Technological optimization of manufacture of probiotic whey cheese matrices.
In attempts to optimize their manufacture, whey cheese matrices obtained via thermal processing of whey (leading to protein precipitation) and inoculated with probiotic cultures were tested. A central composite, face-centered design was followed, so a total of 16 experiments were run using fractional addition of bovine milk to feedstock whey, homogenization time, and storage time of whey cheese as processing parameters. Probiotic whey cheese matrices were inoculated with Lactobacillus casei LAFTIL26 at 10% (v/v), whereas control whey cheese matrices were added with skim milk previously acidified with lactic acid to the same level. All whey cheeses were stored at 7 °C up to 14 d. Chemical and sensory analyses were carried out for all samples, as well as rheological characterization by oscillatory viscometry and textural profiling. As expected, differences were found between control and probiotic matrices: fractional addition of milk and storage time were the factors accounting for the most important effects. Estimation of the best operating parameters was via response surface analysis: milk addition at a rate of 10% to 15% (v/v), and homogenization for 5 min led to the best probiotic whey cheeses in terms of texture and organoleptic properties, whereas the best time for consumption was found to be by 9 d of storage following manufacture.


Different effects of whole-cell and acellular vaccines on Bordetella transmission.
Vaccine development has largely focused on the ability of vaccines to reduce disease in individual hosts, with less attention to assessing the vaccine's effects on transmission between hosts. Current acellular vaccines against Bordetella pertussis are effective in preventing severe disease but have little effect on less severe coughing illness that can mediate transmission. Using mice that are natural host's of Bordetella bronchiseptica, we determined the effects of vaccination on shedding and transmission of this pathogen. Vaccination with heat-killed whole-cell B. bronchiseptica or B. pertussis inhibited shedding of B. bronchiseptica. Differences in neutrophil and B-cell recruitment distinguished sham-vaccine from whole-cell-----vaccine responses and correlated with shedding output. Both B and T cells were essential for vaccine-induced control of shedding. Adoptive transfer of antibodies was able to limit shedding, while depletion of CD4(+) T cells led to increased shedding in vaccinated mice. Finally, whole-cell vaccination was able to prevent transmission, but an acellular vaccine that effectively controls disease failed to control shedding and transmission. Our results highlight discrepancies between whole-cell and acellular vaccination that could contribute to the increased incidence of B. pertussis infection since the transition to the use of acellular vaccination.


Colloid osmotic pressure changes in isolated isogravimetric cat hindlimb.
The development of osmotic pressure, following the addition of bovine serum albumin (BSA) to the perfusate, was measured in an isogravimetric cat hindlimb fully dilated with papaverine. The changes in colloid osmotic pressure were followed by recording the changes in venous pressure (PVI) necessary to maintain constant weight. Capillary filtration coefficient (CFC) and vascular compliances were calculated from weight changes following steps in venous pressure. Venous BSA levels reached arterial within 1 min, and PVI reached a new steady state 13.1 +/- 0.9 (SE) min (n = 9 in 6 limbs) after adding BSA. This apparent delay in the development of the osmotic pressure agrees with earlier reports. However, when the BSA was added under constant venous pressure conditions, the fluid reabsorption reached its maximum rate within 1.5 min. The data suggest that the BSA is osmotically fully effective after the capillary washin. The slowness of the rise of PVI in the isogravimetric state is probably caused by the time necessary to absorb sufficient fluid from the interstitium to raise the capillary pressure to a level that balances the increased oncotic pressure. A mathematical model supports this explanation.


Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity.
To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16-ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG. Experimental study. University. Thirty-two healthy women of reproductive age. Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24 hours after IM administration of 10,000 IU hCG. Granulosa cells were isolated from follicular aspirates obtained from healthy women participating in our IVF program for male factor infertility. Estrogen metabolite concentrations were determined in CL tissue, and VEGF was assessed in conditioned medium. The angiogenic activity was analyzed by bioassay. Concentrations of EMs with proangiogenic activity (16-ketoestradiol and 4-hydroxyestrone) were higher in early and mid-LP CL vs. late-LP CL. These EMs and hCG increased VEGF production and angiogenic activity. Conversely, late-LP CL had significantly higher levels of 2-methoxyestrone and 2-methoxyestradiol, which have antiangiogenic activity. Administration of hCG reduced the production of these EMs. Our findings suggest that the EMs are important paracrine modulators of CL function. Administration of hCG increases the production of EMs with proangiogenic activity and reduces the secretion of those EMs with antiangiogenic action, suggesting a novel mechanism by which the late-LP CL is rescued in conception cycles.


A nationwide survey on the use of heated humidified high flow oxygen therapy on the paediatric wards in the UK: current practice and research priorities.
Heated Humidified High Flow Nasal Cannula Oxygen Therapy (HHFNC) is increasingly used on the paediatric wards and High Dependency Units (HDU) for different types of pathologies and different age groups. We aimed to describe current practice related to the use of HHFNC on the paediatric wards and HDUs, weaning practices and preferred outcome measures for future research. We carried out a cross-sectional online survey of UK paediatric consultants or their delegates working on the paediatric wards. Descriptive analysis of their geographical, and organizational characteristics, their specialties, and their level of experience was investigated. Reasons for HHFNC initiation, weaning criteria, patients' characteristics and their primary pathologies were also analysed. Participation of 218 paediatricians from 81 hospitals (Median: 2.7, Range: 1-11) was registered. HHFNC was provided in most of the surveyed hospitals (93%, 75/81). A High Dependency Unit (HDU) was available in 47 hospitals (58%); less than a third of those have a dedicated paediatrician. Decisions around HHFNC were made solely by paediatricians in (75%) of the cases, mostly at hospitals with no HDU compared to those with dedicated HDUs (70.3% VS 36.6, 95%CI:22.6-50.4%, P < .001). HHFNC was reported by nearly two-thirds (68%) of the practitioners who used it on the wards to be as effective or superior to CPAP (Continuous Positive Airway Pressure) with fewer complications. Failure rate while on HHFNC was identified as the most important outcome measure in any future research followed by the length of need for HHFNC support (37.1, and 28% respectively). This survey showed support for developing paediatric-specific national guidance on the use of HHFNC on the wards. Our list of defined research priorities may help guide further collaborative research efforts in this field.


The development of visual acuity in infant astigmats.
Acuity for vertical, horizontal, and oblique gratings was measured in 77 infant astigmats using a preferential looking procedure. Measurements were made with the refractive error uncorrected. Most of the infant astigmats were slightly to moderately hyperopic with respect to the test distance of 50 cm. Their acuity was not significantly different from that of a group of non-astigmatic infants. Average acuity for vertical and horizontal gratings increased from 6/200 at 1 month of age to 6/24 at 1 yr. Average acuity for oblique gratings increased more slowly, so that by 1 yr of age it was only 6/33. The only infants to show reductions in acuity were those with a strong myopic focus and one infant with a very strong hyperopic focus. When this infant was tested with optical correction, acuity improved to normal levels. This suggests that meridional amblyopia develops sometime after the first year of life or that it is confined to high spatial frequencies.


Emerging perspectives on 3D printed bioreactors for clinical translation of engineered and bioprinted tissue constructs.
3D printed/bioprinted tissue constructs are utilized for the regeneration of damaged tissues and as in vitro models. Most of the fabricated 3D constructs fail to undergo functional maturation in conventional in vitro settings. There is a challenge to provide a suitable niche for the fabricated tissue constructs to undergo functional maturation. Bioreactors have emerged as a promising tool to enhance tissue maturation of the engineered constructs by providing physical/biological cues along with a controlled nutrient supply under dynamic in vitro conditions. Bioreactors provide an ambient microenvironment most appropriate for the development of functionally matured tissue constructs by promoting cell proliferation, differentiation, and maturation for transplantation and drug screening applications. Due to the huge cost and limited availability of commercial bioreactors, there is a need to develop strategies to make customized bioreactors. Additive manufacturing (AM) may be a viable tool to fabricate custom designed bioreactors with better efficiency and at low cost. In this review, we have extensively discussed the importance of bioreactors in functionalizing tissue engineered/3D bioprinted scaffolds for bone, cartilage, skeletal muscle, nerve, and vascular tissue. In addition, the importance and fabrication of customized 3D printed bioreactors for the maturation of tissue engineered constructs are discussed in detail. Finally, the current challenges and future perspectives in translating commercial and custom 3D printed bioreactors for clinical applications are outlined.


Effects of a task failure exercise on the peroneus longus and brevis during perturbed gait.
Ankle inversion injuries represent the most common trauma sustained by athletes. Muscle fatigue from activity may contribute to a delay in the response of the ankle proprioceptors and dynamic restraints during unexpected inversion. The purpose of this investigation was to determine changes in peroneal average EMG, peak EMG, and time to peak EMG following a task failure exercise. Thirty-two subjects (age 20+/-1.43 yrs; 21 male, 11 female) with no lower extremity injuries reported for data collection. Data were collected from each subject's dominant leg using surface electromyography (EMG). EMG electrodes were applied over the peroneus longus (PL) and brevis (PB) using a standard protocol Subjects walked at a fixed pace on a 6.1 m runway with one section that could be unexpectedly dropped into 30 degrees of inversion upon foot contact. Trials with perturbed and unperturbed gait were randomized to reduce prediction of the unexpected inversion. Once 3 trials of perturbed gait were recorded, subjects completed an isotonic activity that isolated the peroneals. The task was completed to failure. Immediately following the task failure exercise, subjects walked on the perturbation runway once again until 3 trials of perturbed gait were recorded. Analysis revealed no significant differences with regard to average muscle activity between pre- and post-task failure exercise for the PL (F1,31 = 0.133; p = 0.718) or for the PB (F1,31 = 0.795; p = 0.380). There was also no significant difference in peak muscle activity pre- to post-task failure for the PL (F1,31 = 0.032; p = 0.859) or the PB (F1,31 = 0.156; p = 0.695). Finally, there was no significant difference in time-to-peak muscle activity pre- to post-task failure for the PL (F1,31 = 0.830; p = 0.369) or the PB (F1,31 = 1.037; p = 0.316). We concluded that the task failure exercise did not contribute to changes in peroneal activity during perturbed gait. These results indicate that peroneal fatigue does not play a significant role in the incidence of inversion ankle sprains.


Molecular Cloning and Characterization of a cDNA Encoding the Retinal Arylalkylamine N-Acetyltransferase of the Rainbow Trout, Oncorhynchus mykiss.
Melatonin synthesis in the retina as well as in the pineal gland exhibits daily variations with higher levels during the dark phase of light-dark cycles. To analyze the molecular mechanism of melatonin synthesis in the retina, we have cloned, sequenced and characterized a putative cDNA for arylalkylamine N-acetyltransferase (AANAT; EC 126.96.36.199), a rate-limiting enzyme in melatonin production, from the retina of the rainbow trout (Oncorhynchus mykiss). The trout AANAT cDNA (1,585 bp) contains an open reading frame encoding 240 amino acid protein (predicted molecular weight, 27,420) that is 51-65% identical to avian and mammalian AANAT. The trout retinal AANAT protein contains motifs A and B that are conserved among the N-acetyltransferase superfamily and eight potential phosphorylation sites. Southern blot analysis demonstrated that the protein is expressed by a single copy gene. A single AANAT transcript (1.6 kb) was detected in the retina but not in the liver by Northern blot analysis. The levels of AANAT mRNA in the retina exhibited day-night changes with 3.3-fold increase at night. These results indicate that in the rainbow trout retina, the activity of AANAT and thus melatonin synthesis are regulated at least in part at the transcriptional level.


CXCR4 but not CXCR7 is mainly implicated in ocular leukocyte trafficking during ovalbumin-induced acute uveitis.
Uveitis is an inflammatory ocular disease characterized by the infiltration of T lymphocytes and other leukocytes into the eye. The recruitment of these inflammatory cells from systemic vasculature to ocular tissue is a well-coordinated multistep process including rolling, firm adhesion and transmigration. CXCL12 (SDF-1alpha) is an endothelial cell-derived cytokine interacting with CXCR4 and CXCR7, two chemokine receptors mainly expressed in T cells, neutrophils and monocytes. Recent studies have shown that CXCR4, CXCR7 and their ligand, CXCL12, are important for the regulation of leukocyte mobilization and trafficking. However, it is unclear whether these two chemokine receptors are implicated in the pathogenesis of uveitis. In this study, we used DO11.10 mice, whose CD4+ T cells are genetically engineered to react with ovalbumin (OVA), to investigate the role of CXCR4 and CXCR7 in an animal model of uveitis. Intravital microscopy revealed that intravitreal OVA challenge of DO11.10 mice caused the infiltration of both T cells and neutrophils. The invasion of these inflammatory cells coincided with the detection of transcriptional up-regulation of CXCR4 and CXCR7 in the eye. In addition, both real-time-PCR and immunohistochemistry revealed an enhanced expression of endothelial CXCL12. Furthermore, intraperitoneal injection of AMD3100 (a specific CXCR4 antagonist) significantly attenuated OVA-induced uveitis and CXCL12-mediated transwell migration. In contrast, intraperitoneal administration of CXCR7 neutralizing antibody did not significantly alter ocular infiltration of inflammatory cells caused by OVA challenge. Our data suggest that CXCR4 but not CXCR7 plays a critical role in antigen-induced ocular inflammation by facilitating leukocyte infiltration. This study not only enhances our knowledge of the immunopathological mechanism of uveitis but also provides a novel rationale to target CXCR4 as an anti-inflammatory strategy to treat uveitis.


Microfills vs. hybrids. Is there a universal composite resin?
An impressive positive evolution has taken place in restorative resins in the past 20 years. Although the types of resin used have not changed significantly, the fillers used in resins have changed enormously. Filler size has changed from particles that approached the size of table salt (over 100 microns) to today's submicron particle size. This article compares types of restorative resins for anterior and posterior use.


Invagination of presynaptic ribbons in the fly's optic lobe following loss of their target neuron.
In the first optic neuropile of the housefly Musca, photoreceptor terminals innervate fixed clusters of interneurons, one of which is the monopolar cell L2; L2's synapses in turn feed back upon the terminals. We examined the ultrastructure of these feedback synapses following degeneration of their normal targets, the receptor terminals; this was accomplished by photo-ablating the receptor cells after intraretinal injections of sulforhodamine. Even when all the terminals degenerated, their deafferentated target cells, including L2, remained structurally intact for at least 14 d. Despite this lack of obvious trans-synaptic degeneration, L2's synaptic connections did alter. Presynaptic organelles of the feedback synapses, synaptic ribbons and associated synaptic vesicles, soon appeared in L2's cytoplasm, separating from their site of attachment at the presynaptic membrane by invagination. Similar free-floating organelles and vesicles also occurred in another monopolar cell, L4. They were also occasionally encountered in L2, in normal, newly emerged flies at a time when a naturally occurring loss of feedback synapses is greatest. We interpret the process of internalization that forms these floating ribbons to be the first step in synaptic loss which occurs spontaneously, and that the rate is enhanced in L2 when its main synaptic targets, the receptor terminals, degenerate.


Host Genetic Factors and Dendritic Cell Responses Associated with the Outcome of Interferon/Ribavirin Treatment in HIV-1/HCV Co-Infected Individuals.
HIV-1/HCV co-infection is a significant health problem. Highly active antiretroviral treatment (HAART) against HIV-1 has proved to be fairly successful. On the other hand, direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns. Therefore PEGylated interferon (PEG-IFN) and ribavirin (RBV) still remain essential components of HCV treatment, and identification of host factors that predict IFN/RBV treatment response is necessary for effective clinical management of HCV infection. Impaired dendritic cell (DC) and T cell responses are associated with HCV persistence. It has been shown that IFN/RBV treatment enhances HCV-specific T cell functions and it is likely that functional restoration of DCs is the underlying cause. To test this hypothesis, we utilized an antibody cocktail (consisting of DC maturation, adhesion and other surface markers) to perform comprehensive phenotypic characterization of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in a cohort of HIV-1/HCV co-infected individuals undergoing IFN/RBV treatment. Our results show that pre-treatment frequencies of mDCs are lower in non-responders (NRs) compared to responders (SVRs) and healthy controls. Although, the treatment was able to restore the frequency of mDCs in NRs, it downregulated the frequency of CCR7+, CD54+ and CD62L+ mDCs. Pre-treatment frequencies of pDCs were lower in NRs and decreased further upon treatment. Compared to SVRs, NRs exhibited higher ratio of PD-L1+/CD86+ pDCs prior to treatment; and this ratio remained high even after treatment. These findings demonstrate that enumeration and phenotypic assessment of DCs before/during therapy can help predict the treatment outcome. We also show that before treatment, PBMCs from SVRs secrete higher amounts of IFN-γ compared to controls and NRs. Upon genotyping IFNL3 polymorphisms rs12979860, rs4803217 and ss469415590, we found rs12979860 to be a better predictor of treatment outcome. Collectively, our study led to identification of important correlates of IFN/RBV treatment response in HIV-1/HCV co-infected individuals.


Purification and characterization of amylases from three freshwater fish species providing new insight application as enzyme molecular markers for zymography.
Purification of amylases from digestive tracts of three freshwater fish species with Q-Sepharose Fast Flow and Sephacryl S-200 columns displayed two isoforms of amylases from Osteochilus hasselti (O1, O2) and three isoforms of those from both Hampala dispar (UB, H1, H2) and Puntioplites proctozystron (P1, P2, P3). The optimum pH values displayed at 7.0 and 8.0, while the optimum temperatures revealed at 40 and 50 °C. Almost isoenzyme activities were activated by NaCl and CaCl2, whereas EDTA and SDS strongly inhibited all enzymatic activities. Verification with an atomic absorption spectrophotometry exhibited the presence of Ca2+ ions in the range of 0.02-13.53 ppm per mg protein indicating that amylases are Ca2+ dependent. Molecular weight analysis revealed 12 to 147 kDa. The UB, O1, and H2 amylases with appropriate molecular masses of 64, 49, and 25 kDa validated with LC-MS/MS were selected. Three certain enzymes revealed high stability in a sample buffer after five cycles of freeze-thawing process upon storage at - 20 °C for 12 weeks. No protein degradation was observed on polyacrylamide gel, and the enzymes still displayed sharp and clear bands on zymograms. The result suggested that the purified fish amylases, which expressed high activities and stabilities, were potentially used as enzyme molecular weight markers for zymography.


Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay.
Background Mortality for infants undergoing complex cardiac surgery is >10% with a 30% to 40% risk of complications. Early identification and treatment of high-risk infants remains challenging. Metabolites are small molecules that determine the minute-to-minute cellular phenotype, making them ideal biomarkers for postsurgical monitoring and potential targets for intervention. Methods and Results We measured 165 serum metabolites by tandem mass spectroscopy in infants ≤120 days old undergoing cardiopulmonary bypass. Samples were collected prebypass, during rewarming, and 24 hours after surgery. Partial least squares-discriminant analysis, pathway analysis, and receiver operator characteristic curve analysis were used to evaluate changes in the metabolome, assess altered metabolic pathways, and discriminate between survivors/nonsurvivors as well as upper/lower 50% intensive care unit length of stay. Eighty-two infants had preoperative samples for analysis; 57 also had rewarming and 24-hour samples. Preoperation, the metabolic fingerprint of neonates differed from older infants ( R2=0.89, Q2=0.77; P<0.001). Cardiopulmonary bypass resulted in progressive, age-independent metabolic disturbance ( R2=0.92, Q2=0.83; P<0.001). Multiple pathways demonstrated changes, with arginine/proline ( P=1.2×10-35), glutathione ( P=3.3×10-39), and alanine/aspartate/glutamate ( P=1.4×10-26) metabolism most affected. Six subjects died. Nonsurvivors demonstrated altered aspartate ( P=0.007) and nicotinate/nicotinamide metabolism ( P=0.005). The combination of 24-hour aspartate and methylnicotinamide identified nonsurvivors versus survivors (area under the curve, 0.86; P<0.01), as well as upper/lower 50% intensive care unit length of stay (area under the curve, 0.89; P<0.01). Conclusions The preoperative metabolic fingerprint of neonates differed from older infants. Large metabolic shifts occurred after cardiopulmonary bypass, independent of age. Nonsurvivors and subjects requiring longer intensive care unit length of stay showed distinct changes in metabolism. Specific metabolites, including aspartate and methylnicotinamide, may differentiate sicker patients from those experiencing a more benign course.


Ru Cluster Incorporated NiMoO(P)4 Nanosheet Arrays as High-Efficient Bifunctional Catalyst for Wind/Solar-To-Hydrogen Generation Systems.
Developing cost-efficient bifunctional water splitting catalysts is crucial for sustainable hydrogen energy applications. Herein, ruthenium (Ru)-incorporated and phosphorus (P)-doped nickel molybdate (Ru-NiMoO(P)4 ) nanosheet array catalysts are synthesized. Due to the synergy of Ru clusters and NiMoO(P)4 by the modulated electronic structure and the rich active sites, impressively, Ru-NiMoO(P)4 exhibits superior OER (194 mV @ 50 mA cm-2 ) and HER (24 mV @ 10 mA cm-2 ) activity in alkaline media, far exceeding that of commercial Pt/C and RuO2 catalysts. Meanwhile, as bifunctional catalyst, to drive the overall water splitting at the current density of 10 mA cm-2 , Ru-NiMoO(P)4 requires only 1.45 V and maintaining stable output for 100 h. Furthermore, Ru-NiMoO(P)4 also possesses excellent capability for seawater electrolysis hydrogen production. Moreover, the successful demonstration of wind and solar hydrogen production systems provide the feasibility of the ultra-low Ru loading catalyst for large-scale hydrogen production in the future.


Superadditive and Subadditive Neural Processing of Dynamic Auditory-Visual Objects in the Presence of Congruent Odors.
Our sensory experiences comprise a variety of different inputs at any given time. Some of these experiences are unmistakable, others are ambiguous and profit from additional sensory information. Here, we explored whether the presence of a congruent odor influences the neural processing and sensory interaction of audio-visual objects using degraded videos (V) and sounds (A) of dynamic objects in unimodal and bimodal (AV) combinations without or with a congruent odor (VO, AO, AVO). Analyses of EEG data revealed superadditive and subadditive interaction effects. The topography and timing of these effects suggest evaluative rather than sensory processes as the underlying cause. Together, the results suggest that the mere presence of an odor affects the processing of A, V, and AV objects differently while multisensory interactions of AV and AVO objects have common neuronal mechanisms pointing to a robust, modality-independent network for the processing of redundant sensory information.


Frequency of subclinical peripheral neuropathy in cases of untreated brucellosis.
Brucellosis is a common zoonotic disease in some areas of the world. It may affect several organs and is known to involve the nervous system in 2.7-17.8% of affected patients. During the progression of brucellosis, peripheral neuropathies (PNs) have been reported. However, there are few studies investigating the presence of subclinical neuropathy in asymptomatic patients. In our study, we aimed to evaluate the presence of peripheral neuropathy using electrophysiological methods in newly-diagnosed untreated brucellosis patients. The study included a control group of 60 healthy volunteers and 60 untreated brucellosis patients with a positive result of 1/160 or above on a brucella tube agglutination test. The patient and control groups were evaluated by electrophysiological methods. In the patient group, all investigated motor nerves had slower average motor conduction speeds, reduced compound muscle action potential (CMAP) amplitudes and delayed F response and terminal latency compared to the control group. The sural nerve sensory conduction speed was slower and the sensory nerve action potential (SNAP) was found to be reduced. Among the 60 patients with acute brucellosis, 18% had sensorimotor peripheral neuropathy of widespread axonal character. Brucellosis can have many effects in the nervous system, including clinical or subclinical peripheral neuropathy in the peripheral nervous system. Brucellosis should be considered for differential diagnosis of patients with unexplained neurological and clinically relevant electrophysiological findings, especially in regions with endemic brucellosis.


Do columnar defects produce bulk pinning?
From magneto-optical imaging performed on heavy-ion-irradiated YBa(2)Cu(3)O(7-delta) single crystals, it is found that at fields and temperatures where strong single vortex pinning by individual irradiation-induced amorphous columnar defects is to be expected, vortex motion is limited by the nucleation of vortex kinks at the specimen surface. In the material bulk, vortex motion occurs through (easy) kink sliding. Depinning in the bulk determines the screening current only at fields comparable to or larger than the matching field, at which the majority of vortices is not trapped by an ion track.


Biological characterization of the virus causing leukoencephalitis and arthritis in goats.
This study describes the biological properties of a strain of virus isolated from tissues of a goat with leukoencephalomyelitis-arthritis. The agent is a retrovirus, having a virion-associated reverse transcriptase enzyme and an antigenic determinant(s) which cross-reacts with the p30 of visna-maedi viruses. Morphogenesis of the virus is also similar to visna virus in terms of virus assembly and the multinucleated giant cell formation which accompanies replication of the latter virus. Despite its cytopathogenic property the goat agent was not lytic in goat cell culture, causing instead a productive infection which persisted through multiple subcultures of the cells. The virus replicated incompletely in sheep cell cultures but could be rescued from the latter, weeks after inoculation, by co-cultivation with goat cells. Our data suggest that this strain of goat leukoencephalitis virus is a variant of the ovine retroviruses with a host range limited to the goat.


Effect of NQO1 C609T polymorphism on prostate cancer risk: a meta-analysis.
Some studies have found that the quinone oxidoreductase 1 (NQO1) SNP609 is associated with an increased risk for several malignancies. Numerous epidemiological studies have evaluated the association between the NQO1 C609T polymorphism and the risk of prostate cancer. However, the results of these studies have been conflicting. The aim of this study was to provide a more precise estimation of its relationship with prostate cancer using a meta-analysis. Electronic searches of several databases were conducted for all publications on the association between the NQO1 C609T polymorphism and prostate cancer before May 2013. The odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis. A total of six studies with 717 cases and 1,794 controls were included. No significant association was found between the NQO1 C609T polymorphism and prostate cancer risk in the total population analysis. In subgroup meta-analysis by ethnicity, a positive association was found in an Asian subgroup (T versus C, OR 1.337, 95% CI 1.014-1.763, P=0.040; TT + CT versus CC, OR 1.419, 95% CI 1.053-1.913, P=0.021). However, no significant association in any genetic models was observed in Caucasians. This meta-analysis showed that the NQO1 SNP609 T allele might be a risk factor for prostate cancer in Asians. However, this result should be verified by additional population-based studies with large sample sizes.


Sperm-oviduct interaction: induction of capacitation and preferential binding of uncapacitated spermatozoa to oviductal epithelial cells in porcine species.
After mating, inseminated spermatozoa are transported to the oviduct. They attach to and interact with oviductal epithelial cells (OEC). To investigate sperm-OEC interactions, we used chlortetracycline to study the capacitation status of boar spermatozoa in coculture with homologous OEC and cells of nonreproductive origin (LLC-PK1, porcine kidney epithelial cell line). Boar spermatozoa were cocultured with OEC and LLC-PK1 cells for 15, 60, 120, or 240 min. The proportion of capacitated spermatozoa in coculture with the isthmic and ampullar cells increased significantly (p < 0.05) during incubation. However, most spermatozoa in coculture with LLC-PK1 cells or blank (medium only) remained uncapacitated. In addition, preferential binding of uncapacitated, capacitated, or acrosome-reacted boar spermatozoa to OEC and the other cell type was investigated. Our approach was to vary the proportions of uncapacitated, capacitated, or acrosome-reacted boar spermatozoa in suspension using long preincubation and lysophosphatidylcholine treatment of semen prior to a very short incubation with OEC or LLC-PK1 cells. The results showed that the majority of spermatozoa that were bound to OEC or LLC-PK1 cells were uncapacitated and that a significant relationship existed between the relative proportion of uncapacitated spermatozoa in the control samples and those bound to LLC-PK1 cells (r2 = 0.43, p < 0.005). However, there was no correlation between the proportion of uncapacitated spermatozoa in the control samples and the proportion of those bound to isthmic or ampullar cells. In conclusion, the results clearly demonstrated the specific nature of the sperm-OEC interaction in the porcine species. This interaction is initiated by uncapacitated spermatozoa binding to OEC and is continued by the induction of capacitation in cocultured spermatozoa.


Impact of cardiovascular risk factors on medical expenditure: evidence from epidemiological studies analysing data on health checkups and medical insurance.
Concerns have increasingly been raised about the medical economic burden in Japan, of which approximately 20% is attributable to cardiovascular disease, including coronary heart disease and stroke. Because the management of risk factors is essential for the prevention of cardiovascular disease, it is important to understand the relationship between cardiovascular risk factors and medical expenditure in the Japanese population. However, only a few Japanese epidemiological studies analysing data on health checkups and medical insurance have provided evidence on this topic. Patients with cardiovascular risk factors, including obesity, hypertension, and diabetes, may incur medical expenditures through treatment of the risk factors themselves and through procedures for associated diseases that usually require hospitalization and sometimes result in death. Untreated risk factors may cause medical expenditure surges, mainly due to long-term hospitalization, more often than risk factors preventively treated by medication. On an individual patient level, medical expenditures increase with the number of concomitant cardiovascular risk factors. For single risk factors, personal medical expenditure may increase with the severity of that factor. However, on a population level, the medical economic burden attributable to cardiovascular risk factors results largely from a single, particularly prevalent risk factor, especially from mildly-to-moderately abnormal levels of the factor. Therefore, cardiovascular risk factors require management on the basis of both a cost-effective strategy of treating high-risk patients and a population strategy for reducing both the ill health and medical economic burdens that result from cardiovascular disease.


Long-stay patients in short-stay hospitals.
In 1980 and 1990, only 4-5 percent of patients in short-stay hospitals were hospitalized for more than 3 weeks. The number of discharges and days of care for these long-stay patients were lower in 1990 as compared with 1980, but they continued to use more than a quarter of all hospital days in 1990. Long-stay patients were more likely than all patients to be 65 years of age and over and have Medicare as their expected principal source of payment. For long-stay and all patients, private insurance covered smaller proportions of discharges and days of care, and Medicaid covered larger proportions in 1990 than in 1980. Long-stay patients were more likely than all patients to be discharged dead or transferred to other hospitals or nursing homes. Long-stay and all patients were more likely to be transferred at discharge in 1990 than in 1981. The Northeast Region had a larger proportion of long-stay patients than of all patients, and that proportion increased from 1980 to 1990. The proportion of long-stay discharges and days of care in the Midwest decreased during this period. In 1980 and 1990, more than 50 percent of the discharges and days of care for long-stay patients were for diseases of the circulatory system, mental disorders, neoplasms, or injury and poisoning. Despite the overall decreases in hospital use by long-stay patients, their discharges and days of care increased significantly from 1980 to 1990 for diagnoses such as septicemia, psychoses, and miscellaneous complications of surgical and medical care. Over time, decreases were seen in long-stay discharges and days of care for a variety of diagnostic categories, including malignant neoplasm of trachea, bronchus, and lung; diabetes mellitus; and fracture of the neck of the femur. Long-stay patients had a higher rate of procedures per 1,000 discharges in 1990 than in 1980, and a higher rate than all patients in both years. Approximately half of all the procedures performed on long-stay patients in 1980 and two-thirds in 1990 were miscellaneous diagnostic and therapeutic procedures, operations on the cardiovascular system, or operations on the digestive system. The rates of numerous procedures, especially diagnostic tests, increased for long-stay and all patients from 1980 to 1990.


MRI characterization of brown adipose tissue in obese and normal-weight children.
Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.


[Effect of the microiontophoretic injection of AMP and cAMP on the calcium current in the dialyzed neuron of the edible snail].
The effect of microiontophoretic injection of AMP and cAMP on the calcium current was investigated in dialyzed snail neurons. It was found that microiontophoretic injection of AMP restores calcium current after its "washout" during the dialysis and enhances its stability. In this case the current-voltage characteristic was shifted by 10 mV in the depolarizing direction. Under these conditions the iontophoretic cAMP injection into a dialyzed neuron produced a reversible decrease of the calcium current.


Microcredentials training in pharmacy practice and education: an exploratory study of its viability and pharmacists' professional needs.
Microcredentials (MCs) are short courses that certify/recognise an individual's achievement of specific skills or knowledge. Schools of pharmacy could be well-placed to contribute to the continuing professional development (CPD) of pharmacists through the inclusion of MCs training in their programs. This study aimed to explore pharmacy professionals' views on the need and viability of MC courses globally. Eleven semi-structured telephone interviews were conducted with pharmacy practitioners, policymakers, and academics across seven countries. The participants were selected using purposive sampling to explore information from varying pharmacy disciplines. Interviews were audio-recorded, transcribed verbatim, and analysed using a general inductive approach. Participants regarded MCs in pharmacy as an innovative idea, well-suited to the increasingly technology-driven world. They believe MCs provide easily accessible means of skills and knowledge acquisition that fulfils the needs of the pharmacy profession. MCs were also perceived as an alternative pathway of meeting the requirements of traditional CPD programmes. Many participants believe universities are well-suited to provide MCs; however, numerous challenges such as recognition, time and resources have been identified as potential barriers to enrolment and implementation. This study provides an insight into the views of pharmacy practitioners and academics on MCs, and their potential utility in pharmacy education and practice. The findings should help in the development of MCs that could be utilised by pharmacy practitioners around the world for CPD purposes. This study comes at a time when alternative models of teaching and learning are being explored as a direct result of the COVID-19 pandemic.


Shorter dosing intervals of sublingual immunotherapy lead to more efficacious treatment in a mouse model of allergic inflammation.
Current day practice of sublingual immunotherapy (SLIT) includes varying modalities of treatment that differ with regard to formulation, dosing and administration regimens. The aim of this study was to explore the importance of the dosing intervals in SLIT. The immunological effect of increased SLIT dosing frequency was tested in a mouse model of allergic inflammation. Mice sensitized to Phleum pratense (Phl p) were SLIT-treated with the same weekly cumulative dose administered with different administration frequencies. A SLIT sham-treated group was also included. All mice were challenged intra-nasally with Phl p extract following SLIT. Local and systemic cytokine production, eosinophil infiltration into airways and the development of Phl p-specific antibody responses were determined. Higher frequency of sublingual administration of allergen extract has a profound positive impact on the effect of SLIT, measured as induction of IgG and IgA antibodies. The once daily SLIT was the only treatment regimen being able to reduce all systemic Th2 cytokines and systemic IgE antibody responses when compared to sham-treated mice after the intra-nasal challenge period. The group receiving SLIT with the highest frequency of administration had the most pronounced effect of the treatment. In the same group, there was also a higher degree of protection against increase in IgE antibody levels after intra-nasal challenge with the allergen, our data demonstrate that a once daily regimen is more efficacious than regimens where SLIT, with the same weekly cumulative allergen dose, is administered with longer intervals but higher doses.


Chronic subdural hematoma: a comparison of recurrence rates following burr-hole craniostomy with and without drains.
To compare the rates of recurrence of chronic subdural hematoma following surgical evacuation by one of two methods, namely, using frontal and parietal burr holes without a drain or a single parietal burr hole with the addition of a subdural drain. This was a randomized controlled trial with two groups of 70 patients each. Patients in group I had two burr holes and those in group II had a single burr-hole. A subdural drain was placed for the second group, and this was removed 48-72 hours later. Patients were followed up for 3 months and symptomatic recurrences underwent re-exploration. 11 out of 70 patients in group I had recurrent hematomas requiring surgery while only two out of 70 patients in group II had symptomatic recurrences. The difference was statistically significant (p=0.0168). The use of a single burr hole with drain appears to be a safe and effective procedure for the treatment of chronic subdural hematoma.


Rapid determination of fumonisins in corn-based products by liquid chromatography/tandem mass spectrometry.
A simple, fast, and robust method was developed for the determination of fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3) in corn-based human food and animal feed (cornmeal). The method involves a single extraction step followed by centrifugation and filtration before analysis by ultra-performance liquid chromatographylelectrospray ionization (UPLC/ESI)-MS/MS. The LC/MS/MS method developed here represents the fastest and simplest procedure (<30 min) among both conventional HPLC methods and other LC/MS methods using SPE cleanup. The potential for high throughput analysis makes the method particularly beneficial for regulatory agencies and analytical laboratories with a high sample volume. A single-laboratory validation was conducted by testing three different spiking levels (200, 500, and 1000 ng/g for FB1 and FB2; 100, 250, and 500 ng/g for FB3) for accuracy and precision. Recoveries of FB1 ranged from 93 to 98% with RSD values of 3-8%. Recoveries of FB2 ranged from 104 to 108%, with RSD values of 2-6%. Recoveries of FB3 ranged from 94 to 108%, with RSD values of 2-5%.


Long-Term Mental Health Service Utilization Among Survivors of Testicular Cancer: A Population-Based Cohort Study.
Testicular cancer survivors may experience mental illness as a consequence of their cancer diagnosis and treatment. All incident cases of testicular cancer treated with orchiectomy in Ontario, Canada (2000-2010), were identified using the Ontario Cancer Registry. Cases were matched to controls in a 1:5 ratio on age and geography. Population-level databases were used to identify mental health service use episodes; outpatient use included visits to a general practitioner for a mental health concern or any visit to a psychiatrist. Negative binomial regression modeling was used to estimate the rate of mental health service use in the pretreatment (2 years prior until 1 month before orchiectomy), peritreatment (1 month before until 1 month after orchiectomy), and post-treatment periods (1 month after orchiectomy until end of follow-up). Rate ratios (RR) comparing cases with controls in the peri- and post-treatment periods were adjusted for baseline mental health service use. Two thousand six hundred nineteen cases of testicular cancer were matched to 13,095 controls. There was no baseline difference in the rate of mental health service use. Cases were significantly more likely than controls to have an outpatient visit for a mental health concern in the peritreatment (adjusted RR [aRR], 2.45; 95% CI, 2.06 to 2.92) and post-treatment periods (aRR, 1.30; 95% CI, 1.12 to 1.52). The difference in mental health service use persisted over a median follow-up of 12 years. In the postorchiectomy period, cases with baseline mental health service use were those most likely to use mental health services (aRR, 5.64; 95% CI, 4.64 to 6.85). Testicular cancer survivors use mental health services more often than healthy controls. Survivorship care plans that address the long-term mental healthcare needs of this population are needed.


Bone mass in prepubertal children: gender differences and the role of physical activity and sunlight exposure.
Retrospective studies have suggested that the prepubertal years may be an important window of opportunity to increase bone mass, but there have been few direct studies and little exploration of gender differences in this age group. In this study, we report the associations among physical activity measures, sunlight exposure, body composition, and bone mass in 8-yr-old children. We studied 330 children in 1996 (115 girls and 215 boys; response rate, 60%) who had previously taken part in a cohort study of cot death in 1988. They had measurement of anthropometrics (height, weight, and body composition), sunlight exposure (by questionnaire), and physical activity [questionnaire, muscle strength by dynamometry, and bicycle ergometric physical work capacity at a pulse of 170 beats/min (PWC170)]. Bone mineral density (BMD) was assessed at the spine, femoral neck, and total body by a Hologic QDR2000 densitometer. In females only, PWC170 [hip, 2.4%/quartile (95% confidence interval (CI), 0.3-4.5); spine, 1.7%/quartile (95% CI, 0.0-3.4); size adjusted] was associated with BMD, whereas in males only, BMD was associated with both sports participation (hip, 4.2% (95% CI, 1.1-7.3); spine, 4.3% (95% CI, 0.9-7.7)] and muscle strength [hip, 1.7%/quartile (95% CI, 0.0-3.4); but not spine; size adjusted]. Winter sunlight exposure was associated with BMD in girls [hip, 2.9%/category (95% CI, 0.7-5.0); spine, 3.6%/category (95% CI, 1.4-5.8)], but not in boys [hip, 0.3%/category (95% CI, -1.4 to +2.0); spine, 1.4%/category (95% CI, -0.7 to +3.5)]. Males and females were very similar in body size. However, males had higher size-adjusted BMD at the hip (9.6%; 95% CI, 6.9-14), whereas females had higher size-adjusted BMD at the spine (3.2%; 95% CI, 0.8-5.6%). In conclusion, this study has suggested that physical activity and exposure to sunlight are important in the bone mineralization of prepubertal male and female children. The magnitude of both gender and environmental differences in bone mass in this age group is substantial, suggesting that modification at this stage of life may influence peak bone mass and possibly fracture risk in later life.


CASC8 lncRNA Promotes the Proliferation of Retinoblastoma Cells Through Downregulating miR34a Methylation.
CASC8 lncRNA has been proven to be oncogenic in a variety of cancers, but its role in other types of cancer remains unclear. This study was to investigate the role of CASC8 in retinoblastoma (Rb). RT-qPCR was performed to determine the expression of CASC8 and miR34a in paired Rb and nontumor tissue. Overexpression of CASC8 and miR34a in Rb cells was achieved to evaluate the interaction between them. Methylation-specific PCR was used to analyze the effect of CASC8 overexpression on MIR34 A gene methylation. CCK8 assays were used to analyze cell proliferation. The results showed that CASC8 expression was upregulated and miR34a expression downregulated in Rb tissue. Moreover, miR34a expression was negatively correlated with the of CASC8 expression in Rb tissue. Overexpression of CASC8 decreased expression of miR34a and increased methylation of MIR 34A in Rb cells. In addition, overexpression of CASC8 reduced the inhibitory effects of miR34a on Rb-cell proliferation. CASC8 may promote Rb cell proliferation by downregulating miR34a methylation.


Possible relationship between birth weight and cancer incidence among young adults.
PURPOSE: Fetal and early life events have been associated with diseases that develop later in life. Low birth weight and the adult onset of hypertension, coronary heart disease, cerebrovascular disease, and non-insulin dependent diabetes have been identified. As well, associations with breast, ovarian, and prostate cancer to high birth weight have been found. An assessment of birth weight and cancer incidence was conducted in a cohort of black and white residents under the age of 46 years.METHODS: Cases were obtained from the Savannah River Region Health Information System cancer registry incident cases (1991-1995) and were limited to South Carolinians born in 1950 and later. Controls were obtained from birth certificate records by choosing the next two records after a cancer case record that matched on year of birth, race, and sex. Results were obtained for 117 cancer cases and 238 controls.RESULTS: After examining the birth distribution, the births were split into two groups based on mean birth weight among controls (3215 grams). Conditional logistic regression (CLR) showed that individuals with higher birth weights (> = 3215 g) were 1.65 (95% CI = 1.03-2.64) times more likely to be cancer cases than those with lower birth weights. When weights were categorized into 500 g increments, a CLR Score statistic showed there was a significant trend (p = 0.0006) of increasing proportion of cancer cases with increasing birth weight. Eight out of the eight cases of lymphoma had birth weights greater than 3579 g.CONCLUSIONS: The results of this preliminary study suggest that cancer incidence among the young may be associated with higher birth weights. One possible reason for this finding, which requires further investigation, might be that larger infants are exposed to higher levels of hormones and/or growth factor than smaller infants in utero that might increase the risk of certain cancers later in life. This may be suggestive of possible environmental factors affecting early growth. These findings support the need for additional study of this association.


Meltwater Pulse 1a drowned fringing reefs around Tahiti 15 000 years ago.
Reconstruction of postglacial sea-level rise using reef cores recovered from Tahiti during IODP Expedition 310 showed that the first major acceleration, known as Meltwater Pulse 1a (MWP-1a), was a 12-22 m rise in 340 years starting at 14.65 ka BP. Although it was reported that the pulse did not drown Tahitian reefs, the subsequent discovery of a fringing reef at the base of several cores implies that its timing, magnitude and impact require revision. Here, we report facies and paleodepth data from this reef, revise sea level, and revisit reef response. We find its reef crest is dominated by surf-adapted corals to a depth of 2.5 m and show that it retreated upslope over an approximately 1000-year interval from 16 ka. Reef development then apparently ceased at 15 ka at -106 m and remained absent for approximately 600 years, before resuming at 14.4 ka further upslope at -93 m. This absence is consistent with reef drowning and requires that MWP-1a had a smaller magnitude of 13.8 ± 1.3 m, and may have started 300 years earlier than previously reported. It confirms MWP-1a was a global event, drowning reefs on Tahiti as well as those in other oceans.


Acido-basic properties of proton pump inhibitors in aqueous solutions.
The pharmacological characteristics of proton pump inhibitors are related to their protolytic behavior estimated by their pK(a) values. Lansoprazole is a potent anti-acid drug from this group. Because of its poor stability a rapid spectrophotometric method was developed for the determination of its pK(a) values. Three pK(a) values were obtained: an acidic pK(a1) = 8.84 and two basic, pK(a2) = 4.15 and pK(a3) = 1.33. These pK(a) values were discussed from the point of lansoprazole structure and instability with the aim of locating basic and acidic moieties in the molecule of proton pump inhibitors. They were also compared with experimentally determined pK(a) values from the literature and with some pK(a) values calculated by different programs.


Characteristics of COVID-19 Pneumonia Survivors With Resting Normoxemia and Exercise-Induced Desaturation.
Survivors of coronavirus disease 2019 (COVID-19) associated pneumonia may show exercise-induced desaturation. We wondered whether these individuals show physiologic and symptom characteristics similar to individuals with chronic respiratory diseases with exercise-induced desaturation, namely COPD or interstitial lung diseases (ILD). We evaluated lung function, exercise capacity, and symptoms in these individuals compared with individuals with COPD or ILD and exercise-induced desaturation. Survivors of COVID-19 associated pneumonia (study individuals), normoxemic at rest with exercise-induced desaturation, underwent assessment of dyspnea, dynamic lung volumes, carbon monoxide diffusion capacity, and the 6-min walk test. Data of individuals with COPD or with ILD and exercise-induced desaturation were also retrospectively analyzed. FVC was lower in individuals with COVID-19 or ILD than in those with COPD. Individuals who had COVID-19 walked < 70% of predicted and, as a whole, had a 6-min walk test performance similar to individuals with ILD but walked significantly less, showed more severe leg fatigue and dyspnea during exercise, and more exercise-induced desaturation than individuals with COPD. Survivors of COVID-19 associated pneumonia, who were normoxemic at rest with exercise-induced desaturation, had alterations in lung function, exercise capacity, and symptoms similar to individuals with ILD but more severe than individuals with COPD and exercise-induced desaturation.


A Scalable, Easy-to-Deploy Protocol for Cas13-Based Detection of SARS-CoV-2 Genetic Material.
The COVID-19 pandemic has created massive demand for widespread, distributed tools for detecting SARS-CoV-2 genetic material. The hurdles to scalable testing include reagent and instrument accessibility, availability of highly trained personnel, and large upfront investment. Here, we showcase an orthogonal pipeline we call CREST (Cas13-based, rugged, equitable, scalable testing) that addresses some of these hurdles. Specifically, CREST pairs commonplace and reliable biochemical methods (PCR) with low-cost instrumentation, without sacrificing detection sensitivity. By taking advantage of simple fluorescence visualizers, CREST allows a binary interpretation of results. CREST may provide a point-of-care solution to increase the distribution of COVID-19 surveillance.


[Comorbidities in the elderly patient with cardiovascular disease].
Comorbid conditions are very common in elderly cardiovascular patients. Therefore, the management of comorbid patients has become an important health problem with the increasing elderly population. There are currently no recommendations in the treatment guidelines that are specific enough for comorbid conditions. In order to improve this patients quality of life holistic approach, good evaluation of risk-benefit ratio and possible drug interactions should be considered carefully.


Improved bioactivity of PAN-based carbon nanofibers decorated with bioglass nanoparticles.
Composite nanofibers composed of polyacrylonitrile (PAN)-based carbon nanofibers and bioactive glass (BG) nanoparticles have been prepared by electrospinning and in situ sintering. Morphology observation showed that the BG nanoparticles of size 20-50 nm were uniformly distributed on the surface of composite nanofibers with 350 nm average diameter after carbonization. Biological mineralization indicated the formation of apatite-like layer on the surface of composite nanofibers, in which the composition of carbonate hydroxyapatite was proved by FTIR and XRD analysis. Cell growth dynamics according to cellular morphology, CCK-8 assay, and alkaline phosphatase activity assay exhibited better cell adhesion, proliferation, and osteogenic induction of bone marrow-derived mesenchymal stem cells cultured on the composite nanofibers, which suggested the higher bioactivity of composite nanofibers compared to pure PAN-based carbon nanofibers.


Detection and treatment of amblyopia in children.
Refractive errors are a common cause of decreased visual acuity. They can be found in 2-4% of preschool children. If not discovered on time and not properly treated, they can lead to amblyopia and strabismus. The active participation of parents and paediatricians is of great importance in timely discovering and treatment of amblyopia. The most common causes of amblyopia are strabismus (50.1%) and refractive error (44.7%). The best treatment results are achieved in amblyopic children with strabismus. The cooperation of physicians of all specialties, above all paediatricians and ophthalmologists, as well as a good collaboration of parents based on their being well-informed, must exist in the process of timely diagnosing and treating of amblyopia.


Effect of process parameters upon the dopamine and lipid peroxidation activity of selected MIG welding fumes as a marker of potential neurotoxicity.
There is growing concern over the neurotoxic effects of chronic occupational exposure to metal fume produced by welding. Elevated iron and manganese levels in the brain have been linked to an increase in lipid peroxidation, dopamine depletion and predisposition to the development of a Parkinson's type condition in advanced cases. Chemical and toxicological analysis of selected welding fumes, generated by model processes, were used in order to evaluate their potential to release solutes that promote oxidation of dopamine and peroxidation of brain lipids in cell free assays. This study compared the effect of shield gas, electrode type and voltage/currect upon the dopamine and brain lipid peroxidation potential of selected welding fume, obtained from metal inert gas (MIG) welding systems. Overall, fume extracts were found to enhance dopamine oxidation and inhibit lipid peroxidation. Significant differences were also found in the oxidising potential of fume generated under differing process conditions; it may therefore be possible to determine the potential neurotoxicity of fumes using this system.


CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway.
Liver fibrosis, with subsequent development of cirrhosis and ultimately portal hypertension, results in the death of patients with end-stage liver disease if liver transplantation is not performed. Hepatic stellate cells (HSCs), central mediators of liver fibrosis, resemble tissue pericytes and regulate intrahepatic blood flow by modulating pericapillary resistance. Therefore, HSCs can contribute to portal hypertension in patients with chronic liver disease (CLD). We have previously demonstrated that activated HSCs express functional chemokine receptor, CXCR4, and that receptor engagement by its ligand, CXCL12, which is increased in patients with CLD, leads to further stellate cell activation in a CXCR4-specific manner. We therefore hypothesized that CXCL12 promotes HSC contraction in a CXCR4-dependent manner. Stimulation of HSCs on collagen gel lattices with CXCL12 led to gel contraction and myosin light chain (MLC) phosphorylation, which was blocked by addition of AMD3100, a CXCR4 small molecule inhibitor. These effects were further mediated by the Rho kinase pathway since both Rho kinase knockdown or Y-27632, a Rho kinase inhibitor, blocked CXCL12 induced phosphorylation of MLC and gel contraction. BAPTA-AM, a calcium chelator, had no effect, indicating that this pathway is calcium sensitive but not calcium dependent. In conclusion, CXCL12 promotes stellate cell contractility in a predominantly calcium-independent fashion. Our data demonstrates a novel role of CXCL12 in stellate cell contraction and the availability of small molecule inhibitors of the CXCL12/CXCR4 axis justifies further investigation into its potential as therapeutic target for portal hypertension.


Hepatic lipase as a focal point for the development and treatment of coronary artery disease.
Recent epidemiological evidence suggests that although lowering low-density lipoprotein (LDL) cholesterol is important in decreasing cardiovascular disease morbidity and mortality, it accounts only for part of the coronary artery disease (CAD) improvement with lipid-lowering therapy. In the last decade, it has become evident that the atherogenicity of LDL particles is associated not only with their plasma levels, but also with their size and density. The presence of small, dense LDL particles is associated with a three fold increase in CAD risk. Hepatic lipase (HL), a key enzyme in the formation of small, dense LDL particles, modulates their phospholipid and triglyceride contents. The higher the HL activity, the smaller, denser, and more atherogenic the resulting lipoprotein particle. It is, therefore, plausible to hypothesize that at least part of the CAD benefits observed in the recent CAD-prevention pharmacological trials, which are not accounted for by the decrease in LDL-C (LDL-cholesterol), might be explained by a pharmacological effect on LDL size and density, possibly mediated by changes in hepatic lipase activity. By studying patients with dyslipidemia and CAD, we have been able to provide strong evidence that regression of coronary atherosclerosis results from at least two independent effects of lipid-lowering therapy on lipoprotein metabolism: the well known one that leads to changes in LDL-C and apo B levels, and a new pathway of HL-mediated improvement in LDL buoyancy. Finally, HL activity and LDL density appear to be significantly affected by the presence of a common C-->T substitution at position -514 with respect to the transcription start site of the HL gene, raising the possibility that the -514 C-->T polymorphism may significantly contribute to differences in individual CAD response to lipid-lowering treatment, as seen in the recent major primary and secondary CAD-prevention clinical trials.


Concordance of white matter and gray matter abnormalities in autism spectrum disorders: a voxel-based meta-analysis study.
There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.


Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU).
This study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation. Patients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation. A total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1-2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]). Female patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries. Level III.


Substantial light woodland and open vegetation characterized the temperate forest biome before Homo sapiens.
The extent of vegetation openness in past European landscapes is widely debated. In particular, the temperate forest biome has traditionally been defined as dense, closed-canopy forest; however, some argue that large herbivores maintained greater openness or even wood-pasture conditions. Here, we address this question for the Last Interglacial period (129,000-116,000 years ago), before Homo sapiens-linked megafauna declines and anthropogenic landscape transformation. We applied the vegetation reconstruction method REVEALS to 96 Last Interglacial pollen records. We found that light woodland and open vegetation represented, on average, more than 50% cover during this period. The degree of openness was highly variable and only partially linked to climatic factors, indicating the importance of natural disturbance regimes. Our results show that the temperate forest biome was historically heterogeneous rather than uniformly dense, which is consistent with the dependency of much of contemporary European biodiversity on open vegetation and light woodland.


Assessing assistive technology requirements in children with written language disorders. A decision tree to guide counseling.
Children with a written language disorder are sometimes dependent upon help from others for their schoolwork. A computer can be a way to circumvent this difficulty. Various software programs and plug-in peripheral devices are available, some of which specifically target the needs of these young people. There is no consensus, however, with regard to how best to counsel parents and children with regard to these tools. Furthermore, written language disorders and existing technical supports are not always clearly understood. In many cases, healthcare and teaching professionals have only limited knowledge of the potentially specific advantages for patients with written language disorders. A child's full integration into daily activities and school life can be hampered by counseling that was inadequately tailored or by a lack of support in using this equipment. Joint consultations involving both an occupational and a speech therapist have been set up in our department to improve counseling with regard to technical supports. Using our daily practice as a basis, we have developed a decision tree that we see as a necessary tool for helping professionals make the most appropriate practical choices.


Stimulation of diuresis and natriuresis by renomedullary infusion of a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase.
The renal medulla, considered critical for the regulation of salt and water balance and long-term blood pressure control, is enriched in anandamide and two of its major metabolizing enzymes, cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH). Infusion of anandamide (15, 30, and 60 nmol·min-1·kg-1) into the renal medulla of C57BL/6J mice stimulated diuresis and salt excretion in a COX-2- but not COX-1-dependent manner. To determine whether endogenous endocannabinoids in the renal medulla can elicit similar effects, the effects of intramedullary isopropyl dodecyl fluorophosphate (IDFP), which inhibits the two major endocannabinoid hydrolases, were studied. IDFP treatment increased the urine formation rate and sodium excretion in a COX-2- but not COX-1-dependent manner. Neither anandamide nor IDFP affected the glomerular filtration rate. Neither systemic (0.625 mg·kg-1·30 min-1 iv) nor intramedullary (15 nmol·min-1·kg-1·30 min-1) IDFP pretreatment before intramedullary anandamide (15-30 nmol·min-1·kg-1) strictly blocked effects of anandamide, suggesting that hydrolysis of anandamide was not necessary for its diuretic effect. Intramedullary IDFP had no effect on renal blood flow but stimulated renal medullary blood flow. The effects of IDFP on urine flow rate and medullary blood flow were FAAH-dependent as demonstrated using FAAH knockout mice. Analysis of mouse urinary PGE2 concentrations by HPLC-electrospray ionization tandem mass spectrometry showed that IDFP treatment decreased urinary PGE2 These data are consistent with a role of FAAH and endogenous anandamide acting through a COX-2-dependent metabolite to regulate diuresis and salt excretion in the mouse kidney.


Prokaryotic diversity of a non-sulfide, low-salt cold spring sediment of Shawan County, China.
The prokaryotic diversity of a non-sulfide, low-salt cold spring sediment was investigated by constructing bacterial and archaeal clone libraries of the 16S rRNA gene. 241 bacterial clones were screened, which could be grouped into 86 ribotypes, based on restriction fragment length polymorphism (RFLP) analysis. These were divided into 11 phyla (Actinobacteria, Acidobacteria, Bacteroidetes, Chlorobi, Cyanobacteria, Firmicutes, Gemmatimonadetes, Nitrospirae, Proteobacteria, Planctomycetes and Verrucomicrobia). Of these, Acidobacteria and Proteobacteria were the most dominant, representing 48% and 25% of the total bacteria clone library, respectively. For the archaeal clone library, 121 positive clones were screened and 22 ribotypes were determined. BLAST analysis indicated that all ribotypes were affiliated with the phylum Crenarchaeota. Phylogenetic analysis classified them into three subgroups (Groups I-III). Groups I and III, belonging to the Soil-Freshwater-subsurface group and Marine group I, respectively, were the dominant groups, representing 50% and 47% of the library, respectively. Of them, 20% of ribotypes were related to the cold-loving Crenarchaeota. These findings show that bacteria in spring sediments are more diverse than are archaea; in addition, the spring harbors a large number of novel bacterial and archaeal species and maybe exist novel lineages.


Visual field defects associated with vigabatrin therapy.
To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.


[Measurements of the activity of the coagulation factors VIII:C, IX,XI, and XII in cats].
Using an optimized test, reference ranges were established for the activity of the coagulation factors VIII:C (72-124%), IX (81-130%), XI (69-134%) and XII (51-142%) in the cat (n = 58 cats, 2.5-97.5% quantile). Compared to a reference curve prepared by using a cat-pool plasma (n = 50), the factor VIII:C activity in humans (commercial human reference plasma) was 7.6%, i.e. the factor VIII:C activity in cats was 13 fold higher than in humans. The values for the factors IX, XI and XII depended distinctly on the dilution step of the human plasma. The activity of the cat in relation to humans was approximately 90% (factor IX), 170% (factor XI) and 135% (factor XII). Two clinically healthy cats who were conspicuous pre-operative because of a distinctly prolonged, activated partial thromboplastin time showed a decreased factor XII activity.


Kyphoplasty in osteoporotic vertebral compression fractures--guidelines and technical considerations.
Osteoporotic vertebral compression fractures are a menace to the elderly generation causing diminished quality of life due to pain and deformity. At first, conservative treatment still is the method of choice. In case of resulting deformity, sintering and persistent pain vertebral cement augmentation techniques today are widely used. Open correction of resulting deformity by different types of osteotomies addresses sagittal balance, but has comparably high morbidity. Besides conventional vertebral cement augmentation techniques balloon kyphoplasty has become a popular tool to address painful thoracic and lumbar compression fractures. It showed improved pain reduction and lower complication rates compared to standard vertebroplasty. Interestingly the results of two placebo-controlled vertebroplasty studies question the value of cement augmentation, if compared to a sham operation. Even though there exists now favourable data for kyphoplasty from one randomised controlled trial, the absence of a sham group leaves the placebo effect unaddressed. Technically kyphoplasty can be performed with a transpedicular or extrapedicular access. Polymethyl methacrylate (PMMA)-cement should be favoured, since calcium phosphate cement showed inferior biomechanical properties and less effect on pain reduction especially in less stable burst fractures. Common complications of kyphoplasty are cement leakage and adjacent segment fractures. Rare complications are toxic PMMA-monomer reactions, cement embolisation, and infection.


Does base excess predict kidney injury in neonates with hypoxic-ischemic encephalopathy?
In neonates with hypoxic-ischemic encephalopathy (HIE), we studied the correlation between cord blood base excess (BE) and kidney function. Among 225 infants, 29 % had oliguria. BE levels differed significantly between oliguric and non-oliguric infants (p < 0.01), with a negative correlation to kidney injury (r = -0.544, p < 0.01). BE < -18 had 85 % specificity and 76 % sensitivity in predicting kidney injury (AUC = 0.88). These findings suggest BE as a valuable indicator of impending kidney injury in HIE infants, though underlying mechanisms may vary.


Onset and migration of spiral troughs on Mars revealed by orbital radar.
The landscape of the north polar layered deposits of Mars (NPLD) is dominated by a pinwheel array of enigmatic spiral troughs. The troughs have intrigued planetary scientists since the Mariner 9 spacecraft returned the first close-up image in 1972, but conclusive evidence of their origin has remained elusive. Debate continues regarding all aspects of the troughs, including the possibility that they have migrated, their age in relation to the current NPLD surface, and whether they are fundamentally erosional or constructional features. The troughs are probably related to climatic processes, yet the nature of this relationship has remained a mystery. Previous data characterizing only the exposed NLPD surface were insufficient to test these hypotheses. Here we show that the central spiral troughs initiated after deposition of three-quarters of the NPLD, quickly reached a stable morphology and migrated approximately 65 kilometres poleward and 600 metres in altitude over the past two million years or so. Our radar stratigraphy rules out hypotheses of erosional incision post-dating deposition, and instead largely validates an early hypothesis for constructional trough migration with wind transport and atmospheric deposition as dominant processes. These results provide hard constraints for palaeo-climate models and a new context for evaluating imagery, spectral data, and now radar sounding data, the better to understand the link between orbital parameters and climate, the role of climate in shaping the polar ice of Mars, and eventually, the age of the polar deposits themselves.


UV activates growth factor receptors via reactive oxygen intermediates.
Exposure of mammalian cells to UV irradiation induces rapid and transient expression of early growth response-1 gene (Egr-1) encoding a transcription factor that plays a role in cell survival. These signals from the irradiated cell surface are likely to involve more than one pathway, and we show here that an essential pathway involves activation of several growth factor receptors by reactive oxygen intermediates (ROI). UVC irradiation causes the tyrosine phosphorylation of EGF receptor (EGFR) in mouse NIH 3T3 fibroblasts and HC11 mouse mammary cells. EGFR activation by irradiation of cells is abrogated by suramin, by antioxidants, and by the presence of a dominant negative EGFR. UV induces the formation of complexes between activated EGFR and SOS, Grb2, PLC gamma, and SHC that can be precipitated with antibodies to EGFR. The activation of EGFR by UV is mimicked by H2O2, suggesting that ROI may function upstream of EGFR activation. Our observations support the hypothesis that ROI and growth factor receptors operate in the early steps of the UV signal that lead to the enhanced expression and activity of Egr-1.


PET versus SPECT for determining myocardial tissue viability using fluorine-18-fluorodeoxyglucose.
The U.S. Food and Drug Administration regulates the manufacture and distribution of 18F-FDG. Acquisition and use of this radiopharmaceutical for myocardial imaging at our institution required approval by our Institutional Review Board. Our initial objective was to present a scientific validation for use of this radiopharmaceutical in adjudicating the "viable versus scarred myocardium question," using either a PET scanner or a gamma camera equipped with 511-keV collimators. We believe that our nuclear medicine colleagues who find themselves in a similar business/legal situation regarding the acquisition and use of 18F-FDG will find this review useful. We reviewed the literature to document the efficacy of 18F-FDG, in general, in assessing myocardial viability. We then did a literature-based comparison of PET scanner methodology versus modified gamma camera methodology for imaging 18F-FDG emissions. Imaging 18F-FDG with a modified gamma camera appears to be an effective alternative to imaging with a standard PET camera for assessing myocardial viability.


Myositis ossificans progressiva. Clinical features of eight patients and their response to treatment.
The clinical features of eight patients with myositis ossificans progressiva are described and the effects of treatment with the diphosphonate EHDP, together with surgical removal of ectopic bone, are assessed. Early correct diagnosis remains unusual, mainly because the significance of the short great toes is unrecognised, and because myositis may be mistaken for bruising, sarcoma or mumps. The diphosphonate disodium etidronate (EDHP) was given to all patients in an attempt to suppress calcification of new lesions; in five of them ectopic bone was removed during the treatment. EHDP sometimes delayed the mineralisation of newly formed bone matrix after surgical removal but this delay could not be predicted. The variable effect of EHDP may depend particularly on the amount absorbed and on the activity of new bone formation.


Determining the initial impact of rear-end collisions by trace evidence left on the vehicle from tires: A case report.
If an automobile happens to crash into the back of another vehicle while travelling at high speeds, both vehicles will be seriously damaged. Consequently, it is not easy to reconstruct the initial collision state between the two vehicles or determine whether or not the risk perception of the driver is normal. The entire picture of the accident cannot be fully understood and thus clarifying the relevant legal responsibility is difficult. The trace evidence of tires, such as pattern, direction, and impression examination as well as other characteristics, can be carefully observed and used as evidence in accident reconstruction. A case report of a fatal collision involving a bus crashing into the frame of a full trailer on a freeway is examined in this study. The police agency used the characteristics of the trace evidence of the bus tires to reconstruct the initial collision state of the two vehicles to clarify the cause of the accident, and these determination guidelines can be used by police while handling similar cases in the future. This case uses new information regarding the initial collision state of road traffic accidents for reconstruction and provides knowledge and interest for the forensic community.


Neurotrophic activity in the adult rat hippocampal formation: regional distribution and increase after septal lesion.
Conditioned medium prepared from slices of the rat hippocampal formation contains an agent that shares the following properties with nerve growth factor (NGF): it promotes neurite growth from embryonic sympathetic ganglia in vitro; and it is inhibited by affinity-purified antibody against mouse submaxillary gland 2.5 S NGF. The NGF-like growth-promoting activity is regionally distributed within the hippocampal formation: the activity is consistently higher in the dentate gyrus-CA3 region than in the CA1 region. Furthermore, the level of activity is significantly increased within 1 week after a medial septal lesion, and, in the dentate-CA3 region, the increased level of activity is maintained for at least 4 weeks after the lesion. Control lesions that fail to interrupt the septohippocampal innervation, but cause equally extensive damage to nearby regions of the central nervous system, do not cause increased levels of activity in the hippocampal formation. These results provide substantial evidence linking the NGF-like agent in hippocampal conditioned medium to the sprouting of sympathetic axons into the dentate gyrus-CA3 region of the hippocampal formation after a medial septal lesion in vivo.


[Growth of obligate-thermophilic bacteria on a medium with paraffin].
The obligate thermophilic bacteria Bacillus stearothermophilus (the optimal growth temperature 55-73 degrees C) and Thermus ruber (the optimal growth temperature 60 degrees C) were isolated from hot water springs of the Kunashir Island for the first time in a liquid mineral medium with paraffin. Some of the bacteria belonging to Bac. stearothermophilus grew at a high rate in a liquid medium with paraffin (strain 16); other strains (12a, 12b) were capable of growing only together with Thermus ruber; some strains could grow only on a solid medium with paraffin (strains 14a, 14b).


Delta-aminolevulinic acid dehydratase polymorphism and risk of brain tumors in adults.
The enzyme delta-aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0-2.6], with the association appearing stronger in males (OR = 3.5; 95% CI, 1.3-9.2) than in females (OR = 1.2; 95% CI, 0.7-2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma.


Population genomics of Populus trichocarpa identifies signatures of selection and adaptive trait associations.
Forest trees are dominant components of terrestrial ecosystems that have global ecological and economic importance. Despite distributions that span wide environmental gradients, many tree populations are locally adapted, and mechanisms underlying this adaptation are poorly understood. Here we use a combination of whole-genome selection scans and association analyses of 544 Populus trichocarpa trees to reveal genomic bases of adaptive variation across a wide latitudinal range. Three hundred ninety-seven genomic regions showed evidence of recent positive and/or divergent selection and enrichment for associations with adaptive traits that also displayed patterns consistent with natural selection. These regions also provide unexpected insights into the evolutionary dynamics of duplicated genes and their roles in adaptive trait variation.


Status of infection control policies and organisation in European hospitals, 2001: the ARPAC study.
Patient safety in hospital care depends on effective infection control (IC) programmes. The Antimicrobial Resistance Prevention and Control (ARPAC) study assessed the organisation, components and human resources of IC programmes in European hospitals. A questionnaire survey of policies and procedures implemented in 2001 for the surveillance and control of nosocomial infection and antibiotic resistance was completed by 169 acute-care hospitals from 32 European countries, categorised by five geographical regions. A formal IC programme existed in 72% of hospitals, and a multidisciplinary IC committee was operational in 90%. Trained IC nurses (ICNs) were present in 80% of hospitals (ranging from 54% in south-east and central-eastern Europe, to 100% in northern Europe), whereas 74% had one or more trained IC doctors (ICDs) (ranging from 46% in south-east Europe to 84% in western Europe). Median staffing levels were 2.33 ICNs/1,000 beds and 0.94 ICDs/1,000 beds. The intensity of IC programmes scored higher in centres from northern and western Europe than from other European regions. Written guidelines promoted hand hygiene for healthcare workers in 89% of hospitals, education in 85%, and audit in 46%. Guidelines recommended use of alcohol-based solutions (70%) and/or medicated/antiseptic soap (43%) for decontamination of non-soiled hands. Use of alcohol-based solutions varied according to region, from 41% in southern Europe to 100% in northern Europe, compared with use of medicated soap from 77% in southern Europe to 11% in northern Europe (p < 0.01). These findings showed that IC programmes in European hospitals suffer from major deficiencies in human resources and policies. Staffing levels for ICNs were below recommended standards in the majority of hospitals. Education programmes were incomplete and often not supported by audit of performance. Hand hygiene procedures were sub-standard in one-third of centres. Strengthening of IC policies in European hospitals should be a public health priority.


Digestive anatomy, physiology, resting metabolism and methane production of captive maras (Dolichotis patagonum).
The digestive physiology of maras (Dolichotis patagonum) has not been investigated in detail. Maras have a particular limb anatomy facilitating a unique cursoriality among rodents. This may also have led to additional adaptations such as a reduced volume of the gastrointestinal tract. We performed macroanatomical measurements of, and determined mean particle size along, the digestive tract of 10 semi-free-ranging animals (7.04 ± 1.05 kg). Additionally, we measured CH4 emission in five captive animals (7.67 ± 0.98 kg) fed a diet of pelleted lucerne, and measured food intake, digestibility, and digesta mean retention time (MRT) of a solute and three particle markers (fed at <2, 10 and 20 mm particle size). The digestive tract contents represented 11.1 ± 1.4% of body mass, similar to other mammals and rodents, and there was slight indication of selective small particle retention in the caecum. Secondary peaks in marker elimination patterns suggested the possibility of caecotrophy. The MRTs were 15.4 h for the solute and 13.6 h, 13.3 h and 13.3 h for the three particle markers, respectively. At a dry matter intake of 61 ± 12 g kg body mass-0.75 d-1, the maras digested organic matter and neutral detergent fibre to 48 ± 8% and 34 ± 10%, respectively, which is in the lower range of results from horses fed on a diet with a similar fibre content. The respiratory quotient (CO2/O2) was 0.93 ± 0.03, the resting metabolic rate 346 ± 35 kJ kg body mass-0.75 d-1, and CH4 emissions averaged at 3.85 ± 0.47 L d-1 and 14.5 ± 5.2 L per kg dry matter intake; this at a CH4/CO2 ratio of 0.042 ± 0.004. Thus, the methane yield was of a magnitude expected for a hypothetical ruminant of this body mass. The results are consistent with the general understanding of hystricomorph rodent digestive physiology, including caecotrophy, but do not indicate a reduction of digestive capacity to support cursoriality. These results, and those obtained from other hystricomorph rodents, suggest that CH4 production may be more prominent in rodents than previously thought.


Elastosis and fragmentation of fibers of the elastic system in fatal asthma.
Fibers of the elastic system (FES) are important in regulating airway patency and lung elastic recoil. Their possible role in modulating bronchoconstriction is not fully understood. Chronic inflammation and mechanical stretching present in asthma could lead to conformational alterations in the FES, participating in the mechanism of airway remodeling observed in this disease. In airway mucosa, two layers of FES are discernible: one superficial network, attached to the basement membrane, and a deeper network, lying close to the airway smooth muscle. Using image analysis and conventional morphometry, we analyzed airway content of FES in central and peripheral airways in 31 cases of fatal asthma and in 10 control lungs. Slides were stained using the oxidized resorcin-fuchsin method. Optical analysis revealed fragmentation of the FES in the superficial network of central asthmatic airways. Morphometry showed the presence of elastosis in central asthmatic airways when the entire thickness of the mucosa was considered. In the superficial network elastic fiber content was significantly decreased. These results indicate that FES participate in airway remodeling in asthma. We also suggest that disrupture of fiber attachments at the basement membrane in the superficial layer could impair the mechanism of airway recoil in asthmatic patients.