Envelope glycosylation determined by lectins in microscopy sections of Acinetobacter venetianus induced by diesel fuel.
It was suggested in a previous study that cells of Acinetobacter venetianus VE-C3 adhere to diesel fuel by synthesizing a capsular polysaccharide containing glucose and/or mannose. To study the fine structure of cells and localization of bacterial polysaccharide in the presence of diesel fuel, two lectins were used: ConA, an agglutinin from Canavalia ensiformis specific for mannose and/or glucose residues, and PNA, an agglutinin from Arachis hypogaea, for terminal galactose residues. The lectins were conjugated with electron dense ferritin for transmission electron microscopy (TEM) and with fluorescein isothiocyanate (FITC) for scanning confocal laser microscopy (SCLM). Samples were prepared by freeze substitution, which allows glycosylation to be determined in situ in thin sections of specimens. The distribution of glycosylation was imaged with and without treatment of specimens with their specific hapten (glucose and galactose). The glycosylation activity produced a polysaccharide capsule. Emulsified diesel fuel nanodroplets were observed at the cell envelope perimeter. Fine structure of vesicles consisted of polysaccharide and diesel fuel nanodroplets. Lectin blotting analysis showed ConA-positive glycoprotein with an apparent molecular mass of 22 kDa in the outer membrane. Its production was induced by diesel fuel. This glycoprotein was probably responsible for bioemulsifying activity at the cell envelope. Several other glycoproteins were positive for PNA lectin, the main constituent migrating with an apparent molecular weight of 17.8 kDa. However, they were all constitutive and probably involved in cell biofilm formation at the oil surface.


D.C. electrical conductivity and conduction mechanism of some azo sulfonyl quinoline ligands and uranyl complexes.
Supramolecular coordination of dioxouranium(VI) heterochelates 5-sulphono-7-(4'-X phenylazo)-8-hydroxyquinoline HL(n) (n=1, X=CH(3); n=2, X=H; n=3, X=Cl; n=4, X=NO(2)) have been prepared and characterized with various physico-chemical techniques. The infrared spectral studies showed a monobasic bidentate behavior with the oxygen and azonitrogen donor system. The temperature dependence of the D.C. electrical conductivity of HL(n) ligands and their uranyl complexes has been studied in the temperature range 305-415 K. The thermal activation energies E(a) for HL(n) compounds were found to be in the range 0.44-0.9 eV depending on the nature of the substituent X. The complexation process decreased E(a) values to the range 0.043-045 eV. The electrical conduction mechanism has been investigated for all samples under investigation. It was found to obey the variable range hopping mechanism (VRH).


A novel and facile Zn-mediated intramolecular five-membered cyclization of beta-tetraarylporphyrin radicals from beta-bromotetraarylporphyrins.
A novel and facile method for the Zn-mediated intramolecular cyclization of beta-porphyrin radicals has been developed for the convenient and effective construction of newly fused five-membered porphyrin systems from readily available beta-bromotetraarylporphyrins.


Biochemical analysis of a blood meal-induced Aedes aegypti glutamine synthetase gene.
Glutamine synthetase (GS) in the mosquito, Aedes aegypti, is induced in the midgut following a blood meal. Mosquito GS message is detected as soon as 1 h post-blood feeding and remains stable for 18 h. Using a PCR product encoding mosquito GS, a lambda gt10 adult female mosquito cDNA library was screened. A cDNA clone, pCl5A2, encoding the full translation product of mosquito GS was isolated and sequence analyses performed. Mosquito GS cDNA is 2.5 kb in length and its putative translation product shares all the conserved regions characteristic of the GS gene family, including the presumed ATP biding site. Glutamine synthetase activity in the mosquito midgut is highest at 18 h post-blood feeding. Activity can be detected over a broad pH range, from 6.0 to 7.5. Unlike other cellular GS enzymes, mosquito GS is not active in the presence of ATP. Very low dosages (0.05 mM) of L-methionine S-sulfoximine are sufficient to partially inhibit mosquito GS activity. Inhibition of GS disrupts the normal formation of the midgut peritrophic matrix, suggesting that GS enzyme might be involved in the initial pathway of chitin synthesis. The unique expression pattern and inducible nature of the mosquito GS gene make it an interesting candidate for studying promoter function. Additionally, the blood meal activation of the GS gene makes this a potentially valuable tool in mosquito transformation studies.


Ball milling synthesis of covalent organic framework as a highly active photocatalyst for degradation of organic contaminants.
Facile, environmentally-friendly fabrication of high-yield and stable covalent organic framework (COF) materials has been a limitation to their large-scale production and application. In this work, ball milling was used to synthesize COF by mechanochemical reaction between 1,3,5-triformylphloroglucinol (Tp) and melamine (MA) at ambient temperature. Different routes (liquid-free, solvent-assisted and catalyst-assisted) and proportions of liquids (solvents or catalyst) were investigated. Two morphologies were obtained when various amounts of liquid were added during grinding. The two forms were interwoven thread-shaped and exfoliative thin ribbon-like structures. Further, visible-light photocatalytic (λ > 400 nm) performance and mechanism of the two structures of COFs were investigated. The exfoliative ribbon-like structures exhibited greater rates of photodegradation of phenol and retained 87.6% of initial photodegradation after being used four times. Addition of liquid catalyst not only improved crystallinity of the COF materials, but also enhanced rates of photocatalytic reactions. Photocatalytic activity of the exfoliative structure of TpMA synthesized by ball milling was comparable with that of the photocatalyst prepared by use of the solvothermal method, while time to prepare the catalyst was shortened by 36-fold and the amount of solvent used was reduced by 8-fold at room temperature. Mechanochemical synthesis is a promising potential tool for large-scale production of COFs, which will make greater use of COFs for degradation of pollutants.


Antifungal activity of Ferulago capillaris essential oil against Candida, Cryptococcus, Aspergillus and dermatophyte species.
This study evaluates the composition, antifungal activity and mechanism of action of the essential oil of Ferulago capillaris (Link ex Spreng.) Cout. and its main components, limonene and α-pinene, against clinically relevant yeasts and moulds. Essential oil from the plant's aerial parts was obtained by hydrodistillation and analysed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS). Essential oil showed high contents of limonene (30.9%) and α-pinene (35.8%). Minimum inhibitory concentrations (MICs) were measured according to the reference Clinical and Laboratory Standards Institute (CLSI) broth macrodilution protocols. Cell suspensions were subcultured in solid medium and the minimum fungicidal concentrations (MFCs) were rendered. The effect of essential oil on germ tube formation, mitochondrial function and ergosterol biosynthesis was investigated. Essential oil and α-pinene displayed low and similar MIC and MFC values against tested organisms (0.08 to 5.0 μL/mL), while limonene showed a weaker activity (0.32 to 20 μL/mL). Essential oil inhibited germ tube formation at sub-inhibitory concentrations on Candida albicans. The exposure of C. albicans to the essential oil resulted in impairment of mitochondrial functions in a dose-dependent manner. No difference in ergosterol content was observed in essential oil-treated C. albicans. F. capillaris and α-pinene display a broad fungicidal activity. The fungicidal activity of F. capillaris on C. albicans can be related to an induced oxidative stress which affects enzymes activity and the membrane potential of mitochondria. The essential oil of F. capillaris was shown to have potential for use in the development of clinically useful therapeutic preparations, particularly for topical application in the management of superficial mycoses.


The significance of "significant" results.
Based upon new analyses we have performed, Martens' (1969) CE data are shown to lack both internal and external validity. Also, compared to other PSI techniques, the chemical mixture used in Martens' study and our (1978) study is shown to produce prints of inconsistent quality.


Garbage enzyme-mediated treatment of landfill leachate: A sustainable approach.
The study evaluates the soluble chemical oxygen demand (sCOD) removal efficiency from landfill leachate by treating it with four different garbage enzymes at two temperatures (room temperature 27 ± 3 °C and higher temperature 42 ± 3 °C). The four different garbage enzymes were prepared by fermenting fruit peels such as pineapple, banana, orange, and lemon peels and treated with landfill leachate at different mixing ratios of 5%, 10%, 15% and 20%. The results show that garbage enzymes made from orange (10%) and lemon (15%) have maximum sCOD reduction of 68.24% and 67.89%, respectively, at room temperature. The maximum solubilization was found in the pineapple and lemon garbage enzyme at 5% concentration. The samples kept at room temperature showed better solubilization and sCOD removal compared to the samples at higher temperatures. The study demonstrates that the garbage enzyme could be used to increase the bioavailability of organics in leachate.


Inhibition of AGEs formation by natural products.
Since advanced glycation end-products (AGEs) inhibitors such as benfotiamine, pyridoxamine and aminoguanidine significantly inhibit the development of retinopathy and neuropathy in streptozotocin-induced diabetic rats, treatment with AGEs inhibitors is believed to be a potential strategy for preventing lifestyle-related diseases such as diabetic complications and atherosclerosis. Furthermore, preventive medicine is the most important approach to preventing lifestyle-related diseases, and improving daily nutritional intake is thought to prevent the pathogenesis of such diseases. Therefore, AGEs inhibitors that can be obtained from daily meals are preferred to prescribed drugs. In this article, we describe a strategy for developing new AGEs inhibitors from natural products.


DNA cross-linking following exposure to cis-platinum in primary and serially passaged cultured cells derived from two murine fibrosarcomas.
We compared the kinetics of the repair of total (ISC plus DPC) cross-links and of proteinase-resistant (ISC) cross-links in cultured cells derived from two murine fibrosarcoma tumors, FSA and NFSA, after treatment with cis-platinum (cis-DDP), using a modification of the alkaline elution technique. The two tumors had previously been characterized for their response to cis-DDP in vivo; FSA cells gradually removed cross-links from their genome, whereas the NFSA cells showed no capacity to repair these lesions. The aim of the present study was to establish whether treatment of cells from these same two tumors grown under controlled culture conditions would affect either the nature of the lesions induced by cis-DDP or the kinetics of repair of these lesions when compared with tumors treated with cis-DDP in vivo. The culture conditions represent two situations: in the first, the cells in culture approximated the proportion of tumor and normal host cells present in vivo, and in the second, the normal host cells had been eliminated by subculturing to produce cultures composed entirely of tumor cells. All cells were exposed to cis-DDP (either 10 or 20 micrograms/ml) for 1 h. The relative amounts of total cis-DDP-induced DNA crosslinks and of ISCs were then determined at various times after treatment. The results show that there was little difference in the behavior of these cultured cells compared to the in vivo response of the tumor from which they were derived. For FSA, each cell culture exhibited a capacity to repair DNA cross-links comparable to that of the tumor in vivo. For NFSA, the passaged cells again paralleled the behavior of that tumor in vivo, although in this case by showing no measurable capacity to repair cross-links. The absence of a significant repair response in the NFSA tumor therefore appears to be an intrinsic characteristic of these tumor cells.


Calcium regulates thioredoxin reductase in human metastatic melanoma.
Thioredoxin reductase has been purified from human metastatic melanotic melanoma and amelanotic melanoma tissues. Enzyme from the melanotic melanoma tissue contains bound calcium showing classical sigmoidal allosteric kinetics, whereas enzyme from the amelanotic melanoma yielded normal Michaelis-Menten saturation with substrate. Calcium inhibition can be partially reversed by oxidized thioredoxin. 45Ca has been used to label the amelanotic melanoma enzyme in order to determine the number of calcium-binding sites. These isotope experiments yielded only one calcium-binding site per enzyme molecule. Enzyme labeled with 45Ca was dialyzed for 24 h without loss of radioactivity, but the addition of oxidized thioredoxin to this labeled enzyme caused 60% calcium exchange in 24 h. Comparative studies with Escherichia coli thioredoxin reductase showed similar calcium inhibition as well as partial reactivation with oxidized thioredoxin. The enzyme from E. coli previously sequenced by others, showed considerable homology with the first EF-hands calcium-binding site of calmodulin. Detailed calcium-binding studies indicated that 10(-5) M of this fast exchange ion was sufficient to cause allosteric regulation in 10 min. This strong calcium-binding property could explain the allosteric nature of the thioredoxin reductase purified from human metastatic melanotic melanoma and its role in the regulation of melanin biosynthesis.


Testosterone serum levels are not predictive of maternal virilization in hyperreactio luteinalis.
Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization. A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in one case of HL managed at our institution. In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2-37.3 nmol/l and 13.7-197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l. From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC-MS/MS should preferably be used for reporting concentrations of circulating testosterone.


In-situ formation of durable akaganeite (β-FeOOH) nanorods on sulfonate-modified poly(ethylene terephthalate) fabric for dual-functional wastewater treatment.
Industrial oily wastewater with dye-pollution is a critical environmental issue for water purification. However, the fabrication of effective and stable materials for oil-water separation and simultaneous degradation of organic contaminants remains a critical challenge. Herein, we report a new process for in-situ formation of akaganeite (β-FeOOH) nanorods layer on the surface of poly(ethylene terephthalate) (PET) fabric via radiation-induced graft polymerization of glycidyl methacrylate, which is then sulfonated and mineralized. The resultant product is labeled as β-FeOOH@PET, which exhibits dual purification by demonstrating an effective oil-water separation and organic dyes photodegradation under the illumination of visible light. It provides stable performance even after 1000 wash cycles. The sulfonated layer acts as not only an electronic transport layer to prevent electron-hole recombination, but also as an anchored interface for immobilizing β-FeOOH nanorods on the sulfonated layer via strong covalent bonds. Overall, the superhydrophilicity and underwater superoleophobicity of β-FeOOH@PET fabric, along with its robustness with a flexible organic substrate and its dual purification function, provide a new insight toward oily wastewater remediation and water purification in large-scale applications.


Efficient one-cycle affinity selection of binding proteins or peptides specific for a small-molecule using a T7 phage display pool.
Here, we report an efficient one-cycle affinity selection using a natural-protein or random-peptide T7 phage pool for identification of binding proteins or peptides specific for small-molecules. The screening procedure involved a cuvette type 27-MHz quartz-crystal microbalance (QCM) apparatus with introduction of self-assembled monolayer (SAM) for a specific small-molecule immobilization on the gold electrode surface of a sensor chip. Using this apparatus, we attempted an affinity selection of proteins or peptides against synthetic ligand for FK506-binding protein (SLF) or irinotecan (Iri, CPT-11). An affinity selection using SLF-SAM and a natural-protein T7 phage pool successfully detected FK506-binding protein 12 (FKBP12)-displaying T7 phage after an interaction time of only 10 min. Extensive exploration of time-consuming wash and/or elution conditions together with several rounds of selection was not required. Furthermore, in the selection using a 15-mer random-peptide T7 phage pool and subsequent analysis utilizing receptor ligand contact (RELIC) software, a subset of SLF-selected peptides clearly pinpointed several amino-acid residues within the binding site of FKBP12. Likewise, a subset of Iri-selected peptides pinpointed part of the positive amino-acid region of residues from the Iri-binding site of the well-known direct targets, acetylcholinesterase (AChE) and carboxylesterase (CE). Our findings demonstrate the effectiveness of this method and general applicability for a wide range of small-molecules.


A comparison of the non-invasive ultrasonic cardiac output monitor (USCOM) with the oesophageal Doppler monitor during major abdominal surgery.
Perioperative interventions, targeted to increase global blood flow defined by explicit measured goals, reduce postoperative complications. Consequently, reliable non-invasive estimation of the cardiac output could have far-reaching benefit. This study compared a non-invasive Doppler device - the ultrasonic cardiac output monitor (USCOM) - with the oesophageal Doppler monitor (ODM), on 25 patients during major abdominal surgery. Stroke volume was determined by USCOM (SVUSCOM) and ODM (SVODM) pre and post fluid challenges. A ≥ 10% change (Δ) SVUSCOM had a sensitivity of 94% and specificity of 88% to detect a ≥ 10% Δ SVODM; the area under the receiver operating curve was 0.94 (95% CI 0.90-0.99). Concordance was 98%, using an exclusion zone of <10% Δ SVODM. 135 measurements gave median SVUSCOM 80 ml (interquartile range 65-93 ml) and SVODM 86 ml (69-100 ml); mean bias was 5.9 ml (limits of agreement -20 to +30 ml) and percentage error 30%. Following fluid challenges SVUSCOM showed good concordance and accurately discriminated a change ≥10% in SVODM.


Preexisting musculoskeletal conditions presenting as school sports injuries.
One hundred thousand insurance claims for secondary school injuries sustained between 1974 and 1986 were analyzed to determine the incidence of diagnosis and misdiagnosis of preexisting musculoskeletal conditions. Seventy-five percent of accident reports described acute injury to normal bones, joints, and soft tissues. Twenty percent were reinjuries or other sequelae of past trauma. Infection, congenital or developmental anomalies, or other nontraumatic conditions were found in 5% of the injuries reported. Patients with preexisting diseases had a higher morbidity than those with an acute primary injury. The majority of preexisting conditions were correctly described and documented by the attending physician. However, for 268 patients with a previous accident residual and 465 patients suffering from infection, pathologic fracture, congenital/developmental disorder, neoplasia, or other diseases, the potential role of the underlying condition was not correctly stated. Correct preexisting diagnoses need to be recognized if treatment is to be optimal.


Influence of Speech Recognition Ability on Acceptable Noise Level for Mandarin (Chinese) Speakers with Normal Hearing.
Noise can induce hearing loss and reduce speech understanding. The Acceptable Noise Level (ANL) test has been widely used in audiology. However, strategies used by listeners to determine ANLs are unclear. The current study evaluated the role of speech recognition in selecting ANL and how well ANL could predict speech understanding in a noisy situation. Forty-five Mandarin speakers with normal hearing were tested in both ears. ANL is defined as Most Comfortable Level (MCL) minus Background Noise Level (BNL). To obtain ANL monaurally with an earphone, the study measured participants' MCL to hear a Mandarin story in quiet and the maximum BNL to tolerate while following the story. Then, based on the participant's ANL, speech recognition in noise was examined using a set of phonemic-balanced Mandarin words. The signal-to-noise ratio (SNR) was adjusted to ANL, ANL - 10 dB ("degraded noise condition"), and ANL + 10 dB ("improved noise condition"). The mean ANLs were 2.4 dB and 2.6 dB for the left and right ears, respectively. The mean speech recognition with SNR adjusted to ANL was relatively high for both ears (81-83% correct). Even for those ear samples with very low ANL (<0 dB), speech performance obtained at SNR = ANL was still high. The mean speech recognition obtained at SNR = ANL was 5 percentage points lower than the mean speech recognition at the improved noise condition and 14 percentage points higher than the mean speech recognition at the degraded noise condition. Speech recognition obtained at SNR = ANL and ANL - 10 dB correlated significantly with ANL. Speech recognition in noise appears to play an important role for listeners with normal hearing in deciding their ANLs. Additionally, ANL can predict speech performance (r-squared = 53-61%) in the degraded noise condition.


Psycho-social correlates of wellbeing among South Africans: An exploration of the 2017 South African Social Attitudes Survey (SASAS).
Wellbeing is a public health variable as it is an index of societal development. According to the most recent World Happiness Reports, South Africa ranks low in the self-reported wellbeing of its citizens. This study set out to understand the contributory factors to wellbeing of South Africans. This study explored the South African Social Attitudes Survey (SASAS) of 2017, a national survey of social attitudes in South Africa for variables that are related to the wellbeing of the citizens. Group identification, national identification, hopefulness for group's future, positive interracial contact, belief in sustaining memory of apartheid, attitude towards immigrants, frequency of group's discrimination experience, and life satisfaction were identified. Statistical analysis showed that these variables are significantly associated with wellbeing for the total sample. Also, analysis by population groups showed that these variables had differential significance for members of different groups. Life satisfaction emerged as the most important predictor of wellbeing for the total sample and Black Africans, Indian/Asians, and Colored groups. The findings of this study showed that different psycho-social factors are critical to the wellbeing of South Africans. It was suggested that the life experiences of the different population groups could influence how important a factor is in wellbeing and this should be considered in efforts to improve wellbeing of the citizens.


Altered vitamin D status in liver tissue and blood plasma from Greenland sledge dogs (Canis familiaris) dietary exposed to organohalogen contaminated minke whale (Balaenoptera acuterostrata) blubber.
This study compared vitamin D3 (vitD3) and 25-OH vitamin D3 (25OHD3) status in Greenland sledge dogs (Canis familiaris) given either minke whale (Balaenoptera acuterostrata) blubber high in organohalogen contaminants (OHCs) or clean porcine (Suis scrofa) fat for up to 636 days. A group of six exposed and six control sister bitches (maternal generation) and their three exposed and four control pups, respectively, were daily fed 112g whale blubber (193µg ∑PCB/day) or porcine fat (0.17µg ∑PCB/day). Mean level of ∑PCB in adipose tissue of exposed bitches and their pups was 3106 and 2670ng/g lw, respectively, which was significantly higher than the mean concentration of 53ng/g lw for all controls (p<0.001). The vitamin analyses showed that 25OHD3 in liver of maternal exposed bitches were significantly lower than in controls (p=0.004) while vitD3 was significantly highest in liver of exposed pups (p<0.003). Regarding blood plasma concentrations, exposed F generation pups had significantly higher concentrations of 25OHD3 than controls (p=0.009). Correlation analyses showed that blood 25OHD3 decreased significantly with increased adipose tissue concentrations of ∑PCB in exposed dogs (R(2)=0.64, p=0.005) and a similar trend was found for liver 25OHD3 (R(2)=0.32, p=0.08). The results indicate that the homeostasis and metabolism of vitamin D compounds may respond differently to the dietary composition of fatty acids and OHC exposure. It is unknown if the lower level of 25OHD3 in the liver of exposed dogs would have any negative effects on immunity and reproduction and more focus should be conducted on this compound in Arctic wildlife.


Selective inhibition of cholesterol synthesis by cell-free preparations of rat liver by using inhibitors of cytoplasmic acetoacetyl-coenzyme A thiolase.
Cytoplasmic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 22.214.171.124) was partially purified from rat liver. The enzyme was irreversibly inactivated by 4-bromocrotonyl-CoA, but-3-ynoyl-CoA, pent-3-ynoyl-CoA and dec-3-ynoyl-CoA. In the case of the alk-3-ynoyl-CoA esters the potency as alkylating agents of acetoacetyl-CoA thiolase decreased with increased chain length of the alk-3-ynoyl moiety. Advantage was taken of the specific action of alk-3-ynoyl-CoA esters on acetoacetyl-CoA thiolase to show that in a postmitochondrial fraction from rat liver they are effective inhibitors of cholesterol synthesis from sodium [2-14C]acetate under conditions when mevalonate conversion into cholesterol and fatty acid synthesis are unafffected. Short-chain alk-3-ynoic acids have little effect on sterol synthesis, although dec-3-ynoic acid is an effective inhibitor owing to its conversion into the CoA ester by the microsomal fatty acyl-CoA synthetase.


Antibacterial activity and characteristics of silver nanoparticles biosynthesized from Carduus crispus.
In recent years' synthesis of metal nanoparticle using plants has been extensively studied and recognized as a non-toxic and efficient method applicable in biomedical field. The aim of this study is to investigate the role of different parts of medical plant Carduus crispus on synthesizing silver nanoparticles and characterize the produced nanoparticle. Our study showed that silver nanoparticles (AgNP) synthesized via whole plant extract exhibited a blue shift in absorption spectra with increased optical density, which correlates to a high yield and small size. Also, the results of zeta potential, X-ray diffraction, photon cross-correlation spectroscopy analysis showed the surface charge of - 54.29 ± 4.96 mV (AgNP-S), - 42.64 ± 3.762 mV (AgNP-F), - 46.02 ± 4.17 mV (AgNP-W), the crystallite size of 36 nm (AgNP-S), 13 nm (AgNP-F), 14 nm (AgNP-W) with face-centered cubic structure and average grain sizes of 145.1 nm, 22.5 nm and 99.6 nm. Another important characteristic, such as elemental composition and constituent capping agent has been determined by energy-dispersive X-ray spectroscopy and Fourier transform infrared. The silver nanoparticles were composed of ~ 80% Ag, ~ 15% K, and ~ 7.5% Ca (or ~ 2.8% P) elements. Moreover, the results of the FTIR measurement suggested that the distinct functional groups present in both AgNP-S and AgNP-F were found in AgNP-W. The atomic force microscopy analysis revealed that AgNP-S, AgNP-F and AgNP-W had sizes of 131 nm, 33 nm and 70 nm respectively. In addition, the biosynthesized silver nanoparticles were evaluated for their cytotoxicity and antibacterial activity. At 17 µg/ml concentration, AgNP-S, AgNP-F and AgNP-W showed very low toxicity on HepG2 cell line but also high antibacterial activity. The silver nanoparticles showed antibacterial activity on both gram-negative bacterium Escherichia coli (5.5 ± 0.2 mm to 6.5 ± 0.3 mm) and gram-positive bacterium Micrococcus luteus (7 ± 0.4 mm to 7.7 ± 0.5 mm). Our study is meaningful as a first observation indicating the possibility of using special plant organs to control the characteristics of nanoparticles.


Randomised trial of telephone counselling to improve participants' adherence to prescribed drugs in a vascular screening trial.
A total of 1446 participants, 65- to 74-year-old men diagnosed with abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD) or high blood pressure (HB) in the Viborg Vascular (VIVA) screening trial, were consecutively included and randomised to a telephone counselling (TC) or no TC 3 months after being screened positive. Data from VIVA were linked to data from Danish registers from 2007 to 2016. The primary outcome was a composite outcome of proportion of days covered by statin, antithrombotic drugs and antihypertensive agents and for each specific drug class at 6-month follow-up. The same outcomes were assessed at 12 and 60 months and considered secondary outcomes. Outcome measures are reported as risk differences (RD). There were no differences between the groups in relation to the composite of all three drug classes over 6 months of follow-up, RD = 4.1 (95% CI: -1.0; 9.1). A significant increase in redeemed statin prescriptions was observed in the intervention group at 6 months, RD = 9.8% (CI 95%: 0.5; 19.0). There was no intervention effect observed after 12 and 60 months. TC 3 months after screening improved adherence to statin at 6-month follow-up, but had no effect on the composite treatment, statins, antithrombotic or antihypertensive treatment over 60 months of follow-up.


Enantioselective recognition of 1,2-amino alcohols by reversible formation of imines with resonance-assisted hydrogen bonds.
A chiral aldehyde with three H-bond donating groups (2) has been synthesized. This aldehyde binds a variety of chiral 1,2-amino alcohols in benzene with the same sense of stereoselectivity. Computational and experimental data indicate that one imine bond, one resonance-assisted H-bond to the imine nitrogen, and two H-bonds to the alcoholic oxygen all play an important role in the stereoselective recognition. [structure: see text]


Dynein achieves processive motion using both stochastic and coordinated stepping.
Processivity, the ability of single molecules to move continuously along a track, is a fundamental requirement of cargo-transporting molecular motors. Here, we investigate how cytoplasmic dynein, a homodimeric, microtubule-based motor, achieves processive motion. To do this, we developed a versatile method for assembling Saccharomyces cerevisiae dynein heterodimers, using complementary DNA oligonucleotides covalently linked to dynein monomers labeled with different organic fluorophores. Using two-color, single-molecule microscopy and high-precision, two-dimensional tracking, we find that dynein has a highly variable stepping pattern that is distinct from all other processive cytoskeletal motors, which use 'hand-over-hand' mechanisms. Uniquely, dynein stepping is stochastic when its two motor domains are close together. However, coordination emerges as the distance between motor domains increases, implying that a tension-based mechanism governs these steps. This plasticity may allow tuning of dynein for its diverse cellular functions.


Antagonistic effects of multi-walled carbon nanotubes and BDE-47 in zebrafish (Danio rerio): Oxidative stress, apoptosis and DNA damage.
In natural environments, organisms are often exposed to several environmental pollutants at any one time, and the potential effects of such co-exposures on human and environmental health are of considerable concern. It is thought that multi-walled carbon nanotubes (MWCNTs) may interact with other pollutants in aquatic systems and induce considerably different effects compared with exposure to a single contaminant. The objective of this study was to evaluate the potential acute combined effects of mixtures of MWCNTs and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on embryonic development stages, oxidative stress, apoptosis and DNA damage in developing zebrafish (Danio rerio). The embryos were treated with BDE-47 (5, 10, and 50 μg/L) and MWCNTs (50 mg/L), either combined or individually, for 96 h. Following exposure, BDE-47 induced significant acute toxicity, while the MWCNTs exhibited slight toxicity. When compared with BDE-47-only exposure, the inhibited growth induced by BDE-47 was weakened in the presence of MWCNTs. Similarly, the levels of oxidative stress biomarkers (reactive oxygen species, superoxide dismutase, catalase activities and malondialdehyde), apoptosis (apoptosis rate, caspase-3 and caspase-9 activities) and DNA damage (comet assay and comet olive tails) decreased in the presence of MWCNTs compared to those exposed to BDE-47 alone. These results demonstrate that MWCNTs can weaken the developmental inhibition, oxidative stress, apoptosis and DNA damage induced by BDE-47 in the early stages of zebrafish development.


p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions.
The AAA+ ATPase p97/VCP adopts at least three conformations that depend on the binding of ADP and ATP and alter the orientation of the N-terminal protein-protein interaction (PPI) domain into "up" and "down" conformations. Point mutations that cause multisystem proteinopathy 1 (MSP1) are found at the interface of the N domain and D1-ATPase domain and potentially alter the conformational preferences of p97. Additionally, binding of "adaptor" proteins to the N-domain regulates p97's catalytic activity. We propose that p97/adaptor PPIs are coupled to p97 conformational states. We evaluated the binding of nucleotides and the adaptor proteins p37 and p47 to wild-type p97 and MSP1 mutants. Notably, p47 and p37 bind 8-fold more weakly to the ADP-bound conformation of wild-type p97 compared to the ATP-bound conformation. However, MSP1 mutants lose this nucleotide-induced conformational coupling because they destabilize the ADP-bound, "down" conformation of the N-domain. Loss in conformation coupling to PPIs could contribute to the mechanism of MSP1.


Adventitial cystic disease of the femoral vein: report of a case.
Adventitial cystic disease (ACD) of the veins is a rare phenomenon, and ACD of the femoral vein is particularly difficult to diagnose due to the similarity in symptoms to those of deep vein thrombosis. We report a case of ACD of the femoral vein, which was initially misdiagnosed as deep vein thrombosis, in a 48-year-old woman who presented with a painless swelling in her right lower leg. The extensive cystic involvement of the femoral vein was completely resected and reconstructed with an 8-mm ringed polytetrafluoroethylene vascular graft with good results.


Construction of a confounder-free clinical MRI dataset in the Mass General Brigham system for classification of Alzheimer's disease.
Deep learning has the potential to standardize and automate diagnostics for complex medical imaging data, but real-world clinical images are plagued by a high degree of heterogeneity and confounding factors that may introduce imbalances and biases to such processes. To address this, we developed and applied a data matching algorithm to 467,464 clinical brain magnetic resonance imaging (MRI) data from the Mass General Brigham (MGB) healthcare system for Alzheimer's disease (AD) classification. We identified 18 technical and demographic confounding factors that can be readily distinguished by MRI or have significant correlations with AD status and isolated a training set free from these confounds. We then applied an ensemble of 3D ResNet-50 deep learning models to classify brain MRIs between groups of AD, mild cognitive impairment (MCI), and healthy controls. From a confounder-free matched dataset of 287,367 MRI files, we achieved an area under the receiver operating characteristic (AUROC) of 0.82 in distinguishing healthy controls from patients with AD or MCI. We also showed that confounding factors in heterogeneous clinical data could lead to artificial gains in model performance for disease classification, which our data matching approach could correct. This approach could accelerate using deep learning models for clinical diagnosis and find broad applications in medical image analysis.


Two drugs facing key patent expirations and potential generic entry from July to August 2020.
A challenge in anticipating generic entry is elucidating which patents and regulatory protections constrain generic entry.


Protection of mice from Bordetella pertussis respiratory infection using microencapsulated pertussis fimbriae.
Conditions have been established which allow the efficient entrapment of Bordetella pertussis fimbriae in poly(lactide-co-glycolide) microspheres. Fimbriae released from the matrix were found to have retained some degree of conformational structure, as determined by assessing the capacity of fimbrial protein to bind to antibodies mapping to either conformational or denatured structures on the fimbriae, either encapsulated in microspheres with a mean diameter of 24 microns and an estimated in vitro protein release rate of approximately 42 days, or conventionally adjuvanted with alhydrogel, elicited vigorous immune responses in mice. The encapsulated fimbriae appear to elicit marginally lower serum antibody levels than those induced by equivalent amounts of alhydrogel-adjuvanted fimbriae. Mice immunised with both preparations were, however, protected against intranasal infection with live B. pertussis as evidenced by the significant reduction in levels of bacterial colonisation observed in the lungs and tracheas of immunised animals when compared to the immunologically naive controls.


[Parallel catalytic hydrogen wave of acetylspiramycin caused by dissolved oxygen and its application].
To propose a novel polarographic method for the determination of acetylspiramycin (ASPM) is proposed. In 0.1 mol x L(-1) NH4Cl-NH3 x H2O (pH 8.9) buffer containing dissolved oxygen, ASPM yielded a sensitive parallel catalytic hydrogen wave with the peak potential of -1.63 V (vs SCE) by single sweep polarography. The 2nd order derivative peak currents (i(p)") of the parallel catalytic hydrogen waves of ASPM showed a linear relationship with its concentrations in the range from 1.74 x 10(-3) microg x mL(-1) to 3.84 microg x mL(-1) (r = 0.9979, n=13). Its detection limit was 5.80 x l0(-4) microg x mL(-1) (3sigma) and RSD (n=13) was 1.24% at the concentration level of 0.871 microg x mL(-1). The proposed method could be applied to the determination of ASPM in ASPM tablets.


Screening and isolation of the liamocin-producing yeast Aureobasidium melanogenum using xylose as the sole carbon source.
Xylose, the main component of xylan, is the second most abundant sugar in nature after glucose. Consequently, xylose represents an attractive feedstock for the production of value-added compounds such as biosurfactants (BSs), which are produced by various bacteria and yeasts. In this study, we screened and isolated yeast strains that synthesize BSs using xylose as the sole carbon source. We applied matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to screen for BS-producing yeasts and isolated eight strains as the liamocin producers. Two of the eight strains, AS37 and SK25, were identified as Aureobasidium melanogenum, which is known as black yeasts, by based on 26S ribosomal RNA gene sequences. Both strains produced a wide variety of liamocin structures from not only xylose but also glucose and sucrose. According to the MALDI-TOF MS analysis, signals corresponding to sodium ion adducts of di-, tri-, tetra-, penta- and hexa-acylated C6-liamocins and di-, tri- and tetra-acylated C5-liamocins were detected. In addition, their mono-acetylated form was also detected. The dominant sugar component of liamocins produced by strains AS37 and SK25 is mannitol as estimated by HPLC analysis. This is the first report to describe the screening of liamocins-producing yeasts using xylose as the sole carbon source.


Games and genes: human diversity meets cytogenetics-Mexico 1968.
The 1968 Olympic Games in Mexico included innovative practices and technological knowledge of human biology. The first time that cytogenetic techniques had been applied to athletes was in the 1966 European Athletics Championship in Budapest and used on Olympic athletes for the first time in Mexico in 1968. The Genetics and Human Biology Program (Programa de Genética y Biología Humanas, PGBH) was created for this purpose in 1966 in close collaboration with the Local Organizing Committee (Comité Organizador, CO), by Mexican geneticists Alfonso León de Garay and Rodolfo Félix Estrada who led the project. The main objective was to study the genetic and anthropological components which determine an Olympic athlete's abilities. This investigation studied 1,265 game participants and included family studies, cytological analyses, research on single genes, and the study of sex determination. In terms of influence beyond Mexico, this Program was significant as a site of transnational collaboration. It mobilized cognitive and financial resources, scientific practices, and material culture to set up a clinical laboratory in the Olympic Village. The Program also hosted three international seminars in Mexico City, two before the games, to calibrate clinical trials and anthropological tests. One in 1969 to analyze the results and proceed to their publication in 1974. This manuscript will focus on the PGBH to show how its work fits in the larger tapestry of post-1945 human biological studies. Also, to explore how the Olympic athlete populations studied can be considered laboratories of knowledge production or sites of cognition conceived as specific entities for scientific inquiry, standardization of medical practices, and the production or application of medicines. Finally, through the narrative of the different trajectories and collaborations of the leaders of the PGBH, this manuscript will show how contact between their scientific practices brought cytogenetics and sports together.


Physical activity status and postprandial lipaemia in older adults.
Physical activity-induced lowering of postprandial lipaemia is short-lived. However, little is known regarding the role of physical activity status on postprandial lipaemia. The purpose of the present study was to compare postprandial triacylglycerol concentrations in active and inactive older adults. A total of 26 older adults (aged 69.8±0.9 years, mean±SEM; 10 male and 16 female) were analysed in a cross-sectional design. Based on accelerometer data, participants were divided into either the active group (≥150 min/week of moderate-intensity physical activity, N=15) or the inactive group (<150 min/week of moderate-intensity physical activity, N=11). After a 48-h period of physical activity avoidance and a 10-h overnight fast, participants consumed a test meal of moderate fat content (35%). Capillary blood samples were collected in the fasted state and at 2, 4, and 6 h postprandially. After adjusting for fasting triacylglycerol concentrations, body mass, body mass index and waist circumference, postprandial capillary triacylglycerol concentrations were significantly lower in the active than inactive group ( P=0.046). These findings demonstrate that regular physical activity lowers postprandial lipaemia independent of the acute effects of physical activity in older adults.


Phacomatosis pigmentovascularis with a selective IgA deficiency.
We report a 1-year-old boy with an extensive cutaneous vascular malformation, oculocutaneous pigmentation, and severe neurologic abnormalities from birth, as well as a selective IgA deficiency. Ultrastructural study demonstrated prominent endothelial cells in the luminal of the blood vessels. The diagnosis of phacomatosis pigmentovascularis type IIb seemed appropriate for this patient.


Inferior oblique muscle recession with and without superior oblique tendon tuck for treatment of unilateral congenital superior oblique palsy.
To compare the surgical results in patients with congenital superior oblique palsy treated with inferior oblique recession (IOR) versus those treated additionally with superior oblique tendon tuck (IOR+SOT). A consecutive, nonrandomized series of patients with congenital superior oblique palsy with vertical deviations in adduction between 10° and 20° were retrospectively reviewed. In the first series, patients were treated with IOR; in the second series, patients were treated with IOR+SOT. We examined the effects of surgery on binocular alignment and on the field of binocular single vision. Each group consisted of 20 patients. Preoperative ocular deviations were similar in both groups. Postoperative residual vertical deviations were not different in the primary position or in downgaze; however, significantly better alignment was achieved in the IOR+SOT group in adduction and downgaze in adduction. Consecutive Brown pattern occurred in 18 of 20 patients who underwent IOR+SOT versus 5 of 20 who underwent IOR. Residual torsion was not statistically different. The field of binocular single vision improved to 92% (range, 28%-100%) after IOR and to 96% (range, 64%-100%) after IOR+SOT (P = 0.20). IOR alone is a suitable procedure for most congenital superior oblique palsies with a moderate-to-large vertical deviation in adduction, resulting in a lower incidence of consecutive Brown pattern than with IOR+SOT.


Cryosurgical treatment of melanin-pigmented gingiva.
Abnormal deposition of melanin in gingiva can often occur. Complaints of "black gums" are common, and demand for depigmentation is usually made for esthetic reasons. A simple and effective cryosurgical technique to eliminate the pigmentation is the subject of this article. Twenty patients with dark gingiva were treated by direct application of liquid nitrogen with a cotton swab for 20 to 30 seconds. The treated gingiva appeared normal within 1 to 2 weeks after 1 or 2 cryosurgical treatments. The acceptance of the treatment was excellent. This was a simple, bloodless cryosurgery for the depigmentation of gingiva, requiring no local anesthesia or sophisticated equipment.


Cytogenetics of benign breast lesions.
This review summarizes the cytogenetic information on benign breast lesions of various histologies, i.e., fibrocystic lesions from women with and without a known hereditary predisposition to breast cancer, fibroadenomas, phyllodes tumors, and papillomas, and relate the chromosomal features with those in breast carcinoma. In general, the frequency of chromosome abnormalities is lower in benign lesions than in breast cancer, and seems to correlate with the histologic features of the tissue, and the corresponding risk of developing invasive mammary carcinoma; aberrations are more common in proliferative than in nonproliferative lesions. The karyotypes are generally less complex than those detected in invasive carcinoma, and more often involve balanced rearrangements. No lesion-specific aberration has so far been detected; on the contrary, changes repeatedly encountered in breast cancer samples can be found in benign lesions as well, e.g., gain of 1q, interstitial deletion of 3p, and trisomies 7, 18, and 20. Especially intriguing is the prevalence of rearrangements of the short arm of chromosome 3, with the minimally deleted bands 3p13-14, in proliferative lesions from prophylactic mastectomies in breast cancer families. The potential tumor suppressor gene(s) in this region remains, however, to be identified.


Perspectives and preferences regarding genomic secondary findings in underrepresented prenatal and pediatric populations: A mixed-methods approach.
Patients undergoing clinical exome sequencing (ES) are routinely offered the option to receive secondary findings (SF). However, little is known about the views of individuals from underrepresented minority pediatric or prenatal populations regarding SF. We explored the preferences for receiving hypothetical categories of SF (H-SF) and reasons for accepting or declining actual SF through surveying (n = 149) and/or interviewing (n = 47) 190 families undergoing pediatric or prenatal ES. Underrepresented minorities made up 75% of the probands. In total, 150 families (79%) accepted SF as part of their child/fetus's ES. Most families (63%) wanted all categories of H-SF. Those who declined SF as part of ES were less likely to want H-SF across all categories. Interview findings indicate that some families did not recall their SF decision. Preparing for the future was a major motivator for accepting SF, and concerns about privacy, discrimination, and psychological effect drove decliners. A notable subset of families (37%) did not want at least 1 category of H-SF, suggesting more hesitancy about receiving all available results than previously reported. The lack of recollection of SF decisions suggests a need for alternative communication approaches. Results highlight the importance of the inclusion of diverse populations in genomic research.


High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study.
Intravenous iron sucrose is becoming a prevailing treatment for individuals undergoing maintenance haemodialysis, but comparisons of dosing regimens are lacking. The aim of this retrospective review was to evaluate the safety and efficacy of proactively administered high-dose iron sucrose versus reactively administered low-dose iron sucrose in patients undergoing maintenance haemodialysis. We analysed the data of 1500 individuals with maintenance haemodialysis who were treated with either high-dose iron sucrose that was proactively administered (Group HD) or low-dose iron sucrose that was reactively administered (Group LD) at the First Affiliated Hospital of Chongqing Medical University from Jan 1, 2008, to Dec 31, 2020. The primary endpoints were the cumulative doses of iron and erythropoiesis-stimulating agent; the secondary endpoints were the events of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, infection rate, and death from any cause. Of the 2124 individuals, 624 individuals were excluded because they met one or more of the exclusion criteria, thus resulting in 1500 individuals who were eligible for inclusion in the study (Group HD, n = 760 and Group LD, n = 740). The median follow-up for the two cohorts was 32 months (range: 25-36). A significant median difference was detected in the monthly iron dose between the groups (1121 mg [range: 800-1274] in the HD group vs. 366 mg [range: 310-690] in the LD group; p < 0.05). The median dose of an erythropoiesis-stimulating agent was 26,323 IU/month (range: 17,596-44,712) in the HD group and 37,934 IU/month (range: 22,402-59,380) in the LD group (median difference: - 7901 IU/month; 95% CI: - 9632--5013; p = 0.000). A significant difference was detected in the secondary endpoints (266 events in 320 cases in the HD group vs. 344 events in 385 cases in the LD group) (HR: 0.62; 95% CI: 0.51-0.79; p < 0.001). A significant difference was not observed in death from any cause (HR: 0.57; 95% CI: 0.48-1.00; p = 0.361). For individuals undergoing maintenance haemodialysis, high-dose iron sucrose that was proactively administered may be superior to low-dose iron sucrose that was reactively administered with low doses of erythropoiesis-stimulating agent.


Predicative factors and development of a nomogram for postoperative delayed neurocognitive recovery in elderly patients with gastric cancer.
Delayed neurocognitive recovery (DNR) is a common complication after radical gastrectomy and closely associated with poor outcomes. This study aimed to investigate predictors and develop a nomogram prediction model for DNR. Elderly gastric cancer (GC) patients (≥ 65 years) undergoing elective laparoscopic radical gastrectomy between 2018 and 2022 were prospectively included in this study. DNR was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V, 2013). Independent risk factors for DNR were screened by the multivariate logistic regression analysis. Based on these factors, the nomogram model was established and validated by R. A total of 312 elderly GC patients were enrolled in the training set, with an incidence of DNR within postoperative 1 month of 23.4% (73/312). Multivariate logistic regression analysis indicated that age (OR: 1.207, 95%CI: 1.113-1.309, P < 0.001), nutritional risk screening 2002 (NRS2002) score (OR: 1.716, 95%CI: 1.211-2.433, P = 0.002), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.976, 95%CI: 1.099-3.552, P = 0.023), albumin-to-fibrinogen ratio (AFR) (OR: 0.774, 95%CI: 0.620-0.966, P = 0.024), and prognostic nutritional index (PNI) (OR: 0.768, 95%CI: 0.706-0.835, P < 0.001) were five independent factors for DNR in elderly GC patients. The constructed nomogram model based on these five factors has a good predictive value for DNR with an area under the curve (AUC) of 0.863. In conclusions, the established nomogram model based on age, NRS-2002, NLR, AFR, and PNI has a well predictive value for postoperative DNR in elderly GC patients.


The effect of iron plaque on lead translocation in soil-Carex cinerascens kukenth. system.
A pot experiment was conducted to investigate the effect of iron plaque on Pb uptake by and translocation in Carex cinerascens Kukenth. grown under open-air conditions. Using Scanning Electron Microscopy and Energy Dispersive X-Ray Spectrometry, iron plaque was present as an amorphous coating on root surfaces with uneven distribution. The amount of iron plaque increased significantly with increasing Fe additions regardless of Pb additions. The presence of iron plaque on the root surface of Carex cinerascens Kukenth. increased the concentrations of Pb adsorbed by iron plaque. The Pb percentage in whole roots increased by 14.52% at 500 mg kg(-1) Fe treatment than at 0 mg kg(-1) Fe, and the distribution coefficient (DC) of Pb and translocation factor (TF) root increased with Fe additions, but translocation factor (TF) shoot decreased with Fe additions. The results suggested that iron plaque could promote the translocation of Pb from soil to roots to some extent, and it played a role to reduce heavy metals pollution of Poyang Lake wetland.


Purification of Low-Concentration Carbonyl Sulfide by Red Mud-Based Adsorbent.
Bauxite residue, also known as red mud (RM), is a kind of industrial solid waste with high alkali content, complex composition and difficult utilization. In this study, a new type of RM-based adsorbent was prepared by using polyethylene glycol modified RM and was used to remove low concentration of COS in flue gas. The optimum preparation conditions of adsorbent and the optimum technological parameters of COS adsorption purification were investigated. Under the optimal conditions, the adsorption efficiency of the new adsorbent exceeds 95%, and the COS adsorption capacity reaches 63.56 mg/m3. The characterization results showed that the main active components of the adsorbent were active alkali, FeOOH and Fe3O4, and the main products were Na2S2O3, Na2SO4, FeS and FeS2.


Impact of deep freezing on the stability of 25 mg/ml vancomycin ophthalmic solutions.
For the treatment of certain eye infections, ophthalmic solutions 'laced' with 25 mg/ml vancomycin are sometimes prepared. Their physical and chemical stability and the maintenance of their sterility were studied after deep freezing at -20 +/- 2 degrees C and thawing, followed or not by refrigeration for 48 h at 4 +/- 2 degrees C. Physical and chemical analysis comprised visual inspection turbidity, determination of pH and osmolality, and assay of vancomycin by high performance liquid chromatography with ultraviolet detection. For microbiological analysis a 25 mg/ml vancomycin ophthalmic solution was filtered through two membranes and cultured on trypticase-soy and Sabouraud-glucose solid media. Any colonies were then counted. These physical, chemical and microbiological analyses demonstrated the stability of 25 mg/ml vancomycin ophthalmic solutions in 5% glucose deep frozen at -20 +/- 2 degrees C for 3 months. The vancomycin concentration varied by no more than 5% of the initial concentration, and no breakdown product was evidenced. Neither pH (mean=3.8 +/- 0.1) nor osmolality (mean=318.3 +/- 5.6 mOsm/kg) varied significantly, and remained compatible with intraocular administration. No particle or bacterial combination was found in the course of the study. The thawing procedure (at ambient temperature or under warm running water from a tap) did not modify the stability of the eye drops. Likewise, storage in a refrigerator for 48 h after thawing did not modify stability. The advantage of storing vancomycin 25 mg/ml ophthalmic solutions for 3 months in deep freeze is that a stock of chemically and microbiologically controlled preparations can be held ready for administration to patients, thereby allowing prompter dispensing, as the eye drops are not made up extemporaneously, while the improved control over production ensures that patients receive solutions of constant quality, as every batch prepared is systematically inspected.


Optimizing transcranial ultrasound delivery at large incident angles by leveraging cranial leaky guided wave dispersion.
We investigate the role of leaky guided waves in transcranial ultrasound transmission in temporal and parietal bones at large incidence angles. Our numerical and experimental results show that the dispersion characteristics of the fundamental leaky guided wave mode with longitudinal polarization can be leveraged to estimate the critical angle above which efficient shear mode conversion takes place, and below which major transmission drops can be expected. Simulations that employ a numerical propagator matrix and a Semi-Analytical approach establish the transcranial dispersion characteristics and transmission coefficients at different incident angles. Experimental transmission tests conducted at 500 kHz and radiation tests performed in the 200-800 kHz range confirm the numerical findings in terms of transmitted peak pressure and frequency-radiation angle spectra, based on which the connection between critical angles, dispersion and transmission is demonstrated. Our results support the identification of transcranial ultrasound strategies that leverage shear mode conversion, which is less sensitive to phase aberrations compared to normal incidence ultrasound. These findings can also enable higher transmission rates in cranial bones with low porosity by leveraging dispersion information extracted through signal processing, without requiring measurement of geometric and mechanical properties of the cranial bone.


Photoswitchable protein degradation: a generalizable control module for cellular function?
In this issue of Chemistry & Biology, Renicke et al. report a photosensitive degron (psd) consisting of the LOV2 domain fused to a protein degradation sequence. This design enabled light-dependent protein degradation in yeast. When psd was fused to cell-cycle-dependent proteins, it controlled cell cycle by light with spatiotemporal precision.


A decision tree approach for the application of drug metabolism and kinetic studies to in vivo and in vitro toxicological and pharmacological testing.
The integration of toxicological and other biological findings with information on drug metabolism and pharmacokinetics is often very important for rational decision making in safety evaluation programmes. This goal is unlikely to be achieved by conducting a routine package of inflexibly defined drug metabolism and pharmacokinetic test protocols for each new chemical. Rather, an intelligent selection of experiments based on the known properties of a chemical is required. A series of decision trees are proposed which serve as an aide memoire in the choice of appropriate drug metabolism and pharmacokinetic experiments. These decision trees cover the physicochemical properties of a chemical, data on animal and human pharmacology and toxicology, and environmental information relevant to possible contamination. In many cases, drug metabolism and pharmacokinetic factors are an important prerequisite to the design of in vitro tests that are relevant to the in vivo situation. A scheme is provided to assist the identification of appropriate conditions for the in vitro testing of individual chemicals.


Characterization of a sequence (hlyR) which enhances synthesis and secretion of hemolysin in Escherichia coli.
A sequence (hlyR) of about 600 bp which enhances the expression of hemolysin (HlyA) more than 50-fold was identified in the plasmid pHly152-specific hemolysin (hly) determinant. Deletion of this entire hlyR sequence led to the same low level of hemolysin synthesis and excretion as that expressed by the recombinant plasmid pANN202-312. HlyR was active in cis but its activity was orientation-dependent. The enhancing sequence, hlyR, is separated from the promoter phlyI transcribing hlyC, hlyA and possibly hlyB by more than 1.5 kb including an IS2 element. Stepwise removal of the hlyR sequence from its 5' end by exonuclease III (ExoIII) digestion yielded several types of deletion mutants which expressed decreasing amounts of hemolysin. A similar observation was made when hlyR was shortened by ExoIII from its 3' end, which suggests that more than one functional region may be present in the hlyR sequence. A deletion of 717 bp within the adjacent IS2 element reduced the activity of hlyR only slightly, indicating that IS2 is not directly involved in the enhancement mechanism but that it may support an optimal positioning in hlyR relative to the hly promoter. The nucleotide sequence of hlyR is rich in A + T and does not contain an extended open reading frame, but exhibits several sequence motives that may represent sites for protein binding and DNA bending.


Isolation of three new naturally occurring compounds from the culture of Micromonospora sp. P1068.
Bioassay guided isolation of an antibacterial extract prepared from the fermentation broth of a Micromonospora sp. P1068 led to the isolation of eight compounds identified as (3R) 3,4',7-trihydroxy-isoflavanone (1), 3-hydroxydehydrodaidzein, daidzein (2), 3-methyl-1H-indole-2-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), 3-(p-hydroxyphenyl)-N-methylpropionamide, N-methylphloretamide (5), phenyl acetic acid (6), 2-hydroxy phenyl acetic acid (7) and 4-hydroxy-5-methoxy-benzoic acid (8). Compounds 1 and 5 were found to be novel chemical entities while 3 was isolated from a natural source for the first time. All compounds were evaluated for their antimicrobial activities against a panel of clinically significant microorganisms. Compound 4 was active against Staphylococcus aureus (MIC, 32 microg/ml), Enterococcus faecium (MIC, 32 microg/ml) and Escherichia coli (MIC, 64 microg/ml).


Evaluation of right ventricular performance and impact of continuous positive airway pressure therapy in patients with obstructive sleep apnea living at high altitude.
Obstructive sleep apnea syndrome (OSAS) can lead to alterations in right ventricular (RV) performance and pulmonary vascular haemodynamics. Additionally, altitude-related hypoxia is associated with pulmonary vasoconstriction, and the effect of high-altitude on the pulmonary circulation in OSAS patients can be further altered. We sought to assess alterations in RV morphology and function in OSAS patients living at high altitude by way of 2-dimensional speckle tracking echocardiography (2D-STE), real-time 3- dimensional echocardiography (RT-3DE) and cardiac biomarkers. We also evaluate the impact of continuous positive airway pressure (CPAP) treatment on RV performance. Seventy-one patients with newly diagnosed OSAS and thirty-one controls were included in this study. All individuals were assessed for cardiac biomarkers as well as underwent 2D-STE and RT-3DE. Forty-five OSAS patients underwent CPAP therapy for at least 24 weeks and were studied before and after CPAP treatment. RT-3DE was used to measure RV volume, and calculate RV 3D ejection fraction (3D RVEF). Peak systolic strain was determined. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide, and cardiac troponin T were also measured. Right atrium volume index, RV volume, RV volume index, systolic pulmonary artery pressure (sPAP), pulmonary vascular resistance (PVR) and level of serum CRP were significantly higher in OSAS group, while OSAS patients showed lower 3D RVEF and RV longitudinal strains. Compared to the patients with sPAP < 40 mmHg, RV longitudinal strains in patients with sPAP ≥ 40 mmHg were lower. Both RV global longitudinal strain and sPAP were associated with apnea-hypopnea index. Patients treated with 6 months of CPAP therapy had significant improvement in RV geometry and performance. RV structural abnormalities and RV function impairments were observed in OSAS patients living at moderate high altitude compared to control highlanders. The reversibility of these changes after application of CPAP were further confirmed.


Visuospatial dysgnosia.
Spatial dysgnosia may occur in patients with various forms of brain disease, including tumors, vascular accidents, Alzheimer's disease, multiple sclerosis, and developmental aberrations. Patients with lesion in the nondominant hemisphere, particularly at the junction of the occipito-temporoparietal regions, may manifest predominantly visuospatial dysgnosia--a loss of the sense of "whereness" in the relation of himself to his environment and in the relation of objects to each other. Visuospatial disturbances caused by lesions in the dominant hemisphere may be masked by other gnostic symptoms. Patients with more extensive lesions, especially those involving similar areas in both hemispheres, may also exhibit other cognitive disturbances associated with vision.


Future directions for antifolate drug development.
We have discussed potential ways by which new antifolates could be designed and utilized to effect both sensitive and resistant cell/tumor inhibition. Targeting of alternative folate-dependent enzymes and increasing net intracellular accumulation (transport) and polyglutamation of antifolates should be useful approaches. In addition, antibodies to and cloned cDNAs of the transport components (e.g., folate transport proteins) will allow better characterization and understanding of de novo and acquired antifolate resistance states and may provide insights into new drug development.


Mucus-producing adenopapillary carcinoma of the oral cavity.
Mucus-producing adenopapillary carcinoma is a rare neoplasm of the oral cavity. The literature is reviewed and a case described, with histological and ultrastructural findings of a tumour which involved the upper lip and recurred following local excision.


Fine motor, sensory and perceptive function of students with attention deficit disorder with hyperactivity.
To characterize and compare the fine motor, sensory and perceptive functions of students with Attention Deficit Disorder with Hyperactivity (ADHD) and students with good academic performance, without behavior alteration. Participants were 22 male students from Elementary School distributed into: GI - 11 children with ADHD; and GII - 11 students with good academic performance and no behavior alteration. Students were submitted to the Protocol for Evaluation of Fine Motor, Sensory and Perceptual Function, and to the Dysgraphia Scale. There were differences between GI and GII in tasks concerning fine motor function, sensory function, and perceptual function, with lower performance from GI. All students in GI presented dysgraphia. Students with Attention Deficit Disorder with Hyperactivity present lower performance regarding fine motor, sensory and perception functions in relation to students with good academic performance. These difficulties can cause significant impact on academic performance, impairing the development of written language and causing dysgraphia in these students.


Artificially decreased vapour pressure deficit in field conditions modifies foliar metabolite profiles in birch and aspen.
Relative air humidity (RH) is expected to increase in northern Europe due to climate change. Increasing RH reduces the difference of water vapour pressure deficit (VPD) between the leaf and the atmosphere, and affects the gas exchange of plants. Little is known about the effects of decreased VPD on plant metabolism, especially under field conditions. This study was conducted to determine the effects of artificially decreased VPD on silver birch (Betula pendula Roth.) and hybrid aspen (Populus tremula L.×P. tremuloides Michx.) foliar metabolite and nutrient profiles in a unique free air humidity manipulation (FAHM) field experiment during the fourth season of humidity manipulation, in 2011. Long-term exposure to decreased VPD modified nutrient homeostasis in tree leaves, as demonstrated by a lower N concentration and N:P ratio in aspen leaves, and higher Na concentration and lower K:Na ratio in the leaves of both species in decreased VPD than in ambient VPD. Decreased VPD caused a shift in foliar metabolite profiles of both species, affecting primary and secondary metabolites. Metabolic adjustment to decreased VPD included elevated levels of starch and heptulose sugars, sorbitol, hemiterpenoid and phenolic glycosides, and α-tocopherol. High levels of carbon reserves, phenolic compounds, and antioxidants under decreased VPD may modify plant resistance to environmental stresses emerging under changing climate.


Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene.
Leopard, a well-known zebrafish mutant that has a spotted skin pattern instead of stripes, is a model for the study of pigment patterning. To understand the mechanisms underlying stripe formation, as well as the spot variation observed in leopard, we sought to identify the gene responsible for this phenotype. Using positional cloning, we identified the leopard gene as an orthologue of the mammalian connexin 40 gene. A variety of different leopard alleles, such as leo(t1), leo(tq270) and leo(tw28), show different skin-pattern phenotypes. In this manuscript we show that the mutation in allele leo(t1) is a nonsense mutation, whereas alleles leo(tq270) and leo(tw28) contain the missense mutations I202F and I31F, respectively. Patch-clamp experiments of connexin hemichannels demonstrated that the I202F substitution in allele leo(tq270) disrupted the channel function of connexin41.8. These results demonstrate that mutations in this gene lead to a variety of leopard spot patterns.


Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis.
To investigate whether digital activity fluorescence optical imaging (FOI) patterns of inflammation can identify distinct rheumatoid arthritis (RA) phenotypes. The hands of newly diagnosed patients with RA were evaluated by clinical examination, musculoskeletal ultrasound, and FOI. Inflammation on FOI was defined when capillary leakage and/or fluorophore perfusion was present. The FOI composite image was quantified into a digital disease activity (DACT) score, using novel computerized algorithms. Unsupervised clustering on FOI inflammatory patterns was used to identify subgroups of patients relative to anticyclic citrullinated peptides (ACPA) and/or rheumatoid factor (RF). Of 1326 examined hand joints in 39 patients with RA (72% female; 56% ever-smokers; 54% RF positive and 69% ACPA positive), 400 (30%) showed inflammation by FOI, and 95% (37 of 39) of patients had DACT-FOI scores greater than 1. Unsupervised analysis on FOI patterns revealed two patient clusters, cluster 1 (n = 29) and cluster 2 (n = 10). The proportion of seropositive patients was significantly higher in cluster 1 versus cluster 2 (90%, 26 of 29 vs. 30%, 3 of 10; P < 0.01), whereas C-reactive-protein levels (minimum-maximum) were significantly higher in cluster 2 (20 mg/l [1-102]) versus cluster 1 (2 mg/l [0-119]; P = 0.01). A wider variety and proportion of inflamed joints emerged for patients with RA in cluster 2 versus cluster 1, in which inflammation was more concentrated around the wrists and the right metacarpophalangeal 2 (MCP2), bilateral MCP3, and, to a lesser degree, left MCP2 and proximal interphalangeal joint and tendon regions. Cluster 1 displayed lower mean (±SD) DACT scores compared with cluster 2 (3.6 ± 2.1 vs. 5.4 ± 2.1; P = 0.03). FOI-based digital quantification of hand joint inflammation revealed two distinct RA subpopulations with and without ACPA and RF related autoantibodies.


Bilateral temporal lobe epilepsy: How many seizures are required in chronic ambulatory electrocorticography to estimate the laterality ratio?
This study was undertaken to measure the duration of chronic electrocorticography (ECoG) needed to attain stable estimates of the seizure laterality ratio in patients with drug-resistant bilateral temporal lobe epilepsy (BTLE). We studied 13 patients with drug-resistant BTLE who were implanted for at least 1 year with a responsive neurostimulation device (RNS System) that provides chronic ambulatory ECoG. Bootstrap analysis and nonlinear regression were applied to model the relationship between chronic ECoG duration and the probability of capturing at least one seizure. Laterality of electrographic seizures in chronic ECoG was compared with the seizure laterality ratio from Phase 1 scalp video-electroencephalographic (vEEG) monitoring. The Kaplan-Meier estimator was used to evaluate time to seizure laterality ratio convergence. Seizure laterality ratios from Phase 1 scalp vEEG monitoring correlated poorly with those from RNS chronic ECoG (r = .31, p = .30). Across the 13 patients, average electrographic seizure frequencies ranged from 1.4 seizures/month to 5.1 seizures/day. A 50% probability of recording at least one electrographic seizure required 9.1 days of chronic ECoG, and 90% probability required 44.3 days of chronic ECoG. A median recording duration of 150.9 days (5 months), corresponding to a median of 16 seizures, was needed before confidence intervals for the seizure laterality ratio reliably contained the long-term value. The median recording duration before the point estimate of the seizure laterality ratio converged to a stationary value was 236.8 days (7.9 months). RNS chronic ECoG overcomes temporal sampling limitations intrinsic to inpatient Phase 1 vEEG evaluations. In patients with drug-resistant BTLE, approximately 8 months of chronic RNS ECoG are needed to precisely estimate the seizure laterality ratio, with 75% of people with BTLE achieving convergence after 1 year of RNS recording. For individuals who are candidates for unilateral resection based on seizure laterality, optimized recording duration may help avert morbidity associated with delay to definitive treatment.


Comparison of office hysteroscopy, transvaginal ultrasonography and endometrial biopsy in evaluation of abnormal uterine bleeding.
A comparison between office hysteroscopy, transvaginal ultrasonography and endometrial biopsy was performed, in terms of detection of intrauterine lesions. A secondary objective was assessment of evaluatory approach in the management of abnormal uterine bleeding in an outpatient setting. Prospective observational study. A total of 54 women were evaluated for abnormal uterine bleeding. Assessment included performance of an endometrial biopsy, a transvaginal ultrasound scan followed by office hysteroscopy. Results of hysteroscopy were taken as the gold standard. Sensitivity and specificity of the investigations were assessed. The bleeding pattern was classified as heavy regular, irregular, postmenopausal and heavy or unscheduled bleeding on hormone replacement therapy. The incidence of focal intrauterine lesions in patients presenting with abnormal bleeding was 52% for all ages and 31% for the postmenopausal group. Seventy-five percent of the patients with Hb < 11 gm% and 67% with an enlarged uterus harbored a focal pathology. The incidence of lesions in patients with heavy regular bleeding was 74%. The sensitivity and specificity of transvaginal ultrasound when compared with results of hysteroscopy was 0.60 and 0.88 respectively. A normal endometrial biopsy had a negative predictive value of 51%. The sensitivity and specificity of endometrial biopsy were 0.04 and 0.83, respectively. Both transvaginal ultrasound and endometrial biopsy exhibited poor sensitivity for detection of focal intrauterine lesions. Considering the significantly high incidence of intrauterine lesions in patients presenting with abnormal bleeding, the most cost-effective approach appears to be proceeding with hysteroscopy early in assessment.


Ghrelin receptor antagonism of fentanyl-induced conditioned place preference, intravenous self-administration, and dopamine release in the nucleus accumbens in rats.
The extended occurrence of fentanils abuse associated with the dramatic increase in opioid fatal overdoses and dependence strongly emphasizes insufficiencies in opioid addiction treatment. Recently, the growth hormone secretagogue receptor (GHS-R1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in opioid abuse is still unclear. Therefore, the aim of our study was to clarify whether the GHS-R1A antagonist JMV2959 could reduce the fentanyl-induced conditioned place preference (CPP), the fentanyl intravenous self-administration (IVSA), and the tendency to relapse, but also whether JMV2959 could significantly influence the fentanyl-induced dopamine efflux in the nucleus accumbens (NAC) in rats, that importantly participates in opioids' reinforcing effects. Following an ongoing fentanyl self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 minutes before three consequent daily 360-minute IVSA sessions under a fixed ratio FR1, which significantly reduced the number of active lever-pressing, the number of infusions, and the fentanyl intake. Pretreatment with JMV2959 also reduced the fentanyl-seeking/relapse-like behaviour tested in rats on the 12th day of the forced abstinence period. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of fentanyl-CPP. The fentanyl-CPP development was reduced after the simultaneous administration of JMV2959 with fentanyl during conditioning. The JMV2959 significantly reduced the accumbens dopamine release induced by subcutaneous and intravenous fentanyl. Simultaneously, it affected the concentration of byproducts associated with dopamine metabolism in the NAC. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of fentanyl.


[Hygienic requirements for the architectural-functional design of intensive care units (author's transl)].
Three standard variants of intensive care units are described. The hygienic-microbiological examinations of the patients' surrounding show in how fat architectural factors influence the propagation of germs responsible for nosocomial infections. The results are hygienic requirements concerning the architectural functional structure of intensive care units to facilitate the maintenance of anti- and asepsis for the nursing personal.


The cell secretome, a mediator of cell-to-cell communication.
We are witnessing the emergence of a novel type of biological regulation, namely, the communication between cells via their secreted substances, the secretome. This brief overview is based on the available published data and our own experience. We discuss three vignettes illustrating the importance of communication via the secretome: (1) the secretome of stem cells and its effects in sepsis and systemic inflammatory response; (2) the profibrotic secretomes partially responsible for development of fibrotic complications; and (3) the contribution of senescence-associated secretory products to the propagation of the senescence phenotype. Considering the richness of secretomes of different cells under diverse conditions, it becomes imperative to gain insights into their individual components in an attempt to harness cell secretomes for therapeutic purposes.


Photochemotherapy of animal tumors with the photosensitizer methylene blue using a krypton laser.
The cytotoxic effect of the photosensitizer Methylene Blue activated with long wavelength laser radiation has been investigated using mice with solid Ehrlich carcinomas. A krypton laser was used as a light source emitting laser radiation at 647 nm and 676 nm. The red spectral range is important for photochemotherapy because it is easily transmitted through tissue. A significant tumor reduction, including complete tumor destruction, has been achieved.


Effects of a new TRH analogue, YM-14673, on disturbance of passive avoidance learning in senescence-accelerated mice.
Effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on disturbance of passive avoidance behavior were observed in senescence-accelerated mice (SAM). Latency of step-through in SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) was significantly shorter than that in SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain). Successive oral administration of YM-14673 (1 and 10 mg/kg) and TRH (10 mg/kg) for 3 weeks prolonged the shortened latency of step-through. These results suggest that YM-14673 is more potent than TRH in antiamnesic activities.


Land Premium Effects of Urban Rail Transit and the Associated Policy Insights for TOD: A Case of Ningbo, China.
With considerable investments, mainly from local government budgets, the construction and operation of urban rail transit (URT) can exert significant spillover effects on the surrounding land use and land prices. In particular, China's local governments are actively committed to developing their URT systems and promoting large-scale transit-oriented development (TOD) projects under the public land leasing policy. However, the connection between the land premium effects and TOD policy and practice is still lacking, particularly in the local government contexts, which exhibit significant policy and spatial heterogeneity. Thus, this research represents an attempt to better address this issue using the city of Ningbo as a case study. First, the premium effects of URT on land prices are examined, after which three crucial policy insights (land value capture [LVC], public-private cooperation [PPC], and urban regeneration) are proposed to enhance the effectiveness and efficiency of TOD, demonstrating its strong connection with the potential premium effects. The findings demonstrate that (1) local governments have adopted different innovative policies-with the ambition-to implement LVC; (2) assisted by PPC, the local rail transit authority can significantly amplify the premium effects, although it must still address the fair distribution of premiums across multiple stakeholders; and (3) transit-oriented urban regeneration can significantly influence land prices/land rents and subsequently generate significant gentrification, which will be further addressed by the TOD policy and practice.


A neonate with anorectal malformation with rare limb defects report of a case.
A 2-day-old male infant, born of a non-consanguineous marriage and uneventful pregnancy was found to have anomalies of vertebral, anal, cardiac, tracheo-esophageal, radial and limb (VACTERL) association. The striking feature was the simultaneous occurrence of two rare limb defects of right upper and lower limb in the baby who also had imperforate anus and ventricular septal defect. These limb defects were-meromelia of the right upper limb (due to transverse deficiency of right humerus and absence of all the bony elements distally), and a short right lower limb due to co-existence of proximal femoral hypoplasia and fibular hemimelia. We could not trace the co-existence of these rare skeletal defects in any case with VACTERL association in the existing English literature, as was observed by us. The simultaneous occurrence of the defects involving distant anatomic sites supports the hypothesis of 'axial mesodermal dysplasia' in our patient, rather than 'caudal regression syndrome', as is popularly held in patients with anorectal malformation (ARM). Further, it points to occurrence of an early embryonic insult, probably taking place at blastogenic stage, when the developing embryo can be considered a polytopic development field. However, in absence of antenatal history suggestive of exposure to a known teratogen and a chromosomal analysis, it appears that the spectrum of anomalies in this neonate might have resulted secondary to early amniotic leak and temporary oligohydramnios.


The pathology of scleroderma vascular disease.
Systemic sclerosis is characterized by three distinct pathologic processes: fibrosis, cellular/humoral autoimmunity, and specific vascular changes. Although a mild vasculitis may sometimes be present, the vascular pathology of scleroderma is not necessarily inflammatory and is best characterized as a vasculopathy. In this article, the authors propose that SSc vasculopathy is the result of an early event involving vascular injury that eventuates in a vicious cycle mediated in part by the immune process. The subsequent vascular malformation and rarefaction may be a function of systemic angiogenic dysregulation, with over expression of vascular endothelial growth factor but a lack of proper interactions with smooth muscle cells needed to stabilize and organize blood vessels.


Submacular surgery for choroidal neovascularization secondary to optic nerve drusen.
To report a case of bilateral choroidal neovascularization (CNV) secondary to optic nerve drusen (OND). Interventional case report. A 9-year-old girl presented with peripapillary CNV of the right eye and peripapillary and subfoveal CNV of the left eye secondary to OND. The CNV was excised with submacular surgery in the left eye. Visual acuity increased from 0.05 to 0.3 in the left eye after submacular surgery and did not change from 0.3 in the right eye during 6-month follow-up. Partial retinal pigment epithelial atrophy, but no recurrence of CNV, was observed after CNV excision. Subfoveal CNV is an uncommon complication of OND and surgical excision may be useful in selected cases.


Early intravesical instillation of adriamycin with oral administration of 5-fluorouracil after transurethral resection for superficial bladder cancer: preliminary results.
In all, 199 patients were entered in this study by 21 collaborating hospitals. Patients with superficial transitional cell carcinoma of the bladder were randomized postoperatively into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of adriamycin (30 mg/30 mg); group B received early instillation of adriamycin with oral administration of 5-fluorouracil (200 mg/day); group C received delayed (7 days after transurethral resection) instillation of adriamycin (30 mg/30 ml); and group D received delayed instillation of adriamycin with oral administration of 5-fluorouracil (200 mg/day). All patients subsequently received instillations weekly for 2 more weeks, and then every 2 weeks for a further 14 weeks. After 4 months, they received one instillation per month for 8 months. 5-Fluorouracil was administered p.o. for 1 year. The postoperative follow-up period was 12 months. After 3 and 6 months there were significant differences in the non-recurrence rates between groups B and C. After 12 months the overall non-recurrence rates were 87.9% in group A, 83.5% in group B, 89.2% in group C, and 82.8% in group D, and there were no significant differences among the four groups. The number of patients entered and the follow-up period are not adequate for firm conclusions, and further studies are necessary. The main side effect was bladder irritation, which was observed in 38.8% of patients in the early instillation groups and in 26.3% of those in the delayed instillation groups. No severe systemic side effects were observed in this study.


New observations on the fine structure of the normal nasopharyngeal epithelium of the mouse.
The ciliated columnar epithelium in the mouse nasopharynx was studied by use of light and electron microscopes. The ciliated cells were divided into 3 types because of the variability in electron density of the ground cytoplasm. The dark ciliated cells were characterized by well-developed rough endoplasmic reticulum and rod-shaped mitochondria with regular arrangements of pronounced cristae. In the light ciliated cells endoplasmic reticulum was poorly developed and mitochondria were vacuolated with irregular arrangements of cristae. Furthermore, there existed the "medium ciliated cells," termed by the authors, of which the cytoplasm was medium in electron density between the dark and the light ciliated cells, and some mitochondria were rod-shaped and others were vacuolated. The medium ciliated cells are regarded to be at a stage of transformation from the dark ciliated cells to the light ones. These findings suggest that the dark ciliated cells swell to decrease their electron density with declining activity, and finally transform into the light ciliated cells. The cells, termed the "potential ciliated cells" by the authors, were scattered between the ciliated cells, reached the lumen and had no cilia. They contained many procentrioles suggesting ciliogenesis and had a cytoplasm of the same electron density as that of the dark ciliated cells. It is considered that the dark ciliated cells originate from the potential ciliated cells.


Hydroxysafflor yellow A improves learning and memory in a rat model of vascular dementia by increasing VEGF and NR1 in the hippocampus.
Hydroxysafflor yellow A (HSYA) has angiogenesis-regulating and neuro-protective effects, but its effects on vascular dementia (VaD) are unknown. In this study, 30 adult Sprague-Dawley rats were randomly allocated to five groups: normal, sham-operation, VaD alone (bilateral carotid artery occlusion), VaD plus saline (control), and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation (LTP) method. Vascular endothelial growth factor (VEGF) and N-methyl-Daspartic acid receptor 1 (NR1) expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze (P < 0.05), and the LTP at CA3-CA1 synapses in the hippocampus was enhanced (P < 0.05). Western blot in the late-phase VaD group showed slight up-regulation of VEGF and downregulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NR1. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.


An updated and comprehensive review of the antiviral potential of essential oils and their chemical constituents with special focus on their mechanism of action against various influenza and coronaviruses.
Essential oils and their chemical constituents have been reported with well documented antimicrobial effects against a range of bacterial, fungal and viral pathogens. By definition, essential oils are a complex mixture of volatile organic compounds which are synthesized naturally in different parts of the plant as part of plants secondary metabolism. The chemical composition of the essential oils is dominated by the presence of a range of compounds including phenolics, terpenoids, aldehydes, ketones, ethers, epoxides and many others inferring that essential oils must be effective against a wide range of pathogens. This review article mainly focuses on the antiviral potential of essential oils and their chemical constituents especially against influenza and coronaviruses. Essential oils have been screened against several pathogenic viruses, including influenza and other respiratory viral infections. The essential oils of cinnamon, bergamot, lemongrass, thyme, lavender have been reported to exert potent antiviral effects against influenza type A virus. The essential oil of Citrus reshni leaves has been shown to be effective against H5N1 virus. The essential oil of Lippia species at a concentration of 11.1 μg/mL has been shown to induce 100% inhibition of yellow fever virus in Vero cells. Essential oils and oleoresins have been shown through in vitro and in vivo experiments to induce antiviral effects against Coronavirus infectious bronchitis virus. A study reported 221 phytochemical compounds and essential oils to be effective against severe acute respiratory syndrome associated coronavirus (SARS-CoV) using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. The main mechanism of antiviral effects of essential oils has been found to cause capsid disintegration and viral expansion which prevents the virus to infect host cells by adsorption via the capsid. Essential oils also inhibit hemagglutinin (an important membrane protein of various viruses) of certain viruses; this membrane protein allows the virus to enter the host cell. Many essential oils and their components could inhibit the late stages of viral life cycle by targeting the redox signalling pathway. Essential oils of Thymus vulgaris, cymbopogon citratus and Rosmarinus officinalis have been found to destabilize the Tat/TAR-RNA complex of HIV-1 virus, this complex being essential for HIV-1 replication. Being lipophilic in nature, essential oils can penetrate viral membranes easily leading to membrane disintegration. The current comprehensive review will facilitate researchers to find chemical entities from plant sources as possible inhibitory agents against various viruses.


Responses of mice immunized with a DNA vaccine encoding carcinoembryonic antigen (CEA).
C57BL/6 and BALB/c mice were immunized with two different plasmids (p91023B and pKCEA66) encoding different forms of the tumor-associated antigen carcinoembryonic antigen (CEA). The wild type form of CEA (p91023B), which is expressed at the cell surface, induces stronger anti-CEA IgG response after DNA-plasmid immunizations than the modified intracellular form of CEA (pKCEA66), which was designed to mount strong cellular responses. Boosting with recombinant CEA (rCEA) increased the anti-CEA IgG response significantly. In the tumor protection model used, where SCID mice are challenged with human tumor cells mixed with splenocytes from immunized mice, both innate and specific immune responses are responsible for the protective effect.


An association between kidney stone composition and urinary metabolic disturbances in children.
To determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors. We studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate. Calcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors. Calciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.