Relationship between salt and blood pressure in hypertensive patients on chronic ACE-inhibition.
We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per day) on blood pressure, erythrocyte sodium transport and the activity in the renin-angiotensin system in six males with primary hypertension, who had attained normotension on chronic enalapril treatment for 4 years. The design was a placebo-controlled, randomized, two-way cross over, double-blind study, i.e. each patient served as his own control. Intracellular erythrocyte sodium and potassium content were measured by flame photomometry. The increase in the intracellular sodium concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain (compared with no-ouabain) was measured to determine the rate of active sodium efflux. 24-h blood pressure registration was performed with Space-lab equipment (SL 90202) before and at the end of the salt load. Left ventricular morphology was evaluated with echocardiography and the minimal vascular resistance of the hand vascular bed with water plethysmography at baseline and after 4 years on enalapril. Four years' enalapril treatment caused a significant decrease in blood pressure, left ventricular mass and minimal vascular resistance. During the 4-day salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2 mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The change (delta) in MAP during high salt intake showed a negative relationship to delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship was found between the blood pressure response to the salt load and structural cardiovascular changes. In conclusion, a short-term oral salt load in hypertensive patients on chronic enalapril treatment caused a blood pressure rise, which was related to cellular sodium transport but not to structural cardiovascular changes.


Markers of oxidative stress in hepatopancreas of crayfish (Orconectes limosus, raf) experimentally exposed to nanosilver.
Silver nanoparticles, chemically neutral particles in the size range of 1-100 nm, express strong antimicrobial activity and therefore have a broad range of applications. The increased use of consumer products with nanosilver (nanoAg) may result in its release into the environment, and may particularly affect aquatic systems. The mechanisms of the harmful effects of nanoAg against aquatic organisms are unclear. Therefore, in the present study we investigate the pro-oxidative potential of these nanoparticles in experimentally exposed crayfish Orconectes limosus. Markers of oxidative stress and parameters of the antioxidant cell defense system such as total glutathione, glutathione reductase and the level of sulfhydryl groups were examined in the hepatopancreas of both sexes of O. limosus collected seasonally from Białe Lake (Poland) and subsequently exposed to nanoAg particles for 2 weeks. Exposure to nanoAg led to a high concentration-dependent increase in the rate of lipid peroxidation and a decrease of protein-bound SH groups which indicates protein oxidation. These markers of oxidative stress were accompanied by decreased levels of thiols and reduced activity of glutathione reductase. These results indicate a deficiency of reduced glutathione and suggest that the exposed organisms have less efficient antioxidative mechanisms available to counter ROS-mediated cellular stress. Furthermore, we find that confocal microscopy is of limited utility in monitoring the presence of silver nanoparticles in tissues of exposed crayfish.


Novel manganese(II) sulfonate-phosphonates with dinuclear, tetranuclear, and hexanuclear clusters.
Hydrothermal reactions of manganese(II) salts with m-sulfophenylphosphonic acid (m-HO3S-Ph-PO3H2, H3L) and 1,10-phenanthroline (phen) led to six novel manganese(II) sulfonate-phosphonates, namely, [Mn2(HL)2(phen)4][Mn2(HL)2(phen)4(H2O)](2).6H2O (1), [Mn4(L)2(phen)8(H2O)2][ClO4](2).3H2O (2), [Mn(phen)(H2O)4]2[Mn4(L)4(phen)4].10H2O (3), [Mn6(L)4(phen)8(H2O)2].4H2O (4), [Mn6(L)4(phen)8(H2O)2].24H2O (5), and [Mn6(L)4(phen)6(H2O)4].5H2O (6). The structure of 1 contains two types of dinuclear manganese(II) clusters, and 2-3 exhibit two types of tetranuclear manganese(II) cluster units. 4-5 feature two different types of isolated hexanuclear manganese(II) clusters, whereas the hexanuclear manganese(II) clusters in 6 are bridged by sulfonate-phosphonate ligands into a 1D chain. Magnetic property measurements indicate that there exist weak antiferromagnetic interactions between magnetic centers in all six compounds.


Rapid progression of an idiopathic leukoplakia to a proliferative verrucous leukoplakia lesion and then squamous cell carcinoma.
The article reports a case of oral proliferative verrucous leukoplakia (OPVL) in a 76-year-old woman, underscoring how an otherwise inconspicuous white plaque lesion can rapidly turn into a phase of verrucous carcinoma and subsequently squamous cell carcinoma.


Leaching modelling of slurry-phase carbonated steel slag.
In the present work the influence of accelerated mineral carbonation on the leaching behaviour of basic oxygen furnace steel slag was investigated. The environmental behaviour of the material as evaluated through the release of major elements and toxic metals under varying pH conditions was the main focus of the study. Geochemical modelling of the eluates was used to derive a theoretical description of the underlying leaching phenomena for the carbonated material as compared to the original slag. Among the investigated elements, Ca and Si were most appreciably affected by carbonation. A very clear effect of carbonation on leaching was observed for silicate phases, and lower-Ca/Si-ratio minerals were found to control leaching in carbonated slag eluates as compared to the corresponding untreated slag sample as a result of Ca depletion from the residual slag particles. Clear evidence was also gained of solubility control for Ca, Mg and Mn by a number of carbonate minerals, indicating a significant involvement of the original slag constituents in the carbonation process. The release of toxic metals (Zn, V, Cr, Mo) was found to be variously affected by carbonation, owing to different mechanisms including pH changes, dissolution/precipitation of carbonates as well as sorption onto reactive mineral surfaces. The leaching test results were used to derive further considerations on the expected metal release levels on the basis of specific assumptions on the relevant pH domains for the untreated and carbonated slag.


Season of birth is associated with adult body mass index in patients with bipolar disorder.
Cardiovascular risk factors, such as abdominal obesity and obesity in general, are very prevalent among patients with bipolar disorder (BD). Although long-term use of psychotropic medications is an important determinant of these risk factors, other evidence suggests that early development may interact with the mood disorder diathesis to exponentially increase the risk of obesity. The goal of our study was to test whether season of birth is associated with adult body mass index (BMI) and abdominal obesity in individuals with bipolar disorder. We compared season of birth effects on BMI in 375 adult patients with bipolar disorder and 196 adult patients with unipolar major depression. We found a significant season of birth effect on BMI in patients with bipolar disorder, but not unipolar. In patients with bipolar disorder, season of birth was also associated with waist circumference, with a stronger effect in males. Season of birth affects adult BMI and waist circumference in patients with bipolar disorder, but not in patients with unipolar depression. Our results suggest that early environmental factors, yet to be identified, interact with specific neurobiological features of bipolar disorder to determine stable traits and disease risk factors in adult life.


Does nitric oxide contribute to the basal vasodilation of pregnancy in conscious rabbits?
Pregnancy produces marked systemic vasodilation, but the mechanism is unknown. Experiments were performed in conscious rabbits to test the hypotheses that increased nitric oxide (NO) production contributes to the increased vascular conductance, but that the contribution varies among vascular beds. Rabbits were instrumented with aortic and vena caval catheters and ultrasonic flow probes implanted around the ascending aorta, superior mesenteric artery, terminal aorta, and/or a femoral artery. Hemodynamic responses to intravenous injection of N(omega)-nitro-L-arginine (L-NA; 20 mg/kg or increasing doses of 2, 5, 10, 15, and 20 mg/kg) were determined in rabbits first before pregnancy (NP) and then at the end of gestation (P). L-NA produced similar increases in arterial pressure between groups, but the following responses were larger (P < 0.05) when the rabbits were pregnant: 1) decreases in total peripheral conductance [-3.7 +/- 0.3 (NP), -5.0 +/- 0.5 (P) ml x min(-1) x mmHg(-1)], 2) decreases in mesenteric conductance [-0.47 +/- 0.05 (NP), -0.63 +/- 0.07 (P) ml x min(-1) x mmHg(-1)], 3) decreases in terminal aortic conductance [-0.43 +/- 0.05 (NP), -0.95 +/- 0.19 ml x min(-1) x mmHg(-1) (P)], and 4) decreases in heart rate [-41 +/- 4 (NP), -62 +/- 5 beats/min (P)]. Nevertheless, total peripheral and terminal aortic conductances remained elevated in the pregnant rabbits (P < 0.05) after L-NA. Furthermore, decreases in cardiac output and femoral conductance were not different between the reproductive states. We conclude that the contribution of NO to vascular tone increases during pregnancy, but only in some vascular beds. Moreover, the data support a role for NO in the pregnancy-induced increase in basal heart rate. Finally, unknown factors in addition to NO must also underlie the basal vasodilation observed during pregnancy.


Visual outcome after cataract surgery complicated by posterior capsule rupture.
Posterior capsule rupture is one of the most common intra-operative complications of cataract surgery and may lead to other sequelae that affect visual outcome. To determine the visual outcome and sequelae at 1 year after cataract surgery complicated by posterior capsule rupture and factors related to poor visual outcome. Retrospective chart reviews of the patients who underwent cataract surgery complicated by posterior capsule rupture in Siriraj Hospital between January 2006 and December 2009 were performed. Data collected included demographic data, underlying systemic diseases, pre-existing ophthalmic diseases, type of cataract, type of operation, vitrectomy methods, type of intraocular lens (IOL) implantation, pre-operative and post-operative visual acuity, subsequent complications and management. There were 525 cases that received cataract surgery complicated by posterior capsule rupture. After excluding 280 cases with the follow-up period of shorter than 1 year 245 eyes of 242 patients were studied. These comprised 111 males and 131 females. The mean age was 69.3 years, ranged from 40 to 92 years. The mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 1 year was 0.43 (median 0.24). The proportion of patients who had BCVA of 0.3 logMAR or better was 64.5%. After excluding eyes with pre-existing diseases, 72.9% got this level of BCVA. Vitrectomy was required in 75.5%; which consisted of anterior vitrectomy (68.6%) and posterior vitrectomy (6.9%). Primary intra-ocular lens insertion was performed in 87.4%, mostly in the ciliary sulcus (75.5%). Subsequent complications occurred in 13.9%, which included secondary glaucoma (4.9%), cystoid macular edema (2.4o), endophthalmitis (1.6%), rhegmatogenous retinal detachment (1.2%o), IOL displacement (1.2%), uveitis (1.2%), corneal decompensation (0.8%) and fibrous ingrowth (0.4%). The factors associated with the poor visual outcome worse than 0.3 logMAR were pre-existing ocular diseases, incision requiring more than 2 stitches, posterior vitrectomy and subsequent complications (p < 0.05). Most of the patients had favorable visual outcome after cataract surgery complicated by posterior capsule rupture. Meticulous vitrectomy to prevent subsequent complications and foldable IOL insertion to minimize the wound size are recommended.


Pre-Existing Microbiome Signature in a SARS-CoV-2 Discordant Family.
Our index patient is a 19-year-old man with Crohn's disease. After developing symptoms consistent with COVID-19, he, his 62-year-old father, and 14-year-old sister tested positive for SARS-CoV-2 in May 2020. Despite a shared household, his 50-year-old mother with a history of asthma and his healthy brother and sister-in-law (a married couple) remained negative. The index patient and his mother had undergone microbiome analysis in May 2019, following his brother and his sister-in-law in November 2020. We observed significant differences between the fecal microbiota of the SARS-CoV-2-positive son and those of his healthy family. There were differences in the bacterial phylum, class, order, family, and genus level with the increased relative abundance of Bacteroidetes and reductions or deletions in bacterial diversity, particularly of the Bifidobacterium family. This unique study may signal a new exploratory avenue for the prevention or treatment of SARS-CoV-2 infections.


The Inflammatory Transcription Factor C/EBPβ Plays a Critical Role in Cardiac Fibroblast Differentiation and a Rat Model of Cardiac Fibrosis Induced by Autoimmune Myocarditis.
The aim of the present study was to investigate the mechanisms of CCAAT/enhancer-binding protein β (C/EBPβ) in cardiac myofibroblast (CMF) differentiation and in a rat model of cardiac fibrosis induced by experimental autoimmune myocarditis (EAM).In vitro studies performed in primary neonatal rat CMF revealed that silencing of C/EBPβ expression (via lentiviral mediated shRNA strategies) was sufficient to reduce C/EBPβ mRNA and protein levels as well as to decrease the expressions of actin cytoskeletal proteins, cofilin, and filamin A (FLNA). TGFβ increased IL-1β, IL-6 and TNF-a production in cardiac fibroblasts (CF), while C/EBPβ knockdown reduced the secretion of these inflammatory mediators. In vivo studies performed in rats exhibiting EAM revealed that lentiviral-mediated silencing of C/EBPβ was sufficient to reduce the expression of C/EBPβ as well as inflammation and fibrosis in the hearts of EAM rats, when compared to controls. Echocardiography further revealed that C/EBPβ knockdown was sufficient to significantly improve cardiac dimensions and function in EAM rats. Immunohistochemical results showed that C/EBPβ knockdown attenuated the expression of C/EBPβ protein as well as the expressions of collagen I, collagen III, MMP-2, MMP-9, and α-SMA in heart tissue sections from rats in the EAM + Lenti-shC/EBPβ group.Strategies targeted at inhibiting C/EBPβ expression can be potentially exploited to regulate cofilin and FLNA expression, thereby regulating actin polymerization/depolymerization, cytoskeleton rearrangement, and CF differentiation into CMF and the production of inflammatory cytokines. C/EBPβ knock down reduces the degree of inflammation-mediated myocardial fibrosis in a rat model of EAM.


Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that attacks pancreatic β-cells, leading to the destruction of insulitis-related islet β-cells. Islet β-cell transplantation has been proven as a curative measure in T1DM. However, a logarithmic increase in the global population with diabetes, limited donor supply, and the need for lifelong immunosuppression restrict the widespread use of β-cell transplantation. Numerous therapeutic approaches have been taken to search for substitutes of β-cells, among which stem cell transplantation is one of the most promising alternatives. Stem cells have demonstrated the potential efficacy to treat T1DM by reconstitution of immunotolerance and preservation of islet β-cell function in recent research. cGMP-grade stem cell products have been used in human clinical trials, showing that stem cell transplantation has beneficial effects on T1DM, with no obvious adverse reactions. To better achieve remission of T1DM by stem cell transplantation, in this work, we explain the progression of stem cell transplantation such as mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), and bone marrow hematopoietic stem cells (BM-HSCs) to restore the immunotolerance and preserve the islet β-cell function of T1DM in recent years. This review article provides evidence of the clinical applications of stem cell therapy in the treatment of T1DM.


The development of the nursing labor force in the United States: a basic analysis.
In this article, we draw together some basic material on the objectives character of the nursing labor force in the United States. First, we present a statistical and descriptive picture of the nursing labor force as it exists today. Then we analyze the historical development of that labor force up to about 1950, stressing its general integration into a hierarchical and concentrated health industry. Finally, we look at the development of the nursing labor force over the past 25 years in terms of factors such as sex, race, age educational credentials, labor force participation, place of work, and the hierarchical division of labor, discussing the general implications of the changes in these factors for worker organization in the health industry. Our main conclusion is that the nursing labor force is in a kiey position to lead a movement for the restructing of the health industry to serve the health needs of the American people rather than the profit and power requirements of the health employers. The primary, and difficult, task ahead is to build labor organization which will have the vision and unity to work this goal.


Semi-synthetic diversification of coronarin D, a labdane diterpene, under Ugi reaction conditions.
The prevalence of 5-hydroxydihydrofuran-2(3H)-one moiety in natural products is exploited for the first time using coronarin D, a labdane diterpene, to afford Ugi reaction product 1a and interrupted Ugi product 2a. The potential of the Ugi reaction was further extended to l-phenylalanine, 2-aminopyridine, and d-glucosamine, which afforded Ugi reaction products 3a-f, 4, and 5a-d, respectively. Cytotoxicity studies in RAW cells reveal that compounds 3e and 5b were non-toxic up to 50 µM, and these compounds were able to reduce the LPS stimulated NO production in RAW cells in par with the standard anti-inflammatory drug dexamethasone.


In vivo molecular pharmacology and antitumor activity of the targeted Akt inhibitor PX-316.
Akt, a serine/threonine kinase that promotes cell survival, is activated by binding of its pleckstrin homology (PH) domain to membrane phosphatidylinositol (PtdIns)-3-phosphates formed by PtdIns-3-kinase. D-3-Deoxy-phosphatidyl-myo-inositols that cannot be phosphorylated on the 3-position of the myo-inositol group are inhibitors of the Akt PH domain. The most active compound is D-3-deoxy-phosphatidyl-myo-inositol 1-[(R)-2-methoxy-3-octadecyloxypropyl hydrogen phosphate] (PX-316). PX-316 administered intraperitoneally to mice at 150 mg/kg inhibits Akt activation in HT-29 human tumor xenografts up to 78% at 10 h with recovery to 34% at 48 h. Phosphorylation of GSK-3beta, a downstream target of Akt, is also inhibited. There is no decrease in PtdIns(3,4,5)-trisphosphate levels by PX-316, showing it is not an inhibitor of PtdIns-3-K in vivo. Gene expression profiling of HT-29 tumor xenografts shows many similarities between the effects of PX-316 and the PtdIns-3-K inhibitor wortmannin, with downregulation of several ribosomal-related genes, while PX-316 uniquely increases the expression of a group of mitochondrial-related genes. PX-316 has antitumor activity against early human MCF-7 breast cancer and HT-29 colon cancer xenografts in mice. PX-316 formulated in 20% hydroxypropyl-beta-cyclodextrin for intravenous administration is well tolerated in mice and rats with no hemolysis and no hematological toxicity. Thus, PX-316 is the lead compound of a new class of potential agents that inhibit Akt survival signaling.


Protective Role of Corticosterone against Hydrogen Peroxide-Induced Neuronal Cell Death in SH-SY5Y Cells.
Stress breaks body balance, which can cause diverse physiological disorders and worsen preexisting diseases. However, recent studies have reported that controllable stress and overcoming from stress reinforce resilience to resist against more intense stress afterwards. In this study, we investigated the protective effect of corticosterone (CORT), a representative stress hormone against hydrogen peroxide (H2O2)-induced neuronal cell death and its underlying molecular mechanism in SH-SY5Y cells, a human neuroblastoma cell line. The decreased cell viability by H2O2 was effectively restored by the pretreatment with low concentration of CORT (0.03 μM for 72 h) in the cells. H2O2-increased expression of apoptotic markers such as PUMA and Bim was decreased by CORT pretreatment. Furthermore, pretreatment of CORT attenuated H2O2-mediated oxidative damages by upregulation of antioxidant enzymes via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that low concentration of CORT with eustressed condition enhances intracellular self-defense against H2O2-mediated oxidative cell death, suggesting a role of low concentration of CORT as one of key molecules for resilience and neuronal cell survival.


Life cycle assessment of capital goods in waste management systems.
The environmental importance of capital goods (trucks, buildings, equipment, etc.) was quantified by LCA modelling 1 tonne of waste treated in five different waste management scenarios. The scenarios involved a 240L collection bin, a 16m(3) collection truck, a composting plant, an anaerobic digestion plant, an incinerator and a landfill site. The contribution of capital goods to the overall environmental aspects of managing the waste was significant but varied greatly depending on the technology and the impact category: Global Warming: 1-17%, Stratospheric Ozone Depletion: 2-90%, Ionising Radiation, Human Health: 2-91%, Photochemical Ozone Formation: 2-56%, Freshwater Eutrophication: 0.05-99%, Marine Eutrophication: 0.03-8%, Terrestrial Acidification: 2-13%, Terrestrial Eutrophication: 1-8%, Particulate Matter: 11-26%, Human Toxicity, Cancer Effect: 10-92%, Human Toxicity, non-Cancer Effect: 1-71%, Freshwater Ecotoxicity: 3-58%. Depletion of Abiotic Resources - Fossil: 1-31% and Depletion of Abiotic Resources - Elements (Reserve base): 74-99%. The single most important contribution by capital goods was made by the high use of steel. Environmental impacts from capital goods are more significant for treatment facilities than for the collection and transportation of waste and for the landfilling of waste. It is concluded that the environmental impacts of capital goods should always be included in the LCA modelling of waste management, unless the only impact category considered is Global Warming.


Distinct roles of light-activated channels TRP and TRPL in photoreceptors of Periplaneta americana.
Electrophysiological studies in Drosophila melanogaster and Periplaneta americana have found that the receptor current in their microvillar photoreceptors is generated by two light-activated cationic channels, TRP (transient receptor potential) and TRPL (TRP-like), each having distinct properties. However, the relative contribution of the two channel types to sensory information coding by photoreceptors remains unclear. We recently showed that, in contrast to the diurnal Drosophila in which TRP is the principal phototransduction channel, photoreceptors of the nocturnal P. americana strongly depend on TRPL. Here, we perform a functional analysis, using patch-clamp and intracellular recordings, of P. americana photoreceptors after RNA interference to knock down TRP (TRPkd) and TRPL (TRPLkd). Several functional properties were changed in both knockdown phenotypes: cell membrane capacitance was reduced 1.7-fold, light sensitivity was greatly reduced, and amplitudes of sustained light-induced currents and voltage responses decreased more than twofold over the entire range of light intensities. The information rate (IR) was tested using a Gaussian white-noise modulated light stimulus and was lower in TRPkd photoreceptors (28 ± 21 bits/s) than in controls (52 ± 13 bits/s) because of high levels of bump noise. In contrast, although signal amplitudes were smaller than in controls, the mean IR of TRPLkd photoreceptors was unchanged at 54 ± 29 bits/s1 because of proportionally lower noise. We conclude that TRPL channels provide high-gain/high-noise transduction, suitable for vision in dim light, whereas transduction by TRP channels is relatively low-gain/low-noise and allows better information transfer in bright light.


Bilateral Squatting Mechanics Are Associated With Landing Mechanics in Anterior Cruciate Ligament Reconstruction Patients.
Proper lower extremity biomechanics during bilateral landing is important for reducing injury risk in athletes returning to sports after anterior cruciate ligament reconstruction (ACLR). Although landing is a quick ballistic movement that is difficult to modify, squatting is a slower cyclic movement that is ideal for motor learning. There is a relationship between lower extremity biomechanics during bilateral landing and bilateral squatting in patients with an ACLR. Descriptive laboratory study. A total of 41 patients after a unilateral ACLR (24 men, 17 women; 5.9 ± 1.4 months after ACLR) completed 15 unweighted bilateral squats and 10 bilateral stop-jumps. Three-dimensional lower extremity kinematics and kinetics were collected, and peak knee abduction angle, knee abduction/adduction range of motion, peak vertical ground-reaction force limb symmetry index (LSI), vertical ground-reaction force impulse LSI, and peak knee extension moment LSI were computed during the descending phase of the squatting and landing tasks. Wilcoxon signed-rank tests were used to compare each outcome between limbs, and Spearman correlations were used to compare outcomes between the squatting and landing tasks. The peak vertical ground reaction force, the vertical ground reaction force impulse, and the peak knee extension moment were reduced in the surgical (Sx) limb relative to the nonsurgical (NSx) limb during both the squatting and landing tasks (P < .001). The relationship between squatting and landing tasks was strong for the peak knee abduction angle (R = 0.697-0.737; P < .001); moderate for the frontal plane knee range of motion (NSx: R = 0.366, P = .019; Sx: R = 0.418, P = 0.007), the peak knee extension moment LSI (R = 0.573; P < .001), the vertical ground reaction force impulse LSI (R = 0.382; P < .014); and weak for the peak vertical ground reaction force LSI (R = 0.323; P = .039). Patients who have undergone an ACLR continue to offload their surgical limb during both squatting and landing. Additionally, there is a relationship between movement deficits during squatting and movement deficits during landing in patients with an ACLR preparing to return to sports. As movement deficits during squatting and landing were related before return to sports, this study suggests that interventional approaches to improve squatting biomechanics may translate to improved landing biomechanics in patients with an ACLR.


Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.
The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC). The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index. Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05). This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.


How Effectively Do People Remember Voice Disordered Speech? An Investigation of the Serial-Position Curve.
We examined how well typical adult listeners remember the speech of a person with a voice disorder (relative to that of a person without a voice disorder). Participants (n = 40) listened to two lists of words (one list uttered in a disordered voice and the other list uttered in a normal voice). After each list, participants completed a free recall test, in which they tried to remember as many words as they could. While the total number of words recalled did not differ between the disordered voice condition and the normal voice condition, an investigation of the serial-position curve revealed a difference. In the normal voice condition, a parabolic (i.e., u-shaped) serial-position curve was observed, with a significant primacy effect (i.e., the beginning of the list was remembered better than the middle) and a significant recency effect (i.e., the end of the list was remembered better than the middle). In contrast, in the disordered voice condition, while there was a significant recency effect, no primacy effect was present. Thus, the increased ability to remember the first words uttered by a speaker (relative to subsequent words) may disappear when the speaker has a voice disorder. Explanations and implications of this finding are discussed.


Barrier contraception.
Barrier contraception is a safe, effective, reversible form of contraception acceptable to many couples. The use of barrier contraception may protect against carcinoma of the cervix and sexually transmitted diseases. Distribution and education in the use of barrier contraception does not always require medical supervision. This must make it an attractive form of contraception for agencies supporting family planning programmes in developing countries. The only marketed recent advance in barrier contraception is the collatex sponge. Effectiveness rates range between 9 and 27 pregnancies per 100 woman-years. This is unlikely to make it the first choice of contraception for couples who would find an unintended pregnancy a severe problem, but the sponge will be acceptable to couples who are simply trying to delay a pregnancy. The new surge of interest in barrier contraception could lead to safer more effective forms of contraception being made available to women without medical supervision. This would have many advantages, but could also detract from the ability of family planning clinics to play an important role in preventative medicine for women.


Demystifying first-cost green building premiums in healthcare.
This study assesses the extent of "first-cost green building construction premiums" in the healthcare sector based on data submitted by and interviews with 13 current LEED-certified and LEED-registered healthcare project teams, coupled with a literature survey of articles on the topics of actual and perceived first-cost premiums associated with green building strategies. This analysis covers both perceived and realized costs across a range of projects in this sector, leading to the following conclusions: Construction first-cost premiums may be lower than is generally perceived, and they appear to be independent of both building size and level of "green" achievement; projects are using financial incentives and philanthropy to drive higher levels of achievement; premiums are decreasing over time; and projects are benefiting from improvements in health and productivity which, although difficult to monetize, are universally valued.


Angiographically-assessed coronary artery disease associates with HDL particle size in women.
It has been suggested that a reduced HDL particle size could be another feature of the atherogenic dyslipidemia found among viscerally obese subjects. To investigate, in women, the relationship between HDL particle size and coronary artery disease (CAD). Average HDL particle size was measured in a sample of 239 women on whom CAD was assessed by angiography. Overall, women who had CAD were characterized by a deteriorated fasting metabolic risk profile, which was accompanied by smaller HDL particles compared to women without CAD (80.4 ± 2.2 Å vs. 81.5 ± 2.7 Å, p < 0.01). In addition, a reduced HDL particle size was a significant correlate of several features of the atherogenic metabolic profile of abdominal obesity such as increased triglyceride and apolipoprotein B concentrations, decreased HDL cholesterol levels, an elevated cholesterol/HDL cholesterol ratio and hyperinsulinemia and was also associated with an increased waist circumference (0.13≤|r|≤0.21, p < 0.05). Odds ratio of being affected by CAD was increased by 2.5-fold (95% CI: 1.4-4.5; p < 0.01) among women with smaller HDL particles compared to women with larger HDL particles. Finally, women characterized by the presence of the NCEP-ATP III clinical criteria or by hypertriglyceridemic waist were characterized by smaller HDL particles compared to women without these clinical phenotypes (p < 0.05). HDL particle size appears to be another relevant feature of a dysmetabolic state which is related to CAD risk in women.


Two-stage testing in microarray analysis: what is gained?
Microarray technology for gene expression studies offers powerful new technology for understanding changes in gene expression as a function of other observable or manipulable variables. However, microarrays also pose a number of new challenges. One of the most prominent of these is the difficulty in establishing a procedure for declaring whether a gene's expression level is associated with the independent variable that offers reasonable and specifiable false-positive (type 1 error) and false-negative (type 2 error) rates. A recent article described a two-stage testing procedure to address these goals. However, information was not provided to indicate whether this procedure would or would not meet its objectives. Herein, we show mathematically that the two-stage procedure proposed does not provide benefits in terms of minimizing false-negatives while controlling the false-positive rate relative to standard single-stage testing. Therefore, investigators are encouraged to consider alternative analytic approaches.


Publication status and reporting quality of case reports on acupuncture-related adverse events: A systematic reviews of case studies.
Case reports on acupuncture-related adverse events (AEs) have been consistently published in the literature. This review aims to assess the current publication status of case reports on acupuncture-related AEs and evaluate their reporting quality in order to identify areas for improvement. This study is a systematic review (SR) of case reports. Studies describing cases for acupuncture-related AEs between 2010 and 2023 (until July) were searched in PubMed, Embase, and local databases (China and Korea), as well as by hand-searching references included in published relevant SRs. A bibliometric analysis was conducted to examine the publication trends of the included literature. The appropriateness of the acupuncture described in the cases, the causality assessment between AEs and acupuncture treatment, and the presence of necessary items from the CAse REport guidelines (CARE) checklist were narratively analyzed. A total of 169 case reports were included in this review. Over the past decade, an average of 12 case reports on acupuncture-related AEs were published annually. However, only 38.2% of the articles provided sufficient information to determine the appropriateness of the acupuncture treatment used in the reported cases, and considerable numbers of the included case reports did not suggest enough information for the assessment of a causal relationship. The majority of cases did not report the timeline (n = 164), patient perspectives (n = 157), and informed consent (n = 121) items from the CARE checklist. Acupuncture-related AEs persist in being frequently reported in the literature. Nonetheless, the information concerning acupuncture and causality assessment within these publications is still found to be insufficient. The development of reporting guidelines for future case reports on acupuncture-related AEs is anticipated to promote an academic environment conducive to more comprehensive reporting.


Epigenetic Reprogramming in Early Animal Development.
Dramatic nuclear reorganization occurs during early development to convert terminally differentiated gametes to a totipotent zygote, which then gives rise to an embryo. Aberrant epigenome resetting severely impairs embryo development and even leads to lethality. How the epigenomes are inherited, reprogrammed, and reestablished in this critical developmental period has gradually been unveiled through the rapid development of technologies including ultrasensitive chromatin analysis methods. In this review, we summarize the latest findings on epigenetic reprogramming in gametogenesis and embryogenesis, and how it contributes to gamete maturation and parental-to-zygotic transition. Finally, we highlight the key questions that remain to be answered to fully understand chromatin regulation and nuclear reprogramming in early development.


Computed tomography demonstrates short axial globe length in cases with idiopathic intracranial hypertension.
Cases with idiopathic intracranial hypertension (IIH) have been anecdotally found to demonstrate relatively short axial lengths on ultrasound A-scans. This finding has not been rigorously documented. We therefore systematically investigated globe shape in these cases using computed tomography. Computed tomographic 0.625-mm sections of 10 cases with IIH and 10 control subjects were reformatted on a workstation. Globe lengths and widths were measured from axial reformats. Globe lengths and heights were measured from oblique sagittal reformats. Two masked observers took all the measurements. The mean axial lengths of the globes of cases with IIH were significantly shorter than those of controls (t test for independent samples, P<0.001). Both observers also found globe height to be significantly greater than globe length in oblique sagittal sections of cases with IIH compared with control subjects (Mann-Whitney U tests, P<0.01). The difference between length and width in axial sections was not different between cases with IIH and control subjects. Using a critical cutoff of 0.6-mm difference between globe height and length in oblique sagittal sections returned a sensitivity of 0.75 and a specificity of 0.75 for IIH detection from both right and left eyes. There are significant differences in globe shape and axial length between cases with IIH and control subjects. The differences in globe shape manifest significantly only in oblique sagittal sections. This imaging sign could be a useful marker for subclinical IIH.


Distribution of NOS isoforms in a porcine endotoxin shock model.
Sepsis is a major cause of morbidity and mortality. NO, an endogenous vasodilator, has been associated with the hypotension, catecholamine hyporesponsiveness, and myocardial depression of septic shock. Although iNOS is thought to be responsible for the hypotension and loss of vascular tone occurring several hours after endotoxin administration, little is known on the effects of constitutive eNOS on LPS-induced organ dysfunction. This study assessed the distribution of eNOS and iNOS in various vascular beds in conscious pigs challenged with LPS. Cardiac and regional hemodynamic parameters were recorded over 8 h in the presence and absence of aminoguanidine, a rather selective inhibitor of iNOS activity, and N-methyl-L-arginine, a nonspecific NOS inhibitor. Our data show that LPS-induced cardiac depression was associated with coronary, renal, and mesenteric vasoconstrictions and a hepatic vasodilatation. LPS also induced increases in eNOS in the heart and lungs, whereas iNOS was mostly detected in the liver. Nitrotyrosine formation was mainly detected in the lungs, with traces in the kidney, liver, and gut. Accordingly, our results suggest that the early decrease in blood pressure and cardiac depression are likely due to activated eNOS, whereas both isoforms are involved in the hepatic vasodilation. In contrast, carotid, coronary, mesenteric, and renal vasoconstrictions were significant at 5 and/ or 6 h after LPS infusion, suggesting that NO is not the primary mediator, facilitating and/or unmasking the release of vasoconstrictor mediators. Consequently, developing newer tissue- or isoform-specific NOS inhibitors can lead to novel therapeutic agents in septic shock.


Flow cytometric detection of lymphocyte proliferation in eyes with immunogenic inflammation.
Identification and analysis of antigen-activated lymphocytes from sites of ocular inflammation is important to understanding of the role of infiltrating immune effectors in ocular inflammatory disease. Unfortunately, few assays can distinguish activated lymphocytes from the antigen-irrelevant lymphocytes that randomly migrate to sites of inflammation. The authors describe a method that allows the quantitative recovery and identification of activated lymphocytes from mouse eyes. Recovered subconjunctival lymphocytes were simultaneously stained for specific cell-surface markers (with fluorescein-labeled antibodies) and for DNA content (with propidium iodide), then analyzed by flow cytometry. For any subpopulation of lymphocytes, the relative percentage and absolute number of cells in each phase of the cell cycle was determined. The activated subset of T and B cells was quantitated by determining the number of proliferating cells (ie, the number of cells in the S + G2 + M phases of the cell cycle). Using this method, T cell proliferation was found to be a specific component of the subconjunctival immunogenic inflammatory response induced by a local graft-versus-host reaction and by subconjunctival delayed hypersensitivity reactions. In addition, proliferating T cells could be distinguished from nonproliferating B cells produced by the subconjunctival inoculation of a T cell tumor.


Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors.
This study evaluated the therapeutic efficacy of interleukin 12 (IL-12) gene therapy in Ewing sarcoma and whether murine mesenchymal stem cells (MSCs) could serve as vehicles for IL-12 gene delivery. MSCs were isolated from murine bone marrow cells. Cells were phenotyped using flow cytometry. Cultured MSCs differentiated into osteocytes and adipocytes using the appropriate media. Freshly isolated MSCs were transfected with adenoviral vectors containing either the beta-galactosidase (Ad:beta-gal) or the IL-12 (Ad:IL-12) gene. Expression of IL-12 was confirmed using reverse transcription polymerase chain reaction. Mice with TC71 Ewing sarcoma tumors were then treated intravenously with MSCs transfected with Ad:beta-gal or Ad:IL-12. Tumors were measured and analyzed by immunohistochemical analysis for expression of IL-12 protein. Expression of both p35 and p40 IL-12 subunits was demonstrated in MSCs transfected in vitro with Ad:IL-12. IL-12 expression was seen in tumors from mice treated with MSCs transfected with Ad:IL-12. Tumor growth was also significantly inhibited compared with that in mice treated with MSCs transfected with Ad:beta-gal. MSCs can be transfected with the IL-12 gene. These transfected cells localize to tumors after intravenous injection and induce local IL-12 protein production and the regression of established tumors.


Understanding the within-host dynamics of influenza A virus: from theory to clinical implications.
Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.


Inelastic collisions of molecular hydrogen: a comparison of results from quantum and classical mechanics.
Full-dimensional quantum and classical calculations have been carried out for inelastic (nonreactive) energy transfer in H2+H2 on the ab initio potential energy surface of Boothroyd et al. [J. Chem. Phys. 116, 666 (2002)]. State-to-state cross sections are determined and compared for transitions from H2(0,j(ab))+H2(1,j(cd)). While there is excellent agreement for transitions involving small Deltaj, for larger Deltaj and for vibrational relaxation, significant differences are observed which exhibit no systematic trends. Reasons for this disagreement are discussed.


Rickettsial Infections among the Undifferentiated Febrile Patients Attending a Tertiary Care Teaching Hospital of Northern India: A Longitudinal Study.
Acute undifferentiated febrile illness (AUFI) is one of the most daunting challenges a physician faces in such settings. Among AUFI, rickettsial infections are most common and related infections (such as anaplasmosis, ehrlichiosis, and Q fever) which are caused by an unusual type of bacteria that can live only inside the cells of another organism. The present study was therefore planned with an objective to estimate the prevalence of rickettsial infection among patients of undifferentiated fever and to determine any association of socio-demographic characteristics with rickettsial disease. Patients presenting with febrile illness and admitted or attending out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar was approached and recruited in the study. Weil Felix Assay, enzyme-linked immunosorbent assay and indirect immunofluorescence assay were done to detect the anti-rickettsial antibodies. Serological evidence of a fourfold increase in IgG-specific antibody titer reactive with spotted fever group rickettsial antigen by indirect immunofluorescence antibody assays between paired serum specimens was considered a confirmatory diagnosis for the rickettsial disease. Most of the patients were males 61.6%, and most 46.2% were in the age group of 20 -39 years. Most of the patients, 80.8% belonged to rural areas, and 48% belonged to the upper middle (II) class of the socio-economic class according to modified Kuppuswamy scale. Of the studied participants, a majority, 47.0%, were determined undiagnosed, while 15.4% studied participants were diagnosed to have a rickettsial disease. In patients positive for typhus group, 67.8% were IgM positive, 28.5% were IgG positive, and only 3% were positive for IgM and IgG. In patients positive for Scrub Typhus Group, 32.7% were positive for IgM, and 62.0% were positive for IgG, and only 5.0% were positive for both IgM and IgG. In patients positive for spotted fever group, 36.1% were positive for IgM, and 58.5% were positive for IgG, and only 5.5% were positive for both IgM and IgG. The prevalence of rickettsial disease was found to be 11.3%. Rickettsial diseases, typhoid and brucellosis, were the most prevalent diseased diagnosed among patients reporting to hospitals with undifferentiated febrile illness. Clinicians must consider rickettsial diseases as one of the differential diagnosis while treating patients with fever.


FREQUENCY-DEPENDENT SEED PRODUCTION AND HYBRIDIZATION RATES: IMPLICATIONS FOR GENE FLOW BETWEEN LOCALLY ADAPTED PLANT POPULATIONS.
Gene flow between genetically distinct plant populations can have significant evolutionary consequences. It can increase genetic diversity, create novel gene combinations, and transfer adaptations from one population to another. This study addresses the roles of frequency-dependent selection and mating system in gene exchange between two subspecies of Gilia capitata (Polemoniaceae). Long-distance migrants are likely to be rare in new habitats, and the importance of immigrant frequency to fitness, gene exchange, and ultimately introgression, has not been explored. To test for the importance of frequency in migration, a field experiment was conducted in which artificial populations (arrays) composed of different mixtures of the two subspecies were placed in the home habitats of both. Female function (seed production) and a portion of male function (hybridization rate) were compared for the two subspecies to assess the potential for gene exchange and introgression between them. Individual fitness (through both hybridization and seed production) for the inland subspecies varied with its frequency as an immigrant at the coastal site. Rare immigrants produced fewer seeds and fathered fewer hybrid offspring. In contrast, both forms of reproductive function were frequency independent for the coastal subspecies when it was an immigrant at the inland site. Seed production was high and insensitive to frequency, and immigrants from the coast never successfully fertilized the inland subspecies' seeds. To control for the effects of frequency-dependent pollinator behavior in the field, hand crosses were performed in the greenhouse using a range of pollen mixtures. The greenhouse experiment demonstrated that cross-fertilization is possible in only one direction, that cross-pollination in the other direction is only partially successful, and that pollen from the coastal subspecies has a strong negative effect on seed production by the inland subspecies. Experimental pollen supplementation in the field verified both the unilateral incompatibility and the negative effect of coastal pollen on inland plant seed production observed in the greenhouse. Contrasts between field array and greenhouse results suggest that pollinator behavior and other ecological factors act to exaggerate reproductive barriers between the two subspecies. In this system, immigrant frequency interacts with reproductive biology and pollinator ecology to enhance gene flow between the populations in one direction, while restricting gene establishment and introgression in the other direction.


An objective comparison between bivalirudin and heparin during peripheral vascular interventions.
Patients undergoing percutaneous peripheral interventions are at increased risk for thrombotic complications hence the routine use of periprocedural anticoagulants. There is currently no American College of Cardiology/American Heart Association guidelines for periprocedural anticoagulants use in percutaneous peripheral interventions. Historically, unfractionated heparin has been the most common periprocedural anticoagulant used during percutaneous peripheral interventions. There may be a role for more predictable periprocedural anticoagulants in percutaneous peripheral interventions as has been demonstrated in percutaneous coronary interventions. Our review focuses on the evidence supporting the use of bivalirudin in percutaneous peripheral interventions.


Secondary Structure Prediction of Protein Constructs Using Random Incremental Truncation and Vacuum-Ultraviolet CD Spectroscopy.
A novel uracil-DNA degrading protein factor (termed UDE) was identified in Drosophila melanogaster with no significant structural and functional homology to other uracil-DNA binding or processing factors. Determination of the 3D structure of UDE is excepted to provide key information on the description of the molecular mechanism of action of UDE catalysis, as well as in general uracil-recognition and nuclease action. Towards this long-term aim, the random library ESPRIT technology was applied to the novel protein UDE to overcome problems in identifying soluble expressing constructs given the absence of precise information on domain content and arrangement. Nine constructs of UDE were chosen to decipher structural and functional relationships. Vacuum ultraviolet circular dichroism (VUVCD) spectroscopy was performed to define the secondary structure content and location within UDE and its truncated variants. The quantitative analysis demonstrated exclusive α-helical content for the full-length protein, which is preserved in the truncated constructs. Arrangement of α-helical bundles within the truncated protein segments suggested new domain boundaries which differ from the conserved motifs determined by sequence-based alignment of UDE homologues. Here we demonstrate that the combination of ESPRIT and VUVCD spectroscopy provides a new structural description of UDE and confirms that the truncated constructs are useful for further detailed functional studies.


Medical risk in patients with bipolar disorder and schizophrenia.
Patients with schizophrenia and bipolar disorder are vulnerable to developing key modifiable risk factors for cardiovascular disease, such as obesity, smoking, hypertension, dyslipidemia, and type 2 diabetes mellitus. In addition, mood stabilizers, anticonvulsants, and antipsychotic medications, which are commonly used to treat schizophrenia and bipolar disorder, have been linked to risk for adverse metabolic changes in patients. This review reports the prevalence of medical risk factors in the general population as well as in those patients with schizophrenia or bipolar disorder and discusses treatment strategies and lifestyle changes that patients can make in order to reduce their risks for certain diseases.


Interactive gene-order comparison for multiple small genomes.
The Genome Organization Analysis Tool (GOAT) is a program that performs comparative sequence analysis on ordered gene lists from annotated genomes, provides visual and tabular output, and provides means of accessing and analyzing related gene sequence data, for the purpose of comparing genome organization at the gene-order level. GOAT can be used to compare any two or more genomes or chromosomes on demand, or configured to provide access to precomputed comparisons of a specific group of genome sequences. Demonstration web server and software download, subject to the Virginia Tech Noncommercial License are available at http://gaia.biotech.vt.edu/goat/. Updates, installation and configuration information are available at http://gaia.biotech.vt.edu/goat.


Post-anthesis Relationships Between Nitrogen Isotope Discrimination and Yield of Spring Wheat Under Different Nitrogen Levels.
Wheat grain yield and nitrogen (N) content are influenced by the amount of N remobilized to the grain, together with pre-anthesis and post-anthesis N uptake. Isotopic techniques in farmed areas may provide insight into the mechanism underlying the N cycle. 15N-labeled urea was applied to microplots within five different fertilized treatments 0 kg ha-1 (N1), 52.5 kg ha-1 (N2), 105 kg ha-1 (N3), 157.5 kg ha-1 (N4), and 210 kg ha-1 (N5) of a long-term field trial (2003-2021) in a rainfed wheat field in the semi-arid loess Plateau, China, to determine post-anthesis N uptake and remobilization into the grain, as well as the variability of 15N enrichment in aboveground parts. Total N uptake was between 7.88 and 29.27 kg ha-1 for straw and 41.85 and 95.27 kg ha-1 for grain. In comparison to N1, N fertilization increased straw and grain N uptake by 73.1 and 56.1%, respectively. Nitrogen use efficiency (NUE) and harvest index were altered by N application rates. The average NUE at maturity was 19.9% in 2020 and 20.01% in 2021; however, it was usually higher under the control and low N conditions. The amount of 15N excess increased as the N rate increased: N5 had the highest 15N excess at the maturity stage in the upper (2.28 ± 0.36%), the middle (1.77 ± 0.28%), and the lower portion (1.68 ± 1.01%). Compared to N1, N fertilization (N2-N5) increased 15N excess in the various shoot portions by 50, 38, and 35% at maturity for upper, middle, and lower portions, respectively. At maturity, the 15N excess remobilized to the grain under N1-N5 was between 5 and 8%. Our findings revealed that N had a significant impact on yield and N isotope discrimination in spring wheat that these two parameters can interact, and that future research on the relationship between yield and N isotope discrimination in spring wheat should take these factors into account.


Structural and functional insights into intramolecular fructosyl transfer by inulin fructotransferase.
Inulin fructotransferase (IFTase), a member of glycoside hydrolase family 91, catalyzes depolymerization of beta-2,1-fructans inulin by successively removing the terminal difructosaccharide units as cyclic anhydrides via intramolecular fructosyl transfer. The crystal structures of IFTase and its substrate-bound complex reveal that IFTase is a trimeric enzyme, and each monomer folds into a right-handed parallel beta-helix. Despite variation in the number and conformation of its beta-strands, the IFTase beta-helix has a structure that is largely reminiscent of other beta-helix structures but is unprecedented in that trimerization is a prerequisite for catalytic activity, and the active site is located at the monomer-monomer interface. Results from crystallographic studies and site-directed mutagenesis provide a structural basis for the exolytic-type activity of IFTase and a functional resemblance to inverting-type glycosyltransferases.


Tracking surface glycans on live cancer cells with single-molecule sensitivity.
Using a combination of metabolically labeled glycans, a bioorthogonal copper(I)-catalyzed azide-alkyne cycloaddition, and the controlled bleaching of fluorescent probes conjugated to azide- or alkyne-tagged glycans, a sufficiently low spatial density of dye-labeled glycans was achieved, enabling dynamic single-molecule tracking and super-resolution imaging of N-linked sialic acids and O-linked N-acetyl galactosamine (GalNAc) on the membrane of live cells. Analysis of the trajectories of these dye-labeled glycans in mammary cancer cells revealed constrained diffusion of both N- and O-linked glycans, which was interpreted as reflecting the mobility of the glycan rather than to be caused by transient immobilization owing to spatial inhomogeneities on the plasma membrane. Stochastic optical reconstruction microscopy (STORM) imaging revealed the structure of dynamic membrane nanotubes.


Dependence of threshold behavior upon surface distribution of polymer chains in a twisted nematic liquid crystal.
On the basis of a general Rapini and Papoular equation and a unified surface anchoring energy theory, dependence of the threshold behavior of the liquid crystal director upon the statistical distribution of polyimide chains is theoretically investigated for a twisted nematic liquid crystal cell. We assumed that the anisotropy distribution of polyimide chains induced by the rubbing can be dominated by a Gaussian distribution around the rubbing direction. Our results show that the threshold behavior of a twisted nematic liquid crystal is affected strongly by the surface distribution of polymer chains.


MDA-7/IL-24 functions as a tumor suppressor gene in vivo in transgenic mouse models of breast cancer.
Melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) is a novel member of the IL-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues. The ability to investigate the critical events underlying cancer initiation and progression, as well as the capacity to test the efficacy of novel therapeutics, has been significantly advanced by the development of genetically engineered mice (GEMs) that accurately recapitulate specific human cancers. We utilized three transgenic mouse models to better comprehend the in vivo role of MDA-7/IL-24 in breast cancer. Using the MMTV-PyMT spontaneous mammary tumor model, we confirmed that exogenously introducing MDA-7/IL-24 using a Cancer Terminator Virus caused a reduction in tumor burden and also produced an antitumor "bystander" effect. Next we performed xenograft studies in a newly created MMTV-MDA-7 transgenic model that over-expresses MDA-7/IL-24 in the mammary glands during pregnancy and lactation, and found that MDA-7/IL-24 overexpression delayed tumor growth following orthotopic injection of a murine PDX tumor cell line (mPDX) derived from a tumor formed in an MMTV-PyMT mouse. We also crossed the MMTV-MDA-7 line to MMTV-Erbb2 transgenic mice and found that MDA-7/IL-24 overexpression delayed the onset of mammary tumor development in this model of spontaneous mammary tumorigenesis as well. Finally, we assessed the role of MDA-7/IL-24 in immune regulation, which can potentially contribute to tumor suppression in vivo. Our findings provide further direct in vivo evidence for the role of MDA-7/IL-24 in tumor suppression in breast cancer in immune-competent transgenic mice.


The influence of monetary compensation on relapse among addicted participants: empirical vs. anecdotal evidence.
Although common, the use of cash incentives to compensate drug-addicted participants is controversial. This is particularly true given concerns that cash incentives might precipitate relapse, as is commonly believed. The following investigation examined whether cash versus money order compensation differentially influenced drug use among 34 non-treatment-seeking, cocaine-dependent individuals. Consistent with past evidence, results did not suggest that form of compensation was associated with likelihood of continued cocaine use or dollar amount of cocaine consumed after participation. Findings do not support commonly held concerns that cash incentives increase the risk of relapse following research participation.


Static and time-resolved fluorescence studies of fluorescent phosphatidylcholine bound to the phosphatidylcholine transfer protein of bovine liver.
Phosphatidylcholine analogues containing a cis- parinaroyl chain at the sn-1, sn-2, or both sn-1 and sn-2 positions (1-PnA-PC, 2-PnA-PC, and diPnA -PC, respectively) have been used to investigate the lipid binding site of the phosphatidylcholine transfer protein (PC-TP) from bovine liver by fluorometric techniques. Binding of these fluorescent lipids to the protein was registered by measuring the enhancement of parinaroyl fluorescence and the quenching of the tryptophanyl fluorescence. The fluorescence intensity of 1-PnA-, 2-PnA- and diPnA -PC bound to PC-TP was proportional to the chromophore content. The energy-transfer efficiency between the tryptophan residues and the bound chromophores was approximately 40% for 1-PnA- and 2-PnA-PC and 60% for diPnA -PC. Quenching of the tryptophanyl fluorescence was, in part, accounted for by a decrease of the fluorescence lifetimes. The orientation of the 1 and 2 fatty acyl chains of the PnA-PC analogues on the transfer protein was analyzed by time-resolved fluorescence anisotropy measurements. The fluorescence anisotropy decayed according to a single exponential function yielding a rotational correlation time of 26 ns for 1-PnA-PC, 11 ns for 2-PnA-PC, and 15 ns for diPnA -PC. These correlation times indicate that both fatty acyl chains are immobilized at different positions on the protein. From the difference in correlation time we propose that the shape of the phosphatidylcholine transfer protein is ellipsoidal (axial ratio congruent to 2.5) with the 1 fatty acyl chain oriented parallel to the long symmetry axis and having an angle of 60-90 degrees with the 2 fatty acyl chain.


The adolescent and young adult microbiome and its association with substance use: a scoping review.
The microbiome is a critical factor in health throughout human development. The aims of this scoping review are to (i) elucidate the differences between the youth (post-natal day 21-65 for rodents, 2-7 years for non-human primates, and 10-25 years for humans) microbiome with other life stages and (ii) identify youth-specific microbial changes associated with substance use. Peer-reviewed studies published up to May 2023 were identified in PubMed and SCOPUS and included gut and oral microbiome studies from rodents, non-human primates, and humans (N = 1733). Twenty-six articles were determined eligible based on inclusion criteria (aim 1: n = 19, aim 2: n = 7). The adolescent and young adult oral and gut microbiomes are distinct compared to other life stages, within both non-human and human models. While there is limited research in this area, the microbiome appears to be vulnerable to substance use exposure earlier in life, including substances commonly initiated and escalated during adolescence and young adulthood (i.e. alcohol, cannabis, and tobacco). Studies across the lifespan indicate that adolescence and young adulthood are distinct periods of development, where the microbiome is sensitive to exposures, including substance use. There is a need for more studies focused on the adolescent and young adult microbiome and substance use, as well as focused on the oral microbiome during this developmental period. Understanding the gut and oral microbiome during adolescence and young adulthood may provide insight into the pathophysiology of substance use disorders.


An Aminopeptidase in the Drosophila Testicular Niche Acts in Germline Stem Cell Maintenance and Spermatogonial Dedifferentiation.
Extrinsic cues from the niche are known to regulate adult stem cell self-renewal versus differentiation. Here, we report that an aminopeptidase Slamdance (Sda) acts in the Drosophila testicular niche to maintain germline stem cells (GSCs) and regulate progenitor germ cell dedifferentiation. Mutations in sda lead to dramatic testicular niche deterioration and stem cell loss. Recombinant Sda has specific aminopeptidase activity in vitro, and the in vivo function of Sda requires an intact aminopeptidase domain. Sda is required for accumulation of mature DE-cadherin, and overexpression of DE-cadherin rescues most sda mutant phenotypes, suggesting that DE-cadherin is an important target of Sda. Finally, Sda is both necessary and sufficient to promote dedifferentiation during aging and recovery from genetically manipulated depletion of GSCs. Together, our results suggest that a niche factor promotes both stem cell maintenance and progenitor cell dedifferentiation.


[Post-traumatic penoscrotal avulsion: cosmetic and uro-andrologic evaluation after surgical reconstruction].
A case of surgical reconstruction after penoscrotal skin avulsion is described. Penile coverage was gained by two full thickness grafts helicoidally placed to avoid retractions. Scrotal reconstruction was carried out in two steps, after testis subcutaneous implantation, with axial flaps expanded in abdominal region. The procedure has the advantage of flaps sure vitality, avoids patient discomfort produced by a perineal expansion with satisfactory cosmetic appearance and restore of a normal sexual function.


Position-specific adaptation in complex cell receptive fields of the cat striate cortex.
1. Responses of complex cells in cat striate cortex were studied with flashed light slit stimuli. The responses to slits flashed in different positions in the receptive field were assessed quantitatively before and after periods of prolonged stimulation of one small region of the receptive field. This type of prolonged stimulation resulted in reduced responsivity over a limited zone within the complex cell receptive field. 2. The adaptation-induced responsivity decrement was generally observed in both the ON and OFF response profiles but could also be restricted to one or the other. In general, the magnitude of the response decrements was greatest in the ON response profiles. The adaptation-induced response decrement did not necessarily spread throughout the receptive field but was restricted to a small region surrounding the adapted receptive field position (RFP). Adaptation spread equally widely across the ON and OFF response profiles despite the smaller adaptation effects in the OFF profile. 3. The adaptation effects from repeated stimulation at a single RFP did not spread symmetrically across the receptive field, and a given cell's preferred direction of motion indicated the direction of the asymmetric spread of the adaptation. RFPs that would be stimulated by a light slit originating at the point of adaptation and moving in the preferred direction (preferred side) showed greater adaptation-induced response decrements than did RFPs that would be stimulated by a light slit moving in the opposite direction from the point of adaptation (nonpreferred side). There was significant enhancement of responses at some RFPs on the non-preferred side of the point of adaptation. This asymmetric spread of adaptation could be caused by adaptation of inhibitory connections that contribute to complex cell direction selectivity. 4. The asymmetry of adaptation was significantly different for the ON and OFF response profiles. The asymmetric spread of adaptation for the ON response profile was similar to that observed previously in simple cells with greater decrements in the preferred direction side of the point of adaptation. However, the OFF response profiles showed less directional asymmetry in the spread of adaptation and showed greater decrements at RFPs in the nonpreferred direction side of the point of adaptation. 5. The similarity between the spread of adaptation in simple and complex cells suggests that the adaptation in these cells is occurring through a common mechanism. The directional asymmetry of the spread of adaptation is likely due to a local postsynaptic mechanism of adaptation rather than presynaptic transmitter depletion.


[The histopathology of basal cell carcinomas (author's transl)].
The authors review the different histological forms of basal cell carcinoma, paying particular attention to early forms, sometimes apparently harmless. They stress the diffusing nature of sclerodermiform carcinoma which is often more widespread than clinical appearances suggest. They indicate the current prevalence of basal cell carcinomas in the young individual aged less than 30 years, apparently the consequence of excessive exposure to sunlight. Finally, they give a number of technical indications which are useful in ensuring better orientation and more complete study of the operative specimen, if a frozen section has not been possible, since for this tumour, purely locally malignant, complete excision from the outset offers the best guarantee of cure.


Development of the femoral bicondylar angle in hominid bipedalism.
The bicondylar angle is the angle between the diaphysis of the femur and a line perpendicular to the infracondylar plane. The presence of a femoral bicondylar angle in Australopithecus afarensis indicates that these 3.5-million-year-old hominids were bipedal. Many studies have linked the formation of the femoral bicondylar angle with bipedality, but the mechanism for the formation of the angle is poorly understood. Mechanical factors, such as stresses and strains, influence the growth process. In particular, previous studies have demonstrated that hydrostatic compressive stress inhibits growth and ossification, and octahedral shear stress promotes growth and ossification. In this study we implemented these mechanobiological principles in a three-dimensional finite-element model of the distal femur. We applied loading conditions to the model to simulate loading during the single-leg stance phase of bipedal gait. The stresses in the physis of the distal femur that result from bipedal loading conditions promote growth and ossification more on the medial side than on the lateral side of the femur, forming the bicondylar angle. This model explains the presence of the bicondylar angle in hominid bipedalism and also the ontogenetic development of the bicondylar angle in growing children. The mechanobiological relationship between endochondral ossification and mechanical loading provides valuable insight into bone development and morphology.


Role of nucleolin in posttranscriptional control of MMP-9 expression.
Matrix-metalloproteinases (MMPs), which are able to degrade extra cellular matrix (ECM) components, are crucial in ECM-remodeling, under physiological (e.g., embryogenesis, wound healing, angiogenesis) or pathophysiological conditions (e.g., arthritis, cancer progression and metastasis, fibrosis). Treating HT1080 cells, a human fibrosarcoma cell line, with the iron chelator 2,2-Dipyridyl, which mimics certain aspects of hypoxia, leads to a 3-fold elevated Matrix-metalloproteinase-9 (MMP-9) protein level. This elevation occurs within 3 h, without any change of mRNA-concentration. The rapid increase in MMP-9 expression is caused by an enhancement of translational efficiency characterized by a recruitment of translationally inactive MMP-9 mRNP-complexes into the rough endoplasmatic reticulum (rER). Reporter gene assays, which depend on the untranslated regions (UTR) of MMP-9 mRNA, reveal that the posttranscriptional regulation is mainly attributed to the 3'UTR. RNA/protein interaction studies indicate that the elevated binding of nucleolin ( approximately 64 kDa form) to the 3'UTR may be of major importance for the increased efficiency of MMP-9 translation. The results show that MMP-9 expression can be regulated posttranscriptionally, affecting the efficiency of translation and localization of the mRNA.


A distinct chemokine axis does not account for enrichment of Foxp3(+) CD4(+) T cells in carcinogen-induced fibrosarcomas.
The frequency of CD4(+) Foxp3(+) regulatory T (Treg) cells is often significantly increased in the blood of tumour-bearing mice and people with cancer. Moreover, Treg cell frequencies are often higher in tumours compared with blood and lymphoid organs. We wished to determine whether certain chemokines expressed within the tumour mass selectively recruit Treg cells, thereby contributing to their enrichment within the tumour-infiltrating lymphocyte pool. To achieve this goal, the chemokine profile of carcinogen-induced fibrosarcomas was determined, and the chemokine receptor expression profiles of both CD4(+) Foxp3(-) and CD4(+) Foxp3(+) T cells were compared. These analyses revealed that the tumours are characterized by expression of inflammatory chemokines (CCL2, CCL5, CCL7, CCL8, CCL12, CXCL9, CXCL10 and CX3CL1), reflected by an enrichment of activated Foxp3(-) and Foxp3(+) T cells expressing T helper type 1-associated chemokine receptors. Notably, we found that CXCR3(+) T cells were significantly enriched in the tumours although curiously we found no evidence that CXCR3 was required for their recruitment. Instead, CXCR3 marks a population of activated Foxp3(-) and Foxp3(+) T cells, which use multiple and overlapping ligand receptor pairs to guide their migration to tumours. Collectively, these data indicate that enrichment of Foxp3(+) cells in tumours characterized by expression of inflammatory chemokines, does not occur via a distinct chemokine axis, thus selective chemokine blockade is unlikely to represent a meaningful therapeutic strategy for preventing Treg cell accumulation in tumours.


United States Medical School Academic Faculty Workforce Diversity, Institutional Characteristics, and Geographical Distributions From 2014-2018.
Purpose Academic healthcare workforce diversity is important in addressing health disparities. Our goal was to evaluate trends and associations in faculty diversity of United States (US) medical schools over a five-year period. Methods We analyzed the Association of American Medical Colleges (AAMC) Faculty Roster data of 151 US medical schools from 2014-2018. Outcome faculty variables were female gender, underrepresented in medicine (UiM), age, and professorial representation. Predictor variables included geographical distributions, and institutional characteristics. Statistical analysis included Jonckheere-Terpstra test, ANOVA, and regression analysis. Results Female faculty increased from 37.6% to 40.4% (p<0.001), senior faculty (age >60 years) from 22.6% to 25.9% (p=0.001) while UiM faculty stayed relatively flat from 9.74% to 10.08% (p=0.773). UiM [adjusted odds ratio (aOR) = 0.39, p=0.015], and female faculty (aOR=0.3, p=0.001) had independently significantly decreased associations with professorial representation, while senior faculty had increased associations (aOR=3.82, p<0.001). Significant independent differences occurred in female, UiM, and professorial faculty distributions within US regions; Hispanic faculty were highest in Southwest (6.57%) and lowest in Midwest region (1.59%), while African-American faculty were highest in Southeast (8.15%) but lowest in the West (3.12%). UiM faculty had significantly independent decreased associations with MD/PhD degree (aOR=0.30, p=0.004) and higher US ranking institutions (aOR=0.45, p=0.009). Conclusions From 2014 to 2018, female faculty increased modestly while the UiM faculty trend remained flat. Female and UiM faculty were less represented at the professor level. UiM faculty were less represented in higher-ranking institutions. Geographic location is associated with faculty diversity.


[Simultaneous determination of 11 quinolones in hotpot ingredients by dispersive solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].
A method for the simultaneous determination of the residues of 11 quinolones in hotpot ingredients by quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and ultra performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was established. The sample was extracted with acetonitrile (containing 5% formic acid) and followed by stratifying with a salting-out agent. Clean-up of the extracts was processed by C18 and PSA, a modified QuEChERS procedure. The analytes were then separated on a Poroshell 120 EC-C18 column, and finally detected by tandem mass spectrometry in positive ESI mode. The linearity of all the 11 quinolones in the range from 1.0 to 100.0 microg/kg had correlation coefficients greater than 0.998. The limits of detection (LOD) of the method were from 1.8 to 3.1 microg/kg and the limits of quantification (LOQ) were from 6.0 to 10.3 microg/kg. The average recoveries of the 11 quinolones were in the range from 70.1% to 100.3%, with relative standard deviations from 2.42% to 10.88%. The established method is sensitive and of good recoveries. It can be applied as a rapid and reliable method for the determination of the 11 quinolones in hotpot ingredients.


Parotid glands tumours: overview of a 10-year experience with 282 patients, focusing on 231 benign epithelial neoplasms.
Salivary gland tumours are uncommon, representing less than 6% of head and neck neoplasm. Pleomorphic adenoma is the most common benign epithelial salivary gland neoplasm, comprising 50%-74% of all parotid tumours. It is followed by Warthin's tumour (4-14%). The authors retrospectively reviewed 282 eligible patients surgically treated for parotid gland tumours in the last 10 years, focusing on 231 benign epithelial neoplasms. Clinical and diagnostic findings, surgical treatment and surgical outcome were discussed. The diagnosis of a parotid gland neoplasm must be considered in any patient presenting with a lump near the mandible. Smoking habit is important in Warthin's tumour pathogenesis. Fine needle aspiration citology (FNAC) can't lead alone to histological diagnosis. Only surgery can give histological certainty of benignity, thus preventing malignant degeneration, lump infection or risk of size-dependent surgical complications. Conservative formal parotidectomy appears to be the treatment of choice. Tumour pseudopodia and capsule ruptures are recognised factors involved in pleomorphic adenoma recurrences but also tumour multicentricity might play an important role.


Genetics of resistance to infection with Candida albicans in mice.
To determine differences in susceptibility, 234 naive mice including xid and beige mutants were infected intravenously with Candida albicans and monitored with survival analysis and quantitative culture of the kidneys. By using survival time as the criterion, animals of seven inbred strains were separated into three groups. C3H/HeJ and Dw/+ were most susceptible; C57BR/cdJ, BRVR and CBA/N (xid) were intermediate in susceptibility; C57BL/KsJ and C57BL/6J were least susceptible. Mean survival times (MST) were markedly influenced by the number of Candida cells injected while the ranking of mouse strains by survival alone was unchanged. There was a dissimilar behaviour of the strains to produce organ weight changes in response to infection when compared with uninfected mice which were matched for age and genetic lineage. Black mice had lower colony forming units (CFU) per mg of tissue at the time of death than animals of other genetic lineage. Nevertheless, the finding that MST and CFU studies were loosely correlated in a few strains of mice indicated that the proliferation of the fungus in the kidneys was not always the major cause of death. The beige mutation was found to determine an increased susceptibility to systemic Candida infection. The differences in survival for beige and nonbeige mice were influenced by the genetic lineage of the host, being much greater in the C57BL/6 strain (36.7 days) than in the C3H/He strain (5 days). C57BL/6 beige-J had significantly higher CFU per organ and per unit of weight than C57BL/6 +/+ mice. These data evinced an important contribution of host genetic factors to resistance to systemic candidiasis. It is suggested that innate resistance genes regulate the differentiation in the bone marrow and the function of cells of granulocyte-macrophage lineage.


RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue.
Neuroblastoma (NB) is the most common type of extracranial solid tumor in children with a high prevalence in toddlers. For childhood cancer survivors, preservation of reproductive potential is an important factor for quality of life. The optimization of NB minimal residual disease (MRD) detection in testicular tissue is crucial to evaluate the risk of malignant cell reintroduction. The first step in the present study was to assess the accuracy of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin (DCX) mRNA expression in frozen/thawed testicular tissues of patients with non-obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or snap freezing. The second step was to determine the expression levels of these markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2 with non-NB malignancy). The yield of extracted RNA was similar in testicular samples frozen by slow or snap freezing. In the in vitro model, TH and DCX transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B mRNA was not detected. There was a strong positive association between the number of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100% for PHOX2B following in vitro contamination with 10 tumor cells. In testicular samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was not observed, but high expression levels of TH and DCX mRNA were detected, which were similar to expression detected in the in vitro model. Among the markers used in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues from males who require fertility preservation.


Effects of Indian herbal formulation Body Revival on human platelet aggregation and myocardial ischemia in rats.
To study the effect of Body Revival (BR), a compound traditional Indian herbal medicine, on human platelet aggregation and isoproterenol (IS)-induced myocardial ischemia (MI) damage in male Wistar rats. BR suspension 10, 20 and 30 μg was mixed with platelet-rich plasma and incubated at 37 degrees centigrade for 30 min, respectively. Then, adenosine diphosphate (ADP, 20 mmol/L) or collagen (2 μg) was added in the mixture and the aggregation was observed against platelet-poor plasma mixed with equal volume of suspension of the same test samples. Wistar rats divided into 4 groups were used to investigate BR's effects on IS-induced MI. Levels of serum creatinine kinase (CK), aspartate transaminase (AST) and alanine transaminase (ALT) were estimated by standard commercial biological kits. Serum nitric oxide (NOx) was also measured. The lipid peroxides (LPO) and protein concentrations in heart tissues were measured. BR could inhibit ADP- or collagen-induced human platelet aggregation dose-dependently. Moreover, it could protect MI caused by IS in rats. BR reduced the levels of serum CK, AST, ALT and NOx dose-dependently and also lowered LPO in heart tissues in comparison with the MI control (P<0.01). BR can inhibit human platelet aggregation and protect MI caused by IS in rats.


Therapeutic Potential of Novel Nano-Based Curcumin Compounds In Vitro and In Vivo
Despite recent advances in cancer medication, malignant tumors continue to be the second leading cause of death worldwide. Furthermore, introducing a therapeutic compound with low-side effects as well as low-price for consumers is controversial. Recent efforts have been focusing on traditional medicines as a rich source of herbal agents. Curcumin, the major turmeric phytochemical, has been widely assessed as an anti-cancer compound in vitro and in vivo. However, the use of curcumin in cancer treatment has limitations because of its low solubility, poor tissue absorption, rapid metabolism and rapid systemic elimination. Recent work has focused on improving the stability of curcumin to facilitate clinical application. Dendrosomal nano-corcumin (DNC) is one of the most successful compounds showing significant cellular absorption and also anti-tumor effects. The present overview of newest applicable strategies for curcumin-based therapy and their clinical potential usefulness has the emphasis on DNC.


[Immunologic and genetic markers of exposure to aromatic hydrocarbons in workers].
Workers exposed to aromatic hydrocarbons appeared to have prevalence of heterozygous variants of CYP1A1 gene (9893 A/G) and tumor necrosis factor gene reliably higher vs. the reference group 2.5 and 3.3 times respectively, and level of anti-benzene antibodies (IgG) increased vs. the reference group. The data presented demonstrate negative immunogenetic associations of aromatic hydrocarbons influence on oil extraction operators.


[Evaluation of high-resolution images application for wild medicinal plants macro monitoring: a case of Apocynum].
To investigate the resources of medicinal plant, such as wild Apocynum, supervised classification based on Principal Component Analysis (PCA) and texture feature were used to monitor wild medicinal plants from image captured by ZY-3 and World-view-2 and compare which satellite Image are more appropriate to monitor the wild medicinal plants. The research results shows that: for more complex growth conditions wild medicinal plants Apocynum, high-resolution images Worldview-2 is more suitable for its remote identification, the low-resolution satellite ZY-3 can only recognizes the wild medicinal plants which distributed intensively. If the study target distribution is more intensive and larger scale, and cultivated type medicinal plants, the use of satellite ZY-3 in low resolution remote sensing data to identify the target can be a good choice, it is not necessary to buy high-resolution data, in order to avoid waste of expenditure, for the scattered distribution, the high-resolution satellite imagery data may be indispensable to identify targets.


Relationship between the pH of enema solutions and intestinal damage in rabbits.
Mechanical enemas can lead to intestinal mucosal injuries and bowel barrier damage, presenting as electrolyte disturbances and functional intestinal disorders. Most researchers believe that the mechanism of injury is related to osmolality, volume and temperature of the solution, infusion pressure, and the composition of the enema tube. We hypothesized that the pH of the enema solution may also contribute to intestinal damage. We administered enema solutions--normal saline, soapsuds, or vinegar (neutral, alkaline, or acidic solutions, respectively)--to three groups of rabbits (n = 20 per group). The solutions were standardized for volume and temperature and the soapsuds and vinegar solutions were adjusted to be isotonic with normal saline or deionized water. We also included a control group (n = 20) in which the enema tubes were inserted but no solution was administered. We biopsied 3 sites (rectum and distal and proximal colon). Damage to intestinal mucosa was observed by light microscopy and transmission electron microscopy. In order to explore the detection of damage using noninvasive methods, cyclooxygenase (COX)-2 gene expression was measured in the exfoliated cells gathered from postenema defecation. Epithelial loss, inflammatory reaction, and cellular microstructure damage was increased in the vinegar and soapsuds groups. Also, exfoliated cells in these groups had higher COX-2 expression than the normal saline group. The acidic and alkaline enema solutions thus caused more severe damage to the intestinal mucosa compared to the neutral liquid, supporting our hypothesis. Further, the detection of COX-2 expression shows promise as a noninvasive method for estimating enema-induced damage.


Gender-dependent effects of exercise training on serum leptin levels in humans.
Leptin, the product of the ob gene, is elevated in obese humans and appears to be closely related to body fat content. The purpose of the present investigation was to determine the effect of aerobic exercise training on systemic leptin levels in humans. Eighteen sedentary middle-aged men (n = 9) and women (n = 9) who did not differ in aerobic capacity (29.4 +/- 1.2 vs. 27.5 +/- 1.2 ml x kg(-1) x min(-1)) or insulin sensitivity index (3.41 +/- 1.12 vs. 4.88 +/- 0.55) were studied. Fat mass was significantly lower in females vs. males (21.83 +/- 2.25 vs. 26.99 +/- 2.37 kg, P < 0.05). Despite this, fasting serum leptin was significantly higher in the females vs. males (18.27 +/- 2.55 vs. 9.88 +/- 1.26 ng/ml, P < 0.05). Serum leptin concentration decreased 17.5% in females (P < 0.05) after 12 wk of aerobic exercise training (4 day/wk, 30-45 min/day) but was not significantly reduced in males. Fat mass was not altered after training in either group. In contrast, both aerobic capacity (+13% males, +9.1% females) and insulin sensitivity (+35% males, +82% females) were significantly improved subsequent to training. These data suggest that 1) women have higher circulating leptin concentrations despite lower fat mass and 2) exercise training appears to have a greater effect on systemic leptin levels in females than in males.


A critical cell-intrinsic role for serum response factor in glial specification in the CNS.
Astrocytes and oligodendrocytes play crucial roles in nearly every facet of nervous system development and function, including neuronal migration, synaptogenesis, synaptic plasticity, and myelination. Previous studies have widely characterized the signaling pathways important for astrocyte differentiation and unveiled a number of transcription factors that guide oligodendrocyte differentiation in the CNS. However, the identities of the transcription factors critical for astrocyte specification in the brain remain unknown. Here we show that deletion of the stimulus-dependent transcription factor, serum response factor (SRF), in neural precursor cells (NPCs) (Srf-Nestin-cKO) results in nearly 60% loss in astrocytes and 50% loss in oligodendrocyte precursors at birth. Cultured SRF-deficient NPCs exhibited normal growth rate and capacity to self-renew. However, SRF-deficient NPCs generated fewer astrocytes and oligodendrocytes in response to several lineage-specific differentiation factors. These deficits in glial differentiation were rescued by ectopic expression of wild-type SRF in SRF-deficient NPCs. Interestingly, ectopic expression of a constitutively active SRF (SRF-VP16) in NPCs augmented astrocyte differentiation in the presence of pro-astrocytic factors. However, SRF-VP16 expression in NPCs had an inhibitory effect on oligodendrocyte differentiation. In contrast, mice carrying conditional deletion of SRF in developing forebrain neurons (Srf-NEX-cKO) did not exhibit any deficits in astrocytes in the brain. Together, our observations suggest that SRF plays a critical cell-autonomous role in NPCs to regulate astrocyte and oligodendrocyte specification in vivo and in vitro.


N-terminal domain-deleted mu transposase exhibits increased transposition activity with low target site preference in modified buffers.
Transposition using MuA and the Mu-transposon is frequently used for insertional and deletional mutagenesis and to introduce primer sequences into DNA of unknown sequence. However, mutagenesis studies are often limited by the number of transposition events taking place within a small target sequence. Although the intrinsic target site preference of MuA is low, it nevertheless may limit the recovery of desired events. In the current study, we have compared the transposition activity of wild-type, C-terminally deleted, N-terminally deleted and both C- and N-terminally deleted MuA. We found that N-terminally deleted MuA was most active with an about sevenfold increase in transposition efficiency compared to wild-type. In addition, we identified a novel reaction condition in which the transposition activity of N-terminally deleted MuA was increased about 45-fold. The use of the N-terminally deleted MuA with the newly established condition enhanced the relative transposition activity about 280-fold compared to that of wild-type MuA with the conventional buffer. In addition, the optimized buffer decreased the target site preference of N-terminally deleted MuA resulting in a more even distribution of integration events throughout the target gene.


Fear of Falling Among Community-Dwelling Older Adults with Heart Disease: Findings from an International Mobility in Aging Study (IMIAS).
Older adults with heart disease (HD) are more likely to report a higher prevalence of falls compared to those without HD. A knowledge gap currently exists regarding the factors associated with fear of falling (FOF) among older adults with HD. Therefore, this study aimed to estimate FOF and identify factors associated with FOF among older adults with HD. Data came from a secondary analysis of the International Mobility in Aging Study (IMIAS) baseline (2012) data. FOF was measured using the Falls Efficacy Scale-International (FES-I). Stepwise linear regression was used to identify factors associated with FOF. A total of 429 participants identified themselves as having heart disease diagnosed by their physician (mean age 69.5 ± 2.9). Older adults with HD reported on average (25.6) higher FOF than those without HD. For older adults with HD, FES-I increased significantly by 1.3, 1.0, and 0.6 points, when the Short Physical Performance Battery, the Leganes Cognitive Test, and QOL total scores decreased by one point. FES-I also significantly increased by 3.2 when income was insufficient compared to sufficient or very sufficient income. FOF is multifactorial, and our findings provide a base for developing future management rehabilitation intervention programs aimed at decreasing FOF among older adults with HD.