Mercury in the atmospheric and coastal environments of Mexico.
In Mexico, published studies relating to the occurrence of Hg in the environment are limited. Among the main sources of Hg in Mexico are mining and refining of Auand Hg, chloralkali plants, Cu smelting, residential combustion of wood, carbo electric plants, and oil refineries. Hg levels are highly variable in the atmospheric compartment because of the atmospheric dynamics and ongoing metal exchange with the terrestrial surface. In atmospheric studies, Hg levels are usually reported as total gaseous Hg (TGM). In Mexico, TGM values ranged from 1.32 ng m-3 in Hidalgo state (a rural agricultural area) to 71.82 ng m-3 in Zacatecas state (an area where brick manufacturers use mining wastes as a raw material).Published information on mercury levels in the coastal environment comprise 21 studies, representing 21 areas, in which sediments constituted the substrate that was analyzed for Hg. In addition, water samples were analyzed for Hg in nine studies.Few studies exist on Hg levels in the Caribbean and in the southwest of the country where tourism is rapidly increasing. Hence, there is a need for establishing baseline levels of mercury in these increasingly visited areas. In regions where studies have been undertaken, Hg levels in sediments were highly variable. Variations in Hg sediment levels mainly result from geological factors and the varying degree of anthropogenic impacts in the studied areas. In areas that still have pristine or nearly pristine environments (e.g., coast, Baja California, Todos Santos Bay, and La Paz lagoon), sediment Hg levels ranged from <0.006 to 0.35 j.lg g-1 on a dry wt basis.When higher levels exist (0.34-57.94 j.lg g-1 on a dry wt basis), the environment generally shows the influence of inputs from mining, oil processing, agriculture,geothermal events, or harmful algal bloom events (e.g., Guaymas Bay and Coatzacoalcos estuary). From chronological studies performed in selected coastal lagoons in NW Mexico, it is clear that Hg fluxes to sediments have increased from2- to 15-fold in recent years. Since the 1940s, historical increases of Hg fluxes have resulted from higher agricultural waste releases and exhaust from the thermo electric plants. The levels of Hg in water reveal a moderate to elevated contamination of some Mexican coastal sites. In Urias lagoon (NW Mexico), moderate to high levels were found in the dissolved and suspended fraction, and these are related to shipping, the fishing industry, domestic effluents, and the presence of a thermoelectric plant. In Coatzacoalcos (SE Mexico), extremely elevated Hg levels were found during the decade of the 1970s. Low to moderate levels of Hg were measured in waters from the Alvarado lagoon (SE Mexico); those concentrations appear to be associated with river waters that became enriched with organic matter and suspended solids inthe brackish mixing zone.Regarding the Hg content in invertebrates, the use of bivalves (oysters and mussels)as biomonitors must be established along the coastal zones of Mexico, because some coastal lagoons have not been previously monitored. In addition, more research is needed to investigate shrimp farms that are associated with agricultural basins and receive effluents from several anthropogenic sources (e.g., mining activity and urban discharges). Hg residues in several vertebrate groups collected in Mexico have been studied.These include mammals, birds, reptiles, and fish. In elasmobranch species, the highest Hg concentration (27.2 flg g-1 dry wt) was found in the muscle of the smooth hammer head shark (Sphyrna zygaena). Teleost fish are the vertebrate group that has been most studied, with regard to Hg residue content; the highest value (5.67 11g g-1dry wt) was detected in the striped marlin (T. audax). Among reptiles, only marine turtles were studied; Hg levels found ranged from 0.795 in the liver to 0.0006flg g-1dry wt in the blood of L. olivacea. In birds, the highest Hg concentration (5.08 flg g-1dry wt) detected was in the liver of the olivaceous cormorant (P. olivaceous).Specimens from stranded marine mammals were also analyzed; levels of Hg ranged from 70.35 flg g-1 dry wt in the liver of stranded spinner dolphin (S. longirostris ), to0.145 flg g-1 dry wt in the muscle of gray whale (E. robustus). The presence of Hgin these marine animals is not thought to have caused the stranding of the animals.Other organisms like macroalgae and vestimentiferan tube worms were used to monitor the occurrence of Hg in the aquatic environment; levels were comparable to data reported on similar organisms from other areas of the world. Few investigation shave been carried out concerning the mercury content in human organs/tissues in Mexico. Considering the potential deleterious effects of Hg on kidney, lung, and the central nervous system, more information about human exposure to organic and inorganic forms of mercury and their effects is needed, both in Mexico and elsewhere.


EQ-VT protocol: one-size-fits-all? Challenges and innovative adaptations used in Egypt: a cross-sectional study.
To present the challenges and adaptations done to the EuroQol Valuation Technology (EQ-VT) protocol to fit the Egyptian culture during the extensive pilot phase of the Egyptian EuroQol 5 Dimension five level (EQ-5D-5L) valuation study DESIGN: This study was a cross-sectional, interviewer-administered face-to-face survey of representative Egyptians using the Arabic version of the EuroQol Group Valuation Technology (EQ-VT-2.1) and a country specific questionnaire pertaining to participants' demographics and opinions about health, life and death SETTING: Participants were recruited from workplaces, university campuses, sporting clubs, shopping malls and other public areas from different Egyptian governorates representing all geographical areas of the country. A total of 1378 participants were interviewed from July 2019 to March 2020 by 12 interviewers to select a representative sample in terms of: geographical distribution, age and gender, of which 75 participants did not complete the interview, 298 interviews were pilot and 1005 interviews were real of which 974 interviews were used for the valuation study. Two participants did not complete the country-specific questionnaire but completed the valuation protocol; therefore, 1301 interviews were included in the final analysis of country specific questions. Some modifications were applied to the protocol. The 'wheelchair example' was modified to 'migraine example' since most of the participants in the pilot interviews considered being in a wheelchair 'worse than dead'. There was some ambiguity in the Egyptian translated version for the EQ-5D-5L between levels 4 and 5 of the pain and depression dimensions. This was overcome by using colour coding to express the different levels of severity. A pictorial representation for the EQ-5D-5L health states was used to interview illiterate and less educated participants. In the Egyptian valuation study, the modifications made to the EQ-VT protocol made it feasible and culturally acceptable to the Egyptian participants.


The stability of early adenovirus mRNA is controlled by the viral 72 kd DNA-binding protein.
H5ts125, a temperature-sensitive mutant of adenovirus type 5, is restricted to the early phase of infection when grown at the nonpermissive temperature. One phenotype of the virus is the overproduction of early viral mRNA at the nonpermissive temperature relative to levels found in wild-type-infected cells, although normal levels are found at the permissive temperature. We have analyzed this phenomenon for the production of RNA from two specific early viral transcription units, E1A and E1B. Transcription rates from both of these regions were found to be the same in ts125-infected cells as in wild-type-infected cells at the nonpermissive temperature. However, when the cytoplasmic stabilities of the E1A and E1B mRNAs were measured in wild-type- and ts125-infected cells, it was found that at the nonpermissive temperature, the RNAs were 3 to 5 times more stable in a ts125 infection than in a wild-type infection. Since the mutation in ts125 maps to the gene for the 72 kd DNA-binding protein, these results imply that a functional 72 kd protein is required for the rapid turnover of early viral mRNA in wild-type-infected cells, indicating that the abundance of early viral mRNA is controlled by the 72 kd DNA-binding protein.


Synthesis and evaluation of quinoxalinones as HIV-1 reverse transcriptase inhibitors.
A series of 3,3-disubstituted quinoxalinones was prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The N-allyl (6b and 6f), N-cyclopropylmethyl (6a, 6g, 6h, and 6k) and N-carboalkoxy (6m-6y) substituted compounds displayed activity comparable or better than Efavirenz and GW420867X.


Tobacco product use and susceptibility to use among sexual minority and heterosexual adolescents.
Sexual identity is associated with tobacco use in adults. We examined tobacco use and susceptibility to use by sexual identity in adolescents. Data were collected in February 2019 via Qualtrics research participant panels. Data analyses were performed in June 2019 and updated in October 2020. Respondents aged 13-17 reported sexual identity (heterosexual vs. sexual minority [lesbian, gay, bisexual, or other]), past-month and lifetime tobacco product use, susceptibility to e-cigarette use, friend(s)' e-cigarette use, tobacco marketing exposure, and demographic characteristics. The sample (n=983) was 72.9% female, 46.5% non-Hispanic white, and 26.1% sexual minority with a mean age of 15.0 years (SD=1.4). Sexual minority adolescents were more likely to have friend(s) who vape (53.0% versus 42.0%; p=0.003). In adjusted models, sexual minority adolescents had greater odds of ever smoking tobacco (odds ratio [OR]=2.06; 95% confidence interval [CI]: 1.42-2.98) or using e-cigarettes (OR=1.55; 95% CI: 1.08-2.25) relative to heterosexual adolescents. Past-month tobacco smoking and e-cigarette use did not differ by sexual identity. Among participants who had never used tobacco products, sexual minority adolescents reported greater susceptibility to e-cigarette use (OR=1.62; 95% CI: 1.04-2.52) compared to heterosexual adolescents. Exposure to cigarette and e-cigarette marketing, e-cigarette use by friends, and respondent sex were significant covariates in all models. The current findings indicate greater susceptibility to use e-cigarettes and greater tobacco product initiation, but not continuation, among sexual minority adolescents. Sexual minority-tailored interventions may be warranted to prevent tobacco product initiation. Worth exploring are the associations between sexual identity, tobacco marketing exposure, and friend(s)' e-cigarette use.


Role of white blood cell and neutrophil counts in predicting spontaneous stone passage in patients with renal colic.
To determine the clinical, imaging and laboratory variables that can predict spontaneous passage of ureteral stones causing renal colic and the role of white blood cell (WBC) and neutrophil counts for the prediction of spontaneous calculi passage. A total of 156 patients who were referred to the emergency department complaining of renal colic due to a ureteral stone entered the analysis. Several clinical, laboratory and imaging parameters were evaluated for their potential ability to predict stone passage in a time interval of 1 month. The study design had two objectives. Primarily we analyzed all patients irrespective of stone size and secondly we analyzed patients with calculi of 10 mm maximum length. Spontaneous stone passage was observed in 96 (61.5%) patients in the overall population and in 84 (65.1%) of 129 patients with calculi <10 mm. Increased concentrations of serum WBCs and neutrophils at the time of the acute phase of a renal colic were associated with increased likelihood of spontaneous passage. In the multivariate analyses we found that WBC and neutrophil counts were the most important predictors of stone elimination. Active surveillance of patients suffering from ureteral lithiasis is an acceptable option. Identifying the parameters which can predict those patients who will mostly benefit from this is of great importance. Based on our results, WBC and neutrophil counts should be considered when patients with renal colic secondary to ureteral calculi are evaluated since they can significantly add to spontaneous elimination prediction. Their consideration in addition to other important factors, like stone size and location, would maximize their predictive ability.


Optical characteristics of the skin with dark circles using pump-probe imaging.
Pump-probe imaging was first used for quantitative analysis of melanin in dark circles' skin to improve the ability to diagnose and treat dark circles on human skin. This study aimed to compare the distribution characteristics in melanin of lower eyelid skin tissues and to determine whether pump-probe imaging has potential for the classification of dark circles in vivo. Specimens obtained from 15 patients undergoing blepharoplasty were examined using pump-probe imaging. Furthermore, adjacent slices were respectively treated with hematoxylin-eosin (HE) and ferrous sulfate (FeSO4) staining for cross-references. Subsequently, the melanin content index (MCI) and mean fluorescence intensity (MFI) were quantitatively analyzed by the pump-probe imaging. The distribution of melanin granules in the pump-probe image and FeSO4 staining was consistent. Meanwhile, the tissues of the skin with dark circles and normal skin demonstrated significant differences in MCI and MFI. These differences can be used to distinguish the skin with dark circles from the normal skin. Pump-probe imaging could be used for the analysis of the microstructure and spectral characteristics of melanin granules in skin with dark circles. Significant differences were noted between the pigmented type of dark circles and the other two groups (normal skin and the vascular type of dark circles), while no significant differences were found between normal skin and the vascular type of dark circles.


Multi-modal MRI Reveals the Neurovascular Coupling Dysfunction in Chronic Migraine.
Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.


Predictive role of endometrial T-bet/GATA3 ratio during mid-luteal phase for live birth in patients undergoing in vitro fertilization: A retrospective observational study.
To investigate whether endometrial T-bet (Th1 lineage-committed transcription factor)/GATA3 (Th2 lineage-committed transcription factor) ratio has predictive potential for embryo implantation in infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). We performed a retrospective observational study. In total, this study included 319 infertile women (253 women as the development cohort and 66 women as the validation cohort). Samples were obtained by endometrial scratching in the mid-luteal phase before IVF-ET treatment. Immunohistochemistry was utilized to analyze the expression levels of T-bet and GATA3 in the endometrium. Predictive value of endometrial T-bet/GATA3 for live birth were analyzed. In the development cohort, the T-bet/GATA3 ratio was significantly lower in women with live birth than those patients with non-live birth [0.148 (0.101, 0.212) vs. 0.246 (0.170, 0.399), P<0.0001]. In the validation cohort, changes in endometrial T-bet/GATA3 were similar among these groups. The endometrial T-bet/GATA3 ratio was an independent predictor of live birth after correction for patient age, anti-Mullerian hormone (AMH), quality of embryos transferred and other clinical characteristics (aOR = 0.280, 95 % CI: 0.169-0.462, P<0.001). We developed and validated that an endometrial T-bet/GATA3 ratio at the cut-off of 0.22 had significant predictive value for live birth (developmental cohort: AUC = 0.76, 95 % CI: 0.70-0.81, P < 0.0001. validation cohort: AUC = 0.85 95 % CI: 0.76-0.95, P < 0.0001). Our results suggest that elevated endometrial T-bet/GATA3 ratio is an independent marker of live birth in infertile patients.


OSMAC strategy integrated with molecular networking discovery peniciacetals A-I, nine new meroterpenoids from the mangrove-derived fungus Penicillium sp. HLLG-122.
Nine new highly oxygenated meroterpenoids, peniciacetals A-I (1-9), along with five known analogues (10-14) were isolated from the mangrove-derived fungus Penicillium sp. HLLG-122 based on the guidance of molecular networking and OSMAC approach. Peniciacetals A-B (1-2) were characterized with a unique 6/6/6/6/5 pentacyclic system possessing an unusual 4,6-dimethyl-2,5-dioxohexahydro-6-carboxy-4H-furo[2,3-b]pyran moiety. Peniciacetals C-D (3-4) possessed an uncommon 3,6-dimethyldihydro-4H-furo[2,3-b]pyran-2,5-dione unit with 6/6/6/5/6 fused pentacyclic skeleton. The structures and absolute configurations of new compounds were elucidated by HR-ESI-MS, 1D and 2D NMR spectroscopic data, X-ray diffraction analysis, and quantum chemical electronic circular dichroism (ECD) calculation. The plausible biosynthetic pathway of 1-9 were also proposed. Compound 14 showed good cytotoxicity against HepG2, MCF-7, HL-60, A549, HCT116 and H929 cell with IC50 values of 6.6, 14.8, 3.2, 5.7, 6.9 and 3.0 μM, respectively. Further research showed that the compound 14 induced necrosis or late apoptosis contributes to the HL-60 cells toxicity.


Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study.
Previous studies have demonstrated an association between HIV infection and coronary artery disease (CAD); little is known about potential associations between HIV infection and extra-coronary calcification (ECC). We analyzed 621 HIV infected (HIV+) and 384 HIV uninfected (HIV-) men from the Multicenter AIDS Cohort Study who underwent non-contrast computed tomography (CT) from 2010-2013. Agatston scores were calculated for mitral annular calcification (MAC), aortic valve calcification (AVC), aortic valve ring calcification (AVRC), and thoracic aortic calcification (TAC). The associations between HIV infection and the presence of each type of ECC (score > 0) were evaluated by multivariable logistic regression. We also evaluated the association of ECC with inflammatory biomarker levels and coronary plaque morphology. Among HIV+ and HIV- men, the age-standardized prevalences were 15% for TAC (HIV+ 14%/HIV- 16%), 10% for AVC (HIV+ 11%/HIV- 8%), 24% for AVRC (HIV+ 23% HIV- 24%), and 5% for MAC (HIV+ 7%/HIV- 3%). After adjustment, HIV+ men had 3-fold greater odds of MAC compared to HIV- men (OR = 3.2, 95% CI: 1.5-6.7), and almost twice the odds of AVC (1.8, 1.1-2.9). HIV serostatus was not associated with TAC or AVRC. AVRC was associated with higher Il-6 and sCD163 levels. TAC was associated with higher ICAM-1, TNF-α RII, and Il-6 levels. AVC and AVRC calcification were associated with presence of non-calcified plaque in HIV+ but not HIV- men. HIV infection is an independent predictor of MAC and AVC. Whether these calcifications predict mortality in HIV+ patients deserves further investigation.


The cyclo-oxygenase inhibitor, piroxicam, enhances cytokine-induced lymphocyte proliferation in vitro and in vivo.
The effects of Piroxicam on the production and activity of lymphoproliferative cytokines (LC) produced by mononuclear phagocytes (MNP) were examined. In vitro, Piroxicam did not affect IL-1 induced thymocyte proliferation (LAF assay). However, the LAF activity from lipopolysaccharide (LPS)-treated MNP cultures was increased after Piroxicam (0.1-20 mumol/L) treatment. The increase in apparent LC activity was largely due to suppression of prostaglandin E2 (PGE2) production. Peripheral blood, spleen and thymus lymphocytes from animals predosed with Piroxicam (5 mg/kg per day for 3 days) synthesized more DNA than untreated mice (as measured by [3H]-thymidine uptake ex vivo). MNP from Piroxicam-treated animals produced significantly more LC. Piroxicam had similar effects in both inflamed and non-inflamed mice. Piroxicam and other non-steroidal anti-inflammatory drugs (NSAID) may therefore stimulate or modulate the immune functions requiring lymphoproliferation by suppressing the formation of PGE2, a natural inhibitor of both LC production and LC-induced lymphoproliferation.


Regulation of cyclic AMP accumulation by peptide hormone receptors in immunocytochemically defined astroglial cells.
Primary cultures of neonatal murine brain have been reported to express multiple receptors that regulate adenylate cyclase activity. Since for the most part these results were obtained with mixed cell cultures, it has been difficult to define receptor profiles for specific cell types. With this concern in mind a series of studies has been initiated designed to identify specific receptors present on highly purified, immunocytochemically defined astroglia derived from the cerebral cortices of neonatal rats. In this study the capacity of a variety of peptide hormones to regulate cyclic AMP metabolism in these cells was examined. Fibroblasts derived from the meninges represent a predictable source of contamination in primary CNS culture. Thus, to assign more clearly specific receptors to the astroglial cell population, receptor-mediated regulation of cyclic AMP accumulation was also examined in fibroblasts. Cyclic AMP accumulation in astroglia was stimulated by catecholamines (acting at beta 1-adrenergic receptors), prostaglandin E1, vasoactive intestinal polypeptide, alpha-melanocyte-stimulating hormone, and adrenocorticotropin. Bombesin, luteinizing hormone-releasing hormone, neurotensin, thyrotropin-releasing hormone, somatostatin, secretin, and vasopressin did not significantly increase cyclic AMP levels in these cultures. Catecholamines, acting at alpha 2-adrenergic receptors, and somatostatin inhibited agonist-stimulated cyclic AMP accumulation. In meningeal cell cultures catecholamines (acting at beta 2- and alpha 2-adrenergic receptors) and prostaglandin E1 regulated cyclic AMP levels. However, vasoactive intestinal peptide did not stimulate and somatostatin did not inhibit cyclic AMP accumulation in these cells.


Xanthohumol hinders invasion and cell cycle progression in cancer cells through targeting MMP2, MMP9, FAK and P53 genes in three-dimensional breast and lung cancer cells culture.
Despite recent advances in the treatment of lung and breast cancer, the mortality with these two types of cancer is high. Xanthohumol (XN) is known as a bioactive compound that shows an anticancer effect on cancer cells. Here, we intended to investigate the anticancer effects of XN on the breast and lung cancer cell lines, using the three-dimensional (3D) cell culture. XN was isolated from Humulus lupulus using Preparative-Thin Layer Chromatography (P-TLC) method and its authenticity was documented through Fourier Transform Infrared spectroscopy (FT-IR) and Hydrogen Nuclear Magnetic Resonance (H-NMR) methods. The spheroids of the breast (MCF-7) and lung (A549) cancer cell lines were prepared by the Hanging Drop (HD) method. Subsequently, the IC50s of XN were determined using the MTT assay in 2D and 3D cultures. Apoptosis was evaluated by Annexin V/PI flow cytometry and NFκB1/2, BAX, BCL2, and SURVIVIN expressions. Cell cycle progression was determined by P21, and P53 expressions as well as PI flow cytometry assays. Multidrug resistance was investigated through examining the expression of MDR1 and ABCG2. The invasion was examined by MMP2, MMP9, and FAK expression and F-actin labeling with Phalloidin-iFluor. While the IC50s for the XN treatment were 1.9 µM and 4.74 µM in 2D cultures, these values were 12.37 µM and 31.17 µM in 3D cultures of MCF-7 and A549 cells, respectively. XN induced apoptosis in MCF-7 and A549 cell lines. Furthermore, XN treatment reduced cell cycle progression, multidrug resistance, and invasion at the molecular and/or cellular levels. According to our results of XN treatment in 3D conditions, this bioactive compound can be introduced as an adjuvant anti-cancer agent for breast and lung cancer.


Circadian misalignment on submarines and other non-24-h environments - from research to application.
Circadian clocks have important physiological and behavioral functions in humans and other organisms, which enable organisms to anticipate and respond to periodic environmental changes. Disturbances in circadian rhythms impair sleep, metabolism, and behavior. People with jet lag, night workers and shift workers are vulnerable to circadian misalignment. In addition, non-24-h cycles influence circadian rhythms and cause misalignment and disorders in different species, since these periods are beyond the entrainment ranges. In certain special conditions, e.g., on submarines and commercial ships, non-24-h watch schedules are often employed, which have also been demonstrated to be deleterious to circadian rhythms. Personnel working under such conditions suffer from circadian misalignment with their on-watch hours, leading to increased health risks and decreased cognitive performance. In this review, we summarize the research progress and knowledge concerning circadian rhythms on submarines and other environments in which non-24-h watch schedules are employed.


Specific response of soil properties to microplastics pollution: A review.
The soil environment is a critical component of the global ecosystem and is essential for nutrient cycling and energy flow. Various physical, chemical, and biological processes occur in the soil and are affected by environmental factors. Soil is vulnerable to pollutants, especially emerging pollutants, such as microplastics (MPs). MPs pollution has become a significant environmental problem, and its harm to human health and the environment cannot be underestimated. However, most studies on MPs pollution have focused on marine ecosystems, estuaries, lakes, rivers, and other aquatic environments, whereas few considered the effects and hazards of MPs pollution of the soil, especially the responses of different environmental factors to MPs. In addition, when many MPs pollutants produced by agricultural activities (mulching film, organic fertilizer) and atmospheric sedimentation enter the soil environment, it will cause changes in soil pH, organic matter composition, microbial community, enzyme activity, animals and plants and other environmental factors. However, due to the complex and changeable soil environment, the heterogeneity is very strong. The changes of environmental factors may react on the migration, transformation and degradation of MPs, and there are synergistic or antagonistic interactions among different factors. Therefore, it is very important to analyze the specific effects of MPs pollution on soil properties to clarify the environmental behavior and effects of MPs. This review focuses on the source, formation, and influencing factors of MPs pollution in soil and summarizes its effect and influence degree on various soil environmental factors. The results provide research suggestions and theoretical support for preventing or controlling MPs soil pollution.


Official recommendations for vitamin D through the life stages in developed countries.
Inadequate vitamin D nutritional status is prevalent worldwide and has been associated with autoimmune disorders, heart disease, deadly cancers, insulin resistance, inflammation, neurological disorders, adverse outcomes in pregnancy, and increased risk for mortality. Expert recommendations for vitamin D intake differ between governmental agencies and practice guidelines from medical societies due to differences in the definition of vitamin D deficiency, insufficiency and sufficiency based on serum 25-hydroxyvitamin D [25(OH)D] concentrations. In addition, separate health promotion bodies also provide targeted recommendations for the prevention of specific disorders such as reducing risk for developing some cancers and autoimmune diseases. We review and provide perspectives regarding various recommendations from the Institute of Medicine (IOM, United States) and Health Canada, the European Food Safety Authority (EFSA), the Scientific Advisory Committee on Nutrition (SACN; United Kingdom), the World Health Organization, the Endocrine Society and other expert groups by life stage as a guide intended for clinician use.


[Flicker perimetry (CFF) in patients with lens opacities--first report].
Comparison of standard W/W and CFF perimetry in patients with cataract and lens opacities. Visual field was measured on Octopus 301 perimeter with option flicker perimetry. W/W and CFF perimetry (Program G1 in TOP strategy) was performed in 44 eyes with cataract and lens opacities. Defects in visual field with CFF perimetry were found in 24% of cases but with W/W perimetry in 100% of cases. Perimetry CFF is a new tool for early detection and follow up of visual field defects in patients with cataract and lens opacities.


The natural history of the anterior cruciate ligament-deficient knee. A review.
The ACL-deficient knee has been a management dilemma for many years and, to this day, no refutable plan exists for treatment of this injury. No true prospective study has been performed that evaluates all types of individuals at a variety of activity levels, and, in this day of apparently reliable methods of reconstructing the ACL, it is doubtful that one will occur. The ACL injury is no longer a mystery to the general public; it has received extensive publicity because of injuries of professional athletes and the successful reconstruction in many of these athletes. This article has not completely cleared up the issue of the future of an ACL-deficient knee. It has provided, however, convincing evidence that an active individual with a nonfunctional ACL is susceptible to meniscus injury (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). There is also the risk of more tears occurring with time. Bray and Dandy found in their follow-up of patients with ACL repairs that, if the pivot shift returned, these patients had a much higher incidence of meniscus tears. Many of these studies indicate that, if the meniscus cannot be repaired and requires partial meniscectomy or worse, the articular surface will deteriorate (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). Satku et al showed only 11% incidence of radiographic changes in patients with ACL-deficient knees with no evidence of meniscus tears compared with 100% in those having meniscectomy more than 5 years previously. Activity levels in general also change following this injury. This is probably the most difficult area to assess. Even though a substantial number of persons returned to their preinjury level of activity, it is not always possible to determine if they are playing with the same behavior and attitude. In other words, athletes who are involved in sports with cutting and jumping may modify the need for these activities and yet remain relatively competitive depending on their previous level of skill and the position they play. It has also been shown that many athletes return to their preinjury level initially but with time have significant increase in their symptoms and must modify their level of participation. More individuals limited their activities from the beginning than returned to their preinjury level (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). Instability varies in these individuals and, as in Chick and Jackson's patients, those with mild instability (no rotatory instability) may do reasonably well.(ABSTRACT TRUNCATED AT 400 WORDS)


IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist.
This is the first large pharmacogenetic investigation of the inflammatory IL-4/IL-13 pathway in patients with moderate-to-severe asthma. We analyzed genomic DNA from participants in a 12-week placebo-controlled efficacy trial of pitrakinra (1, 3, or 10 mg twice daily), a novel IL-4/IL-13 pathway antagonist (Clinicaltrials.govNCT00801853). The primary hypothesis for this analysis is that amino acid changes in the 3' end of the IL-4 receptor α gene (IL4RA) or closely proximal variants would predict reductions in asthma exacerbations for subjects randomized to pitrakinra therapy. Nineteen IL4RA single nucleotide polymorphisms (SNPs) were tested in 407 non-Hispanic white subjects for association with the primary clinical end point of asthma exacerbations and changes in secondary end points for asthma symptom scores. The most consistent pharmacogenetic associations were observed for the correlated tagging SNPs rs8832 and rs1029489 in the IL4RA 3' untranslated and proximal regions, respectively. Subjects homozygous for the rs8832 common G allele randomized to pitrakinra (placebo group nonsignificant) had decreased asthma exacerbations and decreased nocturnal awakenings and activities limited by asthma. There was also a significant pitrakinra dose-response relationship (placebo/1 mg/3 mg/10 mg) for exacerbations in subjects homozygous for the common allele in rs1029489 (P = .005) and rs8832 (P= .009) and the intronic SNPs rs3024585, rs3024622, and rs4787956 (P = .03). This study demonstrates a significant pharmacogenetic interaction between anti-IL-4 receptor α therapy and IL4RA gene variation, identifying an asthma subgroup that is more responsive to therapy with this antagonist.


La terminologie juridique.
There are many ways to approach and analyze juridical terminology. Every approach is useful, even though for a great number of linguists juridical vocabulary is not really considered as a terminology. The first part of this paper is devoted to the presentation of the state of art in the field under scrutiny, including traditional approaches (savant language, technical language, pure language, 'general' theory of terminology) and more recent approaches (socioterminology, text mining terminology, communicative theory of terminology, frame terminology, sociocognitive approach, pragmaterminological approach). The second part explains how the philosophy of language can shed some light on juridical terminology. For this branch of human sciences, legal words and groups of words are lexical units used in legal discourses. Thus, relevant analysis perspectives include enunciation, reference, extension, predication and speech acts.


Health behaviour and its determinants in elderly patients with chronic diseases: evidence from Jiangsu Province, China.
Chronic disease is a major cause of mortality among elderly individuals in China, and treatment is a substantial public health burden. However, behavioural interventions may be more important than mere clinical treatment of these chronic diseases. The paper aimed to assess the health behaviour of a sample of elderly individuals with chronic diseases in Jiangsu Province, China and to identify how demographic characteristics influence health behaviour. Furthermore, the group that would likely need the most health intervention was identified. A version of the Health Promoting Lifestyle Profile II (HPLP-II) was adapted to Chinese to evaluate health behaviours in six dimensions: nutrition, tobacco and alcohol use, physical activity, stress management, health responsibility, and spiritual growth. Multistage random sampling was conducted from October 2020 to May 2021. Questionnaires incorporating the adapted HPLP-II were distributed to 900 elderly patients (i.e., aged 60 and above) with chronic diseases in the three sampled prefectures of Jiangsu Province; of these questionnaires, 791 were completed. Univariate t tests, principal component analysis, and multivariate linear regressions were employed in the analysis. The average total score of respondents on health behaviour was 73.73. The dimensions (ordered from highest to lowest scores) are as follows: "nutrition", "tobacco and alcohol use", "health responsibility", "spiritual growth", "stress management", and "physical activity". The multivariate linear regression suggested that the determinants (P < 0.05) of health behaviour (total score) were income, sex, age, relationship status, residence, and education. Elderly patients with chronic diseases in Jiangsu Province generally behaved in a healthy manner. "Physical activity", "stress management", and "spiritual growth" were the dimensions that would most benefit from health intervention, while elderly single/divorced/widowed patients with lower income and less education should be the target group for health intervention.


Meta-analysis of phase-specific survival after transcatheter versus surgical aortic valve replacement from randomized control trials.
Transcatheter aortic valve replacement (TAVR) is an established alternative to surgical aortic valve replacement (SAVR) for severe symptomatic aortic stenosis, although phase-specific survival and cause of death are implicated following these procedures. Herein, we conducted a phase-specific meta-analysis to compare outcomes after TAVR versus SAVR. A systematic search of databases was performed from inception through December 2022 to identify randomized controlled trials that compared outcomes of TAVR and SAVR. For each trial, the hazard ratio (HR) with 95% confidence interval (CI) of outcomes of interest was extracted for the following each specific phase: the very short-term (0-1 years after the procedure), short-term (1-2 years), and mid-term (2-5 years). Phase-specific HRs were separately pooled using the random-effects model. Our analysis included 8 randomized controlled trials, which enrolled a total of 8885 patients with a mean age of 79 years. The survival after TAVR compared with SAVR was greater in the very short-term periods (HR, 0.85; 95% CI, 0.74-0.98; P = .02) but similar in the short-term periods. In contrast, lower survival was observed in the TAVR group compared with the SAVR group in the mid-term periods (HR, 1.15; 95% CI, 1.03-1.29; P = .02). Similar temporal trends favoring SAVR in the mid-term were present for cardiovascular mortality and rehospitalization rates. In contrast, the rates of aortic valve reinterventions and permanent pacemaker implantations were initially greater in the TAVR group, although SAVR's superiority eventually disappeared in the mid-term. Our analysis demonstrated phase-specific outcomes following TAVR and SAVR.


Evoked responses to rhythmic visual stimulation vary across sources of intrinsic alpha activity in humans.
Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying 'source-level' activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from -0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms.


Microstructure and structural transition in microemulsions stabilized by aldonamide-type surfactants.
Significant efforts were undertaken to characterize the microstructure and structural properties of water-in-oil (w/o), oil-in-water (o/w), and bicontinuous (bc) microemulsions composed of N-alkyl-N-methylgluconamides (n-alkyl = n-C(12)H(25), n-C(14)H(29), n-C(16)H(33)) and n-alcohols (ethanol, n-propanol, n-butanol) or iso-alcohols (iso-propanol, iso-butanol) as cosurfactants, as well as iso-octane and water. The internal structure of so created four-component system was elucidated by means of an analysis of isotropic area magnitudes in phase diagrams and conductivity measurements. Dynamic light scattering (DLS) measurements provided the microemulsion size and polydispersity. Polarity and viscosity of microemulsion microenvironment were acquired by means of electron paramagnetic resonance (EPR), UV-vis absorption spectroscopy (in the case of w/o droplets), and steady-state fluorescence (SSF) (in the case of o/w droplets). The results show that both the surfactant and the cosurfactant types affect the shape and extent of microemulsions. The size of droplets depends strongly on the type of examined microemulsion and the type of cosurfactant (linear or brunched) but is almost independent of the length of the surfactant alkyl chain. The size of microemulsion droplets ranges from 8.1 to 22.6 nm and from 3.7 to 14.3 nm respectively, for o/w and o/w microemulsions, making them good candidates for both template-based reactions and household components solubilizing media.


On so-called atypical psychosis in early and mid-adolescence.
Twenty-three cases of adolescent atypical psychosis were reported, of which 12 were followed for more than three years (at the longest about 18 years). Our cases indicated apparent atypicalness in regard to the symptomatology and to the course, quite different from cyclothymic psychosis and schizophrenia. In an etiological point of view, hereditary predispositions were more frequently recognized in our cases than in schizophrenic cases, but because schizophrenics were found in the families of these patients, it was difficult for us to determine whether our cases belonged to an etiologically independent endogenous psychosis. However, we received the impression that atypical psychosis could be differentiated from others even in adolescents. But this psychosis was seldom found in childhood. While, through the comparison of these patients with adult cases and by considering previous research, we were led to the assumption that adolescent atypical psychosis might be understood as a minor pattern of the fully-developed psychosis in adults but was provided with many properties specific to adolescense.


New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders.
Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction. It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behavior, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several psychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors have provided clues regarding the function of these receptors in the human brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.


Sex Differences in the Gut-Brain Axis: Implications for Mental Health.
The purpose of this article is to highlight how sex differences in the gut-brain axis may contribute to the discrepancies in incidence of neurodevelopmental, psychiatric, and neurodegenerative disorders between females and males. We focus on autism spectrum disorder, psychotic disorders, stress and anxiety disorders, depression, Alzheimer's disease, and Parkinson's disease and additionally discuss the comorbidity between inflammatory bowel disorder and mental health disorders. Human and animal studies show that sex may modify the relationship between the gut or immune system and brain and behavior. Sex also appears to modify the effect of microbial treatments such as probiotics and antibiotics on brain and behavior. There is emerging evidence that assessing the role of sex in the gut-brain axis may help elucidate the etiology of and identify effective treatments for neurodevelopmental, psychiatric, and neurodegenerative disorders.


The impact of temperature on balancing immune responsiveness and growth in Arabidopsis.
Plants have evolved polymorphic immune receptors to recognize pathogens causing disease. However, triggering of resistance needs to be tuned to the local environment to maintain a balance between defense and growth. We consider here the impact of temperature as a key environmental factor influencing immune pathway activation in Arabidopsis. Genetic compensatory and molecular buffering mechanisms affecting the diversification, functionality and subcellular dynamics of immune receptors, reveal multiple points at which temperature intersects with host resistance signaling systems, including a role of at least one receptor in sensing temperature change. Analysis of temperature-dependent autoimmunity caused by allelic mismatches in hybrids of evolutionary diverged Arabidopsis accessions is illuminating processes by which plants maintain 'poise' between immune responsiveness and fitness in natural populations.


Plant tissue extraction for metabolomics.
Plants are not only important producers of foods and energy storages (e.g., sugars, carbohydrates, proteins, and fats) in the form of grains, fruits, and vegetables, they also provide many valuable products to human existence including wood, fibers, oils, resins, pigments, antioxidants, and sources of medicine. Most importantly in light of this book, plants have been a source of therapeutic and health promoting compounds throughout history. This chapter describes several essential considerations for the extraction process when aiming to study plant metabolism or to characterize the chemical composition of plant originated samples using metabolomics technologies.


Estimating the national cost of treating people with HIV disease: patient, payer, and provider data.
Existing estimates of the national cost of treating all people with HIV disease use data from a sample of people with HIV disease to extrapolate the cost of treating all people with HIV disease (patient-based approach). This study derives estimates using two novel approaches (i.e., payer-based and provider-based) and compares these with existing estimates. These include the Health Insurance Association of American and the American Council of Life Insurance 1996 HIV survey, the 1996 State Inpatient Databases (SID) maintained by the Agency for Healthcare Research and Quality, and the IMS America Ltd. survey of independent and chain drugstores. The cost of treating all people with HIV disease in 1996 was between $6.7 and $7.8 billion U.S., and the average annual cost of treating a person with HIV disease was between $20,000 and $24,700 U.S. Analysts should derive estimates of the cost of treating people with HIV disease using several different approaches. K


Changes in tidal breathing biomarkers as indicators of treatment response in AECOPD patients in an acute care setting.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a complication of COPD that typically necessitates intensified treatment and hospitalization. It is linked to higher morbidity, mortality and healthcare spending. Assessment of therapy response for AECOPD is difficult due to the variability of symptoms and limitations in current measures. Hence, there is a need for new biomarkers to aid in the management of AECOPD in acute care settings. Fifteen hospitalized AECOPD patients (GOLD 3-4) were enrolled in this study. Treatment response was assessed daily through clinical evaluations and by monitoring tidal breathing biomarkers (respiratory rate [RR], expiratory time [Tex], inspiratory time [Tin], expiratory pause [Trst], total breath time [Ttot]), using a novel, wearable nanosensor-based device (SenseGuard™). Patients who showed significant clinical improvement had substantial changes in ΔTex/Ttot (+14%), ΔTrst/Ttot (-18%), and ΔTin/Tex (+0.09), whereas patients who showed mild or no clinical improvement had smaller changes (+5%, +3%, and -0.03, respectively). Linear regression between change in physician's assessment score and the median change in tidal breathing parameters was significant for Tin/Tex (R2 = 0.449, ∗p = 0.017), Tex/Ttot (R2 = 0.556, ∗p = 0.005) and Trst/Ttot (R2 = 0.446, ∗p = 0.018), while no significant regression was observed for RR, Tin/(Trst + Tex) and Tin/Ttot. Our study demonstrates the potential of the SenseGuard™ to monitor treatment response in AECOPD patients by measuring changes in tidal breathing biomarkers, which were shown to be associated with significant changes in the patients' respiratory condition as evaluated by physicians. However, further large-scale clinical studies are needed to confirm these findings.


Wide complex tachycardia in a patient with non-ischemic cardiomyopathy: What is the diagnosis?
A 55-year-old male presented with acute heart failure and incessant wide complex tachycardia resembling an outflow tract ventricular tachycardia. Meticulous analysis of the electrocardiograms established the diagnosis of pre-excitation with prolonged atrio-ventricular (A-V) conduction over a decrementally conducting accessory A-V pathway. "Linking" between the accessory A-V pathway and normal A-V conduction system resulted in sustained maximal pre-excitation as well as periodic transition to normal A-V conduction without appreciable change in heart rate. Successful radiofrequency ablation of this unusual accessory A-V pathway was performed at the aortic-mitral junction. This ameliorated the mechanical dysynchrony, allowed discontinuation of hemodynamic/inotropic support, and resulted in sustained symptomatic improvement.


Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury.
The long-term functional recovery of traumatic brain injury (TBI) is hampered by pathological events, such as parenchymal neuroinflammation, neuronal death, and white matter injury. Krüppel-like transcription factor 11 (KLF 11) belongs to the zinc finger family of transcription factors and actively participates in various pathophysiological processes in neurological disorders. Up to now, the role and molecular mechanisms of KLF11 in regulating the pathogenesis of brain trauma is poorly understood. KLF11 knockout (KO) and wild-type (WT) mice were subjected to experimental TBI, and sensorimotor and cognitive functions were evaluated by rotarod, adhesive tape removal, foot fault, water maze, and passive avoidance tests. Brain tissue loss/neuronal death was examined by MAP2 and NeuN immunostaining, and Cresyl violet staining. White matter injury was assessed by Luxol fast blue staining, and also MBP/SMI32 and Caspr/Nav1.6 immunostaining. Activation of cerebral glial cells and infiltration of blood-borne immune cells were detected by GFAP, Iba-1/CD16/32, Iba-1/CD206, Ly-6B, and F4/80 immunostaining. Brian parenchymal inflammatory cytokines were measured with inflammatory array kits. Genetic deletion of KLF11 worsened brain trauma-induced sensorimotor and cognitive deficits, brain tissue loss and neuronal death, and white matter injury in mice. KLF11 genetic deficiency in mice also accelerated post-trauma astrocytic activation, promoted microglial polarization to a pro-inflammatory phenotype, and increased the infiltration of peripheral neutrophils and macrophages into the brain parenchyma. Mechanistically, loss-of-KLF11 function was found to directly increase the expression of pro-inflammatory cytokines in the brains of TBI mice. KLF11 acts as a novel protective factor in TBI. KLF11 genetic deficiency in mice aggravated the neuroinflammatory responses, grey and white matter injury, and impaired long-term sensorimotor and cognitive recovery. Elucidating the functional importance of KLF11 in TBI may lead us to discover novel pharmacological targets for the development of effective therapies against brain trauma.


Clinical outcomes of adenoid cystic carcinoma of the head and neck: a single institution 20-year experience.
This study reports the clinical outcomes of head and neck adenoid cystic carcinoma treatment over a 20-year period. The treatment outcome of 51 head and neck adenoid cystic carcinoma patients treated between 1992 and 2013 were analysed. Patients were stratified into radical treatment and disease control groups. A total of 40 patients underwent surgery and post-operative radiotherapy. The 10-year disease-specific survival rate was 93 per cent. Eleven patients had tumour recurrence: of these, nine were pulmonary metastases. The 11 patients in the disease control group had a median follow up of 21 months (range, 2-172 months); 5 underwent radical radiotherapy with palliative intent. There was late tumour recurrence in over 25 per cent of patients. Adenoid cystic carcinoma has a high tendency to relapse even after radical excision and adjuvant therapy. However, definitive radiotherapy should still be considered on an individual basis because it may provide local control and prolong patient survival.


Ultrastructural correlation of water reabsorption in isolated rat cauda epididymidis.
Electron microscopic study was made on the water reabsorption of the epithelial cells of the rat cauda epididymidis. It was shown that when the epididymal duct was reabsorbing water at a maximal rate, widely dilated intercellular spaces were seen. It is suggested that the standing gradient model of water reabsorption first proposed for the gall bladder may also operate in the cauda epididymidis.


Suction versus slow-pull for endoscopic ultrasound-guided fine-needle aspiration of pancreatic tumors: a prospective randomized trial.
Suction (S) is commonly used to improve cell acquisition during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Slow-pull (SP) sampling is another technique that might procure good quality specimens with less bloodiness. We aimed to determine if SP improves the diagnostic yield of EUS-FNA of pancreatic masses. Patients with pancreatic solid masses were randomized to four needle passes with both techniques in an alternate fashion. Sensitivity, specificity, positive, and negative predictive values were calculated. Cellularity and bloodiness of cytological samples were assessed and compared according to the technique. Sensitivity, specificity, and accuracy of suction vs. SP were 95.2% vs. 92.3%; 100% vs. 100; 95.7% vs. 93%, respectively. As to the association of methods, they were 95.6, 100 and 96%, respectively. Positive predictive values for S and SP were 100%. There was no difference in diagnostic yield between S and SP (p = 0.344). Cellularity of samples obtained with SP and Suction were equivalent in both smear evaluation (p = 0.119) and cell-block (0.980). Bloodiness of SP and suction techniques were similar as well. S and SP techniques provide equivalent sensitivity, specificity, and accuracy. Association of methods seems to improve diagnostic yield. Suction does not increase the bloodiness of samples compared to slow-pull.


Proceedings of the 15th Antiepileptic Drug and Device Trials Meeting: State of the Science.
On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from preclinical models to clinical prognostication. The conference featured regulatory agencies, academic laboratories, and healthcare companies involved in emerging epilepsy therapies and research. The program included discussions around funding and support for investigations in epilepsy and neurologic research, clinical trial design and integrated outcome measures for people with epilepsy, and drug development and upcoming disease-modifying therapies. Finally, the conference included updates from the preclinical, clinical, and device pipeline. Summaries of the talks are provided in this paper, with the various pipeline therapeutics in the listed tables to be outlined in a subsequent publication.


Combining bi-functional Pt/USY and electromagnetic induction for rapid in-situ adsorption-combustion cycling of gaseous organic pollutant.
By exploiting the superior adsorption capacity of ultra-stable Y-type zeolite (USY) and accurate input of energy by electromagnetic induction field (EMIF) technique, we successfully designed a highly energy-efficient system to eliminate gaseous toluene a common air pollutant. Pristine USY as adsorbent enriches gaseous toluene by a factor of fifteen, via room-temperature adsorption and then EMIF-driven thermal desorption. This operation model involving intermittent heating and mass transfer saves a lot of energy. Especially during temperature rising, 98.9% electric energy can be saved by the EMIF heating in comparison with conventional furnace approaches. In the bi-functional "adsorption-catalytic oxidation" 1Pt/USY, the concentrated toluene undergoes direct oxidation into CO2 rather than desorption when the EMIF heating starts, so one-step enrichment and mineralization are realized. In addition, the developed bi-functional system operates between adsorption and catalytic decomposition flexibly, which makes it ideal for cleaning VOCs emitted from intermittent sources.


MRI-Based Radiomics: Associations With the Recurrence-Free Survival of Patients With Hepatocellular Carcinoma Treated With Conventional Transcatheter Arterial Chemoembolization.
Preoperative estimation of hepatocellular carcinoma (HCC) recurrence after conventional transcatheter arterial chemoembolization (c-TACE) is crucial for subsequent follow-up and therapy decisions. To evaluate the associations of radiomics models based on pretreatment contrast-enhanced MRI, a clinical-radiological model and a combined model with the recurrence-free survival (RFS) of patients with HCC after c-TACE, and to develop a radiomics nomogram for individual RFS estimations and risk stratification. Retrospective. In all, 184 consecutive HCC patients. 1.5T or 3.0T, including T2 WI, T1 WI, and contrast-enhanced T1 WI. All HCC patients were randomly divided into the training (n = 110) and validation datasets (n = 74). Radiomics signatures capturing intratumoral and peritumoral expansion (1, 3, and 5 mm) were constructed, and the radiomics models were set up using least absolute shrinkage and selection operator (LASSO) Cox regression. Clinical-radiological features were identified by univariate and multivariate Cox regression. The clinical-radiological model and the combined model fusing the radiomics signature with the clinical-radiological risk factors were developed by a multivariate Cox proportional hazard model. A radiomics nomogram derived from the combined model was established. LASSO Cox regression, univariate and multivariate Cox regression, Kaplan-Meier analysis were performed. The discrimination performance of each model was quantified by the C-index. Among the different peritumoral expansion models, only the 3-mm peritumoral expansion model (C-index, 0.714) showed a comparable performance (P = 0.4087) to that of the portal venous phase intratumoral model (C-index, 0.727). The combined model showed the best performance and the C-index was 0.802. Kaplan-Meier analysis showed that the cutoff values of the combined model relative to a median value (1.7426) perfectly stratified these patients into high-risk and low-risk subgroups. The combined model is more valuable than the clinical-radiological model or radiomics model alone for evaluating the RFS of HCC patients after c-TACE, and the radiomics nomogram can be used to preoperatively and individually estimate RFS. 3 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;52:461-473.


Myelosuppression grading of chemotherapies for hematologic malignancies to facilitate communication between medical and dental staff: lessons from two cases experienced odontogenic septicemia.
Odontogenic diseases can be a risk factor for life-threatening infection in patients with hematologic malignancies during chemotherapy that induces myelosuppression of variable severity. Previous studies noted the necessity of the elimination of all odontogenic foci before hematopoietic stem cell transplantation. To enable planning for the adequate dental intervention, the oral medicine team must understand the general status of patient and the intensity of the chemotherapy, which is sometimes difficult to be fully appreciated by dental staff. Therefore, a simplified grading would facilitate the sharing of information between hematologists, dentists and oral hygienists. This study aimed to introduce our myelosuppression grading of chemotherapies for hematologic malignancies and analyze the timing of occurrence of severe odontogenic infection. 37 patients having received various chemotherapies for hematologic malignancies were enrolled. The chemotherapy regimens were classified into four grades based on the persistency of myelosuppression induced by chemotherapy. Mild myelosuppressive chemotherapies were classified as grade A, moderate ones as grade B, severe ones as grade C, and chemotherapies that caused severe myelosuppression and persistent immunodeficiency (known as conditioning regimens for transplant) as grade D. The timing of occurrence of severe odontogenic infection was retrospectively investigated. Two patients (5.4%) had severe odontogenic infections after grade B or C chemotherapy. One occurred after extraction of non-salvageable teeth; the other resulted from advanced periodontitis in a tooth that could not be extracted because of thrombocytopenia. Both were de novo hematologic malignancy patients. During grade D chemotherapy, no patients had severe odontogenic infections. The simplified grading introduced in this study is considered a useful tool for understanding the myelosuppressive state caused by chemotherapy and facilitating communication between medical and dental staff. During the period around the primary chemotherapy, especially for de novo hematologic malignancy patients who often received grade B to C myelosuppression chemotherapy, caution should be exercised for severe odontogenic infection by the oral medicine team, irrespective of whether invasive treatment is to be performed.


The voluntary reflux phenomenon.
Dental erosion can be caused by recurrent contact with regurgitated gastric acid and there are a number of recognised conditions in which this can occur. A previously undescribed condition, which we have termed the 'voluntary reflux phenomenon', is described, and an illustrative case history given, together with details of several other similar cases. The condition may well be first recognised by the dentist, may have serious psychiatric implications, and has features which can help distinguish it from other causes of gastric acid mediated dental erosion. These features are described and discussed, and some suggestions for initial management in general practice made, should the condition be suspected.


Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively inhibit activities of mammalian replicative DNA polymerases.
Retinoic acids, vitamin A-related compounds, are known to be inhibitors of telomerase. We found that fucoxanthin from the sea alga Petalonia bingamiae is a potent inhibitor of mammalian replicative DNA polymerases (i.e., pol alpha, delta and epsilon). Since fucoxanthin is a carotenoid (provitamin A-related) compound, we characterized the biochemical modes of vitamin A-related compounds including vitamin A and provitamin A in this report. Subsequently, we found that fucoxanthin, all-trans retinal (RAL, vitamin A aldehyde) and all-trans retinoic acid (RA, vitamin A acid) inhibited the activities of replicative DNA polymerases with IC(50) values of 18-190, 14-17 and 8-30 microM, respectively. On the other hand, all-trans retinol (vitamin A) did not influence any of the DNA polymerase activities. RA inhibited not only the activities of pol alpha, delta and epsilon with IC(50) values of 30, 28 and 8 microM, respectively, but of pol beta with an IC(50) value of 27 microM. The tested vitamin A-related compounds did not influence the activities of DNA polymerases from a higher plant, cauliflower, prokaryotic DNA polymerases, or DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. RAL and RA should be called selective inhibitors of mammalian DNA polymerases including telomerase, and RAL was a specific inhibitor of mammalian replicative DNA polymerases. As expected from these results in vitro, some of them could prevent the growth of NUGC-3 human gastric cancer cells, and especially RAL was a potent antineoplastic agent with an LD(50) value of 19 microM. The cells were halted at G1 phase in the cell cycle by RAL.


Computational anatomy in the study of bone structure.
Osteoporosis is a major public health threat for millions of Americans with billions of dollars per year of national direct costs for osteoporotic fractures. Osteoporosis results in a decrease in overall bone mass and subsequent increase in the risk of bone fracture. Bone strength arises from the combination of bone size and shape, the distribution of bone mass throughout the structure, and the quality of the bone material. Advances in medical imaging have enabled a comprehensive assessment of bone structure through the analysis of high-resolution scans of relevant anatomical sites, eg, the proximal femur. However, conventional imaging analysis techniques use predefined regions of interest that do not take full advantage of such scans. Recently, computational anatomy, a set of imaging-based analysis algorithms, has emerged as a promising technique in studies of osteoporosis. Computational anatomy enables analyses that are not biased to one particular region and provide a more complete assessment of the whole structure. In this article, we review studies that have used computational anatomy to investigate the structure of the proximal femur in relation to age, fracture, osteoporotic treatment, and spaceflight effects.


A validated stability-indicating TLC-densitometric method for the determination of stanozolol in pharmaceutical formulations.
Stanozolol is a synthetic derivative of dihydrotestosterone (DHT), and one of the frequently detected anabolic steroids in doping analysis. The current work describes the development and validation of the stability-indicating TLC-densitometric method for sensitive and specific estimation of stanozolol even its degradation product being there. Precoated silica gel TLC aluminium plates were utilized as the stationary phase and the eluent comprised of petroleum ether: acetone (6:4, v/v). Densitometric analysis of stanozolol was achieved at λmax 750 nm in the absorbance mode after staining with phosphomolybdic acid (PMA). Stress degradation of stanozolol was carried out under various reaction conditions including acid, base and neutral hydrolysis, wet and dry heating treatment, oxidation, and photo-degradation. Resulted stress samples and pharmaceutical products were analyzed with the developed TLC method. This system showed a compact spot for stanozolol at Rf value of 0.46 ± 0.02. The data of linear regression analysis indicated a good linear relationship over the range of 200-1200 ng/spot concentrations. The method was validated for robustness, precision and recovery. The LOD and LOQ were 1.6 and 5.1 ng/spot, respectively. Under various stressed conditions, stanozolol showed degradation only under acidic hydrolysis. Peak of a degraded product was well resolved from the stanazolol with reasonably different Rf value and identified as 17, 17-dimethyl-l8-nor-5α-androst-13(14)-eno [3,2c] pyrazole through 1D- and 2D-NMR spectroscopic techniques and ESI-QqTOF-MS/MS analysis. Result reflected that the stanozolol is majorly affected by the acidic condition. Statistical analysis indicated the application of the developed stability-indicating TLC-densitometric method for routine analysis of stanozolol in the presence of its degradation product.


Hypothyroldism in a neonate following excision of a cervical teratoma.
Hypothyroidism developed in a neonate following the excision of a large cervical teratoma. This finding supports the observation that cervical teratomas commonly arise from thyroid tissue. Thyroid function tests should be performed routinely in all patients in whom identifiable residual thyroid tissue is not demonstrated at the conclusion of the operation.


Differential Activation and Functional Plasticity of Multimodal Areas Associated with Acquired Musical Skill.
Training of a musical skill is known to produce a distributed neural representation of the ability to perceive music and perform musical tasks. In the present study we tested the hypothesis that the audiovisual perception of music involves a wider activation of multimodal sensory and sensorimotor structures in the brain, including those containing mirror neurons. We mapped the activation of brain areas during passive listening and viewing of the first 40 s of "Ode to Joy" being played on the piano by an expert pianist. To do this we performed brain functional magnetic resonance imaging during the presentation of 6 different stimulus contrasts pertaining to that musical melody in a pseudo-randomized order. Group data analysis in musically trained and untrained adults showed robust activation in broadly distributed occipitotemporal, parietal and frontal areas in trained subjects and much restricted activation in untrained subjects. A visual stimulus contrast focusing on the visual motion percept of moving fingers on piano keys revealed selective bilateral activation of a locus corresponding to the V5/MT area, which was significantly more pronounced in trained subjects and showed partial linear dependence on the duration of training on the left side. Quantitative analysis of individual brain volumes confirmed a significantly greater and wider spread of activation in trained compared to untrained subjects. These findings support the view that audiovisual perception of music and musical gestures in trained musicians involves an expanded and widely distributed neural representation formed due to experience-dependent plasticity.


Practical application of infection control in endodontics.
The transmission of infections in an endodontic practice is a significant concern for both patients and dental health care providers. This article offers a review and practical application of infection control methods in the practice of endodontics.


Synthesis and glycosylation of a series of 6-mono-, di-, and trifluoro S-phenyl 2,3,4-tri-O-benzyl-thiorhamnopyranosides. Effect of the fluorine substituents on glycosylation stereoselectivity.
A series of 6-mono-, di-, and trifluoro analogs of S-phenyl 2,3,4-tri-O-benzyl-D- or L-thiorhamnopyranoside has been synthesized and used as donors in glycosylation reactions, with activation by the 1-benzenesulfinyl piperidine/triflic anhydride system. The stereochemical outcome of the glycosylation reactions was found to depend on the electron-withdrawing capability of the disarming substituent at the 6-position, i.e., on the number of fluorine atoms present. The results are explained with regard to the increased stability of the glycosyl triflates, shown to be intermediates in the reaction by low-temperature 1H NMR experiments, with increased fluorine content.


High-content screen using zebrafish (Danio rerio) embryos identifies a novel kinase activator and inhibitor.
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos. Screening a 369 kinase member panel we show that compound 1 is a PIM3 kinase inhibitor (IC50=4.078μM) and surprisingly a DAPK1 kinase agonist/activator (EC50=39.525μM). To our knowledge this is the first example of a small molecule activating DAPK1 kinase. We provide a putative model for increased phosphate transfer in the ATP binding domain when compound 1 is virtually docked with DAPK1. Our data indicate that observable phenotypical changes can be used in future zebrafish screens to identify compounds acting via similar molecular signaling pathways.


Tibial cyst formation after anterior cruciate ligament reconstruction using a new bioabsorbable screw.
We report a case of tibial cyst formation twelve months after anterior cruciate ligament reconstruction using hamstring graft. A composite bioabsorbable interference screw made of 'beta tricalcium phosphate and poly L-lactide' fixed the graft distally. The patient presented with acute symptoms of pain and swelling over the proximal tibia. Curettage of the cyst resulted in complete recovery within 3 months.


Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells.
Naringenin (NGEN), one of the most abundant flavonoids in citrus fruits, has been shown to inhibit in vitro growth of in human cancer cells, although the mechanism of action is poorly understood. Herein, we investigated NEGN's pro-apoptotic effect on human leukemia THP-1 cells. NGEN treatment inhibited THP-1 cells' growth a concentration-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies and the accumulation of cells in the sub-G1 phase. NGEN-induced apoptosis was accompanied by increased hyperpolarization of the mitochondrial membrane potential, downregulation of Bcl-2, upregulation of Bax, activation of caspases and subsequent poly(ADP-ribose)polymerase (PARP) cleavages. z-DEVD-fmk, a caspase-3 inhibitor, significantly inhibited both the cytotoxic effect and apoptotic characteristics induced by NGEN treatment demonstrating caspase-3's important role in the observed cytotoxic effect. The induction of apoptosis was also associated with the inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt, and PI3K inhibitor LY29004 significantly increases NGEN-induced cell death. These findings provide evidence that NEGN's pro-apoptotic effect is mediated by the activation of caspases and mitochondria dysfunctions that correlate with the inactivation of the PI3K/Akt pathway in THP-1 cells. Therefore, NGEN has a strong potential as a therapeutic agent for preventing cancers such as leukemia.


Characterization of breakpoint sequences of five rearrangements in L1CAM and ABCD1 (ALD) genes.
Mutations in L1CAM are responsible for X-linked hydrocephalus, whereas those in the ALD gene (ABCD1) cause adrenoleukodystrophy. In both genes, most of the mutations reported so far are short-length mutations and only a few patients with larger rearrangements have been documented. We have characterized three intragenic deletions of the ALD gene at the molecular level and describe here the first two L1CAM rearrangements resulting in deletion of several exons in one case and about 50 kb, including the entire gene, in the second case. At both breakpoints of an ALD deletion, Alu repeats have been found and, additionally, a short Alu region of approximately 130 bp was inserted, suggesting that this rearrangement is the result of a more complex non-allelic homologous recombination event. Only one Alu element was present at the breakpoint of the second ALD rearrangement, including a 26-bp Alu core sequence that was suggested to be a recombinogenic hot spot. These data suggest the involvement of an Alu core sequence-stimulated non-homologous recombination as a possible cause for this rearrangement. Short direct repeats were identified at all putative mispaired sequences in the L1CAM breakpoints and at both breakpoints of the third ALD deletion characterized, suggesting non-homologous (illegitimate) recombination as the molecular mechanism by which these latter deletions occurred. In conclusion, our results indicate that highly repetitive elements as well as short direct repeats are frequently involved in the formation of ALD and L1CAM gene rearrangements.


Global Abortion Policies Database: a new approach to strengthening knowledge on laws, policies, and human rights standards.
The Global Abortion Policies Database (GAPD), launched in June 2017, provides a verifiable, comprehensive, nuanced approach to information and data sources on abortion law and policy. Abortion laws, policies, and guidelines from United Nations (UN) and World Health Organization (WHO) Member States are juxtaposed to information and recommendations from WHO safe abortion guidance, national sexual and reproductive health indicators, and relevant UN human rights bodies' concluding observations to countries. The Global Abortion Policies Database aims to increase transparency of information and accountability of states for the protection of individuals' health and human rights. The database presents current information on abortion laws and policies that goes beyond categories of lawful abortion to include information on additional access requirements, service provision, conscientious objection, and penalties. Wide-ranging variations among countries' legal requirements and criminal penalties raise questions about the evidentiary and human rights basis for abortion laws and policies. Source documents found in the database highlight that in many jurisdictions legal and policy guidance is either non-existent, not clear, or conflicting. By juxtaposing a jurisdiction's abortion laws and policies to relevant WHO guidance and by facilitating comparisons of countries' sexual and reproductive health indicators, the database can enable deep policy analysis of states' obligations to meet the health needs and human rights of individuals in the context of abortion. Policy analysis in the context of authoritative guidance on human rights standards can enable health and rights advocates to hold governments accountable for respecting, protecting, and fulfilling individuals' human rights. The GAPD is a comprehensive tool that can be used to strengthen knowledge, inform law and policy research to generate evidence on the impact of laws and policies in practice, and facilitate greater awareness of the many challenges to creating enabling policy environments for safe abortion.


C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.
Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor β1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.


Ultrastructural features of smooth muscle and endothelial cells of isolated isobaric human placental and maternal arteries.
The ability of a blood vessel to develop tone is dependent upon morphological parameters of the smooth muscle cells (SMC), including density, relationship with the endothelium and subcellular distribution of myofilaments and intracellular organelles. Consequently, wall ultrastructure of isolated human placental chorionic plate arteries (n=12), fixed when pressurised to mimic their in vivo geometry, was examined qualitatively using electron microscopy, and compared with maternal arteries (omental, n=10, myometrial, n=6). Arteries from women with uncomplicated pregnancy were tested for contractile viability before fixing, with some vessels post-fixed in osmium-ferricyanide for sarcoplasmic reticulum (SR) identification. In contrast to maternal arteries, placental arteries had no internal elastic lamina but exhibited considerable extracellular matrix separating circularly orientated SMC. Human SMC contained tightly packed arrays of myofilaments running parallel to the plasma membrane, enveloping cellular organelles. Synthetic SMC, with few myofilaments and much rough SR, were observed in placental arteries only. SR in SMC from maternal arteries was located centrally, often encircling mitochondria, and also near the plasma membrane associated with caveolae. Positive SR staining was rarely observed in SMC of placental arteries. This study highlights ultrastructural differences between placental and maternal arteries that may underlie specialised mechanisms of regulating vascular tone in the placenta.


Complications of Head Immobilization Devices in Children: Contact Mechanics, and Analysis of a Single Institutional Experience.
Head immobilization devices (HIDs) are a staple of neurosurgical procedures, including in the intraoperative magnetic resonance imaging (iMRI) operating rooms (ORs) where material modifications were necessary for compatibility with the magnets utilized. To present the experience in this OR environment and discuss the multifactorial nature of the observed adverse events. A retrospective chart review was performed, utilizing the Department of Neurosurgery and iMRI OR databases to identify patients who suffered complications related to HIDs between November 2007 and March 2016. A literature review was also done to identify the magnitude of the problem and the availability of safety guidelines. Nine hundred and forty patients underwent surgery in the iMRI OR requiring head immobilization. Seven (0.7%) suffered complications related to the HID-depressed skull fractures (n = 7) and epidural hematomas (n = 6). Age at surgery ranged from 1.6 to 10.3 yr. All patients had posterior fossa neoplasms and associated obstructive hydrocephalus. Four patients (57%) suffered permanent neurological deficits. Six patients (86%) underwent a surgical procedure to evacuate the epidural hematomas and repair the depressed skull fracture. In contrast, 1 out of 445 patient (0.2%) suffered HID-related adverse events in the conventional ORs, aged 10.2 yr. HIDs are important to provide stability and support during neurosurgical procedures. Modifications in the material or the shape of the pins can significantly change the pressure exerted. Most of these complications are preventable if certain precautionary measures are taken especially in certain high-risk patients, and the overall benefits of HIDs continue to outweigh the risks. There is a need for consensus on guidelines for the safe use of these devices.


Abdominal aorta tortuosity on computed tomography identifies patients at risk of complications during transfemoral transcatheter aortic valve replacement.
Transcatheter aortic valve replacement is now indicated in patients at intermediate surgical risk and will probably soon be indicated in patients at low surgical risk, for whom the occurrence of serious procedural complications is not acceptable. We aimed to investigate whether simple arterial variables from computed tomography scanning can predict the occurrence of severe early complications in patients undergoing transfemoral TAVR. All patients with symptomatic severe aortic stenosis treated by transfemoral transcatheter aortic valve replacement in our centre, and for whom computed tomography images were available, were included. An exhaustive analysis of preprocedural computed tomography scans was performed retrospectively, in search of arterial tortuosity and vascular calcifications. The primary endpoint was a composite 30-day safety endpoint. Overall, 175 patients were included. The primary endpoint was observed in 60 patients (35%). Abdominal aorta tortuosity was identified in 28 patients (16%) and was strongly associated with the occurrence of a complication (adjusted odds ratio 2.7, 95% confidence interval 1.1-6.6; P=0.03). There was no significant association between iliofemoral tortuosity or vascular calcification and the occurrence of complications. A tortuous abdominal aorta was found to be a predictor of the occurrence of a complication in patients undergoing transfemoral transcatheter aortic valve replacement. This computed tomography variable should therefore be taken into account when choosing the approach, especially for patients at intermediate and low surgical risk.


Recombinant human gelatin nanoparticles as a protein drug carrier.
Considerable attention has been directed to the application of natural gelatin-based nanoparticles. However, there are still critical problems associated with a safety issue of animal-origin gelatins, heterogeneous molecular weight, subsequent nanoparticle size distributions and use of toxic cross-linker. The purpose of this study was to develop a simple, safe and reproducible preparation method of recombinant human gelatin (rHG) nanoparticles via a modified desolvation method using a natural cross-linker for protein drug delivery. The model protein, FITC-BSA, was released from rHG nanoparticles in a biphasic and sustained-release pattern without initial burst. Optimized nanoparticles based on rHG and a natural cross-linker were prepared for the first time and showed great potential for protein drug delivery in terms of sustained release, less initial burst, and safety. In addition, rHG nanoparticles were efficiently internalized in the cell and mainly localized in the cytoplasm without significant cytotoxicity. Overall, these results suggest that rHG nanoparticles are appropriate for a protein drug delivery system with minimal toxicity.


Effects of 9-ene-tetrahydrocannabinol on uterine estrogenicity in the mouse.
Several early (Phase I) and late (Phase II) estrogenic effects of 9-ene-tetrahydrocannabinol (THC) were examined in the adult mouse uterus. An injection of THC (2.5 or 10 mg/kg body wt) in ovariectomized mice neither stimulated uterine water imbibition or accumulation of [125I]bovine serum albumin (Phase I responses) at 6 h, nor antagonized these Phase I responses elicited by estradiol-17 beta (E2). With respect to Phase II responses, although single injections of THC (2.5, 5.0 and 10 mg/kg body wt) alone were ineffective in influencing uterine weight at 24 h or incorporation of [3H]thymidine at 18 h, this drug interfered with these responses elicited by E2 in a dose-dependent manner. In contrast, an injection of THC in progesterone (P4)-primed ovariectomized mice modestly enhanced (61%) uterine incorporation of [3H]thymidine. However, E2-stimulated uterine thymidine incorporation in P4-primed ovariectomized mice was antagonized by THC treatment. Effects of THC on blastocyst implantation were examined. Single or multiple injections of various doses of THC neither induced implantation in P4-primed delayed implanting mice, nor interfered with E2-induced implantation. Furthermore, daily injections of THC (10 mg/kg body wt) during the peri-implantation period had no apparent adverse effects on implantation, or on experimentally induced decidualization (deciduomata). The data suggest that THC is neither pro- nor antiestrogenic with respect to Phase I responses. However as regards Phase II responses, THC is modestly pro-estrogenic in the P4-treated uterus, but is anti-estrogenic in the presence of E2. These estrogen agonistic/antagonistic effects of THC on uterine Phase II responses do not adversely affect the process of implantation and decidualization.


Morphometric assessment of normal, suspect and glaucomatous optic discs with Stratus OCT and HRT II.
To compare morphometric parameters and diagnostic performance of the new Stratus Optical Coherence Tomograph (OCT) Disc mode and the Heidelberg Retina Tomograph (HRT); to evaluate OCT's accuracy in determining optic nerve head (ONH) borders. Controls and patients with ocular hypertension, glaucoma-like discs, and glaucoma were imaged with OCT Disc mode, HRT II, and colour disc photography (DISC-PHOT). In a separate session, automatically depicted ONH shape and size in OCT were compared with DISC-PHOT, and disc borders adjusted manually where required. In a masked fashion, all print-outs and photographs were studied and discs classified as normal, borderline, and abnormal. The Cohen kappa method was then applied to test for agreement of classification. Bland-Altman analysis was used for comparison of disc measures. In all, 49 eyes were evaluated. Automated disc margin recognition failed in 53%. Misplaced margin points were more frequently found in myopic eyes, but only 31/187 were located in an area of peripapillary atrophy. Agreement of OCT with photography-based diagnosis was excellent in normally looking ONHs, but moderate in discs with large cups, where HRT performed better. OCT values were consistently larger than HRT values for disc and cup area. Compared with HRT, small rim areas and volumes tended to be minimized by OCT, and larger ones to be magnified. Stratus OCT Disc protocol performed overall well in differentiating between normal and glaucomatous ONHs. However, failure of disc border recognition was frequently observed, making manual correction necessary. ONH measures cannot be directly compared between HRT and OCT.


What is the optimal timing of embryo transfer when there are only one or two embryos at cleavage stage?
Today, most IVF programs have moved to blastocyst transfer but there is still uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos on day 3. We conducted a retrospective study of 102 patients with one or two cleavage stage embryos that had their embryos transferred on day 3 and 429 patients had their embryos cultured to day 5 for transfer. The number of mature oocytes (4.0 vs 4.6, p = NS) and number of cleavage stage embryos on day 3 was similar in the two groups (1.3 vs. 1.5, p = NS). The clinical pregnancy rate per retrieval (22% vs. 24.6%, p= NS) and the ongoing pregnancy rate per retrieval (20% vs. 20.2%, p = NS) was comparable between the groups. Fifty seven (13.2%) of the patients had cleavage embryo arrest and did not have an embryo to transfer on day 5. We conclude that the cumulative pregnancy rate is the same for patients with 1-2 cleavage stage embryos regardless of whether the embryo is transferred on day 3 or day 5.


In situ expression of cytokines in IgA nephritis.
We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Class III magnetic orthopedic forces on the craniofacial sutures of rhesus monkeys.
The objectives of this study were to develop an intraoral intermaxillary Class III magnetic orthopedic appliance (MOA-III), to investigate the influence of Class III orthopedic forces on the craniofacial sutures of rhesus monkeys, and to elucidate the mechanism of Class III malocclusion orthopedic treatment. Six male rhesus monkeys in the mixed-dentition stage were divided into 3 groups of 2 each: a 90-day experimental group, a 45-day experimental group, and a control group. Six craniofacial sutures were observed. The experimental monkeys received heavy forces (300 g) per side initially, created by opposing Nd(2)Fe(14)B magnetic units in a cast MOA-III. The control groups received no treatment. Before the appliances were inserted, metal implants were placed in each animal as bone markers for direct measurement. To determine the rate of bone apposition, each animal was injected with fluorescent dyes intravenously before and during the experimental period. Intraoral photographs, dental casts, and cephalometric radiographs of each animal were obtained at the beginning and end of the experiment. Distances between metal implants on both sides of the sutures were enlarged in the experimental groups. Cephalometric analysis showed that the treatment effects of MOA-III are a combination of skeletal and dental changes in the maxilla and the mandible. Distinct changes from physiologic growth remodeling were observed in some sutures but not in the control groups. No inflammation was noted in either experimental or control monkeys. The MOA-III can be an efficient intraoral appliance to treat Class III malocclusion that is caused by a deficient maxilla; heavy orthopedic forces (300 g per side) are safe and effective in the rhesus monkey.