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The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.

Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation.

With rising sea levels at the end of the Pleistocene, land-bridge or continental islands were formed around the world. Many of these islands have been extensively studied from a biogeographical perspective, particularly in terms of impacts of island creation on terrestrial vertebrates. However, a majority of studies rely on contemporary faunal distributions rather than fossil data. Here, we present archaeological findings from the island of Zanzibar (also known as Unguja) off the eastern African coast, to provide a temporal perspective on island biogeography. The site of Kuumbi Cave, excavated by multiple teams since 2005, has revealed the longest cultural and faunal record for any eastern African island. This record extends to the Late Pleistocene, when Zanzibar was part of the mainland, and attests to the extirpation of large mainland mammals in the millennia after the island became separated. We draw on modeling and sedimentary data to examine the process by which Zanzibar was most recently separated from the mainland, providing the first systematic insights into the nature and chronology of this process. We subsequently investigate the cultural and faunal record from Kuumbi Cave, which provides at least five key temporal windows into human activities and faunal presence: two at the end of the Last Glacial Maximum (LGM), one during the period of post-LGM rapid sea level rise and island formation, and two in the late Holocene (Middle Iron Age and Late Iron Age). This record demonstrates the presence of large mammals during the period of island formation, and their severe reduction or disappearance in the Kuumbi Cave sequence by the late Holocene. While various limitations, including discontinuity in the sequence, problematize attempts to clearly attribute defaunation to anthropogenic or island biogeographic processes, Kuumbi Cave offers an unprecedented opportunity to examine post-Pleistocene island formation and its long-term consequences for human and animal communities.

A full-scale 120 m path length ITER toroidal interferometer and polarimeter (TIP) prototype, including an active feedback alignment system, has been constructed and undergone initial testing at General Atomics. In the TIP prototype, two-color interferometry is carried out at 10.59 μm and 5.22 μm using a CO2 and quantum cascade laser (QCL) respectively while a separate polarimetry measurement of the plasma induced Faraday effect is made at 10.59 μm. The polarimeter system uses co-linear right and left-hand circularly polarized beams upshifted by 40 and 44 MHz acousto-optic cells respectively, to generate the necessary beat signal for heterodyne phase detection, while interferometry measurements are carried out at both 40 MHz and 44 MHz for the CO2 laser and 40 MHz for the QCL. The high-resolution phase information is obtained using an all-digital FPGA based phase demodulation scheme and precision clock source. The TIP prototype is equipped with a piezo tip/tilt stage active feedback alignment system responsible for minimizing noise in the measurement and keeping the TIP diagnostic aligned indefinitely on its 120 m beam path including as the ITER vessel is brought from ambient to operating temperatures. The prototype beam path incorporates translation stages to simulate ITER motion through a bake cycle as well as other sources of motion or misalignment. Even in the presence of significant motion, the TIP prototype is able to meet ITER’s density measurement requirements over 1000 s shot durations with demonstrated phase resolution of 0.06° and 1.5° for the polarimeter and vibration compensated interferometer respectively. TIP vibration compensated interferometer measurements of a plasma have also been made in a pulsed radio frequency device and show a line-integrated density resolution of m−2. [ABSTRACT FROM AUTHOR]

Background: Indigenous Peoples living on the land known as Canada are comprised of First Nations, Inuit, and Métis people and because of the Government of Canada's mandatory evacuation policy, those living in rural and remote regions of Ontario are required to travel to urban, tertiary care centres to give birth. When evaluating the risk of travelling for birth, Indigenous Peoples understand, evaluate, and conceptualise health risks differently than Eurocentric biomedical models of health. Also, the global COVID-19 pandemic changed how people perceived risks to their health. Our research goal was to better understand how Indigenous parturients living in rural and remote communities conceptualised the risks associated with evacuation for birth before and during the COVID-19 pandemic., Methods: To achieve this goal, we conducted semi-structured interviews with 11 parturients who travelled for birth during the pandemic and with 5 family members of those who were evacuated for birth., Results: Participants conceptualised evacuation for birth as riskier during the COVID-19 pandemic and identified how the pandemic exacerbated existing risks of travelling for birth. In fact, Indigenous parturients noted the increased risk of contracting COVID-19 when travelling to urban centres for perinatal care, the impact of public health restrictions on increased isolation from family and community, the emotional impact of fear during the pandemic, and the decreased availability of quality healthcare., Conclusions: Using Indigenous Feminist Methodology and Indigenous Feminist Theory, we critically analysed how mandatory evacuation for birth functions as a colonial tool and how conceptualizations of risk empowered Indigenous Peoples to make decisions that reduced risks to their health during the pandemic. With the results of this study, policy makers and governments can better understand how Indigenous Peoples conceptualise risks related to evacuation for birth before and during the pandemic, and prioritise further consultation with Indigenous Peoples to collaborate in the delivery of the health and care they need and desire., (© 2024. The Author(s).)

Crystal engineering of two diacetylene monomers was achieved by branching two chiral groups [R = PhC*MeNH(CO 2 )CH 2 ] exhibiting an enantiopure configuration of S , S -( DA2 ) and an achiral R , S - meso -isomer ( DA4 ). The X-ray structures of DA2 and DA4 reveal the presence of supramolecular arrangements driven by intermolecular H-bonding. A significant intermolecular closer proximity in DA4 than that in DA2 is depicted, ultimately resulting in a slow thermal (days) and swift (min) photochemical polymerization of DA4 to form PDA5 , whereas DA2 is unreactive. DFT computations indicate that in both cases the lowest energy-excited state is the charge-transfer state [CT; PhC*MeNH(CO 2 ) → π*(-C≡C-C≡C-)]. Therefore, this outcome illustrates a drastic selectivity via a settle change in a carbon configuration. Analysis demonstrates that PDA5 is nonemissive and that its coloration arises from a π → π* excitation of the polymer backbone (DFT computations)., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A new metal-organic framework (MOF; [Zn 4 O( hett ) 4/3 ( fluo ) 1/2 ( bdc ) 1/2 ] n ; TFT-MOF ) constructed on chromophoric ligands 5,5',10,10',15,15'-hexaethyltruxene-2,7,12-triacetate ( hett ), 9-fluorenone-2,7-dicarboxylate ( fluo ), terephthalate ( bdc ), and the Zn 4 O node has been prepared and identified by powder X-ray diffraction. This luminescent MOF exhibits large mesoporous pores of 2.7 nm based on computer modeling using density functional theory (DFT) calculations. The steady-state and time-resolved fluorescence spectra and photophysical parameters of TFT-MOF have been investigated and compared with those of the free ligands and their basic chromophores. All in all, TFT-MOF exhibits particularly efficient singlet-singlet energy-transfer processes described as 1 ( hett )* → ( fluo ) and 1 ( bdc )* → ( fluo ), leading to fluorescence arising for the fluo lumophore operating only through Förster resonance energy transfer (FRET) with an efficiency of transfer of up to >95%. This experimental conclusion was corroborated by DFT and time-dependent DFT (TDDFT). For the 1 ( hett )* → ( fluo ) process, the approximated overall rate constant of energy transfer was evaluated to be at most 2.04 × 10 10 s -1 (using a Stern-Volmer approach of solution data and the relationship between distance and concentration). This process was analyzed using the Förster theory, where two intrapore energy transfer paths of center-to-center distances of 13 and 25 Å have been identified. TFT-MOF photosensitizes the formation of singlet oxygen ( 1 O 2 ( 1 Σ g )) as detected by its phosphorescence signal at 1275 nm.

The prediction of the metal cluster within a coordination polymer or complex, as well as the dimensionality of the resulting polymer or complex (i.e., 0D, 1D, 2D, or 3D), is often challenging. This is the case for Ph 2 P(CH 2 ) m PPh 2 ligands (1 ≤ m ≤ 8) and CuX salts, particularly for X = I. This work endeavors a systematic statistical analysis combining studies in the literature and new data, mapping the nature of the resulting CuI aggregates with eight different diphoshphines in 2:1, 3:2, 1:1, 2:3, and 1:2 CuI:Ph 2 P(CH 2 ) m PPh 2 molar ratios as a function of m, which lead to either pure products or mixtures. Several trends are made relating stoichiometry and chain length to the CuI cluster formed (i.e., globular vs. quasi-planar). Four new X-ray structures were determined: [Cu 3 I 2 ( L1 ) 3 ]I, Cu 3 I 3 ( L2 ) 2 , Cu 2 I 2 ( L6 ) 2 , and Cu 4 I 4 ( L8 ) 2 , where m is, respectively, 1, 2, 6, and 8, in which the Cu x I y central aggregates adopt triangular bipyramid, diamond, rhomboid, and cubane shaped motifs, respectively. Photophysical measurements assisted the establishment of trends considering the paucity of the crystallographic structures. During this study, it was also found that the 0D-complex Cu 2 I 2 (Ph 2 P(CH 2 ) 5 PPh 2 ) 2 exhibits thermally activated delayed fluorescence.

The eradication and isolation of viruses are two concurrent approaches to protect ourselves from viral infections and diseases. The quite versatile porous materials called metal-organic frameworks (MOFs), have recently emerged as efficient nanosized tools to manage viruses, and several strategies to accomplish these tasks have been developed. This review describes these strategies employing nanoscale MOFs against SARS-CoV-2, HIV-1, tobacco mosaic virus, etc., which include the sequestration by host-guest penetration inside pores, mineralization, design of a physical barrier, controlled delivery of organic and inorganic antiviral drugs or bioinhibitors, photosensitization of singlet oxygen, and direct contact with inherently cytotoxic MOFs.

Purpose: In the present study, we present a large institutional study to determine the influence of age≥ 80 years on breast cancer presentation and prognosis., Methods: The study is a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2007 through December 2013. Clinicopathologic characteristics were correlated with outcomes according to age (<80 years and ≥ 80 years)., Results: During the study period, 2083 women with invasive breast cancer were included of which 160 women aged ≥ 80 years (7.7 %). Overall survival was lower in the oldest old than in younger counterparts (p < 0.0001) as was distant metastasis free survival (p = 0.004). Differences in management included more radical surgeries and less chemotherapy and radiotherapy in case of age≥ 80 years. By multivariate analysis, age ≥ 80 years was an independent predictive factor of poor overall survival., Conclusion: In the present study, age ≥ 80 years was an independent predictive factor of poor overall survival., (Copyright © 2019. Published by Elsevier B.V.)

Several studies have suggested that signals emerging from white adipose tissue can contribute to the control of longevity. In turn, aging is associated with perturbed regulation and partitioning of fat depots and insulin resistance. However, the exact mechanisms involved in these relationships remain undetermined. Using RAP-PCR on adipose tissue of young and old male mice coupled with qPCR validation, we have uncovered the long non-coding RNA Malat1 as a gene robustly downregulated in visceral white adipose tissue (vWAT) during normal aging in male mice and men. Reductions in Malat1 expression in subcutaneous WAT (scWAT) were also observed in genetic (ob and db) as well as diet-induced models of obesity. Based on these findings, Malat1+/+ and Malat1-/- mouse littermates were thus probed to detect whether loss of Malat1 would impact age or diet-induced gain in fat mass and development of glucose intolerance. Contrary to this hypothesis, male and female Malat1-deficient mice gained as much weight, and developed insulin resistance to a similar extent as their Malat1+/+ littermates when studied up to eight months old on regular chow or a high-fat, high-sucrose diet. Moreover, we observed no marked difference in oxygen consumption, food intake, or lipid profiles between Malat1+/+ and Malat1-/- mice. Therefore, we conclude that the overall metabolic impact of the absence of Malat1 on adipose tissue accretion and glucose intolerance is either physiologically not relevant upon aging and obesity, or that it is masked by as yet unknown compensatory mechanisms.

Purpose: We present a large institutional study to determine factors predictive of axillary lymph node (LN) metastasis in breast cancer according to molecular subtype., Methods: We conducted a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2009 through December 2013. Clinicopathologic characteristics were correlated with lymph node status and outcome according to breast cancer molecular subtyping., Results: LN metastases were detected in 464 (32.1%) of 1444 women with breast cancer. By multivariate analysis, independent factors predictive of LN involvement were: for the luminal A subtype (n=776): tumour size: OR=1.05 [95% CI: 1.03-1.07] P<0.0001; lymphovascular invasion: OR=3.06 [95% CI: 1.80-5.20] P<0.0001 and tumour grade: OR=1.65 [95% CI: 1.07-2.58] P=0.026. For luminal B subtype (n=441): age: OR=0.97 [95% CI: 0.95-0.99] P=0.004; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002; lymphovascular invasion: OR=3.21 [95% CI: 1.92-5.44] P<0.0001; inflammatory breast cancer: OR=12.36 [95% CI: 2.18-243.3] P=0.019. For the HER2 subtype (n=72): lymphovascular invasion: OR=7.87 [95% CI: 2.10-35.2] P=0.003. For the triple negative subtype (n=155): parity: OR=1.53 [95% CI: 1.10-2.25] P=0.02; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002 and lymphovascular invasion: OR=7.13 [95% CI: 2.46-22.8] P=0.00048., Conclusion: This retrospective study provides valuable insight into LN involvement of patients with primary breast cancer according to molecular subtyping., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Long non-coding RNAs (lncRNA) are key regulators of gene expression both at the transcriptional and post-transcriptional levels. The lncRNA metastasis associated lung adenocarcinoma transcript 1 (Malat1) is overexpressed in many types of cancer, including hepatocarcinoma, and induces cell proliferation in several cell lines in vitro. However, the direct causal effects of Malat1 on hepatocyte proliferation and liver carcinogenesis in vivo are not fully understood. To better determine the contribution of Malat1 to hepatocarcinoma oncogenesis, this study was aimed at testing the hypothesis that its absence confers resistance to the development of liver tumors. Male Malat1-/- mice and their wild-type (WT) littermates were studied one year after treatment with the genotoxic agent diethylnitrosamine (DEN), a potent inducer of liver cancer. As expected, in WT mice, Malat1 expression was significantly higher in hepatic tumors than in healthy liver regions. Altered hepatic mRNA levels of Ki67, HDAC3, NFκB and p27 were observed in DEN-treated Malat1-/- mice. Despite this, these mice were characterized by similar liver weight, prevalence of tumors, and histological features compared to those of their WT littermates. In parallel, plasma lipids and glucose homeostasis did not significantly differ between DEN-treated groups. These findings support a role for Malat1 as a marker of liver carcinogenesis, but also suggest that its role in the regulation of hepatocyte hyperproliferation in mice is either minimal or masked by redundant and/or overwhelming mechanisms.

Objective: The aim of this study was to evaluate outcomes of patients with breast cancer in function of the body mass index (BMI)., Methods: The study cohort consisted of consecutive women undergoing surgery for breast cancer in our institution between January 2009, and September 2013. Individual records of all patients were reviewed and analyzed. Patient BMI was categorized as underweight, normal, overweight and obese., Results: A total of 1599 patients were evaluated. Patients were followed for one to 265months with a mean of 36.4months. The number of patients in each of the BMI categories was 66, 779, 463 and 291 for underweight, normal, overweight and obese women respectively. Women with higher BMI were more frequently affected by hypertension (18, 21, 35 and 47% respectively, P<0.0001) and diabetes (3, 2, 7 and 7% respectively, P<0.0001). Obese women had more frequently an inflammatory presentation (P=0.006), larger tumour size (P=0.038) and axillary lymph node involvement (P=0.03) with much more positive lymph nodes (P=0.02). Patients had the same protocols of treatment (surgery and adjuvant treatment). There was no statistically significant difference in overall 5-years survival between groups (P=0.30)., Conclusions: Our study demonstrate a more aggressive clinical and histological presentation for obese women with breast cancer., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

A significant portion of parents of children with autism spectrum disorder report high levels of stress related to parenting responsibilities, which have been linked to abnormal cortisol patterns. This study seeks to better understand the parents' adaptation to caregiving demands and use of a service dog, by taking into account longitudinal variations in salivary cortisol and perception of parental stress. Salivary cortisol was collected one day per week for 15 weeks by 98 primary caregivers of children with ASD. Overall, parents perceived high levels of stress at baseline. Mean morning cortisol increase was below expected levels for healthy adults, and perception of stress predicted morning cortisol activity. Hypocorticolism related to chronic stress may be present in parents of children with ASD. Longitudinal analysis revealed that the presence of a service dog in the family had an effect on parenting stress, wakening and morning cortisol levels., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The recently developed MDACC nomogram purports to predict the risk of bone-only metastasis in women with early breast carcinoma based on five clinical and pathological characteristics. We set out to externally validate and assess its robustness using a tertiary breast cancer centre database., Methods: All consecutive women treated for early breast cancer in our centre between January 1989 and December 2013 and who had all the nomogram variables documented were eligible for analysis., Results: We identified 1255 eligible women for external validation analysis. The median follow-up was 54 months (range: 1-312) and time to initial metastasis 20 months (range: 1-80). The correspondence between the actual bone-only metastasis and the nomogram predictions implied poor calibration of the nomogram in the validation cohort, be it in the whole cohort or when stratified by breast cancer subtype., Conclusion: This external validation study of the MDACC nomogram showed limitations in its generalizability to a new and independent European patient population., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Increased expression levels of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) have been associated with enhanced proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark characteristic of solid tumors, has been linked to an increase in the activity of the ATP-generating AMPK protein. Since Malat1 was recently shown to be upregulated during hypoxia, the objective of this study was to determine the contribution of AMPK in the mechanistic pathways regulating Malat1 expression in low oxygen conditions. Compared to those cultured in 21% O2 conditions, HeLa cells incubated in 1.5% O2 expressed more Malat1 transcripts. This observation was mimicked in HEK293T cells using a synthetic reporter construct containing 5.6 kb of the human Malat1 promoter, suggesting that hypoxia directly impacted Malat1 gene transcription. Interestingly, pharmacological stimulation of AMPK increased Malat1 promoter transactivation in 21% O2 conditions, whereas inhibition of either AMPK or its upstream activator CaMKK completely abolished the augmentation of Malat1 under hypoxia. Pharmacological modulation of LKB1, another major regulator of AMPK, had no impact on Malat1 promoter transactivation, suggesting that calcium inputs are important in the control of Malat1 expression by AMPK. Overexpression of hypoxia-inducible factor-1α (HIF-1α) increased Malat1 expression in 21% O2 conditions, whereas pharmacological inhibition of HIF-1α blocked the impact of hypoxia on the Malat1 promoter. Taken together, these findings strongly suggest that Malat1 expression is regulated in hypoxic conditions by a CaMKK/AMPK/HIF-1α axis. More research is needed in physiological settings to test the clinical relevance of this pathway.

The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Carotid cavernous fistulas (CCFs) can be classified as direct and indirect, depending on their flow rates and their etiology. Both forms can cause the same characteristic ophthalmological symptoms and signs. We analyzed these ocular characteristics and determined the prognostics factors associated with treatment outcome. Forty-seven patients with an angiographically confirmed diagnosis of CCF, a preoperative ophthalmic evaluation and at least one ophthalmic sign or symptom at the initial presentation were retrospectively evaluated. The patients were followed-up ophthalmically until the end of treatment, and the complications and the remaining ophthalmological signs and symptoms were then recorded. The patients' ages ranged from 13 to 89 years, with an average of 55.78 (±20.73) years, and a predominance of 28 female (57.8 %) patients. The patients with a direct CCF had a lower average age (p = 0.02). The most common symptoms were blurred vision in 17 (36.2 %) and proptosis in 37 (78.7 %) patients. Elevated intraocular pressure (IOP) was more prevalent in patients with an indirect CCF (p = 0.02). Thrill was more prevalent in patients with direct CCF (p = 0.01). The presence of an initial decrease of visual acuity at the first ophthalmic evaluation was significantly associated with the persistence of ocular symptoms after fistula treatment (odds ratio 3.33). In conclusion our study shows a slight difference in ophthalmic symptoms among patients with different types of fistula. Elevated IOP was significantly associated with indirect fistulas, whereas thrill was significantly associated with direct fistulas. The presence of an initial decrease of visual acuity was significantly associated with a worse ophthalmic prognosis.

The development of human calcified aortic stenosis (AS) includes age-dependent processes that have been involved in atherosclerosis, such as infiltration of macrophages in aortic valves, which then promote production of many pro-inflammatory cytokines, including resistin. However, the molecular mechanisms contributing to these processes are not established. Since Sirt1 has been shown to modulate macrophage biology and inflammation, we examined its levels in human AS and tested its impact on resistin expression. Sirt1 mRNA (p = 0.01) and protein (p<0.05) levels were reduced in explanted valves from AS patients (n = 51) compared to those from control (n = 11) patients. Sirt1 mRNA levels were negatively associated with resistin mRNA levels quantified in AS valves (p = 0.02). Stimulation of Sirt1 by resveratrol or virus-driven overexpression robustly diminished resistin mRNA and protein expression in macrophages, whereas down-regulation of Sirt1 triggered a large increase in resistin expression. These effects were direct, as chromatin immunoprecipitation assays showed that Sirt1 physically interacted with the resistin promoter region at an AP-1 response element. Moreover, Sirt1 blocked c-jun-induced resistin transactivation in gene reporter assays. These findings demonstrate that, in calcified AS, levels of Sirt1 are reduced whereas those of resistin are increased within aortic valve leaflets. Our results also suggest that this loss of Sirt1 expression alleviates its inhibition of resistin transcription in macrophages. Although the overall contribution of this process to the underlying mechanisms for AS disease development remains unresolved, these observations suggest that modification of Sirt1 expression and/or activity could represent a novel approach against inflammation in AS.

Age is an important risk factor for the development of metabolic diseases (e.g. obesity, diabetes and atherosclerosis). Yet, little is known about the molecular mechanisms occurring upon aging that affect energy metabolism. Although visceral white adipose tissue (vWAT) is known for its key impact on metabolism, recent studies have indicated it could also be a key regulator of lifespan, suggesting that it can serve as a node for age-associated fat accretion. Here we show that aging triggers changes in the transcriptional milieu of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) in vWAT, which leads to a modified potential for transactivation of target genes upon ligand treatment. We found that in vWAT of mice, rats and men, aging induced a specific decrease in the expression of steroid receptor coactivator-1 (SRC-1), whose recruitment to PPARgamma is associated with improved insulin sensitivity and low adipogenic activity. In contrast, aging and oxidative stress did not impact on PPARgamma expression and PPARgamma ligand production. Age-induced loss of PPARgamma/SRC-1 interactions increased the binding of PPARgamma to the promoter of the adipogenic gene aP2. These findings suggest that strategies aimed at increasing SRC-1 expression and recruitment to PPARgamma upon aging might help improve age-associated metabolic disorders.

Orbital infections are rare in children. The more posterior the abscess has spread, the more serious it is, with potential intracranial complications. The main etiology is sinusitis, whose location depends on age. The diagnosis is based on clinical examination and CT or MRI. Intravenous antibiotics alone or associated with surgical drainage (for children older than 9 years or those with complications) are performed. Orbital infections in children require good collaboration between ophthalmologists, otolaryngologist, and pediatricians.

We demonstrate tomographic T-ray imaging, using the timing information present in terahertz (THz) pulses in a reflection geometry. THz pulses are reflected from refractive-index discontinuities inside an object, and the time delays of these pulses are used to determine the positions of the discontinuities along the propagation direction. In this fashion a tomographic image can be constructed.

We show that an intense linearly polarized pulse propagating in a nonbirefringent fiber squeezes the perpendicularly polarized vacuum f luctuations through cross-phase modulation. Unlike the generation of squeezed vacuum through self-phase modulation, the mechanism discussed here does not require the use of a nonlinear Sagnac interferometer to separate the pump from the squeezed vacuum.

The continuous-time quantum theory of self-phase modulation (SPM) in lossless, dispersionless, single-mode fiber requires a nonzero response time, to capture the classical SPM limit properly, and an accompanying Raman noise, to ensure commutator preservation. The continuous-wave, four-wave mixing limit of this theory is shown to harbor a Raman-noise limit on fiber-based squeezed-state generation.

The oxidation of glucose and fructose ingested during moderate exercise performed on a cycle ergometer (120 min, 52% VO2max) was compared in ten young males fasted (n = 5) or fed (n = 5) before exercise. The subjects ingested randomly 1.33 g/kg body weight (approximately 96 +/- 9 g) of either enriched 13C-glucose (G), 13C-fructose (F), or water only (W); the solutions were evenly distributed over the exercise period. The fasted subjects began the three exercises with a lower blood glucose (P less than or equal to 0.05 for F only) and insulin (P less than or equal to 0.05) levels and a higher free fatty acid (FFA) concentration (P less than or equal to 0.05) than the fed ones. Throughout the exercise period, blood glucose level was maintained in fasted as well as in fed group for G and F ingestions, while it decreased (P less than or equal to 0.05 at the 100th min in fasted subjects) with water ingestion. Insulin level was similar in both fed and fasted conditions with F and W ingestions and lower than G trials for the fed subjects. For the three ingestions, FFA was lower (P less than or equal to 0.05) in the fasted than in the fed group over the exercise period. Over the 2-h period of exercise, a greater (P less than or equal to 0.05) amount of exogenous F was oxidized in the fasted (49 +/- 6 g) than in the fed (36 +/- 5 g) group, which represent 31% and 20% of the total carbohydrate energy supply, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)