Genomic characterization of MHC class I genes of the horse.
The availability of a contig of bacterial artificial chromosome (BAC) clones spanning the equine major histocompatibility complex (MHC) made possible a detailed analysis of horse MHC class I genes. Prior to this study, only a single horse MHC class I gene had been sequenced at the genomic level. Although many ( approximately 60) MHC class I cDNA sequences had been determined and published, from this information, it was not possible to determine how many class I loci are expressed in horses or to assign individual sequences to allelic series. In this study, 15 MHC class I genes were identified in BAC subclones and fully sequenced. Because the BAC library donor horse had been bred for homozygosity at the MHC, these 15 genomic clones represent distinct MHC class I genes and pseudogenes and not alleles at a smaller number of loci. For five of the genes, cDNA sequences from these loci had previously been identified. Two additional expressed class I genes were discovered, bringing the known total of different equine MHC class I genes (loci) expressed as mRNA to seven. Expression of all seven loci was detected by reverse transcriptase-polymerase chain reaction in adult, fetal, and placental tissues. The remaining eight genes were designated as pseudogenes. This work resulted in moderate expansion of the horse MHC BAC contig length, and the remaining gap was shortened. The information contained in these equine MHC class I sequences will permit comparison of MHC class I genes expressed across different horse MHC haplotypes and between horses and other mammalian species.


Telehealth among substance using justice-involved persons on community supervision: Benefits, challenges, and suggestions for future use.
The purpose of this study was to understand the uses of telehealth with justice-involved adults under community supervision with substance use problems, including their experiences during the pandemic. Structured interviews were administered among 17 justice-involved adults under community supervision about their experiences with telehealth services to treat substance use disorders. Thematic coding was used for the analysis. We identified 5 primary themes: (1) knowledge about and experiences with telehealth services during the pandemic; (2) telehealth services available; (3) service changes during the pandemic; and (4) individual motivations around treatment-seeking behavior. Overall, our findings reveal that many individuals on probation or parole appreciate having access to telehealth and found that modality convenient for counseling services. Findings shed light on participants' understanding of telehealth, their experiences in using the modality, and how this modality may serve their needs in other ways. External and internal barriers to accessing telehealth are also discussed.


Albumin-Binding and Conventional PSMA Ligands in Combination with 161Tb: Biodistribution, Dosimetry, and Preclinical Therapy.
The favorable decay characteristics of 161Tb attracted the interest of clinicians in using this novel radionuclide for radioligand therapy (RLT). 161Tb decays with a similar half-life to 177Lu, but beyond the emission of β--particles and γ-rays, 161Tb also emits conversion and Auger electrons, which may be particularly effective to eliminate micrometastases. The aim of this study was to compare the dosimetry and therapeutic efficacy of 161Tb and 177Lu in tumor-bearing mice using SibuDAB and PSMA-I&T, which differ in their blood residence time and tumor uptake. Methods: [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T were evaluated in vitro and investigated in biodistribution, imaging, and therapy studies using PC-3 PIP tumor-bearing mice. The 177Lu-labeled counterparts served for dose calculations and comparison of therapeutic efficacy. The tolerability of RLT in mice was monitored on the basis of body mass, blood plasma parameters, blood cell counts, and the histology of relevant organs and tissues. Results: The prostate-specific membrane antigen (PSMA)-targeting radioligands, irrespective of whether labeled with 161Tb or 177Lu, showed similar in vitro data and comparable tissue distribution profiles. As a result of the albumin-binding properties, [161Tb]Tb/[177Lu]Lu-SibuDAB had an enhanced blood residence time and higher tumor uptake (62%-69% injected activity per gram at 24 h after injection) than [161Tb]Tb/[177Lu]Lu-PSMA-I&T (30%-35% injected activity per gram at 24 h after injection). [161Tb]Tb-SibuDAB inhibited tumor growth more effectively than [161Tb]Tb-PSMA-I&T, as can be ascribed to its 4-fold increased absorbed tumor dose. At any of the applied activities, the 161Tb-based radioligands were therapeutically more effective than their 177Lu-labeled counterparts, as agreed with the approximately 40% increased tumor dose of 161Tb compared with that of 177Lu. Under the given experimental conditions, no obvious adverse events were observed. Conclusion: The data of this study indicate the promising potential of 161Tb in combination with SibuDAB for RLT of prostate cancer. Future clinical studies using 161Tb-based RLT will shed light on a potential clinical benefit of 161Tb over 177Lu.


The cells observed inside capsules of larvae in the course of experimental trichinellosis in mice.
In the course of trichinellosis in mice the numerous cells inside larval capsules were observed. Beginning on 14 day post infection (dpi) they were seen in about 7% of infected muscles fibers but at 21 dpi the percentage of capsules with the cells amounted to 77. In the next stage of infection the number of capsules containing cells continued to increase and reach almost 100% at 60 dpi. The identification of the cells was carried out by the indirect immunoenzymatic method using anti-CD4+, anti-CD8+ and anti-macrophage (Mac-1 antigen) monoclonal antibodies. In course of observation the level of CD4+ cells decreased from 11.3 to 0.7, of CD8+ from 17.7 to 3.0 and of macrophages from 71.0 to 23.1%. The most numerous CD4+ cells were seen at 14 dpi while the CD8+ and macrophages at 21 dpi. Beginning on 28 dpi negatively reacting cells inside larval capsules were also observed. The number of these cells increased from 23.8 to 73.2% at 60 dpi and their identification requires further investigations. The role and the function of all these cells are discussed.


A decade of interdisciplinary care.
A decade of organizing, implementing, and evaluating interdisciplinary care teams at St Luke's Regional Medical Center has reinforced the value of developing and maintaining clinical and nonclinical competencies. The value of consensus in task delegation cannot be overemphasized. Unit directors have expanded their scope of responsibility and must remain vigilant to avoid fragmentation of care in an interdisciplinary team delivery system.


Alpha-B crystallin in the normal human myocardium and cardiac conducting system.
The alpha crystallins are major protein components of the ocular lens and show both structural and functional homology with the family of small heat shock proteins. alpha B crystallin is also present in various extra-lenticular tissues, with a high concentration in cardiac muscle. In this study, the myocardium and conducting system from 15 adult and 25 fetal and infant hearts were examined by immunohistochemistry using a previously characterized antiserum to alpha B crystallin. Contractile myocardium showed moderate staining, with particular localization to Z bands and intercalated discs. Fibres of the sino-atrial and atrio-ventricular nodes and His bundle showed less intense staining than contractile fibres, whereas fibres of the left and right bundle branches showed more intense staining. This distribution is similar to that previously demonstrated for the intermediate filament desmin. This observation, together with currently available evidence, suggests that cardiac alpha B crystallin may play a role in protecting the cytoskeleton during cell stress. For practical purposes, immunostaining with alpha B crystallin greatly facilitates the identification of cardiac conducting fibres.


[Ambulatory surgery in a urology department. Analysis of the period 2003-2006].
When talking about day surgery we have to differentiate between minor and major ambulatory surgery. Ambulatory surgery enables the patient to stay in the hospital not more than a few hours, showing similar safety and efficacy than conventional surgery. The objective of this paper is to evaluate the results of an ambulatory surgery program. Descriptive retrospective study of the results of the Ambulatory Surgery in a Urology Department, including 4,185 patients in a four-year period, from January 1st 2003 to December 31st 2006. In the study period the global substitution rate was 83.6%. The hospital admission rate was 2.5%, most of which were early admissions. Major complications appeared in 26 patients (0.6%), being major bleeding the predominant one. Most complications were minor or mild, and pain at the site of the surgical wound was the most frequent problem found. The increase and continuous promotion of ambulatory surgery are more than justified. The high satisfaction among patients undergoing this type of surgery, with a very low number of complications registered, provides us with a valuable tool for health-care expenditure control.


[Tuberculosis in Hodgkin's disease in a child].
During its evolution, Hodgkin disease is accompanied by changes in the cell immunity, mainly of delayed type. Tuberculosis can precede Hodgkin disease or complicate its evolution during a simultaneous development of both diseases, or the lymph node tuberculosis can hurry hemopathy onset. Tb lesions in such patients can have atypical features.


Thirteen square centimetre mass causing syncope in a patient with device related infective endocarditis.
A 68-year-old man presented with anorexia, weight loss and severe asthenia starting 2 months before and fever lasting over 2 weeks. Analytical study revealed increased C reactive protein and sedimentation velocity. While thoracic x-ray and urinalysis were unremarkable, blood cultures were consistently positive for Enterococcus faecalis. A thoracic echocardiogram revealed a very large vegetation adherent to the ventricular electrocatheter of the patient's pacemaker, so parenteral antibiotics were started. During his stay at the internal medicine ward, patient suffered three syncopal episodes and maintained intermittent fever. A transesophageal ECG performed at a tertiary centre on the 14th day unmasked a 9-12 cm(2) organised mass, ovoid and with regular borders, adherent to the ventricular electrocatheter at right atrium level and protruding to the ventricle at systole. Patient was referred for cardiothoracic surgery and a 13 cm(2) mass was removed alongside the ventricular electrocatheter. Two weeks following surgery, patient remains stable and asymptomatic.


Characterization of carrot root oil arising from supercritical fluid carbon dioxide extraction.
Carrot root oil (SCO), obtained by supercritical fluid carbon dioxide (SC-CO2) extraction, was characterized and compared to a commercial carrot oil (MCO) and a virgin olive oil (VOO) (cv. Coratina). SCO showed much higher contents of carotenes, phenolics, waxes, phytosterols, and sesquiterpene and monoterpene volatiles. In SCO, the most prominent components present in the fully investigated analytical fractions (fatty acids, triglycerides, waxes, phytosterols, long-chain aliphatic alcohols, superior triterpene alcohols, and volatiles) were, respectively, linolenic acid, trilinolein, waxes C38, beta-sitosterol, campesterol and stigmasterol, 1-hexacosanol, 24-methylencycloartanol and cycloartenol, beta-caryophyllene, alpha-humulene, alpha-pinene, and sabinene. In VOO, the major constituents of the above analytical classes were, respectively, oleic acid, trilinolein, waxes C36, unsaturated volatile C6 aldehydes (trans-2-hexenal most markedly), and the same prominent sterols and superior alcohols found in SCO. In MCO, which also contained a proportion of unknown plant oil, several components showed magnitudes that were lower compared to SCO but higher with respect to VOO. The last had the aliphatic and triterpene alcohol concentration higher compared to that of both SCO and MCO. Several chemometric methods, applied to different analytical data sets, proved to be effective in grouping the three oil kinds.


Validation of functional fetal autonomic brain age score fABAS in 5 min short recordings.
With the objective of evaluating the functional maturation age and developmental disturbances we have previously introduced the fetal autonomic brain age score (fABAS) using 30 min fetal magnetocardiographic recordings (fMCG, Jena). The score is based on heart rate pattern indices that are related to universal principles of developmental biology. The present work aims at the validation of the fABAS methodology on 5 min recordings from an independent database (fMCG, Bochum).We found high agreement of fABAS obtained from Jena normal fetuses (5 min subsets, n = 364) and Bochum recordings (n = 322, normal fetuses). fABAS of 48 recordings from fetuses with intra-uterine growth restriction (IUGR, Bochum) was reduced in most of the cases, a result consistent with IUGR fetuses from Jena previously reported. fABAS calculated from 5 min snapshots only partly covers the accuracy when compared to fABAS from 30 min recordings. More precise diagnosis requires longer recordings.fABAS obtained from fMCG recordings is a strong candidate for standardized assessment of functional maturation age and developmental disturbances. Even 5 min recordings seem to be valuable for screening for maturation problems.


Combined Use of Lachancea thermotolerans and Schizosaccharomyces pombe in Winemaking: A Review.
The combined use of Lachancea thermotolerans and Schizosaccharomyces pombe is a new winemaking biotechnology that aims to solve some modern industrial oenology problems related to warm viticulture regions. These areas are characterized for producing musts with high levels of sugar that can potentially be converted into wines with elevated ethanol contents, which are usually associated with high pH levels. This biotechnology was reported for the first time in 2015, and since then, several scientific articles have been published regarding this topic. These reported scientific studies follow an evolution similar to that performed in the past for Saccharomyces cerevisiae and Oenococcus oeni; they start by reporting results for basic winemaking parameters at the beginning, later continuing with more advanced parameters. This review compares the results of different researchers that have applied this new biotechnology and have studied wine quality parameters such as ethanol, glycerol, malic acid, lactic acid, amino acids, aroma compounds, or anthocyanins. It is shown that the new biotechnology is repeatedly reported to solve specific winemaking problems such as the lack of acidity, biogenic amines, ethyl carbamate, or undesirable color losses. Such results highlight this biotechnology as a promising option for warm viticulture areas.


The timing of booster sessions may not improve resuscitation skill retention among healthcare providers: a randomized controlled trial.
Booster sessions can improve cardiopulmonary resuscitation (CPR) skill retention among healthcare providers; however, the optimal timing of these sessions is unknown. This study aimed to explore differences in skill retention based on booster session timing. After ethics approval, healthcare providers who completed an initial CPR training course were randomly assigned to either an early booster, late booster, or no booster group. Participants' mean resuscitation scores, time to initiate compressions, and time to successfully provide defibrillation were assessed immediately post-course and four months later using linear mixed models. Seventy-three healthcare professionals were included in the analysis. There were no significant differences by randomization in the immediate post-test (9.7, 9.2, 8.9) or retention test (10.2, 9.8, and 9.5) resuscitation scores. No significant effects were observed for time to compression. Post-test time to defibrillation (mean ± SE: 112.8 ± 3.0 sec) was significantly faster compared to retention (mean ± SE: 120.4 ± 2.7 sec) (p = 0.04); however, the effect did not vary by randomization. No difference was observed in resuscitation skill retention between the early, late, and no booster groups. More research is needed to determine the aspects of a booster session beyond timing that contribute to skill retention.


A double-blind clinical trial of hydroxyethylrutosides in Menière's disease.
A double-blind, placebo-controlled, cross-over trial was undertaken in 39 patients with well-defined Menière's disease. After a one-month placebo run-in period, the patients were assigned, on a randomized basis, to three months' treatment with O-(beta-hydroxyethyl)-rutosides (HR) (2 g./day) followed by three months on placebo, or vice-versa. In spite of a very pronounced placebo effect and a marked tendency to a 'carryover' effect from the first sequence with HR into the second placebo sequence, there appeared to be a clear trend to a greater symptomatic improvement with HR treatment than with placebo. The audiometric findings showed a very clear, uniform superiority under HR treatment, for both air and bone conduction and at all five frequencies studied (250, 500, 1,000, 2,000 and 5,000 Hz.) (p values between 0.002 and 0.05). Indeed, whereas there was a worsening of hearing-loss at each frequency under placebo during the first sequence, this was significantly diminished at each frequency under HR treatment. There were no significant changes in vestibulometry (caloric test) which showed wide variations already during the run-in period. Tolerance to HR treatment was excellent, the incidence of side-effects being similar to that in the placebo periods.


Multiple band light trapping in ultraviolet, visible and near infrared regions with TiO2 based photonic materials.
TiO2 based photonic materials (TiO2 PMs) with hierarchical top-nanonet/bottom-nanotube structures were fabricated by a facile two-step electrochemical anodization method. The TiO2 PMs demonstrated multiple band light trapping activity not only in the ultraviolet and visible regions, but also in the near infrared region.


Surgical approaches to the petrous apex: distances and relations with cranial morphology.
Different pathologies may be located at the petrous apex. The primary surgical approaches used to remove such lesions are the pterional, subtemporal, presigmoid, and retrosigmoid. Each has advantages and disadvantages, and the distance to the petrous apex varies with the approach. Anatomical variations in cranial morphology may interfere with these distances. Dolichocephalic skulls have a longer anteroposterior axis than brachycephalic ones. Three hundred computed tomographic scans and 65 dry human skulls were analyzed to determine if cranial morphology could indicate the shortest distance to the petrous apex. The distance between the external cortical table of the skull and the petrous apex in each surgical approach was measured. The lengths of the anteroposterior axis (L) and the widths of the lateral axis (W) were measured to determine the cranial index (W/L x 100). This distance was longest in skulls with a high cranial index (brachycephalic) independent of the approach used. Statistical analysis showed that the distance to the previous apex was longest in the retrosigmoid approach and shortest in the pterional approach in all kinds of skulls. Brachycephalic skulls lose this ellipsoidal shape and the anterior laterolateral diameter is smaller than the posterior laterolateral diameter. Consequently, the distance from the cortical skull table to the petrous apex is shorter in brachycephalic skulls using all surgical approaches described in this article.


Characterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss.
Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss. The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age). The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells. Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.


[Malaria in Brazil: trends in the last ten years].
There have been major changes in the epidemiological patterns for malaria in Brazil in the last ten years. One of the most important features is the tendency towards focal distribution in the Amazon region, instead of spreading transmission zones. This new epidemiological situation has led to changes in the control theory based on the occurrence of focal transmission of the infection. The importance of diversified control measures has thus increased, taking into account the characteristics of each transmission focus. The article comments on new proposals for control presented at the Ministerial Conference in Amsterdam.


Novel genes for airway wall thickness identified with combined genome-wide association and expression analyses.
Airway wall thickness (AWT) is affected by both environmental and genetic factors and is strongly associated with airflow limitation in smaller airways. To investigate the genetic component of AWT. AWT was measured on low-dose computed tomography scans in male heavy smokers participating in a lung cancer screening study (n = 2,640). Genome-wide association studies on AWT were performed under an additive model using linear regression (adjusted for pack-years, lung volume), followed by metaanalysis. An independent cohort was used for validation of the most strongly associated single-nucleotide polymorphisms (SNPs). The functional relevance of significant SNPs was evaluated. Three significant loci on chromosomes 2q (rs734556; P = 6.2 × 10(-7)) and 10q (rs10794108, P = 8.6 × 10(-8); rs7078439, P = 2.3 × 10(-7)) were associated with AWT and confirmed in the metaanalysis in cohorts with comparable lung function: P values = 4.6 × 10(-8), 7.4 × 10(-8), and 7.5 × 10(-8), respectively. SNP rs734556 was associated with decreased lung tissue expression of SERPINE2, a susceptibility gene for emphysema. Two nominally significant SNPs showed effects with similar direction: rs10251504 in MAGI2 (P = 5.8 × 10(-7)) and rs4796712 in NT5C3B (P = 3.1 × 10(-6)). Higher MAGI2 expression in bronchial biopsies of patients with chronic obstructive pulmonary disease was significantly associated with fewer inflammatory cells. The presence of the NT5C3B risk allele was associated with higher lung tissue expression (P = 1.09 × 10(-41)). Genetic variants contribute to AWT. Among others, the identified genes are also involved in emphysema, airway obstruction, and bronchial inflammation.


[Use of digital photoluminescence radiography in traumatology. Report of experiences].
For more than 1 year we have had the opportunity of using a digital photoluminescence radiography system that allows documentation of the radiological findings on a high-contrast scale. In addition to chest X-rays this technical unit has been used to document skeletal findings in the skull, the cervical spine and the shoulder. In all, 211 cases have been evaluated in which digital and conventional X-rays have been taken during treatment. Using a 5-step confidence scale, two experienced investigators have evaluated and compared the digital and conventional X-rays. In respect of image quality, bone outline, and structure and identification of findings, digital documentation has proved at least as good as conventional documentation, and even superior in the case of shoulder X-rays. Improved image quality is caused by the superior bone outline. Therefore, we recommended digital photoluminescence radiography as a routine procedure for the documentation of findings in the skull, cervical spine and shoulder. Repeated investigations will become unnecessary and it will be possible to cope with large numbers of patients.


[Characteristics of mother-child collaboration at 48 months in two number-related tasks].
Preschoolers' number related skills and maternal guidance used to introduce and foster the acquisition of these skills were examined in 193 48-month-olds. Mother-child collaboration was observed during two number-related tasks: a dot-to-dot drawing task and a matching number representations task. Patterns of responsibility sharing in task resolution were coded from videos, using a cross-classification strategy adapted from Parent et al. (2000). Using mother-child interactions as a means to assess early numeracy skills, we replicated past findings obtained when child numeracy skills were assessed autonomously (Baroody & Dowker, 2003; Sinclair, 1988). Results also indicate that mothers adjust their support and the demands of the task to meet their child's skill level. In addition, promoting an enjoyable affective climate and fostering child motivation to complete the task appeared to be a predominant aspect of maternal guidance. Together, these results support the relevance of evaluating children's numeracy skills in a social context and emphasize the importance of taking into account affective dimensions of mother-child interactions when evaluating the development of new cognitive skills.


Production of types A and B spores of Clostridium botulinum by the biphasic method: effect on spore population, radiation resistance, and toxigenicity.
Spores of three strains each of type A and type B Clostridium botulinum were produced both by a biphasic (solid medium overlaid with an aqueous phase) and by a "conventional" (deep broth culture) procedure. Sporogenesis by the biphasic system was more rapid, convenient, and economical, and yielded as many or more heat-resistant (80 C, 10 min) spores per milliliter as by the conventional technique. Of several aqueous phases [thiamine-hydrochloride, yeast extract, (NH(4))(2)SO(4)] tested with strain 62A, the highest spore colony counts were obtained with 2.0% (NH(4))(2)SO(4). The six strains formed maximum spore numbers in 5 to 6 days of incubation. Spores produced by the two methods had essentially equal radiation resistances (D and lag values), and their subcultures gave similar toxin titers (LD(50) values).


Nasal-temporal asymmetric changes in retinal peripheral refractive error in myopic adolescents induced by overnight orthokeratology lenses.
To observe the changes in peripheral refraction in myopic adolescents after overnight orthokeratology and its influencing factors. This was a prospective study among young myopic adolescents aged 8-14 years (n = 21). The peripheral refraction of the subjects was measured at 5, 10, 15, 20, 25, and 30° from the nasal and temporal side to the central fixation by WAM-5500 Open-field refractometer. The axial length, baseline spherical equivalent refraction, and other parameters were measured. The data were measured at baseline and 1, 3, and 12 months after wearing orthokeratology lenses. The relative peripheral refraction at the nasal and temporal side from central to 30° eccentricity revealed relative hyperopic defocus in all subjects at baseline measurement. One month after wearing the orthokeratology lenses, the relative peripheral refraction changed to myopic defocus, the nasal-temporal relative peripheral refraction was asymmetric, and the observed difference was statistically significant. Positive correlations were found between the change amount of nasal relative peripheral refraction and baseline spherical equivalent refraction, the baseline nasal relative peripheral refraction was higher than that on the temporal side, and after orthokeratology, the value of nasal relative peripheral refraction was lower than that on the temporal side. The changes at 30° on both sides were correlated to the axial elongation (rNasal = 0.565, rTemporal = 0.526, p < 0.05). This study demonstrated that after orthokeratology, relative peripheral hyperopia in the myopic patients turned into relative peripheral myopia, and the nasal-temporal asymmetry changed significantly after orthokeratology, which was correlated with the baseline refractive state.


Centipedes subdue giant prey by blocking KCNQ channels.
Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede's venom. The study indicates that centipedes' venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.


Elements of dynamics VI: the dynamic unconscious and unconscious dynamics.
The dynamic unconscious remains in contention in cognitive psychology. Academic settings may not provide the compelling evidence of unconscious dynamics regularly experienced by dynamic psychiatrists, psychoanalysts, and other physicians, including neurologists treating psychogenic motor disorders in the movement disorder clinic. An origin of unconscious motor expression is postulated in the intermodal connectivity of neuromental agencies, extending an idea that originated in Freud's (1950/1966) "Project for a Scientific Psychology." Motoric alexithymia is contrasted with synesthesia. Other examples of unconscious psychodynamics of everyday life are readily found in sexual expression. Dynamic pressures that render processes unconscious may also originate interpersonally. Illustrations are drawn from cultural influence, peer and parental pressure, sports competition, military combat, and reactions to dangerous predators.


Assessing Family Leave Policies and Pregnancy Outcomes Among Gastroenterologists: A Survey of Physicians in the American College of Gastroenterology.
Given variability in parental leave policies in gastroenterology (GI) with little data on outcomes, the American College of Gastroenterology conducted a survey to assess policies and outcomes. A survey was distributed to American College of Gastroenterology members with questions on demographics, fertility, pregnancy outcomes, and parental leave policies. There were 796 responses, with 52.5% female individuals. Many (57%) delayed parenting. High rates of infertility (21%) and pregnancy complications (68%) were observed. Satisfaction with parental leave policies in GI was low (35%). Our survey highlights the need for policies that support the well-being of our GI colleagues and families.


Interval-coded texture features for artifact rejection in automated cervical cytology.
In order to improve the separation between abnormal cells and noncellular artifacts in the CERVIFIP automated cervical cytology prescreening system, 22 different object texture features were investigated. The features were all statistical parameters of the pixel density histograms or one-dimensional filtered values of central and border regions of the object images. The features were calculated for 231 images (100 cells and 131 artifacts) detected as Suspect Cells by the current CERVIFIP and were then tested in hierarchical and linear discriminant classifiers. After selecting the two best features for use in a hierarchical classifier, 83% correct classification was achieved. One of these features was specifically designed to remove poorly focused objects. With maximum likelihood discrimination using all 22 features, an overall correct classification rate of 90% was obtained.


Genome-Wide Tuning of Protein Expression Levels to Rapidly Engineer Microbial Traits.
The reliable engineering of biological systems requires quantitative mapping of predictable and context-independent expression over a broad range of protein expression levels. However, current techniques for modifying expression levels are cumbersome and are not amenable to high-throughput approaches. Here we present major improvements to current techniques through the design and construction of E. coli genome-wide libraries using synthetic DNA cassettes that can tune expression over a ∼10(4) range. The cassettes also contain molecular barcodes that are optimized for next-generation sequencing, enabling rapid and quantitative tracking of alleles that have the highest fitness advantage. We show these libraries can be used to determine which genes and expression levels confer greater fitness to E. coli under different growth conditions.


Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes.
In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures.


Best practice in smoking cessation services for pregnant women: results of a survey of three services reporting the highest national returns, and three beacon services.
The NHS allocated dedicated funds to establish specialist smoking cessation services for pregnant smokers in England in 2000. An early survey revealed some uncertainty as to how the new services should work and monitor their outcome. The current survey focused on identifying examples of good practice in this difficult new field. Three services with the highest number of successful four-week quitters reported for the 2003/4 monitoring year were identified from Department of Health (DH) monitoring records, and three services were nominated from those known in the field as examples of best practice. There was no overlap between the two groups. All six services provided in-depth interviews. All three highest ranking services that reported close to 100 per cent success rates included unaided quitters identified from hospital wards, rather then smokers actually treated. They had only minimal or average genuine treatment provision for pregnant smokers in place. The three beacon services far exceeded the national throughput and outcome average identified in the previous survey, and provided a wealth of useful information. Although they differed in staffing levels and other aspects of their activities, they all shared several key elements, including a systematic training of midwives in how to refer pregnant smokers, offering nicotine replacement treatment to almost all clients and having an efficient system of providing the prescriptions, offering flexible home visits, and providing intensive multi-session treatment delivered by a small number of dedicated staff. Smoking cessation services for pregnant women may need clearer guidance on what they are expected to provide, and how they should monitor their outcome. The key features of the beacon services can serve as a practical model of current best practice applicable across most PCTs.


Preparation and evaluation of a novel hybrid monolithic column based on pentafluorobenzyl imidazolium bromide ionic liquid.
To develop a novel hybrid monolithic column based on pentafluorobenzyl imidazolium bromide ionic liquid, a new ionic liquid monomer was synthesized from 1-vinylimidazole and pentafluorobenzyl bromide. By employing a facile one-step copolymerization of polyhedral-oligomeric-silsesquioxane-type (POSS) cross-linking agent and the home-made ionic liquid monomer, the hybrid monolithic columns were in situ fabricated in fused-silica capillary. The morphology of monolithic column was characterized by scanning electron microscope (SEM) and the chemical composition was confirmed by Fourier-transform infrared spectroscopy (FT-IR) and elemental analysis. Excellent mechanical stability and slight swelling propensity were exhibited which was ascribed to the rigid hybrid monolithic skeleton. Reproducibility results of run-to-run, column-to-column, batch-to-batch and day-to-day were investigated and the RSDs were less than 0.46%, 1.84%, 3.96% and 3.17%, respectively. The mixed-mode retention mechanism with hydrophobic interaction, π-π stacking, ion-exchange, electrostatic interaction and dipole-dipole interaction was explored systematically using analytes with different structure types. Satisfied separation capability and column efficiency were achieved for the analysis of small molecular compounds such as alkylbenzenes, polycyclic aromatic hydrocarbons, nucleosides and halogenated compounds.


Peripheral vascular disease and outcomes following coronary artery bypass graft surgery.
There is an increased operative risk in patients with a history of peripheral vascular disease (PVD) who undergo coronary artery bypass grafting (CABG). There are also outcome differences associated with these patients. A study from a 10-year hospitalization cohort with prospective data collection. Multiple hospitals in the Greater Cincinnati area with 1 surgical group of cardiac surgeons. Cases were CABG patients with PVD, which was defined as having a history of type 1 neurologic injury, prior vascular surgery, or current vascular disease (n = 1561). Controls were CABG patients without PVD (n = 6328). The study examined 42 potential confounding risk factors and 16 outcome variables. Twenty-nine potential risk factors were found to be significantly different between CABG patients with and without PVD. Twenty-six confounding risk factors were correlated with 3 factors. Logistic regression analysis showed that even after controlling for sex, significant associative disorders, and other procedures, CABG patients with PVD still experienced more arrhythmias requiring treatment (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.03-1.33; P = .01), neurological complications (OR, 1.7; 95% CI, 1.43-2.07; P<.001), pulmonary complications (OR, 1.4; 95% CI, 1.23-1.62; P<.001), low output (OR, 1.3; 95% CI, 1.09-1.45; P = .001), and intraoperative complications (OR, 1.39; 95% CI, 1.06-1.83; P = .02). Patients with a PVD history undergoing CABG had more coexistent risk factors. These patients also exhibited higher rates of cardiac, systemic, renal, neurologic, and pulmonary complications.


Targeting of suicide gene delivery in pancreatic cancer cells via FGF receptors.
Pancreatic ductal adenocarcinomas (PDACs) overexpress various cell-surface tyrosine kinase receptors, including the type I high-affinity fibroblast growth factor receptor (FGFR-1). The purpose of this study was to determine whether FGFR-targeted gene therapy is feasible in this disorder. Accordingly, the effects of a conjugate consisting of fibroblast growth factor (FGF)-2 linked to a Fab' fragment against the adenovirus knob region were evaluated in human pancreatic cancer cell lines treated with an adenoviral vector containing the herpes simplex virus thymidine kinase (AdTK) gene. An adenoviral vector containing the firefly luciferase reporter gene (AdLuc) served to assess infection efficiency, and was initially tested in L6 rat myoblasts. In parental L6 cells that express exceedingly low levels of high-affinity FGFRs, transduction with AdLuc was enhanced 7- to 10-fold with the FGF2-Fab' conjugate, whereas in L6 cells transfected to express FGFR-1, it was enhanced 39- to 52-fold. The pancreatic cancer cell lines expressed variable levels of the four high-affinity FGF receptors, and exhibited 2- to 34-fold increases in gene transduction in the presence of the FGF2-Fab' conjugate. In the absence of FGF2-Fab' there was no correlation between surface binding of FGF2 and AdLuc transduction efficiency, whereas in the presence of FGF2-Fab', enhanced AdLuc transduction efficiency correlated with greater surface binding of FGF2. In the absence of AdTK, all the cell lines were insensitive to ganciclovir, whereas after AdTK transduction, only ASPC-1 and PANC-1 cells were resistant to ganciclovir even in the presence of FGF2-Fab'. Ganciclovir-mediated inhibition was dependent on the conjugate in CAPAN-1 and COLO-357 cells, but was independent of the conjugate in T3M4 and MIA-PaCa-2 cells. Real-time quantitative PCR of laser-captured cancer cells revealed high levels of various FGFR mRNA species in six of seven PDAC tumor samples. These findings indicate that transduction efficiency with FGF2-Fab' in pancreatic cancer cells is independent of native adenoviral transduction efficiency and is greatest in cells that exhibit concomitant expression of various high-affinity FGFRs. In view of the overexpression of high-affinity FGFRs in the cancer cells in PDAC, our findings also suggest that the combined use of AdTK, ganciclovir, and FGF2-Fab' may ultimately be a promising therapeutic approach in a subgroup of patients with PDAC.


Effect of the dietary net energy concentration on feed intake and performance of growing-finishing pigs housed individually.
The effect of dietary NE content on feed intake and performance of pigs was investigated using crossbred barrows with initial and final BW of approximately 35 and 110 kg, respectively. Pigs were housed individually and allowed ad libitum access to feed. Pigs were randomly allotted to 6 wheat and soybean meal-based diets (8.1, 8.7, 9.3, 9.9, 10.5, and 11.1 MJ NE/kg) with 16 pigs/diet. Ratios between standardized ileal digestible AA and NE were similar in all diets. Over the entire experiment, increase in dietary NE concentration was associated with a decreased ADFI (3.216, 3.216, 3.122, 2.910, 2.732, and 2.684 kg/d, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; linear, P < 0.01). The NE intake increased as dietary NE increased from 8.1 to 11.1 MJ NE/kg (26.04, 27.98, 29.03, 28.81, 28.68, and 29.77 MJ/d, respectively; linear, P < 0.01, and quadratic, P = 0.06). Average daily gain increased when dietary NE concentration increased (1.046, 1.126, 1.135, 1.177, 1.156, and 1.152 kg/d, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; linear and quadratic, P < 0.01). The increase in dietary NE concentration was associated with an increase in dressing percentage (76.5, 77.0, 77.4, 78.0, 78.2, and 78.4% of BW; linear, P < 0.01) but no differences in lean percentage (58.3, 57.9, 58.0, 57.3, 58.1, and 56.4% of HCW, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; P = 0.12). When dietary NE concentration increased from 8.1 to 11.1 MJ/kg, the G:F increased (0.326, 0.352, 0.364, 0.405, 0.425, and 0.428 kg/kg, respectively; linear, P < 0.01), but the G:F expressed using the NE system did not change (G:F, 39.97 g/MJ NE; P = 0.44). When adjusted to the same dressing yield and lean percentage, the differences in adjusted ADG increased among treatments, but the adjusted G:F expressed using the NE system was not influenced by dietary energy concentration. These results confirm the ability of individually housed pigs to adjust their spontaneous feed intake over a very wide range of NE concentrations (8.7 to 10.5 MJ/kg). Under commercial conditions, pigs may experience less variation in ADFI than the results obtained in this experiment because of differences in dietary energy concentrations. However, it seems that only a severe reduction in dietary energy concentration will be effective in restricting energy intake of pigs that are allowed ad libitum access to feed.


Diwu Yanggan capsule inhibits the occurrence and development of liver cancer in the Solt-Farber rat model by regulating the Ras/Raf/Mek/Erk signaling pathway.
This study sought to determine the effect and explore the mechanism of the Chinese medicinal compound preparation Diwu Yanggan (DWYG) capsule on the occurrence and development of liver cancer using the Solt-Farber rat model. Sprague-Dawley rats were randomly distributed into a normal group, sham group, DWYG group, sorafenib group, and model group. The DWYG group and sorafenib group were given DWYG capsule and sorafenib tablet, respectively, with induction of the model. Hematoxylin-eosin (HE) staining was used to detect liver pathological changes. The content of nuclear DNA in the liver was detected by Feulgen staining, and the expression of PCNA was detected by immunohistochemical staining. Molecular biology methods were used to detect the expression of liver regeneration-related factors and Ras/Raf/Mek/Erk signaling pathway-related proteins and mRNAs. HE staining showed that compared with those in the model group, the liver pathological changes in the DWYG group were significantly reduced (P < 0.05). The nuclear DNA content in the liver based on Feulgen staining and the expression of PCNA in the DWYG group was lower than that in the model group (P < 0.05). The expression of regeneration-related factors and Ras/Raf/Mek/Erk signaling pathway-related proteins and mRNAs was significantly lower in the DWYG group than in the model group (P < 0.05). In conclusion, DWYG capsules to some degree inhibit the occurrence and development of liver cancer in the Solt-Farber rat model, and the effect is not inferior to that of sorafenib. DWYG capsules likely delay the occurrence and development of liver cancer and improve the liver regeneration microenvironment by regulating the Ras/Raf/Mek/Erk signaling pathway and regeneration-related factors.


Differences in Fusarium Species in brown midrib Sorghum and in Air Populations in Production Fields.
Several Fusarium spp. cause sorghum (Sorghum bicolor) grain mold, resulting in deterioration and mycotoxin production in the field and during storage. Fungal isolates from the air (2005 to 2006) and from leaves and grain from wild-type and brown midrib (bmr)-6 and bmr12 plants (2002 to 2003) were collected from two locations. Compared with the wild type, bmr plants have reduced lignin content, altered cell wall composition, and different levels of phenolic intermediates. Multilocus maximum-likelihood analysis identified two Fusarium thapsinum operational taxonomic units (OTU). One was identified at greater frequency in grain and leaves of bmr and wild-type plants but was infrequently detected in air. Nine F. graminearum OTU were identified: one was detected at low levels in grain and leaves while the rest were only detected in air. Wright's F statistic (FST) indicated that Fusarium air populations differentiated between locations during crop anthesis but did not differ during vegetative growth, grain development, and maturity. FST also indicated that Fusarium populations from wild-type grain were differentiated from those in bmr6 or bmr12 grain at one location but, at the second location, populations from wild-type and bmr6 grain were more similar. Thus, impairing monolignol biosynthesis substantially effected Fusarium populations but environment had a strong influence.


Novel Hsp90 inhibitor platycodin D disrupts Hsp90/Cdc37 complex and enhances the anticancer effect of mTOR inhibitor.
Heat shock protein 90 (Hsp90) is a critically conserved molecular chaperone protein and promising therapeutic target for cancer treatment. In this study, platycodin D (PD), a saponin isolated from traditional Chinese herb Platycodonis Radix, was identified as a novel Hsp90 inhibitor. We verified that PD did not affect the ATPase activity of Hsp90. However, PD disrupted the co-chaperone interaction of Hsp90/cell division cycle protein 37 (Cdc37) and subsequently degraded multiple Hsp90 client proteins without the feedback increase of Hsp70. In different genotypes of non-small cell lung cancer cells, co-treatment with the mTOR inhibitor Everolimus and PD enhanced antiproliferation activity and apoptotic effect. The feedback survival signal upon mTOR inhibition was fully terminated by the co-administration with PD through reduced epidermal growth factor receptor (EGFR) and insulin growth factor 1 receptor (IGF1R) expression, suppressed AKT activity, and reinforced 4E-BP1 inhibition. Our results not only identified PD as a novel Hsp90 inhibitor by disrupting the protein-protein interaction of Hsp90/Cdc37 complex, but also provided mechanistic insights into the ineffectiveness of mTOR inhibitors and identified therapeutic strategy for cancer treatment.


Beta 2-microglobulin in otitis media with effusion.
beta 2-Microglobulin (beta 2M) is a low-molecular-weight protein present in serum and other fluids during various autoimmune or chronic inflammatory diseases. beta 2-Microglobulin was measured in middle ear effusion (MEE) and serum samples obtained from 36 patients with chronic otitis media with effusion. Using a quantitative competitive enzyme immunoassay, we were able to demonstrate beta 2M in 98% of the MEE samples. The mean concentration of beta 2M was higher in the MEE samples than in the serum samples. There was considerable variability between ears in those patients with bilateral MEE. There was no correlation between beta 2M concentration and the patients' age, sex, MEE type, and culture results, or cytologic profiles of the MEEs. This increased beta 2M may reflect earlier lymphocyte activity during the inflammatory process.


Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.
Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity. Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasticity, reduced newborn neuron integration, and diminished precision of remote fear memories. Memory precision and neuronal IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spine plasticity. We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM) and that its loss leads to impaired ECM engulfment and a concomitant accumulation of ECM proteins in contact with synapses. These data define a cellular mechanism through which microglia regulate experience-dependent synapse remodeling and promote memory consolidation.


An open study of pamidronate in the treatment of refractory ankylosing spondylitis.
Bisphosphonates inhibit the development of delayed type hypersensitivity chronic inflammation and suppress inflammation and cartilage/bone erosion in diverse murine arthritis models. We evaluated antiinflammatory properties of the bisphosphonate pamidronate in patients with ankylosing spondylitis (AS) refractory to nonsteroidal antiinflammatory drugs. Patients included 14 men and 2 women. The first group of 8 patients (Group 1) received pamidronate as a 30 mg intravenous infusion once a month for 3 months, followed by a 60 mg dose once a month for an additional 3 months. Eight additional patients (Group 2) received only the 60 mg dose once a month for 3 months. Clinical assessments included the BASDAI (Bath AS Disease Activity Index), BASFI (Functional Index), and BASMI (Metrology Index), and laboratory assessments hemoglobin and erythrocyte sedimentation rate (ESR) at baseline and one month after final 60 mg dose of pamidronate. Mean BASDAI score at study entry was 6.7 for both groups. A significant improvement was observed in disease activity score in Group 1 after 6 monthly infusions of pamidronate (mean BASDAI 4.21; p = 0.03), in the BASMI score (p = 0.01), and the ESR (p = 0.009). A significant improvement in the BASMI was noted in Group 2 patients (p = 0.007) after 3 monthly infusions of pamidronate, but not in the BASDAI score (mean 5.01; p = 0.07) or the ESR (p = 0.12). Preliminary data suggest pamidronate may possess antiinflammatory activity in patients with AS, particularly with prolonged administration; this agent deserves further evaluation in a controlled trial.


On the NP-completeness of the Hartree-Fock method for translationally invariant systems.
The self-consistent field method utilized for solving the Hartree-Fock (HF) problem and the closely related Kohn-Sham problem is typically thought of as one of the cheapest methods available to quantum chemists. This intuition has been developed from the numerous applications of the self-consistent field method to a large variety of molecular systems. However, as characterized by its worst-case behavior, the HF problem is NP-complete. In this work, we map out boundaries of the NP-completeness by investigating restricted instances of HF. We have constructed two new NP-complete variants of the problem. The first is a set of Hamiltonians whose translationally invariant Hartree-Fock solutions are trivial, but whose broken symmetry solutions are NP-complete. Second, we demonstrate how to embed instances of spin glasses into translationally invariant Hartree-Fock instances and provide a numerical example. These findings are the first steps towards understanding in which cases the self-consistent field method is computationally feasible and when it is not.


[Vascular access in the elderly: AVF vs CVC. A comment].
The aging population starting hemodialysis treatment raises the question as to which is the best vascular access in an older patient with multiple complications. The center effect is an important element in the choice of a vascular access, as shown by the DOPPS data and by a recent audit held in Lombardy. However, other data show an increase in the use of permanent CVCs in the last years and other factors must be taken into account in this clinical choice. Also the timing of proposing a vascular access to a patient has changed over the years (see K-DOQI 2006 vs 2000). Most of the literature agrees on the strategy of a global clinical evaluation of the patient to decide when to place a vascular access and which type of access to use. Native and prosthetic fistulas are considered superior to CVCs although the latter have certain advantages in selected patients, such as those with severe cardiac problems. The nephrologist has a major role in vascular access management as part of a team made up also by a vascular surgeon and an interventional radiologist. Only in a center where both native and prosthetic fistulas can be constructed and permanent CVCs be placed can a nephrologist choose the most appropriate vascular access for individual patients after evaluation not only of their renal function but their cardiovascular risk as well.


[How and why treat ventricular hyperkinetic arrhythmias].
The Authors present their experience, based on 180 patients, concerning the treatment of chronic ventricular tachycardia. According to the underlying etiology, about 1/3 of the cases were considered idiopathic (most of all in form of salvos), 1/3 were ischemic with a prior myocardial infarction (ventricular tachycardias in the setting of acute myocardial infarction were not considered) and 1/3 had miscellaneous cardiac diseases. Prophylactic treatment of ventricular tachycardia recurrences was divided in three steps: classic antiarrhythmic drugs used in monotherapy (Quinidine or Quinidine-like, betablockers, Verapamil); Amiodarone or recent class I antiarrhythmics (Flecainide, Propafenone); drug combinations. The results of medical treatment were different according to the underlying etiology: the first two steps achieved control of the arrhythmia in 2/3 of patients with idiopathic ventricular tachycardia, in 45% of ventricular tachycardia due to miscellaneous cardiopathy and only in 35% of cases with post-myocardial infarction ventricular tachycardia. Four patients were referred for antiarrhythmic surgery and 3 received a palliative electrical device. During a mean follow-up period of 5 years, there were no deaths in the group with idiopathic ventricular tachycardia, 10% of deaths in the group with miscellaneous cardiopathy and 17% in the group with post-myocardial infarction ventricular tachycardia. Idiopathic ventricular tachycardias seem to bear a minimal risk, and the need to treat them depends only on the severity of functional signs and on the frequency of arrhythmic episodes. In patients with severe underlying cardiopathy, particularly ischemic heart disease, active search for an effective treatment is mandatory, due to the high risk of death.


Self-Referenced Ratiometric Detection of Sulfatase Activity with Dual-Emissive Urease-Encapsulated Gold Nanoclusters.
In this study, on the basis of the biomineralization capability of urease, a facile, one-step, and green synthetic method has been proposed for the fabrication of gold nanoclusters (AuNCs). The prepared urease-encapsulated AuNCs (U-AuNCs) exhibited strong red fluorescence emission (λem = 630 nm) with a quantum yield as high as 17%. Interestingly, at a low concentration, the U-AuNC solution was found to be a dual-emissive system with the blue emission of the dityrosine (diTyr) residues of urease and the red emission of the embedded AuNCs. Further experiments demonstrated that p-nitrophenol (PNP) can selectively suppress the 410 nm emission of the diTyr residues of U-AuNCs without affecting the red emission of the U-AuNCs. The fluorescence quenching mechanism between U-AuNCs and PNP was systematically studied, and the leading role of the inner filter effect (IFE) was identified. Additionally, based on the sulfatase-catalyzed hydrolysis of p-nitrophenyl sulfate (PNPS) to release PNP, a self-referenced ratiometric detection method for sulfatase, which plays a crucial role in sulfur cycling, degradation of sulfated glycosaminoglycans and glycolipids, and extracellular remodeling of sulfated glycosaminoglycans, was developed by using dual-emissive U-AuNCs as the signal readout, in which the diTyr residues served as the probe and the AuNCs functioned as the internal reference. This IFE-based ratiometric sensing strategy showed a good linear relationship over the range of 0.01-1 U/mL ( R2 = 0.997). The detection limit for sulfatase activity was 0.01 U/mL. The developed protocol was successfully used to detect sulfatase activity in human serum samples. The simplicity, rapidity, low cost, high credibility, good reproducibility, and excellent selectivity of the detection platform serve as an inspiration for further applications of fluorescent AuNCs in chemo/biosensing.


Glaucoma.
Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30-50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression.


Origins of task-specific sensory-independent organization in the visual and auditory brain: neuroscience evidence, open questions and clinical implications.
Evidence of task-specific sensory-independent (TSSI) plasticity from blind and deaf populations has led to a better understanding of brain organization. However, the principles determining the origins of this plasticity remain unclear. We review recent data suggesting that a combination of the connectivity bias and sensitivity to task-distinctive features might account for TSSI plasticity in the sensory cortices as a whole, from the higher-order occipital/temporal cortices to the primary sensory cortices. We discuss current theories and evidence, open questions and related predictions. Finally, given the rapid progress in visual and auditory restoration techniques, we address the crucial need to develop effective rehabilitation approaches for sensory recovery.


Specialty training and the personal use of benzodiazepines by physicians affect their proneness to prescribe tranquilizers.
The decision on how to treat a patient does not depend on clinical matters or illness characteristics alone, but also on patient, physician and setting variables such as personality, training, or reimbursement. No research has yet been carried out to answer the question whether personal experience with medications also influences prescribing behavior. In this study, 124 physicians stratified according to specialty (neuropsychiatrists vs. general practitioners), type of institution (private practice vs. hospital), years of professional experience (young vs. old), and region (rural vs. urban) participated in a structured interview to evaluate their proneness to prescribe benzodiazepines for sleep disorders as well as their personal experience in taking benzodiazepines for their own sleep problems. Both specialty and personal experience were significantly related to proneness to prescribe. Other variables tested (region, institution, age, gender) did not help to explain the variance in benzodiazepine prescribing practice. Thus physician variables and, importantly, their own personal experience in taking the medication significantly influence treatment choice. Rational medical decision making and treatment guidelines must therefore take into account medical knowledge as well as knowledge of personal treatment preferences and professional biases.


Controllable gelation of methylcellulose by a salt mixture.
The effects of a salt mixture consisting of a salt-out salt (NaCl) and a salt-in salt (NaI) on the sol-gel transition of methylcellulose (MC) in aqueous solution have been studied by means of micro differential scanning calorimetry and rheometry. The salt mixture was found to have a combined effect from the salt-out and salt-in salts in the mixture, and the salt effect was dependent on the water hydration abilities of the component ions and ion concentration. At a fixed total salt concentration, the sol-gel transition temperature nicely followed a rule of mixing: Tp = m1Tp1 + m2Tp2 where Tp, Tp1, and Tp2 are the gelation peak temperatures for the MC solutions with a salt mixture, NaCl, and NaI, respectively, and mi is the molar fraction of the salt component i in the salt mixture. The linear rule of mixing proved that the effects of NaCl and NaI on the sol-gel transition of MC are completely independent. In addition, the presence of a single salt or a salt mixture in a MC solution does not change the essential mechanism of MC gelation. Therefore, the sol-gel transition of MC can be simply controlled by a salt mixture consisting of a salt-out salt and a salt-in salt. The rheological results supported the micro thermal results excellently. But the gel strength of MC containing salts was influenced by both salt type and salt concentration.


Effects of ex vivo transduction of mesencephalic reaggregates with bcl-2 on grafted dopamine neuron survival.
Survival rates of dopamine (DA) neurons grafted to the denervated striatum are extremely poor (5-20%). Gene transfer of survival promoting factors, such as the anti-apoptotic protein bcl-2, to mesencephalic DA neurons prior to transplantation (ex vivo transduction) offers a novel approach to increase graft survival. However, specific criteria to assess the efficacy of various vectors must be adhered to in order to reasonably predict successful gene transfer with appropriate timing and levels of protein expression. Cell culture results utilizing three different herpes simplex virus (HSV) vectors to deliver the reporter beta-galactosidase gene (lacZ) indicate that transduction of mesencephalic cells with a helper virus-free HSV amplicon (HF HSV-TH9lac) that harbors the 9-kb tyrosine hydroxylase (TH) promoter to drive lacZ gene expression elicits the transduction of the highest percentage (approximately 50%) of TH-immunoreactive (THir) neurons without significant cytotoxic effects. This transduction efficiency and limited cytotoxicity was superior to that observed following transduction with helper virus-containing HSV (HC HSVlac) and helper virus-free HSV amplicons (HF HSVlac) expressing lacZ under the transcriptional control of the HSV immediate-early 4/5 gene promoter. Subsequently, we assessed the ability of HSV-TH9lac and the bcl-2 expressing HSV-TH9bcl-2 amplicon to transduce mesencephalic reaggregates. Although an increase in bcl-2 and beta-galactosidase protein was induced by transduction, amplicon-mediated overexpression of bcl-2 did not lead to an increase in grafted THir neuron number. Even with highly efficient viral vector-mediated transduction, our results demonstrate that ex vivo gene transfer of bcl-2 to mesencephalic reaggregates is ineffective in increasing grafted DA neuron survival.


Seroprevalence of Dengue, Zika, and Chikungunya Viruses in Wild Monkeys in Thailand.
Zoonotic pathogens such as arboviruses have comprised a significant proportion of emerging infectious diseases in humans. The role of wildlife species as reservoirs for arboviruses is poorly understood, especially in endemic areas such as Southeast Asia. This study aims to determine the exposure history of different macaque species from national parks in Thailand to mosquito-borne flaviviruses and alphavirus by testing the serum samples collected from 25 northern pigtailed macaques, 33 stump-tailed macaques, and 4 long-tailed macaques for the presence of antibodies against dengue, Zika, and chikungunya viruses by plaque reduction neutralization assay. Specific neutralizing antibodies against Dengue virus (DENV1-4) and Zika virus (ZIKV) were mainly found in stump-tailed macaques, whereas neutralizing antibody titers were not detected in long-tailed macaques and pigtailed macaques as determined by 90% plaque reduction neutralization assay (PRNT90). One long-tailed macaque captured from the south of Thailand exhibited antibody titers against chikungunya virus (CHIKV), suggesting enzootic of this virus to nonhuman primates (NHPs) in Thailand. Encroachment of human settlements into the forest has increased the interface that exposes humans to zoonotic pathogens such as arboviruses found in monkeys. Nonhuman primates living in different regions of Thailand showed different patterns of arboviral infections. The presence of neutralizing antibodies among wild monkeys in Thailand strongly suggests the existence of sylvatic cycles for DENV, ZIKV, and CHIKV in Thailand. The transmission of dengue, Zika, and chikungunya viruses among wild macaques may have important public health implications.


Memory development and neurophysiology: accomplishments and limitations.
The review of Teyler and Fountain offers developmental psychologists an update on the status of neurophysiological theorizing and findings related to memory and learning. Recent findings of LTP and of localization of different types of memory in different brain areas have potential for enriching our understanding of memory development. However, we note several limitations in Teyler and Fountain's presentation in that they do not: distinguish between learning and memory, nor between storage and retrieval; address the role of knowledge-based or top-down influences in memory and learning; employ concepts that can accommodate such developmental phenomena as stages in the hierarchical reorganization of memory. We conclude that even when the age-old search for the "engram" is accomplished, these issues will remain, and that different levels of neural modeling will be required to accommodate them. It is important for developmental psychologists and neuroscientists to maintain communication for the purpose of mutual refinement of models as their knowledge bases continue to grow.


Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells.
Repetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However, the effect of rLLB exposure on AMs is still unclear. Here, we generated rLLB waves through a miniature manual Reddy-tube and explored their effects on MH-S cell morphology, phenotype transformation, oxidative stress status, and apoptosis by immunofluorescence, real-time quantitative PCR (qPCR), western blotting (WB) and flow cytometry. Ipatasertib (GDC-0068) or PDTC was used to verify the role of the Akt/NF-κB signaling pathway in these processes. Results showed that rLLB treatment could cause morphological irregularities and cytoskeletal disorders in MH-S cells and promote their polarization to the M1 phenotype by increasing iNOS, CD86 and IL-6 expression. The molecular mechanism is through the Akt/NF-κB signaling pathway. Moreover, we found reactive oxygen species (ROS) burst, Ca2+ accumulation, mitochondrial membrane potential reduction, and early apoptosis of MH-S cells. Taken together, our findings suggest rLLB exposure may cause M1 polarization and early apoptosis of AMs. Fortunately, it is blocked by specific inhibitors GDC-0068 or PDTC. This study provides a new treatment strategy for preventing and alleviating health damage in the occupational population caused by rLLB exposure.


Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits.
The function of presynaptic angiotensin II receptors at postganglionic sympathetic terminal axons under conditions of uninterrupted sympathetic impulse traffic was studied in anesthetized rabbits (alfadolone + alfaxalone). Mean arterial pressure, postganglionic renal sympathetic firing rate, the arterial plasma noradrenaline concentration, and heart rate were measured before (basal values) and at the end of 4-min infusions of sodium nitroprusside. Angiotensin II (20 or 100 ng kg-1 min-1) caused dose-dependent increases of basal mean arterial pressure and decreases of basal sympathetic nerve activity and heart rate, but did not change the basal plasma noradrenaline concentration. Moreover, it shifted the sympathetic nerve activity-plasma noradrenaline relationship in a manner indicating an increase of the average release of noradrenaline per action potential. Angiotensin II at 100 ng kg-1 min-1 had an additional effect, at any given blood pressure, sympathetic nerve activity and heart rate were lower than in the controls. Captopril (1 mg kg-1 followed by 1 mg kg-1 h-1) caused no change in any parameter. The results demonstrate that exogenous angiotensin II activates release-facilitating receptors at postganglionic sympathetic neurons in rabbits with ongoing sympathetic nerve activity. Endogenous angiotensin II, however, played no role in cardiovascular regulation under the present, acute experimental conditions. Vasopressin, which was studied for comparison, lacked a presynaptic effect on the release of noradrenaline but caused sympathoinhibition by an action on a central component of the baroreflex.


Orthogonally reactive SAMs as a general platform for bifunctional silica surfaces.
We report the synthesis and self-assembly of azide and amine trimethoxysilanes that result in mixed monolayers on silica. The amine and azide functional groups can be independently reacted with acid chlorides and terminal alkynes, respectively. Consequently, these orthogonally reactive monolayers represent a general starting point for making bifunctional surfaces. Using X-ray photoelectron spectroscopy, we determined the azide/amine surface ratio as well as the reactivity of the azide and amine functional groups in the mixed self-assembled monolayer (SAM). Significantly, the surface azide/amine ratio was much lower than the azide/amine ratio in the self-assembly mixture. After determining the self-assembly mixture composition that would afford 1:1 azide-amine mixed monolayers, we demonstrated their subsequent functionalization. The resulting bifunctional surface has a similar functional group ratio to the azide/amine precursor SAM demonstrating the generality of this approach.


Size and shape dependent deprotonation potential and proton affinity of nanodiamond.
Many important reactions in biology and medicine involve proton abstraction and transfer, and it is integral to applications such as drug delivery. Unlike electrons, which are quantum mechanically delocalized, protons are instantaneously localized on specific residues in these reactions, which can be a distinct advantage. However, the introduction of nanoparticles, such as non-toxic nanodiamonds, to this field complicates matters, as the number of possible sites increases as the inverse radius of the particle. In this paper we present > 10(4) simulations that map the size- and shape-dependence of the deprotonation potential and proton affinity of nanodiamonds in the range 1.8-2.7 nm in average diameter. We find that while the average deprotonation potential and proton affinities decrease with size, the site-specific values are inhomogeneous over the surface of the particles, exhibiting strong shape-dependence. The proton affinity is strongly facet-dependent, whereas the deprotonation potential is edge/corner-dependent, which creates a type of spatial hysteresis in the transfer of protons to and from the nanodiamond, and provides new opportunities for selective functionalization.


Physical training prevents body weight gain but does not modify adipose tissue gene expression.
The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.


Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer.
Introduction: Prostate cancer is the second leading cause of cancer-related death among American men. Prostate tumor cells exhibit significant tropism for the bone and once metastasis occurs, survival rates fall significantly. Current treatment options are not curative and focus on symptom management. Immunotherapies are rapidly emerging as a possible therapeutic option for a variety of cancers including prostate cancer, however, variable patient response remains a concern. Chemotherapies, like cabozantinib, can have immune-priming effects which sensitize tumors to immunotherapies. Additionally, lower doses of chemotherapy can be used in this context which can reduce patient side effects. We hypothesized that a combination of chemotherapy (cabozantinib) and immunotherapy [Interleukin-27 (IL-27)] could be used to treat bone-metastatic prostate cancer and exert pro-osteogenic effects. IL-27 is a multi-functional cytokine, which promotes immune cell recruitment to tumors, while also promoting bone repair. Methods: To test this hypothesis, in vivo experiments were performed where syngeneic C57BL/6J mice were implanted intratibially with TRAMP-C2ras-Luc cells that are able to form tumors in bone. Immunotherapy was administered in the form of intramuscular gene therapy, delivering plasmid DNA encoding a reporter gene (Lucia), and/or a therapeutic gene (IL-27). Sonoporation was used to aid gene delivery. Following immunotherapy, the animals received either cabozantinib or a vehicle control by oral gavage. Bioluminescence imaging was used to monitor tumor size over time. Results: Combinatorial therapy inhibited tumor growth and improved survival. Further, RNA sequencing was used to investigate the mechanisms involved. Microcomputed tomography and differentiation assays indicated that the combination therapy improved bone quality by enhancing osteoblast differentiation and inhibiting osteoclast differentiation. Discussion: Our conclusion is that a chemo-immunotherapy approach such as the one examined in this work has potential to emerge as a novel therapeutic strategy for treating bone-metastatic prostate cancer. This approach will enable a significant reduction in chemotherapy-associated toxicity, enhance sensitivity to immunotherapy, and improve bone quality.


Stimulus-effect relations for left ventricular growth obtained with a simple multi-scale model: the influence of hemodynamic feedback.
Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus-effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach. We evaluated cardiac growth in response to valve disease using various stimulus-effect relations and observed an unphysiological decline pump function. Here we extend that model with a model of hemodynamic feedback that maintains mean arterial pressure and cardiac output through adaptation of peripheral resistance and circulatory unstressed volume. With the combined model, we obtain stable growth and restoration of pump function for most growth laws. We conclude that a mixed combination of stress and strain stimuli to drive cardiac growth is most promising since it (1) reproduces clinical observations on cardiac growth well, (2) requires only a small, clinically realistic adaptation of the properties of the circulatory system and (3) is robust in the sense that results were fairly insensitive to the exact choice of the chosen mechanics loading measure. This finding may be used to guide the choice of growth laws in more complex finite element models of cardiac growth, suitable for predicting the response to spatially varying changes in tissue load. Eventually, the current model may form a basis for a tool to predict patient-specific growth in response to spatially homogeneous changes in tissue load, since it is computationally inexpensive.


Synthesis and Membrane Properties of Sulfonated Poly(arylene ether sulfone) Statistical Copolymers for Electrolysis of Water: Influence of Meta- and Para-Substituted Comonomers.
Two series of high molecular weight disulfonated poly(arylene ether sulfone) random copolymers were synthesized as proton exchange membranes for high-temperature water electrolyzers. These copolymers differ based on the position of the ether bonds on the aromatic rings. One series is comprised of fully para-substituted hydroquinone comonomer, and the other series incorporated 25 mol % of a meta-substituted comonomer resorcinol and 75 mol % hydroquinone. The influence of the substitution position on water uptake and electrochemical properties of the membranes were investigated and compared to that of the state-of-the-art membrane Nafion. The mechanical properties of the membranes were measured for the first time in fully hydrated conditions at ambient and elevated temperatures. Submerged in water, these hydrocarbon-based copolymers had moduli an order of magnitude higher than Nafion. Selected copolymers of each series showed dramatically increased proton conductivities at elevated temperature in fully hydrated conditions, while their H2 gas permeabilities were well controlled over a wide range of temperatures. These improved properties were attributed to the high glass transition temperatures of the disulfonated poly(arylene ether sulfone)s.


Bibliometric analysis of artificial intelligence for biotechnology and applied microbiology: Exploring research hotspots and frontiers.
Background: In the biotechnology and applied microbiology sectors, artificial intelligence (AI) has been extensively used in disease diagnostics, drug research and development, functional genomics, biomarker recognition, and medical imaging diagnostics. In our study, from 2000 to 2021, science publications focusing on AI in biotechnology were reviewed, and quantitative, qualitative, and modeling analyses were performed. Methods: On 6 May 2022, the Web of Science Core Collection (WoSCC) was screened for AI applications in biotechnology and applied microbiology; 3,529 studies were identified between 2000 and 2022, and analyzed. The following information was collected: publication, country or region, references, knowledgebase, institution, keywords, journal name, and research hotspots, and examined using VOSviewer and CiteSpace V bibliometric platforms. Results: We showed that 128 countries published articles related to AI in biotechnology and applied microbiology; the United States had the most publications. In addition, 584 global institutions contributed to publications, with the Chinese Academy of Science publishing the most. Reference clusters from studies were categorized into ten headings: deep learning, prediction, support vector machines (SVM), object detection, feature representation, synthetic biology, amyloid, human microRNA precursors, systems biology, and single cell RNA-Sequencing. Research frontier keywords were represented by microRNA (2012-2020) and protein-protein interactions (PPIs) (2012-2020). Conclusion: We systematically, objectively, and comprehensively analyzed AI-related biotechnology and applied microbiology literature, and additionally, identified current hot spots and future trends in this area. Our review provides researchers with a comprehensive overview of the dynamic evolution of AI in biotechnology and applied microbiology and identifies future key research areas.


Distinct responses of chloroplasts to blue and green laser microbeam irradiations in the centric diatom Pleurosira laevis.
The centric diatom Pleurosira laevis is a large unicellular alga, in which ca 200 chloroplasts migrate toward the nuclear cytoplasm through the transvacuolar cytoplasmic strands in response to blue-light irradiation and, on the contrary, toward the cortical cytoplasm in response to green-light irradiation. We analyzed these light-induced chloroplast migrations using a scanning laser microbeam provided by a confocal microscope for intracellular irradiation. Spot irradiation of a blue laser microbeam induced rapid assemblage of chroloplasts into the nuclear cytoplasm regardless of the spot position and spot number. On the other hand, one or two spots of green laser microbeam induced chloroplast accumulation at the spots, although increasing spot numbers suppressed chloroplast accumulation at each spot. In our experimental condition, ca 1 min of blue-light irradiation was sufficient to stimulate movement, whereas green-light irradiation required uninterrupted and longer irradiation time (ca 15 min). Chloroplast assemblage induced by blue-light required extracellular Ca2+, and was inhibited by Ca2+ channel antagonists. Furthermore, higher efficiencies of chloroplast migration were obtained when a single beam spot was fragmented and scattered over wider area of plasma membrane. These observations suggested that blue-light induced a response at the plasma membrane, which subsequently activated Ca2+ permeable channels. This sequence of physiological events is identical to what was previously observed with chloroplast movement in response to mechanical stimulation. Furthermore, experiments with the cytoskeleton-disrupting agents, colchicine and cytochalasin D, indicated that blue-light-induced chloroplast movement required microtubules whereas the green-light-induced response to beam spot required actin filaments.


Fatal meningococcemia.
Within the past six years, a case of bothWaterhouse-Freidrichsen Syndrome and fulminant meningococcemia have presented to Union Memorial Hospital. Both cases presented in markedly different fashions, differed in microbiologic serogrouping, showed minimal histopathologic similarities; however achieved ultimately the same outcome through two different pathological pathways. The following case reports illustrate two mechanisms through which N. Meningitis may pathogenize a host, both leading to complete cardiovascular collapse in less than 12 hours.


Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.
BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.


[The use of the BAR-Valtrac-type pressure stapler in surgery of the large intestine].
A total of 148 patients underwent colon resection between June 1993 and November 1994 at the General Surgery Division of Busto Arsizio Hospital; anastomosis was performed using BAR Valtrac in 58 patients (39%), namely 28 males and 30 women with a mean age of 66.3 years. Surgery was elective in 90% of cases and in 84% of patients was secondary to neoplastic pathologies. Recanalisation occurred within a mean of 5.5 days after surgery, whereas the average hospital stay was 14.4 days. The authors report the absence of mortality and the low morbidity levels connected to the use of this anastomotic technique. Emphasis is also laid on the absence of anastomotic stenosis in all endoscopic controls performed to date.


Pharmacokinetic evaluation of enrofloxacin in chickens.
1. The pharmacokinetics and bioavailability of enrofloxacin in chickens were investigated following intravenous, intramuscular, subcutaneous and oral administration of 10 mg/kg body weight. A rapid distribution phase was followed by a slower elimination phase. 2. The apparent volume of distribution was 2.2 l/kg. Absorption half lives were 0.37, 0.36 and 0.92 h; elimination half lives were 4.06, 4.48 and 4.29 h and bioavailabilities were 87.5%, 80.8% and 59.6% after intramuscular, subcutaneous and oral administration, respectively. The drug completely disappeared from all tissues after 3 days following oral administration. 3. Based on the bioavailability and disposition kinetics of enrofloxacin, administration of one dose per day should both be practical and adequate to maintain plasma enrofloxacin concentrations within the pharmacologically active but lower than tolerance limit.


Risk indicators of variceal bleeding.
Variceal bleeding is a catastrophic event in the history of liver cirrhotics. However, in more than half of the patients it never occurs. Thus, measures to prevent bleeding should be undertaken only in patients at the highest risk of bleeding. Risk indicators should help to select those patients. Hemodynamic and endoscopic parameters as well as liver function and coagulation status and the patient's history have been studied in relation to the bleeding incidence. The following parameters are correlated with an increased bleeding risk: The first year after diagnosis of varices, a positive history of variceal bleeding, presence of varices with large diameters, high blood pressures or a red colour sign, concomitant gastric varices or development of a liver cell carcinoma. Other parameters may be of less importance for the occurrence of variceal bleeding.


[Specific nasal challenge tests in the diagnosis of allergy].
The paper presents a review of current literature concerning the use and conduction of specific nasal challenge tests (SNCT). The authors call attention to the consensus of the German group of 1990 and report of the European Rhinologic Society (ERS) on nasal challenge tests of 2000. They present own experience and point to the unsolved questions: whether SNCT should be one- or two-sided with allergen on blotting paper or from a spray, and what methods of subjective and objective assessment should be applied. The authors call attention also to the unsolved problem of the influence of nasal cycle on the challenge test result. The paper includes the ERS instruction how to conduct nasal challenge test.


Influence of acetylsalicylic acid and low-molecular weight heparins on the formation of renal hematoma after shock wave lithotripsy.
To investigate the risk of renal hematoma (RHT) after shock wave lithotripsy (SWL) among patients on acetylsalicylic acid (ASA) or low-molecular-weight heparin (LMWH). Retrospective analysis of 434 patients treated with SWL for nephrolithiasis and ureterolithiasis of the proximal ureter. Primary endpoint was detection of RHT by ultrasound the day after SWL. Secondary outcome variables included transfusion of erythrocyte concentrate(s), interventions, hospital readmission or death due to RHT within 30 days of SWL. Binary logistic regression analysis was used including a post hoc one-way analysis. Of 434 patients, 33 (7.6%) and 67 (15.4%) patients were medicated with ASA and LMWH, respectively. RHT was detected in 20 of 434 (4.6%) patients. Of those, 3 (20%) were on ASA, 6 (35%) were on LMWH, 1 (5%) was on ASA and LMWH, and 10 (50%) had no anticoagulation. Univariate analysis showed a statistically significant higher risk for RHT among patients on ASA (p = 0.04) and LWMH (p = 0.02) with an untreated urinary tract infection (UTI) (p = 0.008) and history of cardiovascular disease (p = 0.028). On multivariate analysis, ASA medication, untreated UTI (OR 4.4, 95% CI 1.31-14.75, p = 0.016 and OR 5.79, 95% CI 1.65-20.32, p = 0.03) and a therapeutic dose of LMWH (OR 10.4, 95% CI 1.74-62.27, p = 0.01) were independent predictors for RHT. Before SWL, a patient risk profile should be evaluated. If feasible, LMWH in therapeutic dosing should be avoided, and ASA should be discontinued. UTI should be treated before SWL in any case. http://www.clinicaltrials.gov ; Identifier NCT02875717.


Empirical angle-dependent Biot and MBA models for acoustic anisotropy in cancellous bone.
The Biot and the modified Biot-Attenborough (MBA) models have been found useful to understand ultrasonic wave propagation in cancellous bone. However, neither of the models, as previously applied to cancellous bone, allows for the angular dependence of acoustic properties with direction. The present study aims to account for the acoustic anisotropy in cancellous bone, by introducing empirical angle-dependent input parameters, as defined for a highly oriented structure, into the Biot and the MBA models. The anisotropy of the angle-dependent Biot model is attributed to the variation in the elastic moduli of the skeletal frame with respect to the trabecular alignment. The angle-dependent MBA model employs a simple empirical way of using the parametric fit for the fast and the slow wave speeds. The angle-dependent models were used to predict both the fast and slow wave velocities as a function of propagation angle with respect to the trabecular alignment of cancellous bone. The predictions were compared with those of the Schoenberg model for anisotropy in cancellous bone and in vitro experimental measurements from the literature. The angle-dependent models successfully predicted the angular dependence of phase velocity of the fast wave with direction. The root-mean-square errors of the measured versus predicted fast wave velocities were 79.2 m s(-1) (angle-dependent Biot model) and 36.1 m s(-1) (angle-dependent MBA model). They also predicted the fact that the slow wave is nearly independent of propagation angle for angles about 50 degrees , but consistently underestimated the slow wave velocity with the root-mean-square errors of 187.2 m s(-1) (angle-dependent Biot model) and 240.8 m s(-1) (angle-dependent MBA model). The study indicates that the angle-dependent models reasonably replicate the acoustic anisotropy in cancellous bone.


Rules and mechanisms of punishment learning in honey bees: the aversive conditioning of the sting extension response.
Honeybees constitute established model organisms for the study of appetitive learning and memory. In recent years, the establishment of the technique of olfactory conditioning of the sting extension response (SER) has yielded new insights into the rules and mechanisms of aversive learning in insects. In olfactory SER conditioning, a harnessed bee learns to associate an olfactory stimulus as the conditioned stimulus with the noxious stimulation of an electric shock as the unconditioned stimulus. Here, we review the multiple aspects of honeybee aversive learning that have been uncovered using Pavlovian conditioning of the SER. From its behavioral principles and sensory variants to its cellular bases and implications for understanding social organization, we present the latest advancements in the study of punishment learning in bees and discuss its perspectives in order to define future research avenues and necessary improvements. The studies presented here underline the importance of studying honeybee learning not only from an appetitive but also from an aversive perspective, in order to uncover behavioral and cellular mechanisms of individual and social plasticity.