COP2ING With a New Normal: Navigating the Return to Society for Older Adults With Dementia and Their Caregivers.

COVID-19 has stressed the healthcare system in ways our society has not seen before. Less visibly, elderly patients and their caregivers have been stressed as well, both by the virus and by the public health measures required to slow its spread. After months of isolating, patients with dementia and their caregivers are worried about reentering a society with different rules and expectations. Although an extremely complex topic, the re-entry of individuals with cognitive impairment back into society is critical for both the wellbeing of the person as well as the caregiver. Successful re-entry into society will vary based on a person's interests and baseline cognition, however, the ability to participate in activities and events that previously provided joy and stimulation is the first step. This paper, written by practicing geriatricians and palliative clinicians, offers some concrete counseling strategies and tips for caregivers to help navigate re-entry into society with their loved ones.

Unique hierarchical SiO2@ZnIn2S4 marigold flower like nanoheterostructure for solar hydrogen production.

The novel marigold flower like SiO2@ZnIn2S4 nano-heterostructure was fabricated using an in situ hydrothermal method. The nanoheterostructure exhibits hexagonal structure with marigold flower like morphology. The porous marigold flower assembly was constructed using ultrathin nanosheets. Interestingly, the thickness of the nanopetal was observed to be 5-10 nm and tiny SiO2 nanoparticles (5-7 nm) are decorated on the surface of the nanopetals. As the concentration of SiO2 increases the deposition of SiO2 nanoparticles on ZnIn2S4 nanopetals increases in the form of clusters. The optical study revealed that the band gap lies in the visible range of the solar spectrum. Using X-ray photoelectron spectroscopy (XPS), the chemical structure and valence states of the as-synthesized SiO2@ZnIn2S4 nano-heterostructure were confirmed. The photocatalytic activities of the hierarchical SiO2@ZnIn2S4 nano-heterostructure for hydrogen evolution from H2S under natural sunlight have been investigated with regard to the band structure in the visible region. The 0.75% SiO2@ZnIn2S4 showed a higher photocatalytic activity (6730 µmol-1 h-1 g-1) for hydrogen production which is almost double that of pristine ZnIn2S4. Similarly, the hydrogen production from water splitting was observed to be 730 µmol-1 h-1 g-1. The enhanced photocatalytic activity is attributed to the inhibition of charge carrier separation owing to the hierarchical morphology, heterojunction and crystallinity of the SiO2@ZnIn2S4.

Induction of immunological, hormonal and histological alterations after sublethal exposure of chlorpyrifos in the freshwater fish, Pseudetroplus maculatus (Bloch, 1795).

The present study investigated the induction of immunological, hormonal and histological changes in the freshwater fish, Pseudetroplus maculatus after sublethal exposure of chlorpyrifos. Fish were exposed to chlorpyrifos at one-tenth (0.661µg/L) and one-fifth (1.32 µg/L) of LC50 value, for 15 and 30 d, along with the respective control group. Innate and adaptive immune responses of the fish against the toxicant exposure were measured using lysozyme, complement (ACH50) levels, phagocytic, nitroblue tetrazolium (NBT), myeloperoxidase (MPO), anti-protease and hemagglutination activities, and IgM concentration. The results revealed that sublethal exposure of chlorpyrifos caused significant (p < 0.05) reduction in lysozyme, ACH50, phagocytic, and anti-protease activities whereas there was significant (p < 0.05) increase in NBT, MPO and hemagglutination levels along with serum IgM concentration. Chlorpyrifos treatment showed significant (p < 0.05) decline in the serum levels of cortisol, thyroid, testosterone and estradiol hormones in duration- and concentration-dependent manner. The major histological lesions noted in liver includes necrosis, vacuolization, hepatocytic and cytoplasmic degeneration, while kidneys showed vacoules, necrosis and rupture in renal tubules and glomerulus, whereas spleen were found with melanomacrophage aggregation and necrosis. Similarly, testis showed remarkable changes like reduction in the number of spermatozoa and disintegrated seminiferous tubules while ovarian lesions include degenerated and empty follicles, few atretic oocytes, reduced size of follicles, and broken theca granulosa. The current findings revealed that the use of chlorpyrifos in domestic and agricultural purposes even at sublethal concentration could affect the non-target organisms including fish, and thereby alter the health status of aquatic ecosystems.

Increased Expression of TGF-ß and IFN-γ in Peripheral Blood Mononuclear Cells (PBMCs) Cultured in Conditioned Medium (CM) of K562 Cell Culture.

In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-ß in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-ß compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.

Fullerene C60 nanomaterial induced oxidative imbalance in gonads of the freshwater fish, Anabas testudineus (Bloch, 1792).

The engineered carbon nanomaterial, fullerene C60, with unique physicochemical properties, released into the aquatic environment is known to formulate high risk factor for the aquatic life. The present study was aimed to investigate fullerene C60 induced oxidative imbalance in ovary and testis of the freshwater fish, Anabas testudineus. The median lethal concentration (96 h-LC50) of fullerene C60 in Anabas testudineus was 50 mg/ L, and fish exposed to two sublethal concentrations i.e., 5 mg/ L and 10 mg/ L (one-tenth and one-fifth of LC50) for short-term (24, 48, 72 and 96 h) and long-term (7, 15, 30 and 60 d) durations. The antioxidant parameters such as the activities of superoxide dismutase (SOD), catalase, glutathione reductase, glutathione peroxidase, the levels of hydrogen peroxide generation and lipid peroxidation were analyzed along with histopathological alterations in gonadal tissues. Both sublethal concentrations of fullerene C60 caused significant (P < 0.05) decrease in the activities of antioxidant enzymes, whereas the levels of hydrogen peroxide generation and lipid peroxidation increased significantly (P < 0.05) in gonads. Fullerene exposure significantly (P < 0.05) increased the mucous deposition with significant (P < 0.05) reduction in the weights of gonads and gonado-somatic index. The histopathological analysis showed prominent alterations in testis and ovary of treated fishes when compared to the control groups. After 60 d of sublethal exposure of fullerene C60, fish were left in the toxicant-free water for another 60 d, in which the changes in the activities of the gonadal antioxidant enzymes and histological alterations were not completely recovered. Hence, from the present study, it was illustrated that fullerene C60 caused oxidative imbalance in the gonads, which may possibly affect the reproductive potential of the fish, Anabas testudineus.

Preliminary Analysis of Phytoconstituents and Evaluation of Anthelminthic Property of Cayratia auriculata (In Vitro).

Context:Phytoconstituents of medicinal plants have been playing a key role in treating various diseases all over the world since ancient times. The present study was focused on preliminary analysis of phytoconstituents and evaluation of anthelmintic property (in vitro) of different extracts of Cayratia auriculata (Family: Vitaceae) against earthworms (Pheretima posthuma). Materials and methods:Four different hexane, chloroform, ethyl acetate and methanol extracts of Cayratia auriculata were screened for their phytoconstituents. Cayratia auriculata has been shown to have various phytoconstituents such as flavonoids, phenolic compounds, tannins, alkaloids, saponins, glycosides and steroids. Hexane, chloroform, ethyl acetate and methanol extracts of Cayratia auriculata were analyzed for their anthelmintic property on earthworms (Pheretima posthuma). Each extract at three different concentrations (20 mg/mL, 40 mg/mL and 80 mg/mL) was analysed to evaluate the time taken for paralysis (P) and death (D) of adult earthworms. Albendazole was used as standard and 2% Tween 80 in distilled water as control at a concentration of 10 mg/mL. Results:Our study found that the methanolic extract of Cayratia auriculata at a concentration of 80 mg/mL [21.98±0.88 (P), 79.06±0.87(D)] expressed a stronger anthelmintic property than the standard albendazole (10 mg/mL) [26.73±0.56 (P), 87.70±0.91 (D)]. Conclusions:All extracts expressed a dose dependent anthelmintic activity, with an increasing pattern in the following order: hexane, chloroform, ethyl acetate and methanol.

Survey of knowledge of school children towards the prevalence, severity, management of maxillofacial injuries, and rescue skills in the event of a dog bite.

BACKGROUND: Maxillofacial injuries are reported commonly in children encountering animal/dog attack. The level of knowledge of children on such events can form a sound basis for the prevention of maxillofacial injuries resulting from dog bites/attacks. AIM: This study aims to assess the knowledge of children on maxillofacial injuries resulting from dog bites, their management, and rescue skills to be used during the event of a dog attack. SETTINGS AND DESIGN: The study is a cross-sectional questionnaire survey. MATERIAL AND METHODS: Seven hundred children aged 7-12 years participated in the study. A questionnaire consisting of 21 questions assessed the common site and management of injury resulting from dog bites, the source of exposure, and the knowledge of children on rescue skills to be used in the event of dog attack. This was followed by an awareness program to educate the children on rescue skills and management of dog bite injuries. STATISTICAL ANALYSIS: Descriptive statistics were calculated for all the variables. RESULTS: A significant percentage of dog bite injuries occurred on the face and hands in children. Boys were more common victims. Familiar dogs inflicted injuries to the children commonly than stray dogs. The children lacked knowledge on the management of dog bite injuries; however, they were aware of rabies and its prevention. The children were not well aware of rescue skills to be used in the event of a dog attack. CONCLUSION: Children are innocent and behavior of dogs are unpredictable hence they become victims of the dog attacks. Educating children on safe animal behavior can prove vital in reducing gruesome maxillofacial injuries resulting from dog attacks.

An overview of quinazolines: Pharmacological significance and recent developments.

Most of the drugs and pharmacologically relevant molecules possess heterocyclic ring structures and presence of hetero atoms or groupings divulges privileged specificities in their pharmacological targets. Especially the heterocyclic systems, quinazoline is a biologically imperative scaffold known to be linked with several pharmacological activities. Some of the protuberant pharmacological responses attributed to this system are analgesic, anti-inflammatory, anti-convulsant, sedative-hypnotic, anti-histaminic, anti-hypertensive, anti-cancer, anti-microbial, anti-tubercular and anti-viral activities. This multiplicity in the pharmacological response contours of quinazoline has attracted the consideration of medicinal chemists to explore this system to its multiple potential against numerous activities. Several of these synthetic and pharmacological investigations have been successively studied for structure-activity relationship (SAR) to correlate the particular structural features for their pharmacological target. The emerging understanding of quinazoline derivatives on their pharmacological target offer opportunities for novel therapeutics. This review principally emphases on the medicinal chemistry aspects including drug design, structure-activity relationships (SARs), and mechanism of actions of quinazoline derivatives. This review gives detailed attention on in vitro and in vivo pharmacological activities of quinazoline and its analogs in the perspective of drug discovery and its development.

Effect of Poloxamer on Zingiber Officinale Extracted Green Synthesis and Antibacterial Studies of Silver Nanoparticles.

The Zingiber officinale (Z. officinale) plant is one of the well-known medicinal plants. Poloxamer finds excellent clinical and therapeutic uses for curing of various ailments. The poloxamer 188 polymer and the plant extract of Z. officinale have been used to prepare the silver nanoparticles (AgNPs) by a green synthesis route. The Z. officinale plant extract has been used as a reducing agent, while the poloxamer 188 has been used as a stabilizing agent. The formation of face-centered cubic (fcc) structure AgNPs was confirmed by X-ray diffraction pattern. The effect of addition of poloxamer on the controlling the shape, size and morphologies of the AgNPs has been investigated by transmission electron microscopy (TEM) and dynamic light scattering techniques. The elemental composition of AgNPs was confirmed by energy dispersive X-ray (EDX) analysis. The anti-bacterial activity of AgNPs has been investigated using three human pathogens Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The poloxamer 188 protected AgNPs inhibit the bacterial growth more effectively than the pure Z. officinale extract and the Z. officinale extract AgNPs.

Isolation and Characterization of Chemopreventive Agent from Sphaeranthus amaranthoides Burm F.

OBJECTIVE: To investigate the in vitro cytotoxic effect and to isolate and characterize a chemopreventive secondary metabolite from Sphaeranthus amaranthoides Burm F (sivakaranthai). MATERIALS AND METHODS: In vitro cytotoxic effect was carried out by 3 (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay. Different concentrations of the extracts were tested on three different cell lines namely A549, HT29, and MCF7. The chloroform extract was subjected to column chromatography, and the isolated compound was characterized by various spectral methods and by single crystal X-ray crystallography. RESULTS: The concentration that cause 50% growth inhibition value of chloroform extract was found to be 0.9 and 19 µg/mL against MCF7 and A549 cell lines, respectively. Chloroform extract was subjected to column chromatography for the isolation of phytoconstituent. The structure of the isolated compound was identified by spectroscopic techniques such as infrared, nuclear magnetic resonance, XRD, and mass spectroscopy. On comparison of complete spectral detail of the compound, the proposed structure was identified as chrysosplenol D (a flavonoid). Chrysosplenol D was isolated for the first time from this plant. CONCLUSION: The chloroform extract had higher cytotoxic effect, and the isolated chrysosplenol D may be responsible for the anti-proliferative effect of the plant. SUMMARY: The plant Sphaeranthus amaranthoides Burm F was extracted with solvents of increasing polarity. The chloroform extract was found to have cell inhibition towards MCF 7 and HT 29 cell lines. This was subjected to fractionation. Chrysosplenol D was isolated from the chloroform extract.

Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity.

OBJECTIVE: The adverse events (AEs) with botulinum toxin type-A (BoNTA), used for indications other than spasticity, are widely reported in the literature. However, the site, dose, and frequency of injections are different for spasticity when compared to the treatment for other conditions and hence the AEs may be different as well. The objective of this study was to summarize the AEs reported in Canada and systematically review the AEs with intramuscular botulinum toxin injections to treat focal spasticity. METHODS: Data were gathered from Health Canada (2009-2013) and major electronic databases. RESULTS: In a 4 year period, 285 AEs were reported. OnabotulinumtoxinA (n=272 events): 68% females, 53% serious, 18% hospitalization, and 8% fatalities. The type of AEs reported were - muscle weakness (19%), oropharyngeal (14%), respiratory (14%), eye related (8%), bowel/bladder related (8%), and infection (5%). IncobotulinumtoxinA (n=13): 38% females, 62% serious, and 54% hospitalization. The type of AEs reported were - muscle weakness (15%), oropharyngeal (15%), respiratory (38%), eye related (23%), bowel/bladder related (15%), and infection (15%). Commonly reported AEs in the literature were muscle weakness, pain, oropharyngeal, bowel/bladder, blood circulation, neurological, gait, and respiratory problems. CONCLUSION: While BoNTA is useful in managing spasticity, future studies need to investigate the factors that can minimize AEs. A better understanding of the underlying mechanisms of the AEs can also improve guidelines for BoNTA administration and enhance outcomes.

Antibacterial Studies and Effect of Poloxamer on Gold Nanoparticles by Zingiber Officinale Extracted Green Synthesis.

Poloxamer finds excellent clinical and therapeutic uses for curing of various ailments. The Zin- giber officinale (Z. officinale) is one of the well-known medicinal plants. The poloxamer188 and the rhizome extract of Z. officinale have been used to synthesize the gold nanoparticles (AuNPs) by a green approach. The Z. officinale extract has been used as a reducing agent while the polox- amerl88 has been used as a stabilizing agent. The effect of addition of poloxamer on the controlling the shape and size of the AuNPs has been investigated by transmission electron microscopy (TEM) and dynamic light scattering techniques. The formation of AuNPs has also been confirmed by UV-Visible spectral, energy dispersive X-ray (EDX) and powder X-ray diffraction (XRD) analyses. The anti-bacterial activity of the green synthesized AuNPs has been investigated on the three human pathogens Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia. The poloxamer188 protected AuNPs inhibit the bacterial growth more effectively than the pure Z. officinale extract and the standard tetracycline (TA).

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

BACKGROUND: We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. METHODS: Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. RESULTS: Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. CONCLUSION: It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation.

Assessment of in vitro cytotoxicity and in vivo antitumor activity of Sphaeranthus amaranthoides burm.f.

BACKGROUND: A number of plants have been used in Indian system of medicine such as ayurveda, unani and siddha, but most of these plants were not explored properly. Sphaeranthus amaranthoides (SA) Burm.f., is one such plant used as an energizer in siddha. OBJECTIVE: To evaluate the anticancer effect of chloroform extract of the whole plant of SA Burm.f. against Ehrlich ascites carcinoma bearing Swiss albino mice. MATERIALS AND METHODS: The anticancer effect of chloroform extract was investigated in Swiss albino mice bearing Ehrlich ascites carcinoma at two different dose levels. Acute toxicity studies were also performed to determine the safety of the extract. Mice injected with Ehrlich ascites carcinoma cells were treated with the extract of doses 200 and 400 mg/kg body weight and standard 5-fluorouracil 20 mg/kg body weight for 15 consecutive days. Animals were sacrificed on day 15 for determination of anticancer activity by evaluating tumor volume, nonviable and viable tumor cell count and hematological parameters. RESULTS: Mice treated with the extract showed a significant decrease in tumor volume and viable cell count and an increase in nonviable cell count and mean survival time. The hematological parameters were also found to be restored to a normal level. CONCLUSION: The results indicate that the chloroform extract was producing anticancer activity comparable with that of the standard 5-fluorouracil.

Visceral leishmaniasis diagnosis and reporting delays as an obstacle to timely response actions in Nepal and India.

BACKGROUND: To eliminate visceral leishmaniasis (VL) in India and Nepal, challenges of VL diagnosis, treatment and reporting need to be identified. Recent data indicate that VL is underreported and patients face delays when seeking treatment. Moreover, VL surveillance data might not reach health authorities on time. This study quantifies delays for VL diagnosis and treatment, and analyses the duration of VL reporting from district to central health authorities in India and Nepal. METHODS: A cross-sectional study conducted in 12 districts of Terai region, Nepal, and 9 districts of Bihar State, India, in 2012. Patients were interviewed in hospitals or at home using a structured questionnaire, health managers were interviewed at their work place using a semi-structured questionnaire and in-depth interviews were conducted with central level health managers. Reporting formats were evaluated. Data was analyzed using two-tailed Mann-Whitney U or Fisher's exact test. RESULTS: 92 VL patients having experienced 103 VL episodes and 49 district health managers were interviewed. Patients waited in Nepal 30 days (CI 18-42) before seeking health care, 3.75 times longer than in Bihar (8d; CI 4-12). Conversely, the lag time from seeking health care to receiving a VL diagnosis was 3.6x longer in Bihar (90d; CI 68-113) compared to Nepal (25d; CI 13-38). The time span between diagnosis and treatment was short in both countries. VL reporting time was in Nepal 19 days for sentinel sites and 76 days for "District Public Health Offices (DPHOs)". In Bihar it was 28 days for "District Malaria Offices". In Nepal, 73% of health managers entered data into computers compared to 16% in Bihar. In both countries reporting was mainly paper based and standardized formats were rarely used. CONCLUSIONS: To decrease the delay between onset of symptoms and getting a proper diagnosis and treatment the approaches in the two countries vary: In Nepal health education for seeking early treatment are needed while in Bihar the use of private and non-formal practitioners has to be discouraged. Reinforcement of VL sentinel reporting in Bihar, reorganization of DPHOs in Nepal, introduction of standardized reporting formats and electronic reporting should be conducted in both countries.

Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS).

PURPOSE: We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS). METHODS: Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0-4.9). CONCLUSIONS: Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD.

Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program.

BACKGROUND: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. METHODS: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. RESULTS: Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. CONCLUSIONS: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype.

Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.

PURPOSE: To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. METHODS: 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. RESULTS: Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (ßA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)). CONCLUSIONS: Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.

Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations.

Vitamin D deficiency {defined by the blood concentration of 25-hydroxyvitamin D [25(OH)D]} has been associated with many adverse health outcomes. Genetic and nongenetic factors account for variation in 25(OH)D, but the role of interactions between these factors is unknown. To assess this, we examined 1204 women of European descent from the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative Observational Study. Twenty-nine single nucleotide polymorphisms (SNPs) in 4 genes, GC, CYP2R1, DHCR7, and CYP24A1, from recent meta-analyses of 25(OH)D genome-wide association studies were genotyped. Associations between these SNPs and 25(OH)D were tested using generalized linear regression under an additive genetic model adjusted for age, blood draw month, and ancestry. Results were stratified by season of blood draw and, separately, vitamin D intake for the 6 SNPs showing a significant association with 25(OH)D at the P < 0.01 level. Two nonsynonymous SNPs in GC and 4 SNPs in CYP2R1 were strongly associated with 25(OH)D in individuals whose blood was drawn in summer (P ≤ 0.002) but not winter months and, independently, in individuals with vitamin D intakes ≥400 (P ≤ 0.004) but not <400 IU/d (10 µg/d). This effect modification, if confirmed, has important implications for the design of genetic studies for all health outcomes and for public health recommendations and clinical practice guidelines regarding the achievement of adequate vitamin D status.

Performance of a sheathless porous tip sprayer for capillary electrophoresis-electrospray ionization-mass spectrometry of intact proteins.

The performance of a prototype porous tip sprayer for sheathless capillary electrophoresis-mass spectrometry (CE-MS) of intact proteins was studied. Capillaries with a porous tip were inserted in a stainless steel needle filled with static conductive liquid and installed in a conventional electrospray ionization (ESI) source. Using a BGE of 100 mM acetic acid (pH 3.1) and a positively charged capillary coating, a highly reproducible and efficient separation of four model proteins (insulin, carbonic anhydrase II, ribonuclease A and lysozyme) was obtained. The protein mass spectra were of good quality allowing reliable mass determination of the proteins and some of their impurities. Sheath-liquid CE-MS using the same porous tip capillary and an isopropanol-water-acetic acid sheath liquid showed slightly lower to similar analyte responses. However, as noise levels increased with sheath-liquid CE-MS, detection limits were improved by a factor 6.5-20 with sheathless CE-MS. The analyte response in sheathless CE-MS could be enhanced using a nanoESI source and adding 5% isopropanol to the BGE, leading to improved detection limits by 50-fold to 140-fold as compared to sheath liquid interfacing using the same capillary - equivalent to sub-nM detection limits for three out of four proteins. Clearly, the sheathless porous tip sprayer provides high sensitivity CE-MS of intact proteins.