much progress has been achieved in probing cation-π interactions in aqueous solutions, their impact on the underwater adhesion and cohesion of different soft materials, and the fabrication of functional materials driven by cation-π interactions, including surface coatings, complex coacervates, and hydrogels. These studies have demonstrated cation-π interactions as an important driving force for engineering functional materials. Nevertheless, compared to other noncovalent interactions, cation-π interactions are relatively less investigated and underappreciated in governing the structure and function of supramolecular assemblies. Therefore, it is imperative to provide a detailed overview of recent advances in understanding of cation-π interactions for supramolecular assembly, and how these interactions can be used to direct supramolecular assembly for various applications (e.g., underwater adhesion). In this Account, we present very recent advances in probing and applying cation-π interactions for mussel-inspired supramolecular assemblies as well as their structural and functional characteristics. Particular attention is paid to experimental characterization techniques for quantifying cation-π interactions in aqueous solutions. Moreover, the parameters responsible for modulating the strengths of cation-π interactions are discussed. This Account provides useful insights into the design and engineering of smart materials based on cation-π interactions.


Urologic complications in 718 renal transplant patients.
Urologic complications occurred in 13.2% of the 718 patients who received renal transplants performed during a 26-year period at the Peter Bent Brigham Hospital. The complication rate remained constant over the quarter century period, whereas the rate of death caused by complications decreased significantly during the last decade. This was due, in part, to recent use of ultrasound techniques permitting earlier recognition of complications. The majority of urologic complications occurred during the first month after transplantation. Contributing factors included technical problems, ischemia, and perhaps allograft rejection. No correlation could be found between degree of HLA match or mismatch and likelihood of complication. Internal indwelling stents offered substantial advantages over nephrostomy tubes for temporary urinary diversion. The most serious complications encountered were calyceal-cutaneous fistulas associated with donor kidneys with multiple renal arteries. "Bench" operation has proved to be a major technical advance in the prevention of these fistulas.