Bright light shows promise in improving sleep, depression, and quality of life in women with breast cancer during chemotherapy: findings of a pilot study.

Sleep and fatigue-associated symptoms are prominent during chemotherapy. The purpose of this pilot study was to examine bright light effects on sleep disruption, fatigue, daytime sleepiness, depression, and quality of life (QOL) in women with stage I-III breast cancer undergoing chemotherapy. In this 2-group randomized controlled trial (NCT02658708), participants were randomized to receive either blue-green light of 12,000 lux (experimental) or dim red light of 5 lux (control). Light therapy was self-administered using a light visor cap at home. Both groups received 30-minute daily light therapy for 21 consecutive days following the 2nd cycle of chemotherapy. Sleep quality, fatigue, daytime sleepiness, depression, and QOL were self-reported, and nocturnal sleep was monitored by ambulatory polysomnography before the initiation of chemotherapy (baseline) and following the light intervention (posttest). Relative change was assessed at posttest controlling for pretest scores. At posttest, the experimental group self-reported significantly shorter sleep latency than controls (10 vs. 20 min, p = .045) consistent with polysomnography findings (14 vs. 63 min). Polysomnography also revealed longer total sleep time (467 vs. 315 min) and higher sleep efficiency (74% vs. 58%) in experimental vs. controls. Participants receiving bright light experienced a 30% relative decrease in depression, while there was a 24% increase in the controls. The experimental group reported substantially fewer increases in symptom intensity than controls (33% vs. 166%). These findings suggest that bright light likely improved sleep quality and depression and mitigated worsening intensity of symptoms during the first three cycles of chemotherapy. However, features of bright light, e.g., treatment duration, frequency, and timing in relation to chemotherapy treatment require further investigation.

Effect of an extreme flood event on solute transport and resilience of a mine water treatment system in a mineralised catchment.

Extreme rainfall events are predicted to become more frequent with climate change and can have a major bearing on instream solute and pollutant transport in mineralised catchments. The Coledale Beck catchment in north-west England was subject to an extreme rainfall event in December 2015 that equated to a 1 in 200-year event. The catchment contains the UK's first passive metal mine water treatment system, and as such had been subject to intense monitoring of solute dynamics before and after commissioning. Due to this monitoring record, the site provides a unique opportunity to assess the effects of a major storm event on (1) catchment-scale solute transport, and (2) the resilience of the new and novel passive treatment system to extreme events. Monitoring suggests a modest decline in treatment efficiency over time that is not synchronous with the storm event and explained instead by changes in system hydraulic efficiency. There was no apparent flushing of the mine system during the event that could potentially have compromised treatment system performance. Analysis of metal transport in the catchment downstream of the mine suggests relatively subtle changes in instream chemistry with modest but statistically-significant reductions in zinc in the lower catchment irrespective of flow condition after the extreme event, but most parameters of interest show no significant change. Increased export of colloidal iron and aluminium is associated with major landslips in the mid-catchment after the storm and provide fresh sorption sites to attenuate dissolved zinc more rapidly in these locations, corroborated by laboratory experiments utilising site materials to investigate the attenuation/release of metals from stream and terrestrial sediments. The data are important as they show both the resilience of passive mine water treatment systems to extreme events and the importance of catchment-scale monitoring to ensure continued effectiveness of treatment initiatives after major perturbation.

Tropospheric Emissions: Monitoring of Pollution (TEMPO).

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Dehydroepiandrosterone Heightens Aggression and Increases Androgen Receptor and Aromatase mRNA Expression in the Brain of a Male Songbird.

Dehydroepiandrosterone (DHEA) is a testosterone/oestrogen precursor and known modulator of vertebrate aggression. Male song sparrows (Melospiza melodia morphna) show high aggression during breeding and nonbreeding life-history stages when circulating DHEA levels are high, and low aggression during molt when DHEA levels are low. We previously showed that androgen receptor and aromatase mRNA expression are higher during breeding and/or nonbreeding in brain regions associated with reproductive and aggressive behaviour, although the potential role of DHEA in mediating these seasonal changes remained unclear. In the present study, nonbreeding male song sparrows were captured and held in the laboratory under short days (8 : 16 h light/dark cycle) and implanted with s.c. DHEA-filled or empty (control) implants for 14 days. DHEA implants increased aggression in a laboratory-based simulated territorial intrusion. Brains of DHEA-implanted birds showed higher aromatase mRNA expression in the preoptic area (POA) and higher androgen receptor mRNA expression in the periventricular nucleus of the medial striatum (pvMSt) and ventromedial nucleus of the hypothalamus. The DHEA-induced increases in aromatase expression in the POA and androgen receptor expression in the pvMSt are consistent with previously reported seasonal increases in these markers associated with naturally elevated DHEA levels. This suggests that DHEA facilitates seasonal increases in aggression in nonbreeding male song sparrows by up-regulating steroid signalling/synthesis machinery in a brain region-specific fashion.

Therapeutic effect of flax-based diets on fatty liver in aged laying hens.

This study examined the ability of flax-based ingredients to attenuate nonalcoholic fatty liver disease ( NAFLD: ) in aged laying hens-a novel and more physiologically relevant model of human disease. Our results showed only hens supplemented with whole flaxseed ( WFX: ) reduced steatosis and hepatocellular ballooning. Serum AST was also reduced in hens provided WFX and defatted flaxseed meal ( DFM: ). Hepatic ω-3 PUFA enrichment was improved with supplementation of WFX, DFM, and flaxseed oil ( FXO: ). However, this effect was more evident in the WFX group. In contrast, transcript abundance of genes linked to NAFLD were predominantly modified with FXO supplementation. Taken together, our data indicate a potential synergistic relationship between the fatty acid and lignan content in flaxseed which attenuated the progression of NAFLD in aged laying hens. Although more research is necessary, these findings demonstrate the potential use of whole flaxseed for the treatment and prevention of NAFLD in humans.

Parental behavior correlates to baseline corticosterone of mates and offspring in nesting eastern bluebirds (Sialia sialis).

Raising nestlings in a biparental species involves a complex and dynamic interaction of physiology and behavior among a group of organisms. Parents may be predicted to vary their behaviors based not only upon their own state, but also in relation to the states of both offspring and the other parent. In this study we explore the relationships between parental feeding behaviors and family member condition in eastern bluebirds, with a special emphasis on baseline corticosterone, a hormone associated with energy mediation and stress. We found that the overall number of feeding trips made by both male and female parents were positively correlated to the corticosterone levels of nestlings. Maternal, but not paternal, baseline corticosterone levels were positively correlated to nestling baseline corticosterone levels. Additionally, adult males' feeding behavior was positively correlated to adult females' baseline corticosterone levels. These findings suggest a complex interplay between parental behavior and physiological state not only within a given organism, but also across organisms operating within a family unit. In addition, these results provide evidence that paternal and maternal efforts are influenced by related but distinct pressures, and that male and female parenting may be governed differentially even in species with relatively equitable biparental care.

Effects of exercise on S-IGA and URS in postmenopausal women.

32 postmenopausal women were randomized to a 16-week home-based walking program or control group. Before and after the intervention, each subject completed a graded maximal treadmill test to establish VO(2)max and resting saliva was collected to determine levels of salivary immunoglobulin A. The 16-week walking program resulted in an increase in VO(2)max (+10.4%; p<0.01). Repeated measures ANOVA revealed a marked increase in the resting secretion rate of salivary immunoglobulin A (+37.4%; p<0.05) in the exercise group following training. Independent of study group, both before and after the intervention, the secretion rate of salivary immunoglobulin A ( - 32.3%) and saliva flow rate (- 29.3%) were reduced following acute maximal exercise (p<0.05). Weekly upper respiratory symptomatology logs revealed that the number of incidences of upper respiratory symptoms throughout the intervention period were the same and the duration per incidence (control: 5.3±1.5 days; exercise: 6.3±2.2 days) were similar between study groups. These findings in postmenopausal women support that the secretion rate of salivary immunoglobulin A and saliva flow rate are reduced immediately following maximal exercise. Moreover, a 16-week moderate intense walking program can increase the secretion of salivary immunoglobulin A without affecting upper respiratory symptomatology.

Soy protein isolate modified metabolic phenotype and hepatic Wnt signaling in obese Zucker rats.

We have previously shown that soy protein isolate (SPI) with intact phytoestrogen content prevented obesity-related dysfunction. Recent data have suggested that soy ingredients may act as regulators of adipogenic programming in adipose tissue (AT) and liver. Thus, the current study was undertaken to determine whether the beneficial effects of SPI are linked to changes in adipogenic regulators, such as the Wnt signaling cascade. For this, lean (LZR) and obese Zucker (OZR) rats were provided isocaloric and isonitrogenous diets containing SPI, sodium caseinate, or dairy whey protein for 17 weeks. At termination, SPI increased body weight and total adiposity in rodents, which corresponded with an increase in both adipocyte size and number. Furthermore, markers of inflammation, hypercholesterolemia, and hepatic steatosis were all reduced in OZR rats provided SPI. Transcript abundance of several canonical and noncanonical Wnt signaling intermediates in liver, but not AT, was distinctly modified by SPI. Collectively, these data confirm the protective SPI attenuated obesity-related metabolic dysfunction conceivably through regulation of adipogenic programming, as evident by changes in AT morphology and hepatic Wnt signaling. Collectively, this study confirmed the potential utilization of soy protein and its bioactive ingredients for prevention and treatment of obesity-related comorbidities.

The c-Jun N-terminal kinase mediates the induction of oxidative stress and insulin resistance by palmitate and toll-like receptor 2 and 4 ligands in 3T3-L1 adipocytes.

Saturated fatty acids (SFAs) are known to induce inflammation and insulin resistance in adipocytes through toll-like receptor-4 (Tlr4) signaling, but the mechanisms are not well delineated. Furthermore, the potential roles of Tlr2 and the c-Jun N-terminal kinase (JNK) in inflammation in adipocytes have not been investigated. We demonstrated that palmitate, lipopolysaccharide (LPS), and the toll-like receptor-2 (Tlr2) agonist, zymosan A (ZymA), induced insulin resistance in a time- and dose-dependent manner in 3T3-L1 adipocytes. Corresponding with the reduction of insulin sensitivity was an increased expression of IL-6, as well as activation of the proinflammatory transcription factors, nuclear factor kappa B, and activator protein-1. Reactive oxygen species (ROS) accumulation was also observed in palmitate and Tlr agonist treated adipocytes. The JNK inhibitor, SP600125, attenuated insulin resistance mediated by SFA and Tlr agonists, which corresponded with a diminished proinflammatory response and reduced ROS accumulation. Collectively, these results demonstrated Tlr2 involvement in adipocyte inflammation and therefore implicated the receptor as a potential target for SFA. Moreover, activation of JNK also appeared to be essential to Tlr2-, as well as Tlr4-induced insulin resistance and oxidative stress.

Colonic malakoplakia in a liver transplant recipient.

Malakoplakia is a rare inflammatory condition seen in transplant patients. There are two previously reported cases of malakoplakia involving the gastrointestinal tract in liver transplant patients. The present paper reports a case of colonic malakoplakia in a 58-year-old woman, a liver transplant recipient who was receiving immunosuppressive drugs. She presented with chronic diarrhea while on tacrolimus. There was no history of antecedent infection. Colonoscopy showed patchy mucosal edema, but no discrete yellow plaques or nodules. The diagnosis was made by colon biopsies, which showed chronic inflammation with many histiocytes containing Michaelis-Gutmann bodies. Although rare, malakoplakia is one of many potential causes of diarrhea in a transplant patient. The present case indicates that malakoplakia may be associated with chronic diarrhea, even if there are no macroscopic lesions seen during colonoscopy.

Adipocytes, myofibers, and cytokine biology: new horizons in the regulation of growth and body composition.

Muscle growth in meat animals is a complex process governed by integrated signals emanating from multiple endocrine and immune cells. A generalized phenomenon among meat animal industries is that animals commonly fail to meet their genetic potential for growth in commercial production settings. Therefore, understanding the impact of stress and disease on muscle growth is essential to improving production efficiency. The adipocyte in particular seems to be well positioned as an interface between energy status and immune function, and may thus influence nutrient partitioning and growth through a combination of signals that influence fat metabolism, glucose uptake, and insulin sensitivity. Adipocytes and myofibers are active participants in the innate immune response, and as such, produce a number of metabolic regulators, including leptin, adiponectin, and proinflammatory cytokines. Specifically, adipocytes and muscle cells respond directly to bacterial lipopolysaccharide (LPS) by producing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha). However, adipocytes are also the predominant source of the antiinflammatory hormone adiponectin, which regulates the nuclear factor kappa-B transcription factor. The ability to recognize antigens and produce regulatory molecules strategically positions adipocytes and myofibers to regulate growth locally, and to reciprocally regulate metabolism peripherally.

Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection.

Traumatic brain injury (TBI) causes selective hippocampal cell death, which is believed to be associated with cognitive impairment observed both in clinical and experimental settings. Although neurotrophin administration has been tested as a strategy to prevent cell death following TBI, the potential neuroprotective role of neurotrophin-4/5 (NT-4/5) in TBI remains unknown. We hypothesized that NT-4/5 would offer neuroprotection for selectively vulnerable hippocampal neurons following TBI. Measurements of NT-4/5 in rats subjected to lateral fluid percussion (LFP) TBI revealed two-threefold increases in the injured cortex and hippocampus in the acute period (1-3 days) following brain injury. Subsequently, the response of NT-4/5 knockout (NT-4/5(-/-)) mice to controlled-cortical impact TBI was investigated. NT-4/5(-/-) mice were more susceptible to selective pyramidal cell loss in Ahmon's corn (CA) subfields of the hippocampus following TBI, and showed impaired motor recovery when compared with their brain-injured wild-type controls (NT-4/5(wt)). Additionally, we show that acute, prolonged administration of recombinant NT-4/5 (5 microg/kg/day) prevented up to 50% of the hippocampal CA pyramidal cell death following LFP TBI in rats. These results suggest that post-traumatic increases in endogenous NT-4/5 may be part of an adaptive neuroprotective response in the injured brain, and that administration of this neurotrophic factor may be useful as a therapeutic strategy following TBI.

Heterokaryon formation and parasexual recombination between vegetatively incompatible lineages in a population of the chestnut blight fungus, Cryphonectria parasitica.

Heterokaryosis was recently reported in the chestnut blight fungus, Cryphonectria parasitica, in which individuals contain nuclei that are isogenic except at the mating-type locus (MAT). MAT heterokaryons were found in several natural populations, including a putatively clonal population in West Salem, Wisconsin, providing an opportunity to address the question of how heterokaryons arise. We represented relationships among RFLP fingerprint haplotypes as networks in which loop formation is considered evidence of recombination. From 1990 to 1995, this population was clonal, as indicated by a simple haplotype network without loops, and the correlation of vegetative compatibility (vc) types and mating types with haplotype lineages. By 1999, we observed loops in the haplotype network involving isolates of two vc types (WS-2 and WS-3). Isolates with haplotypes in the loops were either MAT heterokaryons, carried the opposite mating type from other isolates of the same vc type, and/or had two alleles at two or more codominant SCAR (sequence-characterized amplified region) loci. Segregation of markers and recombination were evident among single-spore isolates from one heterokaryon; these single-spore isolates had novel fingerprint haplotypes, also within the loops. In contrast, vc type WS-1, which comprises 85% of the population, was represented by a simple network with no loops, indicating a clonal lineage varying only by mutation. Almost all isolates of WS-1 had the same mating type; the exceptions were five isolates that were MAT heterokaryons. These results are consistent with the hypothesis that heterokaryons formed between vegetatively incompatible individuals, and recombination occurred by a parasexual process.

Recurrent hepatocellular carcinoma after liver transplantation mimicking post-transplantation lymphoproliferative disorder.

Approximately 5% of patients with end-stage cirrhosis undergoing orthotopic liver transplantation have occult hepatocellular carcinoma. Careful follow up is required to detect recurrent tumour, and knowledge of the patterns of recurrence may avoid diagnostic confusion with other malignancies, such as post-transplantation lymphoproliferative disorder. This case report illustrates an unusual presentation of recurrent hepatocellular carcinoma in a 56-year-old man presenting with a para-aortic soft tissue mass, thought clinically and radiologically to represent lymphoma or post-transplantation lymphoproliferative disorder. This case demonstrates that recurrent hepatocellular carcinoma can present late after transplantation as retroperitoneal lymphadenopathy, and should alert physicians and radiologists to be aware of the radiological appearances of recurrence and of the need for early biopsy to avoid diagnostic confusion with other malignancies.

Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies.

Epstein-Barr virus (EBV) is associated with a range of malignancies that largely arise from a defect in EBV-specific cytotoxic T lymphocyte (CTL) immunity and function. Much work has focused on the reconstitution of CTL immunity to EBV in transplant patients, in whom immunosuppression modalities render them susceptible to post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of autologous CTLs is effective at both preventing and curing PTLD in solid organ transplant recipients and can produce a long-term memory response and protection against recurring disease. In this review, the benefits and restrictions of administering EBV-specific CTLs for the treatment of PTLD are discussed and compared with emerging therapies including the generation of allogeneic human leukocyte antigen-matched CTL banks and the anti-CD20 monoclonal antibody therapy, MabThera. Furthermore, studies involving other EBV-associated disorders have described the potential benefit of adoptive transfer of EBV-specific CTLs for Hodgkin's disease, nasopharyngeal carcinoma, chronic active EBV infection, and Burkitt's lymphoma. The challenges of tailor-making therapies for individual diseases and EBV antigen expression latencies are highlighted, in addition to considering vaccination strategies for optimal treatment.

Translabial sonography of vaginal fibroids: report of 2 cases and review of the literature.

OBJECTIVE: To determine the role of translabial sonography in the diagnosis of vaginal fibroids. METHODS: Two women with vaginal masses of undetermined origin were examined by various imaging procedures, including translabial sonography. RESULTS: Initial examinations, which included transabdominal sonography, cystoscopy, and cystourethrography, yielded inconclusive findings. Translabial sonography, however, suggested isolated vaginal leiomyomas in both patients, and in both the diagnosis was confirmed histologically after surgery. CONCLUSIONS: Translabial sonography should be considered as an adjunct to transabdominal and transvaginal sonography for patients with suspected vaginal fibroids.

Unlocking the secrets of cytotoxic granule proteins.

Cytotoxic lymphocytes largely comprise CD8(+) cytotoxic T cells and natural killer cells and form the major defense of higher organisms against virus-infected and transformed cells. A key function of cytotoxic lymphocytes is to detect and eliminate potentially harmful cells by inducing them to undergo apoptosis. This is achieved through two principal pathways, both of which require direct but transient contact between the killer cell and its target. The first, involving ligation of TNF receptor-like molecules such as Fas/CD95 by their cognate ligands, results in mobilization of conventional, programmed cell-death pathways centered on activation of pro-apoptotic caspases. This review concentrates on the second pathway, in which the toxic contents of secretory vesicles of the cytotoxic lymphocyte are secreted toward the target cell, and some toxins penetrate into the target cell cytoplasm and nucleus. In addition to invoking a powerful stimulus to caspase activation, this "granule-exocytosis mechanism" provides a variety of additional strategies for overcoming inhibitors of the caspase cascade that may be elaborated by viruses. The key molecular players in this process are the pore-forming protein perforin and a family of granule-bound serine proteases or granzymes. The molecular functions of perforin and granzymes are under intense investigation in many laboratories including our own, and recent advances will be discussed. In addition, this review discusses the evidence pointing to the importance of perforin and granzyme function in pathophysiological situations as diverse as infection with intracellular pathogens, graft versus host disease, susceptibility to transplantable and spontaneous malignancies, lymphoid homeostasis, and the tendency to auto-immune diseases.

Sex differences in infant rhesus macaque separation-rejection vocalizations and effects of prenatal androgens.

Infant and juvenile rhesus macaques exhibit many sexually dimorphic behaviors, including rough and tumble play, mounting, and time spent with nonmother females. This study investigated sex differences in infant rhesus monkey separation-rejection vocalizations (SRVs), and the effects of altering the prenatal hormone environment on these differences. Pregnant females received exogenous androgen (testosterone enanthate), an androgen antagonist (flutamide), or vehicle injections for 30 or 35 days during the second (early) or third (late) trimester of pregnancy. Control females used a greater percentage of coos and arched screams than did control males. In contrast, males used a greater percentage of geckers and noisy screams than did females. Females also had longer SRV bouts, used more calls, and used more types of vocalizations than did males. Mothers were more likely to respond to the SRVs of male infants than to the SRVs of female infants. Prenatal flutamide treatment early in gestation reduced the likelihood that mothers would respond to their male offspring, but prenatal androgen treatment had no effect on response rates of mothers to female offspring. Early, but not late, androgen treatment produced females who vocalized in a male-typical manner. Similarly, early flutamide treatment produced males who displayed more female-typical SRVs. Late flutamide treatments of females produced as much masculinization of SRVs as did early androgen treatment in females. These results demonstrate sex differences in highly emotional vocalizations in infant rhesus macaques and provide evidence that the timing and form of prenatal hormonal exposure influence such vocalizations.