Growth, carcase and meat traits and gene expression in chickens divergently selected for intramuscular fat content.
1. Changes resulting from divergent selection after 5 generations for intramuscular fat (IMF) content in breast muscle in a population of purebred Beijing-You chickens were investigated. Female chickens from lines selected-up (UL) and selected-down (DL) for 5 generations and random-bred controls (CL) were studied at 120 d of age. 2. In the UL, IMF in breast muscle (4.65%) was 1.38 times that in the DL (3.36%). The IMF content in leg muscle was also higher in UL compared to DL. 3. There were significant differences in growth, carcase traits and meat quality between the two selected lines. However, ultimate pH (pHu) was lower and lightness (L*) and yellowness (b*) were higher in breast muscles of UL birds compared to DL birds. Similar trends for pHu and L* value between UL and DL were observed in leg muscle. 4. Significant mRNA expression differences of the heart fatty acid-binding protein (H-FABP) gene between UL and DL were observed in breast muscle, and a negative correlation between expression of mRNA and IMF% in breast and leg muscles pointed to H-FABP as a potential selection candidate gene.


A comparison of convergently evolved insect silks that share β-sheet molecular structure.
Raspy crickets produce silk webs that are used to build shelters. These webs have been found to consist of both fiber and film components. Raman spectra obtained from both components were found to be very similar for a given species. The protein structure of the fibers and films produced by both species was predominately β-sheet with lesser amounts of β-turns, unordered and α-helical protein also detected. The orientation of the β-sheet backbone in the fiber was determined to be parallel to the fiber axis. Compared to cocoon and dragline silk the orientation distribution exhibits a significant randomly orientated protein component. Amino acid analysis confirmed the presence of glycine, serine, and alanine in both species, which are known to form antiparallel β-sheet structures. Both species, although at significantly different concentrations, where found to contain proline. This amino acid is uncommon in insect silks, and likely involved in increasing fiber elasticity.


Photosynthetic Plasticity in Flaveria brownii: Growth Irradiance and the Expression of C(4) Photosynthesis.
Photosynthesis was examined in leaves of Flaveria brownii A. M. Powell, grown under either 14% or 100% full sunlight. In leaves of high light grown plants, the CO(2) compensation point and the inhibition of photosynthesis by 21% O(2) were significantly lower, while activities of ribulose 1,5-bisphosphate carboxylase/oxygenase and various C(4) cycle enzymes were considerably higher than those in leaves grown in low light. Both the CO(2) compensation point and the degree of O(2) inhibition of apparent photosynthesis were relatively insensitive to the light intensity used during measurements with plants from either growth conditions. Partitioning of atmospheric CO(2) between Rubisco of the C(3) pathway and phosphoenolpyruvate carboxylase of the C(4) cycle was determined by exposing leaves to (14)CO(2) for 3 to 16 seconds, and extrapolating the labeling curves of initial products to zero time. Results indicated that approximately 94% of the CO(2) was fixed by the C(4) cycle in high light grown plants, versus approximately 78% in low light grown plants. Thus, growth of F. brownii in high light increased the expressed level of C(4) photosynthesis. Consistent with the carbon partitioning patterns, photosynthetic enzyme activities (on a chlorophyll basis) in protoplasts from leaves of high light grown plants showed a more C(4)-like pattern of compartmentation. Pyruvate, Pi dikinase and phosphoenolpyruvate carboxylase were more enriched in the mesophyll cells, while NADP-malic enzyme and ribulose 1,5-bisphosphate carboxylase/oxygenase were relatively more abundant in the bundle sheath cells of high light than of low light grown plants. Thus, these results indicate that F. brownii has plasticity in its utilization of different pathways of carbon assimilation, depending on the light conditions during growth.


Biochemical and spectroscopic characterization of the membrane-bound nitrate reductase from Marinobacter hydrocarbonoclasticus 617.
Membrane-bound nitrate reductase from Marinobacter hydrocarbonoclasticus 617 can be solubilized in either of two ways that will ultimately determine the presence or absence of the small (Iota) subunit. The enzyme complex (NarGHI) is composed of three subunits with molecular masses of 130, 65, and 20 kDa. This enzyme contains approximately 14 Fe, 0.8 Mo, and 1.3 molybdopterin guanine dinucleotides per enzyme molecule. Curiously, one heme b and 0.4 heme c per enzyme molecule have been detected. These hemes were potentiometrically characterized by optical spectroscopy at pH 7.6 and two noninteracting species were identified with respective midpoint potentials at Em=+197 mV (heme c) and -4.5 mV (heme b). Variable-temperature (4-120 K) X-band electron paramagnetic resonance (EPR) studies performed on both as-isolated and dithionite-reduced nitrate reductase showed, respectively, an EPR signal characteristic of a [3Fe-4S]+ cluster and overlapping signals associated with at least three types of [4Fe-4S]+ centers. EPR of the as-isolated enzyme shows two distinct pH-dependent Mo(V) signals with hyperfine coupling to a solvent-exchangeable proton. These signals, called "low-pH" and "high-pH," changed to a pH-independent Mo(V) signal upon nitrate or nitrite addition. Nitrate addition to dithionite-reduced samples at pH 6 and 7.6 yields some of the EPR signals described above and a new rhombic signal that has no hyperfine structure. The relationship between the distinct EPR-active Mo(V) species and their plausible structures is discussed on the basis of the structural information available to date for closely related membrane-bound nitrate reductases.


Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory.
Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model's topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over approximately 1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback.


The p53 miRNA interactome and its potential role in the cancer clinic.
p53 is one of the most frequently mutated tumor suppressors. It regulates protein-coding genes and noncoding RNAs involved in many cellular processes, functioning predominantly at the transcriptional level but also through nontranscriptional processes. miRNAs have recently been identified as key mediators of the p53 stress-response pathway. p53 regulates miRNA transcription and processing, and miRNAs regulate p53 activity and expression and, accordingly, various feedback/feed-forward loops have been identified. Many chemotherapeutic agents induce cancer cell death or senescence via DNA damage and the subsequent activation of p53. Resistance to chemotherapy can occur due to the mutation of components in p53 signaling networks. A better understanding of the role of the various components within these pathways and their interactions with each other may allow the modification and improvement of current treatments, and the design of novel therapies. Improving our knowledge of the role of miRNAs in such p53 signaling networks may be crucial to achieving this.


Pregnancy after Fontan repair of tricuspid atresia.
We have described a patient who had a cyanotic congenital heart disease (type Ib tricuspid atresia), with initial palliation accomplished in childhood via a Glenn procedure. In 1985, she had a Fontan repair with the Bjork modification; 3 years later she achieved her first pregnancy at age 27. Maternal Doppler echocardiography in early pregnancy showed good flow through the constructed conduit, with normal left ventricular size and function. Fetal echocardiography at 22 weeks' gestation via two-dimensional, M-mode, pulsed Doppler, and color flow mapping revealed no evidence of fetal cardiac disease. At 25 weeks' gestation recalcitrant preterm labor developed, and the infant was delivered spontaneously. Labor, delivery, and puerperium were uncomplicated, and the newborn (though too premature to survive) was of appropriate weight for gestational age, without evidence of congenital heart disease or other anomalies. We believe this is the first report of pregnancy and spontaneous delivery in a patient who has had Fontan repair of a congenital heart defect.


Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex.
Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo-electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.


Nonequilibrium Dark Space Phase Transition.
We introduce the concept of dark space phase transition, which may occur in open many-body quantum systems where irreversible decay, interactions, and quantum interference compete. Our study is based on a quantum many-body model that is inspired by classical nonequilibrium processes which feature phase transitions into an absorbing state, such as epidemic spreading. The possibility for different dynamical paths to interfere quantum mechanically results in collective dynamical behavior without classical counterpart. We identify two competing dark states, a trivial one corresponding to a classical absorbing state and an emergent one which is quantum coherent. We establish a nonequilibrium phase transition within this dark space that features a phenomenology which cannot be encountered in classical systems. Such emergent two-dimensional dark space may find technological applications, e.g., for the collective encoding of a quantum information.


James Ross (1837-1892) and his forgotten neurology textbook of 1881.
James Ross (1837-1892) was an Aberdeen medical graduate who, after 13 years in rural general practice, mainly in Lancashire, became a pathologist and then physician to the Manchester Royal Infirmary and professor of medicine at Owens College, Manchester. In mid-career he developed a major interest in clinical neurology and became, apart from Byrom Bramwell in Edinburgh, the only contemporary British physician outside London who had widely recognised neurological expertise. Ross made several notable original contributions to neurological knowledge, particularly in relation to aphasia and peripheral neuritis. He wrote the entire contents of the two editions of the massive two-volume A Treatise on the Diseases of the Nervous System (1881 and 1883), which was very favourably reviewed and commercially successful but which, like its author who died at the height of his powers, was soon forgotten once William Gowers' A Manual of Diseases of the Nervous System became available in the late 1880s.


Comparison of wavefront-guided customized ablation vs. conventional ablation in laser in situ keratomileusis.
To compare visual outcome after applying wavefront-guided customized ablation with conventional ablation in laser in situ keratomileusis (LASIK) patients. We performed a prospective, randomized controlled study that included 22 eyes of 11 patients who were treated with LASIK using the Nidek EC-5000 excimer laser system. We applied wavefront-guided customized ablation (study group) in the first eye of each patient. The conventional ablation (control group) was performed in the other eye of the same patient. Best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and high-order aberrations were evaluated preoperatively and at 1 month. High-order aberrations were measured using the Nidek OPD-Scan. Preoperative and 1-month postoperative BSCVA were better than 20/40 (100%) after LASIK with both conventional ablation (control) and wavefront-guided customized ablation. Preoperatively, mean high-order aberrations in the control group were 0.572 and in the study group, 0.428 (Zernike coefficient unit). One-month after LASIK, mean high-order aberrations in the control group were 0.496 and in the study group, 0.476 (Zernike coefficient unit). We found no statistically significant difference between preoperative and 1-month postoperative high-order aberrations in either group. LASIK with both conventional ablation and wavefront-guided customized ablation resulted in the same BSCVA 1 month after LASIK. Preoperative and 1-month postoperative high-order aberrations were not statistically different following LASIK between ablation types.


Mental health awareness among adult attendees of Armed Forces Hospital Southern Region family and community center.
To assess mental health literacy among Saudi adults attending the Ahad Rufaidah extension of Armed Forces Hospitals, Southern Region, 2017. Following a cross-sectional descriptive study design, 400 adult Saudi attendants of the Armed Forces Hospitals, Southern Region - Ahad Rufaidah extension were included in this study. An anonymous interview validated questionnaire was utilized for data collection. It included variables related to participants' personal characteristics, knowledge assessment, and attitude regarding mental illness. More than half of participants (55.3%) had poor knowledge regarding mental health, while 44.8% had satisfactory knowledge. Only 3.6% of participants had a positive attitude toward mentally ill persons, 43% were indifferent toward them, while 53.4% had a negative attitude toward them. Participants' attitudes toward mental health differed significantly according to their knowledge grades (P < 0.001), with the majority of those with positive attitudes having satisfactory knowledge (93.5%) and most of those who had negative attitudes had poor knowledge (66.8%). Participants' knowledge grades differed significantly according to their gender, with more satisfactory knowledge grades among males than females (50.8% and 22.4%, respectively, P < 0.001) and educational level, with more satisfactory knowledge grades among more educated participants (P = 0.002). Participants' attitudes toward mentally ill persons differed significantly according to their gender (P = 0.013) and their educational level, with the highest percentage of positive attitude among university-educated participants (35.3%, P < 0.001). There is widespread mental health illiteracy among attendants in the Ahad Rufaidah extension of Armed Forces Hospitals, Southern Region. Their attitude toward mentally ill persons is rarely positive but largely negative or indifferent.


Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam.
To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of brotizolam. In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of brotizolam was administered orally. Plasma concentrations of brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. Itraconazole significantly (P < 0.001) decreased the apparent oral clearance (CL/F) (16.47 +/- 4.3 vs 3.91 +/- 2.1), increased the area under the concentration-time curves (AUC) from 0 h to 24 h (28.37 +/- 10.8 vs 68.71 +/- 24.1 ng ml h(-1)), and prolonged the elimination half-life (4.56 +/- 1.4 vs 23.27 +/- 10.3 h) of brotizolam. The AUC(0,24 h) of the DSST (P < 0.001) and the item 'sleepiness' of UKU (P < 0.05) were significantly decreased. Itraconazole increases plasma concentrations of brotizolam probably via its inhibitory effect on CYP3A4 brotizolam metabolism.


In situ particle film ATR FTIR spectroscopy of poly (N-isopropyl acrylamide) (PNIPAM) adsorption onto talc.
The adsorption of poly(N-isopropyl acrylamide) (PNIPAM) onto talc from aqueous solutions has been studied using the in situ methodology of particle film attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy. PNIPAM was observed to adsorb significantly onto the talc particle film at a temperature below its lower critical solution temperature (LCST). Peak shifts were seen in the adsorbed layer FTIR spectrum that match those observed when PNIPAM solution is heated above its LCST. This observation indicates that adsorption causes a conformational re-arrangement similar to that seen when PNIPAM undergoes a coil-to-globule transition, in this case presumably induced by hydrophobic interactions between PNIPAM and the talc basal plane surface. The kinetics of adsorption are seen to be complex, with potential influences of conformational rearrangement and differential adsorption kinetics for the two dominant surface regions of talc particles. The adsorbed PNIPAM was seen to be exceptionally resistant to removal, with no desorption occurring when a background electrolyte solution was flowed over the adsorbed layer. Spectra acquired of the adsorbed polymer layer heated above the LCST reveal that a further conformational rearrangement takes place for the adsorbed layer, finalizing the transition from coil-to-globule that was initiated by the interaction with the mineral surface.


Multiparametric MRI reveals dynamic changes in molecular signatures of injured spinal cord in monkeys.
To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multiparametric MRI methods. Quantitative MRI imaging including diffusion tensor imaging, magnetization transfer (MT), and chemical exchange saturation transfer (CEST) were conducted in anesthetized squirrel monkeys at 9.4T. The structural, cellular, and molecular features of the spinal cord were examined before and at different time points after a dorsal column lesion in each monkey. Images with MT contrast enhanced visualization of the gray and white matter boundaries and the lesion and permitted differentiation of core and rim compartments within an abnormal volume (AV). In the early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient, decreased fractional anisotropy, decreased MT ratio, decreased nuclear Overhauser effect, and large CEST effects. Over time, cellular density and fiber density increased, whereas amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst. Multiparametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury.


Mycophenolate mofetil and valsartan inhibit podocyte apoptosis in streptozotocin-induced diabetic rats.
To investigate the effects of mycophenolate mofetil on apoptosis and the expression of Bax and Bcl-2 of podocytes in rats with diabetic nephropathy. A total of 40 male rats were randomly divided into two groups: healthy control group (NC, n = 8) and diabetic nephropathy group (DN, n = 32). The diabetic rat models were induced by streptozotocin, which was injected intraperitoneally. After the DN model was established successfully, the DN group was subdivided into four groups: (1) group treated with the dissolvent (DN), (2) group treated with mycophenolate mofetil (DN + M), (3) group treated with valsartan (DN + V) and (4) group treated with mycophenolate mofetil and valsartan (DN + MV). After 16 weeks of treatment, kidney and body weight, urinary protein level and serum glucose were measured. Histomorphology of renal tissue was observed by an optical microscope. Apoptosis of podocytes was determined by transferase-mediated dUTP nick-end labeling (TUNEL) test. The expression of nephrin and Wilms' tumor suppressor gene (WT1) were detected by immunohistochemistry and real-time PCR, and the protein expression of Bax and Bcl-2 were examined by Western blot. The mRNA and protein expression of nephrin and WT1 were both downregulated. The apoptosis rate, the expression of Bax, caspase-3 activity and cleavage increased, while the expression of Bcl-2 decreased in the DN group compared with the NC group. However, they were all improved in the groups treated with either mycophenolate mofetil or valsartan. Mycophenolate mofetil can protect renal function by increasing Bcl-2 expression and decreasing Bax expression and podocyte apoptosis rate, thereby reducing proteinuria.


Synthetic biology for improving cell fate decisions and tissue engineering outcomes.
Synthetic biology is a relatively new field of science that combines aspects of biology and engineering to create novel tools for the construction of biological systems. Using tools within synthetic biology, stem cells can then be reprogrammed and differentiated into a specified cell type. Stem cells have already proven to be largely beneficial in many different therapies and have paved the way for tissue engineering and regenerative medicine. Although scientists have made great strides in tissue engineering, there still remain many questions to be answered in regard to regeneration. Presented here is an overview of synthetic biology, common tools built within synthetic biology, and the way these tools are being used in stem cells. Specifically, this review focuses on how synthetic biologists engineer genetic circuits to dynamically control gene expression while also introducing emerging topics such as genome engineering and synthetic transcription factors. The findings mentioned in this review show the diverse use of stem cells within synthetic biology and provide a foundation for future research in tissue engineering with the use of synthetic biology tools. Overall, the work done using synthetic biology in stem cells is in its early stages, however, this early work is leading to new approaches for repairing diseased and damaged tissues and organs, and further expanding the field of tissue engineering.


[The effect of Inj. Salviae Miltiorrhizae Co. on the retrograde axoplasmic transport in the optic nerve of rabbits with chronic IOP elevation].
With the horseradish peroxidase histochemical technique and electron microscope, the effects of 0.5% timolol, Inj. Salviae Miltiorrhizae Co. and their combination on the retrograde axoplasmic transport in the optic nerve of 230 rabbit models of chronic IOP elevation were studied. The results showed that (1) the nerve damage in chronic glaucoma was due to multiple factors; (2) the use of a drug that improved microcirculation in combination with an IOP depressor better protected the optic nerve functions than did the latter alone; and (3) Inj. Salviae Miltiorrhizae Co. improved the optic nerve axoplasmic transport under chronic IOP elevation. The mechanism of the drug in protecting the optic nerve could be through its actions of improving the local microcirculation and the tolerance of nerve tissues to anoxia.


Monitoring urinary excretion of 5-hydroxymethyluracil for assessment of oxidative DNA damage and repair.
Abstract Urinary excretion of oxidized nucleobases and nucleosides has been used as a biomarker of oxidative DNA damage and repair. Most studies have focused on the measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine; however, the urinary levels of other DNA modifications may represent useful indicators of oxidative stress. We developed a method for the determination of 5-hydroxymethyluraciI (5-HMUra), consisting of the separation of the modified base in urine by HPLC and quantification by GC/MS in the selective ion monitoring mode. This experimental approach was subsequently validated in human samples, with the effect of storage and the inter- and intra-individual variations in 5-HMUra excretion being evaluated. Results showed that 5-HMUra is stable in samples frozen at-80 °C for at least 4 months. Inter-individual variations in 5-HMUra excretion were observed when the results were expressed either as nmoles excreted per kg per day (1.2-2.4) or corrected by creatinine values (7.2-12.2 nmoles 5-HMUra per mmoles creatinine). Intra-individual variability was low, varying slightly at different time collections for several individuals. Differences in the excretion of 5-HMUra in urine collected at three different 8-h intervals during the day were not significant and, in particular, the levels of 5-HMUra calculated from the overnight or the 24-h samples were highly correlated. These results indicate that monitoring urinary levels of 5-HMUra could be a suitable indicator of oxidative damage in human studies.


The galenic plague: a breakdown of the imperial pathocoenosis. Pathocoenosis and longue durée.
Is 'pathocoenosis', a notion conceived and a word coined by Mirko Grmek (1969), useful as far as ancient history is concerned? The author is interested in Galenic pathocoenosis, that of doctor Galen and his Emperor Marcus Aurelius (IInd cent. A.D.), when a new 'pestilence' or 'plague' (smallpox?) devastated the whole empire, from Mesopotamia to the Danube at least.


Data-Driven Analysis of Fluorination of Ligands of Aminergic G Protein Coupled Receptors.
Currently, G protein-coupled receptors are the targets with the highest number of drugs in many therapeutic areas. Fluorination has become a common strategy in designing highly active biological compounds, as evidenced by the steadily increasing number of newly approved fluorine-containing drugs. Herein, we identified in the ChEMBL database and analysed 1554 target-based FSAR sets (non-fluorinated compounds and their fluorinated analogues) comprising 966 unique non-fluorinated and 2457 unique fluorinated compounds active against 33 different aminergic GPCRs. Although a relatively small number of activity cliffs (defined as a pair of structurally similar compounds showing significant differences of activity -ΔpPot > 1.7) was found in FSAR sets, it is clear that appropriately introduced fluorine can increase ligand potency more than 50-fold. The analysis of matched molecular pairs (MMPs) networks indicated that the fluorination of the aromatic ring showed no clear trend towards a positive or negative effect on affinity; however, a favourable site for a positive potency effect of fluorination was the ortho position. Fluorination of aliphatic fragments more often led to a decrease in biological activity. The results may constitute the rules of thumb for fluorination of aminergic receptor ligands and provide insights into the role of fluorine substitutions in medicinal chemistry.


A steep peripheral ring in irregular cornea topography, real or an instrument error?
To demonstrate that the steep peripheral ring (red zone) on corneal topography after myopic laser in situ keratomileusis (LASIK) could possibly due to instrument error and not always to a real increase in corneal curvature. A spherical model for the corneal surface and modifying topography software was used to analyze the cause of an error due to instrument design. This study involved modification of the software of a commercially available topographer. A small modification of the topography image results in a red zone on the corneal topography color map. Corneal modeling indicates that the red zone could be an artifact due to an instrument-induced error. The steep curvature changes after LASIK, signified by the red zone, could be also an error due to the plotting algorithms of the corneal topographer, besides a steep curvature change.


Distant visual acuity in chronic psychiatric patients. A pilot study.
There is a paucity of systematically collected data on visual impairment in patients with chronic psychiatric disorders. The aim of this pilot study was to estimate the magnitude of impairment of distant visual acuity (DVA) including refractive and non-refractive errors in institutionalized psychiatric patients awaiting resettlement in the community in Hong Kong. DVA was tested using the Snellen method in a randomly selected cohort of 428 institutionalized psychiatric patients from the four long-stay rehabilitation units in Hong Kong. The pinhole method was employed to differentiate between refractive and non-refractive impairment of DVA. Seventy-five percent of the sample had impaired DVA; 39 % of the subjects had refractive error (myopia). Only a small percentage of patients wore spectacles and had adequately corrected vision. Patients with impaired DVA were significantly older than those with normal DVA. While the frequency of myopia corresponds to that found in the general population in Hong Kong, the nature of non-refractive impairment needs further investigation including systematic eye examination, and examination of medication and life-style factors. Periodical eye examinations should be part of comprehensive health assessment for chronic psychiatric patients.


Quantitative Phytochemical Constituents and Antioxidant Activities of the Mistletoe, Phragmanthera capitata (Sprengel) Balle Extracted with Different Solvents.
The investigation aimed to evaluate the in vitro quantitative phytochemical compositions and antioxidant capacity of the dried leaves of Phragmanthera capitata extracted with different solvents. Different phytochemical assays were used to evaluate the phenols, flavonoids, and proanthocyanidin contents of the acetone, methanol, ethanol, and aqueous extracts of the sample. Antioxidant activity was measured using 2,2diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), Ferric reducing antioxidant power (FRAP), nitric oxide, and total antioxidant capacity (TAC) assays. Methanol had the highest extraction yield (21.50%) followed by aqueous (10.87%). Acetone and ethanol yielded 6.87% and 4.3%, respectively. However, acetone and ethanol extracts had more phenolic content (218.6 ± 3.38 and 214.8 ± 3.56 mg gallic acid equivalent (GAE)/g, respectively) that were significantly higher (P < 0.05) than the methanol and aqueous extracts (203.8 ± 1.95 and 175.5 ± 0.32 mg GAE/mg, respectively). Acetone extract also had more flavonoid and proanthocyanidin contents (679.8 ± 6.26 mg quercetin equivalent/g and 645.7 ± 6.35 mg catechin equivalent/g, respectively) that were significantly higher than the other solvent extracts (P < 0.05). All the solvent fractions showed great antioxidant activities with the acetone fraction having the highest capacity based on ABTS, DPPH, and TAC assays (half maximal inhibitory concentration [IC50] = <5 μg/mL, 24.5 μg/mL, and 85 μg/mL respectively). The methanol extract however had FRAP and nitric oxide antioxidant activities (IC50 = 302 μg/mL and < 25 μg/mL respectively). The findings of this study provide evidence that P. capitata has potential as a natural source of antioxidant with acetone showing to be the best extractant of the polyphenolics with corresponding higher antioxidant activities. The study investigated the in vitro polyphenolic content and antioxidant activities of the mistletoe; Phragmanthera capitata, extracted with different solventsThe resultant outcome of the study showed that while methanol had more yield from the extraction, the highest polyphenolic contents was observed in the acetone extractThe acetone extract also showed the highest antioxidant activity in most of the assaysThere was a positive correlation between the polyphenolics and the antioxidant activities: Higher polyphenol content resulted in a better antioxidant activityIf extracting this plant for preparatory works only, methanol would be preferred, but if it were for bioassay screening, acetone will be the solvent of choice. Abbreviations Used: DPPH: 2, 2diphenyl-1-picrylhydrazyl (DPPH)ABTS: 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)FRAP: Ferric reducing antioxidant powerTAC: Total antioxidant capacityGAE: Gallic acid equivalentQE: Quercetin equivalentCE: Catechin equivalentBHT: Butylated hydroxyl toluene.


Increased Energy Drink Use as a Predictor of Illicit Prescription Stimulant Use.
The purpose of this study was to examine energy drink usage patterns and to investigate the relationship between energy drink use and illicit use of prescription stimulants among college students. A sample of 605 undergraduate and graduate students (mean age±SD: 21.96±4.216) from a large midwestern university voluntarily participated in the study. Of the participants, 48.9% (n=296) reported using energy drinks in the past 30 days, whereas 25.3% (n=153) reported using prescription stimulant drugs in the past 30 days. Among prescription stimulant users without a valid medical prescription, Mann-Whitney U tests and logistic regression analysis revealed that the frequency of energy drink consumption was a significant predictor of illicit prescription stimulant use, with the odds for use increasing by 14% with each additional day of energy drink use (odds ratio for using=1.143, P≤.001). Analyses revealed statistically significant differences (P<.05) between prescription stimulant users and nonusers for all energy drink use variables, with the strongest predictors of prescription stimulant use being the number of days using energy drinks in the past 30 days and number of energy drink binges in the past 30 days. Results indicate that the frequency of energy drink use was a significant predictor of the illicit use of prescription stimulants.


Nutritional evaluation of some legume-based dishes consumed in Saudi Arabia.
Chemical composition and nutritional quality of five Saudi dishes based on legumes were evaluated. On fresh weight basis, the dishes contained 35.3-78.1% moisture, 4.4-10.2% protein (NX6.25), 1.2-19.1% fat, 8.0-24.8% carbohydrates, 2.4-7.7% dietary fibre, 1.4-2.9% ash and 71-311 Kcal (297-1301 KJ) per 100 g dish. The contents of vitamin A (retinol equivalent), thiamin, riboflavin and vitamin C ranged from 85-378 micrograms, 0.01-0.12 mg, 0.02-0.46 mg and 0.3-1.2 mg per 100 g respectively. The mineral contents (mg/100 g) were calcium 2.1-22.1, phosphorus 49.1-330.3, iron 1.1-13.3, sodium 348.3-1356.9, and potassium 119.1-624.8. The dishes contributed 13-25%, 15-64% and 16-60% of the total food energy from protein, fat and carbohydrates respectively. Most of the dishes were good sources of dietary fibre, vitamin A and iron.


A Blueprint for Cancer-Related Inflammation and Host Innate Immunity.
Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer-host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events-a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.


Allograft tympanoplasty.
Tympano-ossicular allografts are human transplants of the tympanic membrane alone or with the ossicles included. The authors review its use in their department since the introduction of the technique 40 years ago by J. Marquet. The advantages of the technique (near normal anatomical and physiological reconstruction) are discussed, as well as its disadvantages (time consuming harvesting, risk of disease transmission). Some technical modifications for specific indications have been adapted in our department and are described in detail. The authors believe that the tympano-ossicular allograft is the material of choice in extensively diseased middle ears destroyed by chronic otitis media with or without cholesteatoma.


Effect of Ascorbic and Isoascorbic acids on Survival of Campylobacter jejuni in Poultry Meat 1.
Samples of radiation-sterilized mechanically deboned turkey meat were inoculated with a strain of Campylobacter jejuni , stored at 5°C, and viable counts of the test organism determined during a 7-week period. As compared to results obtained with unsupplemented samples, addition of ascorbic acid or sodium isoascorbate (erythorbate) to the meat, at a concentration of 5 mmol/kg, caused an increase in the death rate of C. jejuni . Autooxidation of these compounds, during storage of the meat, supports the view that their toxic effect is mainly due to their oxidation products.


Anthelmintic efficacy of single active and combination products against commonly occurring parasites in foals.
Parasite control in foals is complicated by the concurrent presence of biologically diverse parasites with differing levels of anthelmintic resistance. Several combination anthelmintic products are available for use in horses, but information on their efficacies against important equine parasites is scarce. Two trials were performed in New Zealand during 2008 and 2011 on four different farms with substantially different anthelmintic treatment histories. The first trial evaluated the efficacy of an ivermectin/praziquantel/oxibendazole combination, a single active oxibendazole, and a single-active macrocyclic lactone (ML) in 49 foals located on three farms. The second trial evaluated two combination anthelmintic products and three single-active ML products and enrolled a total of 110 foals on three farms. Foals in the second trial were allocated to one of six anthelmintic treatment groups; oxfendazole/pyrantel embonate, pyrantel embonate/ivermectin/praziquantel, ivermectin/praziquantel, abamectin/praziquantel, moxidectin/praziquantel, and a placebo-treated control. In both trials, foals were monitored monthly prior to treatment, and fecal egg counts (FECs) of Parascaris spp., strongylid, and Strongyloides westeri were determined. A "rolling enrolment" process was implemented whereby foals were systematically allocated to a treatment group and treated with the corresponding anthelmintic following the first appearance of Parascaris spp. eggs in the faeces. A generalised linear model was used to evaluate the effect of farm and treatment on Day14 FEC (ln) for each parasite. Three different FECR calculation methods were employed as follows; i) FECR(T) pre and post treatment ii) FECR (C) in the treated group compared with control, and iii) FECR (P) pre- and post- treatment in the treated and control groups. Across both trials, treatment with ML single active products failed to achieve >95% reduction in Parascaris spp. FEC on two of three farms. The pyrantel embonate/oxfendazole and ivermectin/ praziquantel/oxibendazole combinations demonstrated full efficacy against Parascaris spp. This is in contrast to the anti-strongylid efficacies determined, where the pyrantel embonate/oxfendazole combination and single active oxibendazole had reduced efficacy on one farm, while the macrocyclic lactones generally had good efficacy. Strongyloides egg counts were sporadic in both trials, and allowed limited insight into anthelmintic efficacy. The study illustrated the importance of keeping an untreated or placebo-treated control group in studies evaluating anti-Parascaris efficacy and it demonstrated the utility of a rolling enrolment procedure, where foals are enrolled over the course of a defined period of time. Furthermore, the study demonstrated the value of a farm specific FECR monitoring programme and the complexity of parasite control in foals, where combination anthelmintic products can be employed to target multiple species of parasites.


A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript.
Polyglutamine diseases, including spinocerebellar ataxia type 3 (SCA3), are caused by CAG repeat expansions that encode abnormally long glutamine repeats in the respective disease proteins. While the mechanisms underlying neurodegeneration remain uncertain, evidence supports a proteotoxic role for the mutant protein dictated in part by the specific genetic and protein context. To further define pathogenic mechanisms in SCA3, we generated a mouse model in which a CAG expansion of 82 repeats was inserted into the murine locus by homologous recombination. SCA3 knockin mice exhibit region-specific aggregate pathology marked by intranuclear accumulation of the mutant Atxn3 protein, abundant nuclear inclusions and, in select brain regions, extranuclear aggregates localized to neuritic processes. Knockin mice also display altered splicing of the disease gene, promoting expression of an alternative isoform in which the intron immediately downstream of the CAG repeat is retained. In an independent mouse model expressing the full human ATXN3 disease gene, expression of this alternatively spliced transcript is also enhanced. These results, together with recent findings in other polyglutamine diseases, suggest that CAG repeat expansions can promote aberrant splicing to produce potentially more aggregate-prone isoforms of the disease proteins. This report of a SCA3 knockin mouse expands the repertoire of existing models of SCA3, and underscores the potential contribution of alternative splicing to disease pathogenesis in SCA3 and other polyglutamine disorders.


Effect of foam densification and impact velocity on the performance of a football helmet using computational modeling.
The NFL recently released validated helmet-impact models to study the performance of currently used helmets. This study used the model of a Riddell Speed Classic helmet to determine the influence of the properties of protective foam padding on acceleration and deformation at two common impact locations to cause concussions. The performance of the helmet was measured before and after manipulating the material properties of the protective foam liner material using FEA software. The densification strain was adjusted by using the scale factor tool in LS-DYNA to create four material categories - soft, standard, stiff, and rigid. The helmet was tested under side and rear impacts using the four material properties at 2.0, 5.5, 7.4, 9.3 and 12.3 m/s impact speeds using the NOCSAE linear impactor model. This study suggests that the standard foam material compresses to a range that could be considered to have "bottomed out" at impact speeds at 5.5 m/s for side impacts. Despite testing a wide range of material properties, the measured accelerations did not vary dramatically across material properties. Rather, impact speed played the dominant role on measured acceleration. This is the first study to demonstrate how open-source impact models can be used to run a design of experiments and investigate the role between different materials used inside a helmet and football helmet performance.


[Guo Feng attends birth control meeting].
The 1980 provincial population growth rate was 8.71/1000, the lowest since the founding of the PRC. In addition, the 1980 provincial birth rate was also the lowest. This reflects the fact that the province has scored great achievements in birth control work. A meeting was held today in the province to commend those collectives and individuals that have achieved advanced results in birth control work, including 10 Red Banner units, 190 advanced collectives, 73 workers, and 27 individuals. The 10 Red Banner units are Dazhong District in Shenyang Municipality; the state-run Liming machinery company; Zhangtiekou and Anjingzi Districts in Dalian Municipality; Jin County; Lishan District in Anshan Municipality; the Anshan iron and steel company; and Yingkou, Dawa, and Heishan Counties. Attending the meeting were Guo Feng, Chen Puru, Liu Wen, and Zhang Zhiyuan. Comrade Chen Puru spoke at the meeting. On behalf of the provincial CCP Committee and People's Government, Comrade Zhang Zhiyuan pointed out to the meeting that the 1981 provincial population growth rate should be set at or below 10/1000. This is an arduous goal because there are some 3 million youths in the province at the legal marriageable age set by the new marriage law. Therefore, we should not blindly hold an optimistic and complacent attitude toward this work. We should intensify propaganda and education work to enhance the ideological and political awareness of youths and continue to implement various policies concerning birth control. Those who deserve commendation should be commended and those who deserve punishment should be punished according to regulations. Comrade Zhang Zhiyuan continued: The practice of birth control is an important policy of the party and the People's Government, and is a duty of every citizen. All communists, CYL members, and cadres should play a leading role in this regard.


Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 1. Anorexia nervosa--restricted type.
Twenty-two female patients with anorexia nervosa, restricted type, 14-35 years old, were treated with a 4-month course of combined cognitive-behavioral therapy, nutritional counselling and antidepressant drugs (nortriptyline for 7, fluoxetine for 15). Patients were monitored for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety (HRS-D and -A). The scores were determined before and after 1, 2 and 4 months of therapy. BMI, depression, anxiety and EDI scores improved significantly and equally in both groups during the 4 months of therapy, while BITE scores did not change.


Radiation-induced risk of ischemic heart disease following breast cancer radiotherapy in Denmark, 1977-2005.
The increase in the risk of heart disease from incidental exposure of the heart during radiotherapy for breast cancer has been estimated previously from retrospective data in Danish and Swedish women. Here we present an analysis of the Danish material updated with new cases and controls, extended follow-up period, and with refined dose estimates using simulator films or CT data. From the database of the Danish Breast Cancer Cooperative Group, we identified 531 women diagnosed with early-stage breast cancer from 1977 to 2005, who developed subsequent ischemic heart disease (cases) and matched them to 1069 controls without heart disease after radiotherapy. Data were available for precise dose estimation for 196 cases and 413 controls receiving tangential photon techniques. The median of the mean heart doses for the women receiving tangential radiotherapy was 2.41 Gy for left- and 0.68 Gy for right-sided radiotherapy. The mean heart dose was higher for cases than controls (0.84 Gy and 0.71 Gy, respectively; p < 0.001). In this group, the linear increase in the excess odds ratio of major coronary events per gray of mean heart dose (K) was 19 percent (95% Confidence Interval(CI) 1% to 63%, p = 0.02). For patients treated with electron techniques, there was no significant association between mean heart dose and the risk of major coronary events (K = -0.05, 95% CI -12% to 9%, p = 1.00). The increase in the excess odds of major coronary events per gray mean heart dose using individual dose estimates is higher than previously reported.


Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes.
In this study, we demonstrate that fluid shear stress (FSS)-induced actin cytoskeletal reorganization and junctional formation in renal epithelial cells are nearly completely opposite the corresponding changes in vascular endothelial cells (ECs) [Thi MM et al. (2004) Proc Natl Acad Sci USA 101:16483-16488]. Mouse proximal tubule cells (PTCs) were subjected to 5 h of FSS (1 dyn/cm(2)) to investigate the dynamic responses of the cytoskeletal distribution of filamentous actin (F-actin), ZO-1, E-cadherin, vinculin, and paxillin to FSS. Immunofluorescence analysis revealed that FSS caused basal stress fiber disruption, more densely distributed peripheral actin bands (DPABs), and the formation of both tight junctions (TJs) and adherens junctions (AJs). A dramatic reinforcement of vinculin staining was found at the cell borders as well as the cell interior. These responses were abrogated by the actin-disrupting drug, cytochalasin D. To interpret these results, we propose a "junctional buttressing" model for PTCs in which FSS enables the DPABs, TJs, and AJs to become more tightly connected. In contrast, in the "bumper-car" model for ECs, all junctional connections were severely disrupted by FSS. This "junctional buttressing" model explains why a FSS of only 1/10 of that used in the EC study can cause a similarly dramatic, cytoskeletal response in these tall, cuboidal epithelial cells; and why junctional buttressing between adjacent cells may benefit renal epithelium in maximizing flow-activated, brush border-dependent, transcellular salt and water reabsorption.


The cyclic hexapeptide AcF attenuates sepsis-induced acute lung injury and mortality in rats.
The purpose of this study was to elucidate the possible beneficial effects of AcF on acute lung injury (ALI) in a rat model of sepsis. Male Sprague-Dawley rats were randomly divided into the following four experimental groups (n = 10 per group): animals undergoing a sham cecal ligature puncture (CLP) (Sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with saline (Saline group) and animals undergoing CLP and treated with AcF (AcF group). At 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight ratio, Protein concentration and the count of inflammatory cells or neutrophils in the BALF were determined. The pathologic changes in lungs were examined with the optical microscopy. Myeloperoxidase (MPO) activity, the expression of inflammatory cytokines were measured in lung tissue and BALF respectively. Survival rates were recorded at 120h in the four groups in another experiment. Histology findings revealed acute lung injury in rats in the CLP group, whereas those in the AcF-treated group had mild lung injury. Treatment with AcF significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung wet/dry ration, protein concentration and the infiltration of inflammatory cells and neutrophils in the lung tissues. In addition, the secretion of inflammatory cytokines, such as TNF-α, IL-6, IL-1b and macrophage inflammatory protein-2 (MIP-2) was decreased in AcF treated group compared with the control saline treated group. AcF administration ameliorates acute lung injury in a rat model of sepsis induced by CLP. AcF can be developed as a novel treatment for severe sepsis-induced ALI.


Ecological differentiation of cryptic species within an asexual protist morphospecies: a case study of filamentous green alga Klebsormidium (Streptophyta).
Taxa of microbial eukaryotes defined on morphological basis display a large degree of genetic diversity, implying the existence of numerous cryptic species. However, it has been postulated that genetic diversity merely mirrors accumulation of neutral mutations. As a case taxon to study cryptic diversity in protists, we used a widely distributed filamentous genus, Klebsormidium, specifically the lineage E (K. flaccidum/K. nitens complex) containing a number of morphologically similar strains. Fourteen clades were recognized in the phylogenetic analysis based on a concatenated ITS rDNA + rbcL data set of more than 70 strains. The results of inferred character evolution indicated the existence of phylogenetic signal in at least two phenotypic characters (production of hydro-repellent filaments and morphology of zoosporangia). Moreover, the lineages recovered exhibited strong ecological preferences to one of the three habitat types: natural subaerial substrata, artificial subaerial substrata, and aquatic habitats. We interpret these results as evidence of existence of a high number of cryptic species within the single morphospecies. We consider that the permanent existence of genetically and ecologically well-defined cryptic species is enabled by the mechanism of selective sweep.


A rare case of dual emission in a neutral heteroleptic iridium(III) complex.
Herein we describe the synthesis and characterization of a neutral heteroleptic iridium complex bearing an unusual 2-pyridyl-6-methylthiazine dioxide ligand (pythdo). X-ray crystallographic analysis reveals that in the complex, the pythdo ligand is twisted and puckered, resulting in very low photoluminescent quantum efficiency. The emission profile is structured. Excited state lifetime measurements along with oxygen quenching studies point to a rare case of dual emission from different excited states whereby the high energy bands possess significant ligand-centered ((3)LC) character while the lower energy bands are predominantly characterized as a mixture of charge transfer ((3)CT) states. A detailed computational analysis corroborates the unusual photophysical behavior.


A human homologue (BICD1) of the Drosophila bicaudal-D gene.
We previously isolated a cDNA fragment homologous to the Drosophila Bicaudal-D gene (Bic-D) using a hybridization selection procedure with cosmids derived from the short arm of human chromosome 12. A PCR-mediated cDNA cloning strategy was applied to obtain the coding sequence of the human homologue (BICD1) and to generate a partial mouse (Bicdh1) cDNA. The Drosophila Bicaudal-D gene encodes a coiled coil protein, characterized by five alpha-helix domains and a leucine zipper motif, that forms part of the cytoskeleton and mediates the correct sorting of mRNAs for oocyte- and axis-determining factors during oogenesis. Analysis of the predicted amino acid sequence of the BICD1 cDNA clones indicates that the sequence similarity is essentially limited to the amphipatic helices and the leucine zipper, but the conserved order of these domains suggests a similar function of the protein in mammalians. A database search further indicates the existence of a second human homologue on chromosome arm 9q and a Caenorhabditis elegans homologue. Northern blot analysis indicates that both the human and the murine homologues produce an mRNA species of congruent with9.5 kb expressed in brain, heart, and skeletal muscle and during mouse embryonic development. The conserved structural characteristics of the BICD1 protein and its expression in muscle and especially brain suggest that BICD1 is a component of a cytoskeleton-based mRNA sorting mechanism conserved during evolution.


Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension.
The prevalence of arterial hypertension (AH) is higher in men than in premenopausal women of the same age. AH has been characterized as a chronic inflammatory disease and activation of Toll-like receptors (TLR) by damage-associated molecular patterns (DAMPs) is involved. Mitochondrial DNA (mtDNA) may be released by end-organ damage, which is recognized and activates TLR9. The serum level of mtDNA is increased in AH. The aim of this study was to compare the serum mtDNA levels between male and female spontaneously hypertensive rats (SHR) and to evaluate the sex differences in the effect of mtDNA on the function, inflammation and signaling pathway related to TLR9 in the vasculature. Male and female 15-week-old SHR and Wistar rats were used to evaluate the arterial blood pressure, serum mtDNA, contractile response, inflammatory markers and signaling pathway related to TLR9. Male SHR had higher arterial blood pressure values and serum mtDNA compared to female SHR and to male and female normotensive Wistar rats. In male SHR aorta, mtDNA incubation increased the contractile response to phenylephrine, which was blunted by inhibition of TLR9, and also increased pro-inflammatory molecules IL-6 and TNF-α. However, in female SHR aorta, mtDNA incubation did not change the contractile response, reduced pro-inflammatory molecules and prevented oxidative stress. mtDNA incubation did not change the expression of TLR9, MyD88 and eNOS neither in male nor in female SHR aorta, but it increased the phosphorylation of ERK1/2 in male and reduced in female SHR aorta. The mtDNA differential modulation of vascular response in male and female SHR might contribute to sex differences in AH. This study contributes to the understanding of a need for more personalized therapeutic strategies for men and women with hypertension. Keywords: Sex differences, Arterial hypertension, Mitochondrial DNA, Toll-Like receptor 9.


Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis.
The prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression. PubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR). Fifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61). Our findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.


Epilepsy surgery in a pediatric population: a retrospective study of 129 children from a tertiary care hospital in a developing country along with assessment of quality of life.
To assess the outcome of a pediatric population operated for drug-resistant epilepsy from a large tertiary care center in India. Retrospectively: quality of life (QOL); prospectively: preoperative assessment included interictal EEG, MRI (as per epilepsy protocol), video-EEG. Ictal SPECT (with subtraction) and PET were performed when required. QOL scores were assessed using the HASS or SSQ for seizure severity, Quality of Life in Childhood Epilepsy (QOLCE) for QOL, and Child Behavior Check List (CBCL) for behavior. 142 were operated from January 2000 to June 2011 by the senior author. 118 patients with at least 1 year of follow-up were included in the study. Mean age at surgery was 9.8 ± 4.3 years. In addition, 40 patients underwent QOL assessment prospectively both before and after surgery. Mean duration of epilepsy was 5.3 ± 3.3 years. A class I outcome (Engel's) was seen in 79.5% patients, class II in 8.6%, class III in 10.7%, and class IV in 1 patient. As per surgical procedures, class I outcome in patients who underwent temporal resection, hemispherotomy and extratemporal resection was 76, 87 and 72%, respectively. QOL scores correlated with duration of seizures, epileptic encephalopathy and outcome of surgery, but not with side of surgery, age and sex. This study, the largest reported from India, has demonstrated satisfactory results for epilepsy surgery in children.


The Family Life Project: an epidemiological and developmental study of young children living in poor rural communities.
About 20% of children in the United States have been reported to live in rural communities, with child poverty rates higher and geographic isolation from resources greater than in urban communities. There have been surprisingly few studies of children living in rural communities, especially poor rural communities. The Family Life Project helped fill this gap by using an epidemiological design to recruit and study a representative sample of every baby born to a mother who resided in one of six poor rural counties over a 1-year period, oversampling for poverty and African American. 1,292 children were followed from birth to 36 months of age. This monograph described these children and used a cumulative risk model to examine the relation between social risk and children's executive functioning, language development, and behavioral competence at 36 months. Using both the Family Process Model of development and the Family Investment Model of development, observed parenting was examined over time in relation to child functioning at 36 months. Different aspects of observed parenting were examined as mediators/moderators of risk in predicting child outcomes. Results suggested that cumulative risk was important in predicting all three major domains of child outcomes and that positive and negative parenting and maternal language complexity were mediators of these relations. Maternal positive parenting was found to be a buffer for the most risky families in predicting behavioral competence. In a final model using both family process and investment measures, there was evidence of mediation but with little evidence of the specificity of parenting for particular outcomes. Discussion focused on the importance of cumulative risk and parenting in understanding child competence in rural poverty and the implications for possible intervention strategies that might be effective in maximizing the early development of these children.


Apparent polycythaemia: diagnosis, pathogenesis and management.
The term "apparent polycythaemia" is applied to a group of patients who have a raised PCV (> 0.51 in males, > 0.48 in females) but a normal red cell mass (less than 25% above their predicted mean normal value). Some have additionally a marked reduction in plasma volume and can be defined as a subgroup: relative polycythaemia. Smoking, hypertension and to a lesser extent obesity, excessive alcohol, low-dose diuretic therapy and hypoxaemia have all been associated with apparent polycythaemia but the mechanism is both uncertain and likely to be complex. This group of patients is unlikely to be uniform in pathogenesis and may well include some normal individuals. Investigation requires exclusion of factors associated with other types of polycythaemia. The possibility of an increased vascular occlusive risk is uncertain in these patients except at the higher PCV values. Reduction of PCV by venesection is sensible at PCV > 0.54 or where there is perceived to be an increased risk of vascular occlusion. The remaining patients should be managed by regular observation to detect further rise in PCV or evolution to absolute polycythaemia (raised red cell mass). In some, the PCV returns to normal.


Impact of chronic critical illness on the psychological outcomes of family members.
The uncertain trajectory of chronic critical illness exposes the patient's family to heightened levels of psychological distress. Symptoms of psychological distress affect more than half of family members exposed to the patient's chronic critical illness. Although symptoms often dissipate over time, a significant proportion of family members will remain at moderate to high risk for psychological distress well after the patient's death or discharge from the intensive care unit. Family members of chronically critically ill patients are often involved in the decision making for the patients. Irrational or uninformed decision making can occur when family members experience high levels of psychological distress. Attention to the psychological needs and provision of support to family members enhance the formulation of treatment decisions consistent with the patient's preferences and mitigate unnecessary resource use. In this article, the impact of chronic critical illness on family members' risk for depression, anxiety, and posttraumatic stress disorder is described and a review of evidence-based strategies to support the psychological needs of family members coping with a patient's chronic critical illness is provided.


Acute and chronic effects of combined exercise on ambulatory blood pressure and its variability in hypertensive postmenopausal women.
The aim of this study was to investigate the acute and chronic effects, and their correlation, after combined aerobic and resistance exercises in blood pressure (BP) and its variability (BPV) in hypertensive postmenopausal women. Fourteen hypertensive postmenopausal women monitored BP at rest and during 24 h by ambulatory BP monitoring in a control day without exercise performance a pretraining (baseline), after an acute exercise session (acute), and after a chronic exercise training for 10 weeks (chronic). After exercise training, systolic BP (SBP, Δ = -150 mmHg.24 h), diastolic BP (DBP, Δ = -96 mmHg.24 h), and mean BP (MBP, Δ = -95 mmHg.24 h) area under the curve were smaller than baseline measurements (P < 0.05) with no difference between acute and baseline measurements. The SBP (ΔSD24 = -2, ΔSDdn = -1.7, and ΔARV24 = -1.9 mmHg), DBP (ΔSD24 = -0.9, ΔSDdn = -0.8, and ΔARV24 = -0.9 mmHg), and MBP (ΔSD24 = -1.5, ΔSDdn = -1.3, and ΔARV24 = -1.2 mmHg) variability reduced in acute session in relation to baseline, with no chronic effects. There are moderate correlations between acute and chronic responses in wake SBP, sleep DBP, and SD24. In conclusion, combined exercise reduces ambulatory BP chronically but not acutely. In contrast, BPV decreases after an acute session but not chronically. Awake SBP, sleep DBP, and SD24indices are promising candidates to predict individual cardiovascular responses to exercise.


Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production.
Studies were performed to determine whether hypoglycemia or the glucagon response to hypoglycemia increases uric acid production in glycogen storage disease type I (glucose-6-phosphatase deficiency). Three adults with this disease had hyperuricemia (serum urate, 11.3-12.4 mg/dl) and reduced renal clearance of urate (renal urate clearance, 1.1-3.1 ml/min). These abnormalities were improved in one patient by intravenous glucose infusion for 1 mo, suggesting a role for hypoglycemia and its attendant effects on urate metabolism and excretion. A pharmacologic dose of glucagon caused a rise in serum urate from 11.4 to 13.0 mg/dl, a ninefold increase in urinary excretion of oxypurines, a 65% increase in urinary radioactivity derived from radioactively labeled adenine nucleotides, and a 90% increase in urinary uric acid excretion. These changes indicate that intravenous glucagon increases ATP breakdown to its degradation products and thereby stimulates uric acid production. To observe whether physiologic changes in serum glucagon modulate ATP degradation, uric acid production was compared during saline and somatostatin infusions. Serum urate, urinary oxypurine, radioactivity, and uric acid excretion increased during saline infusion as patients became hypoglycemic. Infusion of somatostatin suppressed these increases despite hypoglycemia and decreased the elevated plasma glucagon levels from a mean of 81.3 to 52.2 pg/ml. These data suggest that hypoglycemia can stimulate uric acid synthesis in glucose-6-phosphatase deficiency. Glucagon contributes to this response by activating ATP degradation to uric acid.


Immunoelectron microscopy of carbonic anhydrase isozyme VI in human submandibular gland: comparison with isozymes I and II.
Carbonic anhydrase VI (CA VI) was purified from human saliva by inhibitor-affinity chromatography, and its distribution was studied in human submandibular gland by the indirect immunoperoxidase technique with a rabbit polyclonal antibody raised against the isozyme. Polyclonal antibodies to human CA I and CA II purified from erythrocytes were also raised and used for immunostaining. SDS-polyacrylamide gel electrophoresis of the purified isozymes revealed a single protein band (CA VI, 42 KD; CA I and CA II, 30 KD). Antibody raised against CA VI did not crossreact with CA I or CA II either by Western or by dot-blotting. However, antibodies against CA I and CA II showed slight crossreaction with each other's antigen by dot-blotting. In a Western blot of purified submandibular gland CA, antibody to CA VI stained the 42 and 30 KD bands, and antibodies to CA I and CA II stained the 30 KD band. The 42 KD but not the 30 KD molecule was cleaved by endo-beta-N-acetylglucosaminidase F, indicating that the former contains N-linked oligosaccharides. Immunostaining for CA VI was seen in the secretory granules and cytosol of serous acinar cells and in the duct luminal contents. Staining specific for CA II was observed in the cytosol of serous acinar and duct epithelial cells. Antibody to CA I reacted only with the walls of small blood vessels. These results suggest that (a) serous acinar cells secrete 42 KD CA VI which functions in the oral cavity and that (b) serous acinar and duct epithelial cells possess cytosolic CA (30 KD CA VI and CA II) which functions in situ.


Outcomes in threadlift for facial rejuvenation.
The search for less invasive surgical techniques to address the effects of facial aging led to the development of barbed polypropylene sutures for facial suspension. Theoretical advantages of these "threadlifts" included limited scarring, rapid recovery, relative safety, and reduced cost when compared with a standard rhytidectomy. The goal of this study was to evaluate the outcomes of patients undergoing threadlifts to determine the actual complication rates, the durability of results, and the rates of reoperative surgery. A single surgeon's initial 2-year experience with 72 patients undergoing threadlifts was retrospectively reviewed. Preoperative patient demographical and clinical data, operative information, and postoperative outcomes data were compiled and evaluated. A total of 72 thread lifts were performed by 1 surgeon over a 24-month period. Of these patients, 76% underwent threadlift alone, whereas concomitant procedures were performed in 24% of patients. Minor complications were common and usually self-limited. Forty-two percent of patients underwent a secondary procedure after primary threadlift, an average of 8.4 months after the original surgery. Thirty-one percent of patients required revisional surgery for cosmetic reasons an average of 8.7 months after their threadlift. Eleven percent of the patients ultimately required removal of palpable threads. Threadlift is a safe procedure associated with minor complications. Rates of revisional surgery for cosmesis are high after threadlift. Time to revisional surgery for cosmesis is short. Results achieved by threadlift are subtle and short-lived. Threadlift is not a minimally invasive replacement of surgical rhytidectomy. Patients should understand the limitations of this technique and its high rates of revisional surgery.


Metabolic regulation of alpha-amylase gene expression in transgenic cell cultures of rice (Oryza sativa L.).
Expression of two genes in the alpha-amylase gene family is controlled by metabolic regulation in rice cultured cells. The levels of RAmy3D and RAmy3E mRNAs in rice cultured cells are inversely related to the concentration of sugar in the culture medium. Other genes in the rice alpha-amylase gene family have little or no expression in cultured cells; these expression levels are not controlled by metabolic regulation. A RAmy3D promoter/GUS gene fusion was metabolically regulated in the transgenic rice cell line 3DG, just as the endogenous RAmy3D gene is regulated. An assay of GUS enzyme activity in 3DG cells demonstrated that RAmy3D/GUS expression is repressed when sugar is present in the culture medium and induced when sugar is removed from the medium. The 942 bp fragment of the RAmy3D promoter that was linked to the coding region of the GUS reporter gene thus contains all of the regulatory sequences necessary for metabolic regulation of the gene.


A novel protein RLS1 with NB-ARM domains is involved in chloroplast degradation during leaf senescence in rice.
Leaf senescence, a type of programmed cell death (PCD) characterized by chlorophyll degradation, is important to plant growth and crop productivity. It emerges that autophagy is involved in chloroplast degradation during leaf senescence. However, the molecular mechanism(s) involved in the process is not well understood. In this study, the genetic and physiological characteristics of the rice rls1 (rapid leaf senescence 1) mutant were identified. The rls1 mutant developed small, yellow-brown lesions resembling disease scattered over the whole surfaces of leaves that displayed earlier senescence than those of wild-type plants. The rapid loss of chlorophyll content during senescence was the main cause of accelerated leaf senescence in rls1. Microscopic observation indicated that PCD was misregulated, probably resulting in the accelerated degradation of chloroplasts in rls1 leaves. Map-based cloning of the RLS1 gene revealed that it encodes a previously uncharacterized NB (nucleotide-binding site)-containing protein with an ARM (armadillo) domain at the carboxyl terminus. Consistent with its involvement in leaf senescence, RLS1 was up-regulated during dark-induced leaf senescence and down-regulated by cytokinin. Intriguingly, constitutive expression of RLS1 also slightly accelerated leaf senescence with decreased chlorophyll content in transgenic rice plants. Our study identified a previously uncharacterized NB-ARM protein involved in PCD during plant growth and development, providing a unique tool for dissecting possible autophagy-mediated PCD during senescence in plants.


Menadione reduces rotenone-induced cell death in cerebellar granule neurons.
Oxidative stress has been implicated in neuronal death caused by cerebral ischemia or some neurologic disorders. Chemical hypoxia (term defining the simulation by using respiratory inhibitors) chosen as in vitro ischemic model, was induced in primary cultures of rat cerebellar granule neurons by inhibitors of mitochondrial electron transport such as rotenone or paraquat (complex I), 3-nitropropionic acid (3-NPA, complex II), antimycin A (complex III), or sodium azide (complex IV). All compounds caused neuronal death determined by trypan blue staining and MTT-test. On the other hand, neurotoxicity of rotenone and paraquat but not of 3-NPA, antimycin or azide was significantly abolished by menadione (vitamin K3, 2-methyl-1,4-naphthoquinone). This neuroprotective effect of menadione was associated with a decrease of rotenone-induced free radical production.


[Malignant melanoma of the skin].
The incidence of malignant melanoma (MM) of the skin is on the increase. If the mortality of this disease is to be reduced, the identification of persons at risk, and early clinical diagnosis are of decisive importance. The prognosis depends on the stage of the disease and has improved over the last few decades. The present article provides an overview of the risk factors and discusses the latest guidelines for the diagnosis, treatment and follow-up, the aim of which is to make possible a uniform approach to the management of malignant melanoma.


Ganglioglioma in a patient with Turcot syndrome. Case report.
A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.


Comprehensive characterization of grafted expanded poly(tetrafluoroethylene) for medical applications.
Successful implantation of any biomaterial depends on its mechanical, architectural, and surface properties. Materials with good bulk properties seldom possess the appropriate surface characteristics required for good biointegration. The present study investigates the results of surface modification of a highly porous, fully fluorinated polymeric substrate, expanded poly(tetrafluoroethylene) (ePTFE), with a view to improving the surface bioactivity and hence ultimately its biointegration. Modification involved gamma irradiation-induced graft copolymerization with the monomers monoacryloxyethyl phosphate (MAEP) and methacryloxyethyl phosphate (MOEP) in various solvent systems (water, methanol, methyl ethyl ketone, and mixtures thereof). In order to determine the penetration depth of the graft copolymer into the pores and/or the bulk of the ePTFE membranes, angle-dependent X-ray photoelectron spectroscopy (XPS) and magnetic resonance imaging (MRI) were used. It was found that the penetration depth was critically affected by the choice of monomer and solvent as well as by the technique used to remove dissolved oxygen from the grafting mixture: nitrogen degassing versus vacuum. Difficulties due to the porous nature of the membranes in establishing the lateral position of the graft copolymers were largely overcome by combining data from microattenuated total reflectance Fourier transfer infrared (μ-ATR-FTIR) mapping and time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging. Results show that the large variation in graft heterogeneity found between different samples is largely an effect of the underlying substrate and choice of monomer. The results from this study provide the necessary knowledge and experimental data to control both the graft copolymer lateral position and depth of penetration in these porous ePTFE membranes.


Pirfenidone-loaded liposomes for lung targeting: preparation and in vitro/in vivo evaluation.
The purpose of this study was to develop novel pirfenidone (PFD)-loaded liposomes for targeting to the lung. The liposomes were prepared by the film hydration method, and their in vitro/vivo characteristics were evaluated. The PFD liposomes appeared visually as green to yellowish suspensions and were spherical in shape. The particle size was 582.3±21.6 nm and the entrapment efficiency was relatively high (87.2%±5.7%). The liposomes showed typical sustained and prolonged drug-release behavior in vitro and fitted well with the Weibull distribution equation. The relatively slower time taken to reach a minimal plasma PFD concentration in vivo suggests that PFD liposomes have a sustained-release profile, which is consistent with the results of the in vitro release study. The PFD liposomes showed the largest area under the curve for the lung. The high distribution of PFD achieved in the lungs using this liposomal formulation may be explained by physical entrapment of the liposomes in the vascular network of the lung. Histopathological results indicated that liposomal PFD could alleviate pathological injury in lung tissue. This liposomal formulation can enable sustained release of PFD and increase targeting to the lung.


Riboflavin supplementation to patients with multiple sclerosis does not improve disability status nor is riboflavin supplementation correlated to homocysteine.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Riboflavin is involved in myelin formation in nerve cells. Riboflavin is a precursor of flavin adenine D-nucleotide (FAD), which is a coenzyme of methylene tetrahydrofolate reductase (MTHFR), which is an important enzyme for remethylation of homocysteine. Riboflavin supplementation has been shown to affect the serum levels of homocysteine in healthy volunteers. The aim of the present study was to test the effect of riboflavin supplementation on the status and disability of patients with MS and whether this effect could be mediated by serum homocysteine levels. This was a randomized, double-blind, controlled trial in which 29 MS patients with a mean age of 33 were tested with riboflavin, and the placebo group, with a mean age of 31, received either riboflavin supplementation (10 mg) or the placebo daily for six months. Disability, measured by the Expanded Disability Status Scale (EDSS) scores, erythrocyte glutathione reductase activity coefficient (EGRAC), and serum homocysteine levels were measured before and after the study. The mean ± SD of EDSS score was significantly decreased in both groups over the six months of the study (2.3 ± 0.7 vs. 1.6 ± 0.6 for the riboflavin group and 2.8 ± 1.1 vs. 2.3 ± 1.3 for the placebo groups. The comparison across both groups yielded a non-significant change (P = 0.001 and 0.02, respectively). No significant differences were observed between the two groups in terms of EGRAC, riboflavin deficiency levels by EGRAC category, and serum homocysteine levels before and after the study. Riboflavin supplementation (10 mg/day) to patients with MS does not improve disability status. It appears that this effect is not related to serum homocysteine levels.


Effect of varying size of scleral flap and corneal block on trabeculectomy.
Prospectively, 28 eyes of 23 patients undergoing trabeculectomy were divided into two groups. The first group received a large scleral flap (4 mm X 4 mm X 4 mm) and corneal block (3 mm X 3 mm). The second group received a small scleral flap (2 mm X 2 mm X 2 mm) and corneal block (1 mm X 1 mm). No other changes in technique were made. After a mean follow-up of 13 months, there was no significant difference in final intraocular pressure, visual acuity, or complication rates between groups.


Quadriceps torque and integrated electromyography*.
Using surface electromyography, the myoelectric activity and torque of the quadriceps muscles were recorded under isometric conditions. The purpose of the study was to identify the optimal angle of knee flexion for normalization purposes. Additionally, the behavior of the quadriceps as the knee was flexed was investigated. It was found that the subject's sex may affect the angle at which maximal torque and integrated electromyography (lemg) occurs. Maximal torque and lemg occurred at 50 degrees for males and 70 degrees for females. This may have an effect on the normalization procedure when the quadriceps is studied dynamically. The location of maximal myoelectric activity of the quadriceps should influence our treatment of patellofemoral disorders when patellar biomechanics are considered. J Orthop Sports Phys Ther 1985;6(6):309-314.


Mast cells as regulators of skin inflammation and immunity.
Mast cells are known to be the effector cells of immediate-type allergy, but experimental evidence obtained during the last decade has revealed their role in innate and acquired immunity. Upon activation mast cells can undergo an anaphylactic or piecemeal degranulation or degranulation-independent mediator secretion, resulting in rapid or slow release of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express different receptors and ligands on the cell surface, molecules that can activate the cells of the immune system, such as different subsets of T cells. All these mediators and cell surface molecules can promote inflammation in the skin. During the last years, a new role for mast cells has emerged; induction of tolerance or immunosuppression and interaction with regulatory T cells. However, the mechanisms that switch the proinflammatory function of mast cells to an immunosuppressive one are unknown. In this review, the immunoregulatory function of mast cells and its relation to skin inflammation are discussed.


Hydropneumopericardium: A Rare Complication of an Oesophageal Tumour.
Hydropneumopericardium is a rare event with a risk of serious complications. Timely diagnosis and treatment is important as it can improve prognosis. We report the case of a 77-year-old male patient who presented with acute interscapular pain which developed during a meal. An oesophago-pericardial fistula was found in the context of malignant oesophageal disease. Hydropneumopericardium secondary to oesophageal tumour is a rare but life-threatening finding that has a very poor prognosis.A high level of suspicion is needed, as the clinical manifestations are very unspecific and timely treatment can improve prognosis.Successful management of an oesophago-pericardial fistula includes surgical treatment and antibiotic therapy.


Posterior vitreous detachment and work efficiency: a case study.
The paper analyses a case report of a female worker whose job required prolonged near visual effort and who suffered from multiple ophthalmological disorders. The specific case of interaction between the visual apparatus of the operator and the tasks performed is discussed, with particular reference to the unstable compensation that different pathological disorders, when summed together, can produce, thus allowing to subjects to lead a normal working and social life for long periods of time without any limitations and without any significant asthenopic symptoms. Because this compensation is unstable, it can unexpectedly be impaired due to the onset of diseases not involving the visual apparatus. The scientific literature was analysed in order to assess, at least approximately, the prevalence of clinical/functional situations identical or similar to the case described.


Evoked potential tests in clinical diagnosis.
Evoked potentials are used to detect conduction disturbances in the central nervous system. This paper provides an overview of the areas in which evoked potentials are used in clinical neurophysiological diagnostics, with the emphasis on coma and demyelinating disease. The article is based on a literature search in PubMed and the authors' long experience of neurological and neurophysiological diagnostics. Somatosensory evoked potential (SEP) can be a reliable predictor of failure to regain consciousness as early as 24 hours after anoxic coma has occurred. If coma is caused by a brain trauma, cerebrovascular episode or other neurological disease, information about which sensory brainstem pathways are damaged can be obtained from somatosensory evoked potentials and brainstem auditory evoked potentials (BAEP), which can also be useful for planning rehabilitation. Normal SEP and BAEP findings in cases of coma caused by trauma are associated with a favourable prognosis. Visually evoked potential (VEP) can often reveal signs of a history of optic neuritis. SEP and BAEP can also reveal subclinical lesions in the central nervous system and be a supplementary diagnostic test for multiple sclerosis. The clinical value of SEP and BAEP is high in coma cases. Evoked potentials are also important in intraoperative monitoring. The clinical value of VEP is high when a history of optic neuritis is a deciding factor for a multiple sclerosis diagnosis. Some selected patients who are being assessed for demyelinating disease will benefit from a full EP study.


Glycine and uridine prevent D-galactosamine hepatotoxicity in the rat: role of Kupffer cells.
Extrahepatic factors, such as increased gut permeability and bacteria from the gut, have been shown to play a role in D-galactosamine toxicity in rats. Because bacterial endotoxin activates Kupffer cells, the purpose of this study was to clarify the role of Kupffer cells in the mechanism of D-galactosamine hepatotoxicity in rats and determine whether uridine, a compound that rescues animals from D-galactosamine toxicity, affects Kupffer cells. Rats were fed control or glycine (5%) containing diets to prevent Kupffer cell activation or treated with gadolinium chloride (GdCl3, 20 mg/kg) to destroy Kupffer cells selectively before injection of D-galactosamine (500 mg/kg, intraperitoneally). D-galactosamine caused panlobular focal hepatocellular necrosis, polymorphonuclear cell infiltration, and increased serum transaminases significantly at 24 hours. Dietary glycine or pretreatment with GdCl3 prevented these effects. D-galactosamine caused a transient increase in circulating endotoxin that was maximal at 1 hour and was blunted significantly by dietary glycine. Additionally, antisera to tumor necrosis factor-alpha (TNF-alpha) prevented hepatotoxicity caused by D-galactosamine. Moreover, apoptosis in hepatocytes caused by D-galactosamine occurred before necrosis (6 hours) and was prevented by glycine, GdCl3, TNF-alpha antiserum, and uridine. Thus, it was hypothesized that TNF-alpha from Kupffer cells causes apoptosis after D-galactosamine administration in the rat. Indeed, increases in TNF-alpha messenger RNA (mRNA) were detected as early as 2.5 hours after D-galactosamine treatment. Previous work proposed that uridine blocks D-galactosamine toxicity by preventing inhibition of mRNA synthesis. In view of these results, the possibility that uridine might affect Kupffer cells was investigated. Uridine significantly blunted the increase in [Ca2+]i and release of TNF-alpha caused by endotoxin in isolated Kupffer cells and prevented apoptosis caused by D-galactosamine treatment in vivo. These data support the hypothesis that uridine prevents D-galactosamine hepatotoxicity not only by rescuing the hepatocyte in the late phases of the injury but also preventing TNF-alpha release from Kupffer cells thereby blocking apoptosis that occurs early after D-galactosamine treatment. Taken together, these data strongly support the role of Kupffer cell activation by endotoxin early after D-galactosamine treatment as an important event in the mechanism of hepatotoxicity in the rat.


[Autopsy case of drowning caused by accidental carbon dioxide intoxication in a hold tank].
A 49-year-old male captain fell and unfortunately died in a hold tank where he had entered to rescue his fainting co-worker on the disposing waste fluid left there. An autopsy revealed that the captain died from drowning in the waste fluid. In order to clarify the cause of their falling in the tank, the gas in the hold tank was analyzed. The concentration of oxygen was 18.86 to 19.31%, carbon dioxide was 7.28 to 9.07% and the other gases, including hydrogen sulfide, were assessed to be under the normal level. It was concluded that the intoxication of carbon dioxide generated from the waste fluid fermentation was the cause of this fatal accident through loss of consciousness. It is necessary to recognize that carbon dioxide is a dangerous and deleterious gas in circumstances where the gas can be produced.


Management of chronic upper abdominal pain in cancer: transdiscal blockade of the splanchnic nerves.
The use of celiac plexus block to relieve the intractable pain caused by upper abdominal malignancies is well established. However, its effects are inconsistent for many reasons, mainly because of structural anatomic distortion as a consequence for the malignancy. The splanchnic nerve blockade (SNB) seems to be a useful alternative to the celiac plexus block in upper abdominal pain relief. The pain of 109 patients with unresectable upper abdominal or lower esophageal neoplasms was managed by posterior transdiscal SNBs guided by computed tomography at the Instituto Nacional de Cancerología in Mexico City from January 2004 to June 2007. The study evaluated SNB efficacy with regard to pain relief, its adverse effects/complications, and patient satisfaction. Splanchnic nerve blockade efficacy with regard to pain relief was exhibited by a marked decrease in the visual analog score and in opioid consumption, with preprocedural mean values dropping from 6.1 ± 2.4 and 102.4 mg/d of morphine to 2.7 ± 2.4 and 53.3 mg/d at the first postprocedural visit, respectively. These results persisted during the 1-year follow-up period or until death. Minor adverse effects (moderate diarrhea and mild hypotension) were frequent (n = 64 and n = 47, respectively), and severe complications occurred in 1 patient with a transient paraparesis (n = 1). No procedure-related mortality was observed. Splanchnic nerve blockade via a transdiscal approach is a technique that provides analgesia and the alleviation of the secondary undesirable effects of analgesic drugs resulting from the decrease of morphine consumption in patients with upper abdominal malignancies. In experienced teams, the reliability of its analgesic effect is high, with a low rate of severe complications.


[Processing of visually presented verbal stimuli in evoked potentials].
The ERPs to familiar, unfamiliar, and recently learned words were recorded in 20 right-handed students who have recently studied a course in sensory physiology during performance of two tasks. The first task consisted in processing of different types of words, the second task required recognition of terms from sensory physiology. In the first task, three types of words were presented to a subject: familiar words related and unrelated to a given category and unfamiliar words. Subjects had to press the appropriate button responding to the questions whether they considered the presented word be related to the given category and whether they were sure in their answer. In the second task, terms from recently studied physiological material were presented to the students who had to detect whether those terms were related or unrelated to the given sensory system. Significant differences between late ERP components were revealed by Student test for matched samples. In the first task, component N400 of the ERP to unfamiliar words was higher than that of the ERP to familiar words. It was also higher in ERPs to words unrelated to the given category than in ERPs to related words. However, this component did not differ between ERPs to well and poorly acquired words in the test on sensory physiology. On the contrary, the late positive component was more expressed in ERPs to familiar and better acquired words in both tasks. Brain mechanisms of processing of different types of words are discussed.


Evaluation of reproductive function among men occupationally exposed to a stilbene derivative: I. Hormonal and physical status.
This is the first of two reports describing a National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluation conducted in response to complaints of impotence and decreased libido among male employees who manufactured 4,4'-diaminostilbene-2,2' disulfonic acid (DAS; CAS 81-11-8), an intermediate in the manufacture of fluorescent whitening agents. DAS is structurally similar to the synthetic estrogen diethylstilbestrol (DES). Levels of six reproductive hormones in 30 male workers who manufactured DAS (current DAS workers) and 20 former DAS workers were compared to levels of 35 workers who manufactured plastics additives. Current and former DAS workers had lower mean total testosterone (TT) levels compared to additives workers (458 and 442, respectively, vs. 556 ng/dL; p = 0.05 and 0.04). Current and former DAS workers were 3.6 (95% CI, 0.5-24.4) and 2.2 (95% CI, 0.3-18.0) times more likely than additives workers to have lowest quartile TT levels (< 386 ng/dL) after adjustment for age and body mass index. Duration of employment in DAS production was negatively related to the workers' testosterone levels. These data suggest that occupational DAS exposure may be associated with alterations in male reproductive hormone levels.