Assessing the acceptability and feasibility of remote spirometric monitoring for rural patients with interstitial lung disease: a multimethod approach.

INTRODUCTION: Interstitial lung disease encompasses a group of rare lung conditions causing inflammation and scarring of lung tissue. The typical method of monitoring disease activity is through pulmonary function tests performed in a hospital setting. However, accessing care can be difficult for rural patients due to numerous barriers. This study assesses the feasibility and acceptability of home spirometry telemonitoring using MIR-Spirometers and the patientMpower home-monitoring platform for rural patients with interstitial lung disease. METHODS: Unblinded, uncontrolled, prospective, multiple-methods study of the feasibility and utility of remote monitoring of 20 rural subjects with interstitial lung disease. Study assessments include adherence to twice weekly spirometry for 3 months in addition to mMRC dyspnea and EQ-5D-5L health-related quality of life questionnaires with each spirometry maneuver. Upon completion, subjects were encouraged to complete an 11-question satisfaction survey and participate in semi-structured qualitative interviews to further explore expectations and perceptions of rural patients to telehealth and remote patient monitoring. RESULTS: 19 subjects completed the 3-month study period. Adherence to twice weekly spirometry was mean 53% ± 38%, with participants on average performing 2.26 ± 1.69 maneuvers per week. The median (Range) number of maneuvers per week was 2.0 (0.0, 7.0). The majority of participants responded favorably to the patient satisfaction survey questions. Themes regarding barriers to access included: lack of local specialty care, distance to center with expertise, and time, distance, and high cost associated with travel. Remote monitoring was well perceived amongst subjects as a way to improve access and overcome barriers. CONCLUSIONS: Remote spirometry monitoring through web-based telehealth is acceptable and feasible for rural patients. Perceived benefits include overcoming access barriers like time, distance, and travel costs. However, cost, reimbursement, and internet access must be addressed before implementing it widely. Future studies are needed to ensure long-term feasibility and to compare outcomes with usual care.

An Automated Microfluidic Analyzer for In Situ Monitoring of Total Alkalinity.

We have designed, built, tested, and deployed an autonomous in situ analyzer for seawater total alkalinity. Such analyzers are required to understand the ocean carbon cycle, including anthropogenic carbon dioxide (CO2) uptake and for mitigation efforts via monitoring, reporting, and verification of carbon dioxide removal through ocean alkalinity enhancement. The microfluidic nature of our instrument makes it relatively lightweight, reagent efficient, and amenable for use on platforms that would carry it on long-term deployments. Our analyzer performs a series of onboard closed-cell titrations with three independent stepper-motor driven syringe pumps, providing highly accurate mixing ratios that can be systematically swept through a range of pH values. Temperature effects are characterized over the range 5-25 °C allowing for field use in most ocean environments. Each titration point requires approximately 170 µL of titrant, 830 µL of sample, 460 J of energy, and a total of 105 s for pumping and optical measurement. The analyzer performance is demonstrated through field data acquired at two sites, representing a cumulative 25 days of operation, and is evaluated against laboratory measurements of discrete water samples. Once calibrated against onboard certified reference material, the analyzer showed an accuracy of -0.17 ± 24 µmol kg-1. We further report a precision of 16 µmol kg-1, evaluated on repeated in situ measurements of the aforementioned certified reference material. The total alkalinity analyzer presented here will allow measurements to take place in remote areas over extended periods of time, facilitating affordable observations of a key parameter of the ocean carbon system with high spatial and temporal resolution.

Circadian functioning of Locus Cœruleus of the nocturnal rat and diurnal rodent Arvicanthis.

The noradrenergic Locus Cœruleus is one of the major arousal structures involved in inducing wakefulness. While brain noradrenaline (NA) amounts display 24-h variations, the origin of NA rhythm is currently unknown. In this study, we tested the hypothesis that NA rhythm could result from its rhythmic synthesis. Therefore, we investigated the 24-h expression profile of NA rate-limiting enzyme, tyrosine hydroxylase (th), in the Locus Cœruleus (LC) of the nocturnal rat and the diurnal rodent Arvicanthis, under 12 h:12 h light/dark (LD) and constant darkness (DD) conditions. In both species, th mRNA levels vary significantly over 24-h. In nocturnal rats, th mRNA profiles show a unimodal rhythm, with peak values in late day in LD, and in the middle of the subjective day in DD. In contrast, th mRNA rhythm in Arvicanthis is characterized by a bimodal profile, with higher levels at the beginning of the day and of the night in LD, and in the middle of the subjective day and night in DD. The rhythmic pattern of th expression may be dependent on a LC clock machinery. Therefore, we investigated the expression of three clock genes, namely bmal1, per1, and per2, and found that their mRNAs display significant variations between day and nighttime points in both species, but in opposite directions. These data show that NA rhythm may be related to circadian expression of th gene in both species, but differs between nocturnal and diurnal rodents. Furthermore, the phase opposition of clock gene expression in the rat compared to Arvicanthis suggests that the clock machinery might be one of the mechanisms involved in th rhythmic expression.

Effluent degradation followed hydrogen production using near-infrared sensitized nanocomposite of reduced nanographene oxide under visible light.

The purpose of this research work is to synthesize near-infrared dye-sensitized nanocomposites with core-shell nanostructures of titanium dioxide/reduced nanographene oxide (TiO2/r-NGO) to be an effective photocatalyst for effluent degradation followed hydrogen generation under visible light irradiation. The generation of hydrogen using photocatalysts has been intensely researched for the effective utilization of hydrogen in a controlled way. The mechanistic pathway for both hydrogen generation and effluent degradation utilizes the electrons generated through photoexcitation during dye sensitization. For this reason, the squaraine dyes were synthesized by the C-H-direct arylation method and made the nanocomposites with self-assembled core/shell nanocomposites (r-NGOT), where TiO2 serves as the core and r-NGO as the shell. Due to the lack of anchoring groups, VJ-Q was only adsorbed on the surface of r-NGOT through π-π stacking, which is confirmed by Fourier transformed-infrared spectroscopy, X-ray photoelectron spectroscopy, high resolution-transmission electron microscopy, and electron energy loss spectroscopy. The optical absorption spectra of VJ-Q/r-NGOT nanocomposites measured with diffuse reflectance UV/visible absorption spectroscopy covers the whole range of visible light wavelengths up to 800 nm. During the photocatalytic activity, VJ-Q/r-NGOT/Pt followed a ligand-to-metal-charge transfer (LMCT) type mechanism for the electron transfer to the core-shell nanostructure. This mechanistic pathway is utilized for the effluent dye degradation followed hydrogen generation through water splitting. The photocatalytic efficiency of the nanocomposite with adsorbed dye is superior to that of dye-TiO2 due to the large surface area provided by r-NGO and the prevention of dye aggregation. The work is significant due to the limited research works that are carried under dye-sensitized nanocomposites that have been utilized for both dye degradation and hydrogen generation.

Towards a low carbon ASEAN: an environmentally extended MRIO optimization model.

BACKGROUND: Economic growth is dependent on economic activity, which often translates to higher levels of carbon emissions. With the emergence of technologies that promote sustainable production, governments are working towards achieving their target economic growth while minimizing environmental emissions to meet their commitments to the international community. The IPCC reports that economic activities associated with electricity and heat production contributed most to GHG emissions and it led to the steady increase in global average temperatures. Currently, more than 90% of the total GHG emissions of the ASEAN region is attributable to Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. These regions are expected to be greatly affected with climate change. This work analyzes how ASEAN nations can achieve carbon reduction targets while aspiring for economic growth rates in consideration of interdependencies between nations. We thus develop a multi-regional input-output model which can either minimize collective or individual carbon emissions. A high-level eight-sector economy is used for analyzing different economic strategies. RESULTS: This model shows that minimizing collective carbon emissions can still yield economic growth. Countries can focus on developing sectors that have potentials for growth and lower carbon intensity as new technologies become available. In the case study examined, results indicate that the services sector, agriculture, and food manufacturing sector have higher potential for economic growth under carbon reduction emission constraints. In addition, the simultaneous implementation of multiple carbon emission reduction strategies provides the largest reduction in regional carbon emissions. CONCLUSIONS: This model provides a more holistic view of how the generation of carbon emissions are influenced by the interdependence of nations. The emissions reduction achieved by each country varied depending on the state of technology and the level of economic development in the different regions. Though the presented case focused on the ASEAN region, the model framework can be used for the analysis of other multi-regional systems at various levels of resolution if data is available. Insights obtained from the model results can be used to help nations identify more appropriate and achievable carbon reduction targets and to develop coordinated and more customized policies to target priority sectors in a country. This model is currently limited by the assumption of fixed technical coefficients in the exchange and interdependence of different regions. Future work can investigate modelling flexible multi-regional trade where regions have the option of substituting goods and products in its import or export structure. Other strategies for reducing carbon emission intensity can also be explored, such as modelling transport mode choices, or establishing sectors for waste management. Hybrid models which integrate the multi-regional input-output linear program model with data envelopment analysis can also be developed.

Bimodal serotonin synthesis in the diurnal rodent, Arvicanthis ansorgei.

In mammals, behavioral activity is regulated both by the circadian system, orchestrated by the suprachiasmatic nucleus (SCN), and by arousal structures, including the serotonergic system. While the SCN is active at the same astronomical time in diurnal and nocturnal species, little data are available concerning the serotonergic (5HT) system in diurnal mammals. In this study, we investigated the functioning of the 5HT system, which is involved both in regulating the sleep/wake cycle and in synchronizing the SCN, in a diurnal rodent, Arvicanthis ansorgei. Using in situ hybridization, we characterized the anatomical extension of the raphe nuclei and we investigated 24 h mRNA levels of the serotonin rate-limiting enzyme, tryptophan hydroxylase 2 (tph2). Under both 12 h:12 h light/dark (LD) and constant darkness (DD) conditions, tph2 mRNA expression varies significantly over 24 h, displaying a bimodal profile with higher values around the (projected) light transitions. Furthermore, we considered several SCN outputs, namely melatonin, corticosterone, and locomotor activity. In both LD and DD, melatonin profiles display peak levels during the biological night. Corticosterone plasma levels show a bimodal rhythmic profile in both conditions, with higher levels preceding the two peaks of Arvicanthis locomotor activity, occurring at dawn and dusk. These data demonstrate that serotonin synthesis in Arvicanthis is rhythmic and reflects its bimodal behavioral phenotype, but differs from what has been previously described in nocturnal species.

Additively manufactured high-performance polymeric materials and their potential use in the oil and gas industry.

The oil and gas industry has been tagged as among the largest revenue-generating sectors in the world. High-performance polymers (HPPs), on the other hand, are among the most useful industrial materials, while the utility of 3D printing technologies has evolved and transitioned from rapid prototyping of composite materials to manufacturing of functional parts. In this prospective, we highlight the potential uses and industrial applications of 3D-printed HPP materials in the oil and gas sector, including the challenges and opportunities present.

Non-metallic organic dyes as photosensitizers for dye-sensitized solar cells: a review.

The advent of novel technologies has led to the need for environmental and economic integration. Energy consumption plays a vital role in human existence, and thereby sustainable development is the need of the hour. When the methods of energy production are discussed, renewable resources are opted to meet the needs of the future with the key resources being solar and wind energy. Solar energy is widely adapted and harnessed due to its abundance and various benefits. Silicon-based solar cells, though produced higher efficiencies, have many cons due to their toxicity and cost. Dye-sensitized solar cells have been grounded as a better alternative due to their ability to function under low light, wider angles, and low internal temperature. In this review paper, various organic metal-free dyes, and their efficiencies along with their cell parameters are discussed. These metal-free dyes are adopted over conventional ruthenium dyes due to their non-toxicity, availability, and cost.

Pinealectomy and gonadectomy modulate amplitude, but not photoperiodic modulation of Clock gene expression in the Syrian hamster suprachiasmatic nuclei.

The duration of daytime light phase (photoperiod) controls reproduction in seasonal mammals. Syrian hamsters are sexually active when exposed to long photoperiod, while gonadal atrophy is observed after exposure to short photoperiod. The photorefractory period, or photorefractoriness, is a particular state of spontaneous recrudescence of sexual activity that occurs after a long-term exposure to short photoperiod. Expression of core clock genes in the master circadian clock contained in the suprachiasmatic nuclei depends on photoperiodic conditions. Interestingly, the expression of the Clock gene is also modified in photorefractory Syrian hamsters. Since melatonin and testosterone levels in seasonal species are dependent on photoperiod, photoperiodic variations of Clock mRNA levels in the suprachiasmatic clock could be a consequence of these hormonal changes. To test this hypothesis, we analysed the effects of pinealectomy on Clock mRNA changes due to long to short photoperiod transition and of gonadectomy on Clock mRNA levels in photorefractory period. Our data show that the suprachiasmatic integration of the short photoperiod (assessed by a rhythmic expression profile of Clock) is independent of the presence of melatonin. Furthermore, constitutively low expression of Clock observed during the photorefractory period does not require the presence of either melatonin or testosterone. However, we show that both hormones provide positive feedback on average levels of Clock expression. Thus, our data support the hypothesis that daily variations of Clock levels in the suprachiasmatic nuclei are influenced by photoperiodic changes and the time spent in short photoperiod, independently of seasonal modifications of melatonin or testosterone levels.

Skeletal Muscle Index's Impact on Discharge Disposition After Head and Neck Cancer Free Flap Reconstruction.

OBJECTIVE: To determine the role of skeletal muscle index (SMI) in the assessment of frailty and determination of discharge to post-acute care facilities (PACF) after head and neck cancer free flap reconstruction (HNCFFR). STUDY DESIGN: Retrospective cohort. SETTING: Single-institution, academic tertiary referral center. METHODS: Adult patients undergoing HNCFFR from 2014 to 2019 with preoperative abdominal computed tomography imaging were retrospectively analyzed. Patient demographics, 5-factor modified frailty index (5-mFI), body mass index (BMI), SMI at the third lumbar vertebra, oncologic history, perioperative data, and Clavien-Dindo (CD) complications were collected. Binary logistic regression was used to identify independent predictors of discharge disposition. RESULTS: The cohort consisted of 206 patients, 62 (30.1%) of whom were discharged to PACF. Patients discharged to PACF were of older age (65.4 vs 57.1 years, P < .0001) and had a lower SMI (38.8 vs 46.8 cm2/m2, P < .0001), higher 5-mFI (≥3; 25.8% vs 4.2%, P < .0001), and greater incidence of stage IV (80.6% vs 64.1%, P = .0211) aerodigestive cancer (80.6% vs 66.7%, P = .0462). Patients discharged to PACF experienced more blood transfusions (74.2% vs 35.4%, P < .0001), major postoperative complications (CD ≥3, 40.3% vs 12.9%, P < .0001), and delirium (33.9% vs 4.2%, P < .0001). After adjusting for pre- and postoperative factors, multivariate binary logistic regression identified age (P = .0255), 5-mFI (P < .0042), SMI (P = .0199), stage IV cancer (P = .0250), aerodigestive tumor (P = .0366), delirium (P < .0001), and perioperative blood transfusion (P = .0144) as independent predictors of discharge to PACF. CONCLUSIONS: SMI and 5-mFI are independently associated with discharge to PACF after HNCFFR and should be considered in preoperative planning and assessment of frailty.

On the Effect of Ultralow Loading of Microwave-Assisted Bifunctionalized Graphene Oxide in Stereolithographic 3D-Printed Nanocomposites.

Surface functionalization of graphene oxide (GO) is one of the best ways to achieve homogeneous dispersions of GO within polymeric matrices and composites. Nonetheless, studies regarding how the level of GO functionalization affects the macroscopic properties of three-dimensional (3D) printed nanocomposites are still few. Furthermore, the bifunctionalization of GO with the NH2/NH3+ groups to obtain improved thermomechanical macroscopic properties at ultralow loads has not been reported. In this paper, fast and straightforward surface bifunctionalization of GO with a controlled ratio of NH2/NH3+ groups at low, medium, and high functionalization levels (AGOL, AGOM, and AGOH) in a one-step microwave-assisted synthesis is reported for the first time. The functionalization mechanism was disclosed, wherein three graft densities (Gφ) were obtained. A plateau of maximum functionalization (Gφ = 4.9 µmol/m2 = 2.9 molecules/nm2) was reached, suggesting that full coverage of the GO surface is achievable. Also, an increase in the exfoliation of functionalized layers was obtained, ranging from d002 = 8.6 Å up to d002 = 15.8 Å. X-ray photoelectron spectroscopy (XPS) reveals the successful functionalization of GO, as well as an atomic relationship NH2/NH3+ of about 50/50% in all functionalized samples. Stereolithographic (SLA) 3D-printed nanocomposites (AGOL/R, AGOM/R, and AGOH/R) were obtained using ultralow loads (0.01 wt %) of each bifunctionalized material. This ultralow amount was sufficient to enhance thermal stability (up to 4 °C) and a significant increase in the glass transition temperature (93 °C ≤ Tg ≤ 120 °C). Interestingly, we found that low and medium grafting density promotes a ductile material (ε > 5%); meanwhile, a high graft density produces brittle materials. Also, we observe that the toughness can be tuned as a function of the graft density (AGOH: 24 MPa, AGOM: 342 MPa, AGOL: 562 MPa) at ultralow loadings. The 3D-printed nanocomposites using GO with low graft density (AGOL) increase their tensile strain by 90% in comparison with the control sample (without filler). Finally, the underlying mechanisms were discussed to explain the findings.

The dromedary camel displays annual variation in hypothalamic kisspeptin and Arg-Phe-amide-related peptide-3 according to sex, season, and breeding activity.

The dromedary camel (Camelus dromedarius) is a desert mammal whose cycles in reproductive activity ensure that the offspring's birth and weaning coincide with periods of abundant food resources and favorable climate conditions. In this study, we assessed whether kisspeptin (Kp) and arginine-phenylalanine (RF)-amide related peptide-3 (RFRP-3), two hypothalamic peptides known to regulate the mammalian hypothalamo-pituitary gonadal axis, may be involved in the seasonal control of camel's reproduction. Using specific antibodies and riboprobes, we found that Kp neurons are present in the preoptic area (POA), suprachiasmatic (SCN), and arcuate (ARC) nuclei, and that RFRP-3 neurons are present in the paraventricular (PVN), dorsomedial (DMH), and ventromedial (VMH) hypothalamic nuclei. Kp fibers are found in various hypothalamic areas, notably the POA, SCN, PVN, DMH, VMH, supraoptic nucleus, and the ventral and dorsal premammillary nucleus. RFRP-3 fibers are found in the POA, SCN, PVN, DMH, VMH, and ARC. POA and ARC Kp neurons and DMH RFRP-3 neurons display sexual dimorphism with more neurons in female than in male. Both neuronal populations display opposed seasonal variations with more Kp neurons and less RFRP-3 neurons during the breeding (December-January) than the nonbreeding (July-August) season. This study is the first describing Kp and RFRP-3 in the camel's brain with, during the winter period lower RFRP-3 expression and higher Kp expression possibly responsible for the HPG axis activation. Altogether, our data indicate the involvement of both Kp and RFRP-3 in the seasonal control of the dromedary camel's breeding activity.

Asthma specialist care preferences among parents of children receiving emergency department care for asthma.

Objective: To learn factors associated with desire for asthma specialist care among parents of children seeking emergency department (ED) care for asthma, and if referral was indicated based on national asthma guidelines. Methods: We surveyed parents of children ages 0-18 years seeking pediatric ED asthma care, then comparisons were made according to parental level of interest in asthma specialist care, with regard to socio-demographics, asthma morbidity and care, by chi-squared and logistic regression. Results: Of 149 children, 20% reported specialist care, but 75% met guideline criteria for referral. About 80% of parents not seeing an asthma specialist expressed a desire to see one. Higher rates of prior urgent care visits (48% vs. 22%, p = 0.03), ED visits (82% vs. 35%, p < 0.001) and oral steroid use (53% vs. 22%, p = 0.009) were reported by parents who desired an asthma specialist compared with parents who did not. 87% of parents not seeing a specialist attributed this to a perceived lack of necessity by their primary care provider. An ED visit within the prior 12 months was the most significant predictor in parental desire for specialist care (odds ratio 9.75; 95% CI 3.42-27.76) in adjusted logistic regression models. Conclusion: High rates of parental preference for asthma specialist care suggest that directly querying parents may be an efficient method to identify children appropriate for specialist care in the ED.

The relevance of using in situ carbon and nitrogen data and satellite images to assess aboveground carbon and nitrogen stocks for supporting national REDD + programmes in Africa.

BACKGROUND: To reduce the uncertainty in estimates of carbon emissions resulting from deforestation and forest degradation, better information on the carbon density per land use/land cover (LULC) class and in situ carbon and nitrogen data is needed. This allows a better representation of the spatial distribution of carbon and nitrogen stocks across LULC. The aim of this study was to emphasize the relevance of using in situ carbon and nitrogen content of the main tree species of the site when quantifying the aboveground carbon and nitrogen stocks in the context of carbon accounting. This paper contributes to that, by combining satellite images with in situ carbon and nitrogen content in dry matter of stem woods together with locally derived and published allometric models to estimate aboveground carbon and nitrogen stocks at the Dassari Basin in the Sudan Savannah zone in the Republic of Benin. RESULTS: The estimated mean carbon content per tree species varied from 44.28 ± 0.21% to 49.43 ± 0.27%. The overall mean carbon content in dry matter for the 277 wood samples of the 18 main tree species of the region was 47.01 ± 0.28%-which is close to the Tier 1 coefficient of 47% default value suggested by the Intergovernmental Panel on Climate Change (IPCC). The overall mean fraction of nitrogen in dry matter was estimated as 0.229 ± 0.016%. The estimated mean carbon density varied from 1.52 ± 0.14 Mg C ha-1 (for Cropland and Fallow) to 97.83 ± 27.55 Mg C ha-1 (for Eucalyptus grandis Plantation). In the same order the estimated mean nitrogen density varied from 0.008 ± 0.007 Mg ha-1 of N (for Cropland and Fallow) to 0.321 ± 0.088 Mg ha-1 of N (for Eucalyptus grandis Plantation). CONCLUSION: The results show the relevance of using the in situ carbon and nitrogen content of the main tree species for estimating aboveground carbon and nitrogen stocks in the Sudan Savannah environment. The results provide crucial information for carbon accounting programmes related to the implementation of the REDD + initiatives in developing countries.

An Ultradian Feeding Schedule in Rats Affects Metabolic Gene Expression in Liver, Brown Adipose Tissue and Skeletal Muscle with Only Mild Effects on Circadian Clocks.

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6 meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock, but did have mild effects on peripheral clocks. In contrast, genes involved in glucose and lipid metabolism showed differential expression. In conclusion, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby, a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.

Short-term propofol anaesthesia down-regulates clock genes expression in the master clock.

BACKGROUND: Propofol anesthesia triggers phase-advances of circadian rhythms controlled by the suprachiasmatic nuclei (SCN), the master clock. Besides, inhalational anesthesia has been associated with a subsequent reduction of Per2 mRNA levels in the whole brain of rodents. The acute effects of propofol anesthesia per se on the SCN molecular clockwork remain unclear. Here we aim to study the expression of Per1 and Per2 clock genes in the SCN of rats exposed to constant darkness after a single dose of propofol. METHODS: Thirty 2-months old rats were randomly divided into 2 groups receiving a single dose of either 120 mg/kg propofol 1% (n=15), or intralipid® 10% (n=15) in late day (projected circadian time (CT) 10, i.e., 10h after the expected time of lights on). Thereafter, rat brains were sampled in darkness 1h, 2h or 3h after the treatment (projected CT11, CT12 or CT13). Expression of Per1 and Per2 mRNA was analyzed by in situ hybridization in SCN coronal sections. RESULTS: Per1 expression was affected by time and treatment. Per1 expression in the SCN after propofol treatment decreased at CT11 and CT12 when compared to the vehicle group. For Per2 expression, we observed only a treatment effect. Observed in dark conditions without hypothermia or/and concomitant surgery, such down-regulation of clock genes Per is only correlated to propofol treatment. This may explain "jet-lag-like" symptoms described by patients after anesthesia. CONCLUSION: We show here for the first time that short-term propofol anesthesia leads to a transient down-regulation of Per1 and Per2 expression in the SCN.

The lateral habenula interacts with the hypothalamo-pituitary adrenal axis response upon stressful cognitive demand in rats.

The lateral habenula (LHb) is involved in emotional and cognitive behaviors. Recently, we have shown in rats that blockade of excitatory inputs to the LHb not only induced deficits of memory retrieval in the water maze, but also altered swim strategies (i.e., induced excessive thigmotaxis). The latter observation, although consistent with the occurrence of memory deficits, could also possibly be the consequence of an excessive level of stress, further suggesting a role for the LHb in the stress response in our behavioral paradigm. To test this hypothesis we performed in rats intra-LHb infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 267 ng/side in 0.3 µL), or vehicle, and assessed the responsiveness of the hypothalamo-pituitary adrenal (HPA) axis to environmental stressful or non-stressful situations. We have measured plasma corticosterone (CORT) concentrations at different time points before and following intra-LHb infusion of CNQX - or of the same volume of vehicle - in three conditions: during the probe test of a water maze experiment; in an anxiety test, the elevated plus maze; and in a home cage condition. Whereas there were no differences in the home cage condition and in the elevated plus maze, in the water maze experiment we observed that CNQX-treated rats presented, along with memory deficits, a higher level of blood CORT than vehicle-treated rats. These results suggest that perturbations of the modulation of the HPA axis are consecutive to the alteration of LHb function, whether it is the result of a defective direct control of the LHb over the HPA axis, or the consequence of memory deficits.

Simultaneous fabrication of line and dot dual nanopatterns using miktoarm block copolymer with photocleavable linker.

Block copolymers with various nanodomains, such as spheres, cylinders, and lamellae, have received attention for their applicability to nanolithography. However, those microdomains are determined by the volume fraction of one block. Meanwhile, nanopatterns with multiple shapes are required for the next-generation nanolithography. Although various methods have been reported to achieve dual nanopatterns, all the methods need sophisticated processes using E-beam. Here, we synthesized a miktoarm block copolymer capable of cleavage of one block by ultraviolet. Original cylindrical nanodomains of synthesized block copolymer were successfully transformed to lamellar nanodomains due to the change of molecular architecture by ultraviolet. We fabricated dual nanopatterns consisting of dots and lines at desired regions on a single substrate. We also prepared dual nanopatterns utilizing another phase transformation from spheres to cylinders in a block copolymer with higher interaction parameter. Since our concept has versatility to any block copolymer, it could be employed as next-generation nanolithography.

Self-Positioned Nanosized Mask for Transparent and Flexible Ferroelectric Polymer Nanodiodes Array.

High density arrays of ferroelectric polymer nanodiodes have gained strong attention for next-generation transparent and flexible nonvolatile resistive memory. Here, we introduce a facile and innovative method to fabricate ferroelectric polymer nanodiode array on an ITO-coated poly(ethylene terephthalate) (PET) substrate by using block copolymer self-assembly and oxygen plasma etching. First, polystyrene-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) micelles were spin-coated on poly(vinylidene fluoride-ran-trifluoroethylene) copolymer (P(VDF-TrFE)) film/ITO-coated PET substrate. After the sample was immersed in a gold precursor (HAuCl4) containing solution, which strongly coordinates with nitrogen group in P2VP, oxygen plasma etching was performed. During the plasma etching, coordinated gold precursors became gold nanoparticles (GNPs), which successfully acted as self-positioned etching mask to fabricate a high density array of P(VDF-TrFE)) nanoislands with GNP at the top. Each nanoisland shows clearly individual diode property, as confirmed by current-voltage (I-V) curve. Furthermore, due to the transparent and flexible nature of P(VDF-TrFE)) nanoisland as well as the substrate, the P(VDF-TrFE) nanodiode array was highly tranparent, and the diode property was maintained even after a large number of bendings (for instance, 1000 times). The array could be used as the next-generation tranparent and flexible nonvolatile memory device.

Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis.

The PI-3 kinase (PI-3K)/mTOR pathway is critical for cell growth and proliferation. Strategies of antagonising this signaling have proven to be detrimental to cell survival. This observation, coupled with the fact many tumours show enhanced growth signaling, has caused dual inhibitors of PI-3K and mTOR to be implicated in cancer treatment, and have thus been studied across various tumour models. Since PI-3K (class-I)/mTOR pathway negatively regulates autophagy, dual inhibitors of PI-3K/mTOR are currently believed to be autophagy activators. However, our present data show that the dual PI-3K/mTOR inhibition (DKI) potently suppresses autophagic flux. We further confirm that inhibition of Vps34/PI3KC3, the class-III PI-3K, causes the blockade to autophagosome-lysosome fusion. Our data suggest that DKI induces cell death independently of apoptosis and necroptosis, whereas autophagy perturbation by DKI may contribute to cell death. Given that autophagy is critical in cellular homeostasis, our study not only clarifies the role of a dual PI-3K/mTOR inhibitor in autophagy, but also suggests that its autophagy inhibition needs to be considered if such an agent is used in cancer chemotherapy.