Surgical-handling properties of the titanium prosthesis in ossiculoplasty.
Despite the wide variety of ossiculoplasty techniques that are available, success rates are limited. Current use indicates that surgeons prefer ceramic, autograft bone, and plastic pore prostheses. During the past decade, titanium prostheses have been used with great promise. Although their use is not widespread, satisfaction rates are high. An earlier study of ossiculoplasty showed that titanium prostheses were effective in reducing conductive hearing loss. To date, the surgical-handling attributes of titanium middle ear prostheses have not been assessed. We report the results of our survey of 32 otologic surgeons who used the open Tübingen titanium prosthesis for primary and revision ossiculoplasty during tympanoplasty in 400 patients at 12 academic and nonacademic otolaryngology clinics, most of them in Germany. Because the audiometric efficacy of titanium prostheses has been previously reported, our primary outcomes measures included ease of use with respect to the amount of time required to prepare the implants for placement and the surgeons' overall impression of the intraoperative handling characteristics of the implants, taking into consideration factors such as positioning, length adjustment, visibility, and the stability of the coupling. Surgeons also compared the properties of the titanium implant with those of gold, ceramic, and autograft implants that they had used in the past. Based on the results of 383 of the 400 ossiculoplasties, our survey revealed that the titanium implant was significantly superior to the others in all measured respects.


Pharmacodynamics of RP 59500 (quinupristin-dalfopristin) administered by intermittent versus continuous infusion against Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model.
We evaluated the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against fibrin-platelet clots (FPC) infected with two clinical isolates of Staphylococcus aureus, one constitutively erythromycin and methicillin resistant (S. aureus AW7) and one erythromycin and methicillin susceptible (S. aureus 1199), in an in vitro pharmacodynamic infection model. RP 59500 was administered by continuous infusion (peak steady-state concentration of 6 microg/ml) or intermittent infusion (simulated regimens of 7.5 mg/kg of body weight every 6 h (q6h) q8h, and q12h. FPCs were infected with S. aureus to achieve an initial bacterial density of 10(9) CFU/g. Model experiments were run in duplicate over 72 h. Two FPCs were removed from each model at 0, 12, 24, 36, 48, and 72 h, and the bacterial densities (in CFU per gram) were determined and compared to those of growth control experiments. Additional samples were also removed from the model over the 72-h period for pharmacokinetic evaluation. All regimens significantly (P < or = 0.01) decreased bacterial densities in the infected FPCs for both isolates compared to growth controls. This occurred even though MBCs were equal to or greater than the RP 59500 concentrations achieved in the models. There were no significant differences found between the dosing frequencies and levels of killing when examining each isolate separately. However, examination of the residual bacterial densities (CFU per gram at 72 h) and visual inspection of the overall killing effect (killing curve plots over 72 h) clearly demonstrated a more favorable bactericidal activity against 1199 than against the AW7 isolate. This was most apparent when the q8h and the q12h AW7 regimens were compared to all 1199 treatment regimens by measuring the 72-h bacterial densities (P < or = 0.01). Killing (99.9%) was not achieved against the AW7 isolate. However, a 99.9% kill was demonstrated for all dosing regimens against the 1199 isolate. The area under the concentration-time curve from 0 to 24 h was found to be significantly correlated with reduction in bacterial density for the AW7 isolate (r = 0.74, P = 0.04). No resistance was detected during any experiment for either isolate. RP 59500 efficacy against constitutively erythromycin- and methicillin-resistant S. aureus may be improved by increasing organism exposure to RP 59500 as a function of dosing frequency.


[A prospective study of programmed nursing consultation in an urban health center].
A study of the programmed nurse clinic in a health center was carried out to evaluate its different health care activities, the time consumed in them, the type of patients cared for, and the mechanism of organization of the clinic. A remarkable finding was a high number of daily appointments (11.8 persons), with an excellent rate of compliance with the appointment (89.3%). It was found that most of the diseases cared for in the nurse clinic were those most commonly managed with a protocol design in primary care: hypertension (34.1%), diabetes (6.9%), hyperlipoproteinemia (9%) and obesity (12.8%). Other parameters were evaluated, such as mean time per visit, which was predominantly between five and ten minutes, or activities during the visits, with a clear predominance of the clinical protocols. There was a remarkably high efficiency of the nursing staff, with a low rate of referral to the medical clinic (6.9%). We conclude that nurse clinics play an important role in the health centers, as the only possible mechanism to guarantee the correct fulfillment of the different programs. This requires a definite constant physical space for a given minimal period of time of about 2 hours per day.


The effect of macromolecular structure on the rheology and surface properties of amphiphilic random polystyrene-r-poly(meth)acrylate copolymers prepared by RDRP.
In this work rheological and surface properties of various random copolymers of styrene and sodium (meth)acrylate, prepared using reversible deactivation radical polymerization (RDRP), were studied. It is shown that the properties of these polymers in water solution, relevant for several applications, are affected by their chemical structure and molecular weight. Cryo-TEM images of their concentrated water solutions do not show the presence of nano-objects as micelles, however the existence of some aggregates seems to be confirmed by fluorescence measurements using pyrene as a hydrophobic probe and by surface tension measurements. Moreover, interesting results are displayed about the viscosity as well as the surface tension of these water polymer solutions, due probably to different interactions at the molecular level as suggested by fluorescence measurements.


Roles of cysteine proteases Cwp84 and Cwp13 in biogenesis of the cell wall of Clostridium difficile.
Clostridium difficile expresses a number of cell wall proteins, including the abundant high-molecular-weight and low-molecular-weight S-layer proteins (SLPs). These proteins are generated by posttranslational cleavage of the precursor SlpA by the cysteine protease Cwp84. We compared the phenotypes of C. difficile strains containing insertional mutations in either cwp84 or its paralog cwp13 and complemented with plasmids expressing wild-type or mutant forms of their genes. We show that the presence of uncleaved SlpA in the cell wall of the cwp84 mutant results in aberrant retention of other cell wall proteins at the cell surface, as demonstrated by secretion of the proteins Cwp66 and Cwp2 into the growth medium. These phenotypes are restored by complementation with a plasmid expressing wild-type Cwp84 enzyme but not with one encoding a Cys116Ala substitution in the active site. The cwp13 mutant cleaved the SlpA precursor normally and had a wild-type-like colony phenotype. Both Cwp84 and Cwp13 are produced as proenzymes which are processed by cleavage to produce mature enzymes. In the case of Cwp84, this cleavage does not appear to be autocatalytic, whereas in Cwp13 autocatalysis was demonstrated as a Cys109Ala mutant did not undergo processing. Cwp13 appears to have a role in processing of Cwp84 but is not essential for Cwp84 activity. Cwp13 cleaves SlpA in the HMW SLP domain, which we suggest may reflect a role in cleavage and degradation of misfolded proteins at the cell surface.


An image encryption algorithm utilizing julia sets and hilbert curves.
Image encryption is an important and effective technique to protect image security. In this paper, a novel image encryption algorithm combining Julia sets and Hilbert curves is proposed. The algorithm utilizes Julia sets' parameters to generate a random sequence as the initial keys and gets the final encryption keys by scrambling the initial keys through the Hilbert curve. The final cipher image is obtained by modulo arithmetic and diffuse operation. In this method, it needs only a few parameters for the key generation, which greatly reduces the storage space. Moreover, because of the Julia sets' properties, such as infiniteness and chaotic characteristics, the keys have high sensitivity even to a tiny perturbation. The experimental results indicate that the algorithm has large key space, good statistical property, high sensitivity for the keys, and effective resistance to the chosen-plaintext attack.


Impella 5.0 therapy as a bridge-to-decision option for patients on extracorporeal life support with unclear neurological outcomes.
Peripheral venoarterial extracorporeal life support (ECLS) for the treatment of cardiogenic shock has shown to improve survival but is associated with complications. However, if the patient cannot be weaned from ECLS, their therapy options are limited. Although durable left ventricular assist device implantation might be an option in such cases, an unclear neurological outcome is often a contraindication. We hypothesize that Impella 5.0 therapy provides sufficient circulatory support while avoiding ECLS-related complications, thereby allowing for an adequate evaluation of a patient's neurological state and facilitating further treatment options. We retrospectively reviewed data from 22 ECLS patients (mean age 56.5 ± 10.7 years) with an unclear neurological status who underwent Impella 5.0 implantation between January 2016 and July 2018 in our institution. Neurological status was evaluated on a daily basis using the cerebral performance category score and the modified Rankin scale. Sixteen patients (72.7%) were resuscitated before ECLS implantation and 13 patients (59.1%) had acute myocardial infarction. The mean duration on ECLS before Impella 5.0 implantation was 9.3 ± 1.7 days. All patients were successfully weaned from ECLS by Impella 5.0 implantation via the axillary artery. The mean duration on Impella 5.0 was 16.3 ± 4.7 days. In surviving patients, both quantitative measurements of cerebral performance improved after 30 days compared to the baseline (P < 0.01). Six patients (27.3%) were bridged to a durable left ventricular assist device. In 9 patients (40.9%), myocardial function recovered during Impella 5.0 support and the device was successfully explanted. The 30-day survival rate was 68.2%. Impella 5.0 support provides a bridge-to-decision option for patients following ECLS implantation and leads to left ventricular unloading. It allows further evaluation of a patient's neurological situation and facilitates further therapy. About two-thirds of patients survived with acceptable neurological outcomes.


Effects of warming rate, acclimation temperature and ontogeny on the critical thermal maximum of temperate marine fish larvae.
Most of the thermal tolerance studies on fish have been performed on juveniles and adults, whereas limited information is available for larvae, a stage which may have a particularly narrow range in tolerable temperatures. Moreover, previous studies on thermal limits for marine and freshwater fish larvae (53 studies reviewed here) applied a wide range of methodologies (e.g. the static or dynamic method, different exposure times), making it challenging to compare across taxa. We measured the Critical Thermal Maximum (CTmax) of Atlantic herring (Clupea harengus) and European seabass (Dicentrarchus labrax) larvae using the dynamic method (ramping assay) and assessed the effect of warming rate (0.5 to 9°C h-1) and acclimation temperature. The larvae of herring had a lower CTmax (lowest and highest values among 222 individual larvae, 13.1-27.0°C) than seabass (lowest and highest values among 90 individual larvae, 24.2-34.3°C). At faster rates of warming, larval CTmax significantly increased in herring, whereas no effect was observed in seabass. Higher acclimation temperatures led to higher CTmax in herring larvae (2.7 ± 0.9°C increase) with increases more pronounced at lower warming rates. Pre-trials testing the effects of warming rate are recommended. Our results for these two temperate marine fishes suggest using a warming rate of 3-6°C h-1: CTmax is highest in trials of relatively short duration, as has been suggested for larger fish. Additionally, time-dependent thermal tolerance was observed in herring larvae, where a difference of up to 8°C was observed in the upper thermal limit between a 0.5- or 24-h exposure to temperatures >18°C. The present study constitutes a first step towards a standard protocol for measuring thermal tolerance in larval fish.


The Society of Thoracic Surgeons Composite Score for Evaluating Esophagectomy for Esophageal Cancer.
The Society of Thoracic Surgeons (STS) has developed composite quality measures for cardiac surgical procedures and lobectomy for lung cancer. This study sought to develop a composite measure for esophagectomy for esophageal cancer. The STS esophagectomy composite score is derived from two risk-adjusted outcomes: mortality and major complications. General Thoracic Surgery Database data were included from 2012 to 2014, and 95% Bayesian credible intervals were established to determine "star" ratings. STS participants were compared with the National Inpatient Sample as a national benchmark (including non-STS participants). The study population included 4,321 patients who underwent esophagectomy from 167 participating centers. The operative mortality rate was 3.1% (N = 135), and the major complication rate was 33.1% (N = 1,429). Of the 167 participants, 70 reported an average yearly volume of five or more esophagectomies during the study period. With this threshold, reliability for the composite score was 0.58 (95% credible interval, 0.41 to 0.72). Of these 70 participants, 5 (7.1%) were three star, 63 (90.0%) were two star, and 2 (2.9%) were one star. A majority of STS participants, 58.1% (N = 97), did not have sufficient volume to receive a reliable composite score. Benchmarked to the 2012 National Inpatient Sample cohort, STS General Thoracic Surgery Database participants have comparable discharge mortality rates and shorter postoperative lengths of stay. STS has developed a quality measure for esophageal cancer surgical procedures based on a composite score of risk-adjusted operative mortality rates and major complications. The composite rating for esophagectomy has good reliability for programs performing an average of five procedures annually, although almost 60% of participants are not eligible for a star rating because of lower procedure volumes.


Development and validation of limited sampling strategies for tacrolimus and mycophenolate in steroid-free renal transplant regimens.
1) To develop and validate limited sampling strategies (LSSs) for tacrolimus (TAC) and mycophenolic acid (MPA) in renal transplant recipients not receiving corticosteroids; and 2) to evaluate predictive performance of published LSSs (for steroid-based regimens) in a steroid-free population. On administration of steady-state morning TAC and mycophenolate mofetil doses, 12-hour serial blood samples from 28 stable renal transplant recipients were collected and measured by validated high-performance liquid chromatography methods and area under the curve (AUC) by trapezoidal rule. TAC LSSs were developed and validated by multiple regression analysis by a two-group method (index n = 18; validation n = 10) and MPA LSSs by the jackknife method (n = 28). Potential LSSs were those with r ≥ .8 (TAC) or r ≥ 0.7 (MPA) and < 3 time points within 2 hours (TAC) or 4 hours (MPA) postdose. Predictive performance was calculated and other published TAC and MPA LSSs tested using preset criteria for bias and precision of within ± 15%. For TAC, three three-concentration, one two-concentration, and one one-concentration model met preset criteria. The best equations were: TAC AUC = 10.338 + 7.739C0 + 3.589C2 (r = 0.956, bias = -3.4%, precision = 4.7%) and TAC AUC = 29.479 + 5.016C2 (r = 0.862, bias = 3.2%, precision = 9.7%). For MPA, only one model was identified: MPA AUC = 9.328 + 1.311C1 + 1.455C2 + 2.901C4 (r = 0.838, bias = -3.8%, precision = 14.9%). One published TAC (and no MPA) LSS in renal transplant recipients on steroid-based regimens met criteria. To the authors' knowledge, these LSSs are the first to be developed and validated in steroid-free renal transplant recipients and can be used to accurately predict TAC and MPA AUCs for steroid-free regimens. Because the commonly used MPA LSS is based on a steroid regimen and not predictive for steroid-free patients, the newly derived MPA LSS is being applied at the authors' institution. Other renal transplant centers may also wish to validate this equation in their own patients.


Tractography for arteriovenous malformations near the sensorimotor cortices.
We sought to use diffusion-tensor imaging-based tractography to assess the relationship between the arteriovenous malformations (AVM) and the sensorimotor cortices/tracts. Three patients who had an AVM closely situated to the sensorimotor tracts were studied. The relationship between the sensorimotor tracts and the AVM was well demonstrated in all patients. Tractography was also helpful in identifying the location of the motor cortex in some of the cases.


Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.
Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%).


Human balancing of an inverted pendulum: position control by small, ballistic-like, throw and catch movements.
In standing, there are small sways of the body. Our interest is to use an artificial task to illuminate the mechanisms underlying the sways and to account for changes in their size. Using the ankle musculature, subjects balanced a large inverted pendulum. The equilibrium of the pendulum is unstable and quasi-regular sway was observed like that in quiet standing. By giving full attention to minimising sway subjects could systematically reduce pendulum movement. The pendulum position, the torque generated at each ankle and the soleus and tibialis anterior EMGs were recorded. Explanations about how the human inverted pendulum is balanced usually ignore the fact that balance is maintained over a range of angles and not just at one angle. Any resting equilibrium position of the pendulum is unstable and in practice temporary; movement to a different resting equilibrium position can only be accomplished by a biphasic 'throw and catch' pattern of torque and not by an elastic mechanism. Results showed that balance was achieved by the constant repetition of a neurally generated ballistic-like biphasic pattern of torque which can control both position and sway size. A decomposition technique revealed that there was a substantial contribution to changes in torque from intrinsic mechanical ankle stiffness; however, by itself this was insufficient to maintain balance or to control position. Minimisation of sway size was caused by improvement in the accuracy of the anticipatory torque impulses. We hypothesise that examination of centre of mass and centre of pressure data for quiet standing will duplicate these results.


Transient solidlike behavior near the cylinder/disorder transition in block copolymer solutions.
A nearly symmetric polystyrene-block-polyisoprene diblock copolymer dissolved at a concentration of 40% in styrene-selective solvents exhibited a cylinder-to-disorder transition upon heating. The solvents used were diethyl phthalate (DEP) and 75:25 and 50:50 mixtures of DEP with di-n-butyl phthalate (DBP). In DEP, the most styrene-selective of the three solvents, rheological measurements indicated a distinct plateau in the temperature-dependent elastic modulus across the 8 degrees C interval above the order-disorder transition temperature, T(ODT) = 116 degrees C. Previous small-angle neutron scattering measurements in this regime indicated the equilibrium phase to be a liquidlike solution of approximately spherical micelles. An isothermal frequency sweep in this regime indicated a very long relaxation time. Annealing eventually led to the recovery of liquidlike rheological response, over a time scale of hours. Qualitatively similar phenomena were also observed in 75:25 DEP/DBP and 50:50 DEP/DBP solutions, except the fact that the temperature window of the transient response is narrow and the time scale for the recovery diminishes significantly. Neither small-angle X-ray scattering nor static birefringence gave any clear signature of the transient structure. The structure that leads to the transient rheological response is attributed to micellar congestion due to the slow relaxation of anisotropic micelles into an equilibrium distribution of micelles. Possible origins of the remarkable solvent selectivity dependence are also discussed.


In vitro phenotypic evidence for the utilization of iron from different sources and siderophores production in the fish pathogen Tenacibaculum dicentrarchi.
Iron uptake during infection is an essential pathogenicity factor of several bacteria, including Tenacibaculum dicentrarchi, an emerging pathogen for salmonid and red conger eel (Genypterus chilensis) farms in Chile. Iron-related protein families were recently found in eight T. dicentrarchi genomes, but biological studies have not yet confirmed functions. The investigation reported herein clearly demonstrated for the first time that T. dicentrarchi possesses different systems for iron acquisition-one involving the synthesis of siderophores and another allowing for the utilization of heme groups. Using 38 isolates of T. dicentrarchi and the type strain CECT 7612T , all strains grew in the presence of the chelating agent 2.2'-dipyridyl (from 50 to 150 μM) and produced siderophores on chrome azurol S plates. Furthermore, 37 of the 38 T. dicentrarchi isolates used at least four of the five iron sources (i.e. ammonium iron citrate, ferrous sulfate, iron chloride hexahydrate, haemoglobin and/or hemin) when added to iron-deficient media, although the cell yield was less when using hemin. Twelve isolates grew in the presence of hemin, and 10 of them used only 100 μM. Under iron-supplemented or iron-restricted conditions, whole cells of three isolates and the type strain showed at least one membrane protein induced in iron-limiting conditions (c.a. 37.9 kDa), regardless of the isolation host. All phenotypic results were confirmed by in-silico genomic T. dicentrarchi analysis. Future studies will aim to establish a relationship between iron uptake ability and virulence in T. dicentrarchi through in vivo assays.


11β-HSD1 Modulates the Set Point of Brown Adipose Tissue Response to Glucocorticoids in Male Mice.
Glucocorticoids (GCs) are potent regulators of energy metabolism. Chronic GC exposure suppresses brown adipose tissue (BAT) thermogenic capacity in mice, with evidence for a similar effect in humans. Intracellular GC levels are regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, which can amplify circulating GC concentrations. Therefore, 11β-HSD1 could modulate the impact of GCs on BAT function. This study investigated how 11β-HSD1 regulates the molecular architecture of BAT in the context of GC excess and aging. Circulating GC excess was induced in 11β-HSD1 knockout (KO) and wild-type mice by supplementing drinking water with 100 μg/mL corticosterone, and the effects on molecular markers of BAT function and mitochondrial activity were assessed. Brown adipocyte primary cultures were used to examine cell autonomous consequences of 11β-HSD1 deficiency. Molecular markers of BAT function were also examined in aged 11β-HSD1 KO mice to model lifetime GC exposure. BAT 11β-HSD1 expression and activity were elevated in response to GC excess and with aging. 11β-HSD1 KO BAT resisted the suppression of uncoupling protein 1 (UCP1) and mitochondrial respiratory chain subunit proteins normally imposed by GC excess. Furthermore, brown adipocytes from 11β-HSD1 KO mice had elevated basal mitochondrial function and were able to resist GC-mediated repression of activity. BAT from aged 11β-HSD1 KO mice showed elevated UCP1 protein and mitochondrial content, and a favorable profile of BAT function. These data reveal a novel mechanism in which increased 11β-HSD1 expression, in the context of GC excess and aging, impairs the molecular and metabolic function of BAT.


Ethnic variations in the pharmacological and nonpharmacological treatment of hypertension: biopsychosocial perspective.
Blood pressure regulation is a complex, dynamic process influenced by psychosocial, behavioral, and cultural factors. Integrative theories of cross-population differences in the prevalence of hypertension and response to treatment include physiological, social, and genetic perspectives. Ethnic differences in salt sensitivity, calcium regulation of sodium flux, vascular reactivity to psychosocial stress, and drug metabolism are integral components of observed cross-cultural variations in hypertension. In general, pharmacological treatment of hypertension in blacks is most consistently achieved through diuretics and calcium-channel blockers; angiotensin-converting enzyme inhibitors and beta-blockers are more efficacious in whites. These stereotypical patterns are consistent with the higher prevalence of salt sensitivity, stress-induced vasoconstriction and slower natriuresis, and alpha-adrenergic receptor mediated vascular reactivity observed in blacks compared with whites. Some antihypertensive agents produce adverse glucose metabolic side effects, thus contraindicating their use in individuals with high sympathetic tone, insulin resistance, or obesity. Cross-population differences in adopted guidelines for treating hypertension exist but are not likely a factor in observed ethnic differences in rate of treatment or control. Attitudes toward nontraditional treatment options (e.g., herbal medicine), political and individual responsibilities in health care, and adaptations to acculturation and urbanization stress differ between and within societies and thus play a role in observed cross-cultural differences in hypertension as well. The value of regular exercise in controlling hypertension is widely recognized, and reductions in blood pressure reactivity to behavioral stress following acute exercise have been documented; however, empirical studies of ethnic differences in exercise-related blood pressure control are lacking. Overall, increased awareness of the multifactorial nature of hypertension by both the physician and the patient will facilitate treatment of this disease on an individual basis.


Age-dependent terminal declines in reproductive output in a wild bird.
In many iteroparous species individual fitness components, such as reproductive output, first increase with age and then decline during late-life. However, individuals differ greatly in reproductive lifespan, but reproductive declines may only occur in the period just before their death as a result of an age-independent decline in physiological condition. To fully understand reproductive senescence it is important to investigate to what extent declines in late-life reproduction can be explained by age, time until death, or both. However, the study of late-life fitness performance in natural populations is challenging as the exact birth and death dates of individuals are often not known, and most individuals succumb to extrinsic mortality before reaching old age. Here, we used an exceptional long-term longitudinal dataset of individuals from a natural, closed, and predator-free population of the Seychelles warbler (Acrocephalus sechellensis) to investigate reproductive output, both in relation to age and to the time until the death of an individual (reverse-age approach). We observed an initial age-dependent increase in reproductive output that was followed by a decline in old age. However, we found no significant decline in reproductive output in the years directly preceding death. Although post-peak reproductive output declined with age, this pattern differed between terminal and non-terminal reproductive attempts, and the age-dependence of the terminal breeding attempt explained much of the variation in age-specific reproductive output. In fact, terminal declines in reproductive output were steeper in very old individuals. These results indicate that not only age-dependent, but also age-independent factors, such as physiological condition, need to be considered to understand reproductive senescence in wild-living animals.


Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence.
CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc322-331, a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38-parameter CyTOF phenotyping on tetramer-identified Nuc322-331-specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS-CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. We discovered a coordination of the Nuc322-331-specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc322-331-specific CD8+ T cells were predominantly central memory T cells, but continually evolved over a ~6-month period of convalescence. We observed a slow and progressive decrease in the activation state and polyfunctionality of the Nuc322-331-specific CD8+ T cells, accompanied by an increase in their lymph-node homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8+ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence, into a state characteristic of long-lived, self-renewing memory.


Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues.
BACKGROUND; Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view of the limitations of prenatal diagnosis and preimplantation genetic diagnoses, alternatives such as ooplasmic transfer (OT) and nuclear transfer (NT) have been proposed to prevent the transmission of mtDNA mutations. Both OT and NT are radical in the sense that they do not entail genetic selection, but genetic intervention to correct the genetic cause of the disease. After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points. OT is the transfer of normal mitochondria to a carrier's oocyte containing mutant mtDNA. In case of NT, a donated oocyte is enucleated and replaced with the nuclear DNA from a woman carrying a mtDNA mutation. NT can be performed both before and after in vitro fertilization, respectively, with the nucleus of an unfertilized oocyte, with the pronuclei of the zygote, or with the nucleus of a blastomere of an embryo. Conceptual questions regard whether these techniques amount to germ-line modification and human cloning. Normative questions concern, among others, the significance of intervening in the mtDNA, the implications of having 'three genetic parents', the ethics of oocyte donation and the health and safety risks for children conceived as a result of one of these techniques. Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.


Review of drug utilization patterns in NICUs worldwide.
When considering acute care settings, such as the neonatal intensive care unit (NICU), the inappropriate use of medicines poses a great risk to vulnerable babies at the start of their lives. However, there is limited published literature that explores the current medication management practices in NICUs and where the main misuse issues lie. Therefore, the purpose of this review was to give an overview of medicine use in NICUs worldwide and identify therapeutic areas requiring more targeted pharmaceutical care. Specific objectives include the following: identifying the most commonly used medicines, comparing these to the A-PINCH (Anti-infectives, Potassium and other electrolytes, Insulin, Narcotics and sedatives, Chemotherapy agents, Heparin and other anticoagulants), high-risk medicines list, and determining whether there are any differences in medicine use between countries. Quasi-systematic literature review. Google Scholar, MEDLINE/PubMed, Scopus and EMBASE were searched utilizing selected MeSH terms. A total of 19 articles from 12 countries were reviewed. Medication use between countries was very similar with no discernible differences in types of medicines prescribed. The most commonly used medicines included gentamicin, ampicillin, caffeine, furosemide and vitamin K. The median number of medicines prescribed per patient ranged from 3 to 11, and an inverse relationship was identified between gestational age and the number of medications that were prescribed. Nine of the 20 most commonly used medicines were listed as A-PINCH medicines, and included antibiotics, fentanyl, morphine and heparin. Inappropriate prescribing, as well as the high use of off-label/unlicensed medicines, was highlighted as areas of practice that require consideration to improve medication safety and minimize the potential risk for medication errors. Overall, the types of medicines used in NICUs worldwide are similar, with consistent reports on the common use of antibiotics, caffeine and vitamins. However, it cannot be definitively stated that the findings of the review accurately depict current practice in NICUs, due to the limited amount of published literature available. There are several areas of concern that warrant further investigation to improve rational use of medicines in the neonatal populations, including high use of antibiotics and off-label and unlicensed medicines.


Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects in Neurospora.
The replication and segregation of multi-copy mitochondrial DNA (mtDNA) are not under strict control of the nuclear DNA. Within-cell selection may thus favour variants with an intracellular selective advantage but a detrimental effect on cell fitness. High relatedness among the mtDNA variants of an individual is predicted to disfavour such deleterious selfish genetic elements, but experimental evidence for this hypothesis is scarce. We studied the effect of mtDNA relatedness on the opportunities for suppressive mtDNA variants in the fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO. During growth, this plasmid integrates into the mitochondrial genome, generating suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type mtDNA, ultimately culminating in growth arrest and death. We show that regular sequestration of mtDNA variation is required for effective selection against suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from which a 'Kalilo' culture started significantly increased the maximum lifespan and variation in lifespan among cultures. Second, restrictions to somatic fusion among fungal individuals, either by using anastomosis-deficient mutants or by generating allotype diversity, prevented the accumulation of suppressive mtDNA variants. We discuss the implications of these results for the somatic accumulation of mitochondrial defects during ageing.


Addition of EEG improves accuracy of a logistic model that uses neuropsychological and cardiovascular factors to identify dementia and MCI.
To investigate whether addition of EEG would improve accuracy of a logistic model that uses neuropsychological assessment and cardiovascular history to identify dementia and mild cognitive impairment (MCI) as a single group, we collected data and constructed logistic models from a sample of 78 normal adults and 33 patients (aged 50-85 years). To determine accuracy, we compared logistic regression results to a geriatrician's diagnosis of MCI or dementia that included Alzheimer's disease, vascular dementia or mixed dementia. We found that the addition of EEG (non-linear complexity) to a logistic model that included both neuropsychological assessment (ADAS-Cog) and cardiovascular history increased overall accuracy from 80% to 92%. The logistic model identified dementia and MCI as a single group comprised of the following subgroups (with accuracies): Alzheimer's disease (92%; 12/13), vascular dementia (73%; 8/11), mixed dementia (100%; 4/4), and mild cognitive impairment (80%; 4/5). Whereas the analysis is limited by small sample sizes and mixing of diverse pathologies, the findings do provide support that the subgroups may share changes in neuropsychological, cardiovascular, and electroencephalographic factors (specifically ADAS-Cog total score, cardiovascular history, and EEG complexity). Taken together, the study results provide support that EEG might complement the clinician's evaluation of dementia and MCI.


Prediction of the human membrane proteome.
Membrane proteins are key molecules in the cell, and are important targets for pharmaceutical drugs. Few three-dimensional structures of membrane proteins have been obtained, which makes computational prediction of membrane proteins crucial for studies of these key molecules. Here, seven membrane protein topology prediction methods based on different underlying algorithms, such as hidden Markov models, neural networks and support vector machines, have been used for analysis of the protein sequences from the 21,416 annotated genes in the human genome. The number of genes coding for a protein with predicted alpha-helical transmembrane region(s) ranged from 5508 to 7651, depending on the method used. Based on a majority decision method, we estimate 5539 human genes to code for membrane proteins, corresponding to approximately 26% of the human protein-coding genes. The largest fraction of these proteins has only one predicted transmembrane region, but there are also many proteins with seven predicted transmembrane regions, including the G-protein coupled receptors. A visualization tool displaying the topologies suggested by the eight prediction methods, for all predicted membrane proteins, is available on the public Human Protein Atlas portal (www.proteinatlas.org).


Insulin analogues: action profiles beyond glycaemic control.
A variety of studies have documented significant improvements in the treatment of type 1 and 2 diabetes after the introduction of artificial insulins. This review gives an overview of insulin analogues which are currently approved for therapeutical use. Clinical data regarding the efficiency to control blood glucose level as well as improving HbA1c level in comparison to conventional insulin preparations in type 1 and 2 diabetic patients are summarized. Furthermore, special features of insulin analogues regarding their signalling properties are discussed with focus on the proliferative effects of insulin glargine as well as some recent data of insulin detemir.


Dialysis and renal transplantation in HIV-infected patients: a European survey.
To determine prevalence and characteristics of end-stage renal diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV-infected patients. Cross-sectional multicenter survey of EuroSIDA clinics during 2008. Prevalence of ESRD was 0.5%. Of 122 patients with ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73% were males and 43% were black. Median duration of HIV infection was 11 years. Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88% had undetectable viral load. Median CD4(+)T-cell count was 341 cells per cubic millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis (93%) was the most common dialysis modality; 34% of patients were on the RT waiting list. A poor HIV control was the reason for exclusion from RT waiting list in 22.4% of cases. All the RT recipients were all alive at the time of the survey. Acute rejection was reported in 8 patients (30%). Functioning graft was present in 21 (80%). This is the first multinational cross-sectional study of ESRD among European HIV population. Low prevalence of ESRD was found. Two-thirds of patients were excluded from RT for non-HIV/AIDS-related pathologies. Most patients had a functioning graft despite a high acute rejection rate.


Symmetry matters.
985 I. 985 II. 986 III. 987 IV. 988 V. 989 989 References 989 SUMMARY: The development of multicellular organisms depends on correct establishment of symmetry both at the whole-body scale and within individual tissues and organs. Setting up planes of symmetry must rely on communication between cells that are located at a distance from each other within the organism, presumably via mobile morphogenic signals. Although symmetry in nature has fascinated scientists for centuries, it is only now that molecular data to unravel mechanisms of symmetry establishment are beginning to emerge. As an example we describe the genetic and hormonal interactions leading to an unusual bilateral-to-radial symmetry transition of an organ in order to promote reproduction.


Feeding-entrained circadian rhythms in hypophysectomized rats with suprachiasmatic nucleus lesions.
Several pituitary hormones are important in the regulation of metabolism, and their release appears to be controlled by a circadian clock. Consequently, they may be involved in feeding-entrained circadian rhythms. Hypophysectomized (Hypox) and sham-operated male Sprague-Dawley rats had access to food for 4 h each day. Food-anticipatory activity (FAA) and core body temperature (T(b)) were monitored. Both groups entrained to the daily meal with an increase in activity in the 4 h preceding meal access and quickly reentrained after an 8-h phase advance of food access. FAA was not disrupted in either group after suprachiasmatic lesions were added. Core T(b) increased in the sham-operated subjects before mealtime, but Hypox rats failed to show this effect. Rather, T(b) declined during anticipation and throughout the food access period. Respiratory quotient (RQ), an indirect measure of metabolic rate, was measured for 24 h in some subjects. Sham-operated rats showed a dramatic downturn in RQ 1 h before mealtime, whereas Hypox rats showed a steadily decreasing RQ throughout the day. The results show that the pituitary hormones are not necessary for FAA and that in Hypox rats the anticipatory rise in T(b) and changes in RQ become dissociated from anticipatory behavior, indicating that these functions are separate outputs of the food-entrainable circadian oscillator.


Role of selective sentinel lymph node dissection in head and neck melanoma.
Selective sentinel lymph node dissection (SLND) plays an important role in the staging of the regional nodal basins for head and neck (H&N) melanoma. Preoperative lymphoscintigraphy is mandatory to identify the regional nodal basin(s) accurately for a newly diagnosed H&N primary melanoma of at least 1mm or greater. A wide local excision should be delayed if SLN mapping is indicated, to minimize watershed effect and maximize accuracy in identifying the "true" SLN because of the complex lymphatic network in the H&N region. An experienced multidisciplinary team is required for optimal identification of H&N SLNs. In general, selective SLND can replace ELND to minimize the complications of a neck dissection. Completion lymph node dissection is only indicated when the SLN is positive. A nerve stimulator should be used during selective SLND in the parotid and posterior triangle to minimize the injury to the facial and spinal accessory nerve.


Physical therapy interventions for patients with osteoarthritis of the knee: an overview of systematic reviews.
Patients with osteoarthritis of the knee are commonly treated by physical therapists. Practice should be informed by updated evidence from systematic reviews. The purpose of this article is to summarize the evidence from systematic reviews on the effectiveness of physical therapy for patients with knee osteoarthritis. Systematic reviews published between 2000 and 2007 were identified by a comprehensive literature search. We graded the quality of evidence across reviews for each comparison and outcome. Twenty-three systematic reviews on physical therapy interventions for patients with knee osteoarthritis were included. There is high-quality evidence that exercise and weight reduction reduce pain and improve physical function in patients with osteoarthritis of the knee. There is moderate-quality evidence that acupuncture, transcutaneous electrical nerve stimulation, and low-level laser therapy reduce pain and that psychoeducational interventions improve psychological outcomes. For other interventions and outcomes, the quality of evidence is low or there is no evidence from systematic reviews.


Free Fatty Acid Receptors (FFARs): Emerging Therapeutic Targets for the Management of Diabetes Mellitus.
Free fatty acids (FFAs) present in our dietary fats not only act as vital nutrients but also function as signalling molecules and modulate key biological functions through their active involvement in a multitude of energy metabolism pathways. However, it has been reported that excessive intake of dietary fat contributes to the development of different types of Diabetes mellitus. Free fatty acid receptors are the key regulators of most metabolic disorders. Among them, diabetes mellitus is a severe growing disorder and found in every corner of the world. For various metabolic disorders, particularly type 2 diabetes mellitus, these different free fatty acid receptors are being explored as drug targets. In the present review, various FFAs sensing G-protein coupled receptors (GPR) like GPR40 (FFAR1), GPR43 (FFAR2), GPR41 (FFAR3), GPR120 (FFAR4), and GPR84 are being explored as emerging novel therapeutic targets for antidiabetic drugs. Additionally, this review has covered pre-clinical discovery and development of different selective ligands targeted to these receptors starting from hit identification to lead optimization via chemical modification and the challenges and tactics selected by different medicinal chemists to improve potency, physicochemical properties, safety profiles, and pharmacokinetics of different FFAR agonists for making a potential drug candidate. Several molecules have been withdrawn in the clinical trials without reporting any reasons. We believe that this review will help the researchers to find a new direction in the discovery of new antidiabetic drugs.


Functional analysis of autocrine and paracrine signalling at the uterine-conceptus interface in pigs.
The complexity of implantation necessitates intimate dialogue between conceptus and maternal cells, and precise coordination of maternal and conceptus signalling events. Maternal and conceptus-derived steroid hormones, growth factors and cytokines, as well as integrins and their ligands, have important and inter-related roles in mediating adhesion between apical aspects of conceptus trophectoderm and maternal uterine luminal epithelium that leads to formation of an epitheliochorial placenta. Integrin receptors appear to play fundamental roles in the implantation cascade and may interact with extracellular matrix molecules and other ligands to transduce cellular signals through autocrine and paracrine mechanisms. Functional in vitro analyses can be used to monitor individual contributions of specific integrin receptors and ligands to the signalling cascades of the maternal-conceptus interface. Integrative studies of implantation in pigs, using in vivo and in vitro approaches, are required to understand conceptus attachment and implantation in this species, and provide valuable opportunities to understand the fundamental mechanisms of implantation in all species.


Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog.
Reuptake of norepinephrine by cardiac sympathetic nerves before and during two levels of electrical stimulation of the left ansa subclavia was estimated in anesthetized dogs from the cardiac production of dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of norepinephrine. The method depended on the effects of neuronal uptake blockade with desipramine on the cardiac production of [3H]DHPG from intravenously infused [3H]norepinephrine. The ratio of the desipramine-induced decrease in the cardiac extraction of [3H]norepinephrine to the production of [3H]DHPG was used to transform the cardiac production of DHPG from recaptured norepinephrine into a rate for norepinephrine reuptake. Cardiac spillover of norepinephrine into plasma increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min during sympathetic activation. Cardiac DHPG production increased from 108 +/- 18 to 166 +/- 34 and 240 +/- 47 pmol/min. Desipramine decreased resting cardiac DHPG production by 20% and completely blocked the stimulation-induced increase. Thus, most (80%) cardiac DHPG produced at rest was derived from norepinephrine leaking from storage vesicles. This amount remained constant, and that derived from recaptured norepinephrine increased during sympathetic activation. The cardiac extraction of [3H]norepinephrine (126,000 dpm/min) and production of [3H]DHPG (3,790 dpm/min) were decreased by 55-57% after desipramine. Thus, only 3% of the norepinephrine recaptured by cardiac sympathetic nerves appeared in plasma as DHPG. The remainder was sequestered into storage vesicles (more than 94%) or ultimately formed metabolites other than DHPG (less than 3%). Reuptake of norepinephrine by cardiac sympathetic nerves was 1,188 +/- 476 pmol/min and increased in parallel with cardiac norepinephrine spillover to 4,182 +/- 1,982 and 6,594 +/- 2,241 pmol/min during sympathetic stimulation. Of the norepinephrine released by cardiac sympathetic nerves, 16-fold more was recaptured than entered plasma. Combined estimation of norepinephrine reuptake and spillover offers an approach to assess the efficiency of neuronal reuptake in disorders of cardiac function.


Rabbit antithymocyte globulin induction and sirolimus monotherapy supports prolonged islet allograft function in a nonhuman primate islet transplantation model.
We reported that rabbit anti-thymocyte globulin (RATG) induction followed by maintenance immunosuppression with sirolimus supports human kidney allograft survival and asked if this combination would promote islet allograft survival in our primate model. Using intra-arterial streptozotocin infusion, we rendered four cynomolgus primates diabetic with undetectable C-peptide levels. Animals were maintained on insulin therapy for at least 1 month, and then islets from mixed lymphocyte reaction mismatched primates were infused into the portal vein. Immediately before the islet allotransplant and for 6 additional days, primates were infused with RATG (20 mg/kg) and given a sirolimus dose to achieve a 24-hr trough level of 8 to 14 ng/mL. The regimen resulted in profound peripheral and lymph node lymphocyte depletion for up to 1 month. Repopulation was gradual thereafter. One primate remained insulin-independent for 169 days and rejected after a sirolimus-dose reduction. Two primates died on day 23 while insulin independent because of wound dehiscence, and a third died on day 30 with high sirolimus levels. Liver sections revealed well-vascularized islets with no signs of inflammation. Using a nonhuman primate islet transplant model, RATG plus sirolimus supports islet survival as long as proper sirolimus levels are maintained, but the therapy is limited by sirolimus toxicity. Our findings suggest that RATG is not toxic for islets and thus may be considered in future clinical trails while recognizing that sirolimus monotherapy, with its difficult-to-achieve therapeutic dosing, may not be sufficient to maintain long-term islet allograft function in an autoimmune environment.


Structure of acid-stable carmine.
Acid-stable carmine has recently been distributed in the U.S. market because of its good acid stability, but it is not permitted in Japan. We analyzed and determined the structure of the major pigment in acid-stable carmine, in order to establish an analytical method for it. Carminic acid was transformed into a different type of pigment, named acid-stable carmine, through amination when heated in ammonia solution. The features of the structure were clarified using a model compound, purpurin, in which the orientation of hydroxyl groups on the A ring of the anthraquinone skeleton is the same as that of carminic acid. By spectroscopic means and the synthesis of acid-stable carmine and purpurin derivatives, the structure of the major pigment in acid-stable carmine was established as 4-aminocarminic acid, a novel compound.


Nucleotide sequence of the transcriptional initiation region of the yeast GAL7 gene.
The GAL7 gene of Saccharomyces cerevisiae encodes Gal-1-P uridylyl transferase, the second enzyme of Leloir pathway for the galactose catabolism. We have determined the sequence of 1003 base pairs surrounding and upstream of the transcriptional initiation site of the GAL7 gene. The region sequenced also encompasses the 3' end of GAL10 gene. The 5' end of GAL7 mRNA was determined on the DNA sequence by the S1 nuclease- and exonuclease VII mapping, which is located 21 to 22 base pairs upstream from the translation initiating ATG codon. The primary structure of the GAL7 5' flanking region has many features common to those of multicellular eukaryotic genes. The 3' end of GAL10 mRNA was also determined by the mapping technique with the single-strand specific nucleases to be about 600 base pairs upstream from the 5' end of GAL7 mRNA.


Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia: Real-World Data from the Gemelli Hospital HHT Registry.
Although Hereditary Hemorrhagic Telangiectasia (HHT) is characterized by an overwhelming bleeding propensity, patients with this disease may also present medical conditions that require antithrombotic therapy (AT). However, precise information on indications, dosage, duration, effectiveness, and safety of AT in HHT patients is lacking. We performed a retrospective analysis of the HHT Registry of our University Hospital and found 26 patients who received AT for a total of 30 courses (19 courses of anticoagulant therapy and 11 courses of antiplatelet therapy). Indications to treatments included: atrial fibrillation, venous thrombosis and pulmonary embolism, heart valve replacement, retinal artery occlusion, secondary prevention after either stroke or myocardial infarction, and thromboprophylaxis for surgery. The total time of exposure to antiplatelet therapy was 385 months and to anticoagulant therapy 169 months. AT was generally well tolerated, with no fatal bleedings and no significant changes in hemoglobin levels. However, we found three major bleedings, with an incidence rate of 6.5 per 100 patients per year. When only patients treated with anticoagulants were considered, the incidence rate of major bleedings increased to 21.6 per 100 patients per year. Our study indicates that major bleeding may occur in HHT patients receiving AT, with a substantially increased rate in those treated with anticoagulants. Further studies are needed to fully estimate the tolerability of antithrombotic drugs in HHT.


Endofungal bacteria and ectomycorrhizal fungi synergistically promote the absorption of organic phosphorus in Pinus massoniana.
Ectomycorrhizal fungi (ECMFs) that are involved in phosphorus mobilisation and turnover have limited ability to mineralise phytate alone. The endofungal bacteria in the ectomycorrhizal fruiting body may contribute to achieving this ecological function of ECMFs. We investigated the synergistic effect and mechanisms of endofungal bacteria and ECMF Suillus grevillea on phytate mineralisation. The results showed that soluble phosphorus content in the combined system of endofungal bacterium Cedecea lapagei and S. grevillea was 1.8 times higher than the sum of C. lapagei and S. grevillea alone treatment under the phytate mineralisation experiment. The S. grevillea could first chemotactically assist C. lapagei in adhering to the surface of S. grevillea. Then, the mineralisation of phytate was synergistically promoted by increasing the biomass of C. lapagei and the phosphatase and phytase activities of S. grevillea. The expression of genes related to chemotaxis, colonisation, and proliferation of C. lapagei and genes related to phosphatase and phytase activity of S. grevillea was also significantly upregulated. Furthermore, in the pot experiment, we verified that there might exist a ternary symbiotic system in the natural forest in which endofungal bacteria and ECMFs could synergistically promote phytate uptake in the plant Pinus massoniana via the ectomycorrhizal system.


The work of forgetting: germs, aborigines and postcolonial expertise in the Northern Territory of Australia.
Based on anthropological field research (1997-2000) within the Department of Health and Community Services in the Northern Territory in Australia, this paper explores the lingering features of colonial logic in the pastoral work of public health workers in the Northern Territory of Australia. The public health professionals drawn to work in this space are determined to remedy what is wrong with culturally acceptable solutions. But viewed from an anthropological perspective, the way in which health professionals conceptualise the problems they need to solve ultimately serves to reinforce the reality of the need for their continued tutelary presence. This paper aims to draw out the complex ways in which this interventionary effect is secured, concentrating in particular on the role played by progressive ideologies of participatory development and information sharing. It argues that through a complex process of forgetting, the otherwise innocuous gestures of public health goodwill recreate a mandate for more public health intervention. This is not a simple moral tale where analysts can easily identify good and bad practices and thus distance themselves from the difficulties involved. Rather, by emphasising the honest commitments to improvement in situations of mass illness and preventable disease that health professionals bring to their work, and the burden they bear in being conscious of the recent colonial past, the paper aims to avoid the judgement that this sort of work is easy to get right.


Relevance of IgVH gene somatic hypermutation and interphase cytogenetics in lymphomatous presentation of chronic lymphocytic leukemia/small lymphocytic lymphoma.
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are regarded as the same entity, with SLL restricted to tissue cases featuring no leukemic phase. In this study, the authors evaluate a group of SLL cases for cytogenetic abnormalities and IgVH gene mutational status to illicit differences between CLL and SLL. IgVH gene polymerase chain reaction amplification and subsequent sequencing were preformed on formalin-fixed, paraffin-embedded archival tissue of 44 patients (SLL n = 34 or CLL n = 10). Cytogenetic data, CD38, and ZAP-70 expression were also evaluated for these cases. The data indicate that 9/34 (26%) SLL cases have somatic hypermutation >2%, which is less than the CLL group where 40% were mutated (4/10). Cytogenetic abnormalities were seen in 58% of the SLL cases with many showing abnormalities associated with favorable to intermediate prognosis. The authors' attempt to compare CLL with SLL with regards to cytogenetic and IgVH mutational status shows no statistically significant difference.


Lateral and axial cutting efficiency of instruments manufactured with conventional nickel-titanium and novel gold metallurgy.
To isolate the effect of metallurgy in lateral and axial cutting efficacy against plastic and bovine dentine substrates by comparing two rotary systems with identical design but manufactured with either conventional nickel-titanium or heat-treated gold alloy. A total of 258 ProTaper Universal (PTU) and ProTaper Gold (PTG) Shaping instruments were used. Bending behaviour was assessed to determine the appropriate displacement associated with a 2 N force in lateral cutting. Ten instruments of each type were used in lateral action for 60 s against bovine dentine or plastic substrates four consecutive times producing four notches in each specimen. Ten further instruments of each type were used in on axial action in four standardized simulated root canals fabricated from 4-mm thick plastic or dentine discs. Both tests were performed at 300 rpm in a computer-controlled testing platform. Notch area and torsional load were compared with Student's t-tests. Repeated measures ANOVA was used to compare cutting efficiency across the four different time-points. Pearson correlation coefficients between substrates were also determined. For lateral action, all three PTG instruments cut significantly more effectively (P < 0.05) than PTU on the plastic substrate. S1 and S2 PTG cut significantly more after 120 and 180 s (P < 0.05) on bovine dentine substrate. For axial action, S1 and S2 PTG were significantly more efficient in cutting at 180 s on plastic and 120 s on bovine dentine (P < 0.05). Instruments made from heat-treated nickel-titanium gold alloy had equal or greater cutting efficiency when compared to those made from conventional nickel-titanium.


Image subband coding using fuzzy inference and adaptive quantization.
Wavelet image decomposition generates a hierarchical data structure to represent an image. Recently, a new class of image compression algorithms has been developed for exploiting dependencies between the hierarchical wavelet coefficients using zerotrees. This paper deals with a fuzzy inference filter for image entropy coding by choosing significant coefficients and zerotree roots in the higher frequency wavelet subbands. Moreover, an adaptive quantization is proposed to improve the coding performance. Evaluating with the standard images, the proposed approaches are comparable or superior to most state-of-the-art coders. Based on the fuzzy energy judgment, the proposed approaches can achieve an excellent performance on the combination applications of image compression and watermarking.


Mendelian randomization analyses implicate biogenesis of translation machinery in human aging.
Reduced provision of protein translation machinery promotes healthy aging in a number of animal models. In humans, however, inborn impairments in translation machinery are a known cause of several developmental disorders, collectively termed ribosomopathies. Here, we use casual inference approaches in genetic epidemiology to investigate whether adult, tissue-specific biogenesis of translation machinery drives human aging. We assess naturally occurring variation in the expression of genes encoding subunits specific to the two RNA polymerases (Pols) that transcribe ribosomal and transfer RNAs, namely Pol I and III, and the variation in expression of ribosomal protein (RP) genes, using Mendelian randomization. We find each causally associated with human longevity (β = -0.15 ± 0.047, P = 9.6 × 10-4, q = 0.015; β = -0.13 ± 0.040, P = 1.4 × 10-3, q = 0.023; β = -0.048 ± 0.016, P = 3.5 × 10-3, q = 0.056, respectively), and this does not appear to be mediated by altered susceptibility to a single disease. We find that reduced expression of Pol III, RPs, or Pol I promotes longevity from different organs, namely visceral adipose, liver, and skeletal muscle, echoing the tissue specificity of ribosomopathies. Our study shows the utility of leveraging genetic variation in expression to elucidate how essential cellular processes impact human aging. The findings extend the evolutionary conservation of protein synthesis as a critical process that drives animal aging to include humans.


Decreasing Peripherally Inserted Central Catheter Use With Ultrasound-Guided Peripheral Intravenous Lines: A Quality Improvement Project in the Acute Care Setting.
An ultrasound-guided peripheral intravenous (UGPIV) quality improvement project occurred in an 849-bed tertiary care hospital with a goal to reduce the use of central lines, in particular, peripherally inserted central catheters (PICCs). Since implementation, PICCs have decreased by 46.7% overall, and 59 nurses in-hospital are competent in placing UGPIVs. Placement of UGPIVs by the bedside nurse is a key initiative in decreasing PICC use and, potentially, infections.


[Biological properties of the alpha-mannanase of Rhodococcus erythropolis].
When Rhodococcus erythropolis is cultivated under the submerged conditions in a medium containing yeast mannan as a sole carbon source, it synthesizes exocellular alpha-mannanase which hydrolyzes alpha-1,2 and alpha-1,3 bonds in a mannan molecule. The alpha-mannanase of R. erythropolis exerts distinct lectin properties under the conditions which entirely exclude its enzyme activity.


Stones in the common bile duct: experience with medical dissolution therapy.
Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist.


Willingness to pay for implant therapy: a study of patient preference.
This study determined the amount of willingness to pay (WTP) for implant treatment and identified the factors affecting WTP. Subjects attending a university dental hospital were recruited (n=59). They were presented with two hypothetical clinical scenarios: missing one anterior/posterior tooth. The clinical procedures, outcome and plausible complications of various replacement options (fixed and removable partial dentures, implants) and sequelae of no treatment were presented. They were then asked how much they were willing to pay for tooth replacement under the two situations using a bidding method, with a starting bid of Hong Kong (HK)$20,000 in HK$1000 increment/decrement if they were willing/unwilling to pay that amount (1 USD=7.8 HKD). The amount was recorded at which the subject chose the opposite option or it reached HK$0. Demographic data were also collected. WTP values were compared between anterior and posterior replacements, and among various demographic subgroups. Spearman's correlations and linear regression analysis were also conducted. Ninety-four percent and 84% of the subjects chose implant treatment to replace missing anterior and posterior teeth, respectively. The mean WTP amounts for anterior/posterior tooth replacement were HK$11,000/HK$10,000 (P>0.05). Higher WTP amounts were obtained from females, subjects without missing teeth or restorative need, and had attained higher level of education (P<0.05). Gender (P<0.05), level of education (P=0.042), and the presence of missing teeth (P=0.001) were independent predictors of WTP. The estimated WTP value for a single tooth replacement using dental implants was HK$10,000. Gender, level of education and presence of missing teeth were independent predictors that influenced WTP.


Exploring the Antimicrobial Potential and Stability of Black Soldier Fly (Hermentia illucens) Larvae Fat for Enhanced Food Shelf-Life.
The larvae of the Black Soldier Fly (BSF, Hermetia illucens) have been introduced as one of the tools to create a circular economy model, which will be used in areas such as waste management and the treatment of industrial by-products to produce high-added-value food grade ingredients. The main aim of this research was to investigate the fat composition and antimicrobial activity against food pathogens and spoilers of Black Soldier Fly larvae. The research revealed that the Black Soldier Fly larvae fats are predominantly lauric fatty (40.93%), which are followed by palmitic, oleic, myristic, linolenic and palmitoleic fatty acids, accounting for 19.11, 17.34, 6.49, 8.79 and 3.89% of the fatty acid content, respectively. The investigation of the fats showed stability through a one-year monitoring period with no indication of chemical or microbiological spoilage. Different fat fractions were tested for antimicrobial activity, which showed efficiency against Candida albicans (the inhibition zone varied from 10.5 to 12.5 mm), Bacillus subtilis (from 12.5 to 16.5 mm), Staphylococcus aureus (12.5 mm) and Escherichia coli (10.0 mm). The inhibitory effect on Candida albicans was confirmed by shelf-life studies using larvae fat-based oleogel in a model food matrix. GraphPad Prism (ver. 8.0.1) was used for the statistical data processing. This research revealed the potential of Black Soldier Fly larvae fat as a very stable ingredient with promising antibacterial properties that can extend the product shelf-life in food matrixes even when used in relatively small amounts.


Opioid and benzodiazepine misuse in the United States: The impact of socio-demographic characteristics.
In 2021, drug overdose deaths in the United States reached a new record of 107,622. Misuse of opioids and benzodiazepines accounts for a large portion of drug overdose deaths. However, the effects of socio-demographic characteristics on misuse of opioids and benzodiazepines are not evident. Thus, this study examines the socio-demographic characteristics associated with misuse of opioids and benzodiazepines among adults in the United States. Data from 2015-2019 National Survey on Drug Use and Health was utilized in the multinomial logistic regression analysis and included 202,935 adults ages ≥18 years. During 2015-2019, 3.3% of the adults misused opioids, 1.2% misused benzodiazepines, and 0.9% misused both drugs in the preceding year of the survey. Those who were younger, bisexual, non-Hispanic White, had a history of delinquency in the past year, had alcohol dependence/abuse, marijuana dependence/abuse, nicotine dependence and use, and experienced major depressive episodes were more likely to misuse opioids, benzodiazepines, or both. A large portion of US adults are misusing opioids, benzodiazepines, and both drugs. Specifically, bisexual individuals experience higher odds of opioid misuse, benzodiazepine misuse and misuse of both drugs compared with heterosexuals, while males are experiencing lower odds of benzodiazepine misuse compared with females. Individuals aged 26-49 experience the highest odds of opioid misuse, though misuse of both drugs was higher among the 18-25 age group. Findings underscore the use of targeted preventive measures to reduce misuse of these drugs among at-risk populations identified in this study.


Roles of small laccases from Streptomyces in lignin degradation.
Laccases (EC 18.104.22.168) are multicopper oxidases that can oxidize a range of substrates, including phenols, aromatic amines, and nonphenolic substrates. To investigate the involvement of the small Streptomyces laccases in lignin degradation, we generated acid-precipitable polymeric lignin obtained in the presence of wild-type Streptomyces coelicolor A3(2) (SCWT) and its laccase-less mutant (SCΔLAC) in the presence of Miscanthus x giganteus lignocellulose. The results showed that strain SCΔLAC was inefficient in degrading lignin compared to strain SCWT, thereby supporting the importance of laccase for lignin degradation by S. coelicolor A3(2). We also studied the lignin degradation activity of laccases from S. coelicolor A3(2), Streptomyces lividans TK24, Streptomyces viridosporus T7A, and Amycolatopsis sp. 75iv2 using both lignin model compounds and ethanosolv lignin. All four laccases degraded a phenolic model compound (LM-OH) but were able to oxidize a nonphenolic model compound only in the presence of redox mediators. Their activities are highest at pH 8.0 with a low krel/Kapp for LM-OH, suggesting that the enzymes' natural substrates must be different in shape or chemical nature. Crystal structures of the laccases from S. viridosporus T7A (SVLAC) and Amycolatopsis sp. 75iv2 were determined both with and without bound substrate. This is the first report of a crystal structure for any laccase bound to a nonphenolic β-O-4 lignin model compound. An additional zinc metal binding site in SVLAC was also identified. The ability to oxidize and/or rearrange ethanosolv lignin provides further evidence of the utility of laccase activity for lignin degradation and/or modification.


Prenatal glucocorticoids and long-term programming.
Epidemiological evidence suggests that low birth weight is associated with an increased risk of cardiovascular, metabolic and neuroendocrine disorders in adult life. Glucocorticoid administration during pregnancy reduces offspring birth weight and alters the maturation of the lung and other organs. We hypothesised that prenatal exposure to excess glucocorticoids or stress might represent a mechanism linking foetal growth with adult pathophysiology. In rats, birth weight is reduced following prenatal exposure to the synthetic steroid dexamethasone, which readily crosses the placenta, or to carbenoxolone, which inhibits 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the physiological feto-placental 'barrier' to maternal glucocorticoids. As adults, the offspring exhibit permanent hypertension, hyperglycaemic, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behaviour reminiscent of anxiety. Physiological variations in placental 11beta-HSD2 activity correlate directly with foetal weight. In humans, 11beta-HSD2 gene mutations cause low birth weight. Moreover, low-birth-weight babies have higher plasma cortisol levels throughout adult life, indicating HPA axis programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors, key among which is the glucocorticoid receptor (GR) itself. The differential programming of the GR in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the GR gene. Overall, the data suggest that both pharmacological and physiological exposure prenatally to excess glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders in adult life.


Prolonged-release nicotinic acid in patients with atherosclerotic disease in the Netherlands.
High-density lipoprotein (HDL) cholesterol elevation is associated with an improved outcome in patients with atherosclerotic disease. Niaspan, a prolonged-release nicotinic acid, was evaluated during the Niaspan-Induced HDL Elevation for Optimizing Risk Control (NEMO) study in The Netherlands. NEMO was a 6-month, prospective, observational, multicentre, open-label study. Niaspan was prescribed in statin-treated patients with known or suspected atherosclerotic disease. The main outcome measures were treatment-related adverse drug reactions (ADRs) and effects on lipids and cardiovascular-risk score based on the algorithm derived from the Prospective Cardiovascular Münster study. 612 patients were included in The Netherlands. Flushing was the most common ADR (29% of patients during the first month of treatment). The main reasons for treatment discontinuation were flushing (10.5%), patient request (8.0%) and being lost to follow-up (6.0%). About half of all patients (52%) continued treatment after the study. Tolerability was rated 'good' or 'very good' in 54% of these patients. HDL cholesterol increased by 23% from baseline, and triglycerides were reduced by 16%, with little change in low-density lipoprotein or total cholesterol. Cardiovascular risk score was reduced by 3.3 points. The use of the prolonged-release nicotinic acid Niaspan in patients with or at risk for atherosclerotic disease showed good tolerability, a marked increase in HDL cholesterol and a reduced cardiovascular risk score.


Control of Andreev bound state population and related charge-imbalance effect.
Motivated by recent experimental research, we study a superconducting constriction subject to a dc and ac phase bias. We consider the processes whereby the ac drive promotes one quasiparticle from an Andreev bound state to a delocalized state outside the superconducting gap. We demonstrate that with these processes one can control the population of the Andreev bound states in the constriction. We stress an interesting charge asymmetry of these processes that may produce a charge imbalance of accumulated quasiparticles, which depends on the phase.


Single room maternity care and client satisfaction.
Single room maternity care is the provision of intrapartum and postpartum care in a single room. It promotes a philosophy of family centered care in which one nurse cares for the family consistently throughout the intrapartum and postpartum periods. At B.C. Women's Hospital, a tertiary level obstetric teaching hospital in Vancouver, British Columbia, a seven-bed, single room maternity care unit was developed and opened as a demonstration project. As part of the evaluation of this unit, client satisfaction was compared between women enrolled in single room maternity care and those in a traditional setting. The study group included 205 women who were admitted to the single room maternity care unit after meeting the low-risk criteria. Their responses on a satisfaction survey were compared with those of a historical comparison group of 221 women meeting the same eligibility criteria who were identified through chart audits 3 months before the single room maternity care unit was opened. A second, concurrent comparison group comprised 104 women who also met eligibility criteria. Study group women were more satisfied than comparison groups in all areas evaluated, including provision of information and support, physical environment, nursing care, patient education, assistance with infant feeding, respect for privacy, and preparation for discharge. Single room maternity care was associated with a significant improvement in client satisfaction because of many factors, including the physical setting itself, avoidance of transfers, and improved continuity of nursing care.


Influence of presynaptic receptors on neuromuscular transmission in rat.
The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.


The pivotal role played by lipocalin-2 in chronic inflammatory pain.
Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12h after CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2 and its receptor 24p3R were mainly expressed in infiltrating neutrophils and macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were significantly diminished in Lcn2-deficient mice compared to wild-type animals. Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naïve mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.


Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo.
Triple-negative breast cancer (TNBC) has the lowest 5-year survival rate of invasive breast carcinomas, and currently there are no approved targeted therapies for this aggressive form of the disease. The androgen receptor (AR) is expressed in up to one third of TNBC and we find that all AR(+) TNBC primary tumors tested display nuclear localization of AR, indicative of transcriptionally active receptors. While AR is most abundant in the "luminal AR (LAR)" molecular subtype of TNBC, here, for the first time, we use both the new-generation anti-androgen enzalutamide and AR knockdown to demonstrate that the other non-LAR molecular subtypes of TNBC are critically dependent on AR protein. Indeed, AR inhibition significantly reduces baseline proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis in four TNBC lines (SUM159PT, HCC1806, BT549, and MDA-MB-231), representing three non-LAR TNBC molecular subtypes (mesenchymal-like, mesenchymal stem-like, and basal-like 2). In vivo, enzalutamide significantly decreases viability of SUM159PT and HCC1806 xenografts. Furthermore, mechanistic analysis reveals that AR activation upregulates secretion of the EGFR ligand amphiregulin (AREG), an effect abrogated by enzalutamide in vitro and in vivo. Exogenous AREG partially rescues the effects of AR knockdown on proliferation, migration, and invasion, demonstrating that upregulation of AREG is one mechanism by which AR influences tumorigenicity. Together, our findings indicate that non-LAR subtypes of TNBC are AR dependent and, moreover, that enzalutamide is a promising targeted therapy for multiple molecular subtypes of AR(+) TNBC.


Benzothiadiazole Aryl-amine Based Materials as Efficient Hole Carriers in Perovskite Solar Cells.
Four hole transport materials (HTMs) based on a benzothiadiazole (BT) central core have been synthesized and successfully employed in triple-cation mixed-halide perovskite solar cells (PSCs), reaching 18.05% solar to energy conversion efficiency. The synthesis of these HTMs follows the push-and-pull approach to modulate the HOMO energy level by combining the BT group as an electron acceptor and diphenyl- and triphenyl-amines as electron donors. Here we show that despite adjusting the HOMO energy level to that of the perovskite is a believed requisite to achieve efficient interfacial hole transfer, additional factors must be taken into account to design novel and efficient HTMs, such as a high hole mobility, solubility in organic solvents, and thermal stability.


The effect of reflector geometry on the acoustic field and bubble dynamics produced by an electrohydraulic shock wave lithotripter.
A theoretical model for the propagation of shock wave from an axisymmetric reflector was developed by modifying the initial conditions for the conventional solution of a nonlinear parabolic wave equation (i.e., the Khokhlov-Zabolotskaya-Kuznestsov equation). The ellipsoidal reflector of an HM-3 lithotripter is modeled equivalently as a self-focusing spherically distributed pressure source. The pressure wave form generated by the spark discharge of the HM-3 electrode was measured by a fiber optic probe hydrophone and used as source conditions in the numerical calculation. The simulated pressure wave forms, accounting for the effects of diffraction, nonlinearity, and thermoviscous absorption in wave propagation and focusing, were compared with the measured results and a reasonably good agreement was found. Furthermore, the primary characteristics in the pressure wave forms produced by different reflector geometries, such as that produced by a reflector insert, can also be predicted by this model. It is interesting to note that when the interpulse delay time calculated by linear geometric model is less than about 1.5 micros, two pulses from the reflector insert and the uncovered bottom of the original HM-3 reflector will merge together. Coupling the simulated pressure wave form with the Gilmore model was carried out to evaluate the effect of reflector geometry on resultant bubble dynamics in a lithotripter field. Altogether, the equivalent reflector model was found to provide a useful tool for the prediction of pressure wave form generated in a lithotripter field. This model may be used to guide the design optimization of reflector geometries for improving the performance and safety of clinical lithotripters.


[Glycopolymers of microorganisms as a source for creation of ecologically-safe antimicrobial media with specific activity].
Current data concerning structure components of the surface of microorganisms which take direct part in manifestation of their adhesive properties--adhesin, on the one hand, and carbohydrate components of cell receptors, on the other hand, are presented and analyzed in the paper. The prevention or decrease of adhesion by means of competitive inhibition by substances, which enclose structure, analogues of adhesins or their receptors, make up promising trend in the system of treatment and prophylaxis of infectious diseases. The use of synthetic substance of directed action will allow ceasing the development of infectious process without additional chemical loading of the organism-host and pollution of the environment, since as to their structure they resemble biomolecules typical of this organism. It is asummed that the data on the microorganism surface components can serve a basis for conducting fundamental investigations concerning relations between the structure and function of natural biopolymers, specification of phylogenetic relations between certain groups of microorganisms as well as for defining the mechanisms of the action and further perfection of probiotics.


Prospect of making XPS a high-throughput analytical method illustrated for a Cu x Ni1-x O y combinatorial material library.
Combinatorial material science crucially depends on robust, high-throughput characterization methods. While X-ray photoelectron spectroscopy (XPS) may provide detailed information about chemical and electronic properties, it is a time-consuming technique and, therefore, is not viewed as a high-throughput method. Here we present preliminary XPS data of 169 measurement spots on a combinatorial 72 × 72 cm2 Cu x Ni1-x O y compositional library to explore how characterization and evaluation routines can be optimized to improve throughput in XPS for combinatorial studies. In particular, two quantification approaches are compared. We find that a simple integration (of XPS peak regions) approach is suited for fast evaluation of, in the example system, the [Cu]/([Cu] + [Ni]) ratio. Complementary to that, the time-consuming (XPS peak-) fit approach provides additional insights into chemical speciation and oxidation state changes, without a large deviation of the [Cu]/([Cu] + [Ni]) ratio. This insight suggests exploiting the fast integration approach for 'real time' analysis during XPS data collection, paving the way for an 'on-the-fly' selection of points of interest (i.e., areas on the sample where sudden composition changes have been identified) for detailed XPS characterization. Together with the envisioned improvements when going from laboratory to synchrotron-based excitation sources, this will shorten the analysis time sufficiently for XPS to become a realistic characterization option for combinatorial material science.


Influence of the structure of water on the hydrolysis of cytidine 2',3'-phosphate catalysed by bovine pancreatic ribonuclease A.
The study of the temperature dependence of the hydrolysis of cytidine 2',3'-phosphate by bovine pancreatic ribonuclease A (EC 22.214.171.124) at pH 7.0 by using the pH-stat method showed a transition at 4 degrees C [J. A. Biosca and C. M. Cuchillo (1980) Biochem. J. 189, 655-657]. The breaks found in the Van't Hoff and Arrhenius plots at pH 7.0 were confirmed in the present work by following the reaction spectrophotometrically with a stopped-flow spectrophotometer adapted to the use of sub-zero temperatures. Similar results were found at pH 5.5. In addition it was found that the discontinuity disappears when 40% ethyleneglycol is present in the reaction mixture. However, in this latter instance a discontinuity around 0 degrees C appears in the Arrhenius plot. To explore the possibility that all these effects were due to a conformational transition in the protein, thermal perturbation experiments were carried out with the enzyme. A change in the slope of the plot of delta A290 as a function of temperature was found around 6 degrees C at pH 7.0 but not at pH 5.5. The results reported here can be interpreted as due to a change in the protein structure induced by the change of the structure of water. The studies carried out in the presence of ethyleneglycol also open the way to the cryoenzymological experimentation on ribonuclease.


Effect of Feeding an Iodine-Restricted Diet in Cats with Spontaneous Hyperthyroidism.
Exclusive feeding of an iodine-restricted diet has been proposed as a method for controlling clinical manifestations of hyperthyroidism in hyperthyroid cats. To determine the effect of feeding an iodine-restricted diet on TT4 concentrations and clinical signs in cats with spontaneous hyperthyroidism. Forty-nine client-owned cats with spontaneous hyperthyroidism. Retrospective case series. Hyperthyroid cats were exclusively fed a commercially available iodine-restricted diet. Clinical response was assessed by change in weight and heart rate and serum TT4, blood urea nitrogen (BUN), and creatinine concentrations at various times during dietary management (21-60 days, 60-180 days). Serum TT4 normalized in 20/48 cats (42%) and 39/47 cats (83%) at 21-60 days and 61-180 days, respectively. Cats in which the TT4 concentrations were still above reference range at 21-60 days had a significantly higher starting TT4 than those that normalized their TT4 levels during the same time period (P = .038). Body weight did not significantly increase (P = .34) nor heart rate decrease (P = .64) during the study. There was a significant decrease in serum creatinine (P = .028). Cats in the low reference range for serum TT4 concentrations did not have a significant increase in body weight (P = .41) nor creatinine (P = .54) when compared to those with high reference range. Restricted-iodine diets were effective at maintaining serum TT4 concentrations within reference ranges for a majority of cats with spontaneous hyperthyroidism over 1 year, although not all clinical signs of hyperthyroidism improved.


Objective evaluation of video segmentation quality.
Video segmentation assumes a major role in the context of object-based coding and description applications. Evaluating the adequacy of a segmentation result for a given application is a requisite both to allow the appropriate selection of segmentation algorithms as well as to adjust their parameters for optimal performance. Subjective testing, the current practice for the evaluation of video segmentation quality, is an expensive and time-consuming process. Objective segmentation quality evaluation techniques can alternatively be used; however, it is recognized that, so far, much less research effort has been devoted to this subject than to the development of segmentation algorithms. This paper discusses the problem of video segmentation quality evaluation, proposing evaluation methodologies and objective segmentation quality metrics for individual objects as well as for complete segmentation partitions. Both stand alone and relative evaluation metrics are developed to cover the cases for which a reference segmentation is missing or available for comparison.


Knowledge about the mind: links between theory of mind and later metamemory.
This longitudinal study combined, in a single study, different aspects of children's knowledge about mental phenomena and thus could investigate relations among the development of language, theory of mind, and later metamemory. In total, 183 German children were tested at ages 3, 4, and 5. Each time of testing included a set of theory-of-mind tasks, a battery of language development, and additionally, at Time 3, a set of metamemory questions. The findings demonstrate strong relationships between children's language abilities and their theory of mind (both first- and second-order false beliefs). Moreover, both theory-of-mind and language competencies significantly predicted later metamemory, with their relative contribution changing over time. Language may influence metamemory developmentally both directly and indirectly (through theory of mind).


Greater corticostriatal activation associated with facial motor imagery compared with motor execution: a functional MRI study.
Motor imagery (MI) relies on conscious mental simulation of a motor act without overt motor output and can promote motor skill acquisition and facilitate rehabilitation for patients with stroke or neurological conditions. Although a plethora of neuroimaging studies have investigated the neural network of MI regarding different body parts, exploration of the neural correlates to facial MI remains warranted. Here, we used functional MRI with a large cohort of 41 participants who underwent motor execution (ME) and MI runs of mouth-stretching tasks. Then, we carried out conjunction and contrast analyses to investigate the commonalities and differences between the two conditions. Conjunction analysis, representing the shared neural network between ME and MI, showed activation in the primary motor cortex, primary and secondary somatosensory cortices, premotor cortex, parietal lobe, anterior insula, supplementary motor area (SMA) and pre-SMA, thalamus, putamen, and caudate. Contrast analysis showed greater activation of primary motor cortex, primary and secondary somatosensory cortices, SMA, anterior insula, and the thalamus in response to ME than MI and greater activation of the premotor cortex, pre-SMA, putamen, and caudate in response to MI than ME. Interestingly, we found exclusive activation in the anterior cingulate cortex and left ventrolateral prefrontal cortex in response to MI, reflecting the motor inhibition network responsible for blocking the transmission of motor commands to peripheral effectors during mental rehearsal. Taken together, these findings show that, despite the neural overlap between ME and MI, there are different degrees of activation within this overlap, and that MI normally involves motor command inhibition possibly mediated by the anterior cingulate cortex and ventrolateral prefrontal cortex.