Pelvic nerve stimulation-induced pressor responses in corpus cavernosum of anesthetized dogs.
To analyze the mechanism of penile erection and pathogenesis of impotence, pressures in the corpus cavernosum in anesthetized dogs were measured. Pelvic nerve stimulation produced pressor responses in a frequency-dependent manner. Intravenous injections of NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, dose dependently attenuated the response, and the inhibition was reversed by intravenous injection of L-arginine but not of D-arginine. The response was also inhibited by NG-nitro-L-arginine injected into the corpus cavernosum, the potency being approximately 10 times of that applied intravenously. The intracavernous injection of L-arginine restored the response. NG, NG-dimethylarginine, an endogenous NO synthase inhibitor, dose dependently attenuated the stimulation-induced response, which was restored by an intracavernous injection of L-arginine. An intravenous injection of hexamethonium abolished the pressor response to nerve stimulation, whereas phentolamine and atropine did not significantly alter the response. These findings suggest that an increase in intracavernous pressure caused by pelvic nerve stimulation in anesthetized dogs is mediated by NO liberated from postganglionic neurons that originate in the ganglion located in the vicinity of corpus cavernosum.


Protein and lipid expansion microscopy with trypsin and tyramide signal amplification for 3D imaging.
Expansion microscopy, whereby the relative positions of biomolecules are physically increased via hydrogel expansion, can be used to reveal ultrafine structures of cells under a conventional microscope. Despite its utility for achieving super-resolution imaging, expansion microscopy suffers a major drawback, namely reduced fluorescence signals caused by excessive proteolysis and swelling effects. This caveat results in a lower photon budget and disfavors fluorescence imaging over a large field of view that can cover an entire expanded cell, especially in 3D. In addition, the complex procedures and specialized reagents of expansion microscopy hinder its popularization. Here, we modify expansion microscopy by deploying trypsin digestion to reduce protein loss and tyramide signal amplification to enhance fluorescence signal for point-scanning-based imaging. We name our new methodology TT-ExM to indicate dual trypsin and tyramide treatments. TT-ExM may be applied for both antibody and lipid staining. TT-ExM displayed enhanced protein retention for endoplasmic reticulum and mitochondrial markers in COS-7 cell cultures. Importantly, TT-ExM-based lipid staining clearly revealed the complex 3D membrane structures in entire expanded cells. Through combined lipid and DNA staining, our TT-ExM methodology highlighted mitochondria by revealing their DNA and membrane structures in cytoplasm, as well as the lipid-rich structures formed via phase separation in nuclei at interphase. We also observed lipid-rich chromosome matrices in the mitotic cells. These high-quality 3D images demonstrate the practicality of TT-ExM. Thus, readily available reagents can be deployed in TT-ExM to significantly enhance fluorescence signals and generate high-quality and ultrafine-resolution images under confocal microscopy.


Influence of gene flow and breeding tactics on gene diversity within populations.
Expressions describing the accumulation of gene correlations within and among lineages and individuals of a population are derived. The model permits different migration rates by males and females and accounts for various breeding tactics within lineages. The resultant equations enable calculation of the probabilistic quantities for the fixation indices, rates of loss of genetic variation, accumulation of inbreeding, and coefficients of relationship for the population at any generation. All fixation indices were found to attain asymptotic values rapidly despite the consistent loss of genetic variation and accumulation of inbreeding within the population. The time required to attain asymptotic values, however, was prolonged when gene flow among lineages was relatively low (less than 20%). The degree of genetic differentiation among breeding groups, inbreeding coefficients, and gene correlations within lineages were found to be primarily functions of breeding tactics within groups rather than gene flow among groups. Thus, the asymptotic value of S. Wright's island model is not appropriate for describing genetic differences among groups within populations. An alternative solution is provided that under limited conditions will reduce to the original island model. The evolution of polygynous breeding tactics appears to be more favorable for promoting intragroup gene correlations than modification of migration rates. Inbreeding and variance effective sizes are derived for populations that are structured by different migration and breeding tactics. Processes that reduce the inbreeding effective population size result in a concomitant increase in variance effective population size.


Human papillomavirus lesions in association with cervical dysplasias and neoplasias.
A series of 620 cervical biopsy specimens (precancerous and malignant) was assessed morphologically with special reference to the concomitant appearance of human papillomavirus lesions. Tissue samples from 346 of these biopsy specimens were stained for human papillomavirus antigens using the immunoperoxidase-peroxidase-anti-peroxidase (PAP) technique. Papillomavirus lesions were found in 55.6% of the biopsy specimens associated with all degrees of epithelial atypia. The mean age of the women with papillomavirus (condylomatous) changes was significantly lower (P less than .0001) than that of women without these lesions, ie, those who had dysplasia/neoplasia without concomitant papillomavirus changes. Flat and inverted condylomas were most frequent between the ages 20 and 39 and were accompanied by more severe dysplasias than the papillomatous condylomas. In immunoperoxidase-PAP staining, 56% of the papillomavirus lesions were positive, the positivity being inversely related to the degree of epithelial atypia, and bearing some correlation with the condyloma type (papillary 100%, inverted 70%, and flat 52%). Although the results show a clear-cut association of human papillomavirus lesions with premalignant, and to a lesser extent with malignant squamous cell lesions of young sexually active women, thus suggesting a relationship between the virus and cancer, a careful follow-up study is needed to fully elucidate this relationship.


Catch up growth following abuse.
Poor growth in association with child abuse is well recognised, but the eventual outcome with respect to growth has not been clearly defined. In a study of 95 children who had suffered child abuse standard deviation (SD) scores for height and weight were significantly below the mean at presentation and improved at follow up. Sixty four children who remained at home showed significant increase in height SD scores only (p less than 0.01). Twenty children were either taken into long term fostercare or adopted and showed significant increases in height and weight SD scores (p less than 0.001 and p less than 0.01, respectively). The remaining 11 children, who were fostered for short periods only, showed little change in either index. Catch up growth for height defined as a change in SD scores of one or more occurred in seven (11%) of the children at home compared with 11 (55%) of those taken into long term fostercare (p less than 0.001). Catch up growth for weight occurred in 14 (22%) of those at home and 10 (50%) of those in long term fostercare (p less than 0.01). Children suffering child abuse show greater catch up growth when taken into long term fostercare. Growth patterns should be used to decided where these children are placed.


Oxidative instability of hemoglobin E (β26 Glu→Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): Relevance to HbE/β-thalassemia.
When adding peroxide (H2O2), β subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired α subunits within red cells and/or co-inheritance of another β subunit mutant, HbE (β26 Glu→Lys) have been implicated in the pathogenesis and severity of β thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of βCys93 to reflect oxidative instability of β subunits. In the presence of free α subunits and H2O2, both HbA and HbE showed βCys93 oxidation which increased with higher H2O2 concentrations. In the presence of Alpha-hemoglobin stabilizing protein (AHSP), which stabilizes the α-subunit in a redox inactive hexacoordinate conformation (thus unable to undergo the redox ferric/ferryl transition), Cys93 oxidation was substantially reduced in both proteins. These experiments establish two important features that may have relevance to the mechanistic understanding of these two inherited hemoglobinopathies, i.e. HbE/β thalassemia: First, a persistent ferryl/ferryl radical in HbE is more damaging to its own β subunit (i.e., βCys93) than HbA. Secondly, in the presence of excess free α-subunit and under the same oxidative conditions, these events are substantially increased for HbE compared to HbA, and may therefore create an oxidative milieu affecting the already unstable HbE.


Cascades and dissipation ratio in rotating magnetohydrodynamic turbulence at low magnetic Prandtl number.
A phenomenology of isotropic magnetohydrodynamic (MHD) turbulence subject to both rotation and applied magnetic field is presented. It is assumed that the triple correlation decay time is the shortest between the eddy turn-over time and the ones associated to the rotating frequency and the Alfvén wave period. For Pm=1 it leads to four kinds of piecewise spectra, depending on four parameters: injection rate of energy, magnetic diffusivity, rotation rate, and applied field. With a shell model of MHD turbulence (including rotation and applied magnetic field), spectra for Pm ≤ 1 are presented, together with the ratio between magnetic and viscous dissipations.


High-energy, high-repetition-rate picosecond pulses from a quasi-CW diode-pumped Nd:YAG system.
We report on a high-power quasi-CW pumped Nd:YAG laser system, producing 130 mJ, 64 ps pulses at 1064 nm wavelength with a repetition rate of 300 Hz. Pulses from a Nd:YVO(4) oscillator are first amplified by a regenerative amplifier to the millijoule level and then further amplified in quasi-CW diode-pumped Nd:YAG modules. Pulsed diode pumping enables a high gain at repetition rates of several hundred hertz, while keeping thermal effects manageable. Birefringence compensation and multiple thermal-lensing-compensated relay-imaging stages are used to maintain a top-hat beam profile. After frequency doubling, 75 mJ pulses are obtained at 532 nm. The intensity stability is better than 1.1%, which makes this laser an attractive pump source for a high-repetition-rate optical parametric amplification system.


Multiple trichoepitheliomas in an alpaca (Lama pacos).
A 13-yr-old male Alpaca (Lama pacos) presented with multiple ovoid, well-circumscribed, nonulcerated intradermal masses. Individual masses measured 1-4 cm in diameter, and the overlying skin was alopecic. Several of the masses were surgically removed and evaluated microscopically. Histopathologic evaluation demonstrated multiple dermal cysts lined by neoplastic follicular epithelium. The cysts were filled with multiple layers of lamellar keratin and lined by abortive inner and outer root sheaths exhibiting cellular atypia, supporting the diagnosis of trichoepitheliomas. No additional treatment was initiated, and the alpaca continues to do well.


Association between imaging parameter changes and triangular fibrocartilage complex injury after distal radius fractures.
Triangular fibrocartilage complex (TFCC) injury is a frequent soft tissue injury that has been observed to accompany distal radius fractures (DRFs) with concomitant changes in radiologic parameters. The aim of this study was to investigate the relevance of distal radial radiologic parameters associated with DRF and traumatic TFCC injury. A total of 172 patients with distal radius fractures who underwent X-ray, CT, and MRI before undergoing volar locking plate or external splint fixation between October 2021 and December 2022 were included in this study. An analysis of various radiologic parameters and the classification of fracture type and TFCC injuries by CT and MRI was performed. All patients were divided into the TFCC uninjured group and the injured group. The incidence and relevant radiologic parameters were compared. This study included 76 males and 96 females with a mean age of 56.1 years. Among all patients, 33 (19.2%), 40 (23.2%), and 99 (57.6%) had DRF with A, B, and C fractures, respectively, according to the AO/OTA classification. In patients with fractures, the TFCC was found to be injured in 54.1% (93/172) of patients (type 1A in 21, 1B in 46, 1C in 39, and 1D in 35) but uninjured in 45.9% (79/172). There were significant differences between the TFCC injured and uninjured groups regarding the radius length (p = 0.044) and DRUJ distance (p = 0.040) of radiologic parameters that changed with DRF, although there were no differences between the two groups regarding gender, age, injured side, intra- and extra-articular, radius inclination and palmer tilt angle, or sagittal translation. Within the TFCC injured group, the radius length and DRUJ distance were 4.83 mm and 2.95 mm less or wider than 7.19 mm and 1.83 mm of the uninjured group. Moreover, shorter radius length was related to type lB TFCC injury (p = 0.041). Both radius length (AUC = 0.658) and DRUJ distance (AUC = 0.582) had no convincing predictive value for TFCC injury in DRF. 1B TFCC injury is most common in patients with DRF and concomitant TFCC injury. Both radius length and DRUJ distance have a significant statistical correlation with TFCC injury, and patients with TFCC injury tend to have a shortened radius and wider DRUJ distance, although they have no predictive value for TFCC injury in DRF. In addition, a shorter radius length was related to type lB TFCC injury.


Sex differences in the fractal dynamics of force control during maximal handgrip.
This work examines the temporal structure of force fluctuations during maximal handgrip with detrended fluctuation analysis (DFA α). Here, we assess the influence of fatigue and sex on force complexity during unimanual handgrip for the fatigued and the contralateral, non-fatigued hand. Participants randomly completed experimental sessions requiring fatiguing handgrip contractions or control measurements only. Maximal unimanual forces of both hands were measured before and after the fatigue trial or a time-matched control visit. DFA revealed substantially lower alpha values for females (PRE = 1.15, POST = 1.25) compared to males (PRE = 1.30, POST = 1.33) regardless of fatigue (p < 0.01, d = 0.738) for the dominant hand with a similar pattern observed for the contralateral, non-fatigued hand (p = 0.045, d = 0.561). Females also showed greater alpha changes (Δ= 0.09) versus males (Δ = 0.01) following fatigue (p = 0.028, ηp2 = 0.151). The data provide evidence of reduced force complexity during successive maximal handgrip contractions for females, but not males. Our findings highlight task-specific factors involving force control and demonstrate the utility of complexity analyses to provide insights regarding the influence of sex on motor control strategies.


Everyday scale errors.
Young children occasionally make scale errors- they attempt to fit their bodies into extremely small objects or attempt to fit a larger object into another, tiny, object. For example, a child might try to sit in a dollhouse-sized chair or try to stuff a large doll into it. Scale error research was originally motivated by parents' and researchers' informal accounts of these behaviors. However, scale errors have only been documented using laboratory procedures designed to promote their occurrence. To formally document the occurrence of scale errors in everyday settings, we posted a survey on the internet. Across two studies, participants reported many examples of everyday scale errors that are similar to those observed in our labs and were committed by children of the same age. These findings establish that scale errors occur in the course of children's daily lives, lending further support to the account that these behaviors stem from general aspects of visual processing.


Unisexual reproduction.
Sexual reproduction is ubiquitous throughout the eukaryotic kingdom, but the capacity of pathogenic fungi to undergo sexual reproduction has been a matter of intense debate. Pathogenic fungi maintained a complement of conserved meiotic genes but the populations appeared to be clonally derived. This debate was resolved first with the discovery of an extant sexual cycle and then unisexual reproduction. Unisexual reproduction is a distinct form of homothallism that dispenses with the requirement for an opposite mating type. Pathogenic and nonpathogenic fungi previously thought to be asexual are able to undergo robust unisexual reproduction. We review here recent advances in our understanding of the genetic and molecular basis of unisexual reproduction throughout fungi and the impact of unisex on the ecology and genomic evolution of fungal species.


Contrast-enhanced magnetic resonance characteristics of arteriovenous malformations after γ knife radiosurgery: predictors of post-angiographic obliteration hemorrhage.
The reported cumulative risk of post-angiographic obliteration (post-AO) hemorrhage from arteriovenous malformations (AVMs) following gamma knife radiosurgery (GKRS) over 10 years is 2.2%. To identify the warning signs of post-AO hemorrhage by analyzing the characteristics of enhancement on contrast-enhanced MRI magnetic resonance imaging (MRI) of AVMs with post-AO hemorrhage. We performed a retrospective analysis of 121 patients whose AVMs were angiographically obliterated within 5 years of GKRS without hemorrhage and who received at least 1 contrast-enhanced MRI after GKRS (group 1), and 7 patients who experienced post-AO hemorrhage (group 2). We analyzed the enhancement persistence ratio (the percentage of AVMs with persisting enhancement on contrast-enhanced T1-weighted image after obliteration) and the change in size of the enhanced region over time in each patient. The enhancement persistence ratio showed no significant difference between the 2 groups (89.4% vs 100% for groups 1 and 2, respectively; P=.401). While most cases in group 1 showed a tendency to decrease in size and gradually stabilize following GKRS, there were significantly more cases in group 2 with obvious increment of the enhanced regions within 1 year of angiographic obliteration compared with the previous measurement (4.96% vs 71.4% for groups 1 and 2, respectively; P<.0001). Our results suggest that AVMs that show an increase in the size of the enhanced region within 1 year of angiographic obliteration should be followed up with caution for post-AO hemorrhage. Persisting enhancement itself is not positively associated with subsequent hemorrhage.


NSAID enteropathy: appearance at CT and MR enterography in the age of multi-modality imaging and treatment.
CT and MR enterography and capsule endoscopy are increasingly used as routine diagnostic tests for patients with potential small bowel disorders and obscure gastrointestinal bleeding. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs that disrupt prostaglandin synthesis and result in a variety of localized complications within the small bowel ranging from ulcer formation to characteristic circumferential strictures, or diaphragms. NSAID enteropathy encompasses this spectrum of acute and chronic inflammatory sequelae, and is associated with typical findings at capsule endoscopy and surgery. Herein we review the typical clinical presentation of NSAID enteropathy, in addition to its endoscopic appearances, focusing on imaging findings at cross-sectional enterography. Multiple, short-segment strictures are the hallmarks of imaging diagnosis. Strictures may have minimal hyperenhancement or wall thickening, but these findings are typically symmetric and circumferential with respect to the bowel lumen. Multifocal Crohn's strictures, and occasionally radiation-induced strictures or adhesions, will mimic NSAID diaphragms. Multi-phase or multi-sequence imaging at CT and MR enterography increase diagnostic confidence in stricture presence. Strategies for subsequent workup and therapy after enterography are also discussed. Given the frequent use of NSAIDs and typical appearance of these strictures, knowledge of characteristic imaging findings can be particularly useful when evaluating patients with anemia and recurrent small bowel obstruction.


The HrpN effector of Erwinia amylovora, which is involved in type III translocation, contributes directly or indirectly to callose elicitation on apple leaves.
Erwinia amylovora is responsible for fire blight of apple and pear trees. Its pathogenicity depends on a type III secretion system (T3SS) mediating the translocation of effectors into the plant cell. The DspA/E effector suppresses callose deposition on apple leaves. We found that E. amylovora and Pseudomonas syringae DC3000 tts mutants or peptide flg22 do not trigger callose deposition as strongly as the dspA/E mutant on apple leaves. This suggests that, on apple leaves, callose deposition is poorly elicited by pathogen-associated molecular patterns (PAMPs) such as flg22 or other PAMPs harbored by tts mutants and is mainly elicited by injected effectors or by the T3SS itself. Callose elicitation partly depends on HrpW because an hrpW-dspA/E mutant elicits lower callose deposition than a dspA/E mutant. Furthermore, an hrpN-dspA/E mutant does not trigger callose deposition, indicating that HrpN is required to trigger this plant defense reaction. We showed that HrpN plays a general role in the translocation process. Thus, the HrpN requirement for callose deposition may be explained by its role in translocation: HrpN could be involved in the translocation of other effectors inducing callose deposition. Furthermore, HrpN may also directly contribute to the elicitation process because we showed that purified HrpN induces callose deposition.


Healthy eating and physical activity environments in out-of-school hours care: an observational study protocol.
Childcare settings have been widely identified as important venues for promoting healthy lifestyles to children. Out-of-school hours care (OSHC) is a rapidly growing childcare service, yet there has been limited research reported on healthy eating and physical activity (HEPA) environments within the Australian OSHC setting. This research aims to describe the HEPA environments related to foods and beverages served, staff behaviours and child physical activity levels across two local health districts within New South Wales, Australia. This study will provide evidence to support future interventions and policies in Australian OSHC settings. A cross-sectional study design will be used to describe the food and beverages provided and child activity levels, and report on environmental correlates. OSHC programmes will be visited on non-consecutive weekdays between 2018 and 2020. The frequency of foods and beverages offered will be observed and categorised into food groups aligned to the Australian Dietary Guidelines. Children's physical activity will be measured using ActiGraph wGT3X-BT accelerometers. Staff behaviour will be captured via direct observation and the System for Observing Staff Promotion of Activity and Nutrition. Short interviews with programme directors will gather contextual information about OSHC practices and policies. Findings will be disseminated through peer-reviewed scientific journals, conference presentations and individualised feedback to each participating service. Ethical approval was granted by the University of Wollongong Human Research Ethics Committee (HE17/490).


[Endothelin receptor blockers--one more agent for the treatment of pulmonary hypertension].
Data on participation of derangements of pulmonary vessel endothelial function in pathogenesis of pulmonary hypertension served as basis for therapeutic use of prostanoids, sildenafil, and endothelin(ET) receptor blockers. A first representative of the latter group - bosentan (nonselective ET-receptor antagonist) has been recently registered as an agent for the treatment of pulmonary hypertension. Bosentan and other ET receptor antagonists has been studied in several trials. Results of these trials are reviewed in this paper which also contains characteristics of main representatives of ET receptor antagonists as well as information on their tolerability and major side effects.


The ability of three nickel-titanium mechanized systems to negotiate and shape MB2 canals in extracted maxillary first molars: a micro-computed tomographic study.
To evaluate the influence of three engine-driven NiTi file systems manufactured from different NiTi alloys for the preparation of second mesiobuccal (MB2) canals in extracted maxillary first molars using a micro-computed tomographic (micro-CT) scanner. Thirty maxillary molars with two canals in the mesiobuccal root were selected and randomly divided into three groups (n = 10): Reciproc [REC; size 25, .08 taper; VDW, Munich, Germany], ProDesign R [PDR; size 25, .06 taper; Easy, Belo Horizonte, Brazil] and Mtwo [MO; size 25, .06 taper; VDW, Munich, Germany]. Before and after root canal preparation of the MB2 canal, the teeth were scanned using a micro-CT to evaluate canal transportation, centring ability, dentine thickness and volume change. The working time to achieve working length was also evaluated. All parameters were compared statistically using the Kruskal-Wallis and Dunn test for multiple comparisons, with a significance level of 5%. There was no significant difference amongst the groups regarding canal transportation and centring ability (P > 0.05). However, the PDR size 25, .06 taper group had significantly lower canal volume and volume of dentine removal compared with a MO size 25, .06 taper and REC size 25, .08 taper (P < 0.05). A root perforation was detected in MO size 25, .06 taper and REC size 25, .08 taper groups, respectively. Regarding the working time, the PDR size 25, .06 taper required a significantly longer time to achieve working length than MO size 25, .06 taper and REC size 25, .08 taper (P < 0.05). All NiTi systems had similar canal transportation, centring ability and increase in apical volume after preparation of MB2 canals. However, the PDR size 25, .06 taper had less volume of dentine removal, absence of root canal perforation and required a longer time to accomplish the root canal preparation.


Characterization of the activation domain of the Rad53 checkpoint kinase.
Rad53 protein, the yeast orthologue of the human checkpoint kinase Chk2, presents two highly conserved phosphorylatable threonine residues (T354 and T358) in the activation domain, whose phosphorylation is critical to allow the activation of the kinase. In this study we found that Rad53 protein variants in which alanine and/or aspartate replace the threonine residues 354 and/or 358 do not retain kinase activity and do not undergo auto-phosphorylation, leading to defect in the checkpoint response and iper-sensitivity to DNA damage and DNA replication stress agents. Interestingly, we found that the rad53-T358D mutation severely affects the kinase activity and causes accumulation of the S129-phosphorylated isoform of histone H2A, even during an unperturbed cell cycle, thus indicating the accumulation of spontaneous DNA breaks. We further found that the protein level of Sml1, which is the physiological inhibitor of ribonucleotide reductase, remains high during DNA replication in rad53-T358D cells, suggesting that an inadequate pool of dNTPs in checkpoint defective cells causes the accumulation of spontaneous DNA breaks. In conclusion, our results indicate that phosphorylation of both T354 and T358 residues strongly influences the catalytic activity of Rad53 also in unperturbed cell cycles, and support the notion that Rad53 is essential to preserve genome integrity, by controlling the level of Sml1 and the functionality of ribonucleotide reductase.


High Efficiency Breathable Thermoelectric Skin Using Multimode Radiative Cooling/Solar Heating Assisted Large Thermal Gradient.
This study proposes a Janus structure-based stretchable and breathable thermoelectric skin with radiative cooling (RC) and solar heating (SH) functionalities for sustainable energy harvesting. The challenge of the wearable thermoelectric generator arises from the small temperature difference. Thus, this dual-sided structure maximizes the thermal gradient between the body and the surrounding environment, unlike the previous works that rather concentrate on the efficiency of the thermoelectric generator itself. The Janus structure allows the device to switch to the other mode, optimizing electricity generation from a given weather condition. For these functionalities, for the first time, boron nitride-polydimethylsiloxane (BP) and graphene nanoplatelet-polydimethylsiloxane (GP) nanofiber (NF) are developed as substrates. The BP NF generates the RC capability of ΔTcooling = 4 °C, and the high solar absorbance of the GP NF enables it to be photothermally heated. The flip-overable thermoelectric skin (FoTES) achieves a maximum power output (Pmax ) of 5.73 µW cm-2 in RC mode, surpassing SH mode by 5.55 µW cm-2 in the morning. In the afternoon, it generates a Pmax of 18.59 µW cm-2 in SH mode, outperforming RC mode by 15.56 µW cm-2 . This work contributes to the advancement of wearable electronics, offering a sustainable power source in a wearable form.


Parent perceptions of the quality of information received about a child's cancer.
Parents' perceptions of the quality of information communicated by their child's oncologist about the child's cancer are not well understood. We conducted a cross-sectional survey of 194 parents of children with cancer (response rate 70%), treated at the Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Mass, and the children's physicians. Parents were asked to report the quality of information received about the child's cancer in several domains. Most parents reported that information about their child's cancer had been excellent (49%) or good (41%) overall, and ratings were similar for information about diagnosis (P = 0.62) and treatment (P = 0.59). Fewer parents felt they received high quality information about how cancer treatment is working (P < 0.001), likelihood of cure (P < 0.001), what the diagnosis means for the future (P < 0.001), and whether there is a cause for the child's cancer (P < 0.001). In multivariable models, parents were more likely to consider information of high quality when they also rated physician communication style highly. The accuracy of their knowledge on likelihood of cure and the child's future limitations, however, was not associated with quality ratings. Although parents feel that they have received high quality cancer information overall, parents feel they receive lower quality information about issues relating to the child's future. Yet quality ratings are not associated with their actual knowledge. Parent perceptions of quality represent one, but not the only, facet of communication quality.


Common and emerging infectious diseases in the animal shelter.
The beneficial role that animal shelters play is unquestionable. An estimated 3 to 4 million animals are cared for or placed in homes each year, and most shelters promote public health and support responsible pet ownership. It is, nonetheless, inevitable that shelters are prime examples of anthropogenic biological instability: even well-run shelters often house transient, displaced, and mixed populations of animals. Many of these animals have received minimal to no prior health care, and some have a history of scavenging or predation to survive. Overcrowding and poor shelter conditions further magnify these inherent risks to create individual, intraspecies, and interspecies stress and provide an environment conducive to exposure to numerous potentially collaborative pathogens. All of these factors can contribute to the evolution and emergence of new pathogens or to alterations in virulence of endemic pathogens. While it is not possible to effectively anticipate the timing or the pathogen type in emergence events, their sites of origin are less enigmatic, and pathologists and diagnosticians who work with sheltered animal populations have recognized several such events in the past decade. This article first considers the contribution of the shelter environment to canine and feline disease. This is followed by summaries of recent research on the pathogenesis of common shelter pathogens, as well as research that has led to the discovery of novel or emerging diseases and the methods that are used for their diagnosis and discovery. For the infectious agents that commonly affect sheltered dogs and cats, including canine distemper virus, canine influenza virus, Streptococcus spp, parvoviruses, feline herpesvirus, feline caliciviruses, and feline infectious peritonitis virus, we present familiar as well as newly recognized lesions associated with infection. Preliminary studies on recently discovered viruses like canine circovirus, canine bocavirus, and feline norovirus indicate that these pathogens can cause or contribute to canine and feline disease.


High-performance liquid chromatography-tandem mass spectrometry with a new quadrupole/linear ion trap instrument.
The use of a new hybrid quadrupole/linear ion trap known as the Q TRAP offers unique benefits as a LC-MS-MS detector for both small and large molecule analyses. The instrument combines the capabilities of a triple quadrupole mass spectrometer and ion trap technology on a single platform. Product ion scans are conducted in a hybrid fashion with the fragmentation step accomplished via acceleration into the collision cell followed by trapping and mass analysis in the Q3 linear ion trap. This results in triple quadrupole fragmentation patterns with no inherent low molecular mass cutoff. In-trap fragmentation is also possible in order to provide triple MS (MS3) capabilities. There are also several scan modes that are not possible on conventional instruments that enable identification of analytes within complex biological matrixes for subsequent high sensitivity product ion scans. This report will describe the new hybrid instrument and the principles of operation, and also provide examples of the unique scan modes and capabilities of the Q TRAP for LC-MS-MS detection in metabolism identification.


Medical Treatment and Revascularization Options in Patients With Type 2 Diabetes and Coronary Disease.
There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF). This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement. A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy. Among 5,034 subjects, 15% had LVEF <50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT. CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.


Thin Films of n-Si/Poly-(CH3)3Si-Cyclooctatetraene: Conducting-Polymer Solar Cells and Layered Structures.
The optical and electronic properties of thin films of the solution-processible polymer poly-(CH(3))(3)Si-cyclooctatetraene are presented. This conjugated polymer is based on a polyacetylene backbone with (CH(3))(3)Si side groups. Thin transparent films have been cast onto n-doped silicon (n-Si) substrates and doped with iodine to form surfacebarrier solar cells. The devices produce photovoltages that are at the theoretical limit and that are much greater than can be obtained from n-Si contacts with conventional metals. Two methods for forming layered polymeric materials, one involving the spincoating of preformed polymers and the other comprising the sequential polymerization of different monomers, are also described. An organic polymer analog of a metal/insulator/metal capacitor has been constructed with the latter method.


Enantioselective synthesis of amines by combining photoredox and enzymatic catalysis in a cyclic reaction network.
Visible light-driven reduction of imines to enantioenriched amines in aqueous solution is demonstrated for the first time. Excitation of a new water-soluble variant of the widely used [Ir(ppy)3] (ppy = 2-phenylpyridine) photosensitizer in the presence of a cyclic imine affords a highly reactive α-amino alkyl radical that is intercepted by hydrogen atom transfer (HAT) from ascorbate or thiol donors to afford the corresponding amine. The enzyme monoamine oxidase (MAO-N-9) selectively catalyzes the oxidation of one of the enantiomers to the corresponding imine. Upon combining the photoredox and biocatalytic processes under continuous photo-irradiation, enantioenriched amines are obtained in excellent yields. To the best of our knowledge, this is the first demonstration of a concurrent photoredox- and enzymatic catalysis leading to a light-driven asymmetric synthesis of amines.


Factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment in high-burden settings, Mumbai, India: A cohort analysis.
Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment. This study is a cohort analysis of secondary data collected from 1804 HIV-TB co-infected individuals from 16 anti-retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients. The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post-treatment period. Mortality was significantly higher in those with a CD4 count 0-200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post-treatment period. The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post-treatment follow-up and monitoring is important in HIV-TB co-infected patients, and post-treatment mortality should also be considered as one of the indicators for successful TB control programmes.


Wormlike Micelles of a Cationic Surfactant in Polar Organic Solvents: Extending Surfactant Self-Assembly to New Systems and Subzero Temperatures.
Wormlike micelles (WLMs) are long, flexible cylindrical chains formed by the self-assembly of surfactants in semidilute solutions. Scientists have been fascinated by WLMs because of their similarities to polymers, while at the same time, the viscoelastic properties of WLM solutions have made them useful in a variety of industrial applications. To date, most studies on WLMs have been performed in water (i.e., a highly polar liquid), while there are a few examples of "reverse" WLMs in oils (i.e., highly nonpolar liquids). However, in organic solvents with lower polarity than water such as glycerol, formamide, and ethylene glycol, there have been no reports of WLMs thus far. Here, we show that it is indeed possible to induce a long-tailed cationic surfactant to assemble into WLMs in several of these solvents. To form WLMs, the surfactant is combined with a "binding" salt, i.e., one with a large organic counterion that is capable of binding to the micelles. Examples of such salts include sodium salicylate and sodium tosylate, and we find self-assembly to be maximized when the surfactant and salt concentrations are near-equimolar. Interestingly, the addition of a simple, inorganic salt such as sodium chloride (NaCl) to the same surfactant does not induce WLMs in polar solvents (although it does so in water). Thus, the design rules for WLM formation in polar solvents are distinct from those in water. Aqueous WLMs have been characterized at temperatures from 25 °C and above, but few studies have examined WLMs at much lower (e.g., subzero) temperatures. Here, we have selected a surfactant with a very low Krafft point (i.e., the surfactant does not crystallize out of solution upon cooling due to a cis-unsaturation in its tail) and a low-freezing solvent, viz. a 90/10 mixture of glycerol and ethylene glycol. In these mixtures, we find evidence for WLMs that persist down to temperatures as low as -20 °C. Rheological techniques as well as small-angle neutron scattering (SANS) have been used to characterize the WLMs under these conditions. Much like their aqueous counterparts, WLMs in polar solvents show viscoelastic properties, and accordingly, these fluids could find applications as synthetic lubricants or as improved antifreezing fluids.


Deep brain stimulation of ventromedial prefrontal cortex reverses depressive-like behaviors via BDNF/TrkB signaling pathway in rats.
Deep brain stimulation (DBS) is currently under investigation as a potential therapeutic approach for managing major depressive disorder (MDD) and ventromedial prefrontal cortex (vmPFC) is recognized as a promising target region. Therefore, the present study aimed to investigate a preclinical paradigm of bilateral vmPFC DBS and examine the molecular mechanisms underlying its antidepressant-like effects using chronic unpredictable stress (CUS) model in rats. Male rats were subjected to stereotaxic surgery and deep brain stimulation paradigm in non-stressed and CUS rats respectively, and the therapeutic effect of DBS were assessed by a series of behavioral tests including sucrose preference test, open field test, elevated plus maze test, and forced swim test. The potential involvement of the BDNF/TrkB signaling pathway and its downstream effects in this process were also investigated using western blot. We identified that a stimulation protocol consisting of 130 Hz, 200 μA, 90 μs pulses administered for 5 h per day over a period of 7 days effectively mitigated CUS-induced depressive-like and anxiety-like behaviors in rats. These therapeutic effects were associated with the enhancement of the BDNF/TrkB signaling pathway and its downstream ERK1/2 activity. These findings provide valuable insights into the potential clinical utility of vmPFC DBS as an approach of improving the symptoms experienced by individuals with MDD. This evidence contributes to our understanding of the neurobiological basis of depression and offers promise for the development of more effective treatments.


HDAC1: An Essential and Conserved Member of the Diverse Zn2+-Dependent HDAC Family Driven by Divergent Selection Pressure.
Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.


Association of antipsychotic treatment switching in patients with schizophrenia, bipolar, and major depressive disorders.
Aims: To evaluate the association of relapse and healthcare resource utilization in patients with schizophrenia (SZ), bipolar disorder (BD), or major depressive disorder (MDD) who switched antipsychotic medication versus those who did not.Materials and methods: Medicaid claims from six US states spanning six years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD, or MDD, and for the subset of patients who also had ≥1 extrapyramidal symptoms (EPS) diagnosis at baseline, times to the following outcomes were analyzed: underlying disease relapse, other psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission, and EPS diagnosis.Results: Switchers (N = 10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank p < .001) than non-switchers (N = 31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the two-year study period. Subgroup analysis of those with ≥1 EPS diagnosis revealed similar associations.Limitations: Only association, not causation, may be inferred, and there may be differences between the patient groups in parameters not evaluated.Conclusions: These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for patients who switched antipsychotics than for those who did not, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BD, and MDD. This may be attributed to more-severely ill patients being less responsive than those with less-severe illness, which, in turn, may require more episodes of switching.


Aplasia cutis congenita in a CDC42-related developmental phenotype.
Cell division cycle 42 (CDC42) is a small Rho GTPase, which serves as a fundamental intracellular signal node regulating actin cytoskeletal dynamics and several other integral cellular processes. CDC42-associated disorders encompass a broad clinical spectrum including Takenouchi-Kosaki syndrome, autoinflammatory syndromes and neurodevelopmental phenotypes mimicking RASopathies. Dysregulation of CDC42 signaling by genetic defects in either DOCK6 or ARHGAP31 is also considered to play a role in the pathogenesis of Adams-Oliver syndrome (AOS). Here, we report a mother and her child carrying the previously reported pathogenic CDC42 variant c.511G>A (p.Glu171Lys). Both affected individuals presented with short stature, distinctive craniofacial features, pectus deformity as well as heart and eye anomalies, similar to the recently described Noonan syndrome-like phenotype associated with this variant. Remarkably, one of the patients additionally exhibited aplasia cutis congenita of the scalp. Multi-gene panel sequencing of the known AOS-causative genes and whole exome sequencing revealed no second pathogenic variant in any disease-associated gene explaining the aplasia cutis phenotype in our patient. This observation further expands the phenotypic spectrum of CDC42-associated disorders and underscores the role of CDC42 dysregulation in the pathogenesis of aplasia cutis congenita.


Can humans think? The Ergonomics Society Lecture 1991.
For many years, computer scientists have been concerned with whether computers can think. Considerable thought, therefore, goes into designing 'thinking' computer systems and into wondering whether they really can think, or just pretend to. On the other hand, it is 'obvious' that humans can think, and therefore little thought has gone into the related question, 'Can humans think?' This paper explores the ergonomic implications of the affirmative answer. Computers get better treatment than humans, yet humans are more than machines. However, not only do designers seem to forget this, but they do not even treat users with the same respect as they would a machine.


Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients.
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n = 379) and matched population controls (n = 316) were analyzed by antibody suspension bead array targeting 281 proteins. To investigate the differences between SLE and controls, Mann-Whitney U-test with Bonferroni correction, generalized linear modeling and receiver operating characteristics (ROC) analysis were performed. K-means clustering was used to identify molecular SLE subgroups. We identified Interferon regulating factor 5 (IRF5), solute carrier family 22 member 2 (SLC22A2) and S100 calcium binding protein A12 (S100A12) as the three proteins with the largest fold change between SLE patients and controls (SLE/Control = 1.4, 1.4, and 1.2 respectively). The lowest p-values comparing SLE patients and controls were obtained for S100A12, Matrix metalloproteinase-1 (MMP1) and SLC22A2 (padjusted = 3 × 10-9, 3 × 10-6, and 5 × 10-6 respectively). In a set of 15 potential biomarkers differentiating SLE patients and controls, two of the proteins were transcription factors, i.e., IRF5 and SAM pointed domain containing ETS transcription factor (SPDEF). IRF5 was up-regulated while SPDEF was found to be down-regulated in SLE patients. Unsupervised clustering of all investigated proteins identified three molecular subgroups among SLE patients, characterized by (1) high levels of rheumatoid factor-IgM, (2) low IRF5, and (3) high IRF5. IRF5 expressing microparticles were analyzed by flow cytometry in a subset of patients to confirm the presence of IRF5 in plasma and detection of extracellular IRF5 was further confirmed by immunoprecipitation-mass spectrometry (IP-MS). Interestingly IRF5, a known genetic risk factor for SLE, was detected extracellularly and suggested by unsupervised clustering analysis to differentiate between SLE subgroups. Our results imply a set of circulating molecules as markers of possible pathogenic importance in SLE. We believe that these findings could be of relevance for understanding the pathogenesis and diversity of SLE, as well as for selection of patients in clinical trials.


TIMPs and MMPs expression in CSF from patients with TSP/HAM.
The tropical spastic paraparesis or human T-cell lymphotropic virus associated myelopathy (TSP/HAM), has been related with an overexpression of matrix metalloproteinases (MMPs), especially MMP-9. Initial studies of reverse zymography with cerebrospinal fluid (CSF) from TSP/HAM patients, and controls showed the presence of TIMPs, endogenous MMP inhibitors. We determined in CSF the levels of TIMPs by immunoanalysis in 25 patients with TSP/HAM, and compared with two groups: controls and patients with acute and subacute inflammatory neurological diseases. We found that TIMP-2, TIMP-3 and TIMP-4 levels were significantly higher than in controls in both TSP/HAM and inflammatory patients, while TIMP-1 was increased only in the inflammatory group. Levels of MMP-3 and MMP-9 from the two groups of patients showed a significant upregulation in CSF. In the CSF of around the 70% of TSP-HAM and inflammatory patients the presence MMP-9 was detected by zymography, but not in controls. MMP-2 was only overexpressed in the acute inflammatory group. The active form of MMP-2 was observed in both groups of patients with a similar high frequency (60%). MMPs overexpressions are independent of the evolution time of the disease in TSP/HAM. The chronic overexpression of these extracelullar matrix proteins detected in CSF of TSP/HAM should be indirectly produced by secreted viral proteins being responsible for the progression of this disease, accounting for the observed differences with acute inflammatory patients. Our results support the existence of an imbalance between MMPs and their endogenous tissue inhibitors, which could be a pathogenic factor in the chronicity of TSP/HAM.


Critique of the Allen test for continuity of the palmar arch assessed by doppler ultrasound.
The arterial circulation of both hands of 128 adults was assessed by the Allen test, a modified Allen test emphasizing proper hand position and by Doppler ultrasound. Full extension of the fingers during the Allen test resulted incomplete capillary refilling of the hand in 73 per cent of the patients. The modified Allen test, avoiding hyperextension of the wrist and fingers, revealed interruption of the palmar arch in only one patient with absence of the left radialy artery. There was complete concordance of findings by Doppler ultrasound and the modified Allen test, emphasizing the importance of maintaining proper hand position to avoid false interpretations of incomplete circulation of the palmar arch.


Green light-excitable naphthalenediimide acetylide-containing cyclometalated Ir(III) complex with long-lived triplet excited states as triplet photosensitizers for triplet-triplet annihilation upconversion.
Naphthalenediimide (NDI) was connected to the ligand of a cyclometalated Ir(III) complex (Ir-1) via a C≡C triple bond to enhance the absorption in the visible region and to access long-lived triplet excited states. Ir(ppy)2(bpy)[PF6] (Ir-2, ppy = 2-phenylpyridine and bpy = 2,2'-bipyridine) was used as a model complex. The photophysical properties of the complexes were studied with steady state and time-resolved spectroscopy. Ir-1 shows strong absorption in the visible region (ε = 11,000 M(-1) cm(-1) at 542 nm) and in comparison Ir-2 shows typically weak absorption in the visible region (ε < 3000 M(-1) cm(-1) above 400 nm). Room temperature near IR emission at 732 nm (Φ(P) = 0.1%) was observed for Ir-1, which is attributed to the NDI localized emissive triplet excited state, by transient absorption spectra and DFT calculations on the spin density surface. The lifetime of the NDI-localized triplet excited state is up to 130.0 μs, which is rarely reported for Ir(III) complexes. In comparison, Ir-2 shows phosphorescence at 578 nm and the triplet state lifetime is a typical value of 0.3 μs. The complexes were used as triplet photosensitizers for triplet-triplet annihilation (TTA) upconversion and an upconversion quantum yield of 6.7% was observed with Ir-1. No upconversion was observed with Ir-2 as the triplet photosensitizer at the same experimental conditions.


Perceptual organization and curve partitioning.
In this paper we offer a critical evaluation of the partitioning (perceptual organization) problem, noting the extent to which it has distinct formulations and parameterizations. We show that most partitioning techniques can be characterized as variations of four distinct paradigms, and argue that any effective technique must satisfy two general principles. We give concrete substance to our general discussion by introducing new partitioning techniques for planar geometric curves, and present experimental results demonstrating their effectiveness.


Low apolipoprotein A-I levels in Friedreich's ataxia and in frataxin-deficient cells: Implications for therapy.
Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common hereditary ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure. However, the pathophysiology of heart disease in FA is non-vascular and there are conflicting data on HDL-cholesterol in FA. Two studies have shown a decrease in HDL-cholesterol compared with controls and two have shown there was no difference between FA and controls. One also showed that there was no difference in serum Apo-A-I levels in FA when compared with controls. Using a highly specific stable isotope dilution mass spectrometry-based assay, we demonstrated a 21.6% decrease in serum ApoA-I in FA patients (134.8 mg/dL, n = 95) compared with non-affected controls (172.1 mg/dL, n = 95). This is similar to the difference in serum ApoA-I levels between non-smokers and tobacco smokers. Knockdown of frataxin by > 70% in human hepatoma HepG2 cells caused a 20% reduction in secreted ApoA-I. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor caused a 200% increase in HMG-CoA in the control HepG2 cells with a similar increase in the frataxin knockdown HepG2 cells, back to levels found in the control cells. There was a concomitant 20% increase in secreted ApoA-I to levels found in the control cells that were treated with simvastatin. This study provides compelling evidence that ApoA-I levels are reduced in FA patients compared with controls and suggest that statin treatment would normalize the ApoA-I levels.


Spatiotemporal Modulated Scaffold for Endogenous Bone Regeneration via Harnessing Sequentially Released Guiding Signals.
The design of a scaffold that can regulate the sequential differentiation of bone marrow mesenchymal stromal cells (BMSCs) according to the endochondral ossification (ECO) mechanism is highly desirable for effective bone regeneration. In this study, we successfully fabricated a dual-networked composite hydrogel composed of gelatin and hyaluronic acid (termed GCDH-M), which can sequentially release chondroitin sulfate (CS) and magnesium/silicon (Mg/Si) ions to provide spatiotemporal guidance for chondrogenesis, angiogenesis, and osteogenesis. The fast release of CS is from the GCDH hydrogel, and the sustained releases of Mg/Si ions are from poly(lactide-co-glycolide) microspheres embedded in the hydrogel. There is a difference in the release rates between CS and ions, resulting in the ability for the fast release of CS and sustained release of ions. The dual networks between the modified gelatin and hyaluronic acid via covalent bonding and host-guest interactions render the hydrogel with some dynamic feature to meet the differentiation development of BMSCs laden inside the hydrogel, i.e., transforming into a chondrogenic phenotype, further to a hypertrophic phenotype and eventually to an osteogenic phenotype. As evidenced by the results of in vitro and in vivo evaluations, this GCDH-M composite hydrogel was proved to be able to create an optimal microenvironment for embedded BMSCs responding to the sequential guiding signals, which aligns with the rhythm of the ECO process and ultimately boosts bone regeneration. The promising outcome achieved with this innovative hydrogel system sheds light on novel scaffold design targeting bone tissue engineering.


Business Process Management for optimizing clinical processes: A systematic literature review.
Business Process Management is a new strategy for process management that is having a major impact today. Mainly, its use is focused on the industrial, services, and business sector. However, in recent years, it has begun to apply for optimizing clinical processes. So far, no studies that evaluate its true impact on the healthcare sector have been found. This systematic review aims to assess the results of the application of Business Process Management methodology on clinical processes, analyzing whether it can become a useful tool to improve the effectiveness and quality of processes. We conducted a systematic literature review using ScienceDirect, Web of Science, Scopus, PubMed, and Springer databases. After the electronic search process in different databases, 18 articles met the pre-established requirements. The findings support the use of Business Process Management as an effective methodology to optimize clinical processes. Business Process Management has proven to be a feasible and useful methodology to design and optimize clinical processes, as well as to automate tasks. However, a more comprehensive follow-up of this methodology, better technological support, and greater involvement of all the clinical staff are factors that play a key role for the development of its true potential.


[Functional abilities of the teenager's body based on body mass index].
The nutrition status was investigated according to the body weight index (BWI) in teenagers studying at different educational facilities. 77.1% of male teenagers and 70% of female teenagers from among all examined subjects (1456 persons) were assigned to the group with normal BWI ranging from 18.5 to 25.0 kg/m2. Male teenagers with a lower BWI (below 18.5 kg/m20) were more often encountered in boarding schools and specialized technical-and-professional schools; as for female teenagers, subjects with a lower BWI were more often encountered in general education schools and among first-year students of high schools (24 and 43.75%, respectively). An insignificant number of teenagers with an excessive body weight was detected in all educational facilities. Finally, it was concluded that teenagers with normal BWI have the best indices of functional abilities.


The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.
Nicotinic acetylcholine systems play important roles in addiction, and nicotinic receptor stimulation stimulates dopamine release while the nicotinic antagonist mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.] recently found in human cocaine addicts that mecamylamine reduced cue-elicited cocaine craving. The current study assessed the impact of mecamylamine on cocaine self-administration in rats. Female Sprague-Dawley rats (N=7) were implanted with intravenous (iv) catheters and trained to lever press for cocaine (0.32 mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg sc) 10 min before the session. They received the same dose for 1 week with 1 week of uninjected testing between doses. Mecamylamine, compared to saline, significantly (P<.05) reduced the number of cocaine infusions per session with each of these doses. This effect did not appear to be due to a generalized reduction in behavioral activity. Another set of female Sprague-Dawley rats (N=8) were trained to lever press for food reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine doses had no effect on food self-administration. Significant reductions in food self-administration were not seen unless the high dose of 4-mg/kg mecamylamine was used. Nicotinic antagonist treatment reduces cocaine self-administration in rats at doses that do not cause generalized effects on food-reinforced responding. Nicotinic antagonistic treatment may be a useful new approach to treat cocaine addiction.


Relative added value: what are the tools to evaluate it?
The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.


Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet.
Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1-13C] pyruvate MR spectroscopy showed increased lactate conversion (P < .001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1-13C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1-13C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.


Microsurgery and telemicrosurgery training: a comparative study.
Telemicrosurgery (TMS) is a new technique inspired by telesurgery and conventional microsurgery (CMS). One of the difficulties of CMS is learning to control physiological tremor. TMS eliminates the physiological tremor, thus theoretically simplifying microsurgical procedures, but no tactile feedback is provided while tying knots. The objective of this study was to assess if the learning curve for performing microsurgical anastomosis for TMS than with CMS was comparable. Thirty earthworms were anastomosed with 10/0 nylon sutures. In this study 15 anastomoses were performed under operating microscope and 15 under Da Vinci S® robot (Intuitive Surgical, Sunnyvale, CA). A single operator without experience in either technique performed all anastomoses. The evaluation consisted of measuring the time to perform each stitch, as well as to complete the anastomosis. The integrity of the anastomosis was tested by injection of saline solution into the earthworm to assess permeability and watertightness. The average time to complete a single suture was 296 seconds in the CMS group and 529 seconds in the TMS group. Permeability and watertightness of anastomosis was 86.66% in both groups. Learning was faster with CMS than with TMS. For untrained surgeon, the absence of tactile feedback is a limiting factor with TMS, however, the benefits of the TMS are: three-dimensional high definition vision, abolition of physiological tremor, motion scaling of gestures down to 5 times, use of three instruments at once, and extreme mobility.


The early life growth of head circumference, weight, and height in infants with autism spectrum disorders: a systematic review.
The Autism spectrum disorder (ASD) prevalence has increased significantly over the past two decades. This review summarizes the current knowledge of the association between the early life growth of head circumference (HC), weight, and height with ASD in infants. PubMed, Scopus, Science Direct, and Google Scholar databases were searched up to November 2021 using relevant keywords. All original articles are written in English evaluating the early life growth of HC, weight, and height in infants with ASD were eligible for the present review. Totally, 23 articles involving 4959 infants were included in this review. Of 13 studies that evaluated HC of infants at birth, 10 studies (83.33%) showed that the HC at the birth of autistic children was similar to that of the average found in the control group. Among 21 studies that evaluated the HC and weight status in infants, 19 studies (90.47%) showed that autistic children had larger HC and weight than the control group or abnormal acceleration of head growth during infancy. Height growth of infants was investigated in 13 studies, of which 10 cases (76.92%) reported that infants with ASD were significantly longer than control groups. Most of he included studies had a good quality. The findings suggest that in infants with ASD, without the contribution of birth growth factors and sex of the child, the growth of HC, weight, and height probably was faster than in infants with normal development, in early life. Therefore, these measurements might be useful as initial predictive biomarkers for the risk of developing ASD.


Potassium channels act as chemosensors for solute transporters.
Potassium channels form physical complexes with solute transporters in vivo, yet little is known about their range of possible signaling modalities and the underlying mechanisms. The KCNQ2/3 potassium channel, which generates neuronal M-current, is voltage-gated and its activity is also stimulated by binding of various small molecules. KCNQ2/3 forms reciprocally regulating complexes with sodium-coupled myo-inositol transporters (SMITs) in mammalian neurons. Here, we report that the neurotransmitter γ-aminobutyric acid (GABA) and other small molecules directly regulate myo-inositol transport in rat dorsal root ganglia, and by human SMIT1-KCNQ2/3 complexes in vitro, by inducing a distinct KCNQ2/3 pore conformation. Reciprocally, SMIT1 tunes KCNQ2/3 sensing of GABA and related metabolites. Ion permeation and mutagenesis studies suggest that SMIT1 and GABA similarly alter KCNQ2/3 pore conformation but via different KCNQ subunits and molecular mechanisms. KCNQ channels therefore act as chemosensors to enable co-assembled myo-inositol transporters to respond to diverse stimuli including neurotransmitters, metabolites and drugs.


Don't drink and chill: Effects of alcohol on subjective and physiological reactions during music listening and their relationships with personality and listening habits.
Recent research indicates that favorite music can induce chills and alters physiological reactions. People frequently listen to music when they drink alcohol, for example in bars or discotheques. Alcohol has numerous effects on emotions, peripheral physiological and neural reactions. We investigated whether alcohol intake influences chill experiences and physiological reactions during music listening. 39 participants took part in the study and were tested twice: Once in a sober condition and once when they had drunken alcohol. Participants listened to two pieces of music in each of the two conditions: A favorite self-selected song and a control-song that was selected by the research group. Participants had to indicate when they experienced a chill and electrodermal activity and heart rate were measured during music listening. In addition, participants filled out questionnaires concerning the big five personality dimensions, music listening habits and general chill experiences. Results indicate that participants experienced most chills when they were sober and listened to their self-selected song. Electrodermal activity was highest when participants were sober. In addition, alcohol intake led to a dedifferentiation in heart rate activity. After alcohol intake, participants had similar heart rates, no matter whether they listened to their self-selected song or to the control-song. Extraversion was negatively related with physiological reactions, while openness to experiences was positively related with physiological reactions. Music listening habits also showed various relationships with chill experiences and physiological reactions, while general chill experiences did not. We conclude that alcohol intake reduces subjective chill experiences during music listening and alters the physiological reactions to music. Music listening habits and personality seem to influence these effects.


Genetic variation in the rhythmonome: ethnic variation and haplotype structure in candidate genes for arrhythmias.
The 'rhythmonome' is the term we have adopted to describe the set of genes that determine the normal coordinated electrical activity in the heart. Elements of this set include pore-forming ion channels, function-modifying proteins and intracellular calcium control elements. Rare mutations in many of these genes are known to cause unusual congenital monogenic arrhythmia syndromes, and single common variants have been reported to modify arrhythmia phenotypes. Here, we report an evaluation of the variation and haplotype structure in six key components of the rhythmonome. SNPs were typed using DNA extracted from Coriell cell lines to survey allele frequencies and haplotype structure in six genes (ANK2, SCN5A, KCNE1 and 2 gene cluster, KCNQ1, KCNH2 and RYR2) across four human populations (African-American, European American, Han Chinese and Mexican American). A total of 307 SNPs were analyzed across the six genes, revealing significant allele-frequency differences between populations and clear differences in haplotype structure. The pattern of variation we report is an important step towards incorporating common variation across the rhythmonome in studies of arrhythmia susceptibility.


Wellbeing in high-performance swimming: A grounded theory study.
The demands of elite sport have the potential to negatively impact on athletes' wellbeing (e.g., Arnold & Fletcher, 2012; Rice et al., 2016). Despite this, not all elite athletes experience detrimental effects, rather some individuals thrive in an elite sports environment. The reasons why some athletes experience positive wellbeing while others struggle remains unclear although, in part, due to methodological limitations of previous research. To overcome these limitations, the purpose of the current study was to examine how change in high-performance swimmers' wellbeing occurs. Grounded theory methodology was used to enable examination of processes of change. Semi-structured interviews with 22 current and five retired swimmers, eight coaches, and seven support staff were used to generate data alongside observations and field notes. The resultant theory illustrated how a dominant performance narrative influenced the development and maintenance of an exclusive swimmer identity that was tied to performance. Specifically, transitions were highlighted as critical points where wellbeing was likely to be affected, due to the increased potential for change and uncertainty to impact on performance and subsequently identity. However, the use of proactive coping strategies, such as anticipating and planning, as well as accessing and utilising appropriate support were shown to help minimise the impact on wellbeing.


Changes in the levels of mRNAs for GH/prolactin/somatolactin family and Pit-1/GHF-1 in the pituitaries of pre-spawning chum salmon.
Changes in the levels of pituitary mRNAs encoding GH, prolactin (PRL) and somatolactin (SL) were determined in pre-spawning chum salmon (Oncorhynchus keta) caught at a few key points along their homing pathway in 1994 and 1995. Furthermore, we analyzed relationships between expression of pituitary-specific POU homeodomain transcription factor (Pit-1/GHF-1) and GH/PRL/SL family genes. In 1994, seawater (SW) fish and matured fresh-water (FW) fish were sequentially captured at two points along their homing pathway, the coast and the hatchery. In addition to these two points, maturing FW fish were captured at the intermediate of the two points in 1995. The levels of hormonal mRNAs were determined by a quantitative dot blot analysis using single-stranded sense DNA as the standard. Relative levels of Pit-1/GHF-1 mRNAs were estimated by Northern blot analysis. In 1994, the levels of GH/PRL/SL family mRNAs except for PRL mRNA in the male FW fish were 1.8-4 times higher than those in the SW fish. In 1995, the level of PRL mRNA was somewhat sharply elevated in the maturing FW fish soon after entry into the FW environment, while that of SL mRNA was gradually increased during upstream migration from the coast to the hatchery. The levels of 3 kb Pit-1/GHF-1 mRNA in the FW fish were higher than those in the SW fish in both 1994 and 1995. The present results indicate that expression of genes for the GH/PRL/SL family and Pit-1/GHF-1 is coincidentally enhanced in homing chum salmon. Moreover, the present study suggests that expression of the SL gene is elevated with sexual maturation, whereas that of PRL gene is elevated with osmotic change during the final stages of spawning migration.


Protein quantification by MALDI-selected reaction monitoring mass spectrometry using sulfonate derivatized peptides.
The feasibility of protein absolute quantification with matrix-assisted laser desorption/ionization (MALDI) using the selected reaction monitoring (SRM) acquisition mode on a triple quadrupole linear ion trap mass spectrometer (QqQ(LIT)) equipped with a high-frequency laser is demonstrated. A therapeutic human monoclonal antibody (mAb) was used as a model protein, and four tryptic peptides generated by fast tryptic digestion were selected as quantification surrogates. MALDI produces mostly singly charged peptides which hardly fragment under low-energy collision-induced dissociation (CID), and therefore the benefits of using 4-sulfophenyl isothiocyanate (SPITC) as a fragmentation enhancer derivatization agent were evaluated. Despite a moderate impact on the sensitivity, the N-terminus sulfonated peptides generate nearly complete y-ion ladders when native peptides produce few fragments. This aspect provides an alternative SRM transition set for each peptide. As a consequence, SRM transitions selectivity can be tuned more easily for peptide quantitation in complex matrices when monitoring several SRM transitions. From a quantitative point of view, the signal response depending on mAb concentration was found to be linear over 2.5 orders of magnitude for the most sensitive peptide, allowing precise and accurate measurement by MALDI-SRM/MS.


The role of surgery in primary gastric lymphoma: results of a controlled clinical trial.
We began a controlled clinical trial to assess efficacy and toxicity of surgery (S), surgery + radiotherapy (SRT), surgery + chemotherapy (SCT), and chemotherapy (CT) in the treatment of primary gastric diffuse large cell lymphoma in early stages: IE and II1. Management of primary gastric lymphoma remains controversial. No controlled clinical trials have evaluated the different therapeutic schedules, and prognostic factors have not been identified in a uniform population. Five hundred eighty-nine patients were randomized to be treated with S (148 patients), SR (138 patients), SCT (153 patients), and CT (150 patients). Radiotherapy was delivered at doses of 40 Gy; chemotherapy was CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) at standard doses. International Prognostic Index (IPI) and modified IPI (MIPI) were assessed to determine outcome. Complete response rates were similar in the 4 arms. Actuarial curves at 10 years of event-free survival (EFS) were as follows: S: 28% (95% confidence interval [CI], 22% to 41%); SRT: 23% (95% CI, 16% to 29%); that were statistically significant when compared with SCT: 82% (95% CI, 73% to 89%); and CT: 92% (95% CI, 84% to 99%) (P < 0.001). Actuarial curves at 10 years showed that overall survivals (OS) were as follows: S: 54% (95% CI, 46% to 64%); SRT: 53% (95% CI, 45% to 68%); that were statistically significant to SCT: 91% (95% CI, 85% to 99%); CT: 96% (95% CI, 90% to 103%)(P < 0.001). Late toxicity was more frequent and severe in patients who undergoing surgery. IPI and MIPI were not useful in determining outcome and multivariate analysis failed to identify other prognostic factors. In patients with primary gastric diffuse large cell lymphoma and aggressive histology, diffuse large cell lymphoma in early stage SCT achieved good results, but surgery was associated with some cases of lethal complications. Thus it appears that CT should be considered the treatment of choice in this patient setting. Current clinical classifications of risk are not useful in defining treatment.


Genetic progress in sunflower crop in Rio Grande do Sul State, Brazil.
The sunflower has adaptability to growing regions with different climatic and soil characteristics, showing drought tolerance and high-quality oil production. The State of Rio Grande do Sul is the third largest sunflower producer in Brazil, with research related to the sunflower breeding initiated after the decade of 1950. The aim of this study was to evaluate the genetic progress for grain yield, oil content, and oil yield of sunflower (Helianthus annuus L.) in the State of Rio Grande do Sul. Data of grain yield, oil content, and oil yield obtained from 58 sunflower cultivar yield trials in 19 municipalities in Rio Grande do Sul during the period from 2005 to 2014 were used. Genetic progress was studied according to the methodology proposed by Vencovsky and data from sunflower cultivar yield trials were used. Annual genetic progress of sunflower during the period of 10 years (2005-2014) was 132.46 kg⋅ha-1⋅year-1 for grain yield, -0.17%/year for oil content, and 48.11 kg⋅ha-1⋅year-1 for oil yield. The sunflower-breeding programs in the State of Rio Grande do Sul were efficient for the traits grain yield and oil yield and presented no efficiency for oil content.


BtcA, A class IA type III chaperone, interacts with the BteA N-terminal domain through a globular/non-globular mechanism.
Bordetella pertussis, the etiological agent of "whooping cough" disease, utilizes the type III secretion system (T3SS) to deliver a 69 kDa cytotoxic effector protein, BteA, directly into the host cells. As with other T3SS effectors, prior to its secretion BteA binds BtcA, a 13.9 kDa protein predicted to act as a T3SS class IA chaperone. While this interaction had been characterized for such effector-chaperone pairs in other pathogens, it has yet to be fully investigated in Bordetella. Here we provide the first biochemical proof that BtcA is indeed a class IA chaperone, responsible for the binding of BteA's N-terminal domain. We bring forth extensive evidence that BtcA binds its substrate effector through a dual-interface binding mechanism comprising of non-globular and bi-globular interactions at a moderate micromolar level binding affinity. We demonstrate that the non-globular interactions involve the first 31 N-terminal residues of BteA287 and their removal leads to destabilization of the effector-chaperone complex and lower binding affinities to BtcA. These findings represent an important first step towards a molecular understanding of BteA secretion and cell entry.


SEPARATION OF THE SALIVARY AND MOTOR RESPONSES IN INSTRUMENTAL CONDITIONING.
If an instrumental conditioning schedule is arranged so that a dog must repeatedly perform a movement in response to one stimulus in order to secure the presentation of another stimulus, which is then followed by food, a virtually total separation of motor and salivary responses is observed. The first stimulus elicits the trained movement without salivation, and the second stimulus elicits salivation without instrumental responding. These experiments show a relative independence between classical and ìnstrumental conditioned responses and clarify the rather complex relations between the two in the usual experimental procedure.


Potential for primary productivity in a globally-distributed bacterial phototroph.
Aerobic anoxygenic phototrophs (AAnPs) are common in marine environments and are associated with photoheterotrophic activity. To date, AAnPs that possess the potential for carbon fixation have not been identified in the surface ocean. Using the Tara Oceans metagenomic dataset, we have identified draft genomes of nine bacteria that possess the genomic potential for anoxygenic phototrophy, carbon fixation via the Calvin-Benson-Bassham cycle, and the oxidation of sulfite and thiosulfate. Forming a monophyletic clade within the Alphaproteobacteria and lacking cultured representatives, the organisms compose minor constituents of local microbial communities (0.1-1.0%), but are globally distributed, present in multiple samples from the North Pacific, Mediterranean Sea, the East Africa Coastal Province, and the Atlantic. This discovery may require re-examination of the microbial communities in the oceans to understand and constrain the role this group of organisms may play in the global carbon cycle.


Factors associated with the utilization and costs of health and social services in frail elderly patients.
Universal access is one of the major aims in public health and social care. Services should be provided on the basis of individual needs. However, municipal autonomy and the fragmentation of services may jeopardize universal access and lead to variation between municipalities in the delivery of services. This paper aims to identify patient-level characteristics and municipality-level service patterns that may have an influence on the use and costs of health and social services of frail elderly patients. Hierarchical analysis was applied to estimate the effects of patient and municipality-level variables on services utilization. The variation in the use of health care services was entirely due to patient-related variables, whereas in the social services, 9% of the variation was explained by the municipality-level and 91% by the patient-level characteristics. Health-related quality of life explained a major part of variation in the costs of health care services. Those who had reported improvement in their health status during the preceding year were more frequent users of social care services. Low informal support, poor functional status and poor instrumental activities of daily living, living at a residential home, and living alone were associated with higher social services expenditure. The results of this study showed municipality-level variation in the utilization of social services, whereas health care services provided for frail elderly people seem to be highly equitable across municipalities. Another important finding was that the utilization of social and health services were connected. Those who reported improvement in their health status during the preceding year were more frequently also using social services. This result suggests that if municipalities continue to limit the provision of support services only for those who are in the highest need, this saving in the social sector may, in the long run, result in increased costs of health care.


HTLV-1 Tax: Linking transformation, DNA damage and apoptotic T-cell death.
The human T-cell leukemia virus type I (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4-positive T-cell neoplasia. The HTLV-1 proto-oncogene Tax, a potent transcriptional activator of cellular and viral genes, is thought to play a pivotal role in the transforming properties of the virus by deregulating intracellular signaling pathways. During the course of HTLV-1 infection, the dysregulation of cell-cycle checkpoints and the suppression of DNA damage repair is tightly linked to the activity of the viral oncoprotein Tax. Tax activity is associated with production of reactive oxygen intermediates (ROS), chromosomal instability and DNA damage, apoptotic cell death and cellular transformation. Changes in the intracellular redox status induced by Tax promote DNA damage. Tax-mediated DNA damage is believed to be essential in initiating the transformation process by subjecting infected T cells to genetic changes that eventually promote the neoplastic state. Apoptosis and immune surveillance would then exert the necessary selection pressure for eliminating the majority of virally infected cells, while escape variants acquiring a mutator phenotype would constitute a subpopulation of genetically altered cells prone to neoplasia. While the potency of Tax-activity seems to be a determining factor for the observed effects, the cooperation of Tax with other viral proteins determines the fate and progression of HTLV-1-infected cells through DNA damage, apoptosis, survival and transformation.


Human T-cell leukemia virus I provirus and antibodies in a captive gorilla with non-Hodgkin's lymphoma.
Antibodies reactive against human T-cell leukemia virus I (HTLV-I) were detected by indirect immunofluorescence assay using MT-2 as target cells, enzyme linked immunosorbent assay screen and competition assay, and Western blot analysis in three sera (one collected in 1979) from a captive gorilla which developed diffuse histiocytic lymphoma in 1983. The sera from four other healthy gorillas housed separately were HTLV-I antibody negative. All sera were negative for HTLV-III antibodies by enzyme linked immunosorbent assay. Southern blot analysis of DNA from lymphoma tissue after digestion with BamHI and using complete HTLV-I genome probe gave one 10-kilobase fragment and a characteristic 1.05-kilobase internal fragment detected in all known HTLV-I isolates. These results indicate that the gorilla was infected with HTLV-I or a closely related simian virus several years before the development of lymphoma.


-Fructofuranosidases from roots of dandelion (Taraxacum officinale Weber).
1. Three beta-fructofuranosidases were separated by chromatography on a DEAE-cellulose column from the soluble protein extracted from dandelion (Taraxacum officinale Weber) roots. 2. One enzyme, which acted on sucrose, was characterized as an invertase, with a K(m) of 2.00x10(-2)m and pH optimum of 7.5. 3. The other two enzymes are hydrolases (A and B), which act on the inulin series of oligosaccharides [general formula glucose-fructose-(fructose)(n)]. They both have a pH optimum of 4.0 and K(m) of 1.54x10(-2)m but differ in their chromatographic behaviour on DEAE-cellulose. Neither of the hydrolases is inhibited by sucrose. 4. The physiological role of these three hydrolytic enzymes is discussed.


Angiotensin receptors and pressor hyperresponsiveness in renal prehypertensive rabbits.
This study consisted of five different experiments with conscious rabbits. In experiment 1, the angiotensin II (ANG II) antagonist [Sar1-Ala8]ANG II infused iv into one-kidney rabbits with renal artery stenosis (RAS) of 3 days' duration, at a dose that blocked pressor responses to ANG II, did not decrease the exaggerated pressor responses to norepinephrine (NE). In experiment 2, captopril infused iv into one-kidney, 3-day, RAS rabbits blocked pressor hyperresponsiveness to NE, and the concurrent infusion of [Sar1-Ala8]ANG II did not reestablish pressor hyperresponsiveness, indicating that this ANG II analogue had no agonistic action to promote hyperresponsiveness to NE. In experiment 3, infusion of ANG II at a subpressor dose (6.7 pmol . min-1 . kg body wt-1) into normal rabbits resulted in pressor hyperresponsiveness to NE, which was blocked by [Sar1-Ala8]ANG II. Experiment 4 involved infusing [Sar1-Ala8]ANG II or [Sar1-Ile8]ANG II at various doses into 3-day RAS rabbits, to determine their abilities to attenuate the pressor responses to ANG II (100 ng/kg) and the pressor hyper-responses to NE (800 ng . min-1 . kg-1). [Sar1-Ile8]ANG II decreased the ANG II pressor responses at an ID50 dose of 64 +/- 5 (SEM) pmol . min-1 . kg-1 and attenuated the NE pressor hyper-response at an ID50 dose of 65 +/- 5 pmol . min-1 . kg-1; [Sar1-Ala8]ANG II diminished the ANG II pressor response at an ID50 dose of 757 +/- 247 and the NE pressor hyper-response at an ID50 dose of 10,061 +/- 944 pmol . min-1 . kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Survey of antibodies to Leishmania spp. in wild canids from Pennsylvania and Tennessee.
Visceral leishmaniasis (VL) is a zoonosis with worldwide distribution. Infections with the Leishmania donovani complex, including Leishmania infantum, cause the VL. Domestic dogs are the most important reservoir host for human VL, and wild canids are also susceptible. In the United States, infections with L. infantum are common in the foxhound dog breed. Little information is available regarding L. infantum in wild canids in the Unites States. Sera from 11 foxes and 256 coyotes originating in Pennsylvania and Tennessee (USA) were tested for antibodies to visceralizing Leishmania spp. with rapid immunochromatographic dipstick assays, which utilize recombinant antigen K39. Anti-Leishmania spp. antibodies were found in 5 of 267 (1.9%) of wild canids from Pennsylvania, including four coyotes and one red fox. These results suggest that wild canids are exposed to Leishmania spp. at a low level in the United States.


Proteolytic activation can produce a phosphatidylinositol phosphodiesterase highly sensitive to Ca2+.
The phosphatidylinositol phosphodiesterase of rat brain shows little activity under conditions likely to pertain in vivo (neutral pH and micromolar Ca(2+) concentrations). A short incubation of a brain supernatant with trypsin, or a longer pre-incubation of the supernatant alone, produce new forms of the enzyme, which are active under such conditions. A possible role of receptor-linked proteinases in initiating phosphatidylinositol catabolism is discussed.


Stepwise deposition of metal organic frameworks on flexible synthetic polymer surfaces.
Thin films of [Cu(3)(btc)(2)](n) (btc = 1,3,5-benzenetricarboxylate) metal organic framework were deposited in a stepwise manner on surfaces of flexible organic polymers. The thickness of films can be precisely controlled. The deposition of the first cycles was monitored by UV-vis spectroscopy. The porosity was proven by the adsorption of pyrazine, which was monitored by FT-IR and thermogravimetric analysis. The deposition of MOF thin films on flexible polymer surfaces might be a new path for the fabrication of functional materials for different applications, such as protection layers for working clothes and gas separation materials in the textile industry.