Implications of controlled short-wavelength light exposure for sleep in older adults

<p>Abstract</p> <p>Background</p> <p>Environmental and physiological conditions make older adults more likely to lose synchronization to their local time and experience sleep disturbances. A regular, 24-hour light/dark cycle promotes synchronization. It is now well established that the circadian system is maximally sensitive to short-wavelength (blue) light. The purpose of the present study was to measure dose effectiveness (amounts and durations) of short-wavelength (blue) light for stimulating the circadian systems of older adults. We investigated the impact of six corneal irradiances (0.7 to 72 μW/cm²) of 470-nm light on nocturnal melatonin production. Nine participants, each over 50 years of age completed a within-subjects study. Each week, participants were exposed to one of the six irradiances of 470-nm light for 90 minutes.</p> <p>Findings</p> <p>A two-factor (6 corneal irradiances × 10 exposure durations), within-subjects analysis of variance (ANOVA) was conducted using the melatonin suppression levels. The ANOVA revealed a significant main effect of corneal irradiance (F_{5, 30}= 9.131, p < 0.0001), a significant main effect of exposure duration (F_{9, 54}= 5.731, p < 0.0001), and a significant interaction between these two variables (F_45,270= 1.927, p < 0.001). Post hoc t-tests revealed that corneal irradiances as low as 2 μW/cm²reliably suppressed melatonin after 90-minute exposure whereas 0.7 μW/cm²did not.</p> <p>Conclusions</p> <p>Sleep disorders are common and a serious problem for millions of older adults. The present results showed that comfortable, precise and effective doses of light can be prescribed to older adults to reliably stimulate the circadian system that presumably would promote entrainment and, thus, regular sleep. Field studies on the impact of short-wavelength-light doses on sleep efficiency in older adults should be performed.</p

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Multi-site and multi-depth near-infrared spectroscopy in a model of simulated (central) hypovolemia: lower body negative pressure

Purpose: To test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15-2.5 and 25-2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP). Methods: The study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, -20, -40, -60, -80 and -100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS. Results: The main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI. Conclusions: NIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf

Current role of surgery in small cell lung carcinoma

Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasi

Current perspectives on bone metastases in castrate-resistant prostate cancer

Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant prostate cancer, as a result of complex interactions between the microenvironment and tumor cells. The development of 223radium dichloride (Ra-223) to treat symptomatic bone metastases has improved survival in men with metastatic castrate-resistant prostate cancer. Moreover, Ra-223 may have effects on the tumor microenvironment that enhance its activity. Ra-223 treatment has been shown to prolong survival, and its effects on the immune system are under investigation. Because prostate cancer affects a sizable portion of the adult male population, understanding how it metastasizes to bone is an important step in advancing therapy. Clinical trials that are underway should yield new information on whether Ra-223 synergizes effectively with immunotherapy agents and whether Ra-223 has enhancing effects on the immune system in patients with prostate cancer

Quantitative Image Analysis Reveals Distinct Structural Transitions during Aging in Caenorhabditis elegans Tissues

Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio

A C. elegans Model for Mitochondrial Fatty Acid Synthase II: The Longevity-Associated Gene W09H1.5/mecr-1 Encodes a 2-trans-Enoyl-Thioester Reductase

Our recognition of the mitochondria as being important sites of fatty acid biosynthesis is continuously unfolding, especially in light of new data becoming available on compromised fatty acid synthase type 2 (FASII) in mammals. For example, perturbed regulation of murine 17β-HSD8 encoding a component of the mitochondrial FASII enzyme 3-oxoacyl-thioester reductase is implicated in polycystic kidney disease. In addition, over-expression in mice of the Mecr gene coding for 2-trans-enoyl-thioester reductase, also of mitochondrial FASII, leads to impaired heart function. However, mouse knockouts for mitochondrial FASII have hitherto not been reported and, hence, there is a need to develop alternate metazoan models such as nematodes or fruit flies. Here, the identification of Caenorhabditis elegans W09H1.5/MECR-1 as a 2-trans-enoyl-thioester reductase of mitochondrial FASII is reported. To identify MECR-1, Saccharomyces cerevisiae etr1Δ mutant cells were employed that are devoid of mitochondrial 2-trans-enoyl-thioester reductase Etr1p. These yeast mutants fail to synthesize sufficient levels of lipoic acid or form cytochrome complexes, and cannot respire or grow on non-fermentable carbon sources. A mutant yeast strain ectopically expressing nematode mecr-1 was shown to contain reductase activity and resemble the self-complemented mutant strain for these phenotype characteristics. Since MECR-1 was not intentionally targeted for compartmentalization using a yeast mitochondrial leader sequence, this inferred that the protein represented a physiologically functional mitochondrial 2-trans-enoyl-thioester reductase. In accordance with published findings, RNAi-mediated knockdown of mecr-1 in C. elegans resulted in life span extension, presumably due to mitochondrial dysfunction. Moreover, old mecr-1(RNAi) worms had better internal organ appearance and were more mobile than control worms, indicating a reduced physiological age. This is the first report on RNAi work dedicated specifically to curtailing mitochondrial FASII in metazoans. The availability of affected survivors will help to position C. elegans as an excellent model for future pursuits in the emerging field of mitochondrial FASII research

Long-Range Autocorrelations of CpG Islands in the Human Genome

In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI) in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb) and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local) feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes