Nanocarriers for neuromuscular diseases

Overview of the results obtained so far in the frame of a research on suitable nanocarriers for treating myotonic dystroph

The Use Of Corticosteroid For The Prophylaxis Of Fat Embolism Syndrome In Patients With Long Bone Fracture [uso De Corticoide Na Profilaxia Para Síndrome De Embolia Gordurosa Em Pacientes Com Fratura De Osso Longo]

The "Evidence-based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club conducted a critical review of the literature and selected three recent studies on the use of corticosteroids for the prophylaxis of fat embolism syndrome (FES). The review focused on the potential role of corticosteroids administration to patients admitted to the intensive care unit (ICU) at risk of developing post-traumatic fat embolism. The first study was prospective and aimed at identifying reliable predictors, which could be detected early and were associated with the onset of fat embolism syndrome in trauma patients. The second manuscript was a literature review on the role of corticosteroids as a prophylactic measure for FES. The last manuscript was a meta-analysis on the potential for corticosteroids to prophylactically reduce the risk of fat embolism syndrome in patients with long bone fractures. The main conclusions and recommendations reached were that traumatized patients should be monitored with non-invasive pulse oximetry and lactate levels since these commonly-available tests may predict the development of FES, and the lack of evidence to recommend the use of steroids for the prophylaxis of this syndrome.405423426Gopinathan, N.R., Sen, R.K., Viswanathan, V.K., Aggarwal, A., Mallikarjun, H.C., Rajaram Manoharan, S.R., Early, reliable, utilitarian predictive factors for fat embolism syndrome in polytrauma patients (2013) Indian J Crit Care Med., 17 (1), pp. 38-42Sen, R.K., Tripathy, S.K., Krishnan, V., Role of corticosteroid as a prophylactic measure in fat embolism syndrome: A literature review (2012) Musculoskelet Surg., 96 (1), pp. 1-8Bederman, S.S., Bhandari, M., McKee, M.D., Schemitsch, E.H., Do corticosteroids reduce the risk of fat embolism syndrome in patients with long-bone fractures? A meta-analysis (2009) Can J Surg., 52 (5), pp. 386-393Moore, F.A., Haenel, J.B., Moore, E.E., Whitehill, T.A., Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multiple oxygen failure (1992) J Trauma., 33 (1), pp. 58-65. , discussion 65-7Kim, P.K., Deutschman, C.S., Inflammatory responses and mediators (2000) Surg Clin North Am., 80 (3), pp. 885-894Kallenbach, J., Lewis, M., Zaltzman, M., Feldman, C., Orford, A., Zwi, S., 'Low-dose' corticosteroid prophylaxis against fat embolism (1987) J Trauma., 27 (10), pp. 1173-1176Lindeque, B.G., Schoeman, H.S., Dommisse, G.F., Boeyens, M.C., Vlok, A.L., Fat embolism and the fat embolism syndrome. A double-blind therapeutic study (1987) J Bone Joint Surg Br., 69 (1), pp. 128-131Schonfeld, S.A., Ploysongsang, Y., DiLisio, R., Crissman, J.D., Miller, E., Hammerschmidt, D.E., Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients (1983) Ann Intern Med., 99 (4), pp. 438-44

An in vivo study of quantum dots tissue accumulation

Nanotechnology represents a new frontier for the science progress and there are great expectations in relation to diagnostic and therapeutic envelopes [1]. Living organisms are built of cells that are typically 10 \u3bcm across. However, the cell parts are much smaller and are in the sub-micron size domain, for example a red blood cell is approximately 7,000 nm wide. Even smaller are the proteins with a typical size of just 5 nm, which is comparable with the dimensions of smallest manmade nanoparticles. This simple size comparison gives an idea of using nanoparticles as very small probes that would allow us to spy at the cellular machinery without introducing too much interference. Understanding of biological processes on the nanoscale level is a strong driving force behind development of nanotechnologyOur current knowledge of the toxicology of nanoparticles in vivo is poor [2] but suggests that nanoparticles may able to have adverse effects at their portal of entry , for example, the lungs, but that some nanoparticles may also escape the normal defences and translocate from their portal of entry to have diverse effects in other target organs [3].There is no cut-off below witch particles suddenly become harmful, in the lung at least. This is because harmful particles have their effects as a consequence of two factors that act together to determine their potential to cause harm: their large surface area, and the reactivity or intrinsic toxicity of the surface. It is self evident that the smaller particles are, the more surface area they have per unit mass; therefore any intrinsic toxicity of the particles surface will be emphasised. Some of the most complex nanoparticles are likely to be produced for therapeutic purposes, furthermore nanoparticles binding to protein may result in a series of consequences not expected to occur when proteins bind to large particles. Very small particles may be not detected by the normal phagocytic defences, allowing them to gain access to the blood or nervous system [4]. Very small particles are smaller than some molecules and could act like haptens to modify protein structures, either altering their function or rendering them antigenic, raising the potential for autoimmune effects.Tracers that we have used are nanoparticles with optical properties, fluorescent semiconductors, that absorb photons of light and re-emit photons at a different wavelength They are known as quantum dots (QDs), nanocrystals that are nanometres-scale (10-20nm, roughly protein-sized) atom clusters, containing from a few hundred to a few thousand atoms of a semiconductor material (cadmium mixed with selenium), which has been coated with an additional semiconductor shell (zinc sulfide) to improve the optical properties of the material. These nanoparticles fluoresce in a different way than do traditional fluorophores, they exhibit some important differences as compared to organic fluorescent dyes and naturally fluorescent proteins: they have an extinction coefficient 10-50 times bigger than them. These nanoparticles projected around their optical properties: stable , bright and photo-stable fluorescence, observed and measured for hours, and that persists also into isolated tissues. Nanoparticles like QDs, could be targeted and not targeted and provided several unique features and capabilities[5, 6]: the size-effect does the QDs cancer biomarkers and there is the possibility to functionalize their surface area with a several numbers of functional groups that can be linked with multiple diagnostic (e.g. radio-isotopic or magnetic) and therapeutic agents. The aim of the study is to monitor nanoparticles behaviour into blood system: kinetic, T1/2, bio distribution, and tissues accumulation. We would extrapolate from optics parameters physiological ones, in specific districts so as liver and lungs that are the most probably targets of toxicity

South Georgia blue whales five decades after the end of whaling

Blue whales Balaenoptera musculus at South Georgia were heavily exploited during 20th century industrial whaling, to the point of local near-extirpation. Although legal whaling for blue whales ceased in the 1960s, and there were indications of blue whale recovery across the wider Southern Ocean area, blue whales were seldom seen in South Georgia waters in subsequent years. We collated 30 yr of data comprising opportunistic sightings, systematic visual and acoustic surveys and photo-identification to assess the current distribution of blue whales in the waters surrounding South Georgia. Over 34000 km of systematic survey data between 1998 and 2018 resulted in only a single blue whale sighting, although opportunistic sightings were reported over that time period. However, since 2018 there have been increases in both sightings of blue whales and detections of their vocalisations. A survey in 2020 comprising visual line transect surveys and directional frequency analysis and recording (DIFAR) sonobuoy deployments resulted in 58 blue whale sightings from 2430 km of visual effort, including the photo-identification of 23 individual blue whales. Blue whale vocalisations were detected on all 31 sonobuoys deployed (114 h). In total, 41 blue whales were photo-identified from South Georgia between 2011 and 2020, none of which matched the 517 whales in the current Antarctic catalogue. These recent data suggest that blue whales have started to return to South Georgia waters, but continued visual and acoustic surveys are required to monitor any future changes in their distribution and abundance

Surfacing rates, swim speeds, and patterns of movement of Antarctic blue whales

During three surveys in the austral summers of 2013, 2015, 2019, data on Antarctic blue whale blow rates, dive times, swim speeds, and broadscale movements were collected using video photogrammetric tracking and intra-voyage photo-identification. A total of 24.4 hours of video observations were suitable for blow interval or movement analysis. Similar to other blue whale populations, Antarctic blue whale dive behaviour comprised a sequence of short dives followed by a long dive with a mean dive time for short dives of 17.6 s, and a mean long dive time of 189.3 s. Two separate methods were used to estimate the average blow rate for Antarctic blue whales, giving estimates of 59.7 and 63.2 blows per hour. The overall mean swim speed over the course of all suitable video track segments was 1.59 ms-1, but there were significant differences between years in the mean of the overall movement rate for each track; average movement rates were lower in 2015 compared to 2013 and 2019 (0.90 ms-1, 1.84 and 1.55 ms-1 respectively), with higher rates of turning in 2015. In 2019, there was faster overall movement through the study area in a consistent direction. The total number of photo-identified blue whales re-sighted intra-season in 2013 was nine (out of 50 identified individuals); in 2015 it was seven (out of 46); in 2019 two (out of 25). Whales remained for several days with little overall movement within the 2015 study area, whereas they were moving through the study area in 2019, which would explain the low number of intra-season resights. The predominant heading in 2019 was towards the area of Antarctic blue whale concentrations at the entrance to the Ross Sea observed in previous years. The photo-identification data also show a high proportion of resighted whales with coherent movements. This suggests that Antarctic blue whales might travel together, at least over periods of several days or sometimes up to a month. The differences between behaviours in 2015 and 2019 in particular may be related to differences in the characteristics of krill swarms between the study areas

Have whales returned to a historical hotspot of industrial whaling? The pattern of southern right whale Eubalaena australis recovery at South Georgia

Around 176500 whales were killed in the sub-Antarctic waters off South Georgia (South Atlantic) between 1904 and 1965. In recent decades, whales have once again become summer visitors, with the southern right whale (SRW) the most commonly reported species until 2011. Here, we assess the distribution, temporal pattern, health status and likely prey of SRWs in these waters, combining observations from a summertime vessel-based expedition to South Georgia, stable isotope data collected from SRWs and putative prey and sightings reports collated by the South Georgia Museum. The expedition used directional acoustics and visual surveys to localise whales and collected skin biopsies and photo-IDs. During 76 h of visual observation effort over 19 expedition days, SRWs were encountered 15 times (~31 individuals). Photo-IDs, combined with publicly contributed images from commercial vessels, were reconciled and quality-controlled to form a catalogue of 6 fully (i.e. both sides) identified SRWs and 26 SRWs identified by either left or right sides. No photo-ID matches were found with lower-latitude calving grounds, but 3 whales had gull lesions supporting a direct link with Península Valdés, Argentina. The isotopic position of SRWs in the South Georgia food web suggests feeding on a combination of copepod and krill species. Opportunistic reports of SRW sightings and associated group sizes remain steady over time, while humpback whales provide a strong contrast, with increased sighting rates and group sizes seen since 2013. These data suggest a plateau in SRWs and an increasing humpback whale presence in South Georgia waters following the cessation of whaling

Southern right whale vocalizations on foraging grounds in South Georgia

Southern right whale vocalizations were recorded concurrently with visual observations off the sub-Antarctic Island of South Georgia, and the characteristics of these calls were described. Calls were also compared to those of humpback whales at South Georgia, to determine how the two species might reliably be distinguished acoustically. The southern right whale calls measured (which were all upcalls) had lower frequency with peak energy and were mostly shorter in duration than the calls measured from humpback whales. The frequency upsweep and the lack of harmonics of southern right whale calls were also diagnostic characteristics

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Background: Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. Results: We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. One of the patients presented also variants in mitochondrial DNA that may have contributed to the peculiar phenotype. The deleterious effect of the identified missense changes was experimentally validated in yeast model. OPA1 level was reduced in available patients\u2019 biological samples, and a clearly fragmented mitochondrial network was observed in patients\u2019 fibroblasts. Conclusions: This report provides evidence that bi-allelic OPA1 mutations may lead to complex and severe multi-system recessive mitochondrial disorders, where optic atrophy might not represent the main feature

Genetic diversity and connectivity of southern right whales (Eubalaena australis) found in the Brazil and Chile-Peru wintering grounds and the South Georgia (Islas Georgias del Sur) feeding ground

As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur: SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite=208/46), Brazil (nnew mtDNA/microsatellite=50/50), South Africa (nnew mtDNA/microsatellite=66/77, npub mtDNA/microsatellite=350/47), Chile-Peru (nnew mtDNA/microsatellite=1/1), the Indo-Pacific (npub mtDNA/microsatellite=769/126), and SG (npub mtDNA/microsatellite=8/0, nnew mtDNA/microsatellite=3/11) to investigate the position of previously unstudied habitats in the migratory network: Brazil, SG and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of one genetically identified individual between the South American grounds. The single sample from Chile-Peru had a mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic, and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru