Complementary feeding with fortified spread and incidence of severe stunting in 6- to 18-month-old rural Malawians.
To compare growth and incidence of malnutrition in infants receiving long-term dietary supplementation with ready-to-use fortified spread (FS) or micronutrient-fortified maize-soy flour (likuni phala [LP]). Randomized, controlled, single-blind trial. Rural Malawi. A total of 182 six-month-old infants. Participants were randomized to receive 1 year of daily supplementation with 71 g of LP (282 kcal), 50 g of FS (FS50) (256 kcal), or 25 g of FS (FS25) (130 [corrected] kcal). Weight and length gains and the incidences of severe stunting, underweight, and wasting. Mean weight and length gains in the LP, FS50, and FS25 groups were 2.37, 2.47, and 2.37 kg (P = .66) and 12.7, 13.5, and 13.2 cm (P = .23), respectively. In the same groups, the cumulative 12-month incidence of severe stunting was 13.3%, 0.0%, and 3.5% (P = .01), of severe underweight was 15.0%, 22.5%, and 16.9% (P = .71), and of severe wasting was 1.8%, 1.9%, and 1.8% (P > .99). Compared with LP-supplemented infants, those given FS50 gained a mean of 100 g more weight and 0.8 cm more length. There was a significant interaction between baseline length and intervention (P = .04); in children with below-median length at enrollment, those given FS50 gained a mean of 1.9 cm more than individuals receiving LP. One-year-long complementary feeding with FS does not have a significantly larger effect than LP on mean weight gain in all infants, but it is likely to boost linear growth in the most disadvantaged individuals and, hence, decrease the incidence of severe stunting.


Short-term cardiovascular effects of selective phosphodiesterase 3 inhibitor olprinone versus non-selective phosphodiesterase inhibitor aminophylline in a meconium-induced acute lung injury.
Various anti-inflammatory drugs have been used for treatment of neonatal meconium aspiration syndrome (MAS). As their adverse effects are poorly described, this study compared effects of selective phosphodiesterase (PDE) 3 inhibitor olprinone and non-selective PDE inhibitor aminophylline on cardiovascular parameters in animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were intravenously given olprinone (0.2 mg/kg) at a single dose at 0.5 h after meconium instillation, or aminophylline (2.0 mg/kg) at two doses at 0.5 and 2.5 h after meconium instillation, or were left without treatment. Cardiovascular changes were evaluated within 5 min of administration and 5 min after finishing the administration. Furthermore, respiratory and cardiovascular parameters were measured within 5 hours following treatment delivery. Oxidation markers (thiobarbituric acid-reactive substances (TBARS), and total antioxidant status) and markers of cardiovascular injury (aldosterone, gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)) were determined in the plasma. Meconium instillation induced acute lung injury associated with oxidative stress, elevated aldosterone, and slightly increased GGT and AST levels. Both aminophylline and olprinone improved lung functions and reduced oxidation stress. However, the PDE inhibitors acutely increased blood pressure and heart rate, whereas heart rate variability remained higher till the end of experiment and correlated well with markers of cardiovascular injury. Considering that systemic administration of olprinone and aminophylline was accompanied by acute cardiovascular changes in the meconium-instilled animals, use of PDE inhibitors in the newborns with MAS should be carefully monitored.


Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 3: Regeneration of bitumen fumes, inhalation setup, validation.
Undertaking a chronic inhalation study on bitumen fume presents a challenge in terms of generating sufficient amounts of representative fume. The objective of the study described in this and in previous publications was to collect sufficient fume and use this to develop a laboratory-generated exposure atmosphere, for use in chronic inhalation toxicity studies in rats that resembles, as closely as possible, personal exposures seen in workers during road paving operation. To achieve this goal, atmospheric workplace samples were collected at road paving work sites and compared with bitumen fume condensate samples collected from the headspace of hot bitumen storage tanks. In Parts 1 and 2, we described the collection and analysis of workplace samples, the strategy for in-line extraction of a suitable fraction of bitumen fume collected from the headspace of a bitumen storage tank and the comparison of the collected condensate to the workplace samples. This paper (Part 3) describes the regeneration of bitumen fume for inhalation and the exposure setup used for inhalation studies.


Public opinion and policymaking in the states: the case of post-Roe abortion policy.
Whether public opinion should be expected to play a role in the shaping of abortion legislation in the states is a debatable question. Representation is a difficult task, especially if legislators receive mixed cues from the public, activists, and the political parties. In this study, we find that grass-roots activism and public opinion tend to match, and both are reflected in state abortion policy. In addition, more Pro-Life policies are found in states with a tradition of conservative policies in other areas, Republican majorities in the state legislature, more Catholic residents, and fewer women legislators. These patterns hold true for a composite index of abortion policies and for the specific policy area of government funding of abortions. Slightly different patterns occur for parental consent law, though these statutes also tend to reflect general preferences on abortion and interest group activity in a state.


Traumatic brain injury-induced axonal phenotypes react differently to treatment.
Injured axons with distinct morphologies have been found following mild traumatic brain injury (mTBI), although it is currently unclear whether they reflect varied responses to the injury or represent different stages of progressing pathology. This complicates evaluation of therapeutic interventions targeting axonal injury. To address this issue, we assessed axonal injury over time within a well-defined axonal population, while also evaluating mitochondrial permeability transition as a therapeutic target. We utilized mice expressing yellow fluorescent protein (YFP) in cortical neurons which were crossed with mice which lacked Cyclophilin D (CypD), a positive regulator of mitochondrial permeability transition pore opening. Their offspring were subjected to mTBI and the ensuing axonal injury was assessed using YFP expression and amyloid precursor protein (APP) immunohistochemistry, visualized by confocal and electron microscopy. YFP(+) axons initially developed a single, APP(+), focal swelling (proximal bulb) which progressed to axotomy. Disconnected axonal segments developed either a single bulb (distal bulb) or multiple bulbs (varicosities), which were APP(-) and whose ultrastructure was consistent with ongoing Wallerian degeneration. CypD knock-out failed to reduce proximal bulb formation but decreased the number of distal bulbs and varicosities, as well as a population of small, APP(+), callosal bulbs not associated with YFP(+) axons. The observation that YFP(+) axons contain several pathological morphologies points to the complexity of traumatic axonal injury. The fact that CypD knock-out reduced some, but not all, subtypes highlights the need to appropriately characterize injured axons when evaluating potential neuroprotective strategies.


Biomechanical evaluation of 4 techniques of distal biceps brachii tendon repair.
Recent technical improvements have led the way to a resurgence of the single-incision approach for repair of distal biceps tendon injuries. There has been no biomechanical evaluation of all these techniques with comparison to the standard 2-incision bone tunnel technique. There will be no difference under cyclic loading and ultimate failure between the 2-incision bone tunnel technique, suture anchor repair, interference screw, and EndoButton techniques for the repair of distal biceps tendon ruptures. Controlled laboratory study. Sixty-three fresh-frozen cadaveric elbows were randomly assigned to 4 treatment groups (bone tunnel, EndoButton, suture anchor, interference screw). Cyclic loading was then performed from 0 degrees to 90 degrees at 0.5 Hz for 3600 cycles with a 50-N load. A differential variable reductance transducer was placed between the radius and distal tendon to determine displacement. The construct was then pulled to failure at 120 mm/min. A multiple analysis of variance revealed no statistically significant difference for displacement among the 4 repair techniques. Displacement using the bone tunnel was 3.55 mm, EndoButton was 3.42 mm, suture anchor was 2.33 mm, and interference screw was 2.15 mm. There was a statistically significant greater load to failure with EndoButton (440 N) than suture anchor (381 N), bone tunnel (310 N), or interference screw (232 N) (P < .001). The EndoButton technique had the highest load to failure. These data demonstrate the EndoButton to be the strongest repair technique, with no failures during cycling at physiologic loads and with the largest load to failure. These findings are important in maximizing surgical results and stability and suggest that the construct can tolerate early postoperative active range of motion.


Status of equine viral arteritis in Kentucky, 1985.
Clinical cases of equine arteritis virus infection have not been diagnosed in Kentucky since 1984, and there has been no indication that any of the horses involved in the 1984 epizootic have since been responsible for spread of the disease to horses in other states or other countries. Cases of abortion caused by naturally acquired infection with this virus have not been confirmed in 1984 or 1985. Neither field nor vaccine strains of equine arteritis virus have been shown to induce teratologic abnormalities or the carrier state in foals born to infected or vaccinated mares. The carrier stallion appears to have played a major epidemiologic role in the dissemination and perpetuation of the virus. A commercial modified live equine viral arteritis vaccine was found to be safe and efficacious for stallions and mares. The disease can be controlled by immunizing the stallion population and by restricting the breeding of equine arteritis virus-shedding stallions to vaccinated or seropositive mares, followed by an appropriate period of isolation from other nonvaccinated Equidae.


[Shock: a review. I: Pathophysiology].
In the present review, an attempt has been made to describe the modern concept of circulatory shock (Part I). The shock inducing insults (low circulatory volume/vascular capacity equation, heart failure, or disturbance of cellular metabolism induce physiological defense mechanisms, which result in peripheral vasoconstriction in order to maintain adequate blood pressure and perfusion of vital organs (compensatory phase). However, when the insult is too aggressive or too prolonged, deterioration of the cardiovascular system and cellular function ensues as a result of anaerobic metabolism, loss of vascular tone, reperfusion injury, depression of the reticuloendothelial system, disseminated intravascular coagulation, and myocardial failure (decompensatory phase). This leads to widespread cellular destruction, autodigestion, and finally death of the patient. Recent features of shock therapy will be discussed in part II of this review.


L-tryptophan as an antioxidant in human placenta extract.
An antioxidant was purified from human placenta extract (HPE) by using gel filtration, liquid-liquid extraction, silicagel column chromatography, and HPLC. The purified antioxidant was identified to be L-tryptophan (L-Trp). L-Trp showed higher inhibitory activity than mannitol and DMSO on the Fenton reaction-induced degradation of 2-deoxy-D-ribose. L-Trp also had much higher inhibitory activity on the cytochrome P-450-dependent lipid peroxidation than the previously identified antioxidants of HPE, L-phenylalanine, L-tyrosine and uracil. On the other hand, the inhibitory effect of L-Trp on the Fenton reaction-induced protein oxidation was smaller than that of uracil. These results suggest that L-Trp is a main antioxidant of HPE of which the effect is based on the suppression of lipid peroxidation in the oxidative stress status.


Long-term treatment effect of a modified jailed-balloon technique for de Winter syndrome: a case report.
Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.


Clearing the air: improving smoke-free policy compliance at the national oncology hospital in Armenia.
Smoke-free policies shown to reduce population exposure to secondhand smoke (SHS) are the norm in hospitals in many countries around the world. Armenia, a transition economy in the South Caucasus, has one of the highest male smoking rates in the European region. Although smoking in healthcare facilities has been banned since 2005, compliance with this ban has been poor due to lack of implementation and enforcement mechanisms and social acceptability of smoking. The study aimed to develop and test a model intervention to address the lack of compliance with the de jure smoking ban. The national oncology hospital was chosen as the intervention site. This study used employee surveys and objective measurements of respirable particles (PM2.5) and air nicotine as markers of indoor air pollution before and after the intervention. The intervention developed in partnership with the hospital staff included an awareness campaign on SHS hazards, creation of no-smoking environment and building institutional capacity through training of nursing personnel on basics of tobacco control. The survey analysis included paired t-test and McNemar's test. The log-transformed air nicotine and PM2.5 data were analyzed using paired t-test. The survey showed significant improvement in the perceived quality of indoor air, reduced worksite exposure to SHS and increased employees' awareness of the smoke-free policy. The number of employees reporting compliance with the hospital smoke-free policy increased from 36.0% to 71.9% (p < 0.001). The overall indoor PM2.5 concentration decreased from 222 μg/m3 GM (95% CI = 216-229) to 112 μg/m3 GM (95% CI = 99-127). The overall air nicotine level reduced from 0.59 μg/ m3 GM (95% CI = 0.38-0.91) to 0.48 μg/ m3 GM (95% CI = 0.25-0.93). The three-faceted intervention developed and implemented in partnership with the hospital administration and staff was effective in reducing worksite SHS exposure in the hospital. This model can facilitate a tangible improvement in compliance with smoke-free policies as the first step toward a smoke-free hospital and serve as a model for similar settings in transition countries such Armenia that have failed to implement the adopted smoke-free policies.


Initial experience with phacoemulsification and goniotomy using the Kahook dual blade in advanced open-angle glaucoma: Six-month outcomes in Indian eyes.
The aim of this study was to report our initial experience on the outcomes of phacoemulsification in combination with goniotomy using the Kahook Dual Blade (KDB) in eyes with advanced open-angle glaucoma (OAG). The outcomes of phaco-goniotomy with KDB in advanced OAG in Indian eyes were retrospectively analyzed. Based on the Hodapp-Anderson-Parrish criteria of visual field defects, severe glaucoma (mean deviation on standard automated perimetry worse than 12 dB) was considered as advance glaucoma. Preoperative, intraoperative, and postoperative data were collected through 6 months of follow-up. Outcome measures included antiglaucoma medications (AGM), the proportion of eyes achieving >1AGM reduction, intraocular pressure (IOP), and visual acuity. Median (interquartile range) number of AGM in eyes that underwent phaco-KDB goniotomy reduced from 2 (2,3) at baseline to 1 (0,1) at 6 months (P = 0.002). Median IOP reduced from 20 (20,26) mmHg at baseline to 14 (12,15) mmHg at 6 months (P = 0.02). The proportion of eyes achieving >1 medication reduction was 88% eyes (8/9). Adverse events noted were IOP spike (22 mmHg) in 2 eyes and intra-op hyphema in 1 eye on postoperative day-1, both resolved in a week with conservative management. Except one eye with central corneal scar due to prior pterygium surgery, 8 eyes had 20/20 vision at 1 week which was maintained till last follow-up. Phacoemulsification with KDB Goniotomy significantly lowered the need for AGM with moderate IOP reduction in advanced OAG eyes. There were no serious complications and the visual recovery was good and early.


Increased α-Fetoprotein Predicts Steatosis among Patients with Chronic Hepatitis C Genotype 4.
Background. The prognostic importance of α-fetoprotein (AFP) level elevation in patients with chronic hepatitis C and its clinical significance in steatosis associated with HCV infection remain to be determined. The present paper assessed clinical significance of elevated AFP in patients with CHC with and without steatosis. Methods. One hundred patients with CHC were divided into 50 patients with CHC and steatosis and 50 patients with CHC and no steatosis based on liver biopsy. Results. AFP was significantly increased in CHC with steatosis than patients without steatosis (P < 0.001). Highly significant positive correlation was found between serum AFP and necroinflammation as well as the severity of fibrosis/cirrhosis and negative significant correlation with albumin level in chronic HCV with steatosis (P < 0.001) but negative nonsignificant correlation with ALT and AST level (P ≤ 0.778 and 0.398), respectively. Highly significant increase was found in chronic hepatitis patients with steatosis than CHC without steatosis regarding necroinflammation as well as the severity of fibrosis/cirrhosis and AFP (P < 0.001). Conclusion. Patients with chronic HCV and steatosis have a higher AFP levels than those without steatosis. In chronic HCV with steatosis, elevated AFP levels correlated positively with HAI and negative significant correlation with albumin level.


A ratiometric fluorescence sensor with broad dynamic range based on two pH-sensitive fluorophores.
This paper describes a novel ratiometric fluorescence sensor for pH measurement. Two pH-sensitive fluorophores, N-allyl-4-(4'-methyl-piperazinyl)-1,8-naphthalimide (AMPN) and meso-5,10,15,20-tetra-(4-allyloxyphenyl)porphyrin (TAPP), which served as referencing indicators for each other, were co-polymerized with acrylamide, hydroxyethyl methacrylate and triethylene glycol dimethacrylate on the silanized glass surface. The proposed sensor is based on the pH-dependent fluorescence intensities of the two fluorophores in different pH ranges. The sensor covers a broad dynamic range of pH 1.5-9.0. It exhibits satisfactory analytical performance in terms of selectivity, reproducibility and stability. The successful fabrication of the proposed sensor provides an alternative concept to utilizing two or more fluorophores for the development of ratiometric sensors covering a broad range of pH.


The use of toxicokinetic and toxicodynamic data in risk assessment: an international perspective.
Risk assessment of chemicals is a process which is usually based on data derived from animal testing in which the exposure of animals results in toxicological effects. By extrapolation, the dose/exposure in humans, which will not result in toxicological effects ('safe dose', 'safe exposure'), is estimated. Traditional approaches use 'safety factors' or 'uncertainty factors' to extrapolate from animal to man and from the 'mean' subject to the general population, including sensitive subgroups. Traditionally, a default factor of 10 has been used to account for interspecies variation. It is proposed that this factor be subdivided into a subfactor to address the toxicokinetic aspects and a second subfactor for the toxicodynamic aspects. Likewise, a default factor of 10 with subfactors is proposed to account for the intraspecies variability. In the framework of the International Program on Chemical Safety's (IPCS) project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals, an activity has been initiated to provide guidance to risk assessors on the use of quantitative chemical specific data to account for interspecies variation and interindividual variability in risk assessment. To address the toxicokinetic aspects, the active species, the relevant internal exposure and the adequate metrics must be considered. Data quality and availability, in vitro or in vivo, the route of administration and the relevant dose level are relevant information for interspecies extrapolation. The availability of experimental data, including the relevance of the population studied, the number of subjects and/or samples obtained in the relevant group allow one to estimate the population distribution, e.g. difference between central tendency and given percentiles. In a similar fashion, the toxicodynamic data must be addressed. In addition to the identification of the active chemical species, the relevant endpoint must be determined. In extrapolation from animal to man, in most of the cases, the definitive endpoint (e.g. anemia) is lacking. It can be substituted by in vitro data (e.g. in vitro hemolysis) if it is a key event and relevant for the toxicity in animal as well as in humans. In extrapolating from animal to man, the dose-effect relationship plays an important role. To account for the toxicodynamic variability in the human population, similar aspects have to be taken into consideration, which have been discussed for toxicokinetics. The IPCS document is available at the IPCS website and risk assessors are invited to use the framework and report back their experience with it to enable revision and improvement.


Estimation of the status of spiral ganglion neurons and Schwann cells in the auditory neural degeneration mouse using the auditory brainstem response.
The auditory brainstem response (ABR) wave I threshold, latency and amplitude are insensitive to spiral ganglion neurons (SGNs) degeneration, but are sensitive to the degeneration of Schwann cells and can estimate the status of Schwann cells in a neural degeneration mouse model. The thorough pre-operative ABR assessment would be helpful in predicting cochlear implant performance. This study aimed in finding a non-invasive electrophysiological method to evaluate the status of the auditory nerve and the Schwann cells in sensorineural hearing loss (SNHL) and auditory neuropathy (AN) ears, and providing useful information for candidates screening and outcome prediction in cochlear implantation. The frequency-specific acoustic ABR was recorded in mice. The immunohistochemical staining was performed to detect the SGNs and Schwann cells in mice cochlea. The correlations between ABR wave I metrics and SGNs, Schwann cells were investigated. In SNHL and AN mice cochlea, statistically significant correlations between ABR wave I thresholds, latencies and amplitudes at 8, 16, and 32 kHz and their corresponding SGNs densities were found only in wave I amplitude at 8 kHz. While the ABR wave I metrics at all three frequencies showed strong significant correlations with their corresponding Schwann cells densities.


Tethered cervical spinal cord due to a hamartomatous stalk in a young adult. Case report.
The authors report on an unusual case of a congenital tethered cervical spinal cord in young man who presented with progressive tetraparesis. Neuroradiological evaluation of the spine revealed a discrete exophitic cervical spinal cord mass with a stalk of tissue that extended from the mass and terminated in the muscle tissue. The patient underwent a laminectomy with intradural exploration. A stalklike lesion was discovered and excised. Pathological examination showed that the stalk was formed of hamartomatous tissue. The patient improved following surgery, which suggested that tethering of the cervical spinal cord was responsible for his symptoms.


Muscarinic receptor binding of the novel radioligand, [3h]imidafenacin in the human bladder and parotid gland.
The aim of the current study was to demonstrate highly specific and direct binding activity of tritium ([(3)H])-labeled imidafenacin for labeling muscarinic receptors in human bladder and parotid gland. Specific binding of [(3)H]imidafenacin in human tissues was saturable, reversible, and of high affinity. The Kd value for specific [(3)H]imidafenacin binding in the human bladder was approximately 3 times higher than that in the parotid gland. Unlabeled imidafenacin as well as the clinically used antimuscarinic agents, oxybutynin, tolterodine, and solifenacin, competed with [(3)H]imidafenacin for binding sites in the human bladder and parotid gland in a concentrationdependent manner, which indicated pharmacological specificity of [(3)H]imidafenacin binding sites. The Ki for imidafenacin in the human bladder approximately corresponded to pharmacological potency for the competitive blockade of carbachol-induced contractions of bladder, indicating a close correlation between binding affinity of imidafenacin to bladder muscarinic receptors and its pharmacological effects in the bladder. In conclusion, the current study is the first to provide direct evidence to demonstrate that imidafenacin bound muscarinic receptors in the human bladder, supporting its clinical relevance as a therapeutic agent for overactive bladder. [(3)H]Imidafenacin may also be a useful radioligand for labeling the M3 subtype of muscarinic receptors with higher selectivity than other radioligands.


Two-dimensional phase contrast imaging for local turbulence measurements in large helical device (invited).
Two-dimensional phase contrast imaging (2D) installed on the large helical device (LHD) is a unique diagnostic for local turbulence measurements. A 10.6 microm infrared CO(2) laser and 6x8 channel HgCdTe 2D detector are used. The length of the scattering volume is larger than plasma size. However, the asymmetry of turbulence structure with respect to the magnetic field and magnetic shear make local turbulence measurements possible. From a 2D image of the integrated fluctuations, the spatial cross-correlation function was estimated using time domain correlation analysis, then, the integrated 2D k-spectrum is obtained using maximum entropy method. The 2D k-spectrum is converted from Cartesian coordinates to cylindrical coordinates. Finally, the angle in cylindrical coordinate is converted to flux surface labels. The fluctuation profile over almost the entire plasma diameter can be obtained at a single moment. The measurable k-region can be varied by adjusting the detection optics. Presently, k=0.1-1.0 mm(-1) can be measured which is expected region of ion temperature gradient modes and trapped electron mode in LHD. The spatial resolution is 10%-50% of the minor radius.


Functional Imaging of Pheochromocytoma with Ga-DOTATOC and C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia.
Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or (11)C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of (11)C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.


Study on the relationship between the expression of IGF-1 in umbilical cord blood and abnormal glucose metabolism during pregnancy.
To explore the relationship between the expression of insulin-like growth factor-1 (IGF-1) in neonatal umbilical cord blood and abnormal glucose metabolism during pregnancy. We have selected 63 cases of delivery randomly, term birth and maternal from January 2015 to January 2016 in our hospital, gestational diabetes mellitus for Group A, abnormal gestational glucose tolerance for Group B and normal for Group C with 21 cases in each group. The venous blood samples were collected from all the pregnant females 2 weeks before delivery, and the levels of HbA1c in serum were detected by Elisa method. During the delivery, the umbilical cord blood was collected and the levels of IGF-1 were measured by double site immune enzyme analysis. The neonatal weight was recorded and the correlation analysis was made in respect of the measurement results. The level of HbA1c in Group A was significantly higher than that in Group C (p < 0.05); IGF-1 level and neonatal weight of Group B were significantly higher than that of Group C (p < 0.05), IGF-1 has a significant correlation with neonatal weight in Group C, and HbA1c and IGF-1 were positively correlated (p < 0.05); IGF-1 was positively correlated with neonatal weight in Group A and Group B (p < 0.05). There was a significant positive correlation between the IGF-1 level of neonatal umbilical cord blood and the neonatal weight (p < 0.05). Also, the level of HbA1c was positively correlated with the level of IGF-1 in neonatal umbilical cord blood at the end of pregnancy (p < 0.05). The expression level of IGF-1 in the final stage of pregnant females can be detected to predict the expression level of IGF-1 in newborn infants and then the growth status of the fetus can be obtained.


Giant schwannomas of the sciatic nerve.
We report a very rare case of giant schwannomas of the sciatic nerve in a 39-year-old woman who presented with increasing swelling and discomfort in the posterior aspect of her right thigh. We demonstrate that even with such large tumours, surgical excision could be successfully carried out to resolve all symptoms while causing no permanent nerve damage. It remains paramount that large soft tissue tumours get referred to a sarcoma centre and be managed by a specialist multidisciplinary team.


Assessing elements of an extended evolutionary synthesis for plant domestication and agricultural origin research.
The development of agricultural societies, one of the most transformative events in human and ecological history, was made possible by plant and animal domestication. Plant domestication began 12,000-10,000 y ago in a number of major world areas, including the New World tropics, Southwest Asia, and China, during a period of profound global environmental perturbations as the Pleistocene epoch ended and transitioned into the Holocene. Domestication is at its heart an evolutionary process, and for many prehistorians evolutionary theory has been foundational in investigating agricultural origins. Similarly, geneticists working largely with modern crops and their living wild progenitors have documented some of the mechanisms that underwrote phenotypic transformations from wild to domesticated species. Ever-improving analytic methods for retrieval of empirical data from archaeological sites, together with advances in genetic, genomic, epigenetic, and experimental research on living crop plants and wild progenitors, suggest that three fields of study currently little applied to plant domestication processes may be necessary to understand these transformations across a range of species important in early prehistoric agriculture. These fields are phenotypic (developmental) plasticity, niche construction theory, and epigenetics with transgenerational epigenetic inheritance. All are central in a controversy about whether an Extended Evolutionary Synthesis is needed to reconceptualize how evolutionary change occurs. An exploration of their present and potential utility in domestication study shows that all three fields have considerable promise in elucidating important issues in plant domestication and in agricultural origin and dispersal research and should be increasingly applied to these issues.


Receptor mutations and haplotypes in growth hormone receptor deficiency: a global survey and identification of the Ecuadorean E180splice mutation in an oriental Jewish patient.
Eight different mutations were detected in the growth hormone (GH) receptor gene of patients with inherited GH receptor deficiency (GHRD; Laron syndrome) from five continents. All the mutations are located in the extracellular domain of the receptor and are predicted to cause gross structural abnormalities and non-functional receptor molecules. They include three nucleotide changes in the coding region causing translational stop signals, including the newly identified E183X mutation; two nucleotide changes in introns that affect splice junctions; two dinucleotide deletions that result in stop codons downstream; and one single nucleotide change that activates a donor splice site within an exon and results in a transcript missing 24 nucleotides. This latter mutation (E180splice) was first identified in a cohort of patients with GHRD from southern Ecuador. Based on the fact that the E180splice mutation generates a new cleavage site for the restriction enzyme MnlI, a simple diagnostic test has been developed that can be carried out on dried blood spots collected on filter paper. A total of 55 affected individuals from Ecuador has been found to be homozygous for this mutation. Asymptomatic carriers can also be detected, and 104 of 150 individuals screened were found to be carriers. Using this test, the E180splice mutation has recently been detected in one of two oriental Jewish patients from Israel.


Host-related nucleotide composition and codon usage as driving forces in the recent evolution of the Astroviridae.
The evolutionary history of the Astroviridae comprises the ancient separation between avian and mammalian astrovirus lineages followed by diversification among mammalian astroviruses. The latter process included several cross-species transmissions. We found that the recent, but not the ancient, evolution of astroviruses was associated with a switch in nucleotide composition and codon usage among non-human mammalian versus human/avian astroviruses. Virus and hosts phylogenies based on codon usage agreed with each other and matched the hosts' evolutionary emergence order. This recent switch in driving forces acting at the synonymous level points to the adaptation of codon usage by viruses to that of their hosts after cross-species transmissions. This is the first demonstration of nucleotide composition and codon usage being active driving forces during the recent evolutionary history of a virus group in the host-parasite system.


Frustration responses of single and partnered mothers to prolonged infant crying.
Prolonged infant crying can be a trigger for maternal frustration and can even predict intrusive infant-related thoughts of harm. In this study, we compared frustration responses to prolonged infant crying between single and partnered mothers and attempted to identify variables that mediated any difference between the two groups. We also identified acoustic characteristics of infant cries that were related to higher levels of reported maternal frustration. Twenty-five single and 25 partnered mothers with infants under the age of 6 months completed several mental health questionnaires, and then rated their frustration level after listening to each of 50 consecutive 15s infant cry videos from 50 different infants. As expected, greater maternal perceived stress was associated with higher frustration ratings in response to infant crying, and this was mediated by increased maternal negative affect. Also as expected, both financial strain and low social support were associated with greater perceived stress. However, our sample of single mothers did not experience more stress than our sample of partnered mothers. Nor did they find infant crying to be more frustrating, perhaps due to a recruitment bias toward higher functioning single mothers. Finally, several cry acoustic characteristics were associated with increased maternal frustration, including higher fundamental frequency, air energy, shimmer and longer duration of expiratory phonations, as well as a longer cumulative duration of crying. Our results suggest that maternal frustration in response to infant crying may be decreased by lowering maternal stress levels, and this may be achieved by increasing social support and decreasing financial strain. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Reducing suffering to improve quality of life through health promotion.
This paper deals with complex concepts of suffering, quality of life and palliative care in the context of health promotion. Although these concepts have been examined separately, relatively few researchers have attempted to describe and link these concepts with the aim of health promotion. The reason why few attempts have been made is because the concepts are paradoxical and include contrasting ideas. Additionally, a number of core aspects of palliative care are underdeveloped and there is failure to address issues of suffering. Preliminary findings from a phenomenological study of community nurses providing palliative care to suffering clients revealed themes of power and showing the way coming to suffer through not knowing, being as giving by enhancing quality of life and being as giving by sharing. Embedded in these themes are concepts of quality of life, core concerns for managing suffering in terminal illness and ideas for health promotion. These concerns are incorporated in the recommendations for nursing practice and future reseach.


Bit-mapped somatosensory evoked potentials and muscular reflex responses in man: comparative analysis in different experimental protocols.
Bit-colour maps of somatosensory evoked potentials (SEPs) and muscular responses from forearm and hand muscles were simultaneously recorded after median nerve stimulation. Subjects were asked either to relax totally (A), or to contract the examined muscle continuously and isometrically at 10-20% (B) and 80-100% (C) of the maximal strength. Isotonic contractions ipsilateral (D) and contralateral to the stimulus (E) were also examined. Both SEPs and EMG responses were elicited by individual near-motor threshold pulses delivered at 0.2/sec to the median nerve at the elbow. SEPs were maximal in amplitude during complete relaxation, whilst all the components following the parietal N20 were depressed by muscle contraction. Such decrements affected predominantly the parietal and frontal peaks of positive polarity during condition B, whilst the frontal negative component (wave N30) dropped remarkably in conditions C and D. Early EMG responses (V1 = spinal circuitry) were usually absent in condition A; they were present together with later components (= V2 possibly long-loop, transcortical circuitry) in C and D, whilst they were alone recordable in B and E. The amplitudes of the frontal wave N30 in SEPs and of V2 in LLRs were inversely correlated. This observation is consistent with the hypothesis that a change in the reactivity of the sensorimotor brain areas to afferent impulses is coupled to LLR elicitation in forearm and hand muscles.


Regulation of syndecan-4 phosphorylation in vivo.
Recent studies suggest that some of the heparan sulfate-carrying proteoglycans may directly participate in signaling via their cytoplasmic tail. The present investigation addresses the potential involvement of syndecan-4, a widely expressed transmembrane proteoglycan, in this process. We found that the cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue (Ser183) in growth-arrested NIH 3T3 fibroblasts, with a stoichiometry of 0.3 mol Pi/mol syndecan-4. Treatment of the cells with a protein kinase C (PKC)-activating phorbol ester lead to a 2.5-fold increase in Ser183 phosphorylation. This increase was inhibited by a generic PKC inhibitor but not by an inhibitor specific to the calcium-dependent conventional PKCs, suggesting that the cytoplasmic tail of syndecan-4 is phosphorylated by a calcium-independent novel PKC isozyme. Application of 10-30 ng/ml basic fibroblast growth factor (bFGF) produced a 2-3-fold reduction in the phosphorylation of syndecan-4. Because treatment with the phosphatase inhibitor calyculin prevented the bFGF-induced decrease in syndecan-4 phosphorylation, the effect of bFGF appears to be mediated by a protein serine/threonine phosphatase type 1 or 2A. We conclude that the cytoplasmic tail of syndecan-4 is subject to in vivo phosphorylation on Ser183, which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent serine/threonine phosphatase.


RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism.
Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates that necroptosis plays a critical role in the development of AKI. However, it is unclear whether renal tubular cells undergo necroptosis in vivo and how the necroptotic pathway is regulated during AKI. Repulsive guidance molecule (RGM)-b is a member of the RGM family. Our previous study demonstrated that RGMb is highly expressed in kidney tubular epithelial cells, but its biological role in the kidney has not been well characterized. In the present study, we found that RGMb reduced membrane-associated MLKL levels and inhibited necroptosis in cultured cells. During ischemia/reperfusion injury (IRI) or oxalate nephropathy, MLKL was induced to express on the apical membrane of proximal tubular (PT) cells. Specific knockout of Rgmb in tubular cells (Rgmb cKO) increased MLKL expression at the apical membrane of PT cells and induced more tubular cell death and more severe renal dysfunction compared with wild-type mice. Treatment with the necroptosis inhibitor Necrostatin-1 or GSK'963 reduced MLKL expression on the apical membrane of PT cells and ameliorated renal function impairment after IRI in both wild-type and Rgmb cKO mice. Taken together, our results suggest that proximal tubular cell necroptosis plays an important role in AKI, and that RGMb protects against AKI by inhibiting MLKL membrane association and necroptosis in proximal tubular cells.


[Peyronie's disease: treatment with interferon and laser].
To evaluate comparatively the results of treatment with interferon, laser and their association in a group of patients with Peyronie's disease. We performed an experimental study to evaluate the main results of the treatment of Peyronie's disease with interferon and laser, at Hospital Provincial Universitario "Saturnino Lora Torres" and Hospital General Universitario "Dr. Juan Bruno Zayas Alfonso" in the city of Santiago de Cuba from January 2003 to July 2005. Ninety-six patients were included, divided into three treatment groups: interferon, laser and interferon plus loser. After initial evaluation, treatment was started and continued for 28 weeks, with reevaluation six and 12 months after the end of treatment. Final results with combined interferon and laser were: symptoms improvement 84.7%, decrease of the size of the fibrous plaque 90.6% and decrease of penile curvature 87.5%. The combination of both therapies resulted to be more effective than each of them separately, so the recommendation is to incorporate it as another therapeutic alternative in Peyronie's disease.


Low levels of mitochondrial DNA and symbiont diversity in the worldwide agricultural pest, the greenhouse whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae).
Trialeurodes vaporariorum, the greenhouse whitefly, is a cosmopolitan agricultural pest. Little is known about the genetic diversity of T. vaporariorum and the bacterial symbionts associated with this species. Here, we undertook a large phylogeographic study by investigating both the mitochondrial (mt) diversity and the infection status of 38 T. vaporariorum collections from 18 countries around the world. Genetic diversity of T. vaporariorum was studied by analyzing sequence data from the mt cytochrome oxidase I, cytochrome b, and NADH dehydrogenase subunit 5 genes. Maximum-likelihood (ML) phylogeny reconstruction delineated 2 clades characterized by limited sequence divergence: one clade comprised samples only from the Northern hemisphere whereas the other comprised samples from a broader geographical range. The presence of secondary symbionts was determined by PCR using primers specific for Hamiltonella, Rickettsia, Arsenophonus, Cardinium, Wolbachia, and Fritschea. Most individuals examined harbored at least one secondary endosymbiont, and Arsenophonus was detected in almost all male and female individuals. Wolbachia was present at a much lower frequency, and Cardinium was detected in only a few individuals from Greece. Rickettsia, Hamiltonella, and Fritschea were not found. Additionally, we set out to further analyze Arsenophonus diversity by multilocus sequence typing analysis; however, the Arsenophonus sequences did not exhibit any polymorphism. Our results revealed remarkably low diversity in both mtDNA and symbionts in this worldwide agricultural pest, contrasting sharply with that of the ecologically similar Bemisia tabaci.


Induction of complement proteins in a mouse model for cerebral microvascular A beta deposition.
The deposition of amyloid beta-protein (A beta) in cerebral vasculature, known as cerebral amyloid angiopathy (CAA), is a common pathological feature of Alzheimer's disease and related disorders. In familial forms of CAA single mutations in the A beta peptide have been linked to the increase of vascular A beta deposits accompanied by a strong localized activation of glial cells and elevated expression of neuroinflammatory mediators including complement proteins. We have developed human amyloid-beta precursor protein transgenic mice harboring two CAA A beta mutations (Dutch E693Q and Iowa D694N) that mimic the prevalent cerebral microvascular A beta deposition observed in those patients, and the Swedish mutations (K670N/M671L) to increase A beta production. In these Tg-SwDI mice, we have reported predominant fibrillar A beta along microvessels in the thalamic region and diffuse plaques in cortical region. Concurrently, activated microglia and reactive astrocytes have been detected primarily in association with fibrillar cerebral microvascular A beta in this model. Here we show that three native complement components in classical and alternative complement pathways, C1q, C3, and C4, are elevated in Tg-SwDI mice in regions rich in fibrillar microvascular A beta. Immunohistochemical staining of all three proteins was increased in thalamus, hippocampus, and subiculum, but not frontal cortex. Western blot analysis showed significant increases of all three proteins in the thalamic region (with hippocampus) as well as the cortical region, except C3 that was below detection level in cortex. Also, in the thalamic region (with hippocampus), C1q and C3 mRNAs were significantly up-regulated. These complement proteins appeared to be expressed largely by activated microglial cells associated with the fibrillar microvascular A beta deposits. Our findings demonstrate that Tg-SwDI mice exhibit elevated complement protein expression in response to fibrillar vascular A beta deposition that is observed in patients with familial CAA.


Risk Factors for Bilateral Femoroacetabular Impingement Syndrome Requiring Surgery.
To identify the risk factors for contralateral surgery in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Patients who underwent unilateral surgery were compared with those who underwent staged bilateral surgery to identify risk factors associated with bilateral surgery. Variables examined included demographics, comorbidities, and radiographic features. Binary logistic regression was used to identify predictors of bilateral FAIS. A total of 694 patients with an average age of 34.0 ± 13.1 years met were included in the analysis. Overall, 109 patients (15.3%) had staged bilateral hip arthroscopy for FAIS. Risk factors associated for bilateral FAIS requiring surgery were decreased age and lower Charlson Comorbidity Index (CCI). Compared with patients aged <25 years, those aged 25 to 34 years (odds ratio [OR], 0.5; P = 0.031), 35 to 44 years (OR, 0.5; P = 0.034), and ≥45 years (OR, 0.3; P = 0.002) had lower odds of bilateral labral tear. In addition, patients with a CCI <2 were three times more likely to require bilateral FAIS surgery (OR, 3.4; P = 0.044). None of the radiographic parameters predicted bilateral labral tears. Patients younger than 25 years and those with a CCI <2 had markedly increased rates of bilateral FAIS necessitating surgery compared with older patients. This study may be of value in preoperative counseling.


Antimicrobial bacteriophage-derived proteins and therapeutic applications.
Antibiotics have the remarkable power to control bacterial infections. Unfortunately, widespread use, whether regarded as prudent or not, has favored the emergence and persistence of antibiotic resistant strains of human pathogenic bacteria, resulting in a global health threat. Bacteriophages (phages) are parasites that invade the cells of virtually all known bacteria. Phages reproduce by utilizing the host cell's machinery to replicate viral proteins and genomic material, generally damaging and killing the cell in the process. Thus, phage can be exploited therapeutically as bacteriolytic agents against bacteria. Furthermore, understanding of the molecular processes involved in the viral life cycle, particularly the entry and cell lysis steps, has led to the development of viral proteins as antibacterial agents. Here we review the current preclinical state of using phage-derived endolysins, virion-associated peptidoglycan hydrolases, polysaccharide depolymerases, and holins for the treatment of bacterial infection. The scope of this review is a focus on the viral proteins that have been assessed for protective effects against human pathogenic bacteria in animal models of infection and disease.


Antifungal Activities of Dimeric Sesquiterpenes, Shizukaols C and F, Isolated from Chloranthus japonicus Sieb.
Two dimeric sesquiterpenes were separated from Chloranthus japonicus Sieb. and identified as shizukaols C and F. They exhibited potent antifungal activities (MICs = 4-16 μg/ml) in vitro against various plant pathogenic fungi (Pythium ultimum, Phytophthora infestans, Botrytis cinerea, Colletotrichum lagenarium, Alternaria kikuchiana, and Magnaporthe grisea). Shizukaol C showed 88% and 91% protective activities in the greenhouse against Puccinia recondita (wheat leaf rust) and Phytophthora infestans (tomato late blight), respectively, at 100 μg/ml; shizukaol F exhibited 93% antifungal activity against Puccinia recondita at the same concentration. Therefore, these compounds might serve as interesting candidates for effective antifungal agents.


Oriented Self-Assembled Monolayer of Zn(II)-Tetraphenylporphyrin on TiO2 Electrode for Photoelectrochemical Analysis.
The photoelectrochemical performance of a zinc porphyrin sensitized TiO2 photoelectrode fabricated through the axial-coordination strategy has been studied. Zinc(II) tetraphenylporphyrin (TPPZn) was immobilized on the TiO2 electrode through the axial coordination reaction with surface premodified methyl 4-(1 H-imidazol-1-yl)benzoate (PhImMe). Spectral characterizations were carried out to confirm the robust interaction between TPPZn and PhImMe, while the chemical bonding of PhImMe on TiO2 surface has been evidenced by XPS measurement. The modified TiO2 electrode produces a stable and enhanced photocurrent signal under 410 nm irradiation at a bias of 0.2 V in phosphate buffer solution, compared with pristine TiO2. A sensitive increment of the photocurrent is observed with the addition of l-glutathione. A possible mechanism for this photoelectrochemical process includes the photoexcitation of the porphyrin, electron injection from porphyrin toward the TiO2, and the hole-scavenging process by the reductants. The "lying-low" surface conformation of the porphyrin plane might facilitate the PEC process owing to the enhanced electronic coupling between the porphyrin plane and the TiO2 substrate. A PEC analysis on l-glutathione has been carried out to evaluate the photoelectrochemical performance of the modified TiO2 electrode, which presents the wide linear ranges of 5-80 μM and 80-5000 μM, with a lower detection limit of 3.21 μM at an S/N ratio of 3. This work reports for the first time on the PEC performance of metalloporphyrin axially coordinated on a semiconductor surface and could lead to the designing of more efficient photoelectrochemical sensors and devices based on similar electrode structures.


Oral Contraceptives Modulate the Relationship Between Resting Brain Activity, Amygdala Connectivity and Emotion Recognition - A Resting State fMRI Study.
Recent research into the effects of hormonal contraceptives on emotion processing and brain function suggests that hormonal contraceptive users show (a) reduced accuracy in recognizing emotions compared to naturally cycling women, and (b) alterations in amygdala volume and connectivity at rest. To date, these observations have not been linked, although the amygdala has certainly been identified as core region activated during emotion recognition. To assess, whether volume, oscillatory activity and connectivity of emotion-related brain areas at rest are predictive of participant's ability to recognize facial emotional expressions, 72 participants (20 men, 20 naturally cycling women, 16 users of androgenic contraceptives, 16 users of anti-androgenic contraceptives) completed a brain structural and resting state fMRI scan, as well as an emotion recognition task. Our results showed that resting brain characteristics did not mediate oral contraceptive effects on emotion recognition performance. However, sex and oral contraceptive use emerged as a moderator of brain-behavior associations. Sex differences did emerge in the prediction of emotion recognition performance by the left amygdala amplitude of low frequency oscillations (ALFF) for anger, as well as left and right amygdala connectivity for fear. Anti-androgenic oral contraceptive users (OC) users stood out in that they showed strong brain-behavior associations, usually in the opposite direction as naturally cycling women, while androgenic OC-users showed a pattern similar to, but weaker, than naturally cycling women. This result suggests that amygdala ALFF and connectivity have predictive values for facial emotion recognition. The importance of the different connections depends heavily on sex hormones and oral contraceptive use.


Substrate temperature effect on the refractive index and a two-step film method to detect small inhomogeneities in optical films.
Nb2O5 films were deposited by a reactive magnetron sputtering technique. The average refractive index was found to increase with the rise of substrate temperature. Modulated interference transmittance spectra were observed in the two-step films, which were prepared by stopping the deposition process in the middle of the designed sputtering time, and then, after a full cooling down to room temperature, starting the same deposition process again to complete the whole preparation of the films. A linearly graded-index model was used to explain the interference behavior. It was proved that the two-step film method was sensitive to the small inhomogeneity in the films. We also suggest that the inhomogeneity of sputtered films can be minimized by controlling the substrate temperature at a constant value.


The effect of sustainable low-dose sildenafil and cognitive-behavioral training on sexual function in methadone-treated men-a randomized controlled trial.
Sexual dysfunction caused by opioids is one of the serious problems of drug misusers. This study aimed to evaluate and compare the effect of continuous low-dose sildenafil treatment alongside psychological training on the sexual function of methadone-treated patients. This randomized clinical trial was conducted on methadone-treated men with sexual dysfunction. Patients were randomly divided into two treatment groups: sildenafil 25 mg and psychological training. Sexual Quality of Life-Men, Sexual Self-Efficacy Scale-Erectile, and the International Index of Erectile Function were used before and 4 weeks after the end of the intervention. A total of 67 couples were included in the study (34 psychological interventions vs. 33 sildenafil group). After 4 weeks of treatment, the mean of male erectile function (33.73 ± 8.114 and 27.62 ± 6.238, p = 0.003) and sexual self-efficacy score (78.36 ± 12.713 and 69.62 ± 14.940, p < 0.0001) in the sildenafil group were statistically significant compared to the psychological group, however, the sexual quality score of the two groups was not statistically significant (31.48 ± 9.216 and 31.71 ± 11.333, p = 0.342). The sexual function of methadone-treated men in both groups was significantly improved, yet this difference was significantly greater in the pharmaceutical treatment group than the trainings. As a result, due to the high need for treatment, any type of intervention (medication or psychotherapy) will be effective in these patients.


[Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype].
Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.


The effect of celecoxib on orthodontic tooth movement and root resorption in rat.
Inhibition of prostaglandin (PGs) production leads to decrease in orthodontic tooth movement (OTM). It is not known whether inhibition of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2) is the key mechanism for this effect. In this study, the effect of celecoxib, a highly-selective COX-2 inhibitor, was investigated on OTM in rats. Four groups of male rats (seven animals in each goup) were used in the study. A 5mm-long nickel-titanium closed-coil spring was ligated between the right maxillary incisor and the first molar of each rat to deliver an initial force of 60g. All four groups recieved orthodontic appliances, group 1 received no injections, group 2 received celecoxib injections (0.3 mg in 0.1 ml saline solution), group 3 recieved normal saline injections (0.1 ml saline solution), and group 4 recieved needle penetration without injecting any solution. The local injections were carried out every 3 days for 18 days. All injections were subperiosteal and given in the upper right first molar mucosa. The animals were sacrificed 21 days after appliance insertion and OTM was measured. In the animals treated with celecoxib a statistically significant decrease in OTM was observed compared with the other groups. Histological findings revealed that osteoclast count was significantly lower in group 2 compared with the other groups (P<0.05). The amount of root resorption showed a slight, but nonsignificant decrease in group 3. This study suggests that celecoxib decreases OTM and osteoclast count. This might be the result of COX-2 enzyme inhibition and subsequent decrease in prostaglandin production.


Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity.
Small-cell ovarian carcinoma (SCOC) is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT) can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS) can also occur, jeopardizing the patient's outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.


Comparative Study of Hydrogen- and Deuterium-Induced Degradation of Ferroelectric (Pb,La)(Zr,Ti)O3 Capacitors Using Time-of-Flight Secondary Ion Measurement.
Ferroelectric (Pb,La)(Zr,Ti)O3 (PLZT) capacitors were fabricated with Pt, Al:ZnO (AZO), or Sn:In2O3 (ITO) top electrodes. Hydrogen- or deuterium-induced degradation was investigated for the three capacitors by annealing in a 3% H2/balance N2 or 3% D2/balance N2 ambient environment at 200 °C and 1 torr. The remnant polarization of all capacitors decreased after annealing in both H2 and D2 ambient after 45 min, and the remnant polarization of the Pt/PLZT/Pt capacitor significantly decreased after 45-min annealing compared with that of the AZO/PLZT/Pt and ITO/PLZT/Pt capacitors, even though the initial remnant polarization for the Pt/PLZT/Pt capacitor was larger. Time-of-flight secondary ion mass spectrometry showed slight differences in hydrogen content for the three different capacitors after H2 annealing. In contrast, the deuterium content of the Pt/PLZT/Pt and AZO/PLZT/Pt or ITO/PLZT/PT capacitors was significantly different after deuterium annealing. Deuterium depth profiles for the Pt/PLZT/Pt capacitor after annealing showed that deuterium conformally exists in the PLZT layer of the Pt/PLZT/Pt capacitor, and deuterium accumulation under the Pt bottom electrode was also observed. This result suggests that diffusion of deuterium in Pt was much higher than that in PLZT. AZO and ITO top electrodes could act as a hydrogen barrier layer for ferroelectric films.


An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia.
Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children's Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations. Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy. ClinicalTrials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1.


Multi-omics analysis dissects the genetic architecture of seed coat content in Brassica napus.
Brassica napus is an important vegetable oil source worldwide. Seed coat content is a complex quantitative trait that negatively correlates with the seed oil content in B. napus. Here we provide insights into the genetic basis of natural variation of seed coat content by transcriptome-wide association studies (TWAS) and genome-wide association studies (GWAS) using 382 B. napus accessions. By population transcriptomic analysis, we identify more than 700 genes and four gene modules that are significantly associated with seed coat content. We also characterize three reliable quantitative trait loci (QTLs) controlling seed coat content by GWAS. Combining TWAS and correlation networks of seed coat content-related gene modules, we find that BnaC07.CCR-LIKE (CCRL) and BnaTT8s play key roles in the determination of the trait by modulating lignin biosynthesis. By expression GWAS analysis, we identify a regulatory hotspot on chromosome A09, which is involved in controlling seed coat content through BnaC07.CCRL and BnaTT8s. We then predict the downstream genes regulated by BnaTT8s using multi-omics datasets. We further experimentally validate that BnaCCRL and BnaTT8 positively regulate seed coat content and lignin content. BnaCCRL represents a novel identified gene involved in seed coat development. Furthermore, we also predict the key genes regulating carbon allocation between phenylpropane compounds and oil during seed development in B. napus. This study helps us to better understand the complex machinery of seed coat development and provides a genetic resource for genetic improvement of seed coat content in B. napus breeding.


Biological characteristics of Grapholita molesta (Lepidoptera: Tortricidae) induced to diapause in laboratory.
In southern Brazil, Grapholita molesta (Busck) (Lepidoptera: Tortricidae) uses diapause as survival strategy during the winter (May-August). In our study, we evaluated the effect of diapause on biological characteristics of the species for 4 months in laboratory. Newly hatched larvae of G. molesta were induced to diapause changing the photoperiod and temperature (T) (12 ± 1°C), relative humidity (RH) (70 ± 10%), and a photophase of 12 h and, when they started diapause in the prepupal stage, the conditions were kept for 4 months. Afterwards, the insects were induced to finalize the diapause process at T 25 ± 1°C, RH 70 ± 10%, and a photophase of 16 h. We evaluated the duration and viability of the larval stages and pupae, pupae weight at 24 h and sex ratio (sr), periods of preoviposition, oviposition, and postoviposition; adult life span (males and females); fecundity (daily and total); embryonic period duration and eggs viability, comparing the data with insects nondiapause. The results show that diapause greatly affected the viability of pupal-adult stages of the population (21.8%) when compared with insects' nondiapause (80.0%). Total fecundity (83.0 eggs) and mean life span (12.0 d) of insects diapause was significantly lower compared with insects nondiapause (173.0 and 17.0), respectively. However, these differences were not observed in the sr, which was similar to insects diapause (sr = 0.41) and insects nondiapause (sr = 0.49). The diapause induced for 4 months negatively affects reproduction and life span of adults of G. molesta.


Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography.
We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) = Dx-40; 5 X 10(5) = Dx-500; 2 X 10(6) = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.


Antiracism and the level of health services: a sociomedical hypothesis.
Little attention has been paid to the validity of the "reverse discrimination" position that antiracist initiatives in the health sector would be associated with reduced services for whites. This paper advances the sociomedical hypothesis that antiracism leads to an increase in the level of health services and opportunities available to both minority and white populations.FOUR TYPES OF US HEALTH CARE UTILIZATION AND TRAINING DATA ARE EXPLORED: annual rates of discharge from short-stay hospitals, percent of population seeing a physician during the year, rates of hypertension treatment and control, and admissions to the first-year class of US medical schools. These data are examined according to race for years prior and subsequent to the upsurge of antiracist activity that characterized the Civil Rights Movement era.From the early or mid-1960s to the mid- or late 1970s, hospital discharges, physician visits, and hypertension treatment and control for minorities and whites increased substantially. Generally these increases were proportionally greater for minorities. Although the percentage of increase in minority medical school admissions was necessarily accompanied by a decline in percentage of admissions of whites, the absolute number of whites admitted rose substantially as overall class size grew.These data do not support the "reverse discrimination" notion of one racial group benefiting at the expense of another. The data are consistent with the hypothesis that antiracist efforts in the health sector lead to an expansion of services and opportunities for minority and majority populations.


Binaural speech discrimination.
The phenomenon of binaural summation in which the addition of signals presented to the two ears simultaneously takes place at a central level, has been known for many years. It is reasonable to assume that the pattern of summation differs between subjects with central lesions and those with lesions in the peripheral auditory tracts. Various tests have been proposed to aid in locating the site of the lesion which compare the monaural and binaural speech discrimination scores. In the present work, two of these tests have been examined. Three groups of subjects have been used: (1) a normally hearing group; (2) a group with hearing impairment resulting from cochlea pathology, and (3) a group with hearing impairment resulting from lesions at the level of the cochlear nuclei. The results showed that neither test differentiated between peripheral and cochlear nuclei lesions.


Polyphenolic composition, antioxidant activity, and polyphenol oxidase (PPO) activity of quince (Cydonia oblonga Miller) varieties.
Phytochemical profiles (phenolic compounds, L-ascorbic acid, antioxidant and PPO activities) of 13 different quince varieties and 5 genotypes were studied. Polyphenols were identified by LC-PDA-QTof/MS and quantified by UPLC-PDA and UPLC-FL. A total of 26 polyphenolic compounds found in quince tissues were identified and presented: 9 flavan-3-ols ((-)-epicatechin, procyanidin B2, 3 procyanidin dimers and trimers, and 1 tetramer); 8 hydroxycinnamates, derivatives of caffeoylquinic and coumaroylquinic acid; and 9 kaempferol and quercetin derivatives. The content of total polyphenols was between 1709.43 (genotype 'S1') and 3436.56 mg/100 g dry weight ('Leskovač'). Flavan-3-ols, which are the major class of quince polyphenols, represented between 78 and 94% of the total polyphenolic compounds. The activity of PPO enzyme ranged from 709.85 to 1284.59 ΔU/min, and that of L-ascorbic acid ranged from 5.86 to 26.42 mg/100 g. Some quince varieties and their products characterized by a higher content of phenolic compounds may be selected to promote their positive effect on health.


Nanoassemblies of Tissue-Reactive, Polyoxazoline Graft-Copolymers Restore the Lubrication Properties of Degraded Cartilage.
Osteoarthritis leads to an alteration in the composition of the synovial fluid, which is associated with an increase in friction and the progressive and irreversible destruction of the articular cartilage. In order to tackle this degenerative disease, there has been a growing interest in the medical field to establish effective, long-term treatments to restore cartilage lubrication after damage. Here we develop a series of graft-copolymers capable of assembling selectively on the degraded cartilage, resurfacing it, and restoring the lubricating properties of the native tissue. These comprise a polyglutamic acid backbone (PGA) coupled to brush-forming, poly-2-methyl-2-oxazoline (PMOXA) side chains, which provide biopassivity and lubricity to the surface, and to aldehyde-bearing tissue-reactive groups, for the anchoring on the degenerated cartilage via Schiff bases. Optimization of the graft-copolymer architecture (i.e., density and length of side chains and amount of tissue-reactive functions) allowed a uniform passivation of the degraded cartilage surface. Graft-copolymer-treated cartilage showed very low coefficients of friction within synovial fluid, reestablishing and in some cases improving the lubricating properties of the natural cartilage. Due to these distinctive properties and their high biocompatibility and stability under physiological conditions, cartilage-reactive graft-copolymers emerge as promising injectable formulations to slow down the progression of cartilage degradation, which characterizes the early stages of osteoarthritis.


Multiporphyrin arrays on cyclotriphosphazene scaffolds.
We report the synthesis of first examples of hexaporphyrin and dodecaporphyrin assemblies on cyclotriphosphazene scaffold by adopting two different approaches based on Ru-pyridyl "N" coordination in decent yields. The multiporphyrin assemblies were confirmed by (31)P, (13)C, (1)H, (1)H-(1)H COSY, and NOESY NMR spectroscopic studies. The absorption studies showed 2-fold intensity enhancement with negligible changes in peak maxima compared to porphyrin monomers. The redox potentials of multiporphyrin assemblies showed the redox features of the constituted porphyrin monomers and supported weak interactions among the porphyrin units in noncovalent hexaporphyrin and dodecaporphyrin arrays.


Community organisation-researcher partnerships: what concerns arise for community organisations and how can they be mitigated?
Universities and research funders' growing emphasis on community partnerships, engagement and outreach has seen a rise in collaborations between university researchers and staff of community organisations (COs) on research projects. What ethical issues and concerns are experienced as part of these collaborations has largely not been described, particularly from the perspective of COs As part of a recent, broader qualitative study, several concerns arising during health research collaborations between COs and university researchers were captured during thematic analysis. The concerns were described in semistructured interviews by four staff of three COs that work with marginalised groups (ie, migrants and refugees, women who experience domestic violence, indigenous populations) in a high-income country. In this paper, the three concerns are taken as the starting point for ethical analysis. Interview data are first used to illustrate the three concerns: being restricted to a recruitment role in studies, reinforcement of stereotypes of marginalised groups and weakening CO-community relationships. The paper then explores why the concerns are morally troubling and demonstrates how each concern generates feelings of disrespect, creates harm(s), and/or reflects or reinforces unfairness or injustice. It concludes by proposing three ethical criteria for CO-researcher partnerships: fair division of labour, balancing CO advocacy goals with research goals and balancing CO service goals with research goals. Where researchers and COs discuss how to meet these criteria at the start and during research collaborations, it can potentially help mitigate or prevent the occurrence of the concerns described in this paper.


Elderly patients in the accident department and their problems.
During two months in the winter and two in the summer information was gleaned about all patients aged 70 and over attending a large accident and emergency department. Comparative figures for the same periods over the previous 20 years showed an increasing number of elderly attenders, the increase being closely related to the increasing proportion of elderly in the population. Using national census data, attendance rates were shown to increase dramatically with age. With increasing age more elderly attended as a result of accidents in the home. The information suggested that social isolation and paucity of support in the community may be responsible for the decision to come to hospital rather than to consult the general practitioner. The elderly attend accident and emergency departments for a wide range of problems but some do so solely for socioeconomic reasons and are particularly difficult to help.


Differentiation and production of action potentials by embryonic rat retina stem cells in vitro.
Transplantation of retinal stem cells (RSCs) is a potential therapy for retinal degeneration. However, success critically depends on whether RSCs can differentiate into fully functional daughter cells. Whole-cell patch clamp techniques were used to characterize the postinduction developmental profile of membrane potentials and ionic currents in RSCs cultured from embryonic day 17 Long Evans rats. These results were compared to recordings obtained from cultured cells obtained from postnatal day 1 rat pups. Outward rectifying potassium currents (I(K+)) were observed in approximately 15% of cells at day 3 and in all cells by day 7. Voltage-dependent sodium currents took longer to emerge (day 7), and TTX-sensitive channels were not fully mature until day 15. Broad excitatory potentials, characteristic of immature action potentials, could be reliably stimulated by day 10, and spontaneous action potentials were recorded at day 25, which were indistinguishable, in terms of width and amplitude, from the comparison group of developing retinal neurons. The maturation of presumptive retinal ganglion cell electrophysiological properties appears to take at least 15 days under these culture conditions. Knowledge of the timing of voltage-dependent ion channel development could improve the success rate in future transplantation protocols.


Heparin conjugated polymeric micelle for long-term delivery of basic fibroblast growth factor.
Heparin conjugated amphiphilic block copolymer, Tetronic-PCL-heparin (TCH), was developed and its polymeric micelles (PMs) were prepared as an injectable vehicle for long-term delivery of bFGF, which is one of the heparin-binding growth factors (HBGF). TCH PMs were fabricated by a single emulsion and solvent evaporation method. The structural properties of TCH were confirmed by (1)H NMR, FT-IR and GPC. The contents of bound heparin were 0.44 micro g/micro g and the heparin activity by APTT assay was 43.6% when compared to free heparin. The critical micelle concentration (CMC) of TCH PMs was approximately 0.11 g/l. The diameter of TC micelle was approximately 25 nm and its size after conjugation of heparin was increased to 114 nm due to the heparin molecules on the shell of the micelle. The bFGF loading amount of TCH PMs was considerably higher than that of TC, caused by specific interactions between heparin and bFGF. In vitro study, bFGF was released from TCH PMs in a controlled manner over 2 months. The results demonstrated that TCH PMs become a novel candidate for the long-term delivery of various growth factors with heparin-binding domain in tissue engineering.


Analysis of patients undergoing urological intervention amid the COVID-19: experience from the pandemic hospital.
It is reported that surgical procedures performed during the COVID-19 pandemic are accompanied by high complications and risks. In this study, the urological interventions applied with appropriate infrastructure and protocols during the pandemic in the pandemic hospital that is carrying out the COVID-19 struggle are analyzed. Urological interventions were reviewed in the 5-week period between March 11 and April 16. The distribution of outpatient and interventional procedures was determined by weeks concurrently along with the COVID-19 patient workload, and data in the country, subgroups were further analyzed. Patients intervened were divided into four groups as Emergency, High, Intermediate, and Low Priority cases according to the EAU recommendations. The COVID-19-related findings were recorded; staff and patient effects were reported. Of the 160 interventions, 65 were minimally invasive or open surgical intervention, 95 were non-surgical outpatient intervention, and the outpatient admission was 777. According to the priority level, 33 cases had emergency and high priority, 32 intermediate and low priority. COVID-19 quarantine and follow-up were performed at least 1 week in 22 (33.8%) operated patients at the last week, 43 (66.2%) patients who were operated in the previous 4 weeks followed up at least 2 weeks. No postoperative complications were encountered in any patient due to COVID-19 during the postoperative period. In the COVID-19 pandemic, precautions, isolation, and algorithms are required to avoid disruption in the intervention and follow-up of urology patients; priority urological interventions should not be disrupted in the presence of necessary experience and infrastructure.


Effects of coconut and fish oils on ruminal methanogenesis, fermentation, and abundance and diversity of microbial populations in vitro.
Coconut (CO) and fish (FO) oils were previously shown to inhibit rumen methanogenesis and biohydrogenation, which mitigates methane emission and helps improve beneficial fatty acids in meat and milk. This study aimed at investigating the comparative effects of CO and FO on the methanogenesis, fermentation, and microbial abundances and diversity in vitro rumen cultures containing different doses (0, 3.1, and 6.2 mL/L) of each oil and 400mg feed substrate using rumen fluid from lactating dairy cows as inocula. Increasing doses of CO and FO quadratically decreased concentrations of methane, but hydrogen concentrations were only increased quadratically by CO. Both oils linearly decreased dry matter and neutral detergent fiber digestibility of feeds but did not affect the concentration of total volatile fatty acids. However, CO reduced acetate percentage and acetate to propionate ratio and increased the percentages of propionate and butyrate to a greater extent than FO. Ammonia concentration was greater for CO than FO. As determined by quantitative real-time PCR, FO had greater inhibition to methanogens than CO, but the opposite was true for protozoal, Ruminococcus flavefaciens, and Fibrobacter succinogenes. Ruminococcus albus was not affected by either oil. Denaturing gradient gel electrophoresis (DGGE) profiles revealed that bacterial and archaeal community composition were changed differently by oil type. Based on Pareto-Lorenz evenness curve analysis of the DGGE profiles, CO noticeably changed the functional organization of archaea compared with FO. In conclusion, although both CO and FO decreased methane concentrations to a similar extent, the mode of reduction and the effect on abundances and diversity of archaeal and bacterial populations differed between the oils. Thus, the use of combination of CO and FO at a low dose may additively lower methanogenesis in the rumen while having little adverse effect on rumen fermentation.


Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives.
We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.


Nanofibrous Mineralized Electrospun Scaffold as a Substrate for Bone Tissue Regeneration.
Fibrous scaffolds that reconstruct the extracellular matrix (ECM) have been utilized for tissue regeneration demonstrated potential for guiding stem cell differentiation. Nanofibrous scaffolds fabricated by a unique electrospinning method enabled us to create tailored, functional scaffolds on-demand. Several patterned electrospun poly(ε-caprolactone) (PCL) scaffolds were prepared, and then utilized for creating a hybrid composite in which bone-like hydroxyapatite (b-HA) was deposited onto the unique electrospun scaffolds. The mineral deposits onto the patterned PCL scaffolds was confirmed by scanning electron microscope (SEM). When culturing human adipose-derived stem cells (hASC) onto the different SBF-treated electrospun PCL scaffolds, it was found that the hybrid composite can support hASC differentiated into osteoblasts under osteogenic differentiation conditions. Image analysis and alamar blue assay indicated a significant increase of hASC adhesion and proliferation on the SBF-treated PCL scaffolds. Subsequent analysis of osteogenic potential by via gene expression analysis and alkaline phosphatase (ALP) activity also demonstrated that the SBF-treated electrospun PCL made by the modified electrospinning process is more favorable for the osteogenic differentiation hASCs. Additionally, results of alizarin red S staining and ALP staining at days 7 and 14 showed improved deposition of mineralized matrix on the SBF-treated PCL. Therefore, this study indicates that the facile scaffold fabrication method described in this study is promising approach to prepare osteoconductive scaffold for bone tissue engineering.


Updating of Implicit Adaptation Processes through Erroneous Numeric Feedback.
There is debate about how implicit and explicit processes interact in sensorimotor adaptation, implicating how error signals drive learning. Target error information is thought to primarily influence explicit processes, therefore manipulations to the veracity of this information should impact adaptation but not implicit recalibration (i.e. after-effects). Thirty participants across three groups initially adapted to rotated cursor feedback. Then we manipulated numeric target error through knowledge of results (KR) feedback, where groups practised with correct or incorrect (+/-15°) numeric KR. Participants adapted to erroneous KR, but only the KR + 15 group showed augmented implicit recalibration, evidenced by larger after-effects than before KR exposure. In the presence of sensory prediction errors, target errors modulated after-effects, suggesting an interaction between implicit and explicit processes.


Evaluation of drug uptake and deactivation in plant: Fate of albendazole in ribwort plantain (Plantago laceolata) cells and regenerants.
Albendazole (ABZ) is a benzimidazole anthelmintic widely used especially in veterinary medicine. Along with other drugs, anthelmintics have become one of a new class of micro-pollutants that disturb the environment but the information about their fate in plants remains limited. The present study was designed to test the uptake and biotransformation of ABZ in the ribwort plantain (Plantago lancelota), a common meadow plant, which can come into contact with this anthelmintic through the excrements of treated animals in pastures. Two model systems were used and compared: cell suspensions and whole plant regenerants. In addition, time-dependent changes in occurrence of ABZ and its metabolites in roots, basal parts of the leaves and tops of the leaves were followed up. Ultrahigh-performance liquid chromatography coupled with high mass accuracy tandem mass spectrometry (UHPLC-MS/MS) led to the identification of 18 metabolites of ABZ formed in the ribwort. In both model systems, the same types of ABZ biotransformation reactions were found, but the spectrum and abundance of the ABZ metabolites detected in cell suspensions and regenerants differed significantly. Cell suspensions seem to be suitable only for qualitative estimations of drug biotransformation reactions while regenerants were shown to represent an adequate model for the qualitative as well as quantitative evaluation of drug uptake and metabolism in plants.


First total synthesis of (-)-sinularianin B.
The first enantioselective total synthesis of (-)-sinularianin B, a structurally unique sesquiterpenoid isolated from the Formosan soft coral Sinularia sp., has been accomplished in 16 steps with 39.5% overall yield. Key transformations include formation of a cyclopentane possessing a tertiary hydroxy group via a tandem intermolecular-intramolecular alkylation involving a 5-endo cyclization.


Tris(1,10-phenanthroline)sodium 2,4,6-trimercapto-1,3,5-triazin-1-ide.
The title compound, [Na(C(12)H(8)N(2))(3)](C(3)H(2)N(3)S(3)), contains an Na(+) centre which is ionicly bonded to three 1,10-phenanthroline (phen) ligands and one trithiocyanurate(1-) (ttcH(2)) anion. In the crystal structure, the anions are linked via hydrogen bonds to form linear chains. The S and H atoms of the ttcH(2) anion participate in intermolecular N-H.S hydrogen bonding, with N.S distances of 3.298 (2) and 3.336 (2) A. The phen ligands are almost parallel, with dihedral angles of 3.92 (5), 11.75 (5) and 15.45 (5) degrees; moreover, they are nearly perpendicular to the ttcH(2) chains, with angles of 81.94 (7), 85.86 (7) and 85.96 (7) degrees.


Camouflage treatment of skeletal Class III malocclusion with conventional orthodontic therapy.
Nonextraction camouflage treatment along with Class III elastics was used to treat a 39-year-old woman with a skeletal Class III pattern and a low mandibular plane angle and short lower anterior facial height. The total active treatment time was 26 months. Her occlusion, smile esthetics, and soft tissue profile were significantly improved after treatment.


Virus-coded DNA endonuclease from avian retrovirus.
Reverse transcriptase from avian retrovirus has a physically associated DNA endonuclease with novel substrate and cofactor requirements. A similar endonuclease activity copurifies with pp32, a protein from viral cores that has been identified with the non-alpha region of the beta subunit of reverse transcriptase. Several temperature-sensitive mutants of avian retrovirus with thermolabile DNA polymerase were tested for thermal sensitivity of their DNA endonuclease activity. Two pol mutants of Rous sarcoma virus, ts335 and ts337, had thermolabile DNA endonuclease; a temperature-resistant revertant of ts335 had a heat-stable DNA endonuclease. DNA endonuclease is therefore a product of the pol gene and an integral part of the reverse transcriptase. A second class of pol mutants, typified by ts568 and ts553, had thermolabile DNA polymerase, but heat-stable DNA endonuclease.


Heterogeneity of the Ro/SSA antigen. Different molecular forms in lymphocytes and red blood cells.
Ro(SSA) is an intracellular ribonucleoprotein against which autoantibodies are found in a portion of patients with Sjögren's syndrome and systemic lupus erythematosus. A form of Ro(SSA) is described in red blood cells that shares a line of identity with purified Ro(SSA) from bovine spleen and human lymphocytes in counterimmunoelectrophoresis, but has different molecular properties. Ro(SSA) from red blood cells exists in association with only two small RNAs as opposed to four in other cell types, as determined by RNA extraction of protein A-assisted immunoprecipitates. In addition to the common 60-kD Ro(SSA) protein, Western blot analysis revealed an additional 52-kD protein in lymphocytes and a 54-kD protein in red blood cells. The 60-kD form of Ro(SSA) in red cells was found to be antigenically distinct from that in the lymphocyte, because sera were identified that bound each exclusively. Finally, a rabbit antibovine Ro(SSA) serum distinguished red cell from lymphocyte Ro(SSA). These results suggest two distinctive populations of Ro(SSA) proteins and distributions of Ro(SSA) RNAs in the lymphocyte and red blood cell.


High-pressure structures and phase transformations in elemental metals.
At ambient conditions the great majority of the metallic elements have simple crystal structures, such as face-centred or body-centred cubic, or hexagonal close-packed. However, when subjected to very high pressures, many of the same elements undergo phase transitions to low-symmetry and surprisingly complex structures, an increasing number of which are being found to be incommensurate. The present critical review describes the high-pressure behaviour of each of the group 1 to 16 metallic elements in detail, summarising previous work and giving the best present understanding of the structures and transitions at ambient temperature. The principal results and emerging systematics are then summarised and discussed.