Negative effect of heat sterilization on the free amino acid concentrations in infant formula.
Infant formulas are often heat sterilized in hospitals where water contamination or nosocomial infection is a concern, but there are few studies of the effect of high heat on the nutritional value of infant formula. In particular, the effect of heat sterilization on free amino acid (FAA) concentrations is seldom discussed. In view of the importance of these nutrients for infant growth, we investigated the FAA concentrations of infant formula after heat sterilization. Powdered infant formulas were reconstituted with hot water (80 degrees C) in glass bottles and placed in an autoclave for 5 min at 105 degrees C and 5600 kg/m2 of pressure. Additional samples of formula were prepared by conventional methods to serve as controls. After autoclaving, we measured the FAA concentrations with ion exchange chromatography. The results were compared with those obtained after conventional preparation. We found a 19.5% lower amount of total protein after autoclaving compared with conventional preparation. Concentrations of total FAA were significantly lower after autoclaving (696.5 +/- 101.4 vs 899.4 +/- 152.2 micromol/l, P = 0.01). The concentrations of individual amino acids were also lower in autoclaved infant formulas, with differences ranging from -4.1 to 71.5% (mean 22.6%). Concentrations of certain amino acids were more than 30% lower, such as valine (71.5%), citrulline (61.1%), glutamine (60.6%), ethanolamine (54%), and lysine (39.2%). Both essential and nonessential amino acids were similarly affected by autoclaving, 28.17 and 27.13%, respectively, lower than in controls (P = 0.37). The concentration of ammonia was significantly higher after autoclaving (645.2 +/- 76.2 vs 393.2 +/-140.7 micromol/l, P = 0.0003). However, the urea level was significantly lower after autoclaving than after conventional preparation (1110.8 +/- 162.7 vs 1426.5 +/- 209.5 micromol/l, P = 0.0004). The accumulation of ammonia may reflect degradation of protein and amino acids. Autoclaving clearly results in decreased concentrations of FAA in infant formula. The increased concentration of ammonia after autoclaving is of concern if it leads to deleterious effects.


Spatiotemporal dynamics of immature culicines (subfamily Culicinae) and their larval habitats in Mwea Rice Scheme, Kenya.
An ecological study was conducted at three study sites in Mwea Rice Scheme, Kenya to identify the diverse aquatic habitats in which culicine mosquitoes thrived and to explore the best strategies for mosquito control in the area. During the 11-month study period, ten habitat categories and 11 culicine species mainly dominated by Culex quinquefasciatus (72.0%) and Culex annulioris (17.9%) were identified from pupae and late instars larval samples. Two of the 11 culicine species, Ficalbia (Mimomyia) plumosa and Uranotaenia spp., have not been reported previously in the study area. Rurumi had more habitat types than either of the other study sites but the least number of mosquito species. In contrast, Karima had the least number of habitat types but significantly higher density of early instars than the other study sites. The relative abundance of late instars and pupae did not vary significantly among study sites. The contribution of different habitat types to larval production varied markedly between seasons and among study sites. Paddies and canals were perennial contributors of culicine mosquito larvae while the other habitat types were important mainly during the wet season. Some habitat types such as ditches, seeps, marshes, and fishpond were absent in some study sites but of great significance in other study sites. C. quinquefasciatus was positively associated with turbidity at all study sites and also negatively associated with emergent vegetation and distance to the nearest homestead in Karima, emergent vegetation in Kiuria, and other aquatic invertebrates in Rurumi. C. annulioris was positively associated with emergent vegetation at all study sites and also with depth in Kiuria. These findings indicate that besides rice fields and associated habitats, a diversity of other aquatic habitats contribute to culicine adult mosquito production in the study area and that environmental factors that determine the occurrence of a particular mosquito species may vary significantly even among areas of similar land use. This information is critical when designing and implementing mosquito larval control programs.


Development neurobiology of the stress response: multilevel regulation of corticotropin-releasing hormone function.
The ability to respond to adverse environmental cues is present in the neonatal and infant rat, although in an immature form: A number of laboratories have demonstrated stress-induced elevations of plasma glucocorticoids during the first two postnatal weeks. The limbic and hypothalamic mechanisms controlling the hormonal stress-response during this period are not fully understood and are, therefore, the focus of this report. Both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin contribute to the release of ACTH from the pituitary in the adult. The relative roles of these two peptides during the neonatal (first week) and infant (second week) developmental period, are controversial. Evidence is presented that argues strongly for a major role for CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased with cold stress by ninth postnatal day, but not during the first postnatal week. Further, down-regulation of CRH gene expression by glucocorticoids (GC) constitutes a critical "shut-down" mechanism for the hormonal stress response. In vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH synthesis during the first postnatal week are described. CRH-mediated neurotransmission, in both the endocrine and neuronal effector arms of the response to stress may be modulated via alteration of receptor number. The first member of the CRH receptor family, CRF1, probably mediates the neuroendocrine effects of CRH. The developmental profile of CRF1-mRNA reveals several distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at 180% of adult values). In cortex, a steady decline from high postnatal day 2 levels results in adult levels by 12. These findings demonstrate distinct, regional, age-specific control of the synthesis of CRF1. Receptor expression profile may provide important information regarding modulation of the age-specific roles of CRH in different regions. For example, a high ratio of hippocampus/amygdala receptors may preferentially activate negative hippocampal input to the hypothalamus during the neonatal period. Additionally, increased CRH receptor mRNA in the infant compared with the adult provides a mechanism for enhanced excitatory effect of the peptide at this age. In conclusion, increasing evidence exists for multiple control points of the early postnatal response and adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity to GC feedback, and the abundance and distribution of at least two distinct CRH receptors in the limbic central nervous system and the pituitary are developmentally regulated. All serve as control points permitting an effective endocrine, autonomic, and behavioral response to stressful environmental cues.


Recent advances in the treatment of deafness.
By the utilization of reconstructive procedures (tympanoplasty), middle ear and mastoid infections can be eliminated with the acquisition of a clean, dry ear in about nine out of 10 cases, and hearing can be improved in about half of the patients so treated. Incapacitating attacks of Ménière's disease can be successfully treated in selected cases by labyrinthectomy, ultrasound destruction of the vestibular system, or streptomycin treatment. With the advent of the transistor, improved power packs and miniaturization, hearing aids have become more acceptable to patients with sensorineural hearing losses. The most successful procedure for the management of otosclerosis is the stapedectomy operation.


Stabilometric parameters analysis in children with visual disorder.
Although postural changes were already reported in blind adults, no previous study has investigated postural stability in blind children. Moreover, there are few studies which used a stabilometric instrument to measure postural balance. In this study we evaluated stabilometric paramaters in blind children. We evaluated children between 7 to 12 years old, they were divided into two groups: Blind (n = 11) and age-matched control (n = 11) groups by using computerized stabilometry. The stabilometric examination was performed taking the gravity centers displacement of the individual projected into the platform. Thirthy seconds after the period in which this information was collected, the program defined a medium-pressure center, which was used to define x and y axes displacement and the distance between the pressure center and the platform center. Furthermore, the average sway rate and the body sway area were obtained by dividing the pressure center displacement and the time spent on the task; and by an ellipse function (95% percentille), respectively. Percentages of anterior, posterior, left and right feet weight also were calculated. Variables were compared by using the Student's t test for unpaired data. Significance level was considered for p <0.05. Displacement of the x axis (25.55 ± 9.851 vs. -3.545 ± 7.667; p <0.05) and average sway rate (19.18 ± 2.7 vs. -10.55 ± 1.003; p <0.001) were increased in the blind children group. Percentage of left foot weight was reduced (45.82 ± 2.017 vs. 52.36 ± 1.33; p <0.05) while percentage of right foot weight was increased (54.18 ± 2.17 vs. 47.64 ± 1.33; p <0.05) in blind children. Other variables did not show differences. Blind children present impaired stabilometric parameters.


Eosinophilic ulcer of the oral mucosa versus squamous cell carcinoma.
Eosinophilic ulcer of the oral mucosa is a benign, rare, self-limiting, and generally asymptomatic lesion that shows spontaneous regression. Its etiopathogenesis is still uncertain, but trauma seems to play a fundamental role in the occurrence of this tumor. Clinically, this lesion manifests as an isolated ulcer preferentially located on the tongue, showing a raised and indurated border in addition to a white or yellowish bed. Microscopically, eosinophilic ulcer is characterized by an inflammatory infiltrate rich in leukocytes. Since these lesions show spontaneous cure, treatment becomes unnecessary, but in certain cases, cure is obtained by excision of the ulcer during biopsy. In these cases, the differential diagnosis with squamous cell carcinoma is made. A case of very small eosinophilic ulcer of the oral mucosa located on the lateral border of the tongue is presented.


Vitamin D receptor BsmІ polymorphism and ovarian cancer risk: a meta-analysis.
Vitamin D receptor (VDR) FokI polymorphism has been reported to influence ovarian cancer (OC) susceptibility, but the association between VDR BsmI polymorphism and OC risk remains controversial. To clarify the relationship between them, we performed a meta-analysis. A comprehensive literature search was conducted to examine all the eligible studies of VDR BsmI polymorphism and OC risk. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association. Seven separate comparisons consisting of 1977 OC cases and 2832 healthy controls were included in our meta-analysis. The pooled analyses showed no significant association between VDR BsmI G/A polymorphism and OC in all of the comparisons (AA vs GG: OR, 1.01; P = 0.919; AG vs GG: OR, 1.12; P = 0.087; AG + AA vs GG: OR, 1.10; P = 0.146; AA vs AG + GG: OR, 0.96; P = 0.629). However, subgroup analysis showed a significant contribution of the dominant inheritance model to OC development in the European group: AG + AA vs GG (OR, 1.43; P = 0.029); AG vs GG (OR, 1.46; P = 0.031). Vitamin D receptor BsmI G/A gene variant might be a moderate risk factor of OC development in the European population instead of North America or Asian population.


Functional electrical stimulation for upper limb strengthening in traumatic quadriplegia.
The hypothesis of this study was that the functional electrical stimulation (FES)-assisted exercise of partially paralyzed arm muscles would result in significantly greater muscle strength in the arms of spinal cord injured quadriplegics than equal periods of conventional isotonic exercise. Single muscles were studied in seven subjects in a crossover design consisting of equal periods of FES-assisted exercise and conventional exercise. It was concluded that for these subjects using this exercise regime, neither FES-assisted exercise nor conventional exercise produced improvements in maximum voluntary force that were either statistically or functionally significant. The results, although disappointing, have helped these subjects to be more realistic about the potential therapeutic benefits of FES.


Comment on: MALDI ionization mechanisms investigated by comparison of isomers of dihydroxybenzoic acid.
Ionization mechanism of matrix-assisted laser desorption/ionization was recently investigated by Kirmess et al. (J. Mass Spectrom. 2016, 51, 79). The authors compared the ion yields of dihydroxybenzoic acid isomers between experimental measurements and theoretical models and claimed that the predictions of chemical and physical dynamics model are in good agreement with experimental data, but the predictions of thermal model are not. Here, we show that wrong S1-S1 energy pooling rate constants and absorption cross sections were used in the aforementioned article. In addition, we suggest the authors to list the values of many parameters used in their calculations and describe how they obtained these values because these values are completely unknown.


Online simulation for information technology skills training in higher education.
The purpose of this study was to explore student's experiences when practicing information technology skills with an online simulation environment. After using the online simulation environment over a five-week period, 215 undergraduate students were surveyed regarding their usage-related experiences, satisfaction with the environment, and perceived learning. Both quantitative and qualitative data collection methods were employed. The quantitative results suggested that perceived ease of use had a direct effect on student's satisfaction with the online simulation environment, and that the satisfaction with the online simulation environment led to higher perceived learning. The qualitative findings revealed that technical problems, not being able to accomplish the objective of a step due to the precision required by the task, and the inflexibility of certain features of the online simulation environment were the commonly referenced issues, which might have impacted student's satisfaction and their perceived learning.


Plasma amino acids in reptiles after feeding protein or amino acids and after injecting amino acids.
Turtles (Pseudemys scripta elegans) and alligators (Alligator mississipiensis) were fed fish, casein, or free amino acid mixtures, or were injected with free amino acid mixtures, quantities in each case being equivalent to about 42 mmoles of amino acids/kg body weight. The experiments were designed to determine whether protein synthesis normally precedes catabolism of the amino acids absorbed from digesting food. Both animals disposed of free or food-derived amino acids more rapidly than could be accounted for by catabolism alone, but the transient increases in turtle plasma concentrations consisted mostly of essential amino acids, whereas the alligator plasma showed little increase in essential amino acids and considerable rises in four nonessential amino acids, glutamine, glutamic acid, glycine and alanine. Despite some species variation, these two species with low metabolic rates apparently utilized protein synthesis to dispose of amino acid mixtures prior to the necessarily slow process of catabolism for energy.


Synthesis of Ilmenite-type ε-Mn2O3 and Its Properties.
In contrast to the corundum-type A2X3 structure, which has only one crystallographic site available for trivalent cations (e.g., in hematite), the closely related ABX3 ilmenite-type structure comprises two different octahedrally coordinated positions that are usually filled with differently charged ions (e.g., in Fe2+Ti4+O3 ilmenite). Here, we report a synthesis of the first binary ilmenite-type compound fabricated from a simple transition-metal oxide (Mn2O3) at high-pressure high-temperature (HP-HT) conditions. We experimentally established that, at normal conditions, the ilmenite-type Mn2+Mn4+O3 (ε-Mn2O3) is an n-type semiconductor with an indirect narrow band gap of Eg = 0.55 eV. Comparative investigations of the electronic properties of ε-Mn2O3 and previously discovered quadruple perovskite ζ-Mn2O3 phase were performed using X-ray absorption near edge spectroscopy. Magnetic susceptibility measurements reveal an antiferromagnetic ordering in ε-Mn2O3 below 210 K. The synthesis of ε-Mn2O3 indicates that HP-HT conditions can induce a charge disproportionation in simple transition-metal oxides A2O3, and potentially various mixed-valence polymorphs of these oxides, for example, with ilmenite-type, LiNbO3-type, perovskite-type, and other structures, could be stabilized at HP-HT conditions.


Establishing density-dependent longitudinal sound speed in the vertebral lamina.
Focused ultrasound treatments of the spinal cord may be facilitated using a phased array transducer and beamforming to correct spine-induced focal aberrations. Simulations can non-invasively calculate aberration corrections using x-ray computed tomography (CT) data that are correlated to density (ρ) and longitudinal sound speed (cL). We aimed to optimize vertebral lamina-specific cL(ρ) functions at a physiological temperature (37 °C) to maximize time domain simulation accuracy. Odd-numbered ex vivo human thoracic vertebrae were imaged with a clinical CT-scanner (0.511 × 0.511 × 0.5 mm), then sonicated with a transducer (514 kHz) focused on the canal via the vertebral lamina. Vertebra-induced signal time shifts were extracted from pressure waveforms recorded within the canals. Measurements were repeated 5× per vertebra, with 2.5 mm vertical vertebra shifts between measurements. Linear functions relating cL with CT-derived density were optimized. The optimized function was cL(ρ)=0.35(ρ-ρw)+ cL,w m/s, where w denotes water, giving the tested laminae a mean bulk density of 1600 ± 30 kg/m3 and a mean bulk cL of 1670 ± 60 m/s. The optimized lamina cL(ρ) function was accurate to λ/16 when implemented in a multi-layered ray acoustics model. This modelling accuracy will improve trans-spine ultrasound beamforming.


Comparative Evaluation of Three Different Obturating Techniques Lateral Compaction, Thermafil and Calamus for Filling Area and Voids Using Cone Beam Computed Tomography: An Invitro study.
The success of root canal treatment depends upon the proper sealing of root canal system. Improper apical seal leads to the microleakage which can be prevented by proper obturation technique. To compare the quality of three different root canal obturation techniques: lateral compaction, Thermafil and Calamus by using cone beam computed tomography. A total of 30 central incisors were selected. Biomechanical preparation was done by Reciproc file no 25. Teeth were divided into 3 groups of 10 teeth each according to the obturation technique i.e. Calamus, Thermafil and lateral compaction. Cone beam computed tomography was used to measure filling area and voids at coronal, middle and apical third of the root canal after obturation by different techniques. Data was statistically analysed by One-Way Anova and multiple comparison of Tukey HSD tests. The maximum amount of obturating material was observed in Calamus group followed by Thermafil and lateral compaction. Minimum voids were seen in obturation by Calamus technique. Within the limitations of this study, it can be concluded that Calamus may be a good obturation technique.


Work capacity of older men and age-eligibility for Medicare benefits.
Whether the functional capacities of older Americans enable them to remain in the work force longer, is a significant consideration in appraising proposals to advance the normal eligibility age for Medicare benefits. This article analyzes the durations of work capability and work disablement of a representative panel of 5000 white and black men in their sixties and early seventies. The analysis shows that these men and succeeding cohorts of men are expected to function capably for long enough periods to meet the conditions necessary for raising the age of Medicare eligibility.


Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease.
We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus no statin use in a nested 1:2 matched study. The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786 + 3,572) and idiopathic lung fibrosis (n = 261 + 522) was higher for statin users versus never users (log-rank: P = 7 · 10(-9) and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all-cause mortality for statin users versus never users was 0.73 (95% confidence interval, 0.68 to 0.79) in patients with interstitial lung disease and 0.76 (0.62 to 0.93) in patients with idiopathic lung fibrosis. Results were robust in all sensitivity analyses. Among patients with interstitial lung disease statin use was associated with reduced all-cause mortality.


Retrospective Analysis of Geriatric Major Trauma Patients Admitted in the Shock Room of a Swiss Academic Hospital: Characteristics and Prognosis.
Increased life expectancy exposes a great number of elderly people to serious accidents, thus increasing the amount of major geriatric trauma cases. The aim of our study was to determine the profile of elderly patients undergoing major trauma, and the contributing factors predicting mortality in this specific patient group, compared to the younger population. Retrospective analysis of 1051 patients with major trauma admitted over ten years in a Level-1 trauma center was performed. Data collected were: history, nature and type of trauma; age and sex; vital signs on admission; injury severity score; shock index; comorbidities; coagulation diathesis; injury patterns; emergency measures taken; main diagnosis; mortality; and length of hospital and intensive care unit (ICU) stay. Geriatric patients admitted for major trauma have a mortality rate almost four times greater (47%) than their younger counterparts (14%) with the same ISS. According to statistical regression analysis, anti-platelet therapy (OR 3.21), NACA (National Advisory Committee for Aeronautics) score (OR 2.23), GCS (OR 0.83), ISS (OR 1.07) and age (OR 1.06) are the main factors predicting mortality. Conclusion: Geriatric major trauma patients admitted to our trauma resuscitation area have a high mortality rate. Age, GCS, ISS and NACA scores as well as anti-platelet therapy are the main factors predicting mortality.


Pinpoint chemical modification of Asp160 in the 49 kDa subunit of bovine mitochondrial complex I via a combination of ligand-directed tosyl chemistry and click chemistry.
Through a ligand-directed tosyl (LDT) chemistry strategy using the synthetic acetogenin ligand AL1, we succeeded in the pinpoint alkynylation (-C≡CH) of Asp160 in the 49 kDa subunit of bovine complex I, which may be located in the inner part of the putative quinone binding cavity of the enzyme [Masuya, T., et al. (2014) Biochemistry, 53, 2307-2317]. This study provided a promising technique for diverse chemical modifications of complex I. To further improve this technique for its adaptation to intact complex I, we here synthesized the new acetogenin ligand AL2, possessing an azido (-N₃) group in place of the terminal alkyne in AL1, and attempted the pinpoint azidation of complex I in bovine heart submitochondrial particles. Careful proteomic analyses revealed that, just as in the case of AL1, azidation occurred at 49 kDa Asp160 with a reaction yield of ∼50%, verifying the high site specificity of our LDT chemistry using acetogenin ligands. This finding prompted us to speculate that a reactivity of the azido group incorporated into Asp160 (Asp160-N₃) against externally added chemicals can be employed to characterize the structural features of the quinone/inhibitor binding cavity. Consequently, we used a ring-strained cycloalkyne possessing a rhodamine fluorophore (TAMRA-DIBO), which can covalently attach to an azido group via so-called click chemistry without Cu¹⁺ catalysis, as the reaction partner of Asp160-N₃. We found that bulky TAMRA-DIBO is capable of reacting directly with Asp160-N₃ in intact complex I. Unexpectedly, the presence of an excess amount of short-chain ubiquinones as well as some strong inhibitors (e.g., quinazoline and fenpyroximate) did not interfere with the reaction between TAMRA-DIBO and Asp160-N₃; nevertheless, bullatacin, a member of the natural acetogenins, markedly interfered with this reaction. Taking the marked bulkiness of TAMRA-DIBO into consideration, it appears to be difficult to reconcile these results with the proposal that only a narrow entry point accessing to the quinone/inhibitor binding cavity exists in complex I [Baradaran, R., et al. (2013) Nature, 494, 443-448]; rather, they suggest that there may be another access path for TAMRA-DIBO to the cavity.


Cerebrovascular blood oxygenation level dependent pulsatility at baseline and following acute exercise among healthy adolescents.
Arterial stiffness is linked to cerebral small vessel damage and neurodegeneration, but barriers to accessing deep cerebrovascular anatomy limit our ability to assess the brain. This study describes an adaptation of a cardiac-related scrubbing method as a means of generating blood oxygenation level-dependent pulsatility maps based on the cardiac cycle. We examine BOLD pulsatility at rest, based on the non-parametric deviation from null metric, as well as changes following acute physiological stress from 20 min of moderate-intensity cycling in 45 healthy adolescents. We evaluate the influence of repetition time (TR) and echo time (TE) using simulated and multi-echo empirical data, respectively. There were tissue-specific and voxel-wise BOLD pulsatility decreases 20 min following exercise cessation. BOLD pulsatility detection was comparable over a range of TR and TE values when scan volumes were kept constant; however, short TRs (≤500 ms) and TEs (∼14 ms) acquisitions would yield the most efficient detection. Results suggest cardiac-related BOLD pulsatility may represent a robust and easily adopted method of mapping cerebrovascular pulsatility with voxel-wise resolution.


Effect of the H1 blocker d-chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia.
The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A role for histamine is suspected because H2 receptor-blocking drugs blunt the hypoxia-induced increase in cerebral blood flow (CBF). Moreover, in vitro blockade of H1 receptors by chlorpheniramine decreases the vasodilatation of cerebral arteries that is induced by histamine. The present study tested the hypothesis that an H1 receptor blocker (d-chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2 = 0.10; inspired carbon dioxide fraction, FICO2 = 0.035) was induced in 16 conscious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and the other eight dogs received d-chlorpheniramine intravenously (0.5 mg kg-1) to block the H1 receptors. Regional CBF was measured by the radioactive microspheres technique 15 min after each injection of d-chlorpheniramine or saline. In the control group, CBF increased during hypoxia in all regions of the brain. In the d-chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pons, cerebral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of 12 studied regions). It is concluded that the H1 blocker d-chlorpheniramine did not strongly inhibit the increase in CBF during hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.


Size controllable synthesis of ZSM-5 zeolite and its catalytic performance in the reaction of methanol conversion to aromatics.
ZSM-5 zeolites were hydrothermally synthesized with commercial silica sol, and the crystal size was controlled by adding silicalite-1 seed in the synthetic system. The crystal size of ZSM-5 was affected by the crystallization time of seed, seed content and seed size. ZSM-5 zeolites with controllable particle size in the range of 200-2200 nm could be obtained. The prepared samples with different particle sizes were used for the reaction of methanol conversion to aromatics (MTA). The results suggested that the HZSM-5 catalyst with small crystal size showed much longer catalyst lifetime and higher selectivity for C5 + hydrocarbons and aromatics, especially C9 + aromatics in the MTA reaction. Moreover, the introduction of zinc (Zn) into the HZSM-5 zeolites can considerably promote the selectivity to aromatics in the products. Zn modified HZSM-5 zeolites with different Zn loading amounts were prepared by the incipient wetness impregnation method, and the highest aromatics selectivity was obtained when the Zn loading was 1.0%. The improvement of methanol aromatization was ascribed to the synergistic effect of Brønsted acid sites and the newly formed Zn-Lewis acid sites.


Livestock models of human birth defects, reviewed in relation to poisonous plants.
Certain birth defects in livestock induced by poisonous plants possess clinical similarities to congenital deformities in humans. They meet some criteria as models for those corresponding human conditions. They are induced by several plants, including members of the Astragalus, Lupinus, Conium, Nicotiana and Veratrum genera. The terata expressions include effects in bone and soft tissue, particularly in the limbs, spinal cord and cephalic regions. Whether these livestock conditions become extensively used as models of human terata will be determined by how well they meet the criteria sought in good models. These prospective models have many favorable characteristics; however, being large domestic livestock, they have certain logistic disadvantages compared with small rodents as models.


Ethical issues in reporting and referring in research with low-income minority children.
Ethical research with children requires a special concern for their well-being as individuals. Researchers are therefore expected to report problems children experience and to refer children for assistance. This article addresses difficultites that can arise as researchers attempt to meet this obligation in research with low-income ethnic minority children. Potential difficulties include both failure to report and overreporting suspected problems. The role of institutional review boards in researchers' reporting and referring behavior is also discussed.


Role of solvation in pressure-induced helix stabilization.
In contrast to the well-known destabilization of globular proteins by high pressure, recent work has shown that pressure stabilizes the formation of isolated α-helices. However, all simulations to date have obtained a qualitatively opposite result within the experimental pressure range. We show that using a protein force field (Amber03w) parametrized in conjunction with an accurate water model (TIP4P/2005) recovers the correct pressure-dependence and an overall stability diagram for helix formation similar to that from experiment; on the other hand, we confirm that using TIP3P water results in a very weak pressure destabilization of helices. By carefully analyzing the contributing factors, we show that this is not merely a consequence of different peptide conformations sampled using TIP3P. Rather, there is a critical role for the solvent itself in determining the dependence of total system volume (peptide and solvent) on helix content. Helical peptide structures exclude a smaller volume to water, relative to non-helical structures with both the water models, but the total system volume for helical conformations is higher than non-helical conformations with TIP3P water at low to intermediate pressures, in contrast to TIP4P/2005 water. Our results further emphasize the importance of using an accurate water model to study protein folding under conditions away from standard temperature and pressure.


Highly expressed miR-144-3p promotes the proliferation, migration and invasion of colon carcinoma cells by activating the Wnt/β-catenin signaling pathway through targeting SFRP1.
Background: To investigate the influence of miR-144-3p on the proliferation, migration and invasion of colon carcinoma by targeting secreted frizzled-related protein 1 (SFRP1) as well as of the Wnt/β-catenin signaling pathway. Methods: Based on the TCGA database, the association between the expression of miR-144-3p and the clinical information and prognosis of patients with colon carcinoma was examined, and SFRP1 was selected as the target gene for further studies based on bioinformatics prediction tools. CCK8 assay, wound healing assay and transwell invasion assay were employed to examine the impact of miR-144-3p on colon carcinoma cells. The regulation of SFRP1 by miR-144-3p was investigated using a dual-luciferase reporter system, and a rescue experiment was conducted to further elucidate whether miR-144-3p promotes the migration of colon carcinoma cells through targeting SFRP1 or not. The Wnt/β-catenin signaling pathway-mediated effect of miR-144-3p in colon carcinoma was finally validated through the targeting of SFRP1. Results: The bioinformatics analysis showed that the miR-144 expression levels were substantially greater in colon carcinoma tissue than in para-carcinoma tissue and were closely with clinical stage and prognosis. The findings obtained from the trial indicated that miR-144-3p substantially expressed in colon carcinoma tissue sample and the colon carcinoma cells, and the overexpressed miR-144-3p boosted the colon carcinoma cells' proliferation, migration and invasion. The results of dual-luciferase reporter gene assay revealed that miR-144-3p targeted SFRP1, and rescue experiment was carried out and its results indicated that miR-144-3p increased colon carcinoma cells' migration through targeting SFRP1. In addition, the molecular axis of miR-144-3p/SFRP1 may over-activate the Wnt/β-catenin signaling pathway. Conclusions: The present study has identified a novel malignant biological behavior, namely the ability of miR-144-3p to enhance the proliferation, migration and invasion of colon carcinoma cells by targeting SFRP1 and activating the Wnt/β-catenin signaling pathway. Consequently, miR-144-3p emerges as a promising diagnostic and therapeutic target for colon carcinoma.


Acute vision impairment: does it affect an anesthesiologist's ability to intubate the trachea?
The result of impaired vision on an anesthesiologist's ability to intubate the trachea is unknown. We studied 12 attending staff anesthesiologists as they intubated 2 anesthesia mannequins (A and B) under 6 conditions. The conditions were: 1) usual vision, 2) central-vision loss with 20/500 bilaterally and a 24 degrees central scotoma, 3) peripheral-field loss with 20/20 bilaterally and a 7 degrees visual field, 4) peripheral-field loss with 20/20 bilaterally and a 3.5 degrees visual field, 5) central-vision loss with 20/200 bilaterally and a 12 degrees central scotoma, and 6) right eye ocular media opacity and 20/70 left eye usual acuity. The time to intubation was recorded by stopwatch from gripping the laryngoscope until the anesthesiologist signaled that the endotracheal tube was properly placed in the trachea. The mean +/- SD times to intubation for Mannequins A and B were 16.0 +/- 3.3, 31.9 +/- 10.4, 26.4 +/- 9.0, 26.4 +/- 7.7, 22.4 +/- 5.1, 25.5 +/- 16.9 and 16.6 +/- 6.6, 26.9 +/- 10.0, 21.4 +/- 9.2, 21.4 +/- 5.8, 21.5 +/- 7.7, 17.7 +/- 5.1 s for the 6 conditions, respectively. Multiple analysis of variance revealed a highly significant difference for the time to successful intubation between the anesthesiologists' usual vision and the vision-impaired conditions. There was a significant improvement in time to successful intubation from the first to subsequent intubation attempts. There were also more esophageal intubations in the vision-impaired conditions. This implies that anesthesiologists who develop acute severe vision impairment might have more difficulty intubating the trachea, which could initiate more critical incidents. The results of this study cannot be applied to anesthesiologists with chronic vision impairment. We found that acute severe vision impairment adversely affects the anesthesiologist's ability to intubate the trachea. This implies that anesthesiologists with acute onset of severe visual handicaps might have more difficulty intubating the trachea, which could initiate more critical incidents.


[Determination of serum free thyroxine: normal range, relation to the free thyroxine ratio and total thyroxine (author's transl)].
The validity of a commercially available f-T4 radioimmunoassay was investigated in 122 patients with different thyroid status. The normal range of f-T4 was 0.60-2.20 ng/dl in euthyroid patients from an endemic goiter area. No significant difference was found between normals and a group taking oral contraceptives (mean = 1.37 ng/dl vs. 1.45 nd/dl). In patients on thyroid hormone or antithyroid drug therapy, f-T4-values showed a better correlation with the results of an oral TRH-test than total T4 or the free thyroxine ratio (ETR). Specificity of ETR was better than that of f-T4. Sensitivity of f-T4 was higher in the group with negative TRH-test, but lower in hypothyroidism as compared to ETR. Determination of f-T4 by radioimmunoassay is a simple diagnostic procedure. Since f-T4 RIA is not influenced by changes in TBG-levels its use is particularly recommended in cases where such changes are to be expected such as estrogen application or gravidity.


Is It Time to Reconsider Postoperative Epidural Analgesia in Patients Undergoing Elective Ventral Hernia Repair?: An AHSQC Analysis.
We aimed to evaluate the association of epidural analgesia (EA) with hospital length of stay (LOS), wound morbidity, postoperative complications, and patient-reported outcomes in patients undergoing ventral hernia repair (VHR). EA has been shown to reduce LOS in certain surgical populations. The LOS benefit in VHR is unclear. Patients having VHR performed in the Americas Hernia Society Quality Collaborative (AHSQC) were separated into 2 comparable groups matched on several confounding factors using a propensity score algorithm: one group received postoperative EA, and the other did not. The groups were then evaluated for hospital LOS, 30-day wound morbidity, other complications, and 30-day patient-reported outcomes using pain and hernia-specific quality-of-life instruments. A 1:1 match was achieved and the final analysis included 763 patients receiving EA and 763 not receiving EA. The EA group had an increased LOS (5.49 vs 4.90 days; P < 0.05). The rate of wound events was similar between the groups. There was an increased risk of having any postoperative complication associated with having EA (26% vs 21%; P < 0.05). Pain intensity-scaled scores were significantly higher (worse) in the EA group versus the non-EA group (47.6 vs 44.0; P = 0.04). The LOS benefit of EA noted for other operations may not apply to patients undergoing VHR. Further study is necessary to determine the beneficial role of invasive pain management procedures in this group of patients with an extremely common disease state.


Application of InSAR and GIS techniques to ground subsidence assessment in the Nobi Plain, Central Japan.
Spatial variation and temporal changes in ground subsidence over the Nobi Plain, Central Japan, are assessed using GIS techniques and ground level measurements data taken over this area since the 1970s. Notwithstanding the general slowing trend observed in ground subsidence over the plains, we have detected ground rise at some locations, more likely due to the ground expansion because of recovering groundwater levels and the tilting of the Nobi land mass. The problem of non-availability of upper-air meteorological information, especially the 3-dimensional water vapor distribution, during the JERS-1 observational period (1992-1998) was solved by applying the AWC (analog weather charts) method onto the high-precision GPV-MSM (Grid Point Value of Meso-Scale Model) water-vapor data to find the latter's matching meteorological data. From the selected JERS-1 interferometry pair and the matching GPV-MSM meteorological data, the atmospheric path delay generated by water vapor inhomogeneity was then quantitatively evaluated. A highly uniform spatial distribution of the atmospheric delay, with a maximum deviation of approximately 38 mm in its horizontal distribution was found over the Plain. This confirms the effectiveness of using GPV-MSM data for SAR differential interferometric analysis, and sheds thus some new light on the possibility of improving InSAR analysis results for land subsidence applications.


Assessment of the adherence of cardiologists to guidelines for the treatment of atrial fibrillation.
No local studies evaluating the knowledge of cardiologists on the management of atrial fibrillation (AF) and their adherence to these guidelines are available. To evaluate the knowledge of cardiologists on the guidelines and clinical practices for the treatment of AF, correlating it to the time since medical graduation. Cross-sectional study randomly including cardiologists affiliated to the Society of Cardiology of the State of Rio Grande do Sul (Sociedade de Cardiologia do Estado do Rio Grande do Sul - SOCERGS). The physicians were divided into two groups, according to time since graduation: those graduated for more (G1) or less (G2) than 25 years. Of the 859 SOCERGS members, 150 were interviewed, and six refused to participate in the study. G1 comprised 71 physicians, and G2, 73. Differences were observed in regard to the following variables: use of betablockers as the first-choice drug for the control of AF response in 59.2% (G1) vs 91.8% (G2) (p<0.0001); use of digoxin as the preferred drug for the control of AF response in 19.7% (G1) vs 0% (G2) (p< 0.0001); warfarin as the preferred anticoagulant in 71.8% (G1) vs 93.2% (G2) (p=0.009); application of a risk score for anticoagulation in 73.2% (G1) vs 87.7% (G2) (p=0.02). In questions regarding the knowledge about the Brazilian Society of Cardiology's guideline for AF, the overall percentage of right answers was 82.3%. Most of the clinical measures regarding the management of AF comply with the guidelines, and the clinical practice differs according with the time since graduation.


Urinary retention due to mesenteric cyst: An extremely unusual presentation of a rare complication.
Mesenteric cysts are rare intra-abdominal masses, presenting with various clinical signs and symptoms. Mesenteric cysts presenting with a sudden onset of urinary retention is extremely rare. There are no cases reported in the English literature. Here, we report a very rare case of urinary retention, due to mesenteric cyst in a 19-year-old man. The patient presented with abdominal distention with a sudden onset of urinary retention. Ultrasonography and computed tomography scan of the abdomen revealed a huge cystic mass above the bladder that was completely separated from the kidney and bladder. The cyst was removed surgically. The patient experienced no urological difficulty after the surgery. Histological examination confirmed the diagnosis of a mesenteric cyst.


Real-world application, challenges and implication of artificial intelligence in healthcare: an essay.
This essay examines the state of Artificial Intelligence (AI) based technology applications in healthcare and the impact they have on the industry. This study comprised a detailed review of the literature and analyzed real-world examples of AI applications in healthcare. The findings show that major hospitals use AI-based technology to enhance knowledge and skills of their healthcare professionals for patient diagnosis and treatment. AI systems have also been shown to improve the efficiency and management of hospitals´ nursing and managerial functions. Healthcare providers are positively accepting AI in multiple arenas. However, its applications offer both the utopian (new opportunities) as well as the dystopian (challenges). Unlike pessimists, AI should not be seen a potential source of "Digital Dictatorship" in future of 22nd century. To provide a balanced view on the potential and challenges of AI in healthcare, we discuss these details. It is evident that AI and related technologies are rapidly evolving and will allow care providers to create new value for patients and improve their operational efficiency. Effective AI applications will require planning and strategies that transform both the care service and the operations in order to reap the benefits.


Bladder polyp and heavy proteinuria in a patient with Hodgkin's disease in remission.
A 21-year-old man who developed heavy proteinuria 8 years after remission of Hodgkin's disease treated with MOPP chemotherapy and radiation therapy is reported. Evidence of Hodgkin's disease could not be documented, and minimal changes were revealed by renal biopsy. Proteinuria persisted for 20 months and was followed by dysuria and the discovery of an inflammatory polyp of the bladder. The proteinuria decreased 1 month after excision of the polyp, and disappeared during the following year. Rather than indicating relapse of lymphoma, proteinuria in this patient resulted from a lesion not previously associated with Hodgkin's disease, but possibly resulting from long-term effects of therapy.


KN-62, a specific Ca++/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes.
Effects of KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine), a specific Ca++/calmodulin (CaM)-dependent protein kinase inhibitor, were examined on the rate of spontaneous beating and the intracellular Ca++ transient of cultured myocytes from fetal mouse ventricle. KN-62 depressed the rate of beating in a dose-dependent fashion. Spontaneous beating ceased 10 min after the administration of 1 microM KN-62 and recovered gradually after washing with cultured medium. Addition of KN-04 [N-(1-1[P-(5-isoquinolinsulfonyl)benzyl]-2-(4- phenylpiperazinyl)ethyl)-5-isoquinolinsulfonamide; 1 microM], an analog of KN-62, did not change the rate of beating. In the experiment using an intracellular Ca++ fluorescence indicator, fluo-3, KN-62 depressed the fluo-3 intensity at a systolic phase. The kinase activity to syntide-2 of Ca++/CaM kinase II purified from the rabbit heart was inhibited by KN-62, but not by KN-04. Addition of KN-62 inhibited the phosphorylation of phospholamban by Ca++/CaM kinase II in a dose-dependent manner. KN-62 depressed the Ca(++)-pumping ATPase activity in the presence of Ca++ and CaM by 32%. These findings indicate that Ca++/CaM kinase II changes an intracellular Ca++ transient and modulates the rate of beating at least in part.


Design and implementation of electrochemical cytosensor for evaluation of cell surface carbohydrate and glycoprotein.
A new strategy for assessing cell surface carbohydrates and P-glycoprotein (P-gp) expression status and quantifying the cell numbers with an electrochemical immunoassay was designed. In order to construct the base of the cytosensor, a novel 3-D architecture was initially fabricated by combining nitrogen-doped carbon nanotubes, thionine, and gold nanoparticles via a simple layer-by-layer method. The formed architecture provided an effective matrix for concanavalin A (Con A) binding and made the immobilized Con A hold high stability and bioactivity. On the basis of the specific recognition of cell surface mannosyl groups to Con A, the Con A/3-D architecture interface showed a predominant capability for cell capture. With another coupled signal amplification based on a enzymatic catalytic reaction of HRP toward the oxidation of thionine by the H(2)O(2), which was induced by two-step immunoreactions, the proposed cytosensor showed an excellent analytical performance for the detection of HeLa cells ranging from 8.0 x 10(2) to 2.0 x 10(7) cells mL(-1) with a limit of detection of 500 cells mL(-1). Moreover, with the use of preblocking procedures, the mannosyl groups and P-gp on single HeLa cell could be further detected to be (4 +/- 2) x 10(10) molecules of mannose moieties and 8.47 x 10(6) molecules of P-gp. This strategy offers great promise for sensitive detection of cancer cells and cell surface receptors and thus may help improve cancer diagnosis and treatment.


Three-dimensional knee joint kinetics during a golf swing. Influences of skill level and footwear.
This study characterized knee joint kinetics during a golf swing and determined the influence of shoe type and golfer skill on the peak knee joint loads. Thirteen golfers each hit a golf ball using a five iron under two footware conditions: spiked and spikeless golf shoes. Data from a video-based motion capture system and force plates were used to compute the knee joint kinetics. Mean peak forces and moments differed significantly between the lead and trail knees, but these peak loads were not significantly affected by shoe type. Only the lead knee flexion and internal rotation moments were significantly correlated to skill level. The magnitude of some of the peak loads at the knee during the golf swing approached those reached during activities prohibited until late-stage knee rehabilitation. We concluded the following: The type of shoe worn and the skill level of the golfer need not be considered in deciding time to return to golfing; however, the leg that is recovering from surgery or injury should be considered. The most stressful phase of the golf swing, relative to the knee, is the downswing. There is probably no "normal" swing; each golfer seems to possess consistent, characteristic, patterns of knee loading.


[A uniform approach to the synthesis of carbohydrate conjugates of polyhedral boron compounds as potential agents for boron neutron capture therapy].
A uniform approach to the synthesis of carbohydrate conjugates with polyhedral boron compounds (PBCs) was developed. Oligosaccharide derivatives with an aglycone moiety amino group can be coupled with PBC carboxyl derivatives using N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a coupling agent. Both N- and O-glycosides differing in the conformational mobility around the glycoside bond were shown to be useful as oligosaccharides with a functional group in the aglycone moiety. This allows the application of this approach to the synthesis of PBC conjugates with a wide range of oligosaccharides. For example, not only oligosaccharides obtained by chemical synthesis but also reducing oligosaccharides isolated from natural sources can be transformed into N-glycosides. The approach was tested by the example of conjugation of the carboxyl derivatives of ortho-carborane and dodecaborate anion with lactose as a model oligosaccharide. Lactose, an easily available disaccharide, is a ligand for lectins expressed on the surface of melanoma cells. The approach suggested is the first example of the synthesis of such conjugates that does not require protective groups for the carbohydrate residue. It is especially important for obtaining dodecaborate-carbohydrate conjugates for which the removal of protective groups is often a non-trivial task.


SUMO-mimicking peptides inhibiting protein SUMOylation.
The ubiquitin-like protein SUMO is transferred through a core E1-E2 cascade composed of the SUMO-activating enzyme (SAE) and Ubc9 to modify cellular proteins and transmit important biological signals. SAE primarily recognizes the C-terminal tail of SUMO and catalyzes ATP condensation with the SUMO C-terminal carboxylate to activate its transfer through the cascade. Here, we used phage display to show that a broad profile of SUMO C-terminal sequences could be activated by SAE. Based on this, we developed heptamer peptides that could 1) form thioester conjugates with SAE, 2) be transferred from SAE to Ubc9, and 3) be further transferred to the SUMOylation target protein RanGAP1. As these peptides recapitulate the action of SUMO in protein modification, we refer to them as "SUMO-mimicking peptides". We found that, once the peptides were conjugated to SAE and Ubc9, they blocked full-length SUMO from entering the cascade. These peptides can thus function as mechanism-based inhibitors of the protein SUMOylation reaction.


Vacuolar H+-ATPase inhibitor induces apoptosis via lysosomal dysfunction in the human gastric cancer cell line MKN-1.
We investigated the mechanism of apoptosis induced by bafilomycin A(1), an inhibitor of vacuolar H(+)-ATPase. Bafilomycin A(1) significantly inhibited the growth of MKN-1 human gastric cancer cells. Bafilomycin A(1) induced apoptosis as demonstrated by DNA ladder formation and the TUNEL method. We designed a flow cytometric assay to detect the alteration in lysosomal pH using a fluorescent probe, fluorescein isothiocyanate-conjugated dextran. This assay revealed that bafilomycin A(1) dramatically increased lysosomal pH. However, bafilomycin A(1) induced neither significant decrease in mitochondrial transmembrane potential nor the release of mitochondrial cytochrome c into the cytoplasm. Western blotting showed that cathepsin D, but not cathepsin L, was released into the cytoplasm. The activity of caspase-3 was significantly increased by bafilomycin A(1). However, cathepsin D did not directly cleave procaspase-3. These findings suggest that bafilomycin A(1)-induced apoptosis in MKN-1 cells is mediated by other proteases released after lysosomal dysfunction followed by activation of caspase-3 in a cytochrome c-independent manner. The present study showed that flow cytometric analysis of lysosomal pH can be useful to evaluate lysosomal protease-mediated apoptosis.


Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials.
Renal impairment (RI) is a major comorbidity in patients with multiple myeloma (MM). Here we present the pooled safety and efficacy analysis of three clinical trials (MM-002, MM-003, and MM-010) of pomalidomide + low-dose dexamethasone (POM + LoDEX) in patients with moderate RI (creatinine clearance [CrCl] ≥ 30 to <60 mL/min) and without RI (≥ 60 mL/min). Trial protocols were approved by the institutional review board of each site involved. Patients with RI were older than patients without RI, although other baseline characteristics were similar. The dosing and safety profile of POM + LoDEX was similar across RI subgroups. Median overall response rate, progression-free survival, time to progression, and duration of response were not significantly different between RI subgroups. However, patients with vs. without RI had significantly shorter median overall survival (10.5 vs. 14.0 months, respectively; p = .004). This analysis demonstrates that POM + LoDEX is a safe and effective treatment for patients with moderate RI. The trials were registered at ClinicalTrials.gov as NCT00833833 (MM-002), NCT01311687 (MM-003), and NCT01712789 (MM-010) and at EudraCT as 2010-019820-30 (MM-003) and 2012-001888-78 (MM-010).


Successful treatment of Paecilomyces lilacinus keratitis in a patient with a history of herpes simplex virus keratitis.
To report a case of Paecilomyces lilacinus keratitis, initially misdiagnosed as Penicillium sp., in a patient with a long-standing history of herpes simplex virus (HSV) keratitis. A retrospective case report. A 62-year-old man developed P. lilacinus keratitis. He was treated with topical steroids for immune stromal keratitis secondary to HSV before developing the fungal keratitis. Initial corneal cultures were positive for Penicillium sp., but subsequent cultures identified P. lilacinus to be the causative organism. The patient later developed an anterior chamber abscess. Three penetrating keratoplasties, as well as intravitreal injection of amphothericin B, topical miconazole, subconjunctival miconazole, and systemic fluconazole, were required to eradicate the infection. To our knowledge, this is a first report of P. lilacinus keratitis in a patient with a previous history of HSV keratitis. The causative organism was initially reported as Penicillium sp. on 2 occasions, before the correct diagnosis was made. Paecilomyces keratitis progressed to an anterior chamber abscess in this eye. Aggressive treatment, including a therapeutic penetrating keratoplasty, intravitreal amphothericin B injection, topical miconazole, and systemic fluconazole can be successful in eradicating this extremely difficult-to-treat infection.


The Evidence-Based Practice of Applied Behavior Analysis.
Evidence-based practice (EBP) is a model of professional decision-making in which practitioners integrate the best available evidence with client values/context and clinical expertise in order to provide services for their clients. This framework provides behavior analysts with a structure for pervasive use of the best available evidence in the complex settings in which they work. This structure recognizes the need for clear and explicit understanding of the strength of evidence supporting intervention options, the important contextual factors including client values that contribute to decision making, and the key role of clinical expertise in the conceptualization, intervention, and evaluation of cases. Opening the discussion of EBP in this journal, Smith (The Behavior Analyst, 36, 7-33, 2013) raised several key issues related to EBP and applied behavior analysis (ABA). The purpose of this paper is to respond to Smith's arguments and extend the discussion of the relevant issues. Although we support many of Smith's (The Behavior Analyst, 36, 7-33, 2013) points, we contend that Smith's definition of EBP is significantly narrower than definitions that are used in professions with long histories of EBP and that this narrowness conflicts with the principles that drive applied behavior analytic practice. We offer a definition and framework for EBP that aligns with the foundations of ABA and is consistent with well-established definitions of EBP in medicine, psychology, and other professions. In addition to supporting the systematic use of research evidence in behavior analytic decision making, this definition can promote clear communication about treatment decisions across disciplines and with important outside institutions such as insurance companies and granting agencies.


Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells.
The anticancer agent genistein inhibits cell growth of tumor cell lines from various malignancies. In our study, we investigated the effectiveness of combined treatment of ionizing radiation (IR) with genistein on cervical HeLa cells and its possible mechanism. It was found that the inhibitory rate in cells with combined treatment was significantly higher than that of the cells treated with IR or genistein alone. After treatments of IR (4 Gy) combined with genistein (40 micromol/L), the apoptotic index of the cells was significantly increased and the cells were arrested in the G2/M phase. Survivin mRNA expression increased after IR (4 Gy), while it significantly decreased after combined treatment. These findings indicated that genistein enhanced the radiosensitivity of cervical cancer HeLa cells, and the mechanisms for this action might include increase of apoptosis, decrease of survivin expression, and prolongation of cell cycle arrest.


Association of Adiponectin with Lung Function Impairment and Disease Severity in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) is not only restricted to the pulmonary inflammation and airway obstruction but is also associated with comorbidities, which affect the therapeutic intervention and the quality of life and survival. Markers that can predict the systemic inflammation and a decline in the pulmonary function are of scientific interest. Adiponectin (APN) appears to be one such biomarker and can be used as a potential indicator of severity and response to treatment in patients of COPD. The study aims to find out the role of APN as a marker of inflammation in the pathogenesis of COPD and explore its relationship with the severity of the disease. This was a cross-sectional study. The study group consisted of 60 patients of COPD, which included 30 males admitted with acute exacerbation of COPD (AECOPD) and 30 males with stable COPD. The study group was compared with 30 healthy, age-matched males. APN was estimated by commercially available ELISA kits. Pulmonary function tests were performed on all cases and controls using standardized protocols on SPIROLAB III. Statistical analysis was performed using Student's t-test and Pearson's correlation coefficient. The levels of APN were found to be significantly higher in patients with COPD as compared to the controls and the levels increased with the severity of the disease were 16.10 ± 4.97 ng/ml and 11.43 ± 4.22 ng/ml, respectively, in AECOPD and COPD. A significant positive correlation was found between the levels of APN and interleukin (IL)-8 in patients of COPD, while the levels correlated negatively with percentage of forced expiratory volume in 1 s (FEV1%). The results reveal that APN is associated with the inflammatory process of COPD as suggested by its significant inverse relationship with FEV1% and positive correlation with a marker of inflammation such as IL-8. It can thus be used as a biomarker for disease severity and progression in patients of COPD, therefore aiding in risk stratification and therapeutic intervention.


The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for Down syndrome in Ontario, Canada.
To examine the cost and performance implications of introducing cell-free fetal DNA (cffDNA) testing within modeled scenarios in a publicly funded Canadian provincial Down syndrome (DS) prenatal screening program. Two clinical algorithms were created: the first to represent the current screening program and the second to represent one that incorporates cffDNA testing. From these algorithms, eight distinct scenarios were modeled to examine: (1) the current program (no cffDNA), (2) the current program with first trimester screening (FTS) as the nuchal translucency-based primary screen (no cffDNA), (3) a program substituting current screening with primary cffDNA, (4) contingent cffDNA with current FTS performance, (5) contingent cffDNA at a fixed price to result in overall cost neutrality,(6) contingent cffDNA with an improved detection rate (DR) of FTS, (7) contingent cffDNA with higher uptake of FTS, and (8) contingent cffDNA with optimized FTS (higher uptake and improved DR). This modeling study demonstrates that introducing contingent cffDNA testing improves performance by increasing the number of cases of DS detected prenatally, and reducing the number of amniocenteses performed and concomitant iatrogenic pregnancy loss of pregnancies not affected by DS. Costs are modestly increased, although the cost per case of DS detected is decreased with contingent cffDNA testing. Contingent models of cffDNA testing can improve overall screening performance while maintaining the provision of an 11- to 13-week scan. Costs are modestly increased, but cost per prenatally detected case of DS is decreased.


The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella.
Salmonella enterica subsp. enterica sv. Typhimurium str. LT2 (hereafter S. Typhimurium) synthesizes adenosylcobalamin (AdoCbl, CoB12) de novo only under anoxic conditions, but it can assemble the lower ligand loop (a.k.a. the nucleotide loop) and can form the unique C-Co bond present in CoB12 in the presence or absence of molecular oxygen. During studies of nucleotide loop assembly in S. Typhimurium, we noticed that the growth of this bacterium could be arrested by the lower ligand nucleobase, namely 5,6-dimethylbenzimidazole (DMB). Here we report in vitro and in vivo evidence that shows that the structural similarity of DMB to the isoalloxazine moiety of flavin cofactors causes its deleterious effect on cell growth. We studied DMB inhibition of the housekeeping flavin dehydrogenase (Fre) and three flavoenzymes that initiate the catabolism of tricarballylate, succinate or D-alanine in S. Typhimurium. Notably, while growth with tricarballylate was inhibited by 5-methyl-benzimidazole (5-Me-Bza) and DMB, growth with succinate or glycerol was arrested by DMB but not by 5-Me-Bza. Neither unsubstituted benzimidazole nor adenine inhibited growth of S. Typhimurium at DMB inhibitory concentrations. Whole genome sequencing analysis of spontaneous mutant strains that grew in the presence of inhibitory concentrations of DMB identified mutations effecting the cycA (encodes D-Ala/D-Ser transporter) and dctA (encodes dicarboxylate transporter) genes and in the coding sequence of the tricarballylate transporter (TcuC), suggesting that increased uptake of substrates relieved DMB inhibition. We discuss two possible mechanisms of inhibition by DMB.


Abnormal populations and functions of natural killer cells in patients with myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis that lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disease. Different levels or mechanisms of natural killer (NK) cells in patients with MDS have been measured in previous studies, making it challenging to understand the pathogenesis of NK cytotoxicity. The present study investigated the frequency of NK cell-mediated antibody-dependent cellular cytotoxicity and explored the function of NK cells by their activating receptors, inhibition signals, degranulation and cytotoxicity factors. In the present study, levels of cluster of differentiation (CD)3-CD56+ NK cells, CD16+-expressing NK cells and subset CD56dim NK cells were decreased in the peripheral blood of patients with MDS. Altered expression of NK protein 44, NK group 2 member D, killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) and KIR2DL3 on NK cell effector signaling pathways may trigger tumor cell lysis in patients with MDS. The weak cellular adhesion and decreased cytotoxicity of NK cells may lead to ineffective antitumor activity in MDS. These observations suggested that NK cells may serve as immunological determinants in MDS and may permit the development of NK cell-based immunotherapy for the treatment of patients with MDS.


Fish in a Dish: Using Zebrafish in Authentic Science Research Experiences for Under-represented High School Students from West Virginia.
Early research experiences positively affect students' interest in STEM careers, and develop practical science and critical thinking skills. However, outreach opportunities are not equally accessible for all students. In states like West Virginia, where many students live in rural Appalachian communities, opportunities for engaging in STEM experiences are limited. In addition, rural teachers may not be equipped to provide authentic research experiences for students due to lack of resources or support. For many students in West Virginia, the Health Sciences and Technology Academy (HSTA) is a major opportunity for STEM engagement. Since its inception in 1998, HSTA has spread to 26 of 55 counties in West Virginia. The program recruits first-generation, low-socioeconomic status, rurally living, and African American high school students who are under-represented in STEM fields. Our research laboratory partnered with HSTA to implement an innovative, hands-on research camp using zebrafish for students participating in their annual junior-level biomedical sciences summer camp. Our camp was held in-person and adapted to an online format during the Covid-19 pandemic. We used pre-post surveys in both camps to assess impacts on science confidence and to collect information about general perceptions of zebrafish, research, and STEM fields. We found that students participating in the in-person and online camps experienced similar overall gains in science confidence. We also identified strong interest in zebrafish, research, and STEM degrees among online students. Online students did not prefer virtual learning experiences; however, they still enjoyed our camp. We also surveyed high school teachers volunteering for HSTA to identify factors that would encourage use of zebrafish in classrooms. The most prominent needs include classroom supplies, experience, and funding. Our successful science-education partnership demonstrates that zebrafish research experiences foster positive outcomes for under-represented students, and can inform future outreach efforts and collaborations with teachers.


Construction of uric acid biosensor based on biomimetic titanate nanotubes.
A uric acid biosensor has been fabricated through the immobilization of uricase on glassy carbon electrode modified by biomimetic titanate nanotubes of high specific surface area synthesized by hydrothermal decomposition. The so-constructed biosensor presents a high affinity to uric acid with a small apparent Michaelis-Menten constant of only 0.66 mM. The biosensor exhibits fairly good electrochemical properties such as the high sensitivity of 184.3 microAcm(-2)mM(-1), the fast response of less than 2 s, as well as the wide linear range from 1 microM to 5 mM. These performances indicate that titanate nanotubes could provide a favorable microenvironment for uricase immobilization, stabilize its biological activity, and function as an efficient electron conducting tunnel to facilitate the electron transfer. This suggests an important potential of titanate nanotubes in uric acid biosensors.


Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels.
Alternative splicing of the P/Q-type channel (Ca(V)2.1) promises customization of the computational repertoire of neurons. Here we report that concerted splicing of its main alpha1A subunit, at both an EF-hand-like domain and the channel C terminus, controls the form of Ca2+-dependent facilitation (CDF), an activity-dependent enhancement of channel opening that is triggered by calmodulin. In recombinant channels, such alternative splicing switches CDF among three modes: (1) completely "ON" and driven by local Ca2+ influx through individual channels, (2) completely "OFF," and (3) partially OFF but inducible by elevated global Ca2+ influx. Conversion from modes 1 to 3 represents an unprecedented dimension of control. The physiological function of these variants is likely important, because we find that the distribution of EF-hand splice variants is strikingly heterogeneous in the human brain, varying both across regions and during development.


Structural perspective of peptidoglycan biosynthesis and assembly.
The peptidoglycan biosynthetic pathway is a critical process in the bacterial cell and is exploited as a target for the design of antibiotics. This pathway culminates in the production of the peptidoglycan layer, which is composed of polymerized glycan chains with cross-linked peptide substituents. This layer forms the major structural component of the protective barrier known as the cell wall. Disruption in the assembly of the peptidoglycan layer causes a weakened cell wall and subsequent bacterial lysis. With bacteria responsible for both properly functioning human health (probiotic strains) and potentially serious illness (pathogenic strains), a delicate balance is necessary during clinical intervention. Recent research has furthered our understanding of the precise molecular structures, mechanisms of action, and functional interactions involved in peptidoglycan biosynthesis. This research is helping guide our understanding of how to capitalize on peptidoglycan-based therapeutics and, at a more fundamental level, of the complex machinery that creates this critical barrier for bacterial survival.


The active straight leg raising test (ASLR) in pregnant women: differences in muscle activity and force between patients and healthy subjects.
Pregnancy-related low back and pelvic pain (PLBP) is a frequent complication of pregnancy. Although pathological mechanisms underlying PLBP are obscure, dysfunction of the sacroiliac joints (SI-joints) seems to play an important role. A cross-sectional study was performed on 24 pregnant women with and without PLBP. The objective was to determine muscle activation patterns of trunk and leg muscles during the active straight leg raising test (ASLR) and static hip flexion, and to determine maximal hip flexion force at 0 and 20 cm leg raise height. Moreover, the effort to raise the leg was scored. The measurements resulted in several significant differences between the patients and healthy controls; among others (a) patients scored subjectively more effort during ASLR, (b) at both 0 and 20 cm leg raise height patients had less hip flexion force, and (c) patients developed more muscle activity during ASLR. Since pregnant women with PLBP developed a higher muscle activity during ASLR with a significantly lower output at 0 and 20 cm than healthy pregnant women, it could be proposed that the ASLR demonstrates a disturbed load transfer across the SI-joints in this population.


Computer simulation study of a single polymer chain in an attractive solvent.
The behavior of a linear polymer chain is studied in a solvent with high affinity for the polymer. The coil dimensions and specific heat are calculated as a function of chain length, solvent concentration, and polymer-solvent attraction strength epsilon(ps). All other interactions are limited to excluded volume repulsion, which implies that the Flory-Huggins chi parameter is negative. Using both on-lattice and off-lattice models of a polymer chain in explicit solvent, we study a transition from weak to strong association regimes. In all cases studied, the system's heat capacity is a nonmonotonic function of epsilon(rhos) with a maximum at attraction strengths of the order of several k(B)T. This peak originates from restriction of local conformational degrees of freedom due to the associated solvent rather than from a partial chain collapse which onsets as attractive solvent content is decreased.


Occurrence of composite cardiac endpoints with change in resting heart rate among Chinese patients with coronary artery disease: Chinese cohort from the real-world BISO-CAD study.
We evaluated change in resting heart rate (RHR) and its impact on prognosis in Chinese coronary artery disease (CAD) patients treated with bisoprolol, and also assessed drug safety and tolerability. This phase IV, single arm observational study was a sub-study of the BISO-CAD study conducted across 20 hospitals in China between October 2011 and July 2015 with follow-up at 6, 12 and 18 months after baseline. The primary endpoint was occurrence of composite cardiac events. A total of 663 CAD patients (baseline RHR 75.47 ± 6.62 bpm) were enrolled in the intent-to-treat (ITT) set, and 513 patients were included in the efficacy analysis (EA) set. In the ITT set, the risk and the number of composite cardiac events in patients with mean RHR 69-74 bpm were significantly higher than in the <65 bpm group (ITT: estimate 1.03 ± 0.47, p = .029). The incidence of the composite cardiac endpoint was not affected by continuous mean RHR (p = .5070). RHR significantly decreased from baseline to 18 months, most obviously in the first 6 months (p < .0001). Ejection fraction and fractional shortening significantly improved in both the ITT and EA sets. An average RHR of 69-74 bpm had a significant effect on admission to hospital for acute coronary syndrome in the ITT (estimate 1.10, HR 3.004, p = .0196) and EA (estimate 1.26, HR 3.526, p = .0132) groups. Seven (1.1%) patients reported drug related adverse events. Reduction in RHR with bisoprolol lowered the incidence of composite cardiac events along with an acceptable safety and tolerability profile.


[Characterization of a multimer type III antifreeze protein gene from the Antarctic eel pout (Lycodichthys dearborni)].
To survive the freezing marine environment, the Antarctic eel pout, Lycodichthys dearborni synthesizes high concentration of type III antifreeze proteins (AFP III). In the process of characterizing the various types of AFP III mRNA present in the L. dearboni liver, a 2.87 kb mRNA encodes for multiple domains of AFP III was identified. This cDNA encodes 12 tandemly repeated segments, each translates into a 7 kD AFP III molecule plus a 9-amino acid linker. This naturally occurred and functional multimer type III antifreeze protein gene is the first of this kind being identified. The organization strongly mimics the polyprotein structure found in the genes for another type of bio-antifreezes, the antifreeze glycoprotein, AFGP. The AFP III and AFGP are compositionally and structurally completely different, and synthesized by fishes in different suborders. The presence of the similar polyprotein structures in the different types of antifreeze genes may imply a common organizational mechanism in the fish genomes for adapting to the extremely cold polar environment.


Aggregated human gamma-globulin-induced proliferation and polyclonal activation of murine B lymphocytes.
Murine splenic B lymphocytes are stimulated to proliferate and undergo polyclonal activation in the presence of heat-aggregated human gamma-globulin (AHGG). Splenic macrophages are required to generate the proliferative and polyclonal antibody responses. The polyclonal response as opposed to the proliferative response is dependent upon the presence of T lymphocytes. The stimulatory molecule responsible for the AHGG-induced proliferative and polyclonal activation is derived from incubation of AHGG with splenic macrophages. The biologically active moiety is derived from the Fc portion of the HGG molecule and is approximately 14,000 m.w. The method of aggregation is critical for the generation of stimulatory HGG preparations. Heat aggregation is the only method produced a biologically active preparation


Comparison of endovenous radiofrequency versus 810 nm diode laser occlusion of large veins in an animal model.
Endovenous occlusion using radiofrequency (RF) energy has been shown to be effective for the elimination of sapheno-femoral reflux and subsequent elimination of varicose veins. Recently, endovenous laser occlusion has been introduced with initial clinical reports indicating effective treatment for varicose veins. However, in our practice we note increased peri-operative hematoma and tenderness with the laser. Little is known regarding the mechanism of action of this new laser vein therapy. To better understand the mechanism of action of endovenous laser vs. the endovenous RF procedure in the jugular vein of the goat model. A bilateral comparison was performed using 810 nm diode laser transmitted by a bare-tipped optical fiber vs. the RF delivery by engineered electrodes with a temperature feedback loop using a thermocouple (Closure procedure) in three goat jugular veins. Immediate and one-week results were studied radiographically and histologically. Temperature measurements during laser treatment were performed by using an array of up to five thermocouples, spaced 2 mm apart, placed adjacent to a laser fiber tip during goat jugular vein treatment. Immediate findings showed that 100% of the laser-treated veins showed perforations by histologic examination and immediate contrast fluoroscopy. The RF-treated side showed immediate constriction with maintenance of contrast material within the vein lumen and no perforations. The difference in acute vein shrinkage was also dramatic as laser treatments resulted in vein shrinkage of 26%, while RF-treated veins showed a 77% acute reduction in diameter. At one week, extravasated blood that leaked into the surrounding tissue of laser treated veins acutely, continued to occupy space and impinge on surrounding structures including nerves. For the laser treatment, the highest average temperature was 729 degrees C (peak temperature 1334 degrees C) observed flush with the laser fiber tip, while the temperature feedback mechanism of the RF method maintains temperatures at the electrodes of 85 degrees C. Vein perforations, extremely high intravascular temperatures, failure to cause significant collagen shrinkage, and intact endothelium in an animal model justify a closer look at the human clinical application of the 810 nm endovenous laser technique. Extravasated blood impinging on adjacent structures may theoretically lead to increased peri-operative hematoma and tenderness. Further study and clinical investigation is warranted.


DNA topoisomerase II interacts with Lim15/Dmc1 in meiosis.
Lim15/Dmc1 is a meiosis specific RecA-like protein. Here we propose its participation in meiotic chromosome pairing-related events along with DNA topoisomerase II. Analysis of protein-protein interactions using in vitro binding assays provided evidence that Coprinus cinereus DNA topoisomerase II (CcTopII) specifically interacts with C.cinereus Lim15/Dmc1 (CcLim15). Co-immunoprecipitation experiments also indicated that the CcLim15 protein interacts with CcTopII in vivo. Furthermore, a significant proportion of CcLim15 and CcTopII could be shown to co-localize on chromosomes from the leptotene to the zygotene stage. Interestingly, CcLim15 can potently activate the relaxation/catenation activity of CcTopII in vitro, and CcTopII suppresses CcLim15-dependent strand transfer activity. On the other hand, while enhancement of CcLim15's DNA-dependent ATPase activity by CcTopII was found in vitro, the same enzyme activity of CcTopII was inhibited by adding CcLim15. The interaction of CcLim15 and CcTopII may facilitate pairing of homologous chromosomes.


Modern mapping and ablation of idiopathic outflow tract ventricular arrhythmias.
Outflow tract (OT) premature ventricular complexes (PVCs) are being recognized as a common and often troubling, clinical electrocardiographic finding. The OT areas consist of the Right Ventricular Outflow Tract (RVOT), the Left Ventricular Outflow Tract (LVOT), the Aortomitral Continuity (AMC), the aortic cusps and the Left Ventricular (LV) summit. By definition, all OT PVCs will exhibit an inferior QRS axis, defined as positive net forces in leads II, III and aVF. Activation mapping using the contemporary 3D mapping systems followed by pace mapping is the cornerstone strategy of every ablation procedure in these patients. In this mini review we discuss in brief all the modern mapping and ablation modalities for successful elimination of OT PVCs, along with the potential advantages and disadvantages of each ablation technique.


Do post-surgical multiresistant urinary infections occur in horses? Case of unilateral pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria as a complication of cystotomy.
Pyelonephritis is a serious condition that is rarely described in horses. In contrast, urinary tract infections are common in humans and small animals, and multi-drug-resistant urinary infections are an emerging threat. In this report, we describe a horse with unilateral pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria belonging to the Enterobacter cloacae complex. [Correction added on 9 August 2023, after first online publication: The preceding sentence was corrected.] An 11-year-old Swedish warmblood gelding was diagnosed with a cystolith and a cystotomy through an open left para-inguinal approach was performed. Seven days after surgery the horse presented with pyrexia, dullness and colic. Diagnostic testing and renal transabdominal ultrasonography confirmed the presence of a right-sided pyelonephritis. Culture and antimicrobial susceptibility testing revealed a pure growth of extended-spectrum beta-lactamases-producing E. cloacae complex bacteria with resistance against beta-lactams, aminoglycoside and trimethoprim-sulphonamide classes. Treatment included prolonged oral antimicrobials according to susceptibility testing results (enrofloxacin), judicious use of non-steroidal anti-inflammatory drugs, fluid therapy and gastric ulcer prophylaxis. The horse recovered successfully and is currently in good health (follow-up of 5 years). Once the infection resolved, unilateral renal scarring occurred. Multidrug-resistant upper-urinary infections occur in horses and should be considered in a post-surgical patient that develops fever. Early diagnosis, urine bacterial culturing and antimicrobial susceptibility testing were crucial in this case to successful management.


Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction.
Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in beta cells. Although vascular TRPM3 mRNA has been reported, there is no knowledge of TRPM3 protein or its regulation and function in the cardiovascular system. To determine the relevance and regulation of TRPM3 in vascular biology. TRPM3 expression was detected at mRNA and protein levels in contractile and proliferating vascular smooth muscle cells. Calcium entry evoked by pregnenolone sulfate or sphingosine was suppressed by TRPM3 blocking antibody or knock-down of TRPM3 by RNA interference. Low-level constitutive TRPM3 activity was also detected. In proliferating cells, channel activity was coupled negatively to interleukin-6 secretion via a calcium-dependent mechanism. In freshly isolated aorta, TRPM3 positively modulated contractile responses independently of L-type calcium channels. Concentrations of pregnenolone sulfate required to evoke responses were higher than the known plasma concentrations of the steroids, leading to a screen for other stimulators. beta-Cyclodextrin was one of few stimulators of TRPM3, revealing the channels to be partially suppressed by endogenous cholesterol, the precursor of pregnenolone. Elevation of cholesterol further suppressed channel activity and loading with cholesterol to generate foam cells precluded observation of TRPM3 activity. The data suggest functional relevance of TRPM3 in contractile and proliferating phenotypes of vascular smooth muscle cells, significance of constitutive channel activity, regulation by cholesterol, and potential value of pregnenolone sulfate in therapeutic vascular modulation.


Inter-hemispherical shoreline surveys of anthropogenic marine debris - A binational citizen science project with schoolchildren.
Anthropogenic marine debris (AMD) is a global problem and the identification of its sources is essential for adequate mitigation strategies. Herein we examined whether AMD density and composition differed between two countries with contrasting socio-economic backgrounds and marine litter sources (i.e. Chile and Germany). In nationwide beach litter surveys, we used a citizen science approach with schoolchildren and their teachers. Litter densities were substantially higher in Chile than in Germany. The different geographic zones surveyed in both countries showed strong grouping tendencies according to their main economic activities (tourism, shipping, fisheries/aquaculture), major litter sources, and AMD composition, in terms of dominance and diversity of AMD types. The results suggest that beach litter composition can be used as a simple proxy to identify AMD sources, and also that law enforcement and education can help mitigate the problem; however, for efficient solutions, production and consumption of plastics must be reduced.


Enhanced pulmonary toxicity in copper-deficient rats exposed to hyperoxia.
The antioxidant enzyme superoxide dismutase (SOD) found in the cytosol of eucaryotic cells and the plasma protein ceruloplasmin are copper containing proteins though to be important in providing protection from oxygen toxicity. To investigate the hypothesis that copper deficiency in the rat could result in decreased lung SOD activity and plasma ceruloplasmin concentration resulting in increased susceptibility to O2 lung damage, we performed a series of experiments exposing copper-deficient and control rats to normobaric and hyperbaric hyperoxia. Lung SOD activity in the copper-deficient rats was found to be 56% of control and ceruloplasmin content was 6% of control. The copper-deficient rats exhibited increased mortality and enhanced pulmonary toxicity as evidenced by increased pathologic damage and lung edema during the normobaric exposure to 85% O2. Copper-deficient animals also showed increased susceptibility to a hyperbaric exposure of 4 ata of 100% O2 with a decreased time of survival. The copper-deficient rat represents a new model for the study of oxidant injury.


Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis.
A 70-year old man with a 14 year history of Sjögren syndrome, interstitial pneumonia, and autoimmune hepatitis (AIH) was admitted to our hospital due to hyponatremia with a one month history of fatigue, thirst, and nausea. Laboratory tests on admission revealed that this patient had a central adrenal insufficiency. Pituitary magnetic resonance imaging (MRI) further showed swelling of the stalk and posterior lobe of his pituitary, suggesting infundibulo-hypophysitis. Based on his past history of autoimmune disease, his serum IgG4 levels were measured and found to be remarkably high (924 mg/ dL). Previous biopsy specimens from his liver, lung, and parotid gland were immunostained for IgG4, which revealed a marked infiltration of IgG4-positive plasma cells. As a result of our tests, we made a diagnosis of IgG4-related systemic disease. Interestingly, a subsequent MRI scan at three weeks after the patient commenced glucocorticoid replacement therapy for adrenal insufficiency showed that the swelling of his pituitary stalk was reduced. This finding suggested that IgG4-related hypophysitis may improve either as a result of a supplemental dose of glucocorticoid or possibly spontaneously. Although six cases of IgG4-related hypophysitis have been reported in the scientific literature published in English, our current case is the first in which IgG4-related hypophysitis likely occurred as a result of a long-term history of IgG4-related systemic disease. We report this case herein and review the relevant literature.


Limb apraxia in a patient with cerebral infarct: diffusion tensor tractography study.
We report on a patient with ideomotor apraxia (IMA) and limb-kinetic apraxia (LKA) following cerebral infarct, which demonstrated neural tract injuries by diffusion tensor tractography (DTT). A 67-year-old male was diagnosed as cerebral infarct in the left frontal cortex (anterior portion of the precentral gyrus and prefrontal cortex) and centrum semiovale. The patient presented with severe paralysis of the right upper extremity and mild weakness of the right lower extremity at onset. At the time of DTT scanning (5 months after onset), the patient was able to move all joint muscles of the right upper extremity against gravity, except for the finger extensors, which he could extend partially against gravity. The patient showed intact ideational plan for motor performance; however, his movements were slow, clumsy, and mutilated when executing grasp-release movements of his affected hand. The patient's score on the ideomotor apraxia test was 20 (cut-off score < 32). DTTs for premotor cortex fibers, supplementary motor area fibers, and superior longitudinal fasciculus of the left hemisphere showed partial injuries, compared with those of the right side, and these injuries appeared to be responsible for IMA and LKA in this patient.


Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.
Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.


Efficacy of single fraction conventional radiation therapy for painful uncomplicated bone metastases: a systematic review and meta-analysis.
Single fraction radiotherapy (SFRT) and multiple fraction radiotherapy (MFRT) are effective for painful uncomplicated bone metastases and have been shown to be of similar efficacy. The optimal conventional external beam SFRT dose for maximum pain relief remains uncertain. The aim of this systematic review was to comprehensively review and synthesize overall pain response rates by dose. A literature search was conducted in Ovid MEDLINE(R) (1946 to June 2016 week 3), Embase Classic & Embase (1947 to 2016 week 26) and Cochrane Central Register of Controlled Trials (May 2016) using keywords such as bone metastases, radiotherapy and single fraction (SF). The 635 results from the search were screened, and ultimately 27 were included for quantitative synthesis. The review indicated that 10 and 6 Gy may produce superior overall response (OR) and complete response (CR) rates compared to 8 Gy, and 6 Gy may result in better partial response (PR) than 8 Gy. However, only a few studies documented doses other than 8 Gy. In trials that directly compared 8 Gy to 4 Gy or 6 Gy, 8 Gy was deemed statistically superior. 8 Gy SFRT was the most commonly administered dose for palliation of bone metastases supporting its efficacy and safety. Future studies should explore the efficacy of 10 Gy while minimizing its side effects.


[Exercise test in athletes].
The particularities of exercise tests in athletes concern mainly the exertion protocols adapted to their increased physical capacities and the interpretation of ECG tracing which can sometimes be very special at rest and also misleading during exercise. In the great majority of cases, the test used is both cardiac and pulmonary, in order to assess the aerobic capacities, the maximal aerobic power, and the determination of ventilation thresholds (programming and follow-up of training...). More infrequently, the test is used to detect cardiovascular diseases, especially during a longitudinal follow-up of high-level athletes, or to exclude it in case of cardiovascular symptoms, atypical resting ECG or even in case of suspicion of disease (arrhythmia, cardiac chamber hypertrophy or dilation at echocardiography). In more aged sportsmen (athletes masters), exercise tests performed are usually required for screening coronary heart disease. In this case the test protocols should be more adapted for screening than for the assessment of sportive capacities.


Safety of unwrapped spherical orbital implants.
To determine the exposure rate of unwrapped spherical orbital implants after enucleation surgery. Retrospective review of consecutive case series. All patients undergoing orbital implantation during enucleation surgery from October 1999 to September 2003 were included. Charts were reviewed for preoperative diagnoses, type and size of implant, use of a wrapping material, and complications. Twenty-six consecutive patients underwent enucleation surgery without wrapping material. Nineteen patients received porous polyethylene, 5 patients received polymethylmethacrylate, and 2 received hydroxyapatite. Mean implant diameter was 21.03 mm. Mean follow-up was 17.1 months (range, 2 to 43 months). There were no complications of implant extrusion, exposure, infection, or migration. The use of unwrapped spherical orbital implants may be associated with a low rate of early exposure. Careful choice of implant type may help reduce the risk of implant exposure.