Paravasation with cyclophosphamide - Case report of tissue necrosis in a patient with primary breast cancer

Background: Paravasation is a rare but severe complication of treatment with cytotoxic agents. Some anticancer drugs are considered to be of high toxicity (vesicant), some are merely irritant, and some are regarded as nearly non-toxic to healthy tissue as is the case with cyclophosphamide. Case Report: In this report, we present the first case of severe tissue damage caused by a paravasation of cyclophosphamide in a breast cancer patient receiving chemotherapy. Conclusion: Therefore, every attending oncological physician should be aware of the possibility of severe tissue damage as a consequence of cyclophosphamide paravasation

Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.

BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight

House dust mite reduction and avoidance measures for treating eczema

BACKGROUND: Eczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can relapse and remit over time. As many as a third of people with eczema who have a positive test for allergy to house dust mite have reported worsening of eczema or respiratory symptoms when exposed to dust. OBJECTIVES: To assess the effects of all house dust mite reduction and avoidance measures for the treatment of eczema. SEARCH METHODS: We searched the following databases up to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant studies. We handsearched abstracts from international eczema and allergy meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any of the house dust mite reduction and avoidance measures for the treatment of eczema, which included participants of any age diagnosed by a clinician with eczema as defined by the World Allergy Organization. We included all non‐pharmacological and pharmacological interventions that sought to reduce or avoid exposure to house dust mite and their allergenic faeces. The comparators were any active treatment, no treatment, placebo, or standard care only. DATA COLLECTION AND ANALYSIS: Two authors independently checked the titles and abstracts identified, and there were no disagreements. We contacted authors of included studies for additional information. We assessed the risk of bias using Cochrane methodology. MAIN RESULTS: We included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high‐quality vacuuming of carpets and mattresses, and sprays that kill house dust mites. Four studies assessed our first primary outcome of 'Clinician‐assessed eczema severity using a named scale'. Of these, one study (n = 20) did not show any significant short‐term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high‐filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low‐filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups. With regard to the secondary outcomes 'Participant‐ or caregiver‐assessed global eczema severity score' and the 'Amount and frequency of topical treatment required', one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed 'Sensitivity to house dust mite allergen using a marker'; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials. None of the seven included studies assessed our second primary outcome 'Participant‐ or caregiver‐assessed eczema‐related quality of life using a named instrument' or the secondary outcome of 'Adverse effects'. We were unable to combine any of our results because of variability in the interventions and paucity of data. AUTHORS' CONCLUSIONS: We were unable to determine clear implications to inform clinical practice from the very low‐quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High‐quality long‐term trials of single, easy‐to‐administer house dust mite reduction or avoidance measures are worth pursuing

Permeabilised skeletal muscle reveals mitochondrial deficiency in malignant hyperthermia-susceptible individuals

Background: Individuals genetically susceptible to malignant hyperthermia (MH) exhibit hypermetabolic reactions when exposed to volatile anaesthetics. Mitochondrial dysfunction has previously been associated with the MH-susceptible (MHS) phenotype in animal models, but evidence of this in human MH is limited. Methods: We used high resolution respirometry to compare oxygen consumption rates (oxygen flux) between permeabilised human MHS and MH-negative (MHN) skeletal muscle fibres with or without prior exposure to halothane. A substrate-uncoupler-inhibitor titration protocol was used to measure the following components of the electron transport chain under conditions of oxidative phosphorylation (OXPHOS) or after uncoupling the electron transport system (ETS): complex I (CI), complex II (CII), CI+CII and, as a measure of mitochondrial mass, complex IV (CIV). Results: Baseline comparisons without halothane exposure showed significantly increased mitochondrial mass (CIV, P=0.021) but lower flux control ratios in CI+CII(OXPHOS) and CII(ETS) of MHS mitochondria compared with MHN (P=0.033 and 0.005, respectively) showing that human MHS mitochondria have a functional deficiency. Exposure to halothane triggered a hypermetabolic response in MHS mitochondria, significantly increasing mass-specific oxygen flux in CI(OXPHOS), CI+CII(OXPHOS), CI+CII(ETS), and CII(ETS) (P=0.001–0.012), while the rates in MHN samples were unaltered by halothane exposure. Conclusions: We present evidence of mitochondrial dysfunction in human MHS skeletal muscle both at baseline and after halothane exposure

Miniaturized wet-wet differential pressure sensor

We report a miniaturized wet-wet differential pressure sensor with applications in pressure and flow sensing in water networks and other harsh environments. The device is similar in concept to a conventional wet-wet differential pressure sensor in that the sensing element is protected from the external environment by oil-filled cavities closed off by corrugated diaphragms. However, with a package envelope of 11.0 x 4.8 x 3.4 mm 3 , corresponding to a volume of only 0.18 cm 3 , the device is considerably smaller than commercially available wet-wet differential pressure sensors. A high degree of miniaturization has been achieved by using micromachining to fabricate the corrugated diaphragms. Preliminary experimental results are presented showing operation of the device as a delta-pressure flow speed sensor in a water flow test rig

Demonstrating the translocation of nanoplastics across the fish intestine using palladium-doped polystyrene in a salmon gut-sac

Fish are widely reported to ingest microplastics with low levels accumulating in the tissues, but owing to analytical constraints, much less is known about the potential accumulation of nanoplastics via the gut. Recently, the labelling of plastics with inorganic metals (e.g., palladium) has allowed measurements of nanoplastic uptake. The aim of the current study was to quantitatively assess the uptake of nanoplastics by the fish gut using palladium-doped nanoplastics (with a mean hydrodynamic radius of 202 ± 7 nm). By using an ex vivo gut sac exposure system, we show that in 4 h between 200 and 700 million nanoplastics (representing 2.5–9.4% of the administered nanoplastics dose) can enter the mucosa and muscularis layers of the intestine of salmon. Of the particles taken up, up to 700,000 (representing 0.6% of that taken into the tissue) of the nanoplastics passed across the gut epithelium of the anterior intestine and exit into the serosal saline. These data, generated in highly controlled conditions provide a proof-of-concept study, suggesting the potential for nanoplastics to distribute throughout the body, indicating the potential for systemic exposure in fish.Demonstrating the translocation of nanoplastics across the fish intestine using palladium-doped polystyrene in a salmon gut-sacpublishedVersio

A cross-sectional study of Victorian mobile intensive care ambulance paramedics knowledge of the Valsalva manoeuvre

<p>Abstract</p> <p>Background</p> <p>The Valsalva Manoeuvre (VM) is a primary measure for terminating haemodynamically stable supraventricular tachycardia (SVT) in the emergency care setting. The clinical use and termination success of the VM in the prehospital setting has not been investigated to date. The objective of this study was to determine Melbourne Mobile Intensive Care Ambulance (MICA) Paramedic knowledge of the VM, and to compare this understanding with an evidence-based model of VM performance.</p> <p>Methods</p> <p>A cross-sectional study in the form of a face-to-face interview was used to determine Melbourne MICA Paramedic understanding of VM instruction between January and February, 2008. The results were then compared with an evidence-based model of VM performance to ascertain compliance with the three criteria of position, pressure and duration. Ethics approval was granted.</p> <p>Results</p> <p>There were 28 participants (60.9%) who elected a form of supine posturing, some 23 participants (50%) selected the syringe method of pressure generation, with 16 participants (34.8%) selecting the "as long as you can" option for duration. On comparison, one out of 46 MICA Paramedics correctly identified the three evidence-based criteria.</p> <p>Conclusions</p> <p>The formal education of Melbourne's MICA Paramedics would benefit from the introduction of an evidence based model of VM performance, which would impact positively on patient care and may improve reversion success in the prehospital setting. The results of this study also demonstrate that an opportunity exists to promote the evidence-based VM criteria across the primary emergency care field.</p

An Optimal Distributed Discrete Log Protocol with Applications to Homomorphic Secret Sharing

The distributed discrete logarithm (DDL) problem was introduced by Boyle et al. at CRYPTO 2016. A protocol solving this problem was the main tool used in the share conversion procedure of their homomorphic secret sharing (HSS) scheme which allows non-interactive evaluation of branching programs among two parties over shares of secret inputs. Let $g$ be a generator of a multiplicative group $\mathbb{G}$. Given a random group element $g^{x}$ and an unknown integer $b \in [-M,M]$ for a small $M$, two parties $A$ and $B$ (that cannot communicate) successfully solve DDL if $A(g^{x}) - B(g^{x+b}) = b$. Otherwise, the parties err. In the DDL protocol of Boyle et al., $A$ and $B$ run in time $T$ and have error probability that is roughly linear in $M/T$. Since it has a significant impact on the HSS scheme\u27s performance, a major open problem raised by Boyle et al. was to reduce the error probability as a function of $T$. In this paper we devise a new DDL protocol that substantially reduces the error probability to $O(M \cdot T^{-2})$. Our new protocol improves the asymptotic evaluation time complexity of the HSS scheme by Boyle et al. on branching programs of size $S$ from $O(S^2)$ to $O(S^{3/2})$. We further show that our protocol is optimal up to a constant factor for all relevant cryptographic group families, unless one can solve the discrete logarithm problem in a \emph{short} interval of length $R$ in time $o(\sqrt{R})$. Our DDL protocol is based on a new type of random walk that is composed of several iterations in which the expected step length gradually increases. We believe that this random walk is of independent interest and will find additional applications

Survival of the Systems

This is the author accepted manuscript. The final version is available from cell Press via the DOI in this recordSince Darwin, individuals and more recently genes have been the focus of evolutionary thinking. The idea that selection operates on non-reproducing, higher-level systems including ecosystems or societies has met with scepticism. But research emphasising that natural selection can be based solely on differential persistence invites reconsideration of their evolution. Self-perpetuating feedback cycles involving biotic as well as abiotic components are critical to determining persistence. Evolution of autocatalytic networks of molecules is well studied, but the principles hold for any ‘self-perpetuating’ system. Ecosystem examples include coral reefs, rainforests and savannahs. Societal examples include agricultural systems, dominant belief systems and economies. Persistence-based selection of feedbacks can help us understand how ecological and societal systems survive or fail in a changing world