Cell biology of lipid droplets.
Lipid storage has attracted much attention in the past years, both by the broader public and the biomedical scientific community. Driven by concerns about the obesity epidemic that affects most industrialized countries and even substantial parts of the population in less and least developed countries, work from researchers of many disciplines has shed light on the genetics, the physiology, and the cellular mechanisms of fat accumulation. This review focuses on the actual organelle of fat deposition, the lipid droplet (LD), and on the recent progress in mechanistic understanding of processes like LD biogenesis, LD growth and degradation, protein targeting to LDs and LD fusion.


A study of plaque vascularization and inflammation using quantitative contrast-enhanced US and PET/CT.
Contrast-enhanced ultrasound (CEUS) is an in vivo methodology to quantify carotid plaque vascularization. Increased metabolism in plaques, measured as FDG uptake in PET/CT examination, has been associated with markers of inflammation in histological samples. In this study, we tested the association between FDG uptake and vascularization measured by CEUS to assess whether CEUS can be used as an in vivo marker of plaque vulnerability. After informed consent, subjects aged >60 years with carotid plaque height exceeding 2.5mm were recruited. CEUS was performed and analyzed using earlier described protocol and software, Contrast Quantification Program, which calculates the fraction of the plaque being contrast positive (CQP value). PET/CT examination was performed within 3 months of CEUS (median time 7 days). PET/CT images were acquired 90 min after FDG injection (2.7 MBq/kg). FDG uptake was measured as tissue background index (TBI), calculated using Spearman's rho as mean standard uptake value (SUV) of the plaque divided by mean SUV in the jugular vein (mean of 7 measuring points). Local ethics committee approved the study. We recruited 13 subjects (5 women) with a mean age of 71 years, 6 had a history of stroke or TIA, 1 had a history of ipsilateral stroke. CQP values showed a significant, positive correlation with TBI of carotid plaques, r=0.67, p<0.02. Plaque vascularization measured by CEUS correlates positively with FDG uptake measured by PET/CT in humans. This indicates an association between vascularization and inflammation and/or hypoxia, supporting the use of CEUS as a non-invasive method to detect plaque vulnerability.


Are lionfish set for a Mediterranean invasion? Modelling explains why this is unlikely to occur.
The Atlantic invasion of Indo-Pacific lionfish (Pterois volitans/P. miles) has been as swift as it has been disastrous. Lionfish are non-native to the Mediterranean, but an invasion is perhaps even more likely than for the Atlantic. First, as for the Atlantic, there are many major cities on the coast of the Mediterranean (where aquarium-keeping is a common practice and chances of accidental and deliberate releases are high), and second, lionfish are native to the Red Sea, to which the Mediterranean is connected via the Suez Canal. Furthermore, there have already been four records of lionfish in the Mediterranean and so the pretext for an invasion is already in place. Up until now, however, it has been difficult to gauge the likelihood of an infestation of lionfish in the Mediterranean as, unlike the Atlantic, this sea has not been examined in terms of its hydrodynamics, ocean climate, and bathymetry, all factors known to be relevant to assessing the possibility of invasion. Motivated by this knowledge-gap, this study used remote sensing and computer modeling to investigate the connectivity between areas along the Mediterranean coastline that fulfill the necessary physical criteria to serve as potential lionfish habitat. Model results from the Mediterranean were compared and contrasted to those from the Atlantic and eastern Pacific. The Atlantic was considered because the lionfish invasion there has been voracious. Meanwhile, the eastern Pacific is interesting as a site without native lionfish, but with plenty of opportunity for their introduction, but no invasion yet recorded. Results indicated that, unlike in the Atlantic, connectivity among potential lionfish habitats in the Mediterranean was low in the study and comparable to that in the eastern Pacific. Although oceanographic conditions in the Mediterranean were found unfavorable for wide dispersion of lionfish larvae, hotspots where numerous lionfish sightings would forewarn an impending invasion were identified. This paper can therefore serve as a guide to the most efficient monitoring of lionfish in the Mediterranean and to where removal efforts should be concentrated, should the species become established.


Amine-tethered solid adsorbents coupling high adsorption capacity and regenerability for CO2 capture from ambient air.
Silica supported poly(ethyleneimine) (PEI) materials are prepared via impregnation and demonstrated to be promising adsorbents for CO(2) capture from ultra-dilute gas streams such as ambient air. A prototypical class 1 adsorbent, containing 45 wt% PEI (PEI/silica), and two new modified PEI-based aminosilica adsorbents, derived from PEI modified with 3-aminopropyltrimethoxysilane (A-PEI/silica) or tetraethyl orthotitanate (T-PEI/silica), are prepared and characterized by using thermogravimetric analysis and FTIR spectroscopy. The modifiers are shown to enhance the thermal stability of the polymer-oxide composites, leading to higher PEI decomposition temperatures. The modified adsorbents present extremely high CO(2) adsorption capacities under conditions simulating ambient air (400 ppm CO(2) in inert gas), exceeding 2 mol(CO (2)) kg(sorbent)(-1), as well as enhanced adsorption kinetics compared to conventional class 1 sorbents. The new adsorbents show excellent stability in cyclic adsorption-desorption operations, even under dry conditions in which aminosilica adsorbents are known to lose capacity due to urea formation. Thus, the adsorbents of this type can be considered promising materials for the direct capture of CO(2) from ultra-dilute gas streams such as ambient air.


Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption.
In the present study we sought to determine the effect of CoCl2, an inhibitor of PHD (prolyl hydroxylase domain protein), on the development of AAA (abdominal aortic aneurysm). AAA was induced in C57BL/6 mice by periaortic application of CaCl2 (AAA group). NaCl (0.9%)-treated mice were used as a sham control (SHAM group). Mice were treated with 0.05% CoCl2 in the drinking water (AAA/CoCl2 group). At 1 and 6 weeks after the operation, aortic tissue was excised for further examination. After 6 weeks of CaCl2 treatment, aortic diameter and macrophage infiltration into the aortic adventitia were increased in the AAA group compared with the SHAM group. Treatment with CoCl2 reduced the aneurysmal size and macrophage infiltration compared with the AAA group. Aortic expression of inflammatory cytokines and MCP-1 (monocyte chemoattractant protein-1) and the activities of MMP-9 (matrix metalloproteinase-9) and MMP-2 were enhanced in the AAA group and attenuated in the AAA/CoCl2 group. Expression of cytokines and the activities of MMPs were already increased after 1 week of CaCl2 treatment, but were suppressed by CoCl2 treatment in association with reduced NF-κB (nuclear factor κB) phosphorylation. Treatment with CoCl2 in mice prevented the development of CaCl2-induced AAA in association with reduced inflammation and ECM (extracellular matrix) disruption. The results of the present study suggest that PHD plays a critical role in the development of AAA and that there is a therapeutic potential for PHD inhibitors in the prevention of AAA development.


Syntheses, crystal structures, optical and theoretical studies of the actinide thiophosphates SrU(PS4)2, BaU(PS4)2, and SrTh(PS4)2.
Three new actinide thiophosphates, SrU(PS4)2, BaU(PS4)2, and SrTh(PS4)2, have been synthesized by high-temperature solid-state methods, and their crystal structures were determined from single-crystal X-ray diffraction studies. These three isostructural compounds crystallize in a new structure type in space group D4h13-P42/mbc of the tetragonal system. Their structure features infinite one-dimensional chains of ∞1[An(PS4)2(2–)] anions (An = U or Th). Each An atom is coordinated by eight S atoms in a bicapped trigonal prism, and each P atom is tetrahedrally bonded to four S atoms. The compounds are readily charge balanced as Ak2+An4+(P5+(S2–)4)2. Optical studies on single crystals of SrU(PS4)2 and BaU(PS4)2 as well as ground single crystals of SrTh(PS4)2 revealed a direct band gap of 2.13(2) eV and an indirect band gap value of 1.99(2) eV for SrU(PS4)2 and a direct and indirect gap of about 2.28(2) eV for BaU(PS4)2. SrTh(PS4)2 has a relatively large band gap of 3.02(2) eV. DFT calculations for SrU(PS4)2 and BaU(PS4)2 using the HSE functional predict both compounds to be antiferromagnetic and have very similar electronic structures with band gaps of 2.7 eV. The band gap calculated for SrTh(PS4)2 is 3.2 eV.


[Sonographic vascular analysis in segmental aplasia-hypoplasia of the inferior vena cava].
The absence or hypoplasia of the hepatic segment of the inferior vena cava with azygos continuation is a rare entity, sometimes associated with congenital heart disease, situs inversus or polysplenia syndrome. Ultrasonography as an easy, non-invasive procedure enables reliable diagnosis of this anomaly replacing inferior cavography. Ultrasonic scans performed in various directions allow a more subtle analysis of vessels and location of azygos continuation. We present an analysis of the sonographic feature in this anomaly, as studied in 2 patients. The diagnosis of this usually incidental finding (chest X-ray) can be of major clinical importance e.g. if special surgical procedures such as ligature of the azygos vein are considered.


Effects of retinoids on proliferation and plasminogen activator expression in a bovine mammary epithelial cell line.
Effects of two natural (retinol and retinoic acid, RA) and one synthetic N-(4-hydroxyphenyl) retinamide (4-HPR) retinoids on proliferation and expression of urokinase-plasminogen activator (u-PA) by bovine mammary epithelial cells were examined. The BME-UV1 established bovine mammary epithelial cell line was used as a model system. All retinoids tested (retinol, RA and 4-HPR) were effective inhibitors of cell proliferation. When cells were cultured in the absence of fetal bovine calf serum (FBCS), inhibition occurred at concentrations as low as 1 nM for all retinoids tested. The effect of retinoids on cell proliferation was not dose-related when cells were cultured in the absence of FBCS. All retinoids (retinol, RA, 4-HPR), when used in the range 1 nM-10 microM (noncytotoxic concentrations), were equally effective and had identical inhibition patterns. Inhibition of cell proliferation by RA was apparent by 6 h and was higher after 24 h in culture. In contrast, when cells were cultured in the presence of FBCS, the effect of RA and retinol on cell proliferation was dose-related. RA and retinol inhibited cell proliferation (P<0.01) when added to the culture medium in concentrations as low as 10 nM and 100 nM, respectively. 4-HPR was inhibitory (P<0.01) in concentrations as low as 1 nM. Higher concentrations of 4-HPR in the range 1 nM-1 microM had no further effect on cell proliferation. None of the retinoids tested, when added to cultures in the presence or absence of FBCS, could completely arrest cell proliferation at noncytotoxic concentrations. RA at 1 microM inhibited (P<0.05) insulin or IGF-I-induced cell proliferation but had no effect (P>0.05) on u-PA mRNA levels or u-PA activity. Furthermore, RA inhibited cell proliferation in the presence of FBCS but had no effect (P>0.05) on u-PA mRNA levels. Thus, retinoids are effective inhibitors of bovine mammary epithelial cell proliferation and this growth inhibition does not seem to correlate with any changes in u-PA mRNA or u-PA activity.


Medication prior authorization in pediatric hematology and oncology.
Medication prior authorization (PA) is a commonly occurring requirement, particularly for medications used for rare conditions. Based on standard definitions, cancer and many blood disorders affecting children are rare. The study aims were to describe the relative frequency of PA requests and their association with payers and medications in order to identify opportunities to improve system efficiency. Requests for medication PA were logged prospectively for patients seen at a single institution over a 7-month period. Period prevalence was used to estimate the relative frequency of PA requests. Descriptive statistics summarized the relationship among payers, medications, and approvals relative to the frequency of PA requests. For the study duration of 150 clinic days, there were 5,583 patient visits. A total of 142 medication PA requests were received resulting in a period prevalence rate of 2.5% patient visits. Of the 137 medication PA requests with available outcome data, 135 (98.5%) were ultimately approved with additional provider efforts. The median clinic staff time spent per request was 46 min with an interquartile range of 25-80 min. There was striking process heterogeneity among different payers. Virtually no medication PA request in pediatric hematology and oncology (PHO) leads to alterations in care. Medication utilization management strategies in PHO fail to provide benefits reported in other areas of medicine and have unmeasured negative effects on timeliness of care and parenteral psychological/emotional health. There is opportunity for increasing efficiency through payer and provider collaboration on the creation of prescribing standards for PHO patients.


Characterization of the cDNA corresponding to a phosphoprotein (p43) intermediary in the action of ACTH.
We have previously isolated and partially-sequenced a soluble phosphoprotein (p43) that acts as intermediary in the stimulation of steroid synthesis. In this report we have used synthetic peptides whose sequences match those obtained from p43 to generate antipeptide antibodies and show that these antibodies bind to purified p43 protein as determined by immunoblot analysis. The presence of p43 was detected by Western blot in both steroidogenic and non-steroidogenic tissues. One of the antibodies was also used to purify p43 on immunoaffinity chromatography columns. Proteins eluting from affinity columns produce a twelve-fold stimulation of progesterone synthesis. This effect was blocked by the use of an inhibitor of phospholipase A2. These results suggest the involvement of p43 in transducing the adrenocorticotropin signal to mitochondria in zona fasciculata cells. We also describe a partial cDNA clone with a predicted amino acid sequence that matches the sequences of the internal peptides of p43.


Behaviour of whey protein emulsion gel during oral and gastric digestion: effect of droplet size.
A set of whey protein stabilized-emulsion gels with different droplet size distributions (D4,3 = ∼1, 6 and 12 μm) was produced, and the mechanical properties of the gels in the linear viscoelastic region and at large deformation were measured, along with the physicochemical and structural changes of the gels during oral mastication and gastric digestion. The gels containing 1 μm oil droplets had an aggregated particle structure with proteins coating at oil droplets whereas the gels containing 12 μm oil droplets had a particle-filled structure with spatially continuous matrix. During oral processing, the release of oil droplets from the gels increased as the droplet size increased, with coalescence being seen in gels containing oil droplets of 6 and 12 μm diameter. Under gastric digestion, high degrees of coalescence and phase separation of oil droplets occurred in the gels containing 6 and 12 μm oil droplets because of oil droplet release from the gel matrix; this led to slow gastric emptying. The gels were finally broken down into peptide aggregates and oil droplets (or free oil). The gels, containing 1 μm oil droplets disintegrated into various particles of several to several tens of microns with a low degree of oil droplet release and coalescence. Protein breakdown was slower in these gels, suggesting that the protein structures of the gel matrices were affected by the sizes of the incorporated oil droplets.


Image Denoising via Bandwise Adaptive Modeling and Regularization Exploiting Nonlocal Similarity.
This paper proposes a new image denoising algorithm based on adaptive signal modeling and regularization. It improves the quality of images by regularizing each image patch using bandwise distribution modeling in transform domain. Instead of using a global model for all the patches in an image, it employs content-dependent adaptive models to address the non-stationarity of image signals and also the diversity among different transform bands. The distribution model is adaptively estimated for each patch individually. It varies from one patch location to another and also varies for different bands. In particular, we consider the estimated distribution to have non-zero expectation. To estimate the expectation and variance parameters for every band of a particular patch, we exploit the nonlocal correlation in image to collect a set of highly similar patches as the data samples to form the distribution. Irrelevant patches are excluded so that such adaptively learned model is more accurate than a global one. The image is ultimately restored via bandwise adaptive soft-thresholding, based on a Laplacian approximation of the distribution of similar-patch group transform coefficients. Experimental results demonstrate that the proposed scheme outperforms several state-of-the-art denoising methods in both the objective and the perceptual qualities.


Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model.
Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug.


[Plastic surgery of the sequelae of suppurative mastitis].
Results of the surgical correction of consequences of purulent mastitis in 53 patients with 73 plastic operations are described. They were aimed at elimination of scarring deformation and asymmetry and restoration of the volume and form of the breast. Specific features of the surgical technique for performing the reconstructive-restorative operations in this group of patients are described.


Diagnosis of nonconvulsive status epilepticus (NCSE) in adults with altered mental status: clinico-electroencephalographic considerations.
The high incidence of nonconvulsive status epilepticus (NCSE) and difficulties encountered in rapid diagnosis have only recently become apparent and most neurophysiology textbooks have yet to fully address this topic. There is an immediate need to provide neurologists, neurology residents, and electroneurodiagnostic technologists with information to assist them in achieving early, accurate diagnosis of NCSE in patients they encounter on a daily basis. Instead of attempting to write a comprehensive review of the topic, we examined over 90 NCSE publications since 1972 and focused our efforts on extracting and summarizing those EEG and clinical considerations we found most useful for accurate diagnosis of NCSE in an adult population. The wide overlap between the clinical symptoms of NCSE and many other disorders causing change in mental status limits the usefulness of clinical measures for diagnosis. Those clinical parameters which have some utility are outlined. EEG testing and accurate interpretation is needed to identify NCSE in most instances. EEG patterns of NCSE are detailed and examples provided in order of progressive complexity. Timely treatment reduces patient risk for morbidity attributed to NCSE. Electroneurodiagnostic technologists who learn to recognize the entire spectrum of NCSE EEG patterns are better able to alert electroencephalographers to EEGs likely needing expedited review. This may facilitate early diagnosis if electroencephalographers determine that NCSE is indeed present. Electroencephalographers correlate the EEG pattern, clinical activity, and other diagnostic information to provide the treating medical doctors with an interpretation and recommendation in a timely manner. Lastly, EEG and clinical checklists and an algorithm which uses benzodiazepine response in conjunction with continuous EEG monitoring are provided to help reduce uncertainty in interpretation of equivocal EEG patterns of NCSE.


Suppression of menthyl anthranilate (UV-A sunscreen)-sensitized singlet oxygen generation by Trolox and α-tocopherol.
Menthyl anthranilate (MA, tradename meradimate) is a UV-A absorber. The interactions of ground-state molecular oxygen with the long-lived triplet state of MA produce singlet oxygen through energy transfer. The quantum yield of singlet oxygen generation is 0.12 in air-saturated ethanol. Kinetic traces of the near-IR phosphorescence of singlet oxygen generated by MA-photosensitization have been measured in the absence and presence of Trolox (a water-soluble analogue of vitamin E and a quencher of singlet oxygen) and α-tocopherol (vitamin E, a natural antioxidant) in ethanol. Fluorescence and transient absorption measurements suggest that Trolox and α-tocopherol quench the lowest excited singlet and triplet states of MA. As a result, Trolox and α-tocopherol suppress MA-photosensitized singlet oxygen generation. Not only the quenching of singlet oxygen but also the suppression of singlet oxygen generation is the mechanism of antioxidant properties of Trolox and α-tocopherol for MA. The ability of α-tocopherol to suppress the MA-photosensitized singlet oxygen generation in isododecane, used as a solvent for an oil-soluble UV absorber, is close to that in ethanol. Suppression of sunscreen-photosensitized singlet oxygen generation is an important method for the formulation of safe cosmetic sunscreens.


Prevalence of pain and association with psychiatric symptom severity in perinatally HIV-infected children as compared to controls living in HIV-affected households.
This cross-sectional study evaluated the prevalence of pain and psychiatric symptoms in perinatally HIV-infected children at entry into P1055, a multicenter investigation of the prevalence and severity of psychiatric symptoms in HIV-infected children. Subjects 6-17 years of age and their primary caregivers were recruited from 29 International Maternal Pediatric Adolescent AIDS Clinical Trials sites in the USA and Puerto Rico. A total of 576 children (320 HIV and 256 HIV- children) were enrolled from June 2005 to September 2006. Subject self-reports of pain were measured by the Wong-Baker visual analog scale and Short-Form McGill Pain Questionnaire. Symptomatology for anxiety, depression, and dysthymia was assessed through Symptom Inventory instruments. Caregiver's assessment of their child's pain and psychiatric symptomatology was similarly measured. Logistic regression models were used to evaluate predictors of pain. We found that a higher proportion of HIV-infected than uninfected subjects reported pain in the last two months (41% vs 32%, p=0.04), last two weeks (28% vs 19%, p=0.02), and lasting more than one week (20% vs 11%, p=0.03). Among HIV-infected youth, females (OR=1.53, p=0.09), White race (OR=2.15, p=0.04), and Centers for Disease Control (CDC) Class C (OR=1.83, p=0.04) were significantly more likely to report pain. For all subjects, only 52% of caregivers recognized their child's pain and just 22% were aware that pain affected their child's daily activities. The odds of reported pain in HIV increased with higher symptom severity for generalized anxiety (OR=1.14, p=0.03), major depression (OR=1.15, p=0.03), and dysthymia (OR=1.18, p=0.01). This study underscores the importance of queries concerning pain and emotional stressors in the care of HIV and uninfected children exposed to HIV individuals. The discordance between patient and caregiver reports of pain and its impact on activities of daily living highlights that pain in children is under-recognized and therefore potentially under-treated.


Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-gamma.
IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV)NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response IFN-gamma has different effects.


Ant Diversity and Distribution along Elevation Gradients in the Australian Wet Tropics: The Importance of Seasonal Moisture Stability.
The threat of anthropogenic climate change has seen a renewed focus on understanding contemporary patterns of species distribution. This is especially the case for the biota of tropical mountains, because tropical species often have particularly narrow elevational ranges and there are high levels of short-range endemism. Here we describe geographic patterns of ant diversity and distribution in the World Heritage-listed rainforests of the Australian Wet Tropics (AWT), revealing seasonal moisture stability to be an important environmental correlate of elevational patterns of species composition. We sampled ants in leaf litter, on the litter surface and on tree trunks at 26 sites from six subregions spanning five degrees of latitude and elevation ranges from 100-1,300 m. A total of 296 species from 63 genera were recorded. Species richness showed a slight peak at mid elevations, and did not vary significantly with latitude. Species composition varied substantially between subregions, and many species have highly localised distributions. There was very marked species turnover with elevation, with a particularly striking compositional disjunction between 600 m and 800 m at each subregion. This disjunction coincides with a strong environmental threshold of seasonal stability in moisture associated with cloud 'stripping'. Our study therefore provides further support for climatic stability as a potential mechanism underlying patterns of diversity. The average height of orographic cloud layers is predicted to rise under global warming, and associated shifts in seasonal moisture stability may exacerbate biotic change caused by rising temperature alone.


Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease.


Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age.
We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.


DNA vaccines for cervical cancer.
Human papillomavirus (HPV), particularly type 16, has been associated with more than 99% of cervical cancers. There are two HPV oncogenic proteins, E6 and E7, which play a major role in the induction and maintenance of cellular transformation. Thus, immunotherapy targeting these proteins may be employed for the control of HPV-associated cervical lesions. Although the commercially available preventive HPV vaccines are highly efficient in preventing new HPV infection, they do not have therapeutic effects against established HPV infection or HPV-associated lesions. Since T cell-mediated immunity is important for treating established HPV infections and HPV-associated lesions, therapeutic HPV vaccine should aim at generating potent E6 and E7-specific T cell-mediated immune responses. DNA vaccines have now developed into a promising approach for antigen-specific T cell-mediated immunotherapy to combat infection and cancer. Because dendritic cells are the most potent professional antigen-presenting cells, and are highly effective in priming antigen-specific T cells, several DNA vaccines have employed innovative strategies to modify the properties of dendritic cells (DCs) for the enhancement of the DNA vaccine potency. These studies have revealed impressive pre-clinical data that has led to several ongoing HPV DNA vaccine clinical trials.


Stacking Order in Graphite Films Controlled by van der Waals Technology.
In graphite crystals, layers of graphene reside in three equivalent, but distinct, stacking positions typically referred to as A, B, and C projections. The order in which the layers are stacked defines the electronic structure of the crystal, providing an exciting degree of freedom which can be exploited for designing graphitic materials with unusual properties including predicted high-temperature superconductivity and ferromagnetism. However, the lack of control of the stacking sequence limits most research to the stable ABA form of graphite. Here, we demonstrate a strategy to control the stacking order using van der Waals technology. To this end, we first visualize the distribution of stacking domains in graphite films and then perform directional encapsulation of ABC-rich graphite crystallites with hexagonal boron nitride (hBN). We found that hBN encapsulation, which is introduced parallel to the graphite zigzag edges, preserves ABC stacking, while encapsulation along the armchair edges transforms the stacking to ABA. The technique presented here should facilitate new research on the important properties of ABC graphite.


Dosing frequency and adherence in chronic psychiatric disease: systematic review and meta-analysis.
The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases. A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder. Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS(®)), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71-2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86-2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%-75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis. Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.


TP53 gene mutations and 17p deletions in human astrocytomas.
Astrocytomas, including the most malignant form, glioblastoma multiforme, are the most frequent and deadly primary tumors of the human nervous system. Recent molecular genetic analyses of astrocytomas have demonstrated frequent chromosome 17 deletions involving the telomeric region of the short arm (17p12-pter). This region contains a candidate tumor suppressor gene, TP53, which has recently been implicated in the etiology of a broad array of human cancers. To study the possible role of TP53 in astrocytoma development, 24 randomly chosen human astrocytic tumors were examined for genomic TP53 sequence aberrations using primer-directed DNA amplification in conjunction with direct sequencing. Five of the 11 grade III astrocytomas (glioblastoma multiforme), but only one of seven grade II astrocytomas (anaplastic astrocytoma) and none of either the grade I astrocytomas or oligodendrogliomas demonstrated distinct point mutations involving the TP53 gene. These data suggest that TP53 mutations may play a role in astrocytoma development and are predominantly associated with higher grade tumors.


Neutrophil elastase increases airway ceramide levels via upregulation of serine palmitoyltransferase.
Altered sphingolipid metabolism is associated with increased inflammation; however, the impact of inflammatory mediators, including neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. Using a well-characterized mouse model of NE oropharyngeal aspiration, we investigated a potential link between NE-induced airway inflammation and increased synthesis of various classes of sphingolipids, including ceramide species. Sphingolipids in bronchoalveolar lavage fluids (BAL) were identified and quantified using reverse-phase high-performance liquid chromatography/electrospray ionization tandem mass spectrometry analysis. BAL total and differential cell counts, CXCL1/keratinocyte chemoattractant (KC) protein levels, and high-mobility group box 1 (HMGB1) protein levels were determined. NE exposure increased BAL long-chain ceramides, total cell and neutrophil counts, and upregulated KC and HMGB1. The mRNA and protein levels of serine palmitoyltransferase (SPT) long-chain subunits 1 and 2, the multimeric enzyme responsible for the first, rate-limiting step of de novo ceramide generation, were determined by qRT-PCR and Western analyses, respectively. NE increased lung SPT long-chain subunit 2 (SPTLC2) protein levels but not SPTLC1 and had no effect on mRNA for either subunit. To assess whether de novo ceramide synthesis was required for NE-induced inflammation, myriocin, a SPT inhibitor, or a vehicle control was administered intraperitoneally 2 h before NE administration. Myriocin decreased BAL d18:1/22:0 and d18:1/24:1 ceramide, KC, and HMGB1 induced by NE exposure. These results support a feed-forward cycle of NE-generated ceramide and ceramide-driven cytokine signaling that may be a potential target for intervention in lung disease typified by chronic neutrophilic inflammation.


Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease.
Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.


Assessment of greenness for the determination of voriconazole in reported analytical methods.
Analytical research with adverse environmental impact has caused a severe rise in concern about the ecological consequences of its strategies, most notably the use and emission of harmful solvents/reagents into the atmosphere. Nowadays, industries are searching for the best reproducible methods. Voriconazole is a second-generation azole derivative used effectively in the treatment of Candida and Aspergillus species infections and oropharyngeal candidiasis in AIDS patients. Recently it has become the drug of choice in treating mucormycosis in several countries, which raises the need for production in large quantities. The present review deals with various recent important analytical techniques used to estimate voriconazole and its combination in pharmaceutical formulations and biological fluids. The methods show their own unique way of analyzing voriconazole in different matrices with excellent linearity, detection, and quantification limits. Additionally, this article deals with methods and solvents analyzed for their impact on the environment. This is followed by estimating the degree of greenness of the methods using various available assessment tools like analytical eco-scale, national environmental method index, green analytical procedure index, and AGREE metrics to confirm the environmental impact. The scores obtained with the evaluation tools depict the quantum of greenness for the reported methods and provide an ideal approach adopted for VOR estimation. Very few methods are eco-friendly, which shows that there is a need for the budding analyst to develop methods based on green analytical principles to protect the environment.


Indomethacin blocks the febrile response induced by interleukin-8 in rabbits.
Interleukin (IL)-8 induces fever in rats by a mechanism independent of the release of cyclooxygenase products. The purpose of this study was to investigate whether a similar mechanism is responsible for the pyrogenic effect of IL-8 in rabbits. Intravenous (0.31-5.0 ng/kg) or intracerebroventricular (15.6-250 pg) injections of IL-8 induced a dose-dependent increase in body temperature. The correlations between the doses of recombinant human IL-8 and the fever index were 0.98 and 0.99 for the intravenous and intracerebroventricular injections, respectively. The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS), inasmuch as the Limulus amoebocyte lysate test showed < 10 pg endotoxin/micrograms IL-8, and boiled IL-8 lost its pyrogenic activity. Indomethacin (2 and 5 mg/kg i.p.) abolished the febrile response induced by the intravenous injection of LPS (5.0 ng/kg), IL-1 beta (5 ng/kg), and IL-8 (5 ng/kg). Indomethacin also abolished the fever induced by the intracerebroventricular injection of IL-8 (62.5 pg) but only partially reduced the response induced by the injection of IL-1 beta (25 pg icv). These results show that, different from rats, indomethacin blocks the febrile response induced by the central or peripheral administration of IL-8 in rabbits.


Comparison of outcomes in patients with probable versus definite cardiac sarcoidosis.
Patients with probable cardiac sarcoidosis (CS) who satisfy only clinical cardiac findings for CS are not uncommon. The aim of this study was to compare outcomes between patients with probable CS and those with definite CS treated with steroids. The study population consisted of 101 consecutive patients who satisfied clinical cardiac findings for CS. Patients with definite CS were defined as having histologic or clinical confirmation of CS according to the guidelines and were treated with steroids. Patients with probable CS were defined as having only clinical cardiac findings but not definite CS because of no histologic confirmation or extracardiac sarcoidosis and were not treated with steroids. The end point was major adverse cardiac events. Forty-seven patients had definite CS, and the other 54 had probable CS. Except for serum angiotensin-converting enzyme levels and left ventricular dysfunction, clinical characteristics were similar between the 2 groups. Over a median follow-up period of 15 months, major adverse cardiac events occurred more frequently in patients with probable CS than in those with definite CS (74% vs 53%, p=0.029). The event-free survival rate was worse in patients with probable CS than in those with definite CS (log-rank test, p=0.006). Cox proportional-hazards analysis showed that probable CS was an independent predictor of major adverse cardiac events. In conclusion, outcomes were worse in patients with probable CS than in those with definite CS treated with steroids. The initiation of steroid treatment may be considered for patients who satisfy only clinical cardiac findings for CS.


GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients.
Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.


The role of anticipated decision regret and the patient's best interest in sterilisation and medically assisted reproduction.
There is a clear discrepancy in the way those who request medical assistance in pursuit of their reproductive choices are treated. On the one hand, women who request a sterilisation are urged to consider possible future regrets and are sometimes refused treatment in anticipation of such regrets. This is despite the fact that for all age ranges, the majority of women undergoing a sterilisation do not regret the decision. Moreover, women who are voluntarily childless are likely to have a happier and more gratifying life than parents. On the other hand, women who request fertility treatment are not urged to second guess their desire for parenthood. Although the fact that the probability of regret is expected to be higher in the former case than in the latter justifies this difference in treatment to a certain extent, the gap between the two different approaches is wider than it ought to be if we also take future well-being into consideration, instead of focussing exclusively on anticipated decision regret.


Inversion probability of three-bladed self-propelled rotors after forced stops of different durations.
We investigated self-propelled rotation of a symmetric three-bladed rotor on water under periodic halt and release operations. The rotation was driven by the difference in the surface tension around the blades of the rotor because camphor molecules developed from three camphor disks glued at the blade ends. Spontaneous inversion of rotation direction was observed after a forced stop of the rotor and the subsequent release. The probability of such inversion decreased with an increase in the halting time. The asymmetric distribution of camphor molecules around the blades was also inverted after the forced stop and the degree of asymmetry increased with an increase in the angular velocity characterizing the stationary rotation of the rotor. Our experimental results for rotors with different shapes indicate that there is a strong correlation between the stationary angular velocity of the rotor and the maximum time duration of the forced stop for which a high probability of inversion is observed.


Therapeutic effects of hydrogen on chronic graft-versus-host disease.
The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values.


Metastatic tumors of the foot.
Four metastatic tumors of the foot, of colonic, renal and humeral origin, are described. They involved three calcanei and two tali. All four patients died within a few months after the appearance of metastasis to the foot. Bony destruction, pain, and swelling can closely resemble the clinical signs and symptoms of osteomyelitis. Diagnostic roentgenograms must be obtained to rule out the possibility of metastatic disease, and biopsies are usually required for accurate diagnosis.


Indomethacin Enhances Fat Graft Retention by Up-Regulating Adipogenic Genes and Reducing Inflammation.
Cell-assisted lipotransfer has been promisingly applied to restore soft-tissue defects in plastic surgery; however, the harvesting of stromal vascular fraction increases morbidity and poses potential safety hazards. The authors investigated whether adding indomethacin, an antiinflammatory proadipogenic drug, to the fat graft at the time of transplantation would enhance the final graft volume compared with cell-assisted lipotransfer. In vitro, human adipose-derived stem cells were cultured in conditioned growth media supplemented with various doses of indomethacin to investigate adipogenesis and the expression of the adipogenic genes. In vivo, lipoaspirate mixed with stromal vascular fractions or indomethacin was injected into the dorsum of mice. Tissues were harvested at weeks 2, 4, and 12 to evaluate histologic changes. In vitro, polymerase chain reaction analysis revealed that increased up-regulation of adipogenic genes and activation of the peroxisome proliferator-activated receptor-γ pathway. In vivo, the percentage volume of adipocytes in the indomethacin-assisted groups was higher than that in the lipoaspirate-alone (control) group at 12 weeks (p = 0.016), and was equivalent to the volume in the cell-assisted groups (p = 1.000). Indomethacin improved adipose volumes but had no effect on vascularity. A larger number of small adipocytes appeared in the treatment samples than in the controls at 2 weeks (p = 0.044) and 4 weeks (p = 0.021). Pretreating lipoaspirate with indomethacin enhances the final volume retention of engrafted fat. This result is explained in part by increased adipogenesis and possibly by the inhibition of inflammatory responses.


Neuropsychological sequelae of brain tumors.
Investigation of the neuropsychological sequelae of brain tumors is extremely complex largely because the neurobehavioral consequences of brain tumors depend upon complex interactions among disease and treatment variables as well as patient characteristics. To illustrate some of these complexities, we present case studies of two patients in whom the behavioral outcome was not easily predictable on the basis of our current understanding of brain-behavior relationships in tumor patients. The case studies do illustrate how neuropsychological evaluation aids in identifying cognitive deficits which have implications for subsequent quality of life. Recommendations for future experiments and statistical analyses of neurobehavioral data of this population are given.


The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review.
Purpose. Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn's disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis. Methods. A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement. Results. After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP). Conclusion. Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker.


Geometric morphometric analyses of hominid proximal femora: taxonomic and phylogenetic considerations.
The proximal femur has long been used to distinguish fossil hominin taxa. Specifically, the genus Homo is said to be characterized by larger femoral heads, shorter femoral necks, and more lateral flare of the greater trochanter than are members of the genera Australopithecus or Paranthropus. Here, a digitizing arm was used to collect landmark data on recent human (n=82), chimpanzee (n=16), and gorilla (n=20) femora and casts of six fossil hominin femora in order to test whether one can discriminate extant and fossil hominid (sensu lato) femora into different taxa using three-dimensional (3D) geometric morphometric analyses. Twenty proximal femoral landmarks were chosen to best quantify the shape differences between hominin genera. These data were first subjected to Procrustes analysis. The resultant fitted coordinate values were then subjected to PCA. PC scores were used to compute a dissimilarity matrix that was subjected to cluster analyses. Results indicate that one can easily distinguish Homo, Pan, and Gorilla from each other based on proximal femur shape, and one can distinguish Pliocene and Early Pleistocene hominin femora from those of recent Homo. It is more difficult to distinguish Early Pleistocene Homo proximal femora from those of Australopithecus or Paranthropus, but cluster analyses appear to separate the fossil hominins into four groups: an early australopith cluster that is an outlier from other fossil hominins; and two clusters that are sister taxa to each other: a late australopith/Paranthropus group and an early Homo group.


An MRI method for measuring T2 in the presence of static and RF magnetic field inhomogeneities.
A magnetic resonance imaging method for measuring the T2 relaxation time constant is proposed. It is based on the assumption that, under very general conditions, the MR signal near a spin echo has a special symmetry arising from the refocusing nature of the 180 degrees RF pulse. A gradient echo sampling of the spin echo (GESSE) sequence is implemented to evaluate T2 by collecting multiple gradient echoes before and after the spin echo. This approach is a modification of the GESFIDE sequence proposed by Ma and Wehrli. However, our approach compares images that are not separated by any RF pulses and, as a result, is insensitive to slice profile imperfections. In addition, the calculated T2 value does not rely on any special assumptions about the MRI signal behavior in the presence of an inhomogeneous static magnetic field and, hence, is insensitive to the presence of static magnetic field inhomogeneities.


The composition of lung microbiome in lung cancer: a systematic review and meta-analysis.
Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association between the lung microbiome and lung cancer has not been extensively studied. Conflicting reports of individual studies on respiratory microbiome alterations in lung cancer complicate the matter for specifying how the lung microbiome is linked to lung cancer. Consequently, as the first meta-analysis on this topic, we integrate publicly available 16S rRNA gene sequence data on lung tissue samples of lung cancer patients to identify bacterial taxa which differ consistently between case and control groups. The findings of the current study suggest that the relative abundance of several bacterial taxa including Actinobacteria phylum, Corynebacteriaceae and Halomonadaceae families, and Corynebacterium, Lachnoanaerobaculum, and Halomonas genera is significantly decreased (p < 0.05) in lung tumor tissues of lung cancer patients in comparison with tumor-adjacent normal tissues. Despite the underlying need for scrutinizing the findings further, the present study lays the groundwork for future research and adds to our limited understanding of the key role of the lung microbiome and its complex interaction with lung cancer. More data on demographic factors and tumor tissue types would help establish a greater degree of accuracy in characterizing the lung microbial community which accords with subtypes and stages of the disease and fully capturing the changes of the lung microbiome in lung cancer.


Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury.
Changes in plasma aromatic amino acids (AAA = phenylalanine, tryptophan, tyrosine) and branched chain amino acids (BCAA = isoleucine, leucine, valine) levels possibly influencing intracranial pressure (ICP) and cerebral oxygen consumption (SjvO(2)) were investigated in 19 sedated patients up to 14 days following severe traumatic brain injury (TBI). Compared to 44 healthy volunteers, jugular venous plasma BCAA were significantly decreased by 35% (p < 0.001) while AAA were markedly increased in TBI patients by 19% (p < 0.001). The BCAA to AAA ratio was significantly decreased by 55% (p < 0.001) which persisted during the entire study period. Elevated plasma phenylalanine was associated with decreased ICP and increased SjvO(2), while higher plasma isoleucine and leucine levels were associated with increased ICP and higher plasma leucine and valine were linked to decreased SjvO(2). The amount of enterally administered amino acids was associated with significantly increased plasma levels with the exception of phenylalanine. Contrary to the initial assumption that elevated AAA and decreased BCAA levels are detrimental, increased plasma phenylalanine levels were associated with beneficial signs in terms of decreased ICP and reduced cerebral oxygen consumption reflected by increased SjvO(2); concomitantly, elevated plasma isoleucine and leucine levels were associated with increased ICP while leucine and valine were associated with decreased SjvO(2) following severe TBI, respectively. The impact of enteral nutrition on this observed pattern must be examined prospectively to determine if higher amounts of phenylalanine should be administered to promote beneficial effects on brain metabolism and if normalization of plasma BCAA levels is without cerebral side effects.


Components of emotion regulation flexibility and psychosis: The association between psychosis-proneness and context sensitivity.
Emotion regulation flexibility has been conceptualized as a multi-componential construct involving context sensitivity, repertoire and feedback responsiveness. Psychosis research has yet to incorporate these new developments in the study of emotion regulation. Thus, we sought to advance even further the knowledge on emotion regulation in psychosis by adopting the emotion regulation flexibility approach as proposed by Bonanno and Burton (Perspectives on Psychological Science, 2013, 8, 591). In total, 401 participants completed 4 scales assessing the multi-components of emotion regulation flexibility and psychosis-proneness. Our results indicated that Context Sensitivity (i.e., Cue Absence) and Feedback Responsiveness (i.e., Evaluation) were associated with psychosis-proneness. Cue absence was specifically associated with the positive dimension, while both Cue Absence and Enhancement ability were associated with the negative dimension. Overall, our results suggest that emotional context insensitivity is the most relevant component of regulatory flexibility in the case of psychosis-proneness. Thus, the disruption in this first step of flexible emotion regulation might be already present in those prone to psychosis. Difficulties in decoding appropriately the contextual cues might further disrupt the other steps of emotion regulation contributing to the psychotic (-like) experiences. This study needs replication in clinical and non-clinical samples.


Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.
See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.


[Polypeptide growth factors in animal embryogenesis].
Data about polypeptide growth factors in animal cells during embryogenesis and about the sensitivity of these cells to regulatory effect of the factors have been systematically reviewed. The conclusion was drawn that they play an important role in molecular mechanisms controlling cell proliferation and differentiation at the early embryonic stages. Information has also been provided about transforming growth factors and about the products of some proto-oncogenes, which are detected in the embryonic cells in amounts comparable with those in the transformed cells. However, this does not lead to malignant growth. Moreover, microenvironment of an intact embryo exerts an antitransforming influence on tumor cells. Studies of the "normalizing" effect of the embryonic cells may help in developing new methods of suppression of the malignant growth.


Evaluation of five peanut (Arachis hypogaea) genotypes to identify drought responsive mechanisms utilising candidate-gene approach.
Drought can significantly limit yield and quality in peanut (Arachis hypogaea L.), depending on its timing, duration and severity. The objective of this study was to identify potential molecular mechanism(s) utilising a candidate-gene approach in five peanut genotypes with contrasting drought responses. An early season drought stress treatment was applied under environmentally controlled rain-out shelters. When water was completely withheld for 3 weeks, no physical differences were observed for treated plants compared with their fully irrigated counterparts as indicated by relative water content; however, yield, grades (total sound mature kernel, TSMK), specific leaf area, and leaf dry matter content showed significant differences. Comparing expression levels of candidate genes, 'C76-16' exhibited significantly higher levels for CuZnSOD, NsLTP and drought protein 1 week earlier compared to the other genotypes, followed by significantly lower levels for the same genes. This suggested an early recognition of drought in C76-16 followed by an acclimation response. Cultivar 'Georgia Green' showed different patterns of gene-expression than C76-16. AP-3, a susceptible genotype, showed generally lower levels of gene-expression than C76-16 and Georgia Green. Myo-inositol phosphate synthase gene-expression showed high levels in irrigated treatment, ranging from 4-fold for 08T-12 to 12-fold for Georgia Green, but were significantly inhibited in drought treatment after 2 weeks of drought and after recovery.


Biological activities of extracts from Chenopodium ambrosioides Lineu and Kielmeyera neglecta Saddi.
Chenopodium ambrosioides and Kielmeyera neglecta are plants traditionally used in Brazil to treat various infectious diseases. The study of the biological activities of these plants is of great importance for the detection of biologically active compounds. Extracts from these plants were extracted with hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and ethanol (EtOH) and assessed for their antimicrobial properties, bioactivity against Artemia salina Leach and antifungal action on the cell wall of Neurospora crassa. Extracts from C. ambrosioides (Hex, DCM and EtOH) and K. neglecta (EtOAc and EtOH) showed high bioactivity against A. salina (LD50 < 1000 μg/mL), which might be associated with cytotoxic activity against cancer cells. C. ambrosioides Hex and DCM showed specific activity against yeasts, highlighting the activity of hexanic extract against Candida krusei (MIC = 100 μg/mL). By comparing the inhibitory concentration of 50% growth (IC 50%) with the growth control, extracts from K. neglecta EtOAc and EtOH have shown activities against multidrug-resistant bacteria (Enterococcus faecalis ATCC 51299 and Staphylococcus aureus ATCC 43300), with IC 50% of 12.5 μg/mL The assay carried out on N. crassa allowed defining that extracts with antifungal activity do not have action through inhibition of cell wall synthesis. Generally speaking, extracts from C. ambrosioides and K. neglecta showed biological activities that have made the search for bioactive substances in these plants more attractive, illustrating the success of their use in the Brazilian folk medicine.


Opposite associations of osteoprotegerin and ZBTB40 polymorphisms with bone mineral density of the hip in postmenopausal Taiwanese women.
An elevated annual incidence rate of hip fracture has been reported among elderly Taiwanese. Moreover, bone mineral density (BMD) is the single most reliable predictor of fragility fractures. We aimed to identify the association between gene sequence variants and hip BMD in postmenopausal Taiwanese women. We prospectively analyzed data from 163 postmenopausal Taiwanese women to test an association between rs7524102, rs6696981, or rs6993813 single-nucleotide polymorphisms (SNPs) and hip BMD. Our study showed that rs6993813 (osteoprotegerin gene) and rs6696981 (ZBTB40 gene) SNPs have an opposite association with hip BMD. For rs6993813 genotypic frequencies, the adjusted odds ratio for hip osteoporosis was 9.53 for individuals with T/T minor allele homozygotes, compared with that of participants with C/C wild-type homozygotes. Hip BMD also had an association with rs6993813 SNPs, especially in T/T minor allele homozygotes. For rs6696981 SNPs, hip BMD in G/T heterozygotes and at least one mutated T allele was higher than that in wild-type G/G homozygotes. The gene sequence variant rs6993813 reduced hip BMD and increased the risk of hip osteoporosis, whereas rs6696981 increased hip BMD in postmenopausal Taiwanese women. This indicated that the two SNPs may provide some explanation for the high risk of hip fracture in this population.


Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem.
Microinjection of neuropeptide Y (NPY) into the nucleus tractus solitarius (NTS) induces an initial and reversible fall in arterial pressure (AP) and heart rate (HR), along with a delayed and long-lasting blockade of cardiovascular responses to L-glutamate (L-Glu) injected into the same site and an inhibition of the baroreflex arc. By injecting NPY-receptor subtype selective agonists and NPY-related peptides into NTS we have sought to characterize the receptors that mediate these responses. Unilateral injections into NTS (9-90 pmol) of NPY as well as the Y1 receptor selective agonist [34Pro]NPY and the Y2 receptor selective fragment NPY 13-36 evoked comparable dose-dependent falls of AP and HR in the anesthetized and paralyzed rat. Injections into NTS of peptide YY or pancreatic polypeptide had no effect. Preinjection of NPY, [34Pro]NPY, NPY 13-36 (all at 90 pmol) as well as norepinephrine (6.7 nmol) virtually abolished the fall in AP and HR evoked by subsequent injections of L-Glu into NTS. Injection of peptide YY or pancreatic polypeptide (both at 90 pmol) did not affect the cardiovascular responses evoked by L-Glu in NTS. Injection of NPY (90 pmol) into the caudal ventrolateral medulla induced a slight fall in AP of -17 +/- 5 mm Hg (P less than .05) and a sustained fall in HR of -44 +/- 8 beats per min (P less than .01). Injection of NPY also abolished the fall in HR and AP evoked by L-Glu in the caudal ventrolateral medulla. The profile of the cardiovascular effects elicited by the NPY-related peptides in NTS does not correspond to either of the Y1 or the Y2 receptor subtypes. The findings suggest that NPY acts on an atypical receptor in NTS to lower AP and HR. Moreover, this receptor may also interfere with the L-Glu-evoked neurotransmission in the NTS. Finally, norepinephrine shared with NPY the ability to inhibit L-Glu-evoked responses in NTS; however, a much higher dose of norepinephrine (than NPY) was required.


Machine Learning-Based Analysis of Encrypted Medical Data in the Cloud: Qualitative Study of Expert Stakeholders' Perspectives.
Third-party cloud-based data analysis applications are proliferating in electronic health (eHealth) because of the expertise offered and their monetary advantage. However, privacy and security are critical concerns when handling sensitive medical data in the cloud. Technical advances based on "crypto magic" in privacy-preserving machine learning (ML) enable data analysis in encrypted form for maintaining confidentiality. Such privacy-enhancing technologies (PETs) could be counterintuitive to relevant stakeholders in eHealth, which could in turn hinder adoption; thus, more attention is needed on human factors for establishing trust and transparency. The aim of this study was to analyze eHealth expert stakeholders' perspectives and the perceived tradeoffs in regard to data analysis on encrypted medical data in the cloud, and to derive user requirements for development of a privacy-preserving data analysis tool. We used semistructured interviews and report on 14 interviews with individuals having medical, technical, or research expertise in eHealth. We used thematic analysis for analyzing interview data. In addition, we conducted a workshop for eliciting requirements. Our results show differences in the understanding of and in trusting the technology; caution is advised by technical experts, whereas patient safety assurances are required by medical experts. Themes were identified with general perspectives on data privacy and practices (eg, acceptance of using external services), as well as themes highlighting specific perspectives (eg, data protection drawbacks and concerns of the data analysis on encrypted data). The latter themes result in requiring assurances and conformance testing for trusting tools such as the proposed ML-based tool. Communicating privacy, and utility benefits and tradeoffs with stakeholders is essential for trust. Furthermore, stakeholders and their organizations share accountability of patient data. Finally, stakeholders stressed the importance of informing patients about the privacy of their data. Understanding the benefits and risks of using eHealth PETs is crucial, and collaboration among diverse stakeholders is essential. Assurances of the tool's privacy, accuracy, and patient safety should be in place for establishing trust of ML-based PETs, especially if used in the cloud.


Academic Debate: Publications Which Promote Political Agendas Have no Place in Scientific and Medical Journals, and Academics Should Refrain from Publishing in Such Journals.
This paper presents the full debate held on October 1, 2014, which focused on the following resolution: "Publications which promote political agendas have no place in scientific and medical journals, and academics should refrain from publishing in such journals." The debate moderator was Professor Shimon Glick. Taking the pro stance was Professor A. Mark Clarfield; the con stance was held by Professor Rael D. Strous. Following the first part of the debate, Dr Richard Horton, Editor-in-Chief of The Lancet, gave his thoughts on the topic. This was followed by the opportunity for rebuttal by Professors Clarfield and Strous. The debate was summarized and closed by Professor Glick. This paper provides a slightly edited text of the debate, for ease of reading.


Neurosurgical trauma call: use of a mathematical simulation program to define manpower needs.
Resource criteria for trauma centers (TC) mandate a first plus backup neurosurgeon (NS) coverage, an unnecessary expense for TC treating few neurosurgery patients. This report uses a mathematical modeling system to define optimal NS trauma coverage. Random data from 749 patients treated with emergency neurosurgery operations (OR) within 24 hours of admission at 97 TC were used to create a 1-year profile of admission by month, day, and hour, operation times, and operation duration. These data were entered into a simulation program to define the frequency that a patient needing a NS consult would wait beyond 30 minutes because the NS was in the operating room at a trauma center with one, two, or three neurosurgeons on-call. One thousand iterations were done for each sample size of 25 to 300 patients in 25-patient increments. The probability that a patient could not be seen promptly by one NS in a trauma center operating on 25, 50, 75, or 100 patients per year is 0.23, 0.9, 1.6, and 3.66 patients per year. Fewer than one patient (0.75) per year will wait more than 30 min in a trauma center doing 225 emergency ORs when two neurosurgeons are on-call. One patient in 10 years would wait more than 30 min in a trauma center doing 300 ORs with a third NS on-call. Mathematical modeling of patient data helps define optimal hospital resources. Mandatory NS backup for TC performing fewer than 25 neurosurgery procedures is unneeded.


Mechanical ventilatory constraints during incremental exercise in healthy and cystic fibrosis children.
To analyze breathing pattern and mechanical ventilatory constraints during incremental exercise in healthy and cystic fibrosis (CF) children. Thirteen healthy children and 6 children with cystic fibrosis volunteered to perform an incremental test on a treadmill. Exercise tidal flow/volume loops were plotted every minute within a maximal flow/volume loop (MFVL). Expiratory flow limitation (expFL expressed in %Vt) was evaluated and end-expiratory and end-inspiratory lung volumes (EELV and EILV) were estimated from expiratory reserve volume relative to vital capacity (ERV/FVC) and from inspiratory reserve volume relative to vital capacity (IRV/FVC). During the incremental exercise, expFL was first observed at 40% of maximal aerobic speed in both groups. At maximal exercise, 46% of healthy children and 83% of CF children presented expFL, without significant effect of cystic fibrosis on the severity of expFL. According to the two-way ANOVA results, both groups adopted similar breathing pattern and breathing strategies as no significant effect of CF has been revealed. But, according to one-way ANOVA results, a significant increase of ERV/FVC associated with a significant decrease of IRV/FVC from resting value shave been observed in healthy children at maximal exercise, but not in CF children. The hypothesis of this study was based on the assumption that mild cystic fibrosis could induce more frequent and more severe mechanical ventilatory constraints due to pulmonary impairment and breathing pattern disturbances. But, this study did not succeed to highlight an effect of mild cystic fibrosis on the mechanical ventilatory constraints (expFL and dynamic hyperinflation) that occur during an incremental exercise. This absence of effect could be due to the absence of an impact of the disease on spirometric data, breathing pattern regulation during exercise and breathing strategy.


Quantitative large-volume sampling technique.
A filtration technique for high-volume sampling of water has been developed that, when combined with the most probable number procedure, permits the quantitation of microorganisms present at very low densities.


A machine learning-based clinical decision support system to identify prescriptions with a high risk of medication error.
To improve patient safety and clinical outcomes by reducing the risk of prescribing errors, we tested the accuracy of a hybrid clinical decision support system in prioritizing prescription checks. Data from electronic health records were collated over a period of 18 months. Inferred scores at a patient level (probability of a patient's set of active orders to require a pharmacist review) were calculated using a hybrid approach (machine learning and a rule-based expert system). A clinical pharmacist analyzed randomly selected prescription orders over a 2-week period to corroborate our findings. Predicted scores were compared with the pharmacist's review using the area under the receiving-operating characteristic curve and area under the precision-recall curve. These metrics were compared with existing tools: computerized alerts generated by a clinical decision support (CDS) system and a literature-based multicriteria query prioritization technique. Data from 10 716 individual patients (133 179 prescription orders) were used to train the algorithm on the basis of 25 features in a development dataset. While the pharmacist analyzed 412 individual patients (3364 prescription orders) in an independent validation dataset, the areas under the receiving-operating characteristic and precision-recall curves of our digital system were 0.81 and 0.75, respectively, thus demonstrating greater accuracy than the CDS system (0.65 and 0.56, respectively) and multicriteria query techniques (0.68 and 0.56, respectively). Our innovative digital tool was notably more accurate than existing techniques (CDS system and multicriteria query) at intercepting potential prescription errors. By primarily targeting high-risk patients, this novel hybrid decision support system improved the accuracy and reliability of prescription checks in a hospital setting.


Effects of zinc supplementation on oxidant/antioxidant and lipids status of pesticides sprayers.
Background Excess exposure to pesticides induces oxidative stress and causes alteration in the lipid profile Objectives The study aimed to evaluate the effects of Zinc (Zn) supplementation on the oxidant/antioxidant and lipid status in pesticide sprayers. Methods Forty pesticide sprayers were included in the study. Blood lipids, malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and Zn were estimated; before and after Zn supplementation. Results Statistical analysis revealed that after Zn supplementation, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and MDA were significantly decreased. However, there was a significant increase in the high density lipoprotein (HDL), SOD, GPx, and Zn levels. After Zn supplementation, significant inverse correlations were detected between the Zn and the levels of MDA, TG, and VLDL, while positive correlation between Zn and the levels of HDL and TC. Conclusions Zn supplementation improves the oxidative/antioxidants and lipid status in pesticide sprayers.


Simple model for self-propulsion of microdroplets in surfactant solution.
We propose a simple active hydrodynamic model for the self-propulsion of a liquid droplet suspended in micellar solutions. The self-propulsion of the droplet occurs by spontaneous breaking of isotropic symmetry and is studied using both analytical and numerical methods. The emergence of self-propulsion arises from the slow dissolution of the inner fluid into the outer micellar solution as filled micelles. We propose that the surface generation of filled micelles is the dominant reason for the self-propulsion of the droplet. The flow instability is due to the Marangoni stress generated by the nonuniform distribution of the surfactant molecules on the droplet interface. In our model, the driving parameter of the instability is the excess surfactant concentration above the critical micellar concentration, which directly correlates with the experimental observations. We consider various low-order modes of flow instability and show that the first mode becomes unstable through a supercritical bifurcation and is the only mode contributing to the swimming of the droplet. The flow fields around the droplet for these modes and their combined effects are also discussed.


Imaging of the non-traumatic brachial plexus.
The first line imaging of the non-traumatic brachial plexus is by MRI. Knowledge of the anatomy and commonest variants is essential. Three Tesla imaging offers the possibility of 3D isotropic sequences with excellent spatial and contrast enhancement resolutions, which leads to time saving and quality boosting. The most commonly seen conditions are benign tumor lesions and radiation damage. Gadolinium is required to assess inflammatory or tumour plexopathy. MRI data should be correlated with FDG-PET if tumor recurrence is suspected.


Cell cycle regulation and cytoskeletal remodelling are critical processes in the nutritional programming of embryonic development.
Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common "gatekeepers" which may drive nutritional programming.Both protein and iron deficiency in utero reduced the nephron complement in adult male Wistar and Rowett Hooded Lister rats (P<0.05). This occurred in the absence of damage to the glomerular ultrastructure. Microarray, proteomic and pathway analyses identified diet-specific and strain-specific gatekeeper genes, proteins and processes which shared a common association with the regulation of the cell cycle, especially the G1/S and G2/M checkpoints, and cytoskeletal remodelling. A cell cycle-specific PCR array confirmed the down-regulation of cyclins with protein restriction and the up-regulation of apoptotic genes with iron deficiency.The timing and experimental design of this study have been carefully controlled to isolate the common molecular mechanisms which may initiate the sequelae of events involved in nutritional programming of embryonic development. We propose that despite differences in the individual genes and proteins affected in each strain and with each diet, the general response to nutrient deficiency in utero is perturbation of the cell cycle, at the level of interaction with the cytoskeleton and the mitotic checkpoints, thereby diminishing control over the integrity of DNA which is allowed to replicate. These findings offer novel insight into the primary causes and mechanisms leading to the pathologies which have been identified by previous programming studies.


Identification of differentially expressed genes in anagen dermal papilla by suppression subtractive hybridization.
We constructed a cDNA subtractive library of dermal papilla cells (DPCs) in anagen with suppression subtractive hybridization (SSH) technique and clone differentially expressed genes related to DPCs in anagen. Total mRNA was isolated from DPCs of anagen and telogen follicles. Moreover, single-strand (ss) and double-strand (ds) cDNAs were synthesized in turn using SMART PCR cDNA synthesis technology. ds cDNAs then were digested with Rsa I and divided into two groups, and ligated to the specific adaptor 1 and adaptor 2R, respectively. After cDNAs were hybridized with each other twice and underwent two rounds of nested PCR. PCR products were ligated with arms of T/A plasmid vectors to set up the subtractive library. Selected clones were demonstrated by reverse Northern blot and sequenced. The acquired sequence data were aligned against the Genbank nucleotide database. cDNA subtractive library of DPCs in anagen follicles was set up successfully with high subtractive efficiency. Thirty-five genes were identified in this study with 22 known functional genes and 13 unknown functional genes. All results confirm the effectiveness and sensitivity of SSH in detecting differentially expressed genes from a small amount of clinical samples. Information about such alterations in gene expression could be useful for elucidating the genetic events in hair follicle growth regulation.


Neonatal transport of very low birth weight infants in Jerusalem, revisited.
Maternal transport, rather than neonatal transport, to tertiary care centers is generally advocated. Since a substantial number of premature deliveries still occur in hospitals with level I and level II nurseries, it is imperative to find means to improve their outcome. To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very low birth weight infants, accounting for sociodemographic, obstetric and perinatal variables, with reference to earlier published data. We compared 129 premature infants with birth weights of 750-1250 g delivered between 1996 and 2000 in a hospital providing neonatal intensive care to 99 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistical significant association with the outcome variables and dissimilar distribution in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. Accounting for the covariates, the odds ratios (outborns relative to inborns) were 0.31 (95% confidence interval = 0.11-0.86, P = 0.03) for mortality, 1.37 (95% CI = 0.64-2.96, P = 0.42) for severe intraventricular hemorrhage, and 0.86 (95% CI = 0.38-1.97, P = 0.78) for bronchopulmonary dysplasia. The odds ratio for survival without severe intraventricular hemorrhage was 1.10 (95% CI = 0.55-2.20, P = 0.78). Comparing the current results with earlier (1990-94) published data from the same institution showed that mortality decreased in both the outborn and inborn infants (OR = 0.23, 95% CI = 0.09-0.58, P = 0.002 and 0.46; 95% CI = 0.20-1.04, P = 0.06, respectively), but no significant change in the incidence of severe intraventricular hemorrhage or brochopulmonary dysplasia was observed. Increased survival was observed also in these infants receiving surfactant, more so among the outborn. The latter finding could be attributed to the early, pre-transport surfactant administration, implemented only in the current study. Our data suggest that very low birth weight outborn infants may share an outcome comparable with that of inborn babies, if adequate perinatal care including surfactant administration is provided prior to transportation to a tertiary center.


A C-terminal region dictates the apical plasma membrane targeting of the human sodium-dependent vitamin C transporter-1 in polarized epithelia.
The human sodium-dependent vitamin C transporter (hSVCT1) mediates sodium-dependent cellular uptake of the essential micronutrient l-ascorbic acid (vitamin C). However, the molecular determinants that control the cell surface expression, subcellular distribution, and dynamics of hSVCT1 remain undefined. To identify molecular determinants involved in hSVCT1 targeting in polarized epithelia, we used live cell imaging approaches to resolve the targeting and trafficking dynamics of hSVCT1 truncation mutants in renal and intestinal cells. Confocal imaging demonstrated that hSVCT1 was expressed at the apical cell surface and video rate measurements revealed hSVCT1 also resided in a heterogeneous population of intracellular organelles with discrete dynamic properties. By progressive truncation of the cytoplasmic C-terminal tail of hSVCT1, we delimited an essential role for an embedded ten amino acid sequence PICPVFKGFS (amino acids 563-572) in defining the physiological targeting of hSVCT1. Intriguingly, this sequence bears significant homology to recently identified apical targeting motifs in two other sodium-dependent transporters, and we suggest this conservation is reflected topologically through the adoption of a beta-turn confirmation in the cytoplasmic C-tail of each transporter. Our results provide the first direct resolution of functional hSVCT1 expression at the apical cell surface of polarized epithelia and define an apical targeting signal of relevance to transporters of diverse substrate specificity.


Selective defect of natural killer and killer cell activity against lymphomas in SJL mice: low responsiveness to interferon inducers.
Three unrelated inbred strains of H-2s mice, SJL/JN, A.SW, and B10.S, were classified according to the levels of splenic NK activity against susceptible lymphoma targets, with or without prior administration of the interferon (IFN) inducer p-I:C to the prospective donors of splenocytes: 1) SJL/JN had low endogenous activity that responded poorly to p-I:C-induced augmentation; 2) A.SW exhibited low levels of spontaneous activity that were inducible to higher levels by p-I:C; and 3) B10.S showed high endogenous levels of activity that were augmented to a still higher level by p-I:C treatment. In vitro incubation of spleen cells with partially purified IFN-beta for up to 12 hr augmented NK activity of A.SW and B10.S but not of SJL mice. The relative levels of K cell-mediated ADCC in the three strains were similar to those of NK activity, including augmentability by p-I:C; however, the capacity to perform three additional cell-mediated immune functions, i.e., natural cytotoxicity against a fibrosarcoma target, adherent cell-mediated ADCC against antibody-coated chicken RBC, and alloimmune T cell-mediated cytotoxicity against appropriate targets, did not distinguish one strain from another. The low NK phenotype in SJL/JN remained distinctive throughout postnatal life, but there was a tendency for the highest levels of NK activity to occur in 4 to 8-wk-old mice.