Publications

Abstract Nonrandom mating whereby parents are related is expected to cause a reduction in effective population size because their gene frequencies are correlated and this will increase the genetic drift. The published equation for the variance effective size, Ne, which includes the possibility of nonrandom mating, does not take into account such a correlation, however. Further, previous equations to predict effective sizes in populations with partial sib mating are shown to be different, but also incorrect. In this paper, a corrected form of these equations is derived and checked by stochastic simulation. For the case of stable census number, N, and equal progeny distributions for each sex, the equation is [formula: see text], where Sk2 is the variance of family size and alpha is the departure from Hardy-Weinberg proportions. For a Poisson distribution of family size (Sk2 = 2), it reduces to Ne = N/(1 + alpha), as when inbreeding is due to selfing. When nonrandom mating occurs because there is a specified system of partial inbreeding every generation, alpha can be substituted by Wright's FIS statistic, to give the effective size as a function of the proportion of inbred mates.

Valsartan administration at bedtime as opposed to on wakening improves the sleep time–relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest (≈24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4±12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time–relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time–relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.

Abstract Myristica fragrans (Houtt.) is an evergreen tree native to the Maluku Islands, Indonesia. M . fragrans kernel is extensively used in Indian traditional medicines to treat various diseases. Several studies attempt to compile and interpret the pharmacological potential of Myristica fragrans (Houtt.) aqueous and various chemical extracts. Thus, the pharmacological potential of nutmeg essential oil has not been reviewed phytochemically and pharmacologically. Therefore, the present study aimed to share appropriate literature evidence regarding the plant essential oil chemical composition and therapeutic potential of Myristica fragrans essential oil (MFEO). MFEO of leaf, mace, kernel, and seed were used worldwide as potential Ayurvedic medicine and fragrance. MFEO extracted by various methods and oil yield was 0.7–3.2, 8.1–10.3, 0.3–12.5, and 6.2–7.6% in leaf, mace, seed, and kernel. The primary chemical constituents of MFEO were sabinene, eugenol, myristicin, caryophyllene, β‐myrcene, and α‐pinene. Clinical and experimental investigations have confirmed the antioxidant, antimicrobial, antiinflammatory, anticancer, antimalarial, anticonvulsant, hepatoprotective, antiparasitic, insecticidal, and nematocidal activities of MFEO. It is the first attempt to compile oil yield, composition, and the biological activities of MFEO. In future, several scientific investigations are required to understand the mechanism of action of MFEO and their bioactive constituents.

Abstract Multicolor fluorescent containers : A silica coating procedure has been devised for the preparation of multifluorescent dye‐loaded zeolite L crystals with luminescent anisotropic cores and isotropic shells. The method comprises a combination of the polyelectrolyte layer‐by‐layer technique and Stöber synthesis (see scheme, TEM image, and fluorescence microscopy images). magnified image

In the first 25 generations of his classical mutation accumulation experiment, T. Mukai estimated a large rate of early linear decay for the relative viability of Drosophila melanogaster chromosome II (Δ M II = 0.004). Mukai forced through zero the regression of viability decline on generation number, but it has recently been shown (Fry, 2001) that a similar decline (Δ M II = 0.006) is obtained from unforced regression even if generation 32 instead of generation 25 (whose validity has been questioned) is included. We show that, from the perspective of the whole long-term experiment, it is hard to decide up to which generation viability can be considered to decline linearly. Depending on this decision, and on whether or not the regression is forced through the origin, very different estimates are obtained. Furthermore, the particular behaviour of the lines used as control suggests that they could have been different from the remaining lines at the beginning of the experiment, and casts doubts on the adequacy of a forced regression. Estimates from the linear unforced regression (Δ M II = 0.011) or from the linear term in a quadratic unforced regression (Δ M II = 0.001) are very different. The data fit both models very well, and the choice between them should be based on biological grounds.

Blood pressure (BP) follows a circadian variation, increasing during active hours, showing a small postprandial valley and a deeper decrease during sleep. Nighttime reduction of 10–20% relative to daytime BP is defined as a dipper pattern, and a reduction of less than 10%, as a non-dipper pattern. Despite this BP variability, hypertension’s diagnostic criteria and therapeutic objectives are usually based on BP average values. Indeed, studies have shown that chrono-pharmacological optimization significantly reduces long-term cardiovascular risk if a BP dipper pattern is maintained. Changes in the effect of antihypertensive medications can be explained by circadian variations in their pharmacokinetics (PK) and pharmacodynamics (PD). Nevertheless, BP circadian variation has been scarcely included in PK-PD models of antihypertensive medications to date. In this work, we developed PK-PD models that include circadian rhythm to find the optimal dosing time ( Ta ) of first-line antihypertensive medications for dipper and non-dipper patterns. The parameters of the PK-PD models were estimated using global optimization, and models were selected according to the lowest corrected Akaike information criterion value. Simultaneously, sensitivity and identifiability analysis were performed to determine the relevance of the parameters and establish those that can be estimated. Subsequently, Ta parameters were optimized to maximize the effect on BP average, BP peaks, and sleep-time dip. As a result, all selected models included at least one circadian PK component, and circadian parameters had the highest sensitivity. Furthermore, Ta with which BP>130/80 mmHg and a dip of 10–20% are achieved were proposed when possible. We show that the optimal Ta depends on the therapeutic objective, the medication, and the BP profile. Therefore, our results suggest making chrono-pharmacological recommendations in a personalized way.

Flavonoids from Marchantia convoluta (MCF) were studied for their ability to inhibit the proliferation of 2.2.15 cells. All concentration of MCF inhibited the secretion of HBsAg and HBeAg in the cultured medium by 2.2.15 cells. Analysis of morphological changes of MCF-treated cells by phase-contrast microscopy revealed a possible mode of action for MCF: inhibition of proliferation of 2.2.15 cells by inducing apoptosis.

A High Performance Ion Chromatographic (HPIC) method for the determination of nine components in Bayer liquors was reported.Formic, acetic, propionic, oxalic, succinic, glutaric anion, F -, Cl -, and SO 4 2-were separated and determined by High Performance Ion Chromatography with conductivity detector.The analytes were removed from Bayer liquor by using an ion-exchange resin column.The chromatographic separation was achieved with only one IonPac AS11-HC column thermostated at 30 °C.The precision results showed that the repeatability and reproducibility were <2.94 and <1.37%, respectively.The accuracy of the method was assessed by the recoveries ranging from 86.3 to 105.6 %.Under optimum conditions the detection limits ranged from 0.008 to 0.053 mg/l.

Mesenchymal stem cells (MSCs) are frequently employed in transplantation therapies for chronic inflammatory diseases. However, the impact of the inflammatory microenvironment on the functionality of MSCs remains poorly understood. Tumor necrosis factor-alpha (TNF-α) is a prevalent inflammatory mediator at transplantation sites, and prior research has indicated that the role of TNF-α in MSCs transplantation is ambiguous. The mechanisms by which TNF-α modulates the function of MSCs require further elucidation. To investigate this, we conducted comprehensive OLINK proteomic and transcriptomic analyses. The results showed After TNF stimulation, MSCs underwent apoptosis and aging, and their immune regulation, cell migration, and differentiation function were reduced. The signaling pathways involved include NF-KB, MAPK, stem cell pluripotency, etc. In conclusion, TNF activates the immune response of MSCs and impairs their stemness, thereby significantly affecting their capacity for cartilage differentiation.

The main aim of the present work was to evaluate the suitability of recycled paperboard coated on its internal face for use in containers that contact fried foods. Suitability was assessed in terms of overall migration into fatty food simulants and in terms of the residue extracted into n-heptane. Testing of the packaging was carried out following the guidelines laid down by the EU for plastic packaging, and also those established by the FDA for the extractive testing of paper and paperboard for use in food contact. With a view to simplifying the test procedures, the results of the official tests were compared with those obtained using alternative fatty food simulants under comparable sets of test conditions. The overall migration test using olive oil as the fatty food simulant was an adaptation of the European Committee for Standardization (CEN) test developed for plastic materials. Two methods for determination of the amount of olive oil absorbed by the paperboard during the tests were compared: a gravimetric method and a modification of the CEN gas chromatographic method. Finally, the packaging materials were extracted with solvents of several different polarities in order to develop a test allowing preliminary identification of major potential migrating components in paperboard contributing to EU overall migration levels and FDA extractive levels. Keywords: Food safety; recycled paperboard coated for food contact; EU overall migration tests; FDA extractive tests; fatty food contact

Preeclampsia and gestational hypertension are major contributors to perinatal morbidity and mortality. Several studies aimed to test the effects of low-dose aspirin (ASA) in the prevention of preeclampsia concluded that the beneficial effects of such treatment outweigh adverse ones. Such benefits have not been fully corroborated by larger randomized trials usually carried out in low-risk women, testing a dose of 60 mg/d ASA presumably ingested in the morning, and including women randomized as late as at 26-32 wks of gestation. The authors conducted a prospective, randomized, double-blind, placebo-controlled, chronotherapy trial on 350 high-risk pregnant women (183 nulliparous), 30.7 ± 5.3 (mean ± SD) yrs of age, and 13.5 ± 1.4 wks of gestation at the time of recruitment. Women were randomly assigned to one of six groups, defined according to treatment (placebo or ASA, 100 mg/d) and time of treatment: upon awakening, 8 h after awakening, or at bedtime. Intervention started at 12-16 wks of gestation and continued until delivery. Blood pressure (BP) was measured by ambulatory monitoring (ABPM) for 48-h at baseline, every 4 wks until the 7th month of gestation, every 2 wks thereafter until delivery, and at puerperium. The effects of ASA on ambulatory BP were markedly dependent on administration time: there was no effect on BP, compared with placebo, when ASA was ingested upon awakening, but the BP reduction was highly statistically significant when low-dose ASA was ingested 8 h after awakening and, to a greater extent, at bedtime (p < .001). At puerperium, 6-8 wks after discontinuation of treatment, there was no statistically significant difference in 24-h BP means between the groups of women who ingested ASA at different circadian times. Women ingesting low-dose ASA, compared with placebo, evidenced a significantly lower hazard ratio (HR) of serious adverse outcomes, a composite of preeclampsia, preterm delivery, intrauterine growth retardation (IUGR), and stillbirth (.35, 95% confidence interval [CI]: .22-.56; p < .001). The HR of individual outcome variables, i.e., preeclampsia, preterm delivery, IUGR, and gestational hypertension, were also significantly lower with ASA versus placebo (p always < .041). There were small and nonsignificant differences in outcomes between placebo and low-dose ASA ingested upon awakening. These four groups combined showed highly significant greater event rate of serious adverse outcomes than women ingesting ASA either in the evening or at bedtime (HR: .19, 95% CI: .10-.39; p < .001). There was no increased risk of hemorrhage, either before or after delivery, with low-dose ASA relative to placebo (HR: .57, 95% CI: .25-1.33; p = .194). Results indicate that (i) 100 mg/d ASA should be the recommended minimum dose for prevention of complications in pregnancy; (ii) ingestion of low-dose ASA should start at ≤16 wks of gestation; and (iii) low-dose ASA ingested at bedtime, but not upon awakening, significantly regulates ambulatory BP and reduces the incidence of preeclampsia, gestational hypertension, preterm delivery, and IUGR. ABPM evaluation at the first trimester of pregnancy provides sensitive endpoints for identification of women at high risk for preeclampsia who might benefit most from the cost-effective preventive intervention with timed low-dose ASA.