Modulation of Macrophages Differentiation by Nanoscale-Engineered Geometric and Chemical Features.

Macrophage differentiation into M1 (inflammatory) and M2 (healing) phenotypes plays a vital role in determining the fate of biomaterials. The biophysical properties of the extracellular matrix are known to affect macrophage behavior. Mimicking these special biophysical properties of the extracellular matrix has led to increasing interest in biomaterial constructs with tailor-engineered surface nanotopographical and chemical properties. However, a significant gap of knowledge exists in the role played by the combinational effect of surface nanotopography and chemistry. To address this gap, we have fabricated nanoporous surfaces of controlled pore size (30, 65, and 200 nm) and lateral spacing with uniform outermost surface chemistry tailored with amines (NH2), carboxyl (COOH-) and hydrocarbon (CH3-) functionalities. We show that the combinatory effects of surface properties can direct the differentiation of macrophages to the pro-healing M2 phenotype. This is most evident on the surface featuring nanopores of 200 nm and -COOH functionality. Overall, the concentration of pro-inflammatory cytokines significantly decreases, while the concentration of anti-inflammatory cytokines increases many folds on nanotopographically, and chemically, modified surfaces compared to their planar counterparts. Our data provide pioneering knowledge that could provide pathways to tuning inflammatory and foreign body responses and instruct the design of tailor-engineered biomaterial implants to enable better clinical outcomes.

Ankyloglossia as a risk factor for maxillary hypoplasia and soft palate elongation: A functional - morphological study.

OBJECTIVES: To characterize associations between restricted tongue mobility and maxillofacial development. SETTING AND SAMPLE POPULATION: Cross-sectional cohort study of 302 consecutive subjects from an orthodontic practice. MATERIAL AND METHODS: Tongue mobility (measured with tongue range of motion ratio [TRMR] and Kotlow free tongue measurement) was correlated with measurements of the maxillofacial skeleton obtained from dental casts and cephalometric radiographs. RESULTS: Tongue range of motion ratio and Kotlow measures of restricted tongue mobility were associated with (i) ratio of maxillary intercanine width to canine arch length, (ii) ratio of maxillary intermolar width to canine arch length and (iii) soft palate length. Restricted tongue mobility was not associated with hyoid bone position or Angle's skeletal classification. CONCLUSIONS: Restricted tongue mobility was associated with narrowing of the maxillary arch and elongation of the soft palate in this study. These findings suggest that variations in tongue mobility may affect maxillofacial development.

Reproductive biology of black seabream Acanthopagrus schlegelii, threadfin porgy Evynnis cardinalis and red pargo Pagrus major in the northern South China Sea with consideration of fishery status and management needs.

The reproductive biology of three commercially significant seabream species (family: Sparidae) Acanthopagrus schlegelii, Evynnis cardinalis and Pagrus major, taken from Hong Kong and adjacent northern South China Sea (SCS) waters, were investigated for their sexual patterns, spawning seasons, length at maturity and exploitation in relation to their conservation and management status. Histological analysis showed E. cardinalis and P. major to be functionally gonochoristic, the latter having a bisexual juvenile stage and being a rudimentary hermaphrodite. Acanthopagrus schlegelii is a protandric hermaphrodite. Standard length (LS ) at 50% sex change for A. schlegelii is 291 mm. LS at 50% female maturity for E. cardinalis and P. major are 117 and 332 mm, respectively. For all three species, the spawning period falls between November and March. The study highlights geographical differences in reproductive biology among the species and a paucity of fishery or other population-related data. While heavy fishing pressure, life-history characteristics and absence of effective management throughout the geographic ranges of these species make them susceptible to overfishing, they nonetheless appear to be generally more resilient than many other taxa that comprise the multi-species fisheries of the region, possibly due to their relatively rapid sexual maturation and spatial movement patterns. Overall, however, little is known of the biology, fishing history and current fishery status of sparids in general in the northern SCS and the current study is one of the first to examine such aspects of this family in the region and to consider appropriate management options.

Mesoscale iron enrichment experiments 1993-2005: synthesis and future directions.

Since the mid-1980s, our understanding of nutrient limitation of oceanic primary production has radically changed. Mesoscale iron addition experiments (FeAXs) have unequivocally shown that iron supply limits production in one-third of the world ocean, where surface macronutrient concentrations are perennially high. The findings of these 12 FeAXs also reveal that iron supply exerts controls on the dynamics of plankton blooms, which in turn affect the biogeochemical cycles of carbon, nitrogen, silicon, and sulfur and ultimately influence the Earth climate system. However, extrapolation of the key results of FeAXs to regional and seasonal scales in some cases is limited because of differing modes of iron supply in FeAXs and in the modern and paleo-oceans. New research directions include quantification of the coupling of oceanic iron and carbon biogeochemistry.

Nature of phosphorus limitation in the ultraoligotrophic eastern Mediterranean.

Phosphate addition to surface waters of the ultraoligotrophic, phosphorus-starved eastern Mediterranean in a Lagrangian experiment caused unexpected ecosystem responses. The system exhibited a decline in chlorophyll and an increase in bacterial production and copepod egg abundance. Although nitrogen and phosphorus colimitation hindered phytoplankton growth, phosphorous may have been transferred through the microbial food web to copepods via two, not mutually exclusive, pathways: (i) bypass of the phytoplankton compartment by phosphorus uptake in heterotrophic bacteria and (ii) tunnelling, whereby phosphate luxury consumption rapidly shifts the stoichiometric composition of copepod prey. Copepods may thus be coupled to lower trophic levels through interactions not usually considered.

Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts.

BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air-tissue interfaces. This work reports the use of spiral-in trajectories that begin at the edge of k-space and end at the origin, and spiral in/out trajectories in which a spiral-in readout is followed by a conventional spiral-out trajectory. The spiral-in trajectory reduces the dropout and increases the BOLD contrast. The spiral-in and spiral-out images can be combined in several ways to simultaneously achieve increased signal-to-noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions.

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization.

Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.

Effect of iron supply on Southern Ocean CO2 uptake and implications for glacial atmospheric CO2.

Photosynthesis by marine phytoplankton in the Southern Ocean, and the associated uptake of carbon, is thought to be currently limited by the availability of iron. One implication of this limitation is that a larger iron supply to the region in glacial times could have stimulated algal photosynthesis, leading to lower concentrations of atmospheric CO2. Similarly, it has been proposed that artificial iron fertilization of the oceans might increase future carbon sequestration. Here we report data from a whole-ecosystem test of the iron-limitation hypothesis in the Southern Ocean, which show that surface uptake of atmospheric CO2 and uptake ratios of silica to carbon by phytoplankton were strongly influenced by nanomolar increases of iron concentration. We use these results to inform a model of global carbon and ocean nutrients, forced with atmospheric iron fluxes to the region derived from the Vostok ice-core dust record. During glacial periods, predicted magnitudes and timings of atmospheric CO2 changes match ice-core records well. At glacial terminations, the model suggests that forcing of Southern Ocean biota by iron caused the initial approximately 40 p.p.m. of glacial-interglacial CO2 change, but other mechanisms must have accounted for the remaining 40 p.p.m. increase. The experiment also confirms that modest sequestration of atmospheric CO2 by artificial additions of iron to the Southern Ocean is in principle possible, although the period and geographical extent over which sequestration would be effective remain poorly known.

Importance of stirring in the development of an iron-fertilized phytoplankton bloom.

The growth of populations is known to be influenced by dispersal, which has often been described as purely diffusive. In the open ocean, however, the tendrils and filaments of phytoplankton populations provide evidence for dispersal by stirring. Despite the apparent importance of horizontal stirring for plankton ecology, this process remains poorly characterized. Here we investigate the development of a discrete phytoplankton bloom, which was initiated by the iron fertilization of a patch of water (7 km in diameter) in the Southern Ocean. Satellite images show a striking, 150-km-long bloom near the experimental site, six weeks after the initial fertilization. We argue that the ribbon-like bloom was produced from the fertilized patch through stirring, growth and diffusion, and we derive an estimate of the stirring rate. In this case, stirring acts as an important control on bloom development, mixing phytoplankton and iron out of the patch, but also entraining silicate. This may have prevented the onset of silicate limitation, and so allowed the bloom to continue for as long as there was sufficient iron. Stirring in the ocean is likely to be variable, so blooms that are initially similar may develop very differently.

Centronuclear myopathy and nursing pattern caries: management of a 1 year old.

The pathognomonic open mouth of centronuclear and other myopathies can also have implications for oral health. These patients are at greater risk for gingivitis, dental caries as a result of the mouth breathing and loss of lip seal. Low tongue posture may impede the lateral expansion of the maxilla resulting in a constricted maxillary arch with resultant posterior crossbites and functional shifts. Excessive molar eruption may also occur, resulting in anterior open bites and increases in the anterior lower vertical height.

A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.