Management of canalicular injury associated with eyelid burns.
To develop a protocol for treatment of injuries to the puncta and canaliculi associated with eyelid burns. We retrospectively reviewed the records of seven patients who required treatment of punctal and canalicular stenosis caused by burns to the medial eyelids. Seven patients were treated within 5 days of injury: one by punctal dilation and six by surgical debridement, punctoplasty or canaliculoplasty, and silicone intubation. All remained free of epiphora. Early evaluation and treatment of punctal and canalicular burn injuries are beneficial. If the puncta are only slightly stenotic, close observation with serial lacrimal testing and punctal dilation is recommended. If the puncta and lateral canaliculi are severely stenotic or obliterated, surgical débridement and punctoplasty or canaliculoplasty followed by placement of a silicone stent effectively prevents permanent lacrimal stenosis and epiphora.


Sequencing and characterization of complete mitogenome DNA of Rasbora tornieri (Cypriniformes: Cyprinidae: Rasbora) and its evolutionary significance.
The yellowtail rasbora (Rasbora tornieri) is a miniature ray-finned fish categorized under the genus Rasbora in the family of Cyprinidae. In this study, a complete mitogenome sequence of R. tornieri was sequenced using four primers targeting two halves of the mitogenome with overlapping flanking regions. The size of mitogenome was 16,573 bp, housing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organization was detected between this species and other members of Rasbora genus. The heavy strand encompassed 28 genes while the light strand accommodated the other nine genes. Most protein-coding genes execute ATG as start codon, excluding COI and ND3 genes, which utilized GTG instead. The central conserved sequence blocks (CSB-E, CSB-F and CSB-D), variable sequence blocks (CSB-1, CSB-3 and CSB-2) as well as the terminal associated sequence (TAS) were conserved within the control region. The maximum likelihood phylogenetic family tree revealed the divergence of R. tornieri from the basal region of the Rasbora clade, where its evolutionary relationships with other Rasbora members are poorly resolved as indicated by the low bootstrap values. This work acts as window for further population genetics and molecular evolution studies of Rasbora genus in future.


Dietary l-carnitine Supplementation Modifies the Lipopolysaccharide-Induced Acute Phase Reaction in Dairy Cows.
l-carnitine plays an important role in energy metabolism through supporting the transport of activated fatty acids to the subcellular site of β-oxidation. An acute phase reaction (APR) is known as an energy consuming process. Lipopolysaccharides (LPS) are often used in animal models to study intervention measures during innate immune responses such as APR. Thus, the aim of the study was to investigate the effects of dietary l-carnitine supplementation during an LPS-induced APR in mid-lactating German Holstein cows. Animals were assigned to a control (CON, n = 26) or l-carnitine group (CAR, n = 27, 25 g rumen-protected l-carnitine/cow/d) and received an intravenous injection of LPS (0.5 μg/kg body weight) at day 111 post-partum. Blood samples were collected from day 1 pre-injection until day 14 post-injection (pi). From 0.5 h pi until 72 h pi blood samplings and clinical examinations were performed in short intervals. Clinical signs of the APR were not altered in group CAR except rumen motility which increased at a lower level compared to the CON group after a period of atonia. Group CAR maintained a higher insulin level compared to group CON even up to 72 h pi which might support glucose utilization following an APR.


Levels of ambient air pollution according to mode of transport: a systematic review.
Controversy exists about the differences in air pollution exposure and inhalation dose between mode of transport. We aimed to review air pollution exposure and inhaled dose according to mode of transport and pollutant and their effect in terms of years of life expectancy (YLE). In this systematic review, we searched ten online databases from inception to April 13, 2016, without language or temporal restrictions, for cohort, cross-sectional, and experimental studies that compared exposure to carbon monoxide, black carbon, nitrogen dioxide, and fine and coarse particles in active commuters (pedestrian or cyclist) and commuters using motorised transport (car, motorcycle, bus, or massive motorised transport [MMT-ie, train, subway, or metro]). We excluded studies that measured air pollution exposure exclusively with biomarkers or on the basis of simulated data, reviews, comments, consensuses, editorials, guidelines, in-vitro studies, meta-analyses, ecological studies, and protocols. We extracted average exposure and commuting time per mode of transport and pollutant to calculate inhaled doses. We calculated exposure and inhaled dose ratios using active commuters as the reference and summarised them with medians and IQRs. We also calculated differences in YLE due to fine particle inhaled dose and physical activity. We identified 4037 studies, of which 39 were included in the systematic review. Overall, car commuters had higher exposure to all pollutants than did active commuters in 30 (71%) of 42 comparisons (median ratio 1·22 [IQR 0·90-1·76]), followed by those who commuted by bus in 57 (52%) of 109 (1·0 [0·79-1·41]), by motorcycle in 16 (50%) of 32 (0·99 [0·86-1·38]), by a car with controlled ventilation settings in 39 (45%) of 86 (0·95 [0·66-1·54]), and by MMT in 21 (38%) of 55 (0·67 [0·49-1·13]). Overall, active commuters had higher inhalation doses than did commuters using motorised transport (median ratio car with controlled ventilation settings 0·16 [0·10-0·28]; car 0·22 [0·15-0·30]; motorcycle 0·38 [0·26-0·78]; MMT 0·49 [0·34-0·81]; bus 0·72 [IQR 0·50-0·99]). Commuters using motorised transport lost up to 1 year in YLE more than did cyclists. Proximity to traffic and high air interchange increased the exposure to air pollution of commuters using motorised transport. Larger inhalation rates and commuting time increased inhaled dose among active commuters. Benefits of active commuting from physical activity are larger than the risk from an increased inhaled dose of fine particles. Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS), National Health and Medical Research Council, Nestlé Nutrition (Nestec), Metagenics, and AXA.


The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngologic surgery.
Non-opioid analgesics are often used to supplement opioids for the management of perioperative pain. In this randomized, double-blinded, placebo-controlled study, we examined the effects of acetaminophen and a cyclooxygenase type-2 inhibitor, celecoxib, when administered alone or in combination, before elective otolaryngologic surgery in 112 healthy outpatients. Subjects were assigned to 1 of 4 study groups: Group 1, placebo (vitamin C, 500 mg per os [PO]); Group 2, acetaminophen 2000 mg PO; Group 3, celecoxib 200 mg PO; or Group 4, acetaminophen 2000 mg and celecoxib 200 mg PO. All patients received a standardized anesthetic technique. During the postoperative period, pain was assessed using a 10-point verbal rating scale. Recovery times, the need for rescue analgesics, side effects, and patient satisfaction scores were also recorded. The combination of acetaminophen and celecoxib was significantly more effective than placebo in reducing postoperative pain. Celecoxib, when administered alone or in combination with acetaminophen, improved patients' satisfaction with their postoperative analgesia. With the combination of acetaminophen and celecoxib, an additional expenditure of $6.16 would be required to obtain complete satisfaction with postoperative pain management in one additional patient who would not have been completely satisfied if he/she had received the placebo. However, oral celecoxib or acetaminophen alone was not significantly more effective than placebo in reducing postoperative pain when administered before surgery. We conclude that oral premedication with a combination of acetaminophen (2000 mg) and celecoxib (200 mg) was highly effective in decreasing pain and improving patient satisfaction after outpatient surgery. Oral premedication with a combination of acetaminophen (2000 mg) and celecoxib (200 mg) was effective in decreasing pain and improving patient satisfaction after otolaryngologic surgery. However, acetaminophen (2000 mg) or celecoxib (200 mg) alone was not significantly more effective than placebo in reducing postoperative pain.


PEF-1, an epithelial cell transcription factor which activates the long control region of human papillomavirus type 16, is glycosylated with N-acetylglucosamine.
Infection by human papillomavirus type 16 (HPV-16) has been linked to cervical cancer. The transcription of viral genes in HPV-16 is partially controlled by a number of cellular transcription factors. We have previously identified a novel cellular transcription factor, PEF-1, from its ability to interact with the long control region (LCR) of HPV-16. This factor has a molecular mass of about 110 kDa and binds to a GC-rich sequence in the section of the LCR responsible for cell type-specific transcription from viral DNA. The factor Sp1 has similar properties and also interacts with the HPV-16 LCR. We show that PEF-1 and Sp1 are distinct transcription factors: they recognize different DNA sequences, have different electrophoretic mobilities and different glycosylation patterns. Sp1 is O-glycosylated while PEF-1 appears to have a novel type of glycosylation, as shown by the interaction with pokeweed lectin and by the inhibition of this interaction by tunicamycin.


Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program.
This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (<or=0.40) in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) program. Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure. This paradox creates a dilemma for physicians and may explain why low BP is reported as a reason for under-use of these agents. The interaction between treatment and baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) was examined with patients divided into 6 SBP categories (<or=100, 101 to 110, 111 to 120, 121 to 130, 131 to 140 and >or=141 mm Hg) and 4 DBP categories (<or=60, 61 to 70, 71 to 80 and >or=81 mm Hg). Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.


Medical Management of Dyslipidemia for Secondary Stroke Prevention: Narrative Review.
Dyslipidemia is a major risk factor for stroke, following hypertension, diabetes, and smoking, and is an important risk factor for the prevention and treatment of coronary artery disease and peripheral vascular disease, including stroke. Recent guidelines recommend considering low-density lipoprotein cholesterol (LDL-C)-lowering therapies, such as statins (preferably), ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to prevent the occurrence or recurrence of stroke, adhering to the "lower is better" approach. In this review, we examined the evidence supporting lipid-lowering medications like statins, ezetimibe, and PCSK9 inhibitors for secondary stroke prevention and dyslipidemia management in different stroke subtypes. Stroke guidelines advocate for administering the maximum tolerable dose of statins as the primary treatment and as soon as possible despite the potential for new-onset diabetes mellitus and possible muscle and liver toxicity due to their demonstrated benefits in secondary prevention of cardiovascular diseases and mortality reduction. When statin use is insufficient for LDL lowering, ezetimibe and PCSK9 inhibitors are recommended as complementary therapies. It is essential to establish lipid-lowering therapy goals based on the stroke subtype and the presence of comorbidities.


Modeling the tendency for music to induce movement in humans: first correlations with low-level audio descriptors across music genres.
Groove is often described as the experience of music that makes people tap their feet and want to dance. A high degree of consistency in ratings of groove across listeners indicates that physical properties of the sound signal contribute to groove (Madison, 2006). Here, correlations were assessed between listeners' ratings and a number of quantitative descriptors of rhythmic properties for one hundred music examples from five distinct traditional music genres. Groove was related to several different rhythmic properties, some of which were genre-specific and some of which were general across genres. Two descriptors corresponding to the density of events between beats and the salience of the beat, respectively, were strongly correlated with groove across domains. In contrast, systematic deviations from strict positions on the metrical grid, so-called microtiming, did not play any significant role. The results are discussed from a functional perspective of rhythmic music to enable and facilitate entrainment and precise synchronization among individuals.


Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation.
Human rhinoviruses (HRVs) are the major cause of the common cold and account for 30-50% of all acute respiratory illnesses. Although HRV infections are usually harmless and invade only the upper respiratory tract, several studies demonstrate that HRV is involved in the exacerbation of asthma. VP1 is one of the surface-exposed proteins of the viral capsid that is important for the binding of rhinoviruses to the corresponding receptors on human cells. Here we investigated its potential usefulness for vaccination against the common cold. We expressed VP1 proteins from two distantly related HRV strains, HRV89 and HRV14, in Escherichia coli. Mice and rabbits were immunised with the purified recombinant proteins. The induced antibodies reacted with natural VP1 and with whole virus particles as shown by immunoblotting and immunogold electron microscopy. They exhibited strong cross-neutralising activity for different HRV strains. Therefore, recombinant VP1 may be considered a candidate HRV vaccine to prevent HRV-induced asthma exacerbations.


Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment.
Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus. Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor. We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.


The primary cilium as a novel extracellular sensor in bone.
Mechanically induced adaptation of bone is required to maintain a healthy skeleton and defects in this process can lead to dramatic changes in bone mass, resulting in bone diseases such as osteoporosis. Therefore, understanding how this process occurs could yield novel therapeutics to treat diseases of excessive bone loss or formation. Over the past decade the primary cilium has emerged as a novel extracellular sensor in bone, being required to transduce changes in the extracellular mechanical environment into biochemical responses regulating bone adaptation. In this review, we introduce the primary cilium as a novel extracellular sensor in bone; discuss the in vitro and in vivo findings of primary cilia based sensing in bone; explore the role of the primary cilium in regulating stem cell osteogenic fate commitment and finish with future directions of research and possible development of cilia targeting therapeutics to treat bone diseases.


Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent Dunning R-3327-AT-1 rat prostate cancer.
The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.


Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition.
Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3,000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.


A minor microtubule-associated protein is responsible for the stimulation of vesicular stomatitis virus transcription in vitro.
An activity found in bovine brain microtubule-associated proteins (MAPs) which stimulated vesicular stomatitis virus (VSV) transcription in vitro co-eluted from a gel filtration column (Sepharose CL-6B) with a minor MAP subset of an apparent Mr of 100,000 to 250,000. The activity did not appear to be closely associated with MAPs 1, MAPs 2, tau or tubulin. Anti-MAPs 1 and anti-MAPs 2 IgG did not reduce or abolish the stimulatory activity. The bovine brain MAPs stimulatory activity was similar to that found in HeLa cell extracts: both were heat-resistant, and both co-purified with the MAPs fraction of cell extracts; also amounts of each which gave maximum stimulation when used separately did not give additional stimulation when combined. Fractions from the Sepharose CL-6B column that contained the greatest amount of stimulatory activity exhibited little or no cAMP-dependent or -independent kinase activity. The MAPs stimulatory activity required the presence of both L and NS polymerase subunits.


Climate change reduces offspring fitness in littoral spawners: a study integrating organismic response and long-term time-series.
Integrating long-term ecological observations with experimental findings on species response and tolerance to environmental stress supports an understanding of climate effects on population dynamics. Here, we combine the two approaches, laboratory experiments and analysis of multi-decadal time-series, to understand the consequences of climate anomalies and ongoing change for the population dynamics of a eurythermal littoral species, Carcinus aestuarii. For the generation of cause and effect hypotheses we investigated the thermal response of crab embryos at four developmental stages. We first measured metabolic rate variations in embryos following acute warming (16-24 °C) and after incubation at 20 and 24 °C for limited periods. All experiments consistently revealed differential thermal responses depending on the developmental stage. Temperature-induced changes in metabolic activity of early embryonic stages of blastula and gastrula suggested the onset of abnormal development. In contrast, later developmental stages, characterized by tissue and organ differentiation, were marginally affected by temperature anomalies, indicating enhanced resilience to thermal stress. Then, we extended these findings to a larger, population scale, by analyzing a time-series of C. aestuarii landings in the Venice lagoon from 1945 to 2010 (ripe crabs were recorded separately) in relation to temperature. Landings and extreme climatic events showed marked long-term and short-term variations. We found negative relationships between landings and thermal stress indices on both timescales, with time lags consistent with an impact on crab early life stages. When quantitatively evaluating the influence of thermal stress on population dynamics, we found that it has a comparable effect to that of the biomass of spawners. This work provides strong evidence that physiological responses to climatic anomalies translate into population-level changes and that apparently tolerant species may be impacted before the ontogeny of eurythermy. These ontogenetic bottlenecks markedly shape population dynamics and require study to assess the effects of global change.


Contribution of Walking to School to Individual and Population Moderate-Vigorous Intensity Physical Activity: Systematic Review and Meta-Analysis.
This study estimated the contribution of walking to/from school to objectively measured daily moderate-vigorous intensity physical activity (MVPA) in individuals and populations. MEDLINE, PsycINFO and SPORTDiscus were systematically searched up to February 2015. Two reviewers independently screened titles/abstracts/full-text articles, and assessed study quality. Of 2430 records, 129 were eligible for full-text screening. Twelve studies met the inclusion criteria of reporting objectively obtained measures of MVPA (total and while walking to/from school) in children and adolescents. The weighted mean MVPA accumulated in walking to and from school was 17 min/day in primary school pupils (9 samples, n = 3422) and 13 min/day in high school pupils (4 samples, n = 2600). Pooled analysis suggested that walking to and from school contributed 23% and 36% of MVPA on schooldays in primary school age children and high school pupils, respectively. All included studies were of high methodological quality. Walking to and from school makes a meaningful contribution to individual schoolday MVPA for active commuters in western countries. Since schooldays represent only around half of all days, and prevalence of walking to school is low in many countries, the contribution of walking to school to population MVPA is probably low.


Molecular description of the LCST behavior of an elastin-like polypeptide.
Elastin-like polypeptides (ELPs) with the repeat sequence of VPGVG are widely used as a model system for investigation of lower critical solution temperature (LCST) transition behavior. In this paper, the effect of temperature on the structure, dynamics and association of (VPGVG)18 in aqueous solution is investigated using atomistic molecular dynamics simulations. Our simulations show that as the temperature increases the ELP backbones undergo gradual conformational changes, which are attributed to the formation of more ordered secondary structures such as β-strands. In addition, increasing temperature changes the hydrophobicity of the ELP by exposure of hydrophobic valine-side chains to the solvent and hiding of proline residues. Based on our simulations, we conclude that the transition behavior of (VPGVG)18 can be attributed to a combination of thermal disruption of the water network that surrounds the polypeptide, reduction of solvent accessible surface area of the polypeptide, and increase in its hydrophobicity. Simulations of the association of two (VPGVG)18 molecules demonstrated that the observed gradual changes in the structural properties of the single polypeptide chain are enough to cause the aggregation of polypeptides above the LCST. These results lead us to propose that the LCST phase behavior of poly(VPGVG) is a collective phenomenon that originates from the correlated gradual changes in single polypeptide structure and the abrupt change in properties of hydration water around the peptide and is a result of a competition between peptide-peptide and peptide-water interactions. This is a computational study of an important intrinsically disordered peptide system that provides an atomic-level description of structural features and interactions that are relevant in the LCST phase behavior.


Operational Assessment of Long-Lasting Insecticidal Nets by Using an Anopheles Salivary Biomarker of Human-Vector Contact.
The widespread implementation of long-lasting insecticidal nets (LLINs) is a major intervention method for malaria control. Although the LLINs coverage increases, information available on the physical integrity (PI) of implemented LLINs is incomplete. This study aimed to validate human IgG antibody (Ab) response to Anopheles gSG6-P1 salivary peptide antigen, previously demonstrated as a pertinent biomarker of human exposure to Anopheles bites, for evaluating the PI of LLINs in field conditions. We analyzed data from 262 randomly selected children (< 5 years of age) in health districts of Benin. Anti-gSG6-P1 IgG responses were assessed and compared with the PI of LLINs that these same children slept under, and evaluated by the hole index (HI). Specific IgG levels were positively correlated to LLINs HI (r = 0.342; P < 0.0001). According to antipeptide IgG level (i.e., intensity of vector exposure), two categories of LLINs PI were defined: 1) group "HI: [0, 100]" corresponding to LLINs with "good" PI and 2) "HI > 100" corresponding to LLINs with "bad" PI. These results suggest that human Ab response to salivary peptide could be a complementary tool to help defining a standardized threshold of efficacy for LLINs under field use.


Expression of androgen receptor target genes in skeletal muscle.
We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR)-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (AR(ΔZF2)) versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR(∆ZF2) muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57(Kip2), Igf2 and calcineurin Aa, was increased in AR(∆ZF2) muscle, and the expression of all but p57(Kip2) was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.


Follow-up of the re-evaluation of glycerol (E 422) as a food additive.
Glycerol (E 422) was re-evaluated in 2017 by the former EFSA Panel on Food Additives and Nutrient sources added to Food (ANS). As a follow-up to that assessment, in this opinion, the Panel on Food Additives and Flavourings (FAF) addresses the data gaps identified to support an amendment of the EU specifications for E 422 in Commission Regulation (EU) No 231/2012. The Panel performed a risk assessment of undesirable impurities present in E 422. The Panel concluded that the maximum limits in the EU specifications for the four toxic elements (arsenic, lead, mercury and cadmium) should be lowered based on actual levels in the commercial food additive E 422. The Panel recommended setting a numerical limit value for acrolein in the specifications for E 422. The potential exposure to free 3-monochloropropanediol at the maximum limit of 0.1 mg/kg, as laid out in the specifications for E 422, does not give rise to a health concern. The Panel recommended to consider modifying the definition of E 422 in Commission Regulation (EU) No 231/2012 indicating that E 422 is obtained only from vegetable oils and fats and undergoes purification processes that involve distillation, and other clean up steps to obtain refined glycerol. Overall, the Panel concluded that the technical data provided support an amendment of the specifications for glycerol (E 422).


Treatment of severe borderline personality disorder with clozapine.
Patients with borderline personality disorder (BPD) show significant impairment in the domain of interpersonal and social functioning and may use the resources of health and social services extensively, with little beneficial outcome. At present there are no clear guidelines in literature for the use of pharmacotherapy in the management of BPD. According to the scanty literature available in the form of case reports and small studies, clozapine has been demonstrated to be effective in the management of BPD. The case presented here describes the effectiveness of clozapine in a young female patient with severe BPD (without psychotic features), who had repeated and prolonged periods of hospitalization and was successfully treated with a moderate dose of clozapine, following a failure to improve with other psychotropic medications. More studies are suggested to evaluate the efficacy of clozapine in patients with BPD, both with and without psychotic features, to find out the optimum dose and to weigh the risk and benefits of clozapine.


Structural basis for poor uracil excision from hairpin DNA. An NMR study.
Two-dimensional NMR and molecular dynamics simulations have been used to determine the three-dimensional structures of two hairpin DNA structures: d-CTAGAG GATCCUTTTGGATCCT (abbreviated as U1-hairpin) and d-CTAGAGGATCCTTUTGGATCCT (abbreviated as U3-hairpin). The 1H resonances of both of these hairpin structures have been assigned almost completely. NMR restrained molecular dynamics and energy minimization procedures have been used to describe the three-dimensional structures of these hairpins. This study and concurrent NMR structural studies on two other d-CTAGAGGA TCCTUTTGGATCCT (abbreviated as U2-hairpin) and d-CTAGAGGATCCTTTUGGATCCT (abbreviated as U4-hairpin) have shed light upon various interactions reported between Echerichia coli uracil DNA glycosylase (UDG) and uracil-containing DNA. The backbone torsion angles, which partially influence the local conformation of U12 and U14 in U1 and U3-hairpins, respectively, are probably locked in the trans conformation as in the case of U13 in the U2-hairpin. Such a stretched-out backbone conformation in the vicinity of U12 and U14 is thought to be the reason why the Km value is poor for U1- and U3-hairpins as it is for the U2-hairpin. Furthermore, the bases U12 and U14 in both U1- and U3-hairpins adopt an anti conformation, in contrast with the base conformation of U13 in the U2-hairpin, which adopts a syn conformation. The clear discrepancy observed in the U-base orientation with respect to the sugar moieties could explain why the Vmax value is 10- to 20-fold higher for the U1- and U3-hairpins compared with the U2-hairpin. Taken together, these observations support our interpretation that the unfavourable backbone results in a poor Km value, whereas the unfavourable nucleotide conformation results in a poor Vmax value. These two parameters therefore make the U1- and U3-hairpins better substrates for UDG compared with the U2-hairpin, as reported earlier [Kumar, N. V. & Varshney, U. (1997) Nucleic Acids Res. 25, 2336-2343.].


Natural history and prognostic factors for survival in patients with acquired immune deficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL).
The incidence of primary central nervous system lymphoma (PCNSL) is increasing rapidly. It will be the most common primary malignant neoplasm of the brain by the year 2000. PCNSL is an important lethal complication in acquired immunodeficiency syndrome (AIDS) patients. Our objective was to study the natural history and prognostic factors for survival in patients with AIDS-related PCNSL. This is a retrospective cohort study of 75 patients with the diagnosis of AIDS-related PCNSL followed at Jackson Memorial Hospital/University of Miami. Medical records were abstracted for information about age, gender, race, and ethnicity. The method of diagnosis, treatment, and outcome of AIDS and PCNSL in this group were examined. Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median age was 37 years. Males comprised 84% of the patients and 55% of the patients were Hispanic. The most common human immunodeficiency virus (HIV) risk factors were homosexuality and multiple sexual partners. The median cluster designation (CD) 4 count was 15/microl and the median lactic dehydrogensase (LDH) was 1.5x normal. Computed-assisted tomographic (CT) scans of the brain showed multiple lesions in 44% of the patients. Single-photon emission CT scan (SPECT) Thallium-201 of the brain was performed in two-thirds of patients. The most common histologies were immunoblastic and large cell lymphoma. Cranial radiation was given to 72% of the patients, and 55% of them did not complete treatment. The median survival of the group was 1.3 months. Univariate and multivariate analysis showed that longer survival was associated with good performance status (ECOG = 1 to 2 vs. 3 to 4). The presence of prior opportunistic infections, risk factors for AIDS, CD4 counts, level of LDH, ethnicity, gender, duration of symptoms before diagnosis, and race did not influence survival. PCNSL is a neoplasm with a very poor prognosis and short survival even with CNS radiation therapy. Performance status appears to be the main prognostic factor for survival. No significant differences in presentation or outcome were detected between the Hispanic and non-Hispanic patients.


Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA.
Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts.


A telerobotic haptic system for minimally invasive stereotactic neurosurgery.
Medical robotics and computer assisted surgery are feasible and promising applications of robotic technology, whose main goals are surgical augmentation, information enhancement and improved surgical action. Neurosurgery probably presents the most major challenges, and can considerably benefit from the introduction of computers and robots to guide surgical procedures. This paper presents an innovative master-slave haptic robotic system for minimally invasive neurosurgery, which can help surgeons overcome human shortcomings and perform more accurate, repeatable, and reliable stereotactic neurosurgery. The system, named LANS, consists of a slave mechatronic actuator and a haptic master. The slave is designed to move linearly a laser pointer, a biopsy needle or a low-energy X-ray emitter along a pre-planned axis. The tool insertion into the brain is guided by the surgeon through the haptic master which also provides force feedback to the operator. Not only can the haptic master reproduce the contact force between the surgical tool and the treated tissue, but it can also produce virtual forces aimed at assisting surgeons during the operations. Experiments have been conducted to prove the soundness and accuracy of the overall system mechanical design and to assess the effectiveness of the control schemes synthesized for the master and the slave.


Effects of swimming and environmental hypoxia on coronary blood flow in rainbow trout.
Previous studies have suggested that trout cardiac performance is highly dependent on coronary blood flow during periods of increased activity or hypoxia. To examine the relationship between coronary perfusion and cardiac performance in swimming trout, cardiac output (Q), coronary blood flow (qcor), and dorsal aortic blood pressure were measured in rainbow trout (Oncorhynchus mykiss) during normoxia and hypoxia (PO2 approximately 9 kPa). In normoxic trout, stepwise changes in cardiovascular variables were observed as the swimming speed was incrementally increased from 0.15 body lengths (bl)/s to 1.0 bl/s. At 1.0 bl/s, qcor and cardiac power output had both increased by approximately 110%, and coronary artery resistance (Rcor) had decreased by 40%. During hypoxia, resting qcor was 35% higher, and Rcor was 20% lower, compared with normoxic values. In hypoxic swimming trout, the maximum changes in qcor (155% increase) and Rcor (50% decrease) were recorded at 0.75 bl/s. In contrast, cardiac power output and Q increased by an additional 40 and 20%, respectively, as swimming speed was increased from 0.75 to 1.0 bl/s. The results indicate that 1) increases in qcor parallel changes in cardiac power output; 2) during hypoxia there are compensatory increases in cardiac performance and coronary perfusion; and 3) the scope for increasing qcor in swimming trout is approximately 150%. In addition, results from preliminary experiments suggest that beta-adrenergic, but not cholinergic, mechanisms are involved in the regulation of coronary blood flow during exercise.


Prioritizing targets for structural biology through the lens of proteomics: the archaeal protein TGAM_1934 from Thermococcus gammatolerans.
ORFans are hypothetical proteins lacking any significant sequence similarity with other proteins. Here, we highlighted by quantitative proteomics the TGAM_1934 ORFan from the hyperradioresistant Thermococcus gammatolerans archaeon as one of the most abundant hypothetical proteins. This protein has been selected as a priority target for structure determination on the basis of its abundance in three cellular conditions. Its solution structure has been determined using multidimensional heteronuclear NMR spectroscopy. TGAM_1934 displays an original fold, although sharing some similarities with the 3D structure of the bacterial ortholog of frataxin, CyaY, a protein conserved in bacteria and eukaryotes and involved in iron-sulfur cluster biogenesis. These results highlight the potential of structural proteomics in prioritizing ORFan targets for structure determination based on quantitative proteomics data. The proteomic data and structure coordinates have been deposited to the ProteomeXchange with identifier PXD000402 (http://proteomecentral.proteomexchange.org/dataset/PXD000402) and Protein Data Bank under the accession number 2mcf, respectively.


How temperature changes reset a circadian oscillator.
Circadian rhythms control many physiological activities. The environmental entrainment of rhythms involves the immediate responses of clock components. Levels of the clock protein FRQ were measured in Neurospora at various temperatures; at higher temperatures, the amount of FRQ oscillated around higher levels. Absolute FRQ amounts thus identified different times at different temperatures, so temperature shifts corresponded to shifts in clock time without immediate synthesis or turnover of components. Moderate temperature changes could dominate light-to-dark shifts in the influence of circadian timing. Temperature regulation of clock components could explain temperature resetting of rhythms and how single transitions can initiate rhythmicity from characteristic circadian phases.


Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae.
Sister chromatid cohesion (SCC), which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC). In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability.


Mechanisms to increase propulsive force for individuals poststroke.
Propulsive force generation is critical to walking speed. Trialing limb angle and ankle moment are major contributors to increases in propulsive force during gait. For able-bodied individuals, trailing limb angle contributes twice as much as ankle moment to increases in propulsive force during speed modulation. The aim of this study was to quantify the relative contribution of ankle moment and trailing limb angle to increases in propulsive force for individuals poststroke. A biomechanical-based model previously developed for able-bodied individuals was evaluated and enhanced for individuals poststroke. Gait analysis was performed as subjects (N = 24) with chronic poststroke hemiparesis walked at their self-selected and fast walking speeds on a treadmill. Both trailing limb angle and ankle moment increased during speed modulation. In the paretic limb, the contribution from trailing limb angle versus ankle moment to increases in propulsive force is 74% and 17%. In the non-paretic limb, the contribution from trailing limb angle versus ankle moment to increases in propulsive force is 67% and 22%. Individuals poststroke increase propulsive force mainly by changing trailing limb angle in both the paretic and non-paretic limbs. This strategy may contribute to the inefficiency in poststroke walking patterns. Future work is needed to examine whether these characteristics can be modified via intervention.


Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory.
The RNA modification N6-methyladenosine (m6A) regulates the interaction between RNA and various RNA binding proteins within the nucleus and other subcellular compartments and has recently been shown to be involved in experience-dependent plasticity, learning, and memory. Using m6A RNA-sequencing, we have discovered a distinct population of learning-related m6A- modified RNAs at the synapse, which includes the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1). RNA immunoprecipitation and mass spectrometry revealed 12 new synapse-specific learning-induced m6A readers in the mPFC of male C57/BL6 mice, with m6A-modified Malat1 binding to a subset of these, including CYFIP2 and DPYSL2. In addition, a cell type- and synapse-specific, and state-dependent, reduction of m6A on Malat1 impairs fear-extinction memory; an effect that likely occurs through a disruption in the interaction between Malat1 and DPYSL2 and an associated decrease in dendritic spine formation. These findings highlight the critical role of m6A in regulating the functional state of RNA during the consolidation of fear-extinction memory, and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.SIGNIFICANCE STATEMENT We have discovered that learning-induced m6A-modified RNA (including the long noncoding RNA, Malat1) accumulates in the synaptic compartment. We have identified several new m6A readers that are associated with fear extinction learning and demonstrate a causal relationship between m6A-modified Malat1 and the formation of fear-extinction memory. These findings highlight the role of m6A in regulating the functional state of an RNA during memory formation and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.


Increasing rate of anti-SARS-CoV-2 antibodies between the first and second waves of COVID-19 in São Paulo, Brazil: A cross-sectional blood donors-based study.
SARS-CoV-2 infections rapidly spread along with Brazilian territory with heterogeneous transmission and mortality rates, mostly depending on region and period. Investigation of SARS-CoV-2 antibodies is an important tool to understand virus circulation. Given that blood donors are a representative casuistic of a healthy population, the authors evaluated the seroprevalence of IgG and IgM COVID-19 antibodies in 2,806 blood donors from a blood bank located in São Paulo, Brazil. Aiming to evaluate viral behavior over time, the authors selected samples from blood donors who donated in June and October 2020, and February 2021. To determine whether socio-demographic features affected the seroprevalence, the authors analyzed samples from three different regions from São Paulo (capital, metropolitan and countryside regions) and evaluated predictors as gender, age, educational level, race, and use of public transportation. As expected, the authors observed that seroprevalence increased over time. Seroprevalence was greater in São Paulo city compared to metropolitan and countryside regions, being smallest in the countryside. Characteristics associated with a lower percentage of antibodies were age above 50 years, higher educational level, self-declared Caucasian, and use of individual transportation. In conclusion, blood donors' samples proved to accurately reflect virus circulation in the healthy population.


A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.


Reaction-based machine learning representations for predicting the enantioselectivity of organocatalysts.
Hundreds of catalytic methods are developed each year to meet the demand for high-purity chiral compounds. The computational design of enantioselective organocatalysts remains a significant challenge, as catalysts are typically discovered through experimental screening. Recent advances in combining quantum chemical computations and machine learning (ML) hold great potential to propel the next leap forward in asymmetric catalysis. Within the context of quantum chemical machine learning (QML, or atomistic ML), the ML representations used to encode the three-dimensional structure of molecules and evaluate their similarity cannot easily capture the subtle energy differences that govern enantioselectivity. Here, we present a general strategy for improving molecular representations within an atomistic machine learning model to predict the DFT-computed enantiomeric excess of asymmetric propargylation organocatalysts solely from the structure of catalytic cycle intermediates. Mean absolute errors as low as 0.25 kcal mol-1 were achieved in predictions of the activation energy with respect to DFT computations. By virtue of its design, this strategy is generalisable to other ML models, to experimental data and to any catalytic asymmetric reaction, enabling the rapid screening of structurally diverse organocatalysts from available structural information.


Endodontic drug delivery for root surface disinfection: a laboratory feasibility evaluation.
This study aims to assess the potential of a mixture of three antibiotics (TreVitaMix, TVM) as an intracanal dressing to disinfect the outer root surface by applying a new in vitro model. Fifty freshly extracted bovine roots were endodontically treated. Forty samples were then thoroughly scaled, mounted to petri dishes, gas sterilized, and randomly allocated to four groups (n = 10/group) according to their intracanal medication: sterile saline (NaCl; control, A); the TVM carrier material alone, i.e., propylene glycol (PG; B); TVM (C); and calcium hydroxide (D). In an additional group (E), the cementum was not removed and TVM was placed. Petri dishes were filled with Fastidious Anaerobe Agar, inoculated with Fusobacterium nucleatum suspension and then anaerobically incubated during 48-h intervals at 37 °C up to 192 h. Inhibition zones around the roots were then measured after each incubation period (mm(2)). Only teeth inoculated with the TVM dressing showed inhibition at all time points, whereas the other treatments showed no peri-radicular growing inhibition. Presence of cementum had no negative effect on disinfection (p = 0.9320). TVM was able to penetrate through the dentine and inhibit the bacterial growth of F. nucleatum up to 192 h. TVM might have the potential to sustainably disinfect the outer root surface in perio-endo lesions and serve as an adjunctive antimicrobial agent.


Treatment of pseudoarthrosis of the upper limb using expanded mesenchymal stem cells: a pilot study.
In orthopedic field is growing interest in the use of stem cells: this mesenchymal multipotent line (MSCs) can lead to differentiation into osteocytes and thus the formation of bone tissue. In literature applications of this line are described in injuries of tendons and ligaments, small bony avulsions, nonunion fractures and cartilage defects. Utilize MSCs expanded in laboratory in case of atrophic pseudoarthrosis of the upper limb. We obtain the amount of cell necessary for the implant by the collaboration with the UO Haematological Department. For the procedure we make a blood sample from the iliac crest bone marrow and a subsequent phase of selection and cultivation of mesenchymal line for 3 weeks, to get a sufficient amount of tissue to be used, which is presented at the time of surgery on a scaffold made by autologous plasma gel and CaCl(2). We reassessed our experience in 8 different types of upper limb fractures result in pseudarthrosis and delayed of consolidation: 4 women and 4 men, average 44 years old followed with a follow-up of 50.3 months. In all cases the site of non-union has been revitalized (by microfractures and drilling) and a synthesis was performed with a rigid plate. So we fill the bone gap with autologous bone and mesenchymal stem cells expanded in the laboratory. We have a radiographic healing in 8 cases and no adverse events were highlighted. Using this cells line we obtained encouraging but certainly not conclusive impressions, according to the limited number of cases and lack of adequate comparative studies. In tissue engineering are also certainly needed further investigations and developments.


Effectiveness of the gaze direction recognition task for chronic neck pain and cervical range of motion: a randomized controlled pilot study.
We developed a mental task with gaze direction recognition (GDR) by which subjects observed neck rotation of another individual from behind and attempted to recognize the direction of gaze. A randomized controlled trial was performed in test (n = 9) and control (n = 8) groups of subjects with chronic neck pain undergoing physical therapy either with or without the GDR task carried out over 12 sessions during a three-week period. Primary outcome measures were defined as the active range of motion and pain on rotation of the neck. Secondary outcome measures were reaction time (RT) and response accuracy in the GDR task group. ANOVA indicated a main effect for task session and group, and interaction of session. Post hoc testing showed that the GDR task group exhibited a significant simple main effect upon session, and significant sequential improvement of neck motion and relief of neck pain. Rapid effectiveness was significant in both groups. The GDR task group had a significant session-to-session reduction of RTs in correct responses. In conclusion, the GDR task we developed provides a promising rehabilitation measure for chronic neck pain.


[Upper femoral neck fractures at a local hospital. A retrospective study from the Sandnessjøn hospital 1988-91].
The frequency of patients treated for hip fracture at Sandnessjøen hospital was recorded for the years 1988-91. In a population of about 29,000, the discharge from hospital was 1.89 per 1,000 inhabitants, corresponding to 6.5% of the total number of discharges. The ratio of females to males was 2.7. The fractures were equally distributed between the medial and lateral subtypes, but perioperative complications were more frequently noted with the former. The most common occurrence was segmental collapse of the femoral head, together with local pain. Based on a questionnaire, about 3/4 of the patients complained of reduced physical fitness after the operation. During the previous 22 years, only seven out of 40 local hospitals in Norway had undertaken some sort of survey of patients with this common fracture. It appears that as many as about 40% of the patients who were treated for hip fracture suffered from some form of complication following the operation.


Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal.
Gliomas are the most common primary brain tumor and one of the most lethal solid tumors. Mechanistic studies into identification of novel biomarkers are needed to develop new therapeutic strategies for this deadly disease. The objective for this study was to explore the potential direct impact of IL-17-IL-17R interaction in gliomas. Immunohistochemistry and flow cytometry analysis of 12 tumor samples obtained from patients with high grade gliomas revealed that a considerable population (2-19%) of cells in all malignant gliomas expressed IL-17RA, with remarkable co-expression of the glioma stem cell (GSC) markers CD133, Nestin, and Sox2. IL-17 enhanced the self-renewal of GSCs as determined by proliferation and Matrigel® colony assays. IL-17 also induced cytokine/chemokine (IL-6, IL-8, interferon-γ-inducible protein [IP-10], and monocyte chemoattractant protein-1 [MCP-1]) secretion in GSCs, which were differentially blocked by antibodies against IL-17R and IL-6R. Western blot analysis showed that IL-17 modulated the activity of signal transducer and activator of transcription 3 (STAT3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), glycogen synthase kinase-3β (GSK-3β) and β-catenin in GSCs. While IL-17R-mediated secretion of IL-6 and IL-8 were significantly blocked by inhibitors of NF-κB and STAT3; NF-κB inhibitor was more potent than STAT3 inhibitor in blocking IL-17-induced MCP-1 secretion. Overall, our results suggest that IL-17-IL-17R interaction in GSCs induces an autocrine/paracrine cytokine feedback loop, which may provide an important signaling component for maintenance/self-renewal of GSCs via constitutive activation of both NF-κB and STAT3. The results also strongly implicate IL-17R as an important functional biomarker for therapeutic targeting of GSCs.


Therapeutic decisions for patients with symptomatic severe aortic stenosis: room for improvement?
Symptomatic severe aortic stenosis is an indication for aortic valve replacement. Some patients are denied intervention. This study provides insight into the proportion of conservatively treated patients and into the reasons why conservative treatment is chosen. Of a patient cohort presenting with severe aortic stenosis between 2004 and 2007, medical records were retrospectively analyzed. Only symptomatic patients (n=179) were included. We studied their characteristics, treatment decisions, and survival. Mean age was 71 years, 50% were male. During follow-up (mean 17 months, 99% complete) 76 (42%) patients were scheduled for surgical treatment (63 conventional valve replacement, 10 transcatheter, 1 heart transplantation, 2 waiting list) versus 101 (56%) who received medical treatment. Reasons for medical treatment were: perceived high operative risk (34%), symptoms regarded mild (19%), stenosis perceived non-severe (14%), and patient preference (9%). In 5% the decision was pending at the time of the analysis and in 20% the reason was other/unclear. Mean age of the surgical group was 68 years versus 73 years for medically treated patients (p=0.004). Predicted mortality (EuroSCORE) was 7.8% versus 11.3% (p=0.006). During follow-up 12 patients died in the surgical group (no 30-day operative mortality), versus 28 in the medical group. Two-year survival was 90% versus 69%. A large proportion (56%) of symptomatic patients does not undergo aortic valve replacement. Often operative risk is estimated (too) high or hemodynamic severity and symptomatic status are misclassified. Interdisciplinary team discussions between cardiologists and surgeons should be encouraged to optimize patient selection for surgery.


Contribution of amenable mortality to life expectancy differences between the Dutch Caribbean islands of Aruba and Curaçao and the Netherlands.
To identify specific health care areas whose optimization could improve population health in the Dutch Caribbean islands of Aruba and Curaçao. Comparative observational study using mortality and population data of the Dutch Caribbean islands and the Netherlands. Mortality trends were calculated, then analyzed with Joinpoint software, for the period 1988-2014. Life expectancies were computed using abridged life tables for the most recent available data of all territories (2005-2007). Life expectancy differences between the Dutch Caribbean and the Netherlands were decomposed into cause-specific contributions using Arriaga's method. During the period 1988-2014, levels of amenable mortality have been consistently higher in Aruba and Curaçao than in the Netherlands. For Aruba, the gap in amenable mortality with the Netherlands did not significantly change during the study period, while it widened for Curaçao. If mortality from amenable causes were reduced to similar levels as in the Netherlands, men and women in Aruba would have added, respectively, 1.19 years and 0.72 years to their life expectancies during the period 2005-2007. In Curaçao, this would be 2.06 years and 2.33 years. The largest cause-specific contributions were found for circulatory diseases, breast cancer, perinatal causes, and nephritis/nephrosis (these last two causes solely in Curaçao). Improvements in health care services related to circulatory diseases, breast cancer, perinatal deaths, and nephritis/nephrosis in the Dutch Caribbean could substantially contribute to reducing the gap in life expectancy with the Netherlands. Based on our study, we recommend more in-depth studies to identify the specific interventions and resources needed to optimize the underlying health care areas.


Computer-aided biochemical programming of synthetic microreactors as diagnostic devices.
Biological systems have evolved efficient sensing and decision-making mechanisms to maximize fitness in changing molecular environments. Synthetic biologists have exploited these capabilities to engineer control on information and energy processing in living cells. While engineered organisms pose important technological and ethical challenges, de novo assembly of non-living biomolecular devices could offer promising avenues toward various real-world applications. However, assembling biochemical parts into functional information processing systems has remained challenging due to extensive multidimensional parameter spaces that must be sampled comprehensively in order to identify robust, specification compliant molecular implementations. We introduce a systematic methodology based on automated computational design and microfluidics enabling the programming of synthetic cell-like microreactors embedding biochemical logic circuits, or protosensors, to perform accurate biosensing and biocomputing operations in vitro according to temporal logic specifications. We show that proof-of-concept protosensors integrating diagnostic algorithms detect specific patterns of biomarkers in human clinical samples. Protosensors may enable novel approaches to medicine and represent a step toward autonomous micromachines capable of precise interfacing of human physiology or other complex biological environments, ecosystems, or industrial bioprocesses.


Terahertz-field-induced polar charge order in electronic-type dielectrics.
Ultrafast electronic-phase change in solids by light, called photoinduced phase transition, is a central issue in the field of non-equilibrium quantum physics, which has been developed very recently. In most of those phenomena, charge or spin orders in an original phase are melted by photocarrier generations, while an ordered state is usually difficult to be created from a non-ordered state by a photoexcitation. Here, we demonstrate that a strong terahertz electric-field pulse changes a Mott insulator of an organic molecular compound in κ-(ET)2Cu[N(CN)2]Cl (ET = bis(ethylenedithio)tetrathiafulvalene), to a macroscopically polarized charge-order state; herein, electronic ferroelectricity is induced by the collective intermolecular charge transfers in each dimer. In contrast, in an isostructural compound, κ-(ET)2Cu2(CN)3, which shows the spin-liquid state at low temperatures, a similar polar charge order is not stabilized by the same terahertz pulse. From the comparative studies of terahertz-field-induced second-harmonic-generation and reflectivity changes in the two compounds, we suggest the possibility that a coupling of charge and spin degrees of freedom would play important roles in the stabilization of polar charge order.


Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposes.
Long noncoding RNAs (lncRNAs) are a class of noncoding RNA, involved in regulation of diverse physiological and pathological processes. Ovarian cancer is the leading cause of death among all gynecological malignancies in the world and its underlying mechanism is still unclear. LncRNAs exhibit multiple biological functions in various stages of ovarian cancer development. We will discuss and summarize the new and important lncRNAs and their involvement in disease, which might represent promising therapeutic targets. Therapeutic intervention based on silencing or functional inhibition of target lncRNAs will be beneficial for ovarian cancer patients.


Sleep problems in individuals with spinal cord injury: frequency and age effects.
The two objectives of this study were (a) to replicate the previous finding of more severe sleep difficulties in a sample of individuals with spinal cord injury (SCI) compared with normative samples, and (b) to examine the associations between aging variables (specifically, chronological age, duration of SCI, age at SCI onset) and the severity of sleep difficulties. Cross-sectional survey. A survey was administered to 620 individuals with SCI that included measures of demographic characteristics and sleep difficulties. The findings indicated that sleep problems are more common in individuals with SCI than in normative samples. In addition, younger participants in our sample reported more sleep problems than did older participants. Duration of SCI and age at onset, however, were not significantly associated with sleep difficulties. The analyses used in this study provide a model for examining age effects using concurrent survey data that may be useful for other investigators interested in studying the associations between age-related variables and important health-related domains.


Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand.
Monkeys and human subjects were exposed to a series of thermal stimuli before and after a 53 degrees C, 30-second burn to the glabrous skin of the hand. The responses of C- and A-fiber nociceptive afferents in the monkeys and subjective responses by the humans were compared. The burn resulted in increased sensitivity of the A fibers, decreased sensitivity of the C fibers, and increased pain sensibility (hyperalgesia) in the human subjects.


Cracking outer membrane biogenesis.
The outer membrane is a distinguishing feature of the Gram-negative envelope. It lies on the external face of the peptidoglycan sacculus and forms a robust permeability barrier that protects extracytoplasmic structures from environmental insults. Overcoming the barrier imposed by the outer membrane presents a significant hurdle towards developing novel antibiotics that are effective against Gram-negative bacteria. As the outer membrane is an essential component of the cell, proteins involved in its biogenesis are themselves promising antibiotic targets. Here, we summarize key findings that have built our understanding of the outer membrane. Foundational studies describing the discovery and composition of the outer membrane as well as the pathways involved in its construction are discussed.


Effective mass anisotropy of gamma electrons in GaAs/AlGaAs quantum wells.
Resonant magnetotunneling in GaAs/Al(0.28)Ga0.72As double barrier structures is used to demonstrate that the effective mass of confined Gamma conduction electrons becomes anisotropic when an electric field is applied perpendicular to the interfaces. Although several authors have previously reported Gamma-related optical anisotropy, this is the first example of a corresponding electrical anisotropy. The results are explained using a quantum mechanical model involving interface band mixing that contains additional features not found in the optical case.


The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation.
Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well. Potential side-effects due to prostate cancer-related radiation therapy include bowel inflammation, erectile dysfunction, urethral stricture, rectal bleeding and incontinence. Currently, radiation therapy for prostate cancer does not include the administration of therapeutic agents to reduce these side effects and protect normal tissues from radiation-induced damage. In the current study, we show that the small molecular weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin, prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected from erectile dysfunction, a persistent problem regardless of the type of radiation techniques used because the penile neurovascular bundles lay in the peripheral zones of the prostate, where most prostate cancers reside. Based on previous studies showing that MnTE-2-PyP, in combination with radiation, further reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an excellent radioprotectant in combination radiotherapy for cancer in general and specifically for prostate cancer.


Resistance to neutralization by broadly reactive antibodies to the human immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid change.
A neutralization-resistant variant of human immunodeficiency virus type 1 (HIV-1) that emerged during in vitro propagation of the virus in the presence of neutralizing serum from an infected individual has been described. A threonine-for-alanine substitution at position 582 in the gp41 transmembrane envelope glycoprotein of the variant virus was responsible for the neutralization-resistant phenotype (M.S. Reitz, Jr., C. Wilson, C. Naugle, R. C. Gallo, and M. Robert-Guroff, Cell 54:57-63, 1988). The mutant virus also exhibited reduced sensitivity to neutralization by 30% of HIV-1-positive sera that neutralized the parental virus, suggesting that a significant fraction of the neutralizing activity within these sera can be affected by the amino acid change in gp41 (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. Robert-Guroff, J. Virol. 64:3240-3248, 1990). It is shown here that the change of alanine 582 to threonine specifically confers resistance to neutralizing by antibodies directed against both groups of discontinuous, conserved epitopes related to the CD4 binding site on the gp120 exterior envelope glycoprotein. Only minor differences in binding of these antibodies to wild-type and mutant envelope glycoproteins were observed. Thus, the antigenic structure of gp120 can be subtly affected by an amino acid change in gp41, with important consequences for sensitivity to neutralization.


Characteristics and gender influence on outcomes of burns in adolescents.
The aim of this study was to investigate the characteristics and influence of gender difference on the outcome of adolescent burns. A retrospective study was conducted on 641 burn patients (10 - 19 years old) admitted to the Viet Nam National Burn Hospital over a three-year period (2016 - 2018). Demographic data, burn features and outcome including complications, length of hospital stay and mortality of male and female groups were compared. The results indicated that adolescents accounted for 6.5% of total admitted burn patients, with a predominance of males (69.3%). Higher proportions of burn due to dry heat (flame or hot surface contact) and electricity were seen in the male group (p < .001). No significant differences were seen between male and female groups in terms of age, admission time, season of burn and burn severity. Compared to females, males experienced more surgical interventions and stayed longer in hospital with higher LA50 (71.2% vs. 56.5% TBSA). It is necessary to conduct prevention and intervention to improve the outcome of adolescent burns, especially for female patients.


Dissolved organic matter differentially influences arsenic methylation and volatilization in paddy soils.
The effect of dissolved organic matter (DOM), derived from composted pig manure or rice straw, on arsenic methylation and subsequent biovolatilization in paddy soils was investigated. Arsine production following pig manure DOM application was 2.7- and 9.6-fold higher than that of soils treated with rice straw DOM and the control, respectively. Trimethylarsine was the dominant arsine at 54 %, followed by dimethylarsine at 22 %, arsine at 21 %, and monomethylarsine at 3 %. The copy numbers of the total and As-methylating bacteria were significantly enhanced in paddy soils treated with DOM. Pig manure DOM altered soil bacterial profile by increasing the OTU number of As methylation-inducing bacteria, such as Proteobacteria, Bacteroidetes, Geobacter, Sphingomonas, Streptomyces, and Rhodopseudomonas, thereby promoting As volatilization and methylation in paddy soils. The higher relative content of alkyl-C, N-alkyl C, and carboxyl-C in pig manure DOM was responsible for the increase in total and arsM-carrying bacteria in paddy soils, leading to enhanced As methylation. These observations will promote a better understanding of the role of DOM in mediating As methylation and volatilization, along with how organic fertilization affects straighthead disorder of rice, a condition caused by methylated arsenic species.


A long-term follow-up of male alcohol abuse.
This study attempted to determine the course of male alcohol abuse from the age of 40 years to 60 or 70 years, to estimate the duration of abstinence required for stable remission and to study the hypothesis of progression of symptoms in chronic alcohol abuse. The subjects were 268 former Harvard University (Cambridge, Mass) undergraduates (college sample) and 456 nondelinquent inner-city adolescents (core city sample) who had been repeatedly studied in multidisciplinary fashion since 1940. Since 47 years of age, these men have been followed up biennially by questionnaire and every 5 years by physical examination. At some point during their lives, 55 (21%) of the college and 150 (33%) of the core city men met DSM-III criteria for alcohol abuse. The college cohort has been followed until the age of 70 years, the core city cohort until age 60 years. The dependent variables were mortality and alcohol abuse status every 5 years. By 60 years of age, 18% of the college alcohol abusers had died, 11% were abstinent, 11% were controlled drinkers, and 59% were known to be still abusing alcohol. By 60 years of age, 28% of the core city alcohol abusers had died, 30% were abstinent, 11% were controlled drinkers, and only 28% were known to be still abusing alcohol. In three respects the two socially divergent samples resembled each other. After abstinence had been maintained for 5 years, relapse was rare. In contrast, return to controlled drinking without eventual relapse was unlikely. Alcohol abuse could continue for decades without remission or progression of symptoms. The samples differed in that the core city men began to abuse alcohol when younger and, although they were more likely than the college men to become alcohol dependent, the core city men were twice as likely to achieve stable abstinence.


Is nematode colonisation in the presence of Scolelepis in tropical sandy-beach sediment similar to the colonisation process in temperate sandy beaches?
The role of a dominant macrobenthic polychaete, Scolelepis squamata, in the colonisation of defaunated tropical sediments by sandy-beach nematodes was investigated and compared with a previous colonisation experiment carried out on a temperate sandy beach. Experimental cylinders, equipped with lateral windows allowing infaunal colonisation, were filled with defaunated sediment containing two treatments, with and without S. squamata. These cylinders were inserted into microcosms containing sediment with indigenous meiofauna collected from the field. The treatments were incubated in the laboratory at ambient temperature and salinity for 7, 14 and 21 days. The nematode assemblages in both treatments did not differ in composition between treatments and from the natural assemblages, suggesting that all the species were equally able to colonise the experimental cores. The presence of the polychaete did not affect the development of the nematode community composition, in contrast to the results from a previous temperate-beach experiment. However, our results did not indicate whether the difference in results was caused by the different behaviour of the polychaete specimens, or by the different composition and response of the present nematode community.


Design, Synthesis, and Anti-Inflammatory Activity of Some Coumarin Schiff Base Derivatives: In silico and in vitro Study.
Inflammation is a fundamental response of the immune system during tissue damage or pathogen infection to protect and maintain tissue homeostasis. However, inflammation may lead to life-threatening conditions. The most common treatment of inflammation is non-steroidal anti-inflammatory drugs (NSAIDs). Nowadays, the development of safer new NSAIDs is critical as most of the existing NSAIDs have serious adverse effects, such as gastrointestinal (GI) toxicity and cardiotoxicity. In the present study, four compounds as Schiff base derivatives of 7-hydroxy-4-formyl coumarin and 7-methoxy-4-formyl coumarin were designed and synthesized aiming to develop a lead compound that exhibits anti-inflammatory activity and circumvents the side effects of NSAIDs, especially GI toxicity. Lipinski's rule of five was applied for each designed molecule to evaluate the drug-likeness properties. Molecular docking studies were performed using the ligands and the cyclooxygenase-2 (COX-2) protein to select the best-scored molecule using AutoDock 4.2.6. The molecules were then synthesized and characterized. An in vitro anti-inflammatory assay of the compounds against the COX-2 receptor was realized through a protein denaturation assay. All four synthesized ligands passed Lipinski's rule of five and exhibited higher binding free energy compared to the positive standard control (ibuprofen), and the Ki values of compounds 5, 7, and 8 were in the nanomolar range. However, only compounds 6 and 7 obtained a higher percentage of inhibition of protein denaturation relative to ibuprofen. The present study suggested that compound 7 may be a lead molecule because this ligand not only exhibited the best computational and experimental results but also exhibited the strongest correlation between the concentration and percentage of protein denaturation (R = 0.986 and R2 = 0.972) with the lowest P-value (0.014).


Integrating community health workers into a patient-centered medical home to support disease self-management among Vietnamese Americans: lessons learned.
There is evidence that patient-centered medical homes (PCMHs) and community health workers (CHWs) improve chronic disease management. There are few models for integrating CHWs into PCMHs in order to enhance disease self-management support among diverse populations. In this article, we describe how a community-based nonprofit agency, a PCMH, and academic partners collaborated to develop and implement the Patient Resource and Education Program (PREP). We employed CHWs as PCMH care team members to provide health education and support to Vietnamese American patients with uncontrolled diabetes and/or hypertension. We began by conducting focus groups to assess patient knowledge, desire for support, and availability of community resources. Based on findings, we developed PREP with CHW guidance on cultural tailoring of educational materials and methods. CHWs received training in core competencies related to self-management support principles and conducted the 4-month intervention for PCMH patients. Throughout the program, we conducted process evaluation through structured team meetings and patient satisfaction surveys. We describe successes and challenges associated with PREP delivery including patient recruitment, structuring/documenting visits, and establishing effective care team integration, work flow, and communication. Strategies for mitigating these issues are presented, and we make recommendations for other PCMHs seeking to integrate CHWs into care teams.


Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation.
Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia-reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single-center study was to determine if hepatic ischemia-reperfusion injury, estimated by peak peri-operative serum amino-transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500-2999 and ≥ 3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia-reperfusion injury demonstrates a strong relationship with peri-operative AKI in DBD liver transplant recipients.


Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts.
Binding of CD95 (Fas/APO-1) by its ligand (CD95L) commonly induces apoptosis. Apoptosis of activated T cells, induced by CD95L expressed in the rodent testis, has been proposed to be the mechanism of immune privilege [Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A. & Duke, R. C. (1995) Nature (London) 377, 630-632]. To test whether CD95L could protect pancreatic islet grafts from rejection, we made transgenic mice expressing murine CD95L on their islet beta cells and transplanted fetal pancreata under the kidney capsules of allogeneic animals. Expression of CD95L failed to protect the grafts from rejection. However, transgenic mice developed a granulocytic infiltration in their pancreata. These results demonstrate a pro-inflammatory function of CD95L and suggest that expression of CD95L may not be sufficient to protect organ allografts.


FTIR spectral components of schwertmannite.
Fourier transform infrared (FTIR) spectral components of three dominant groups of sulfate species in synthetic schwertmannite (Fe(8)O(8)(OH)(6-x)(SO(4))(x)*nH(2)O) are presented. These components were extracted by multivariate curve resolution analysis of spectra obtained from N(2)(g)-dry samples initially reacted in aqueous solutions (pH 3-9) at room temperature. Each component contains complex sets of bands that correspond to mixtures of similar species. We tentatively assign these components to sulfate ions that are hydrogen- (components I and III) and iron-bonded (component I) to schwertmannite. Another component (II) is assigned to protonated sulfate species. Heating experiments to 130 degrees C moreover confirmed this possibility for component II. The spectral components extracted from this study can be used to identify dominant sulfate species in FTIR spectra of naturally occurring schwertmannite samples.


Diffusion of heavy meromyosin in the presence of F-actin and ATP.
We looked for evidence that the diffusion of heavy meromyosin is modified by its interaction with actin. To be able to observe diffusion in one dimension, we electrophoresed the complex of F-actin and heavy meromyosin in agarose gels in thin capillaries. The intensity profile of the electrophoretic band of the complex showed a sharp peak, which in 1% agarose in the electric field of 17.8 V cm-1 at room temperature migrated at 3.2 cm h-1. The time evolution of the profile after the electrophoresis ended was a measure of the diffusion of heavy meromyosin. After 10 min the intensity profile of heavy meromyosin diffusing in the presence of F-actin and ATP had undergone as much change as the profile of free heavy meromyosin. Modelling of the diffusion process showed that the mean diffusion coefficient of heavy meromyosin moving over actin in the presence of ATP was 7.2 x 10(-7) cm2 s-1 and that it was not statistically different from the diffusion coefficient of free heavy meromyosin. This data is interpreted to show that the diffusion of heavy meromyosin is not modified by its interaction with actin.


Comparison of grating designs for the Lyman Far-Ultraviolet Spectroscopic Explorer spectrograph.
Various grating designs have been proposed by several investigators for possible use with the Lyman/Far-Ultraviolet Spectroscopic Explorer mission. The image quality, the feasibility, and the efficiency of five designs are compared, each using a distinct type of grating: (1) a grating ruled on a deformed ellipsoidal or toroidal blank, (2) an ellipsoidal grating recorded holographically with two auxiliary spherical mirrors, (3) a spherical holographic grating recorded with two auxiliary spherical holographic gratings, (4) a spherical ruled grating with variable spacing and straight grooves, and (5) a spherical ruled grating with a groove pattern that is determined theoretically (hybrid grating). From a purely theoretical viewpoint, grating (5) provides the finest images, followed by gratings, (3), (1), (4), and (2). In view of the current technological limitations, the order of practical importance is gratings (4), (1), (2), (3), and (5).


Assigning protein functions by comparative genome analysis: protein phylogenetic profiles.
Determining protein functions from genomic sequences is a central goal of bioinformatics. We present a method based on the assumption that proteins that function together in a pathway or structural complex are likely to evolve in a correlated fashion. During evolution, all such functionally linked proteins tend to be either preserved or eliminated in a new species. We describe this property of correlated evolution by characterizing each protein by its phylogenetic profile, a string that encodes the presence or absence of a protein in every known genome. We show that proteins having matching or similar profiles strongly tend to be functionally linked. This method of phylogenetic profiling allows us to predict the function of uncharacterized proteins.


Subregional Differences in Alcohol Modulation of Central Amygdala Neurocircuitry.
Alcohol use disorder is a highly significant medical condition characterized by an impaired ability to stop or control alcohol use, compulsive alcohol seeking behavior, and withdrawal symptoms in the absence of alcohol. Understanding how alcohol modulates neurocircuitry critical for long term and binge-like alcohol use, such as the central amygdala (CeA), may lead to the development of novel therapeutic strategies to treat alcohol use disorder. In clinical studies, reduction in the volume of the amygdala has been linked with susceptibility to relapse to alcohol use. Preclinical studies have shown the involvement of the CeA in the effects of alcohol use, with lesions of the amygdala showing a reduction in alcohol drinking, and manipulations of cells in the CeA altering alcohol drinking. A great deal of work has shown that acute alcohol, as well as chronic alcohol exposure via intake or dependence models, alters glutamatergic and GABAergic transmission in the CeA. The CeA, however, contains heterogeneous cell populations and distinct subregional differences in neurocircuit architecture which may influence the mechanism by which alcohol modulates CeA function overall. The current review aimed to parse out the differences in alcohol effects on the medial and lateral subregions of the CeA, and what role neuroinflammatory cells and markers, the endocannabinoid system, and the most commonly studied neuropeptide systems play in mediating these effects. A better understanding of alcohol effects on CeA subregional cell type and neurocircuit function may lead to development of more selective pharmacological interventions for alcohol use disorder.


Ethical and health policy issues in the treatment of children with major craniofacial deformities.
The advent of craniofacial surgery and neonatal intensive care has made it possible for children with serious craniofacial deformities to live and possibly to experience effective habilitation. These therapeutic innovations also raise important social and ethical issues that are rarely examined. This paper reviews the dilemmas that relate to the gatekeeper role for physicians, the impact of prenatal diagnosis, and the allocation of scarce fiscal and health resources to craniofacial care. The high degree of cost, the intense investment of medical resources, and the uncertain outcomes in the care of children with major craniofacial deformities, must be considered in the distribution of resources within a health system. The rationing of health resources is discussed as a future determinant of how care for major craniofacial deformities may be delivered in the United States.


Metabolic profile differences in ACTH-dependent and ACTH-independent Cushing syndrome.
The most common etiologies of Cushing's syndrome (CS) are adrenocorticotropic hormone (ACTH)-producing pituitary adenoma (pitCS) and primary adrenal gland disease (adrCS), both of which burden patients with metabolic disturbance. The aim of this study was to compare the metabolic features of pitCS and adrCS patients. A retrospective review including 114 patients (64 adrCS and 50 pitCS) diagnosed with CS in 2009-2019 was performed. Metabolic factors were then compared between pitCS and adrCS groups. Regarding sex, females suffered both adrCs (92.2%) and pitCS (88.0%) more frequently than males. Regarding age, patients with pitCS were diagnosed at a younger age (35.40 ± 11.94 vs. 39.65 ± 11.37 years, p = 0.056) than those with adrCS, although the difference was not statistically significant. Moreover, pitCS patients had much higher ACTH levels and more serious occurrences of hypercortisolemia at all time points (8 AM, 4 PM, 12 AM) than that in adrCS patients. Conversely, indexes, including body weight, BMI, blood pressure, serum total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, fasting plasma glucose, and uric acid, showed no differences between adrCS and pitCS patients. Furthermore, diabetes prevalence was higher in pitCS patients than in adrCS patients; however, there were no significant differences in hypertension or dyslipidemia prevalence between the two. Although adrCS and pitCS had different pathogenetic mechanisms, different severities of hypercortisolemia, and different diabetes prevalences, both etiologies had similar metabolic characteristics.


Microscopic Mechanisms of Glasslike Lattice Thermal Transport in Cubic Cu_{12}Sb_{4}S_{13} Tetrahedrites.
Materials based on cubic tetrahedrites (Cu_{12}Sb_{4}S_{13}) are useful thermoelectrics with unusual thermal and electrical transport properties, such as very low and nearly temperature-independent lattice thermal conductivity (κ_{L}). We explain the microscopic origin of the glasslike κ_{L} in Cu_{12}Sb_{4}S_{13} by explicitly treating anharmonicity up to quartic terms for both phonon energies and phonon scattering rates. We show that the strongly unstable phonon modes associated with trigonally coordinated Cu atoms are anharmonically stabilized above approximately 100 K and continue hardening with increasing temperature in accord with experimental data. This temperature-induced hardening effect reduces scattering of heat carrying acoustic modes by reducing the available phase space for three-phonon processes, thereby balancing the conventional ∝T increase in scattering due to phonon population and yielding nearly temperature-independent κ_{L}. Furthermore, we find that very strong phonon broadening leads to a qualitative breakdown of the conventional phonon-gas model and modify the dominant heat transport mechanism from the particlelike phonon wave packet propagation to incoherent contributions described by the off-diagonal terms in the heat-flux operator, which are typically prevailing in glasses and disordered crystals. Our work paves the way to a deeper understanding of glasslike thermal conductivity in complex crystals with strong anharmonicity.