Burden of respiratory disease attributable to secondhand smoke exposure at home in children in Spain (2015).
This study aimed to estimate the number of incident cases and hospital admissions attributable to secondhand smoke (SHS) exposure at home for asthma, otitis media (OM), and lower respiratory infections (LRI) in children in Spain. The burden of respiratory disease caused by SHS exposure was estimated in terms of incident cases and hospitalized cases for asthma, OM, and LRI. Estimates were calculated using the population attributable fraction. The age-specific (0-1 year, 0-4 years, 5-11 years, and 0-11 years) prevalence of SHS exposure in children was estimated through a telephone survey performed in a representative sample of Spanish households with children in 2016. The risk estimates for all diseases were selected from international meta-analyses. The number of hospitalized cases was obtained for each disease from the Hospital Minimum Data Set provided by the Ministry of Health of Spain. Incident cases were obtained from the Global Health Data Exchange. In 2015, SHS exposure caused an estimated total of 136,403 incident cases of the following respiratory diseases: 9058 (8.5%) cases of asthma, 120,248 (8.5%) of OM, and 7097 (13.5%) of LRI in children aged 0-14 years old in Spain. Likewise, SHS exposure caused a total of 3028 hospitalized cases, with 379 (8.5%) for asthma and 167 (8.5%) for OM in children 0-11 years old, and 2482 (11.6%) for LRI in children <2 years old. The high burden of respiratory disease attributed to SHS exposure supports the need to improve protection of children against SHS exposure by extending smoke-free regulations to homes and cars.


Accessing five oxidation states of uranium in a retained ligand framework.
Understanding and exploiting the redox properties of uranium is of great importance because uranium has a wide range of possible oxidation states and holds great potential for small molecule activation and catalysis. However, it remains challenging to stabilise both low and high-valent uranium ions in a preserved ligand environment. Herein we report the synthesis and characterisation of a series of uranium(II-VI) complexes supported by a tripodal tris(amido)arene ligand. In addition, one- or two-electron redox transformations could be achieved with these compounds. Moreover, combined experimental and theoretical studies unveiled that the ambiphilic uranium-arene interactions are the key to balance the stabilisation of low and high-valent uranium, with the anchoring arene acting as a δ acceptor or a π donor. Our results reinforce the design strategy to incorporate metal-arene interactions in stabilising multiple oxidation states, and open up new avenues to explore the redox chemistry of uranium.


Impact of internal female migration on unmet need for modern contraception in Zambia.
Unmet need for contraception, the proportion of women who want to limit or delay childbirth but use no form of contraception, is the core indicator to evaluate the effectiveness of family planning programs. Understanding how migration influences unmet need is important to identify to whom and how to target sexual and reproductive health programs. We assessed how migration status in rural and urban settings is associated with having an unmet need for family planning. Data on sexually active, fecund, reproductive-aged (15-49 years) women from the 2013-14 Zambia Demographic and Health Survey were analysed through univariate and multivariate logistic regression models. Unmet need for modern contraceptive methods was significantly higher among rural to rural migrant women (OR 1.30, 95%CI 1.00-1.70 p < 0.05) and rural non-migrant women (OR 1.41, 95%CI 1.06-1.85 p < 0.01) compared to urban non-migrant women after controlling for age, marital status, parity, religion, education and wealth. Women residing in, and migrating between, rural areas were significantly more likely to have an unmet need for contraception. Our findings highlight the importance of understanding migration and migrant streams to strengthen family planning programs. In Zambia, a focus on rural-rural migrants, rural non-migrants and the poorest could improve the health of the entire population.


New Topical Therapies for Psoriasis.
Psoriasis is a chronic immune-mediated skin disease with a significant impact on patients' quality of life. Mild-to-moderate forms of the disease usually require long-term topical treatment, but prolonged use of corticosteroids and vitamin D analogues is limited by adverse effects. With further understanding of psoriasis pathogenesis, new molecules are emerging aiming to fulfil these clinical needs. Tapinarof, an aryl hydrocarbon receptor modulator, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile. It additionally appears to have a promising remitting effect as patients presented with an average relapsing time of over 3 months. Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects. Roflumilast was evaluated as an option for intertriginous areas with good outcomes in a small sample, but larger trials are required. The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis.


Ultrafast Bilateral DCE-MRI of the Breast with Conventional Fourier Sampling: Preliminary Evaluation of Semi-quantitative Analysis.
The study aimed to evaluate the feasibility and advantages of a combined high temporal and high spatial resolution protocol for dynamic contrast-enhanced magnetic resonance imaging of the breast. Twenty-three patients with enhancing lesions were imaged at 3T. The acquisition protocol consisted of a series of bilateral, fat-suppressed "ultrafast" acquisitions, with 6.9- to 9.9-second temporal resolution for the first minute following contrast injection, followed by four high spatial resolution acquisitions with 60- to 79.5-second temporal resolution. All images were acquired with standard uniform Fourier sampling. A filtering method was developed to reduce noise and detect significant enhancement in the high temporal resolution images. Time of arrival (TOA) was defined as the time at which each voxel first satisfied all the filter conditions, relative to the time of initial arterial enhancement. Ultrafast images improved visualization of the vasculature feeding and draining lesions. A small percentage of the entire field of view (<6%) enhanced significantly in the 30 seconds following contrast injection. Lesion conspicuity was highest in early ultrafast images, especially in cases with marked parenchymal enhancement. Although the sample size was relatively small, the average TOA for malignant lesions was significantly shorter than the TOA for benign lesions. Significant differences were also measured in other parameters descriptive of early contrast media uptake kinetics (P < 0.05). Ultrafast imaging in the first minute of dynamic contrast-enhanced magnetic resonance imaging of the breast has the potential to add valuable information on early contrast dynamics. Ultrafast imaging could allow radiologists to confidently identify lesions in the presence of marked background parenchymal enhancement.


p53 dephosphorylation and p21(Cip1/Waf1) translocation correlate with caspase-3 activation in TGF-beta1-induced apoptosis of HuH-7 cells.
The p53 tumor suppressor gene product plays an important role in the regulation of apoptosis. Transforming growth factor beta1 (TGF-beta1)-induced apoptosis in hepatic cells is associated with reduced expression of the retinoblastoma protein (pRb) and subsequent E2F-1-activated expression of apoptosis-related genes. In this study, we explored the potential role of p53 in TGF-beta1-induced apoptosis. HuH-7 human hepatoma cells were either synchronized in G1, S and G2/M phases, or treated with 1 nM TGF-beta1. The results indicated that greater than 90% of the TGF-beta1-treated cells were arrested in G1 phase of the cell cycle. This was associated with enhanced p53 dephosphorylation and p21(Cip1/Waf1) expression, which coincided with decreased Cdk2, Cdk4, and cyclin E expression, compared with synchronized G1 cells. In addition, p53 dephosphorylation coincided with caspase-3 activation, and translocation of p21(Cip1/Waf1) and p27(Kip1) into the cytoplasm, all of which were suppressed by caspase inhibition of TGF-beta1-induced apoptosis. Finally, phosphatase inhibition and pRb overexpression partially inhibited p53-mediated apoptosis. In conclusion, the results demonstrated that TGF-beta1-induced p53 dephosphorylation is associated with caspase-3 activation, and cytosolic translocation of p21(Cip1/Waf1) and p27(Kip1), resulting in decreased expression of Cdks and cyclins. Further, p53 appears to mediate TGF-beta1-induced apoptosis downstream of the pRb/E2F-1 pathway.


A new HLA-B antigen, BHT: definition by serological and biochemical means.
In 3 unrelated individuals, a new, so far unknown HLA-B-locus antigen was found. This HLA-B antigen, provisionally termed 'BHT', is recognized by extra reactions with alloantisera against the B5 cross-reactive group. BHT can be clearly discerned from all cross-reactive antigens by one-dimensional isoelectro focusing (1D IEF), as it reveals, on IEF gels, a characteristic, rather neutral double-banding pattern different from all known HLA class I bands. The BHT banding pattern, which is identical in all 3 BHT-positive individuals, segregates with the haplotype A28, BHT, Cw7, DRw6.


[Conditions for blood components return, after storage in a depot].
Recent changes in the regulation of blood components depots has allowed the Etablissement français du sang (EFS) to re-introduce blood components in the stock when they come back from the health establishment. This process is the responsibility of both EFS and health establishment. So collaboration between them is necessary to set an organisation to guarantee that blood components are transported and stored at optimum conditions. To achieve this, a checking procedure for the return process of blood components and a method that tracks the conditions they are exposed to during transportation are necessary. There are many temperature sensitive indicators available to track each unit of blood component. This article presents an organisation using a follow-up by electronic temperature monitors to record the temperature during the transportation and storage processes.


Expanding scope: Impact and preferred implementation strategies for statewide test and treat protocols.
Arkansas Act 503 allows pharmacists to test and treat health conditions performed with waived tests using a statewide protocol. To guide development and implementation of these protocols, this study was conducted after enactment of Act 503 and before protocols were published. The objectives were to determine pharmacy leaderships' perceived impact on point-of-care testing (POCT) services in Arkansas and preferred implementation strategies for expanding scope of practice. A cross-sectional electronic survey of pharmacies holding a Clinical Laboratory Improvement Amendments certificate of waiver in Arkansas was conducted. The primary point of contact of 292 pharmacies was invited by e-mail. Chain, regional, or multi-independent pharmacies of the same company completed one survey on behalf of their organization. The questions assessed perceptions of Act 503 on POCT services and preferred implementation strategies. Study data were collected using REDCap and analyzed using descriptive statistics. One hundred and twenty-five invitations were e-mailed to pharmacy owners or representatives with a response rate of 64.8% (n = 81 surveys). This represented 238 of 292 invited pharmacies (81.5%). In 2021, 82.6% of pharmacies provided POCT services, specifically 27% influenza, 26% streptococcus, and 47% coronavirus disease 2019. Ninety pharmacies (37.9%) reported they are certain or almost certain they will prescribe using the protocol. More pharmacies (63%) reported the youngest age they would prescribe treatment is 6 to 12 years. Most pharmacies (82.2%) do not anticipate or are unsure about increasing their fee once the protocol is adopted. Most pharmacies (> 95%) reported virtual training, online modules, central contact, and a one-page resource with key protocol information would be most helpful in implementing new statewide protocols. Arkansas pharmacies are willing to use a protocol for 6 years and older and did not anticipate increasing fees to support the expanded service. Pharmacists indicated virtual training and one-page resources would be most helpful. This work highlights implementation strategies that could be most useful as pharmacy scope expands in other states.


Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema.
To determine the long-term safety of high-density subvisible diode micropulse photocoagulation (810 nm), compare the clinical findings with computational modeling of tissue hyperthermia and to report results for a subset of eyes treated for diabetic macular edema (ME) documented pre- and postoperatively by spectral-domain optical coherence tomography. All eyes treated for ME from diabetic retinopathy (diabetic ME) and branch retinal vein occlusion between April 2000 and January 2010 were reviewed for subvisible diode micropulse laser-induced retinal damage. Therapeutic outcomes were reviewed for a subgroup treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography. Laser-induced retinal thermal effects were modeled computationally using Arrhenius formalism. A total of 252 eyes (212 diabetic ME, 40 branch retinal vein occlusion) of 181 patients qualified. None of the 168 eyes treated at irradiance <350 W/cm2 and 7 of 84 eyes at ≥ 590 W/cm2 had retinal damage (P = 0.0001) (follow-up 3-120 months, median, 47). Sixty-two eyes of 48 patients treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography with median 12 months follow-up had no retinal injury by infrared, red-free, or fundus autofluorescence photos; fluorescein angiography or indocyanine green angiography; or spectral-domain optical coherence tomography. Central foveal thickness (P = 0.04) and maximum macular thickness decreased (P < 0.0001). Modeling of retinal hyperthermia demonstrates that the sublethal clinical regimen corresponds to Arrhenius integral >0.05, while damage is likely to occur if it exceeds 1. Subvisible diode micropulse can effectively treat retinovascular ME without laser-induced retinal damage, consistent with Arrhenius modeling of pulsed hyperthermia.


Arterial thoracic outlet syndrome: a 32-year experience.
Clinical manifestations of thoracic outlet syndrome (TOS) differ depending on the compromised anatomic structure. Arterial TOS is the least common (1-5% of all cases of TOS), yet the most threatening, due to the risk of limb loss. We conducted a retrospective review of consecutive patients treated for arterial TOS between January 1979 and June 2012. Medical records and diagnostic images were reviewed, and follow-up was obtained. Nineteen procedures were performed in 18 patients for symptomatic arterial TOS. The average age was 34 years (range 16-69 years), and 12 patients were female (63.2%). Surgical indications were upper limb critical ischemia in 8 (acute in 5 cases and acute-on-chronic in 3 cases) and claudication in 11. Imaging studies revealed a subclavian aneurysm in 7 patients, stenosis in 4 patients, and 2 patients with subclavian artery occlusion. The 6 remaining cases had symptoms caused by arterial compression in dynamic studies without arterial wall damage at rest. All limbs underwent surgery with outlet decompression; in addition, 13 underwent arterial reconstruction, and 7 were treated for distal embolic complications. There were no deaths, amputations, or early reoperations; 1 patient was readmitted 2 weeks after surgery for chylothorax, which resolved with conservative measures. During a mean follow-up of 155.8±103.1 months, 1 patient underwent successful reintervention at 4 months for bypass occlusion. Arterial TOS is an infrequent but relevant manifestation of TOS. An accurate and early diagnosis allows for timely surgery and adequate results, as shown in this group of patients.


Consolidated bioprocessing of cellulosic biomass: an update.
Biologically mediated processes seem promising for energy conversion, in particular for the conversion of lignocellulosic biomass into fuels. Although processes featuring a step dedicated to the production of cellulase enzymes have been the focus of most research efforts to date, consolidated bioprocessing (CBP)--featuring cellulase production, cellulose hydrolysis and fermentation in one step--is an alternative approach with outstanding potential. Progress in developing CBP-enabling microorganisms is being made through two strategies: engineering naturally occurring cellulolytic microorganisms to improve product-related properties, such as yield and titer, and engineering non-cellulolytic organisms that exhibit high product yields and titers to express a heterologous cellulase system enabling cellulose utilization. Recent studies of the fundamental principles of microbial cellulose utilization support the feasibility of CBP.


Design, characterization and in vitro evaluation of thin films enriched by tannic acid complexed by Fe(III) ions.
Materials based on carbohydrate polymers may be used for biomedical application. However, materials based on natural polymers have weak physicochemical properties. Thereby, there is a challenge to improve their properties without initiation of toxicity. The alternative method compared to toxic chemical agents' addition is the use of metal complexation method. In this study, chitosan/tannic acid mixtures modified by Fe(III) complexation are proposed and tested for potential applications as wound dressings. Thereby, surface properties, blood compatibility as well as platelet adhesion was tested. In addition, the periodontal ligament stromal cells compatibility studies were carried out. The results showed that the iron(III) addition to chitosan/tannic acid mixture improves properties due to a decrease in the surface free energy and exhibited a reduction in the hemolysis rate (below 5%). Moreover, cells cultured on the surface of films with Fe(III) showed higher metabolic activity. The current findings allow for the medical application of the proposed materials as wound dressings.


Chromosome-level genome assembly of Microplitis manilae Ashmead, 1904 (Hymenoptera: Braconidae).
Microplitis manilae Ashmead (Hymenoptera: Braconidae) is an important parasitoid of agricultural pests in lepidopteran species. So far, two extant genome assembles from the genus Microplitis are fragmented. Here, we offered a high-quality genome assembly of M. manilae at the chromosome level with high accuracy and contiguity, assembled by ONT long-read, MGI-SEQ short-read, and Hi-C sequencing methods. The final assembled genome size was 282.85 Mb, with 268.17 Mb assigned to 11 pseudochromosomes. The scaffold N50 length was 25.23 Mb, and the complete BUSCO score was 98.61%. The genome contained 152.37 Mb of repetitive elements, representing 53.87% of the total genome size. We predicted 15,689 protein-coding genes, of which 13,580 genes were annotated functionally. Gene family evolution investigations of M. manilae revealed 615 expanded and 635 contracted gene families. The high-quality genome of M. manilae reported in this paper will be a useful genomic resource for research on parasitoid wasps in the future.


Production of xylitol by recombinant microalgae.
Microalgae have received significant attention recently as a potential low-cost host for the production of next-generation biofuels and natural products. Here we show that the chloroplast genome of the eukaryotic green microalga Chlamydomonas reinhardtii can be genetically engineered to produce xylitol through the introduction of a gene encoding a xylose reductase (XR) from the fungi Neurospora crassa. Increased levels of heterologous protein accumulation and xylitol production were achieved by synthesizing the XR gene in the chloroplast codon bias and by driving expression of the codon-optimized XR gene using a 16S/atpA promoter/5'-UTR fusion. These results demonstrate the feasibility of engineering microalgae to produce xylitol, and show the importance of codon optimizing the XR gene and using the 16S/atpA promoter/5'-UTR fusion to express XR in the chloroplast of C. reinhardtii.


A rapid preparation technique for studying highly water-swollen membranes with a scanning electron microscope (SEM) supplied with a cryo-unit.
In this study the cryo-unit is introduced as a new and useful instrument to investigate water-containing specimens with the SEM. Often water-containing biological specimens are studied, but in our case we used water-swollen polymer membranes. The results show that application of a cryo-unit permits the study of this material at low temperatures up to magnifications of about 10 000 times, while other techniques failed to give reproducible results.


Whole brain N-acetylaspartate concentration is conserved throughout normal aging.
We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker--the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)--a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 ± 5.8 years old) and 100 (64 male, 72.6 ± 7.3 years old) cognitively normal elderly. The 12.8 ± 1.9 mM WBNAA of the young was not significantly different from the 13.1 ± 3.1 mM in the elderly (p > 0.05). In contrast, both fBPV (87.3 ± 4.7% vs. 74.8 ± 4.8%) and WHNAA (11.1 ± 1.7 mM vs. 9.8 ± 2.4 mM) were significantly higher in the young (approximately 14%; p < 0.0001 for both). The similarity in mean WBNAA between 2 cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue.


Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum.
In addition to the virus-coded large-T and small-t antigens, two new classes of proteins were immunoprecipitated by anti-simian virus 40 (SV40) tumor serum from extracts of various SV40-transformed cell lines. These were as follows: (i) proteins (termed "super-T proteins") with an Mr higher than that of large-T antigen (86,000), which were found in many SV40-transformed cell lines derived from mouse and rat cells (super-T proteins and large-T antigen appeared to have closely related structures as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides); (ii) proteins (termed "55K proteins") with an Mr ranging from 50,000 to 60,000, which were present in all SV40-transformed cell lines examined so far, including those obtained by chromosome-mediated gene transfer. The 55K proteins were not structurally related to large-T antigens, as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides. Our data are compatible with the assumption that the 55K proteins are largely or totally cell coded.


Biochemistry of metallocenes. Identification of the major metabolite of acetylruthenocene.
1. After oral administration of acetylruthenocene to rats, metabolites were detected in bile and urine. 2. The major metabolite, which is present in both bile and urine, is a glucuronide with the structure: C5H5-Ru-C5H4-CO-CH2-O-C6H9O6 3. The metabolite was identified by mass spectrometry of the permethylated glucuronide and mass spectrometry and n.m.r. of the aglycone. 4. The nature of the metabolite is discussed, and a comparison is made with the metabolism of the benzene analogue, acetophenone.


Comment on time-varying eddy currents effects on diffusion-weighting echo-planar imaging.
This commentary addresses the recent paper entitled "Dynamic correction of artifacts due to susceptibility effects and time-varying eddy currents in diffusion tensor imaging" (Truong et al., 2011) and discusses their findings in relation to previous studies from the late 1990s that showed equivalent findings regarding the complex time-varying nature of eddy currents during the imaging readout. The similarities between the findings from these studies are highlighted, and their possible implications for present commonly used eddy current reduction methods are discussed.


Patenting cDNA 1993: efforts and happenings (Human Genome Project; NIH: US PTO; onco-mouse; European Patents).
The National Institute of Health (NIH) and Dr. J.C. Venter applied for patents for the sequences of cDNA fragments from a brain library. The scientific community objected strenuously on emotional grounds. The NIH argues that these sequences might never be patentable even when completed. The issue became an international one with the British applying for patents to protect their position while the French, Italians and Japanese vowed not to patent cDNA. The United States Patent Trademark Office (US PTO) strongly rejected the NIH's application. The NIH is appealing the decision.


Antinociceptive activity of alcoholic extract of Hemidesmus indicus R.Br. in mice.
The ethanolic extract of roots of Hemidesmus indicus R.Br. (family: Asclepiadaceae) was investigated for possible antinociceptive effect in mice. Three models were used to study the effects of extracts on nociception, which was induced, by acetic acid (Writhing test), formalin (Paw licking test) and hot plate test in mice. Hemidesmus indicus R.Br. extract was administered in the dose range of 25, 50 and 100mg/kg orally 1h prior to pain induction. The preliminary phytochemical screening of the extract showed the presence of triterpenes, flavonoids, pregnane glycosides and steroids. Oral administration of Hemidesmus indicus extract revealed dose-dependent antinociceptive effect in all the models for antinociception and it blocked both the neurogenic and inflammatory pain and the nociceptive activity was comparable with the reference drug. The results indicate that alcoholic extract of Hemidesmus indicus R.Br. possesses a significant antinociceptive activity. The activity can be related with the significant phytochemicals such as triterpenes, flavonoids, and sterols reported in the root extract.


Antibiotic content of selective culture media for isolation of Capnocytophaga species from oral polymicrobial samples.
In oral microbiome, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of fastidious Capnocytophaga species. The performances of six culture media (blood agar, chocolate blood agar, VCAT medium, CAPE medium, bacitracin chocolate blood agar and VK medium) were compared with literature data concerning five other media (FAA, LB, TSBV, CapR and TBBP media). To understand variable growth on selective media, the MICs of each antimicrobial agent contained in this different media (colistin, kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, vancomycin, aztreonam and bacitracin) were determined for all Capnocytophaga species. Overall, VCAT medium (Columbia, 10% cooked horse blood, polyvitaminic supplement, 3·75 mg l(-1) of colistin, 1·5 mg l(-1) of trimethoprim, 1 mg l(-1) of vancomycin and 0·5 mg l(-1) of amphotericin B, Oxoid, France) was the more efficient selective medium, with regard to the detection of Capnocytophaga species from oral samples (P < 0·001) and the elimination of commensal clinical species (P < 0·001). The demonstrated superiority of VCAT medium, related to its antibiotic content, made its use indispensable for the optimal isolation of Capnocytophaga species from polymicrobial samples. Isolation of Capnocytophaga species is important for the proper diagnosis and treatment of the systemic infections they cause and for epidemiological studies of periodontal flora. We showed that in pure culture, a simple blood agar allowed the growth of all Capnocytophaga species. Nonetheless, in oral samples, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of Capnocytophaga species. The demonstrated superiority of VCAT medium made its use essential for the optimal detection of this bacterial genus. This work showed that extreme caution should be exercised when reporting the isolation of Capnocytophaga species from oral polymicrobial samples, because the culture medium is a determining factor.


Facile synthesis of new imidazo[1,2-a]pyridines carrying 1,2,3-triazoles via click chemistry and their antiepileptic studies.
The present article reports the synthesis and anticonvulsant studies of new 2-arylimidazo[1,2-a]pyridines carrying suitably substituted 1,2,3-triazoles as well as their intermediates. The structures of newly synthesized compounds were confirmed by various spectroscopic techniques. The anticonvulsant study was carried out by MES and scPTZ screening methods, while their toxicity study was performed following Rotarod method. The active compounds showed enhanced seizure control in scPTZ method when compared with that of MES method. Compounds 3f, 4c, 4f, 5k, 5p and 5w carrying active pharmacophores exhibited complete protection against seizure and their results were comparable with standard drug diazepam. Majority of new compounds were found to be non-toxic, while few of them showed toxicity at 100 mg/kg. The clogP values of target compounds are in the range of 3.5-5.3, which confirm their lipophilic nature.


Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography.
Current thinking is that amiodarone-induced thyrotoxicosis (AIT) might be either iodine-induced thyrotoxicosis in latent hyperthyroidism (Type 1) or destructive thyroiditis (Type 2), and also that colour-flow Doppler sonography (CFDS) of the thyroid and serum interleukin 6 (IL-6) are tools that can classify AIT and direct treatment. To assess the validity of this thinking, our objective was to determine whether CFDS and IL-6 identified AIT subgroups with distinct features. Retrospective case-note audit of all patients presenting with AIT to the Endocrine Department of a UK teaching hospital over a 3-year period. To assess proportions of Type 1 vs. Type 2 AIT and to compare and contrast their clinical features. 37 patients were identified with AIT (mean age 65, range 20-86 years). In 30 patients in whom AIT persisted, 25 underwent CFDS. In 25 patients who underwent CFDS, 10 (40%) were classified as Type 1, 10 (40%) as Type 2 and 5 (20%) as indeterminate type. In the patients classified by CFDS in whom AIT persisted, 40% of Type 1 patients were male vs. 90% of Type 2 patients. Also, free T4 tended to be lower in patients presenting with Type 1 AIT (52.1 +/- 7.5 pmol/l) compared to Type 2 (74.8 +/- 8.1 pmol/l, P = 0.08), free T3 was lower (8.8 +/- 0.9 vs. 15.6 +/- 3.0 pmol/l, P = 0.03) and the cumulative amiodarone dose was lower (66 +/- 20 vs. 186 +/- 28 g, P = 0.002). We used less prednisolone to achieve euthyroidism in patients with Type 1 AIT whereas carbimazole doses were not different and the time to euthyroidism was the same in both groups (81 +/- 21 vs. 88 +/- 13 days). IL-6 was raised in two patients with Type 1 and in one patient with Type 2 AIT. CFDS could characterize two distinct subtypes in patients with AIT. Conversely, IL-6 seemed to be an unhelpful test in this context.


Observational evaluation of outcomes and resource utilization from hemostatic matrices in spine surgery.
Studies have indicated that outcomes may differ by choice of flowable hemostat, but there is limited evidence in spine surgery. The objective of this study was to conduct a comparison of outcomes following use of advanced flowable hemostatic matrices in a large spine surgery population. This is an observational retrospective cohort analysis using Premier's US Perspective Hospital Database. Two commonly-used hemostatic matrices (Floseal and Surgiflo kitted with thrombin) were compared in cases categorized as either major or severe spine surgery. Outcomes included complications, blood product administration, hospital length of stay (LOS), surgery time, and amount of matrix used in surgery. Major spine surgery patients treated with Surgiflo were associated with increased risk of blood product transfusion (OR = 2.56, 95% CI = 1.79-3.65, p < 0.001), longer surgery time (+8.84 min, p < 0.0001), and increased product usage (+3.34 mL, p < 0.001), compared to Floseal; however, risk of complications and LOS did not differ by choice of matrix in this patient group. Severe spine surgery patients treated with Surgiflo were associated with longer surgical time (+26.9 min, p < 0.001) and increased product usage (+1.52 mL, p < 0.01), compared to Floseal; however, risk of complications, transfusion and LOS did not differ by choice of matrix in this patient group. Inherent to limitations associated with database analysis, this study did not evaluate potential physician differences such as skill and experience, assess long-term outcomes, nor include cases with missing data. The results from this analysis indicated that surgery time, risk of blood transfusion, and amount of matrix used are greater with Surgiflo patients, compared to Floseal patients. Choice of matrix did not appear to impact hospital LOS or risk of surgical complications. Future research should evaluate the cost consequences of increased clinical and resource utilization by choice of hemostatic matrix in spine surgery.


Control of the flow properties of DNA by topoisomerase II and its targeting inhibitor.
The flow properties of DNA are important for understanding cell division and, indirectly, cancer therapy. DNA topology controlling enzymes such as topoisomerase II are thought to play an essential role. We report experiments showing how double-strand passage facilitated by topoisomerase II controls DNA rheology. For this purpose, we have measured the elastic storage and viscous loss moduli of a model system comprising bacteriophage λ-DNA and human topoisomerase IIα using video tracking of the Brownian motion of colloidal probe particles. We found that the rheology is critically dependent on the formation of temporal entanglements among the DNA molecules with a relaxation time of ∼1 s. We observed that topoisomerase II effectively removes these entanglements and transforms the solution from an elastic physical gel to a viscous fluid depending on the consumption of ATP. A second aspect of this study is the effect of the generic topoisomerase II inhibitor adenylyl-imidodiphosphate (AMP-PNP). In mixtures of AMP-PNP and ATP, the double-strand passage reaction gets blocked and progressively fewer entanglements are relaxed. A total replacement of ATP by AMP-PNP results in a temporal increase in elasticity at higher frequencies, but no transition to an elastic gel with fixed cross-links.


Pilot study of continuation cognitive-behavioral therapy for major depression in adolescent psychiatric patients.
To determine whether continuation of cognitive-behavioral therapy (CBT-C) could prevent relapse in adolescent psychiatric patients who had remitted from major depressive disorder (MDD). Seventeen patients who continued to have CBT-C for 6 months after remission from MDD were compared with a historical control group of 12 cases who had no further treatment after remission. Only 1 of the 17 cases who continued with CBT-C dropped out. The cumulative relapse risk during CBT-C was significantly lower (0.2) than it had been in the historical control group (0.5). CBT-C warrants further investigation in a randomized, controlled trial.


Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: evidence for a direct negative chronotropic effect of prazosin.
To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+0.97 versus +0.73 liters/min per m2, P less than 0.01) and mean arterial pressure decreased less (-13.7 versus -18.3 mm Hg, P less than 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m2 with nitroprusside and +6.6 with prazosin). Therefore, the differences in the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (-8 beats/min) than with nitroprusside (-2 beats/min, P less than 0.05). These clinical data support experimental evidence suggesting that there is a significant negative chronotropic action of prazosin independent of its peripheral vascular effects.


Revision neural monitored surgery for recurrent thyroid cancer: Safety and thyroglobulin response.
To evaluate the quantitative biochemical response, recurrence rate, and rate of surgical complications for thyroid cancer revision surgery. Retrospective review. This is a single institution analysis of a prospective database of 181 patients undergoing reoperation for local recurrent thyroid cancer by the same surgeon from 2004 to 2013 with intraoperative neural monitoring. Main outcome measures included pathologic findings, surgical complications, effect of reoperation on thyroglobulin (Tg) levels, and recurrence rate. We defined biochemical complete remission as postoperative stimulated Tg of 0.2 ng/mL or less. Fourteen percent of the patients presented with permanent vocal cord palsy (VCP), and 20% of the patients presented with hypocalcemia prior to surgery. Among them, 70% of the patients underwent first revision surgery; whereas in 30% the surgery represented second or higher revision surgery, with 8% being a third or higher revision. None developed temporary or permanent VCP. Temporary hypocalcemia occurred in 9% of the patients, and permanent hypocalcemia occurred in 4.2%. The rate of cervical node recurrence was 5% at a median follow-up of 3.4 years. There were no disease-specific deaths. Mean preoperative basal Tg was 22.3 ng/mL and mean postoperative Tg was 5.7 ng/mL, a decline of 74% (P = 0.023, paired t test). Biochemical complete remission was achieved in 58% of all revision cases. Reoperative neural monitored surgery for recurrent thyroid cancer is a safe and effective procedure with limited morbidity in experienced hands, even in the setting of multiple prior revision surgeries and existing comorbidities such as VCP and hypocalcemia. 4.


Photoluminescent carbon nanotags from harmful cyanobacteria for drug delivery and imaging in cancer cells.
Using a simple method of mass production of green carbon nanotags (G-tags) from harmful cyanobacteria, we developed an advanced and efficient imaging platform for the purpose of anticancer therapy. Approximately 100 grams of G-tags per 100 kilograms of harmful cyanobacteria were prepared using our eco-friendly approach. The G-tags possess high solubility, excellent photostability, and low cytotoxicity (<1.5 mg/mL for 24 h). Moreover, doxorubicin-conjugated G-tags (T-tags; >0.1 mg/mL) induced death in cancer cells (HepG2 and MCF-7) in-vitro at a higher rate than that of only G-tags while in-vivo mice experiment showed enhanced anticancer efficacy by T-tags at 0.01 mg/mL, indicating that the loaded doxorubicin retains its pharmaceutical activity. The cancer cell uptake and intracellular location of the G- and T-tags were observed. The results indicate that these multifunctional T-tags can deliver doxorubicin to the targeted cancer cells and sense the delivery of doxorubicin by activating the fluorescence of G-tags.


Who becomes addicted and to what? psychosocial predictors of substance and behavioral addictive disorders.
A multitude of psychological and social factors likely contribute to the development and maintenance of addictive disorders. As different people develop different addictions, it is important to understand whether psychosocial factors are related differently to different types of addictive disorders. In this study, we examined the unique interaction of personality traits, family environment, and life events in predicting substance (drugs, alcohol) and behavioral (gambling, sex) addictive disorders, among 207 participants suffering from an addictive disorder and 79 controls. Results identified several psychosocial factors, including impulsivity and reported negative life events, that predicted all types of addictive disorders. There was also a unique prediction model for each addiction. Drug and alcohol use disorders were predicted by lower agreeableness and less intellectual-cultural family orientation, with alcohol use disorder further predicted by lower extraversion and higher family organization. Gambling disorder was predicted by a family with lower intellectual-cultural orientation and higher organization and control, whereas compulsive sexual behavior was predicted by lower extraversion and agreeableness and higher neuroticism, and by higher family control. These findings suggest that the complex interplay among psychosocial factors is manifested differently across addictive disorders and may thus have important implications for research, prevention, and intervention.


Severe Bone Marrow Aplasia Following Macrophage Activation Syndrome in Systemic Lupus Erythematosus.
Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases, characterized by activated macrophages with hemophagocytosis and multiple organ damage. We report a case of MAS associated with systemic lupus erythematosus that initially presented with severe liver dysfunction. Although it was improved with steroids and plasmapheresis, severe pancytopenia was subsequently experienced, and the bone marrow showed severe aplasia similar to aplastic anemia. Nevertheless, the administration of immunosuppressants resulted in the recovery of blood counts within two weeks. When severe MAS results in cytokine overproduction, bone marrow aplasia may occur, for which immunosuppressive therapy may be highly effective.


Relevance of vesico-ureteric reflux in development of lipid A antibodies in recurrent urinary tract infections in children--a preliminary study.
The serum titres of IgG and IgM antibodies to lipid A were measured in 24 children with chronic pyelonephritis (PN), 55 with recurrent lower urinary tract infections (LUTI), 13 with gram-negative sepsis (S), and in 50 control children using an enzyme-linked immunosorbent assay (ELISA). Children ranged in age from 1 month-17 years. Patients with PN were differentiated by the presence or absence of an acute infectious episode and/or vesico-ureteric reflux (VUR). During an acute episode in PN and LUTI, IgG titres were significantly higher than in controls, but only PN patients with an acute infectious episode also had significantly elevated IgM titres. Overall, children with LUTI showed a significantly lower frequency of detectable IgG lipid A antibodies (27%) than in PN (63%). In PN children with VUR not accompanied by an infectious episode, lipid A antibody was found at relatively low titres, while an episode not accompanied by VUR displayed significantly elevated IgG titres, and an episode accompanied by VUR showed elevation of both IgG and IgM anti-lipid A antibody titres.


X-box binding protein 1 enhances adipogenic differentiation of 3T3-L1 cells through the downregulation of Wnt10b expression.
Differentiation of preadipocytes into adipocytes is controlled by various transcription factors. Recently, the pro-adipogenic function of XBP1, a transcription factor upregulated by endoplasmic reticulum stress, has been reported. In this study, we demonstrated that XBP1 suppresses the expression of Wnt10b, an anti-adipogenic Wnt, during the differentiation of 3T3-L1 preadipocytes. The expression pattern of XBP1 was reciprocal to that of Wnt10b during the early stage of adipogenesis. The intracellular protein levels of β-catenin were negatively regulated by XBP1. Direct binding of XBP1 to the Wnt10b promoter and the subsequent decrease of the β-catenin signalling pathway represent a novel adipogenic differentiation mechanism.


Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies.
To describe our initial clinical experience with intensity-modulated whole pelvic radiotherapy (IM-WPRT) in women with gynecologic malignancies. Between February 2000 and August 2001, 40 gynecology patients underwent IM-WPRT. After fabrication of customized immobilization, all patients underwent contrast-enhanced CT, and a clinical target volume was contoured consisting of the upper vagina, parametria, uterus (if present), and presacral and pelvic lymph node regions. The clinical target volume was expanded by 1 cm to create a planning target volume (PTV). Using commercially available software, 7- or 9-field, 6-MV, coplanar IM-WPRT plans were generated for all patients. The worst acute gastrointestinal and genitourinary toxicity during treatment was scored on a 4-point scale: 0, none; 1, mild, no medications required; 2, moderate, medications required; and 3, severe, treatment breaks or cessation, hospitalization. As a comparison, acute toxicities in 35 previously treated conventional WPRT patients were analyzed. No significant differences were noted in the clinicopathologic and treatment factors between the two groups. IM-WPRT plans provided excellent PTV coverage, with considerable sparing of the surrounding normal tissues. On average, 98.1% of the PTV received the prescription dose. The average percentage of the PTV receiving 110% and 115% of the prescription dose was 9.8% and 0.2%, respectively. IM-WPRT was well tolerated, with no patient developing Grade 3 toxicity. Grade 2 acute gastrointestinal toxicity was less common in the IM-WPRT group (60 vs. 91%, p = 0.002) than in the conventional WPRT group. Moreover, the percentage of IM-WPRT and WPRT patients requiring no or only infrequent antidiarrheal medications was 75% and 34%, respectively (p = 0.001). Although less Grade 2 genitourinary toxicity was seen in the IM-WPRT group (10% vs. 20%), this difference was not statistically significant (p = 0.22). IM-WPRT is a promising approach in gynecology patients. IMRT planning resulted in excellent PTV coverage, with considerable sparing of normal tissues. Treatment was well tolerated and associated with less acute gastrointestinal sequelae than conventional WPRT. Longer follow-up and more patients are needed, however, to evaluate the full merits of this novel approach.


Molecular characterization of ten zinc (Zn) transporter genes and their regulation to Zn metabolism in freshwater teleost yellow catfish Pelteobagrus fulvidraco.
Zn is an essential trace element for vertebrates, and Zn uptake and transport is related with the ZIP family of Zn transporters. Meantime, Zn also influenced the expression of ZIP family members. We cloned and characterized the full-length cDNA sequences of ten Zn transport-relevant genes (ZIP1, ZIP3, ZIP6, ZIP7, ZIP8, ZIP9, ZIP10, ZIP11, ZIP13 and ZIP14) from yellow catfish Pelteobagrus fulvidraco, investigated their mRNA tissue expression. These ZIP mRNA expression was also assessed in the primary hepatocytes and intestinal epithelial cells of yellow catfish in response to three Zn levels (0, 30 μM and 60 μM, respectively). All these genes shared the similar domains with the corresponding members in mammals. The mRNA expression of the ten ZIP genes was detected in nine-tested tissues, but variable among these tissues. Flow cytometry analysis and confocal microscopy observation indicated that intracellular free Zn2+ concentration in hepatocytes and intestinal epithelial cells increased with increasing Zn incubation concentration at both 24 h and 48 h. Zn incubation differentially influenced mRNA levels of ZIP transporters in the hepatocytes and intestinal epithelial cells, in a time- and cells-dependent manners. In the hepatocytes, at 24 h, compared to the control, Zn addition down-regulated mRNA levels of ZIP1, ZIP3, ZIP6, ZIP7, ZIP8, ZIP9, ZIP11 and ZIP14; however, ZIP10 mRNA levels were lower in 60 μM Zn group than those in the control and 30 μM Zn group. At 48 h, mRNA levels of ZIP1, ZIP6, ZIP7, ZIP9, ZIP10 and ZIP14 declined with increasing Zn incubation concentrations; ZIP3 mRNA levels were the lowest in 60 μM Zn group and showed no significant differences between the control and 30 μM Zn group. In the intestinal epithelial cells, at 24 h, Zn addition down-regulated mRNA levels of ZIP1, ZIP6, ZIP7, ZIP8, ZIP9, ZIP10, ZIP11, ZIP13 and ZIP14; ZIP3 mRNA levels were lower in 60 μM Zn group than those in the control and 30 μM Zn group. At 48 h, Zn addition up-regulated mRNA levels of ZIP6 and ZIP9, but down-regulated mRNA levels of ZIP8, ZIP10 and ZIP13. ZIP7, ZIP11 and ZIP14 mRNA abundances were the lowest in 60 μM Zn group and showed no significant differences between the control and 30 μM Zn group. For the first time, our study characterized ten ZIP family members in yellow catfish, explored their mRNA tissue expression. Their regulation to Zn addition were also investigated in the hepatocytes and intestinal epithelial cells of yellow catfish. Our study revealed the mechanism of cells exposed to Zn addition and provided novel insights for the regulatory mechanism of Zn homeostasis.


Case reports of aconite poisoning in mainland China from 2004 to 2015: A retrospective analysis.
Aconitum species have long been used in key traditional medicines in China, but cases of fatal aconite poisoning have also been reported. This paper presents a review of 40 single and multi-person cases of fatal aconite poisoning. The cases involved 53 victims in mainland China described in 27 case reports published between January 2004 and September 2015. We summarize the details of the case reports in order to highlight the features of fatal aconite-poisoning cases in China, including victims' sex and age, route of intoxication, clinical symptoms, medicolegal autopsy findings, and results of toxicological analysis. Our results indicate a need for legal medical experts encountering cases of fatal aconite poisoning to pay increased attention to the methods used for collecting biological samples. In addition, prevention strategies should focus on increasing public awareness regarding the potential toxicity of Aconitum, harm caused by medicinal liquors containing aconitine, and possibility of Aconitum alkaloids accumulating in the body.


Safety culture and perception of warning signs of chemical hazards among hospital cleaning workers: a cross-sectional study.
Due to the type of activities and the long-term exposure to chemicals, hospital cleaning workers require the necessary knowledge about the chemicals used and proper safety culture. This study aimed to evaluate the safety culture and perception of hospital cleaning workers' warning signs of chemical hazards. This cross-sectional study was conducted in 2022 with the participation of 68 cleaning workers with the mean age ± (SD) and work experience ± (SD) of 36.19 ± (7.619) and 9.21 ± (5.462), respectively, in four selected Tehran hospitals in Iran. After ensuring the confidentiality of the received information and completing the demographic information checklist, each participant completed Global Harmonization System (GHS) sign perception and the safety culture questionnaires in this survey. Data were analyzed using regression and Pearson correlation tests. This study showed that the participant's correct perception in nine cases (81.8%) of presented GHS signs was lower than the ANSI Z535.3 standard. Among the investigated signs, "Flammable substances" and "Harmful to the environment" signs had the highest, and "Skin irritant" signs had the lowest correct perception. In addition, it was found that 55 people (80.9%) had an overall positive attitude toward the safety culture. The levels of "Work environment" (83.8%) and "Information exchange" (76.5%) had the highest and lowest positive scores for safety culture. Furthermore, there is a direct and significant relationship between the overall score of safety culture and the overall perception of the symptoms of GHS (CC = 0.313, P = 0.009). According to the obtained results, it is recommended to take the necessary measures to increase the employees' perception of the signs of chemical substances and improve their safety culture.


Cortical potential correlates of selective attention in multidimensional scaling.
Cortical evoked potentials were recorded from the vertex of subjects performing a similarity rating task. Proximity data were analysed according to INDSCAL (Carroll and Chang, 1970). Brain activity was averaged separately for different stimulus attributes and different stages of the judgement process. The amplitudes of the two positive deflections of the averaged evoked potential, peaking around 160 and 330 msec after stimulus onset respectively, were systematically influenced by two factors: The weight, which the evoking attribute received in the overall dissimilarity judgement, and the position of the evoking attribute in the stimulus train. The results support the hypothesis that differences in the perception of similarity are due to differences in attentional set. Reference is made to the 'additive-difference model' of scaling behaviour (Tversky and Krantz, 1970) and Broadbent's (1970) distinction between stimulus set and response set attention.


Interventional ultrasound for adrenal masses.
To determine the value of interventional ultrasound (US) for adrenal masses, especially incidentally discovered adrenal masses. Demographic, clinical, and pathological data were reviewed for eight patients who underwent percutaneous US-guided puncture or biopsy for adrenal masses from September 1994 through March 2002 in our institute. US-guided intervention was successfully performed for seven patients: two with adrenal cysts, two with adrenocortical adenomas, and three with metastatic adrenal tumors (one from prostate cancer, one from lung cancer, and one from renal cell carcinoma). The remaining patient had bilateral adrenal masses, and a biopsy specimen could not be obtained because safe puncture was difficult. For all patients there was no postoperative hemorrhage or pain, and no major complications were observed during the procedure. Interventional US using the color Doppler method for adrenal masses is a useful procedure for safe puncture to reveal the orientation of adjacent viscera and blood vessels at the puncture site and to avoid complications including hemorrhage and pneumothorax. US, including color Doppler US, is also useful for detection of complications and follow-up studies because it is noninvasive and can be used for real-time examinations. In addition, pathological examination of specimens obtained by percutaneous biopsy or fine needle aspiration is useful for avoiding unnecessary surgery in patients with metastatic adrenal masses.


Music and academic performance.
In a previous study we demonstrated that listening to a pleasant music while performing an academic test helped students to overcome stress, to devote more time to more stressful and more complicated task and the grades were higher. Yet, there remained ambiguities as for the causes of the higher test performance of these students: do they perform better because they hear music during their examinations, or would they perform better anyway because they are more gifted/motivated? This motivated the current study as a preliminary step toward that general question: Do students who like/perform music have better grades than the others? Our results confirmed this hypothesis: students studying music have better grades in all subjects.


The possible role of an [FeFe]-hydrogenase-like protein in the plant responses to changing atmospheric oxygen levels.
The knockdown of a [FeFe]-hydrogenase-like gene in the model plants Medicago truncatula and Arabidopsis thaliana resulted in a mutant with a dwarf phenotype. Surprisingly, the phenotype is undistinguishable from wild type under hypoxic conditions. The heterologous expression of the plant gene in Escherichia coli indicates that the resulting protein probably coordinates two [Fe-S] clusters with different magnetic properties. Sequence alignment analysis indicates that these two clusters would be topologically equivalent to the mesial and proximal [Fe-S] centers of [FeFe]-hydrogenases. A possible role of the gene product in oxygen signaling pathways is discussed.


SMS-based family planning communication and its association with modern contraception and maternal healthcare use in selected low-middle-income countries.
The objectives of this study were to 1) measure the percentage of women who received SMS-based family planning communication, and 2) its association with modern contraception and maternal healthcare services among mothers. In recent years, there has been a growing interest surrounding mobile phone-based health communication and service delivery methods especially in the areas of family planning and reproductive health. However, little is known regarding the role of SMS-based family planning communication on the utilisation of modern contraception and maternal healthcare services in low-resource settings. Cross-sectional data on 94,675 mothers (15-49 years) were collected from the latest Demographic and Health Surveys in 14 low-and-middle-income countries. The outcome variables were self-reported use of modern contraception and basic maternal healthcare services (timely and adequate use of antenatal care, and of facility delivery services). Data were analysed using multivariate regression and random effect meta-analyses. The coverage of SMS-based family planning communication for the pooled sample was 5.4% (95%CI = 3.71, 7.21), and was slightly higher in Africa (6.04, 95%CI = 3.38, 8.70) compared with Asia (5.23, 95%CI = 1.60, 8.86). Among the countries from sub-Saharan Africa, Malawi (11.92, 95%CI = 11.17, 12.70) had the highest percent of receiving SMS while Senegal (1.24, 95%CI = 1.00, 1.53) had the lowest. In the multivariate analysis, SMS communication shown significant association with the use of facility delivery only (2.22 (95%CI = 1.95, 2.83). The strength of the association was highest for Senegal (OR = 4.70, 95%CI = 1.14, 7.33) and lowest for Burundi (OR = 1.5; 95%CI = 1.01, 2.74). Meta analyses revealed moderate heterogeneity both in the prevalence and the association between SMS communication and the utilisation of facility delivery. Although positively associated with using facility delivery services, receiving SMS on family planning does not appear to affect modern contraceptive use and other components of maternal healthcare services such as timely and adequate utilisation of antenatal care.


Nephrogenic fibrosing dermopathy in a patient with systemic lupus erythematosus and acute lupus nephritis.
Nephrogenic fibrosing dermopathy is a recently recognized skin disorder similar in appearance to scleromyxedema but without the systemic involvement. We describe a 14-year-old girl with new-onset systemic lupus erythematosus and acute lupus nephritis who developed on the lower extremities confluent hyperpigmented, woody, indurated plaques that contained groups of coalescing erythematous papules. Nephrogenic fibrosing dermopathy was diagnosed histologically. Possible etiologies are discussed.


DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines.
Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells. This study demonstrates that MGMT expression, CpG island methylation, and histone acetylation vary between melanoma cell lines. Combined treatment with 5-Aza-2'-deoxycytidine and Trichostatin A led to reexpression of MGMT, indicating that DNA methylation and histone deacetylation are associated with silencing of MGMT in melanoma. This study provides information on the role of epigenetic modifications in malignant melanoma that may enable the development of new strategies for treating malignant melanoma.


Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury.
Traumatic brain injury (TBI) and hemorrhage remain the leading causes of death after trauma. We have previously shown that a dose of valproic acid (VPA) at (150 mg/kg) can decrease brain lesion size and hasten neurologic recovery. The current Food and Drug Administration-approved dose of VPA is 60 mg/kg. We evaluate neurologic outcomes and brain lesion size of a single dose of VPA at a level currently within Food and Drug Administration-approved dose in swine subjected to TBI and hemorrhagic shock. Swine (n = 5/group) were subjected to TBI and 40% blood volume hemorrhage. Animals remained in shock for 2 hours before randomization to normal saline (NS) resuscitation alone (control), NS-VPA 150 mg/kg (VPA 150), or NS-VPA 50 mg/kg (VPA 50). Neurologic severity scores (range, 0-32) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day (PID) 3. Shock severity and laboratory values were similar in all groups. Valproic acid-treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs. VPA 150 mg/kg = 8 ± 7 or VPA 50 mg/kg = 6 ± 6; p = 0.02 and 0.003). Valproic acid-treated animals had significantly smaller brain lesion sizes (mean volume in mm3, control = 1,268.0 ± 241.2 vs. VPA 150 mg/kg = 620.4 ± 328.0 or VPA 50 mg/kg = 438.6 ± 234.8; p = 0.007 and 0.001). In swine subjected to TBI and hemorrhagic shock, VPA treatment, in a dose that is approved for clinical use, decreases brain lesion size and reduces neurologic impairment compared with resuscitation alone.


Centrality of the childhood cancer experience and its relation to post-traumatic stress and growth.
Event centrality, the degree to which a traumatic event is perceived as central to one's identity, has been associated with post-traumatic stress (PTS) symptoms and post-traumatic growth (PTG) outcomes in various trauma samples. Trauma frameworks are widely used to understand the psychological impact of pediatric cancer; however, event centrality has not been studied in this population. We investigated event centrality in pediatric cancer survivors and healthy comparisons, and its relation with PTS and PTG outcomes. Cancer survivors, age 13-23 (N = 196) and healthy comparisons (N = 131) completed the Centrality of Events Scale and PTS and PTG measures in reference to their most traumatic life event. Cancer survivors who first identified a non-cancer-related event repeated all measures in reference to cancer. Centrality scores were significantly higher when referencing cancer compared to non-cancer events, even in survivors for whom cancer was not rated as most stressful (53.1%). Centrality scores for non-cancer events were not significantly different between survivors and healthy comparisons. Event centrality showed significant positive relations to both PTS and PTG outcomes. The pediatric cancer experience is perceived as central to survivors' identity regardless of whether the experience is perceived as highly traumatic. Centrality of cancer is a significant predictor of both positive and negative psychological outcomes in cancer survivors.


Outcomes of concomitant mesh placement and intestinal procedures during open ventral hernia repair.
The concept of mesh use during open ventral hernia repair with a concomitant intestinal procedure remains controversial and it remains unclear whether the SSI profile of contaminated fields in this setting more closely resembles clean-contaminated or dirty wounds. Patients who underwent an open ventral hernia repair and intestinal procedures were extracted from the ACS-NSQIP database. Data analysis was performed for mesh versus no mesh groups in aggregate and matched cohorts. The 30-day outcomes including mortality, morbidity, surgical site infections (SSI), readmission, reoperation, and length of stay were compared between the groups. Of 5104 patients in the mesh group, 3297 patients were matched 1:1 with patients without mesh. Mesh placement was associated with higher overall morbidity (35.1% vs. 29.8%; p < 0.001), overall SSI (27.1% vs. 18%; p < 0.001), deep SSI (5.9% vs. 4.3%; p = 0.003), organ-space SSI (6.8% vs. 5.5%; p = 0.027), reoperation (9.9% vs. 8.2%; p = 0.016), readmission (16.7% vs. 12.7%; p < 0.001), and longer hospital stays (10.9 ± 15.2 vs. 9.7 ± 10.7; p < 0.001). When mesh was used, the SSI profile of contaminated fields was similar to dirty wounds (26.4% vs. 27.5%; p = 0.702), rather than clean-contaminated fields (26.4% vs. 19.2%; p < 0.001). Concomitant bowel procedure and mesh placement at the time of open ventral hernia repair was associated with worse outcomes. The SSI profile of the contaminated fields was more similar to dirty wounds. When deciding whether to place mesh during ventral hernia repairs with concomitant bowel procedures, strong consideration should be given to the increased risk of short-term complications versus the potential long-term benefits.


Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients.
Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis.


Single cell profiling of capillary blood enables out of clinic human immunity studies.
An individual's immune system is driven by both genetic and environmental factors that vary over time. To better understand the temporal and inter-individual variability of gene expression within distinct immune cell types, we developed a platform that leverages multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to enable simplified, cost-effective profiling of the human immune system across people and time at single-cell resolution. Using the platform, we detect widespread differences in cell type-specific gene expression between subjects that are stable over multiple days.


Finite element analysis of the release of slowly dissolving drugs from cylindrical matrix systems.
Drug release from matrix systems of cylindrical shape is analyzed in detail by using the finite element method. The model used combines the Noyes-Whitney and diffusion equations, and thus takes the effects of a finite dissolution rate into account. The model is valid for all drug solubilities and dissolution rates, and allows accurate predictions of the drug release to be made. Anisotropic drug transport that may result from the manufacturing process is properly accounted for. Model calculations show that a finite dissolution rate may affect the release profile significantly, producing an initial delay. The equivalence between anisotropic release and isotropic release from a matrix with different dimensions is demonstrated. Comparisons are made with the predictions of a recently proposed pseudo-steady state (PSS) analysis of drug release from cylindrical matrices [Y. Zhou, J. S. Chu, T. Zhou, X. Y. Wu, Modeling of dispersed-drug release from two-dimensional matrix tablets, Biomaterials 26 (2005) 945-952]. This comparison reveals that important discrepancies exist between the numerical and analytical results, which are attributed to the simplifying assumption made in the PSS analysis that the region containing solid drug remains cylindrical in shape throughout the release process. The proposed model is shown to describe experimental release data well.


Musical ability is associated with enhanced auditory and visual cognitive processing.
Musical ability has always been linked to enhanced cognitive and intellectual skills. We were interested in the relation between musical ability and short-time cognitive processing as measured by event-related potentials, in particular in visual processing, since previous studies have already suggested such a link for acoustic cognitive processing. We measured auditory and visual event-related potentials as elicited by an oddball paradigm in 20 healthy subjects (10 musicians and 10 non-musicians; 10 female; mean age 24 ± 2 years). In addition, the Seashore test and a test developed by the authors to detect relevant amusia, the latter one with a high ceiling effect, were also applied. The most important finding was that there is a significant linear correlation between musical ability as measured by these tests and the P3 latencies of both the auditory and visual event-related potentials. Furthermore, musicians showed shorter latencies of the event-related potentials than non-musicians. We conclude that musical ability as measured by neuropsychological tests is associated with improved short-time cognitive processing both in the auditory and, surprisingly, also in the visual domain.


Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?
The purpose of this study is to review the literature on the risk of malignancy in patients with inflammatory eye disease (IED) treated with systemic immunosuppressive (IS) therapy. Relevant databases in transplant medicine, autoimmune diseases and literature regarding uveitis and scleritis were reviewed. Literature with regards systemic IS therapy in transplant recipients and patients with autoimmune diseases revealed a significant increase in malignancies, especially non-melanocytic skin cancers and lymphomas. Studies of patients with IED were limited in number and scope, with no studies adequately evaluating the incidence of malignancy in these patients. Difficulties associated with the evaluation of the risk of malignancy associated with IS therapy in patients with IED include the heterogeneity of the disease and treatment regimens as well as the low frequency of IED, its variable severity and the lack of adequate long-term follow-up studies. Systemic IS therapy is an important therapeutic option in the treatment of patients with severe IED. A well-designed, comprehensive, multi-centre long-term follow-up study is required to evaluate the risk of malignancy in patients with specific IED diseases treated with defined systemic IS therapy. Until such evidence is available, we recommend the adoption of preventative strategies to help minimise the risk of malignancy in such patients.


Morphological and ultrastructural description of Pleistophora dammami sp. n. infecting the intestinal wall of Saurida undosquamis from the Arabian Gulf, Saudi Arabia.
Pleistophora dammami sp. n. is described from Saurida undosquamis from the Arabian Gulf in Saudi Arabia. Infection appeared as whitish cysts in the intestinal wall. Cysts ranged in size from 1 to 4 mm. The prevalence of the infection across both fish sexes was 17.5% (24/420). Two kinds of spores were recognized, microspores and macrospores, and each were ovoid in shape. The microspores measured ~2.5 × 2.0 μm in size, while the macrospores measured ~6.0 × 3.0 μm. Ultrastructurally, the parasite did not form xenoma but it formed cysts surrounded by thick cyst wall. All stages of development as meronts, sporonts, sporoblast and spores occurred in the cytoplasm of the host cells within sporophorous vesicles. The stages of development occurred asynchronously and thus all stages were randomly distributed within the cysts. Meronts were elliptical and multinucleated, with unpaired nuclei which constantly divided giving rise to new sporonts. During the transition to sporonts, the border of the meronts increased in thickness to form dense discontinuous cell coat. Later, the sporont divided into sporoblast cells which gradually differentiated the typical organelles of the spores. In mature spores, the polar filament was arranged in 20-24 coils in two rows either side of the posterior vacuole. All ultrastructural and morphological criteria indicate that the described species belongs to the genus Pleistophora.


Immunomodulating properties of two synthetic adjuvants: dependence upon type of antigen, dose, and time of administration.
The effects of two synthetic adjuvants on the antibody response to sheep red blood cells (SRBC) as a thymus dependent (TD) antigen and to dinitrophenyl59-Ficoll as a thymus-independent (TI-1) antigen were investigated in mice. Both dimethyldioctadecylammonium bromide (DDA) and dextran sulfate (DXS) augmented the humoral response to SRBC but not to dinitrophenyl59-Ficoll if injected simultaneously with antigen. Dose-response curves of both antigen and adjuvant revealed that DXS compared to DDA is a more effective adjuvant for the induction of a humoral response to SRBC. Intraperitoneal injection of DDA or DXS evoked a sequence of distinct immune responsive states in mice, measured by the capacity to develop an anti-SRBC response. A short immune-potentiating period (less than 6 hr) is followed by a suppressive, second immune-potentiating state. The immune suppressive state lasted for a period of about 8 days and was restricted to TD-antigens. Suppression could be totally overridden by injection of DDA or DXS simultaneously with antigen, suggesting that the suppressive state was reversible. The kinetics of the observed alteration of the immune response by DDA and DXS were very similar. It is concluded that differences in the modulation of the immune response by DDA and DXS are limited to the initial state. Long-term effects like the induction of a succession of distinct immune responsive states, are more or less similar for both adjuvants. Possible mechanisms by which these immunomodulators interfere with the immune system are discussed.


Meta-Analysis of Outcomes of a Single-Radius Versus Multi-Radius Femoral Design in Total Knee Arthroplasty.
Although the single-radius (SR) femoral design is known to have theoretical advantages in many aspects, studies of clinical outcomes that compare the SR with the multiple-radius (MR) femoral design are controversial. We performed a meta-analysis to address the hypothesis that a SR femoral design in primary total knee arthroplasty improves patient outcomes. The meta-analysis identified 15 articles reporting the clinical outcomes of 2212 knee replacements using the SR (n = 948) compared with the multiradius (MR; n = 1361) femoral design. Comparing SR with MR, we examined the Knee Society Score for the knee (KSS-knee), KSS-function, knee flexion, range of motion, complications, isometric peak torque of knee, and survival rate. The range of motion of SR knees was lower than that of MR knees. No differences were found in the analyses of KSS-knee, KSS-function, knee flexion, complications, isometric peak torque of the knee, and survival rate. Our meta-analysis does not provide clinical support for the previously reported theoretical advantages of the SR implant design.


Pseudoneutropenia as a factor-limiting access to chemotherapy for cancer patients: the effect of a simple meal.
Absolute neutrophil count (ANC) below 1.5 G/l or 1 G/l is commonly used as a factor to determine the decision to administer antineoplastic treatment including chemotherapy and novel agents to cancer patients. This practice is based on observations that below this ANC, there is an increased risk of bacterial and fungal infection. This is further based on the assumption that this parameter always correctly reflects the true shortage of these germ-fighting cells in patients. In reality, the circulating pool of neutrophils is only one of four reservoirs (bone marrow, circulating, marginal and tissue pools) and its size is influenced not only by shortage but also by transient shift of cells between these reservoirs. The aim of this study was to evaluate whether repeated blood collection affects ANC in the patient. We retrospectively analysed the medical records of cancer patients with 0.8 G/l ≤ ANC < 1.5 G/l in whom CBC was repeated based on the physician's decision, which was done on the same day roughly 2 h after the first one. The patients at the time of repeating CBC had consumed breakfast. In 31 out of 32 patients, ANC exceeded 1 G/l or 1.5 G/l and antineoplastic treatment was administered as originally planned. There were no infectious complications observed. Cancer patients should not be fasting prior to blood collection, with the exception of special and rare situations. To achieve the maximum clinical benefit, delays and/or reductions of antineoplastic treatment should be avoided wherever possible. Pseudoneutropenia is an unnecessary reason for postponing chemotherapy.


Exposure to a moderate intensity static magnetic field enhances the hypotensive effect of a calcium channel blocker in spontaneously hypertensive rats.
We investigated the combined effects of a moderate intensity static magnetic field (SMF) and an L-type voltage-gated Ca(2+) channel blocker, nicardipine in stroke-resistant spontaneously hypertensive rats during the development of hypertension. Five-week-old male rats were exposed to SMF intensity up to 180 mT (B(max)) with a peak spatial gradient of 133 mT/mm for 14 weeks. Four experimental groups of 14 animals each were examined: (1) sham exposure with intraperitoneal (ip) saline injection (control); (2) SMF exposure with ip saline injection (SMF); (3) sham exposure with ip nicardipine injection (NIC); (4) SMF exposure with ip nicardipine injection (SMF + NIC). A disc-shaped permanent magnet or a dummy magnet was implanted in the vicinity adjacent to the left carotid sinus baroreceptor region in the neck of each rat. Nicardipine (2 mg/kg ip) was administered three times a week for 14 weeks, and then 15 min after each injection, arterial blood pressure (BP), heart rate (HR), baroreflex sensitivity (BRS), skin blood flow (SBF), skin blood velocity (SBV), plasma nitric oxide (NO) metabolites (NO(x) = NO(2) (-) + NO(3) (-)), plasma catecholamine levels and behavioral parameters of a functional observational battery were monitored. The action of nicardipine significantly decreased BP, and increased HR, SBF, SBV, plasma epinephrine and norepinephrine in the NIC group compared with the control respective age-matched group without changing plasma NO(x) levels. Neck exposure to SMF alone for 5-8 weeks significantly suppressed or retarded the development of hypertension together with increased BRS in SMF group. Furthermore, the exposure to SMF for 1-8 weeks significantly promoted the nicardipine-induced BP decrease in the SMF + NIC group compared with the respective NIC group. Moreover, the SMF induced a significant increase in plasma NO(x) in the nicardipine-induced hypotension. There were no significant differences in any of the physiological or behavioral parameters measured between the SMF + NIC and the NIC groups, nor between the SMF and the control groups. These results suggest that the SMF may enhance nicardipine-induced hypotension by more effectively antagonizing the Ca(2+) influx through the Ca(2+) channels compared with the NIC treatment alone. Furthermore, the enhanced antihypertensive effects of the SMF on the nicardipine-treated group appear to be partially related to the increased NO(x). Theoretical considerations suggest that the applied SMF (B(max) 40 mT, 0 Hz) can be converted into a changing magnetic field (B(max) 30-40 mT, 5.7-6.5 Hz or 7.5-8.3 Hz) in the baroreceptor region by means of the carotid artery pulsation. Therefore, we propose that the moderate intensity changing magnetic field, i.e., the magnetic field modulated by the pulse rate, may influence the activity of baroreceptor and baroreflex function.


Pathologic concordance of sporadic synchronous bilateral renal masses.
To review the collective experience evaluating pathologic concordance rates of sporadic bilateral synchronous renal tumors reported in the Surveillance, Epidemiology, and End Results (SEER) database and the published English literature and treated at Fox Chase Cancer Center; specifically, to analyze concordance rates of malignant versus benign disease, histologic type, tumor stage, and nuclear grade. We reviewed the SEER database, the published English language literature, and our own institutional tumor registry to identify all cases of sporadic, synchronous localized (cT1-3N0M0) bilateral renal masses. Malignant and benign concordance rates were defined as agreement of any benign or malignant tumor type bilaterally. Histologic concordance was defined as bilateral histologic agreement. Tumors with mixed histologies were discordant unless all patterns were identical bilaterally. Nuclear grades were concordant if bilateral tumors were either "high" grade or "low" grade. The malignant concordance rate in the SEER data was 99% (273 of 274), and benign concordance was 0 (0 of 1). In the published literature and Fox Chase Cancer Center series, malignant concordance rates ranged from 84% to 95%, whereas benign concordance ranged from 39% to 67%. The SEER data revealed a histologic concordance rate of 93% (256 of 274), and nuclear grade concordance was 85% (88 of 103). These data demonstrate that in cases of bilateral sporadic localized synchronous renal masses, a diagnosis of ipsilateral renal cell carcinoma is associated with contralateral renal cell carcinoma in the vast majority of patients, whereas ipsilateral benign pathology is associated with contralateral benign disease at a substantially lower rate. Histologic concordance is similarly high, meaning most cases of clear cell or papillary tumors ipsilaterally are concordant in the contralateral kidney. Concordance rates of nuclear grade were slightly lower. These data are important when counseling and managing patients with bilateral synchronous sporadic renal tumors.


Comparisons of in vivo and in vitro photosensitivities and DNA repair in fibroblast and keratinocyte cells.
Minimal erythema dose of ultraviolet light correlated significantly with the UV-sensitivity of fibroblast cells from 5 patients with xeroderma pigmentosum, 13 patients with keratinocytic neoplasms of the skin, and 21 control subjects, but not with that of cells from 6 patients with photosensitive dermatitis. In unscheduled DNA synthesis after UV irradiation, the number of grains per nucleus was much less in keratinocytes than in fibroblasts, but the relative dose-response relationship was similar. This indicates that keratinocytes can also be used in vitro UV-sensitivity studies.


Hypolipidemic activity of okra is mediated through inhibition of lipogenesis and upregulation of cholesterol degradation.
Little is known about the hypolipidemic activity of okra; therefore, we investigated the hypolipidemic activity of okra and its interaction with gene expression of several key components involved in lipid homeostasis. Male C57BL/6 mice were randomly divided into three groups and fed with hyperlipidemic diet or two hyperlipidemic diets supplemented with 1% or 2% okra powder for eight weeks. Results demonstrated that okra dose-dependently decreased serum and hepatic total cholesterol and triglyceride, and enhanced fecal excretion of bile acids. Gene expression analysis revealed that okra upregulated cholesterol 7α-hydroxylase (CYP7A1) expression, downregulated expression of sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthase (FAS), with no effect on sterol regulatory element-binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), low-density lipoprotein receptor (LDLR) and carnitine palmitoyltransferase-1A (CPT1A). It was suggested that hypolipidemic activity of okra was mediated most likely by upregulation of cholesterol degradation through CYP7A1 and by inhibition of lipogenesis through SREBP1c and FAS. Okra raw and fractionated polysaccharide showed strong bile acid binding capacity in vitro, which may contribute to the hypolipidemic activity observed. In conclusion, okra has potential application in the management of hyperlipidemia and its associated metabolic disorders.


Improvement of biodegradability of PVA-containing wastewater by ionizing radiation pretreatment.
Polyvinyl alcohol (PVA) has been widely used as sizing agents in textile and manufacturing industry, and it is a refractory compound with low biodegradability. The objective of this paper was to treat the PVA-containing wastewater using gamma irradiation as a pretreatment strategy to improve its biodegradability and to determine the roles of different kinds of radical species played during pretreatment. Gamma radiation was carried out in a (60)Cobalt source station, PVA concentration was analyzed by using a visible spectrophotometer and specific oxygen uptake rate (SOUR, milligram of O(2) per gram of mixed liquor volatile suspended solids (MLVSS) per hour) was measured by a microrespirometer. The results showed that the biodegradability of PVA-containing wastewater with low initial concentration (e.g., 327.8 mg/l) could be improved greatly with increasing irradiation dose. However, PVA gel formation was observed at higher initial PVA concentration (e.g., 3,341.6 mg/l) and higher irradiation dose, which inhibited PVA degradation by aerobic microorganisms. However, the formed gel could be separated by microfiltration, which led to more than 90% total organic carbon (TOC) removal. Ionizing radiation could be used as a pretreatment technology for PVA-containing wastewater, and its combination with biological process is feasible.


Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study.
Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping. Objectives of this population pharmacokinetic (PK) analysis were to evaluate the dose-exposure relationship of tepotinib and its major circulating metabolite, MSC2571109A, and to identify the intrinsic/extrinsic factors that are predictive of PK variability. Data were included from 12 studies in patients with cancer and in healthy participants. A sequential modeling approach was used to analyze the parent and metabolite data, including covariate analyses. Potential associations between observed covariates and PK parameters were illustrated using bootstrap analysis-based forest plots. A two-compartment model with sequential zero- and first-order absorption, and a first-order elimination from the central compartment, best described the plasma PK of tepotinib in humans across the dose range of 30-1400 mg. The bioavailability of tepotinib was shown to be dose dependent, although bioavailability decreased primarily at doses above the therapeutic dose of 500 mg. The intrinsic factors of race, age, sex, body weight, mild/moderate hepatic impairment and mild/moderate renal impairment, along with the extrinsic factors of opioid analgesic and gefitinib intake, had no relevant effect on tepotinib PK. Tepotinib has a long effective half-life of ~ 32 h. Tepotinib shows dose proportionality up to at least the therapeutic dose, and time-independent clearance with a profile appropriate for once-daily dosing. None of the covariates identified had a clinically meaningful effect on tepotinib exposure or required dose adjustments.


Ultrahigh-resolution and 3-dimensional optical coherence tomography ex vivo imaging of the large and small intestines.
Ultrahigh-resolution optical coherence tomography (OCT) has an axial resolution of <5 microm, 2 to 3 times finer than standard OCT. This study investigates ultrahigh-resolution and three-dimensional OCT for ex vivo imaging of the large and small intestines and correlates images with histology. Ultrahigh-resolution OCT imaging was performed on fresh surgical specimens from the large and small intestines in the pathology laboratory, and images were correlated with histology. OCT was performed at 1.3-microm wavelength with 4.5-microm axial x 11-microm transverse resolution and at 1.1-microm wavelength with 3.5-microm axial x 6-microm transverse resolution. Three-dimensional OCT also was investigated. Normal and pathologic areas from 23 surgical specimens of the large and small intestines were imaged. Ultrahigh-resolution OCT distinguished the epithelial layer of the mucosa and visualized individual villi, glands, and crypts. Finer transverse resolutions improved visualization of features, e.g., the epithelium, but reduced the depth of field. Architectural distortion of glands from inflammatory and neoplastic processes was observed. Three-dimensional rendering enabled visualization of surface pit pattern and mucosal folds as well as subsurface crypt microstructure. This study evaluates new OCT technology and can provide a baseline for interpreting future ultrahigh-resolution endoscopic OCT studies.


Radial Access for Peripheral Interventions.
Peripheral vascular intervention (PVI) improves quality of life and reduces major adverse limb events in patients with peripheral arterial disease. PVI is commonly performed via the femoral artery, and the most common adverse periprocedural event is a vascular access complication. Transradial access for PVI has the potential to reduce vascular access complications and improve patient outcomes. Further study is needed to elucidate the risks of stroke, acute kidney injury, and radiation exposure in the setting of transradial PVI. As transradial access for PVI progresses, it will be important to build the evidence base along with procedural experience.


A lectin recognizes differential arrangements of O-glycans on mucin repeats.
Interaction of Vicia villosa agglutinin-B4 (VVA-B4) to glycopeptides with O-linked GalNAc residues was investigated by surface plasmon resonance. The affinity was shown to be influenced by the arrangement of O-glycosylation sites on a peptide, PTTTPITTTTK, representing the tandem repeat of MUC2. The association rate constant was relatively high with a particular category of GalNAc-peptides in which more than three amino acid residues were placed between GalNAc-Thr residues. PTT( *)T( *)PITT( *)T( *)TK (T( *) indicates GalNAc-Thr) had the highest association rate constant among the glycopeptides tested. The dissociation rate constant was low in the peptides containing consecutive GalNAc residues and PT( *)TTPIT( *)T( *)T( *)TK was the lowest of the glycopeptides tested. Dissociation constant (K(D)), calculated as k(d)/k(a) was the lowest with PTT( *)T( *)PITT( *)T( *)TK. Therefore, the arrangement but not the quantity of GalNAc residues apparently determines the affinity between VVA-B4 and peptides with attached GalNAc residues.


Expression patterns of ADAMs in the developing chicken lens.
In the present study the expression patterns of ADAM (a disintegrin and metalloprotease) genes in the chicken developing lens were analyzed. Using in situ hybridization, we found that seven members of the ADAM family including ADAM9, ADAM10, ADAM12, ADAM13, ADAM17, ADAM22, and ADAM23 are expressed in the developing embryonic lens. From embryonic incubation day (E) 2 to E3, most of the ADAMs investigated here are expressed in the lens placode and lens vesicle. From E5 to E7, all seven ADAMs, but predominantly ADAM9 and ADAM10, are throughly expressed in the central epithelium, as well as in the proliferating lens epithelium and the equatorial lens epithelium. From E9 to E14, expression of ADAM9, ADAM10, and ADAM17 decreases moderately in these regions. ADAM12 and ADAM13 are weakly expressed in the central epithelium and the lens epithelium, and are not detectable from E14 onward. ADAM22 and ADAM23 are expressed in the central epithelium, the lens epithelium and the equatorial lens epithelium at E5 and decrease gradually afterwards in the same regions. At E16, only weak ADAM9, ADAM10 and ADAM17 signals are found in the anterior lens epithelium. The changing spatiotemporal expression of the seven ADAMs suggests a regulatory role for these molecules during chicken lens development.


Explicit knowledge and real-time action control: anticipating a change does not make us respond more quickly.
When the target of a goal-directed reach changes location, people normally respond rapidly and automatically to the target shift. Here, we investigate whether explicit knowledge about a moving target (knowing whether a location change is likely/unlikely) improves responsiveness, with the goal of understanding top-down effects on real-time reaching. In Experiment 1, we presented participants with pre-cues that indicated a 20 or 80% likelihood of a target perturbation on that trial. When participants made pro-pointing responses to the target perturbations, their online response occurred later for 20% trials than for 80% trials, but this effect may have been due to suppression of the online response on 20% trials, rather than enhancement of the response on 80% trials. In Experiment 2, we presented participants with 50 and 100% likelihood pre-cues, and observed no shortening of the latency on 100% trials compared to 50% trials, which suggests that expectation does not enhance the automatic response to a perturbation. However, we did observe more vigorous responses to the perturbation on the 100% trials, and this contributed to shorter movement times relative to the 50% trials. We also examined, in Experiment 2, whether prior knowledge about the direction of the target perturbation would shorten the latency of the online response, but we did not observe any reduction in latency. In sum, the onset of the automatic response appears to be suppressible, but not augmentable by top-down input. The possibility that the forcefulness of the automatic response is modifiable by expectation is examined, but not resolved.


Prevalence of anti-legionella antibodies among Italian hospital workers.
This study evaluated the prevalence of anti-legionella antibodies in workers at hospitals with a long-term history of legionella contamination. The hospitals are located in Milan and Turin, northern Italy, and in Naples and Bari, southern Italy. Antibody prevalence and titres of healthcare workers, medical and dental students and blood donors were assessed. In total 28.5% of subjects were antibody positive, most frequently to L. pneumophila serogroups 7-14. Major differences were observed in seroprevalence and type of legionella antibody in persons from different geographic areas. Healthcare workers had a significantly higher frequency of antibodies compared with blood donors in Milan (35.4 vs 15.9%, P<0.001), whereas in Naples both groups exhibited high antibody frequency (48.8 vs 44.0%) and had a higher proportion of antibodies to legionella serogroups 1-6. Dental workers had a higher seroprevalence than office staff in Bari, but not in Turin, where daily disinfecting procedures had been adopted to avoid contamination of dental unit water. No association was found between the presence of antibodies and the presence of risk factors for legionellosis, nor with the occurrence of pneumonia and/or flu-like symptoms. In conclusion, the presence of legionella antibodies may be associated with occupational exposure in the hospital environment, but there was no evidence of any association with disease.