[Effect of substrate of edible mushroom on continuously cropping obstacle of Rehmannia glutinosa].
The continuous cultivation of Rehmannia glutinosa causes the accumulation of phenolic acids in soil. It is supposed to be the reason of the so called "continuously cropping obstacle". In this study, phenolic acids (hydroxybenzoic acid, vanillic acid, eugenol, vanillin and ferulic acid) were degraded by the extracta of all the tested spent mushroom substrate (SMS) and the maximal degradation rate was 75.3%, contributed by extraction of SMS of Pleurotus eryngii. Pot experiment indicated that hydroxybenzoic acid and vanillin in soil were also degraded effectively by SMS of P. eryngii. The employment of SMS enhanced ecophysiology index to near the normal levels, such as crown width, leaves number, leaf length, leaf width and height. At the same time, the fresh and dry weight and total catalpol concentration of tuberous root weight of R. glutinosa was increased to 2.70, 3.66, 2.25 times by employment of SMS, respectively. The increase of bacteria, fungi and actinomycetes numbers in rhizosphere soil were observed after the employment of SMS by microbial counts. The employment of SMS also enhanced the enzyme activity in soils, such as sucrase, cellulase, phosphalase, urease and catelase. These results indicated that the employment of SMS alleviated the continuously cropping obstacle of R. glutinosa in some extent.


[Vesico-intestinal fistula in Crohn disease: the role of echography in its diagnosis].
Ultrasound is in widespread use in the study of gastrointestinal pathologies. In Crohn disease it is helpful in diagnosing complications such as thickening of the bowel loop walls, abscesses, lymph node enlargement and vesical-enteric fistulas. This report presents two cases in which vesical-enteric fistulas were visualized by US; confirming a diagnosis of Crohn's disease in one case, and diagnosing the fistula during the follow-up in the second patient in whom Crohn's disease had previously been diagnosed.


[Depression in the elderly patient].
Depression is the most usual mental disorder in the elderly, but underdiagnosed and undertreated. Its prevalence is variable and depends on type and severity of episode. Nevertheless, even subsyndromic depression needs to be correctly treated. Depressive symptomatology observed in the elderly is often similar to adult presentation, but it can be masked and difficult to recognise. The different clinical features are described with underlining their particularities. Secondary depressions are also evoked with individualisation of "vascular" depression and its etiopathogenic hypotheses in relationship with observations given by cerebral neuro-imagery. Risk factors of depression in old age are known, but recent studies have reviewed some of them, particularly by distinguishing late onset depression and early onset depression. According to therapeutic response and prognosis, it appears necessary to better discriminate them. Risk of dementia after depression seems to be related with type of depressive episode and with the treatment efficacy. Finally, the problem of detection of depression in old age is discussed with a suggestion to use assessment instruments as the mini-GDS in all medical practices, to optimise diagnosis and management.


Randomized, placebo-controlled, phase 3 study of itraconazole for the treatment of onychomycosis.
Itraconazole, approved for treatment of toenail fungal infection onychomycosis, provides antifungal activity at a dosage requiring once-daily (QD) administration of 2 100-mg capsules for 12 weeks. Utilizing the Meltrex® technology delivery system, a novel 200-mg formulation of itraconazole was developed delivering the same dosage as 2 capsules in a single tablet. This phase 3, randomized, placebo-controlled trial investigated the noninferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsules dosed QD for 12 weeks, with a 40-week follow-up period. Clinical Cure (Investigator's Global Assessment plus mycological examination) was the primary outcome measure and Clinical Improvement was a secondary endpoint. Safety and efficacy of itraconazole 200-mg tablets were also compared with placebo. Significantly more patients in the intent-to-treat per-protocol populations on itraconazole (200-mg tablet or 2 100-mg capsules) achieved Complete Cure and Clinical Improvement compared with placebo. For both endpoints, itraconazole 200-mg tablet QD was noninferior to itraconazole 100-mg capsules and superior to placebo. All treatment groups demonstrated a similar safety profile with no new safety signals identified. Absolute patient blinding was not possible; the number of tablets versus capsules differed, and the appearance of the active drugs could not be masked. However, efficacy was based on objective assessments from blinded investigators. Once-daily itraconazole 200-mg was well-tolerated, and may be an effective alternative to 2 itraconazole 100-mg capsules for the treatment of toenail onychomycosis. The convenience of a simpler dosing regimen may improve patient compliance


Inter-half-cycle spectral interference in high-order harmonic generation from monolayer MoS2.
The enhancement of even-order harmonics near the cut-off of high-order harmonic spectra from monolayer MoS2 has been experimentally observed recently by several groups. Here we demonstrate that this enhancement can be interpreted as a result of spectral interference between half-cycles with opposite polarity by adopting a fully quantum mechanical calculation. We found that, due to the energy modulation induced by Berry connections, only half-cycles with the same polarity can generate high-order harmonics near the cut-off frequency, thus the lack of destructive interference leads to the enhanced intensity of the corresponding even-order harmonics. The explanation is supported by the frequency shift of the measured harmonic peaks. Our finding revealed the role of inter-half-cycle interference in high-harmonic generation (HHG) from non-centrosymmetric materials.


Expression of neuronal nitric oxide synthase in rabbit carotid body glomus cells regulates large-conductance Ca2+-activated potassium currents.
Our previous studies show that a decrease in endogenous nitric oxide (NO) is involved in the blunted outward K(+) currents in carotid body (CB) glomus cells from chronic heart failure (CHF) rabbits. In the present study, we measured the effects of the neuronal nitric oxide synthase (nNOS) transgene on the K(+) currents in CB glomus cells from pacing-induced CHF rabbits. Using single-cell real-time RT-PCR and immunofluorescent techniques, we found that nNOS mRNA and protein are expressed in the rabbit CB glomus cells and CHF decreased the expression of nNOS mRNA and protein in CB glomus cells. After 3 days of an adenoviral nNOS (Ad.nNOS) gene transfection, the expression of nNOS protein was increased to the level found in sham CB glomus cells. In whole cell patch-clamp experiments, Ad.nNOS markedly reversed the attenuated K(+) currents in CB glomus cells from CHF rabbits. The specific nNOS inhibitor (S-methyl-l-thiocitrulline [SMTC]) and large-conductance Ca(2+)-activated K(+) (BK) channel blocker (iberiotoxin) fully abolished the effect of Ad.nNOS on the K(+) currents in the CB glomus cells from CHF rabbits. However, neither CHF nor Ad.nNOS altered the protein expression of BK channel alpha-subunit. These results suggest that a decrease of NO induced by an attenuated nNOS activity lowers the activation of the BK channels but not the protein expression of the BK channel alpha-subunit in the CB glomus cells during CHF.


The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer.
Currently, alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases worldwide, representing one of the main etiologies of cirrhosis and hepatocellular carcinoma (HCC). Although we do not know the exact mechanisms by which only a selected group of patients with ALD progress to the final stage of HCC, the role of the gut microbiota within the progression to HCC has been intensively studied in recent years. To date, we know that alcohol-induced gut dysbiosis is an important feature of ALD with important repercussions on the severity of this disease. In essence, an increased metabolism of ethanol in the gut induced by an excessive alcohol consumption promotes gut dysfunction and bacterial overgrowth, setting a leaky gut. This causes the translocation of bacteria, endotoxins, and ethanol metabolites across the enterohepatic circulation reaching the liver, where the recognition of the pathogen-associated molecular patterns via specific Toll-like receptors of liver cells will induce the activation of the nuclear factor kappa-B pathway, which releases pro-inflammatory cytokines and chemokines. In addition, the mitogenic activity of hepatocytes will be promoted and cellular apoptosis will be inhibited, resulting in the development of HCC. In this context, it is not surprising that microbiota-regulating drugs have proven effectiveness in prolonging the overall survival of patients with HCC, making attractive the implementation of these drugs as co-adjuvant for HCC treatment.


The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro.
Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV treatment of HNSCC and normal oral keratinocyte cell lines, we carried out MTT analysis (cell viability), flow cytometry (cell cycle analysis), (immuno) fluorescence and western blotting (DNA double strand breaks, DNA damage response, apoptosis and mitotic catastrophe). The growth of the cell lines was inhibited by CDV treatment and resulted in γ-H2AX accumulation and upregulation of DNA repair proteins. CDV did not activate apoptosis but induced S- and G2/M phase arrest. Phospho-Aurora Kinase immunostaining showed a decrease in the amount of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe. In conclusion, CDV inhibits cell growth in HPV-positive and -negative HNSCC cell lines and was more profound in the HPV-positive cell lines. CDV treated cells show accumulation of DNA DSBs and DNA damage response activation, but apoptosis does not seem to occur. Rather our data indicate the occurrence of mitotic catastrophe.


Negative reflection of Lamb waves at a free edge: Tunable focusing and mimicking phase conjugation.
The paper studies the interaction of Lamb waves with the free edge of a plate. The reflection coefficients of a Lamb mode at a plate free edge are calculated using a semi-analytical method, as a function of frequency and angle of incidence. The conversion between forward and backward Lamb modes is thoroughly investigated. It is shown that at the zero-group velocity (ZGV) frequency, the forward S1 Lamb mode fully converts into the backward S2b Lamb mode at normal incidence. Besides, this conversion is very efficient over most of the angular spectrum and remains dominant at frequencies just above the ZGV-point. This effect is observed experimentally on a Duralumin plate. First, the S1 Lamb mode is selectively generated using a transducer array, second the S2b mode is excited using a single circular transducer. The normal displacement field is probed with an interferometer. The free edge is shown to retro-focus the incident wave at different depths depending on the wave number mismatch between the forward and backward propagating modes. In the vicinity of the ZGV-point, wave numbers coincide and the wave is retro-reflected on the source. In this frequency range, the free edge acts as a perfect phase conjugating mirror.


The impact of increasing similar interfering experiences on mnemonic discrimination: Electrophysiological evidence.
The accumulation of similar interfering experiences hampers our ability to retrieve information. To reduce interference, pattern separation allows the separation of similar memories and build detailed memory representations that are less easily confused. To investigate mnemonic interference, previous research has used a mnemonic discrimination paradigm in which the participants have to mnemonically discriminate between two similar items. Unique from previous studies, electrophysiological brain activity was recorded while 26 healthy participants performed a visual mnemonic discrimination task in which we parametrically manipulated the number of studied exemplars from each category. According to our expectations, as the number of exemplars from the same object category increased, participants were less able to discriminate between old and similar presented items. A 'parietal' old/new effect in a temporal window associated with recollection was observed when interference was higher. Increasing the number of exemplars presented also modulated the ERP amplitude in a temporal window associated with familiarity.


Two new phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity.
A new biphenyl-furocoumarin, named morescoumarin A (1), and a new prenylated flavanone, named morflavanone A (2) were isolated from the root bark of Morus alba L., together with four known compounds (3-6). Their structures were determined by extensive spectroscopic analyses and comparison with literature data. The cardioprotective effects of these compounds against doxorubicin-induced cell death were evaluated by MTT method.


Differential diagnosis of cerebral palsy: Lesch-Nyhan syndrome without self-mutilation.
Athetotic cerebral palsy was diagnosed in a 6-month-old boy with no history of perinatal trauma. Lesch-Nyhan syndrome (i.e., complete deficiency of hypoxanthine-guanine phosphoribosyltransferase [HGPRT] ) was diagnosed only when the boy began biting his lower lip at the age of 10 years. It is suggested, on the basis of this case and others like it in the literature, that the delayed onset or absence of self-mutilation in patients with Lesch-Nyhan syndrome may be more common than has been previously suspected. In all males said to have cerebral palsy, HGPRT deficiency must be ruled out, preferably by measuring the ratio of uric acid to creatinine in a random urine specimen.


Cloning and functional analysis of Δ6-desaturase gene and its upstream region from Mortierella sp. AGED.
Δ6-desaturase belonging to membrane-bound enzyme is a key enzyme involved in the synthesis of polyunsaturated fatty acids (PUFAs). This study aimed to clone and characterise Δ6-desaturase gene and its upstream regulatory region of Mortierella sp. AGED. Glucose and soybean meal are best for lipid and arachidonic acid accumulation of Mortierella sp. AGED. A 1375-bp Δ6-desaturase gene AGfad6 which contains a 1275-bp open reading frame encoding 424 amino acids without signal peptide was cloned. The putative protein contained three conserved histidine-rich motifs and a conserved cytochrome b5 HPGG (H: Histine, P: Proline, G: Glycine, G: Glycine) motif, with a mass of 48.3 kDa and an isoelectric point of 5.96. AGfad6 was successfully expressed in Pichia pastoris GS115, which exerted the effect on converting linoleic acid to γ-linolenic acid. The 1712-bp upstream region contained basic transcriptional elements including TATA, GC and GATA box, putative target-binding sites for transcription factors such as TATA binding protein, transcription activator, CCAAT-enhancer-binding protein, activator protein 1, alcohol dehydrogenase gene regulator 1 and metabolic regulators p40x in fungi, stress-related elements including GT-1 (light-responsive, salicylic acid-inducible), stress response element, heat stress-responsive element, which might participate in regulation of PUFAs synthesis. The present finding could enable us to understand the evolution and regulatory mechanism of Δ6-desaturase gene.


Familiarity with images affects how dogs ( Canis familiaris) process life-size video projections of humans.
A central problem of behavioural studies providing artificial visual stimuli for non-human animals is to determine how subjects perceive and process these stimuli. Especially in the case of videos, it is important to ascertain that animals perceive the actual content of the images and are not just reacting to the motion cues in the presentation. In this study, we set out to investigate how dogs process life-sized videos. We aimed to find out whether dogs perceive the actual content of video images or whether they only react to the videos as a set of dynamic visual elements. For this purpose, dogs were presented with an object search task where a life-sized projected human was hiding a target object. The videos were either normally oriented or displayed upside down, and we analysed dogs' reactions towards the projector screen after the video presentations, and their performance in the search task. Results indicated that in the case of the normally oriented videos, dogs spontaneously perceived the actual content of the images. However, the 'Inverted' videos were first processed as a set of unrelated visual elements, and only after some exposure to these videos did the dogs show signs of perceiving the unusual configuration of the depicted scene. Our most important conclusion was that dogs process the same type of artificial visual stimuli in different ways, depending on the familiarity of the depicted scene, and that the processing mode can change with exposure to unfamiliar stimuli.


Catecholamine Derivatives: Natural Occurrence, Structural Diversity, and Biological Activity.
Catecholamines (CAs) are aromatic amines containing a 3,4-dihydroxyphenyl nucleus and an amine side chain. Representative CAs included the endogenous neurotransmitters epinephrine, norepinephrine, and dopamine. CAs and their derivatives are good resources for the development of sympathomimetic or central nervous system drugs, while they also provide ligands important for G-protein coupled receptor (GPCR) research. CAs are of broad interest in the fields of chemical, biological, medical, and material sciences due to their high adhesive capacities, chemical reactivities, metal-chelating abilities, redox activities, excellent biocompatibilities, and ease of degradability. Herein, we summarize CAs derivatives isolated and identified from microorganisms, plants, insects, and marine invertebrates in recent decades, alongside their wide range of reported biological activities. The aim of this review is to provide an overview of the structural and biological diversities of CAs, the regularity of their natural occurrences, and insights toward future research and development pertinent to this important class of naturally occurring compounds.


[Severe imported malaria in adults: a retrospective study of thirteen cases admitted to the Intensive Care Unit in Marrakech].
Imported malaria is being seen with increasing frequency in non-endemic areas. Severe forms represent 10% of cases of Plasmodium falciparum malaria. In Morocco, more than 50 cases of malaria occur each year, 83% of which with Plasmodium falciparum malaria. All patients with severe malaria admitted to the Intensive Care Unit during the period between 1 November 2009 and 31 December 2015 were enrolled in our study. The main epidemiological data, the reasons for admission, the management and the outcomes of patients were studied. Thirteen patients were included in our study. The average age was 31 years. All patients had been living in sub-Saharan Africa and had no immunity to malaria. Chemoprophylaxis was adequate in 33% of cases. The mean time between symptom onset and treatment initiation was six days. Mean initial parasitemia was 12%. The main reasons for ICU admission included coma (15%), convulsion (07%), respiratory distress 07%), prostration (07%), renal failure (07%), shock associated with jaundice and acidosis (07%) and kidney failure associated with coma (07%). All patients were treated with intravenous quinine loading dose. Mortality rate was 23%. The causes of death were multi-system organ failure and acute respiratory distress syndrome. Mortality associated with severe malaria remains high. The adequacy of chemoprophylaxis associated with early diagnosis and treatment would significantly improve the prognosis of this parasitic infection.


The effects of heat applications on macrocyclic lactone-structured antiparasitic drug residues in cows' milk.
The study aimed to evaluate the effects of heat on macrocyclic lactone residues in cows' milk. Ivermectin, abamectin, doramectin, eprinomectin and moxidectin were added to raw milk in three concentrations. The milk was then pasteurised (40 seconds at 74°C or 1 minute at 80°C) and boiled (10 minutes at 100°C). The analyses were performed with a validated method: LC-MS/MS. Thermal treatment resulted in a statistically significant decrease in the abamectin, eprinomectin, and moxidectin concentrations in the milk; however, the residues did not completely degrade. Boiling resulted in a greater decrease in the moxidectin concentrations than was observed with pasteurisation. The high pasteurisation and boiling processes had a greater effect on the eprinomectin residues than did the low pasteurisation process. The pasteurisation and boiling processes did not have an effect on the doramectin and ivermectin. The study concluded that the macrocyclic lactones are generally resistant to such processes.


Whole exome sequencing reveals a stop-gain mutation of PKD2 in an autosomal dominant polycystic kidney disease family complicated with aortic dissection.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder characterized by progressive cyst formation and expansion in the kidneys, which culminates in end-stage renal disease. Aortic dissection is a rare vascular complication of ADPKD and related literature is currently limited. In this report, we described a patient with asymptomatic Stanford B aortic dissection. Further investigation revealed a positive family history of ADPKD and normal renal function. Whole exome sequencing identified a stop-gain mutation c.1774C > T, p.Arg592Ter in the PKD2 gene that segregated in the family. To our knowledge, this is the first report of ADPKD complicated with aortic dissection caused by PKD2 mutation. The case illustrates the importance of aorta imaging and molecular diagnosis in ADPKD patients in order to achieve early recognition of the deadly vascular complication.


Retrospective observational study on the effects and tolerability of flutamide in a large population of patients with various kinds of hirsutism over a 15-year period.
The aim of the study was to evaluate the long-term effects and tolerability of flutamide (Flu) in hirsute women. To the best of our knowledge, this study represents the largest report, concerning the population studied and the duration of treatment, to evaluate Flu use in hirsutism treatment. Over a 15-year period spanning from January 1991 to January 2006, a total of 414 premenopausal women with hirsutism of different aetiopathogeneses received yearly reducing doses (250, 125 and 62.5 mg/day) of Flu alone or in combination with oral contraceptives for a period varying from at least 3 to 8 years and more. Clinical and endocrine evaluations were assessed half-yearly and yearly respectively in the first 3 years of the study, and yearly in the following years. Liver function evaluations were assessed quarterly. Both the groups of patients under Flu therapy showed a marked decrease in hirsutism scores after 12 months compared with basal values. The maximum drug effect was observed after 2 years, and it was maintained during the following years of treatment. Androgens were strongly suppressed during treatment. During the first year of treatment, 6.0% of patients abandoned the study due to hepatic disorders related to the drug. During the following years with the lowest treatment regimen, none of the patients abandoned the study due to hepatic discomfort. Flu is a satisfactory therapeutic regimen for any form of hirsutism in the long run. Moreover, the use of very low doses of Flu is associated with minimal side-effects and high compliance.


[Aspects of Hansen's disease in the urban area of the municipality of São Paulo - undifferentiated Hansen's disease, 1963-1977].
The purpose of this work is to analyze the epidemiological changes that have occurred in São Paulo due to geographical and historical influences. This research was made during the period of 1963 to 1977, covering 6,664 cases and two main aspects: origin and age. In 1977, Sao Paulo presented 5,179 inhabitants per square kilometer and a percentage of 5,3 hanseniasis patients per square kilometer. The data compiled during the research have led to the following conclusions: São Paulo has become an important economical center and as such a point of attraction to intense migratory currents; this increase has caused the formation of unplanned and outnumbered populational centers in the outskirts which are obstacles to medical and social welfare assistance and to diagnosis and control as well; changes in the social and economical structures leading to a poorer family life; increase in the possibilities of transmission of hanseniasis either by non-intimate or long-termed contacts; decrease in the number of cases in the same family and, finally, the characterization of hanseniasis as a grown-up and urban disease.


[Otoacoustic emissions measurements in children during the chemotherapy because of the acute lymphoblastic leukemia].
Chemotherapy is associated with an increased risk of ototoxic changes. The predictive value of conventional pure-tone audiometry on early detection of ototoxicity has been questioned. Otoacoustic emissions (OAEs) appear to be more sensitive to cochlear insult than the conventional pure-audiometry. The purpose of our study was (a) investigation the clinical usefulness of Distortion Product Otoacoustic Emissions (DPOAEs) as early indicator of chemotherapy-induced ototoxicity, (b) determination which of the protocols of chemotherapy is most ototoxic as measured by DPOAEs, (c) comparison of the short-term and long-term effects of chemotherapy on DPOAEs. Tonal audiometry (0,25-8 kHz), immitance audiometry and DPOAEs were measured in 10 children with acute lymphoblastic leukemia (ALL). Measurements were performed before and after each protocol of ALL IC-BFM 2002 chemotherapy: protocol I: vincristine (VCR), L-asparaginase (L-ASP), daunorubicin (DNR), cyclophosphamide (CPM), cytarabine (ARA-C), 6-mercaptopurine (6-MP), methotrexate (MTX); protocol mM: 6-MP, MTX; protocol II: VCR, doxorubicin (DOX), L-ASP, CMP, ARA-C, thioguasine (6-TG), MTX; protocol III: VCR, DOX, L-ASP, CMP, ARA-C, 6-TG, MTX. DPOAEs were measured using ILO2 92 Otodynamics Analyser. Cochlear activity was evaluated by recording 2f1-f2 DPOAEs with L1 = 65 and L2 = 60 dB SPL. Comparisons of the DP-grams amplitudes were performed between baseline measurements and those recorded before and after each chemotherapy course. Our results indicate that: a)DPOAE is a more sensitive technique for the assess of chemotherapy-induced ototoxicity than conventional audiometry, b) with DPOAE monitoring very subtle hearing changes can be detected, c) DPOAE amplitude was significantly decreased at all frequencies studied in 50% children with leukemia, d) depression of DPOAE amplitude was evident only during and after first protocol, e) long-term DPOAE monitoring reviled reversibility of ototoxicity in all children, f) a large individual variability in the DPOAE response following the chemotherapy was observed, g) in a few cases a transient increase in DPOAE amplitude had been observed before it was reduced. Distortion product otoacoustic emissions measurements are very sensitive on early detection of the changes in cochlear function and are recommended for monitor hearing in patients during chemotherapy.


Anesthesia for cesarean delivery in a patient with large anterior mediastinal tumor presenting as intrathoracic airway compression.
Anterior mediastinal mass is a rare pathology that presents considerable anesthetic challenges due to cardiopulmonary compromise. We present a case that was referred to us in the third trimester of pregnancy with severe breathlessness and orthopnea. An elective cesarean delivery was performed under combined spinal epidural anesthesia with a favorable outcome. We discuss the perioperative considerations in these patients with a review of the literature.


Remote epitaxial interaction through graphene.
The concept of remote epitaxy involves a two-dimensional van der Waals layer covering the substrate surface, which still enable adatoms to follow the atomic motif of the underlying substrate. The mode of growth must be carefully defined as defects, e.g., pinholes, in two-dimensional materials can allow direct epitaxy from the substrate, which, in combination with lateral epitaxial overgrowth, could also form an epilayer. Here, we show several unique cases that can only be observed for remote epitaxy, distinguishable from other two-dimensional material-based epitaxy mechanisms. We first grow BaTiO3 on patterned graphene to establish a condition for minimizing epitaxial lateral overgrowth. By observing entire nanometer-scale nuclei grown aligned to the substrate on pinhole-free graphene confirmed by high-resolution scanning transmission electron microscopy, we visually confirm that remote epitaxy is operative at the atomic scale. Macroscopically, we also show variations in the density of GaN microcrystal arrays that depend on the ionicity of substrates and the number of graphene layers.


Bufospirostenin A and Bufogargarizin C, Steroids with Rearranged Skeletons from the Toad Bufo bufo gargarizans.
Bufospirostenin A (1) and bufogargarizin C (2), two novel steroids with rearranged A/B rings, were isolated from the toad Bufo bufo gargarizans. Compound 1 represents the first spirostanol found in animals. Compound 2 is an unusual bufadienolide with a cycloheptatriene B ring. Their structures were elucidated by spectroscopic analysis, single crystal X-ray diffraction analysis, and computational calculations.


Stability in the South, Turbulence Toward the North: Evolutionary History of Aurinia saxatilis (Brassicaceae) Revealed by Phylogenomic and Climatic Modelling Data.
The Balkan Peninsula played an important role in the evolution of many Mediterranean plants and served as a major source for post-Pleistocene colonisation of central and northern Europe. Its complex geo-climatic history and environmental heterogeneity significantly influenced spatiotemporal diversification and resulted in intricate phylogeographic patterns. To explore the evolutionary dynamics and phylogeographic patterns within the widespread eastern Mediterranean and central European species Aurinia saxatilis, we used a combination of phylogenomic (restriction-site associated DNA sequencing, RADseq) and phylogenetic (sequences of the plastid marker ndhF) data as well as species distribution models generated for the present and the Last Glacial Maximum (LGM). The inferred phylogenies retrieved three main geographically distinct lineages. The southern lineage is restricted to the eastern Mediterranean, where it is distributed throughout the Aegean area, the southern Balkan Peninsula, and the southern Apennine Peninsula, and corresponds to the species main distribution area during the LGM. The eastern lineage extends from the eastern Balkan Peninsula over the Carpathians to central Europe, while the central lineage occupies the central Balkan Peninsula. Molecular dating places the divergence among all the three lineages to the early to middle Pleistocene, indicating their long-term independent evolutionary trajectories. Our data revealed an early divergence and stable in situ persistence of the southernmost, eastern Mediterranean lineage, whereas the mainland, south-east European lineages experienced more complex and turbulent evolutionary dynamics triggered by Pleistocene climatic oscillations. Our data also support the existence of multiple glacial refugia in southeast Europe and highlight the central Balkan Peninsula not only as a cradle of lineage diversifications but also as a source of lineage dispersal. Finally, the extant genetic variation within A. saxatilis is congruent with the taxonomic separation of peripatric A. saxatilis subsp. saxatilis and A. saxatilis subsp. orientalis, whereas the taxonomic status of A. saxatilis subsp. megalocarpa remains doubtful.


Targeted Treatment of Age-Related Fibromyalgia with Supplemental Coenzyme Q10.
Fibromyalgia is a common chronic pain condition of unknown aetiology, although mitochondrial dysfunction, oxidative stress, and inflammation have been implicated in the pathophysiology of this disorder. Treatment generally involves physiotherapy, anticonvulsants, and antidepressant therapy; however, the symptomatic relief conferred by these treatments can be very variable, and there is a need for additional therapeutic strategies. One such treatment which is gaining a lot of interest is the use of coenzyme Q10 (CoQ10) supplementation. The therapeutic efficacy associated with CoQ10 supplementation is thought to arise from the ability of supplementation to restore an underlying deficit in CoQ10 status which has been associated with fibromyalgia together with the ability of CoQ10 to improve mitochondrial activity, restore cellular antioxidant capacity, and ameliorate inflammation. This chapter outlines the evidence supporting the therapeutic utility of CoQ10 in the treatment of fibromyalgia.


[International academic exchange in China in medical history in the 1980s:An Interview with].
Li Jingwei is one of the first experts on medical history philology in New China. He studied under Chen Bangxian and then began to work in the field of medical history philology in Beijing. He had several meetings and academic discussions with Professor Joseph Needham, a well-known scientist in the history of science, technology and medicine. In the 1980s, as a representative in the field of medical history in China, he participated in meetings for academic exchange with scholars from Thailand, Japan, Germany and the United States, through seminars and conferences such as the Thailand Chinese Academic Exchange Seminar in 1983, the Seminar of the 150th Anniversary of The American Association for the Advancement of Science in 1984, the 86th Annual Conference of Japanese Medical History Society in 1985, and the International Chinese Science and Technology History Seminar in the UK in 1990. In these seminars, he made friends with scholars, such as Manfred Porkert, Saburo Miyashita and Wu Yanhe. He witnessed and participated in international academic exchanges in the beginning of the reform and opening-up in China.


Functional outcomes and complications following B-TURP versus HoLEP for the treatment of benign prostatic hyperplasia: a review of the literature and Meta-analysis.
To conduct a systematic review and Meta-analysis of the literature on the efficacy and safety of B-TURP versus HoLEP for the treatment of benign prostatic hyperplasia (BPH) in terms of demographic and clinical baseline characteristics, peri-operative variables, and postoperative outcomes and complications. Trials comparing B-TURP and HoLEP were identified systematically using Pubmed, Embase, CNKI, Web of Science and the Cochrane Library. Primary outcomes were the peak urinary flow rate (Qmax), post-void residual volume (PVR) and international prostate symptom score (IPSS). Secondary outcomes were operation time, irrigation duration, catheterization duration, resected tissue and complications. Four trials assessing B-TURP and HoLEP were considered eligible for Meta-analysis, including three randomized controlled trials (RCTs) and one retrospective study. There was no statistically significant difference between B-TURP and HoLEP in terms of Qmax, IPSS, PVR at 3-6 months follow-up, operation duration, catheterization duration, resected tissue and complications (p > 0.05). HoLEP was associated with a significantly shorter irrigation time as compared with B-TURP (p < 0.05). Both B-TURP and HoLEP are safe and minimally invasive techniques that are similar in terms of symptomatic relief, although these findings need further validation in larger RCTs involving larger numbers of patients and over a longer follow-up duration for B-TURP or HoLEP before a new gold standard procedure emerges for surgical treatment of BPH.


Characterization of a Unique Outer Membrane Protein Required for Oxidative Stress Resistance and Virulence of Francisella tularensis.
Francisella tularensis, the causative agent of tularemia, lacks typical bacterial virulence factors and toxins but still exhibits extreme virulence. The bacterial multidrug efflux systems consist of an inner membrane, a transmembrane membrane fusion protein, and an outer membrane (OM) component that form a contiguous channel for the secretion of a multitude of bacterial products. Francisella contains three orthologs of the OM proteins; two of these, termed TolC and FtlC, are important for tularemia pathogenesis. The third OM protein, SilC, is homologous to the silver cation efflux protein of other bacterial pathogens. The silC gene (FTL_0686) is located on an operon encoding an Emr-type multidrug efflux pump of F. tularensis The role of SilC in tularemia pathogenesis is not known. In this study, we investigated the role of SilC in secretion and virulence of F. tularensis by generating a silC gene deletion (ΔsilC) mutant and its transcomplemented strain. Our results demonstrate that the ΔsilC mutant exhibits increased sensitivity to antibiotics, oxidants, silver, diminished intramacrophage growth, and attenuated virulence in mice compared to wild-type F. tularensis However, the secretion of antioxidant enzymes of F. tularensis is not impaired in the ΔsilC mutant. The virulence of the ΔsilC mutant is restored in NADPH oxidase-deficient mice, indicating that SilC resists oxidative stress in vivo Collectively, this study demonstrates that the OM component SilC serves a specialized role in virulence of F. tularensis by conferring resistance against oxidative stress and silver.IMPORTANCEFrancisella tularensis, the causative agent of a fatal human disease known as tularemia, is a category A select agent and a potential bioterror agent. The virulence mechanisms of Francisella are not completely understood. This study investigated the role of a unique outer membrane protein, SilC, of a multidrug efflux pump in the virulence of F. tularensis This is the first report demonstrating that the OM component SilC plays an important role in efflux of silver and contributes to the virulence of F. tularensis primarily by providing resistance against oxidative stress. Characterization of these unique virulence mechanisms will provide an understanding of the pathogenesis of tularemia and identification of potential targets for the development of effective therapeutics and prophylactics for protection from this lethal disease.


[H5N1: vaccine solutions for humans and other animals].
The hypervirulence of H5N1 influenza virus makes it impossible to produce a vaccine traditionally (with egg embryos), but there are alternative solutions. A live recombinant fowl-pox H5 virus is used for avian pathology. An inactivated H5N2 adjuvant vaccine is rendered immunogenic by using hemagglutinin H5 (DIVA technique). Disease prevention strategies differ between European and Asian countries. WHO has opted for a recombinant vaccine based on a non pathogenic virus (PR8) to which modified H5 and N1 from a pandemic virus are grafted The poor immunogenicity of this vaccine will require the use of large doses and immunostimulants. A live vaccine based on an adenovirus coupled to the H5 gene was recently developed. Finally, Chinese authors are examining the preventive and curative potential of hyperimmune serum raised in animals.


Glioactive ATP controls BDNF recycling in cortical astrocytes.
We have recently reported that long-term memory retention requires synaptic glia for proBDNF uptake and recycling. Through the recycling course, glial cells release endocytic BDNF, a mechanism that is activated in response to glutamate via AMPA and mGluRI/II receptors. Cortical astrocytes express receptors for many different transmitters suggesting for a complex signaling controlling endocytic BDNF secretion. Here, we demonstrated that the extracellular nucleotide ATP, activating P2X and P2Y receptors, regulates endocytic BDNF secretion in cultured astrocytes. Our data indicate that distinct glioactive molecules can participate in BDNF glial recycling and suggest that cortical astrocytes contributing to neuronal plasticity can be influenced by neurotransmitters in tune with synaptic needs.


[Radiotherapy for breast cancer: respiratory and set-up uncertainties].
Adjuvant Radiotherapy has been shown to significantly reduce locoregional recurrence but this advantage is associated with increased cardiovascular and pulmonary morbidities. All uncertainties inherent to conformal radiation therapy must be identified in order to increase the precision of treatment; misestimation of these uncertainties increases the potential risk of geometrical misses with, as a consequence, underdosage of the tumor and/or overdosage of healthy tissues. Geometric uncertainties due to respiratory movements or set-up errors are well known. Two strategies have been proposed to limit their effect: quantification of these uncertainties, which are then taken into account in the final calculation of safety margins and/or reduction of respiratory and set-up uncertainties by an efficient immobilization or gating systems. Measured on portal films with two tangential fields, CLD (central lung distance), defined as the distance between the deep field edge and the interior chest wall at the central axis, seems to be the best predictor of set-up uncertainties. Using CLD, estimated mean set-up errors from the literature are 3.8 and 3.2 mm for the systematic and random errors respectively. These depend partly on the type of immobilization device and could be reduced by the use of portal imaging systems. Furthermore, breast is mobile during respiration with motion amplitude as high as 0.8 to 10 mm in the anteroposterior direction. Respiratory gating techniques, currently on evaluation, have the potential to reduce effect of these movements. Each radiotherapy department should perform its own assessments and determine the geometric uncertainties with respect of the equipment used and its particular treatment practices. This paper is a review of the main geometric uncertainties in breast treatment, due to respiration and set-up, and solutions proposed to limit their impact.


Changes in subgenome types of adenovirus type 4 isolated from patients with ocular disease between 1985 and 1989 in Sapporo, Japan.
A total of 122 adenovirus type 4 (Ad4) strains isolated from patients with epidemic keratoconjunctivitis at an eye clinic in Sapporo, Japan, from 1985 to 1989 were identified as Ad4a. By the use of HinfI and TaqI restriction endonucleases, these Ad4a strains were classified into 12 subgenome types. During this observation period, two epidemics of Ad4 infection relating to epidemic keratoconjunctivitis occurred. During the Ad4a epidemic in 1985, three subgenome types became predominant successively. However, except for one strain, the prevalent strains isolated during the epidemic of Ad4a in 1988 all belonged to a single subgenome type. In the years when an Ad4a epidemic was not observed, such Ad4a strains were new or previous subgenome types. The prevalent subgenome types tended to change within several years.


Organization of transfer ribonucleic acid genes in the Escherichia coli chromosome.
The arrangement of transfer ribonucleic acid (RNA) genes in the chromosome of Escherichia coli K-12 (C600) was examined with the techniques of restriction endonuclease digestion and Southern blotting. The number and size of restriction fragments containing transfer or ribosomal RNA sequences or both were estimated by a variety of restriction endonucleases, including EcoRI, BglI, SmaI, SalI, BamHI, and PstI. EcoRI liberated a minimum of 27 fragments which hybridized to transfer RNA and 16 which hybridized to ribosomal RNA. Enzymes which did not cut within the ribosomal RNA operons (PstI and BamHI) liberated 16 and 13 fragments, respectively, which hybridized to transfer RNA. Five PstI and six BamHi fragments also hybridized to ribosomal RNA, suggesting that there may be at least 11 chromosomal locations distinct from ribosomal RNA operons which encode transfer RNA genes. In addition, our data indicated that several transfer RNA genes may be very close to the 5' proximal ends of certain ribosomal RNA operons and close to the 3' distal ends of all seven ribosomal RNA operons. Similar studies have been carried out with 22 purified species of transfer RNA, and we report here the number and size of EcoRI restriction fragments which hybridize to these transfer RNA species.


Sensitivity of the BASC-2 Adaptive Skills Composite in detecting adaptive impairment in a clinically referred sample of children and adolescents.
The Behavior Assessment Scale for Children (BASC-2) is widely used to assess for internalizing/externalizing behavior problems; however, the role of its adaptive scales is not well established. This study examined the sensitivity of the parent version of the BASC-2 Adaptive Skills Composite (ASC) in identifying children with impairments on a more comprehensive measure of adaptive functioning, the Adaptive Behavior Assessment System (ABAS-II). Participants were referred for neuropsychological assessment (N = 1884, M age = 10.96 years, SD = 3.50, 65% male). The ASC, rather than individual BASC-2 adaptive scales, showed the strongest correlations with the ABAS-II General Adaptive Composite (GAC) and domains. Receiver operating characteristic analysis showed that the BASC-2 ASC discriminated children with impaired adaptive functioning on the ABAS-II (≥ -2 SD) from those without impairment (area under curve range = .86[social domain] to .78[practical domain]); however, sensitivity was inadequate at the typical -2 SD cut-off (48%). A -1 SD cut-off on the BASC-2 (T-score ≤ 40) was more appropriate for predicting impairment on the ABAS-II (89%). Among children with impaired IQ, the ABAS-II GAC was impaired in 69% compared to only 36% on the ASC. Findings have implications for the diagnosis of Intellectual Disability and for quantifying the functional impact of other diagnoses, particularly with the release of DSM-5.


Mapping potential energy surfaces.
A recently proposed dynamical method [A. Laio and M. Parrinello, Proc. Natl. Acad. Sci. U.S.A. 99, 12562 (2002)] allows us to globally sample the free energy surface. This approach uses a coarse-grained non-Markovian dynamics to bias microscopic atomic trajectories. After a sufficiently long simulation time, the global free energy surface can be reconstructed from the non-Markovian dynamics. Here we apply this scheme to study the T=0 free energy surface, i.e., the potential energy surface in coarse-grained space. We show that the accuracy of the reconstructed potential energy surface can be dramatically improved by a simple postprocessing procedure with only minor computational overhead. We illustrate this approach by conducting conformational analysis on a small organic molecule, demonstrating its superiority over traditional unbiased approaches in sampling potential energy surfaces in coarse-grained space.


Actions of growth hormone-release inhibiting hormone (somatostatin) on the renin aldosterone system.
Administration of growth hormone-release inhibiting hormone (GH-RIH, somatostatin), as a 90 minute infusion (10 mug/min), to 3 healthy young men under conditons of active renin secretion acheived by pretreatment with furosemide (80 mg daily for 5 days), caused a mean 30% fall in plasma renin activity, which returned to basal levels immediately after stopping the GH-RIH infusion. Plasma aldosterone levels were not affected during the course of this experiment.


Fitness Outcomes Related to Glyphosate Resistance in Kochia (Kochia scoparia): What Life History Stage to Examine?
A fast-spreading weed, kochia (Kochia scoparia), has developed resistance to the widely-used herbicide, glyphosate. Understanding the relationship between the occurrence of glyphosate resistance caused by multiple EPSPS gene copies and kochia fitness may suggest a more effective way of controlling kochia. A study was conducted to assess fitness cost of glyphosate resistance compared to susceptibility in kochia populations at different life history stages, that is rate of seed germination, increase in plant height, days to flowering, biomass accumulation at maturity, and fecundity. Six kochia populations from Scott, Finney, Thomas, Phillips, Wallace, and Wichita counties in western Kansas were characterized for resistance to field-use rate of glyphosate and with an in vivo shikimate accumulation assay. Seed germination was determined in growth chambers at three constant temperatures (5, 10, and 15 C) while vegetative growth and fecundity responses were evaluated in a field study using a target-neighborhood competition design in 2014 and 2015. One target plant from each of the six kochia populations was surrounded by neighboring kochia densities equivalent to 10 (low), 35 (moderate), or 70 (high) kochia plants m-2. In 2015, neighboring corn densities equivalent to 10 and 35 plants m-2 were also evaluated. Treatments were arranged in a randomized complete block design with at least 7 replications. Three kochia populations were classified as glyphosate-resistant (GR) [Scott (SC-R), Finney (FN-R), and Thomas (TH-R)] and three populations were classified as glyphosate-susceptible (GS) [Phillips (PH-S), Wallace (WA-S) and Wichita (WI-S)]. Of the life history stages measured, fitness differences between the GR and GS kochia populations were consistently found in their germination characteristics. The GR kochia showed reduced seed longevity, slower germination rate, and less total germination than the GS kochia. In the field, increases in plant height, biomass accumulation, and fecundity were not clearly different between GR and GS kochia populations (irrespective of neighbor density). Hence, weed management plans should integrate practices that take advantage of the relatively poor germination characteristics of GR kochia. This study suggests that evaluating plant fitness at different life history stages can increase the potential of detecting fitness costs.


Location and removal of misplaced or embedded intrauterine devices by hysteroscopy.
Hysterosopic examinations were performed on 22 patients for IUDs suspected of being misplaced or embedded. Devices included 11 Majzlin springs, nine Lippes loops and two other types. Preoperative preparation and hysteroscopic techniques for extraction are described.


Iron represses the expression of CFA/I fimbriae of enterotoxigenic E. coli.
Experiments were designed to study the effect of iron on the expression of CFA/I fimbriae by enterotoxigenic E. coli (ETEC). Addition of 0.05 mM ferrous sulfate to growth media decreased CFA/I antigen and fimbrial production by the CFA/I-positive ETEC strain H-10407 as measured by quantitative ELISA and hemagglutination assay. The repressive effect was reversed by the addition of the iron chelators, sodium citrate or dipyridyl. With a CFA/I subunit gene promoter-lacZ fusion, it was found that the activity of the subunit gene promoter was significantly higher in the presence of iron chelators than in medium containing iron in the fur+ strain DHB24. This difference was not observed in the fur mutant strain SBC24, suggesting that the global E. coli metalloregulatory protein Fur (ferric uptake regulation) is involved in the repression. The repressor may bind to the promoter of the CFA/I subunit gene since several potential Fur-binding sites were identified in the promoter area.


Pharmacodynamics and tolerability of low doses of tendamistate given with starch.
Six healthy male volunteers participated in a double-blind cross-over study in which 12,5 mg, 25 mg, or 50 mg tendamistate (HOE 467), an alpha-amylase inactivator, or placebo were administered with 100 g maize meal, which contains 85,5 g pure starch. Serial blood specimens for measurement of plasma glucose concentrations, which served as a criterion of starch absorption, were taken up to 3 hours after each starch meal, and side-effects were recorded. The administration of HOE 467 with a starch meal resulted in a significant inhibition of starch absorption. Side-effects were not severe. Flatulence occurred in the placebo phase as well as after administration of the active drug. Loose stools were reported by 1 subject after 25 mg tendamistate.


Swarm motility of Salmonella enterica serovar Typhimurium is inhibited by compounds from fruit peel extracts.
Controlling spread of human pathogens on fresh produce is a top priority for public health reasons. Isolation of compounds from agricultural waste that would control spread of human pathogens was explored using Salmonella enterica serovar Typhimurium as a model organism. In the environment, micro-organisms migrate as a 'community' especially when they move on moist surfaces. This type of motility is characterized as swarming motility. We examined extracts from agricultural waste such as soya bean husk, peels of orange, pineapple, avocado and pomegranate for antiswarming activity. Avocado and pineapple peels showed moderate (~40%) inhibition of swarming motility while pomegranate peel extract had high antiswarming activity (~85% inhibition) and was examined in further detail. Although the pomegranate peel extract was acidic, swarm-inhibitory activity was not due to low pH and the peel extract did not inhibit growth of Salmonella. Among the key swarm motility regulatory genes, class II (fliF, fliA, fliT and fliZ) and class III (fliC and fliM) regulators were downregulated upon exposure to pomegranate peel extract. Pomegranate peels offer great potential as a bioactive repellent for pathogenic micro-organisms on moist surfaces. Controlling the spread of food-borne pathogens in moist environments is an important microbial food safety issue. Isolation of compounds from agricultural waste (such as fruit peels) that would control spread of human pathogens was explored using Salmonella enterica serovar Typhimurium as a model organism. Pomegranate peels offer great potential as a bioactive repellent for pathogenic micro-organisms.


History of education in medicine and surgery, first hospitals development of urology in danzig/Gdańsk.
The aim of the study is to present the development of hospital services and the teaching of medicine, and the development of urology in Danzig (Gdańisk). Well known Danzig surgeons who were interested in surgery of the genitourinary system are also presented. The beginning of urological surgery and its development within the framework of the department of surgery and as an independent facility at the Medical Academy of Gdafisk in the post-war period is also described. Extensive research was undertaken for the collection of literature and documents in German and Polish archives and libraries in order to prepare this study. The history of hospitals in Danzig goes back to the arrival of the Teutonic Knights in 1308. The earliest institution, according to historical sources, was the Hospital of the Holy Spirit, built in the years 1310-1311. It was run by the Hospitalet Order until 1382, and was intended for the sick, elderly and disabled people, orphans and needy pilgrim, and the poor. Later centuries saw the further development of hospital services in Danzig. In the 19th century, the city's increas ing population, the development of the sciences, and rapid advances in medicine subsequently led to the establishment of three more hospitals in Gdafisk: The Hospital for Obstetrics and Gynaecological Disease (1819), the Holy Virgin Hospital (1852), and the Evangelical Hospital of Deaconess Sisters (1857), in addition to the old Municipal Hospital. In 1911, new modern buildings of Municipal Hospital in Danzig were finished. On the basis of the Municipal Hospi- tal, the Academy of Practical Medicine was established in 1935. It was known under the name Staatliche Akademie fiir Praktische Medizin in the Free City of Danzig. Five years later (in 1940) the Academy was developed and changed to the Medical Academy of Danzig (Medizinische Akad- emie Danzig - MAD). The beginning of medical teaching at the middle level in Danzig (Gdafsk) dates back to the 16th century. It had its origins in the Chair of Anatomy and Medicine at Danzig Academic Gymnasium (GA; Sive Illustre), an establishment which lasted for 239 years, from 1584 to 1812. The history of surgery in Danzig has its roots in the centuries-old tradition of the medical practice of surgeons who were associated in the Surgeons Guild, teaching, as well medical and scientific research. The Surgeons Guild existed in Danzig from 1454 to 1820. Over the centuries manual intervention was also in the hands of academically uneducated persons such as bath house attendants, barbers, and wandering surgeons. Until the end of 1946 there was no separate urology department in Danzig. Urological surgery was in the hands of surgeons. Interventions and operations on genitourinary organs were carried out, more or less, in all surgical departments. The end of World War II created a new political situation in Europe. Danzig (now Gdafisk) and Pomerania became part of Poland. In 1945, on the basis of the former MAD, the Polish Government established the Polish Academy of Physicians, later renamed the Medical Academy in Gdafisk (Gdafiska Akademia Medyczna - GAM). In 2009, GAM was again renamed, as the Medical University of Gdafisk (Gdaiski Uniwersytet Medyczny). The political changes after World War II accelerated the process of the separation of urology from surgery. In May 1947, a 30-bed Urological Ward was opened in Gdanisk, in Debinki Street, forming part of the First Surgical Clinic of the Academy of Physicians (headed by Prof. Kornel Michejda, 1887-1960, later by Prof. Stanislaw Nowicki, 1893-1972, and lastly by Prof. Zdzislaw Kieturakis, 1904-1971). The first head doctor of the new urological ward was Dr. Tadeusz L$renz (1906-1986), a urologist from Lvov (Lemberg). After the departure of Professor Lorenz to Wrodclaw (Breslau) in 1958, Dr. Jan Renkielski was acting as Head of the Urological Ward until 1971. In 1971 the ward was transformed to the separate Department of Urology. Docent ("lecturer"), and later Professor, Kazimierz Adamkiewicz from Zabrze (Hindenburg) became its Head. Professor Adamkiewicz organized and equipped the Department, leading it quickly to the level of modern departments in the areas of research, teaching, and therapy. During Professor Adamkiewicz's ill- ness, and after his retirement in 1988, Docent Kazimierz Krajka, Later Professor) headed the urological department until his retirement in 2012. Since 1 October 2012, Associate Professor (Docent) Marcin Matuszewski (*1965) has been the head of the Department of Urology in Gdańisk.


Two new terrestrial species of Hydraena Kugelann from the island of Bioko, Gulf of Guinea (Coleoptera: Hydraenidae).
The knowledge of the Hydraenidae of sub-Saharan Africa, and in particular of the genus Hydraena Kugelann, 1794, is most incomplete. As an example, in southern Africa only three species were described before the revision of Perkins (2014), which raised the number to 31. Only 15 species are currently known from Central Africa, between the Sahel and South Africa, all belonging to subgenus Hydraenopsis Janssens, 1972 (Trizzino et al. 2013), but many more remain to be described and discovered. The islands of the Gulf of Guinea are no exception to this lack of knowledge (Jones 1994), and only one species of the family was previously known, H. (Hydraenopsis) pagaluensis Hernando & Ribera, 2001 from Annobón (Hernando & Ribera 2001; Trizzino et al. 2013). In this paper we describe the first known species of Hydraenidae from Bioko, the largest and closest to the continent of these islands. The species were collected by our friend and colleague Vasily Grebennikov during a survey of the forest litter fauna of Annobón and Bioko. Despite considerable efforts no Hydraenidae were found in Annobón, and only these two species, in a single locality, in Bioko.


Transscleral YAG laser photocoagulation for uncontrollable glaucoma in corneal patients.
Control of intraocular pressure (IOP) in patients with severe alkaline burns is one of the most difficult problems facing the corneal specialist. Currently, when medical therapy cannot control intraocular pressure, the usual procedure of choice is cyclocryotherapy. This procedure, however, can be complicated by phthisis, retinal detachment, or macular edema. We have used transscleral YAG laser cyclophotocoagulation (TSYLC) to control the IOP in a patient with severe glaucoma after an alkali burn. This patient had previously had an unsuccessful cyclocryotherapy. After the TSYLC procedure, he suffered no complications and his IOP was normal. Our experience with this patient indicated that the TSYLC procedure might be an effective alternate to cyclocryotherapy, especially in corneal patients with uncontrollable inflammatory glaucoma.


Purebreeding of Red Maasai and crossbreeding with Dorper sheep in different environments in Kenya.
The aim of this article was to study opportunities for improvement of the indigenous and threatened Red Maasai sheep (RM) in Kenya, by comparing purebreeding with crossbreeding with Dorper sheep (D) as a terminal breed, in two different environments (Env. A and a harsher Env. B), assuming different levels of genotype-by-environment interaction (G × E). Breeding goals differed between environments and breeds. Four scenarios of nucleus breeding schemes were stochastically simulated, with the nucleus in Env. A. Overall, results showed an increase in carcass weight produced per ewe by more than 10% over 15 years. Genetic gain in carcass weight was 0.17 genetic SD/year (0.2 kg/year) across scenarios for RM in the less harsh Env. A. For survival and milk yield, the gain was lower (0.04-0.05 genetic SD/year). With stronger G × E, the gain in the commercial tier for RM in the harsher Env. B became increasingly lower. Selection of females also within the commercial tier gave slightly higher genetic gain. The scenario with purebreeding of RM and a subnucleus in Env. B gave the highest total income and quantity of meat. However, quantity of meat in Env. A increased slightly from having crossbreeding with D, whereas that in Env. B decreased. A simple and well-designed nucleus breeding programme would increase the genetic potential of RM. Crossbreeding of RM with D is not recommended for harsh environmental conditions due to the large breed differences expected in that environment.


Learning in oral biology: a comparison between deep and surface approaches.
It has been suggested that students approach their learning in at least two qualitatively different ways. In the surface approach, students see tasks as being imposed, for which they develop coping strategies focused on reproduction of essentials and memorising information for assessment rather than for understanding. In the deep approach, students seek to understand ideas to allow them to relate and integrate knowledge from other parts of their study and thereby develop conceptual frameworks from which they can derive solutions to novel problems. To these two approaches, a third, achieving approach, is often added, in which students aim to obtain the highest grades, whether or not they grasp the learning material. In this study we used a subject-specified version of Biggs' Study Process Questionnaire to obtain data about the way dental and dental technology students perceived and approached their learning in oral biology. Questionnaires were distributed to 62 second-year dental students and 23 second-year dental technology students. Within each group the dependent variables examined were deep, surface or achieving approaches to learning. Analysis of these data showed that significant differences between dental and dental technology students centred on their approaches to learning. However, there were no significant differences attributable to gender, country of origin or ethnicity. While dental students, who had a relatively well developed understanding of the nature of their studies in oral biology at the start of their course, adopted deep learning strategies, dental technology students, who had had no prior experience of university education per se, were significantly more surface-orientated.


[Fatty acid composition and cholesterol content in naturally canned jurel, sardine, salmon, and tuna].
To obtain more information about fatty acid profile and cholesterol content of fat extracted from canned fish in brine habitually consumed in Chile, four different species Jurel (Trachurus murphyi), Sardine (Sardinops sagax), Salmon (Oncorhynchus kisutch) and Tuna (Thunnus alalunga) were analyzed. The GLC of fatty acid methyl esters showed that the main group of fatty acids belongs to polyunsaturated, being omega-3 family the more important. The principal representants were eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), with percentages between 5%-11% and 12%-22% respectively. Omega-6 family was represented mainly by arachidonic acid (AA) with percentages between 2%-4%. Cholesterol content was similar to the values found in other animal origen meats. The figures were between 41-86 mg of cholesterol per 100 g of edible product, Tuna in brine, was the product with the lowest content of cholesterol. The calculated amount of EPA, DHA and total omega-3 fatty acids indicated values between 95-604, 390-1163 and 609-2775 mg respectively per 100 g of edible product. Due these results is important to emphasize the consumption of this type of canned fish in brine, that they really represent a good dietary source of mainly polyunsaturated omega-3 fatty acids. The international recommendations indicate to increase the consumption of fish, due the beneficial effects described in relation with cardiovascular disease, which is the mean cause of death in Chile, country with a wide variety of marine origen foods, but with a contradictory answer about its consumption which is not incorporated in the current diet.


Elements of transcription factor network design for T-lineage specification.
The complex spectrum of cell types produced in mammalian hematopoiesis can be understood as the output of highly combinatorial transcription factor action. The generation of multiple diverse combinations of transcription factors from the common starting state of the hematopoietic stem cell must be explained through the cross-regulatory interactions of these transcription factors at several levels. Here, the operation of such a network is addressed through a focus on murine T cell development, where we have recently established regulatory linkages between GATA-3 and PU.1 and multiple other factors essential to this differentiation pathway. The action of both essential/rate-limiting factors and factors with effects that shift qualitatively with dose and time of action can be traced through the regulatory interaction network. Hypothetical models are proposed to indicate the network nodes that are differentially activated in normal T cell lineage progression and in cells diverted to other potential fates.


Angiocentric B-cell lymphoma of the lung in an immunocompromised boy.
An angiocentric IgA-kappa bilateral pulmonary lymphoma developed in a 9-year-old boy treated with chemotherapy for 3 1/2 years for acute lymphoblastic leukemia. The tumor was confined to the lungs and had extensive infarction secondary to vascular involvement. This and 2 similar reported cases suggest that compromise of the host's immune system may contribute to the development of pulmonary lymphoma in children, an uncommon site and probably labeled previously as lymphomatoid granulomatosis.


Bioinspired Hierarchical Surface Structures with Tunable Wettability for Regulating Bacteria Adhesion.
To circumvent the influence from varied topographies, the systematic study of wettability regulated Gram-positive bacteria adhesion is carried out on bioinspired hierarchical structures duplicated from rose petal structures. With the process of tuning the interfacial chemical composition of the self-assembled films from supramolecular gelators, the varied wettable surfaces from superhydrophilicity to superhydrophobicity can be obtained. The investigation of Gram-positive bacteria adhesion on the hierarchical surfaces reveals that Gram-positive bacteria adhesion is crucially mediated by peptidoglycan due to its different interaction mechanisms with wettable surfaces. The study makes it possible to systematically study the influence mechanism of wettability regulated bacteria adhesion and provides a sight to make the bioinspired topographies in order to investigate wettability regulated bioadhesion.


Selective reoperation after primary resection as a feasible and safe treatment strategy for recurrent pancreatic cancer.
Local recurrence frequently occurs in patients with pancreatic cancer after intended curative resections. However, no treatment strategies have been established for isolated local recurrence. Several series have demonstrated a survival benefit for reoperation in selected pancreatic recurrence cases. This study compares the difference in overall survival (OS) between surgery and nonsurgery groups in recurrent pancreatic cancer.All patients from 1990 to 2014 with recurrent pancreatic cancer who underwent curative resections were investigated and retrospectively reviewed. Clinicopathological features and OS were compared.A total of 332 patients were recruited in this series. The majority had histologically pancreatic adenocarcinoma (289 patients, 87.0%). Fourteen of 332 patients (4.2%) with recurrent pancreatic cancer received subsequent resection. Most of these patients underwent curative surgery (R0 resection, 13 patients, 92.9%), and only 1 patient (7.1%) had microscopic residual tumor (R1 resection). Disease-free survival (DFS), OS, and postrecurrence survival (PRS) were all significantly longer in the surgery group (DFS 10.6 vs 6.1 months, P = 0.044; OS 57.8 vs 14.0 months, P < 0.001; PRS 14.1 vs 6.0 months, P < 0.001). The median survival times were comparable in patients with recurrent pancreatic adenocarcinoma who received surgery and those who did not (DFS 10.6 vs 6.1 months, P = 0.226; OS 23.7 vs 14.0 months, P = 0.074; PRS 8.9 vs 5.8 months, P = 0.183). However, the OS and PRS were superior in the patients who did not display adenocarcinoma histologically but underwent operation for recurrence (OS 97.2 vs 16.9 months, P = 0.016; PRS 65.7 vs 6.9 months, P = 0.010). Notably, DFS levels were similar (16.0 vs 7.0 months, P = 0.265).Surgery can feasibly and safely provide survival benefits in selective recurrent pancreatic cancer. In patients who are histologically negative for adenocarcinoma, survival is prolonged when the operation is performed with R0 resection. Patients with isolated recurrent pancreatic adenocarcinoma need multidisciplinary therapy. In addition to operation, chemoradiotherapy and intraoperative radiotherapy may also be considered; their roles should be further investigated.


Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review.
The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.


[Sampling study on practitioners' attitude to the prevention of infectious endocarditis].
BACKGROUNDS AND METHODS: The opinions and the experience of Veneto practitioners about prevention of infective endocarditis were detected through a sample survey among the 386 practitioners of Health and Social Unit Nr 16, 17, and 36 of Veneto Region. The interview was carried out through a questionnaire, sent by mail, asking for: 1) general information on the practitioner's profession; 2) information about the previous experience in diagnosis and care of heart diseases, particularly of infective endocarditis, of atrial septal defect ostium secundum type without pulmonary hypertension, of unstable angina, and moderate mitral stenosis; 4) attitudes in the prevention of infective endocarditis. Of 386 practitioners surveyed, 186 (48.2%) responded. More than 60% of the responders held a diploma of specialization and 7% were cardiologists, half of the responders had worked in public hospitals. The 63.8% of the practitioners had patients over sixty in a percentage of 15-44%. In 1990 only 5.9% of the practitioners observed new cases of infective endocarditis, while half of them stated that some of their patients had suffered from this disease in the past. The assessment of the level of severity for every heart disease is ranged between 0 (the minimum) and 10 (the maximum). The statistical analysis showed that the minimum arithmetic mean (+/- SD) is given for atrial septal defect without pulmonary hypertension with 4.6 +/- 2. Then for moderate mitral stenosis with 7.1 +/- 1.6, unstable angina pectoris with 7.4 +/- 2 and the maximum mean is given for infectious endocarditis with 8 +/- 1.7. ANOVA statistical analysis applied on the four paired series of assessment of severity carried out a high significant difference (F of Snedecor = 328.2; P < 0.001) among assessments, and among practitioners (F = 1.71; P < 0.01). High significant linear correlation (at least P < 0.01) is observed among the severity of the four heart diseases. Vice versa not significant association is showed between severity for every heart diseases and the experience of the interviewed. Most practitioners would prescribed prophylaxis for infective endocarditis to patients with rheumatic valve disease (91% of the responders), with previous episodes of infective endocarditis (90.4%), with prosthetic valve (67.6%) or with degenerative valve disease (57.3%). On the contrary most practitioners would not prescribe the prevention for infective endocarditis to patients with coronary heart disease (84.9%), with coronary bypass (71.4%), with mitral valve prolapse without insufficiency (60.6%), with dilatative cardiomyopathy (67%) or with obstructive cardiomyopathy (57.8%). A prevailing trend in case of congenital heart disease and mitral valve prolapse with insufficiency was not observed. The 86.6% of practitioners would prescribe the prophylaxis for infective endocarditis in case of dental extraction, but only the 64.4% would prescribe it in case of any potentially haemorrhagic oral or dental procedure. The 61.7% of the responders would not prescribe the prevention for infective endocarditis to patients receiving the prophylaxis for rheumatic fever. The practitioners would use in the following order: amoxicillin (77.3%), erythromycin (76.9%), penicillin V (76.3%) and ampicillin-gentamycin (61.3%). On the contrary, most responders would prescribe neither tetracycline (73%) nor spiramycin (69.8%). There is no prevailing trend to the employ of oral cephalosporins. The 90.3% of the practitioners think that infective endocarditis can be a quite interesting and useful subject for an up-to-date course.


Computer-aided nutrition - Effects on nutrition and growth in preterm infants <32 weeks of gestation.
Preterm infants are often discharged from the NICU with suboptimal growth. The aim of our intervention study was to determine if a computer-aided nutrition calculation program could help to optimise the nutrition and secondary improve the growth of preterm infants. Intake of macro- and micronutrients and anthropometric data was collected in 78 preterm infants with GA ≤32+0 from birth to postnatal week 7. The nutrition of 43 preterm infants was ordinated with help of the program Nutrium™ (IG). Before the introduction of the program 35 consecutive preterm infants served as control group (CG). Their data were collected in retrospect. Amino acid, carbohydrate, fluid intake and total energy intake were statistically different at all time points. Fatty acid intake was statistically different expect for week 2 and 4. Similar differences were found for magnesium, calcium and phosphorus, zinc, copper and selenium. In contrast vitamin intake was higher in the control group. At birth there were no differences between the groups with respect to anthropometric data. Weight, length and head circumference (HC) SDS decreased in both groups from birth to day 28 of life (CG -1.2 SDS; -1.2 SDS; -0.8 SDS vs IG -0.9 SDS; -0.8 SDS; -0.4 SDS). The infants in the CG showed until discharge a partial catch-up but remained below birth SDS for weight and length (-0.5 SDS; -0.9 SDS). In the IG, infants reached birth values for weight and length (-0.1 SDS; 0 SDS). For HC both groups showed similar values at the time point for birth and discharge (CG +0.3 SDS vs IG +0.5 SDS). By using a computer-aided nutrition calculation program better postnatal growth was achieved. Nutritional intake was increased in respect to nearly all micro- and macronutrients. There were no adverse effects. In contrast there was a tendency of decreased incidence of BPD, infection rate and PDA.


Using a multiscale image processing method to characterize the periodic growth patterns on scallop shells.
The fine periodic growth patterns on shell surfaces have been widely used for studies in the ecology and evolution of scallops. Modern X-ray CT scanners and digital cameras can provide high-resolution image data that contain abundant information such as the shell formation rate, ontogenetic age, and life span of shellfish organisms. We introduced a novel multiscale image processing method based on matched filters with Gaussian kernels and partial differential equation (PDE) multiscale hierarchical decomposition to segment the small tubular and periodic structures in scallop shell images. The periodic patterns of structures (consisting of bifurcation points, crossover points of the rings and ribs, and the connected lines) could be found by our Space-based Depth-First Search (SDFS) algorithm. We created a MATLAB package to implement our method of periodic pattern extraction and pattern matching on the CT and digital scallop images available in this study. The results confirmed the hypothesis that the shell cyclic structure patterns encompass genetically specific information that can be used as an effective invariable biomarker for biological individual recognition. The package is available with a quick-start guide and includes three examples: http://mgb.ouc.edu.cn/novegene/html/code.php.


Incidence of Straight-Channel Screw-Retained Single Crown Following Immediate Implant Placement and Provisionalization in the Esthetic Zone: A CBCT Study.
The purpose of this cone beam computed tomography (CBCT) study was to investigate the probability of using straight screw-channel screw-retained restorations following an immediate implant placement and provisionalization protocol in maxillary anterior teeth utilizing implant planning software. A retrospective review of CBCT images was done. The midsagittal images of maxillary anterior teeth (right canine to left canine) were created in implant planning software, screen-captured, and transferred to a presentation program. The digital implant templates were created for 3.5-mm-diameter (used for central and lateral incisors) and 4.5-mm-diameter (used for central incisors and canines) tapered implants with lengths of 13, 15, and 18 mm. The frequency percentages of immediate implant placement and provisionalization and immediate implant placement and provisionalization with straight screw-channel screw-retained restorations were recorded and compared among all maxillary anterior teeth. CBCT images from 1,200 teeth were evaluated. The overall frequency percentages of immediate implant placement and provisionalization and immediate implant placement and provisionalization with straight screw-channel screw-retained restoration were 84% (range = 74% to 92%) and 14% (range = 10% to 24%), respectively. Although the probability of being able to employ immediate implant placement and provisionalization with a straight screw-channel screw-retained restoration in the esthetic zone is low, the use of smaller-diameter implants can substantially increase the probability.


Sucrose-induced stomatal closure is conserved across evolution.
As plants evolved to function on land, they developed stomata for effective gas exchange, for photosynthesis and for controlling water loss. We have recently shown that sugars, as the end product of photosynthesis, close the stomata of various angiosperm species, to coordinate sugar production with water loss. In the current study, we examined the sugar responses of the stomata of phylogenetically different plant species and species that employ different photosynthetic mechanisms (i.e., C3, C4 and CAM). To examine the effect of sucrose on stomata, we treated leaves with sucrose and then measured their stomatal apertures. Sucrose reduced stomatal aperture, as compared to an osmotic control, suggesting that regulation of stomata by sugars is a trait that evolved early in evolutionary history and has been conserved across different groups of plants.


The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated Resolution of Inflammation.
Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs-naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair-associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation.


Cartoon Network: A tool for open-ended exploration of neural circuits.
Cartoon Network is an open-source simulator for neural circuits. It was designed to provide a microworld for the playful exploration of neural networks (similar to the niche Logo/Scratch fills for computer programming). The simulator makes it easy to construct and experiment with closed-loop circuits, enabling students to explore how small sets of neurons can generate complex patterns of activity (oscillations, reverberation). Cartoon Network can be connected to the Finch robot from BirdBrain Technologies, a cheap USB robotics platform. This enables students to design a nervous system for a Finch, creating sensory neurons which read Finch inputs (touch, light, and temperature), motor neurons which control Finch outputs (wheels, lights, and sound), and interneurons to produce intrinsic activity and/or link together inputs and outputs in ways that can produce complex and surprising behaviors. Students use Cartoon Network by taking on structured challenges (For example, can you make the Finch follow a light? Can it turn and run when it bumps a wall?) that require deep engagement with important principles of neural circuit operation (e.g., lateral inhibition, parallel processing, positive- and negative-feedback). On successfully completing a challenge, students can systematically explore the neural properties that help control the behavior, compare their work to other successful designs, and/or reflect on how the circuit they designed might be modified via evolution to produce different behaviors. Cartoon Network has proven an engaging and effective activity for undergraduates and is accessible for students as young as late elementary school. Download it for free at: https://github.com/rcalinjageman/cartoon_network.


Merocyclophanes C and D from the Cultured Freshwater Cyanobacterium Nostoc sp. (UIC 10110).
Merocyclophanes C and D (1 and 2) were isolated from the cell extract of the cultured cyanobacterium UIC 10110. The structures were determined by one-dimensional nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry and confirmed by 2D NMR techniques. The absolute configurations were determined using electronic circular dichroism spectroscopy. Merocyclophanes C and D represent the first known analogues of the merocyclophane core structure, a recently discovered scaffold of [7,7] paracyclophanes characterized by an α-branched methyl at C-1/C-14; 1 and 2 showed antiproliferative activity against the MDA-MB-435 cell line with IC50 values of 1.6 and 0.9 μM, respectively. Partial 16S analysis determined UIC 10110 to be a Nostoc sp., and it was found to clade with UIC 10062 Nostoc sp., the only other strain known to produce merocyclophanes. The genome of UIC 10110 was sequenced, and a biosynthetic gene cluster was identified that is proposed to encode type I and type III polyketide synthases that are potentially responsible for production of the merocyclophanes; however, further experiments will be required to verify the true function of the gene cluster. The gene cluster provides a genetic basis for the observed structural differences of the [7,7] paracyclophane core structures.


Esmolol does not improve quality of postsurgical recovery after ambulatory hysteroscopy: A prospective, randomized, double-blinded, placebo-controlled, clinical trial.
Intraoperative systemic esmolol has been shown to reduce postsurgical pain. Nonetheless, it is unknown whether the use of intraoperative systemic esmolol can improve patient-reported postsurgical quality of recovery. The main objective of the current investigation was to evaluate the effect of intraoperative esmolol on postsurgical quality of recovery. We hypothesized that patients receiving intraoperative esmolol would report better quality of postsurgical recovery than the ones receiving saline. The study was a prospective randomized double-blinded, placebo-controlled, clinical trial. Healthy female subjects undergoing outpatient hysteroscopic surgery under general anesthesia were randomized to receive intravenous esmolol administered at a rate of 0.5 mg/kg bolus followed by an infusion of 5 to 15 μg/kg/min or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included postoperative opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. Seventy subjects were randomized and 58 completed the study. There was not a clinically significant difference in the global QoR-40 scores between the esmolol and saline groups at 24 hours, median (interquartile range) of 179 (171-190) and 182 (173-189), respectively, P = .82. In addition, immediate post-surgical data in the post-anesthesia care unit did not show a benefit of using esmolol compared to saline in regard to pain scores, morphine consumption, and postoperative nausea and vomiting. Despite current evidence in the literature that intraoperative esmolol improves postsurgical pain, we did not detect a beneficial effect of intraoperative esmolol on patient-reported quality of recovery after ambulatory surgery. Our results confirm the concept that the use of patient-centered outcomes rather than commonly used outcomes (e.g., pain scores and opioid consumption) can change the practice of perioperative medicine.


Prenatal diagnosis of deletion 17p13 associated with DiGeorge anomaly.
A fetus, subsequently shown to have the deletion 17p13, was detected at 30 weeks' gestation because of multiple anomalies and polyhydramnios on ultrasonography. The fetus died and was born at 34 weeks of gestation. Pathologic examination showed intrauterine growth retardation, double outlet right ventricle (a conotruncal cardiac defect), and thymic hypoplasia suggesting partial DiGeorge anomaly. To our knowledge, DiGeorge anomaly has not been reported previously in conjunction with del(17p) nor in the Miller-Dieker syndrome. Since this deletion is the largest deletion of distal 17p observed so far, one explanation for this association may be the presence of a gene on proximal 17p for neural crest development.


Free-Living Amoebae as Hosts for and Vectors of Intracellular Microorganisms with Public Health Significance.
Free-living amoebae (FLA) are parasites within both humans and animals causing a wide range of symptoms and act as hosts of, and vehicles for phylogenetically diverse microorganisms, called endocytobionts. The interaction of the FLA with sympatric microorganisms leads to an exceptional diversity within FLA. Some of these bacteria, viruses, and even eukaryotes, can live and replicate intracellularly within the FLA. This relationship provides protection to the microorganisms from external interventions and a dispersal mechanism across various habitats. Among those intracellularly-replicating or -residing organisms there are obligate and facultative pathogenic microorganisms affecting the health of humans or animals and are therefore of interest to Public Health Authorities. Mimiviruses, Pandoraviruses, and Pithoviruses are examples for interesting viral endocytobionts within FLA. Future research is expected to reveal further endocytobionts within free-living amoebae and other protozoa through co-cultivation studies, genomic, transcriptomic, and proteomic analyses.


Genotoxic and cytotoxic evaluation of Jatropha dioica Sessé ex Cerv. by the micronucleus test in mouse peripheral blood.
Jatropha dioica Sessé ex Cerv. is a medicinal plant credited with low cytotoxicity in vitro. Thus, the objective of this work was to evaluate the possible genotoxic and cytotoxic effect in vivo of the J. dioica aqueous extract by means of micronucleus assay in mouse peripheral blood. Four different J. dioica aqueous extract dose-units were evaluated (30, 60, 100, and 300 mg/kg). The extract was administered orally to male Balb-C-strain mice every 24 h during 5 days. Blood samples were taken at 0, 24, 48, 72, 96, and 120 h from the mouse's tail and were performed in duplicate extensions. The number of Polychromatic Erythrocytes (PCE), Polychromatic Micronucleus Erythrocytes (PCEMN), and Micronucleus Erythrocytes (MNE) was determined at the different sampling times in the different study groups. Our results showed that the group that received 60 mg/kg of cyclophosphamide (positive control) presented a significant decrease in the PCE (p = 0.044) proportion and a significant increase in MNE (p = 0.032, p = 0.0001). The groups that received the different J. dioica aqueous extract doses did not present either a PCE decrease or an increase in PCEMN and MNE. J. dioica exerts neither a genotoxic nor a cytotoxic effect on mouse peripheral blood at high doses.


Three-dimensional structure of an Fab-peptide complex: structural basis of HIV-1 protease inhibition by a monoclonal antibody.
F11.2.32, a monoclonal antibody raised against HIV-1 protease (Kd = 5 nM), which inhibits proteolytic activity of the enzyme (K(inh) = 35(+/-3)nM), has been studied by crystallographic methods. The three-dimensional structure of the complex between the Fab fragment and a synthetic peptide, spanning residues 36 to 46 of the protease, has been determined at 2.2 A resolution, and that of the Fab in the free state has been determined at 2.6 A resolution. The refined model of the complex reveals ten well-ordered residues of the peptide (P36 to P45) bound in a hydrophobic cavity at the centre of the antigen-binding site. The peptide adopts a beta hairpin-like structure in which residues P38 to P42 form a type II beta-turn conformation. An intermolecular antiparallel beta-sheet is formed between the peptide and the CDR3-H loop of the antibody; additional polar interactions occur between main-chain atoms of the peptide and hydroxyl groups from tyrosine residues protruding from CDR1-L and CDR3-H. Three water molecules, located at the antigen-antibody interface, mediate polar interactions between the peptide and the most buried hypervariable loops, CDR3-L and CDR1-H. A comparison between the free and complexed Fab fragments shows that significant conformational changes occur in the long hypervariable regions, CDR1-L and CDR3-H, upon binding the peptide. The conformation of the bound peptide, which shows no overall structural similarity to the corresponding segment in HIV-1 protease, suggests that F11.2.32 might inhibit proteolysis by distorting the native structure of the enzyme.


Assessment of surface hardness of acrylic resins submitted to accelerated artificial aging.
The aim of this study was to assess the influence of accelerated artificial aging (AAA) on the surface hardness of acrylic resins. The following three commercial brands of acrylic resins were tested: Vipi Flash (autopolymerized resin), Vipi Wave (microwave heat-polymerized resin) and Vipi Cril (conventional heat-polymerized resin). To perform the tests, 21 test specimens (65x10x3 mm) were made, 7 for each resin. Three surface hardness readings were performed for each test specimen, before and after AAA, and the means were submitted to the following tests: Kolmogorov-Smirnov (P>0.05), Levene Statistic, Two-way ANOVA, Tukey Post Hoc (P<0.05) with the SPSS Statistical Software 17.0. The analysis of the factors showed significant differences in the hardness values (P<0.05). Before aging, the autopolymerized acrylic resin Vipi Flash showed lower hardness values when compared with the heat-polymerized resin Vipi Cril (P=0.001). After aging, the 3 materials showed similar performance when compared among them. The Vipi Cril was the only one affected by AAA and showed lower hardness values after this procedure (Pp=0.003). It may be concluded that accelerated artificial aging influenced surface hardness of heat-polymerized acrylic resin Vipi Cril.


Influenza virus hemagglutinin-specific antibodies isolated from a combinatorial expression library are closely related to the immune response of the donor.
Antibodies specific for the influenza virus hemagglutinin have been isolated from a combinatorial expression library generated using mRNA obtained from an immunized donor mouse. Sequence analysis indicates that the antibody heavy chain variable regions were derived from members of an expanded hemagglutinin-specific B-cell clone, in conjunction with one of two light chain variable regions. Moreover, the most frequently identified heavy chain variable/light chain variable combination is extremely similar to a heavy chain variable/light chain variable combination that has previously been identified among hemagglutinin-specific hybridoma antibodies. The results, therefore, demonstrate that these antibodies bear a close relationship to the immune status of the donor mouse and suggest that simple adaptations of this procedure might allow evaluation of the immune responses of species, such as man, in which conventional hybridoma techniques have to date proven ineffective.


Timolol promotes reactivation of latent HSV-1 in the mouse iontophoresis model.
The present study examined the effect of topical timolol, a nonspecific beta 1 and beta 2 blocker on reactivation and ocular shedding of latent HSV-1 in an improved mouse iontophoresis model. Latent trigeminal ganglionic infection was established in Balb/C mice following inoculation by corneal scarification with HSV-1 W strain, a clinical isolate, and confirmed by co-cultivation. On day 30, postinfection (pi), the mice were divided into two groups, and treatment begun with coded eye drops (timolol 0.5% or placebo) BID OU for 5 days. On day 31 pi, iontophoresis with 1% 6-hydroxydopamine was performed, and daily treatment with topical epinephrine and 1% prednisolone was administered. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. Results demonstrated that the timolol-treated group had a significantly greater number of positive eyes, multiple shedding episodes, and total shedding days compared to the control group. We conclude that beta blockade promotes recurrent ocular shedding induced by epinephrine in the mouse iontophoresis latency model.