Soft X-ray induced radiation damage in thin freeze-dried brain samples studied by FTIR microscopy.

In order to push the spatial resolution limits to the nanoscale, synchrotron-based soft X-ray microscopy (XRM) experiments require higher radiation doses to be delivered to materials. Nevertheless, the associated radiation damage impacts on the integrity of delicate biological samples. Herein, the extent of soft X-ray radiation damage in popular thin freeze-dried brain tissue samples mounted onto Si3N4 membranes, as highlighted by Fourier transform infrared microscopy (FTIR), is reported. The freeze-dried tissue samples were found to be affected by general degradation of the vibrational architecture, though these effects were weaker than those observed in paraffin-embedded and hydrated systems reported in the literature. In addition, weak, reversible and specific features of the tissue-Si3N4 interaction could be identified for the first time upon routine soft X-ray exposures, further highlighting the complex interplay between the biological sample, its preparation protocol and X-ray probe.

Biodiversity impacts due to food consumption in Europe.

Food security and biodiversity conservation are closely interconnected challenges to be addressed to achieve a sustainable food system on a global scale. Due to the complex nature of food production and consumption system, quantifying the impacts of food supply chains on biodiversity is challenging. Life cycle assessment (LCA) allows for systematically addressing environmental impacts along supply chains, representing a reference methodology that can be applied for assessing food systems. In the present study, 32 representative food products of consumption in the European Union (EU) were selected and their environmental impacts calculated through a process-based LCA. The potential contribution of EU food consumption to the current biodiversity decline has been evaluated adopting both midpoint and endpoint indicators. A comparison of the impact drivers was performed. Meat products, the underpinning land use for agricultural purposes, and climate change represent the main hotspots of impacts on biodiversity. Notwithstanding several drivers of biodiversity loss can be accounted for with LCA, the evidence of the increasing biodiversity decline on both a European and a global scale indicates that the assessment system should be further expanded, especially for what concerns refining impact categories such as ecotoxicity, and including resource overexploitation, and impact due to invasive species. This study illustrates: how far the current LCA based impact assessment framework may help to address the drivers of biodiversity loss; which are the main uncertainties associated to results stemming from the application of different endpoint methods; which aspects need to be elaborated further to ensure a comprehensive assessment of biodiversity impacts due to food production and consumption.

Assessing the decoupling of economic growth from environmental impacts in the European Union: A consumption-based approach.

Pursuing a responsible and sustainable development, the United Nations urged to decouple economic growth from environmental impacts. Several European Union (EU) policies have been implemented towards such goal. Although multiple authors have evaluated the decoupling of the economic growth from the resource use or environmental concerns, the environmental assessment mostly focused on pressures rather than impacts, and used single indicators assumed to be a proxy of the overall effects on the environment. Furthermore, no studies were found using a process-based life cycle approach to quantify the environmental impacts of consumption. To solve such research gap, this paper assesses the decoupling in the EU focusing on potential environmental impacts, complementing a production-based approach with two options for accounting for the impacts of consumption. The aim of this paper is to evaluate the decoupling of the economic growth (in terms of Gross Domestic Product) from the environmental impacts due to EU-28 consumption, assessed by means of life cycle assessment (LCA). The decoupling is then assessed in impact terms rather than limited to pressures by using the Environmental Footprint (EF2017) indicators, which allows assessing 16 different impacts. The Consumption Footprint indicator quantified the environmental impacts of EU apparent consumption, including the territorial impacts (Domestic Footprint) and the embodied impacts in both imports and exports (Trade Footprint). The inventory of pressures for the trade component is compiled either with a bottom-up approach (process-based LCA of representative traded goods) or a top-down approach (input-output-based LCA). Methodological aspects influencing the decoupling assessment and the resulting outputs are presented and discussed. According to the results, the environmental impacts of EU-28 consumption showed decoupling during the last decades (2005-2014), between relative to absolute decoupling depending on the inventory modeling approach taken. Some countries showed higher decoupling levels than others displaying a heterogeneous map of EU-28 decoupling, which was led by acidification, particulate matter, land use and eutrophication impacts. Notwithstanding current limitations, the assessment of decoupling using consumption-based environmental indicators is very promising for supporting policy-making towards addressing the actual impacts driven by the EU production and consumption system.

Intraosseous migration of tendinous calcifications: two case reports.

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations.

Lipid-based nanovesicles for nanomedicine.

Molecular self-assembly has enabled the fabrication of biologically inspired, advanced nanostructures as lipid-based nanovesicles (L-NVs). The oldest L-NVs, liposomes, have been widely proposed as potential candidates for drug delivery, diagnostic and/or theranostic applications and some liposome-based drug products have already stepped from the lab-bench to the market. This success is attributed to their ability to encapsulate both hydrophobic and/or hydrophilic molecules, efficiently carry and protect them within the body and finally deliver them at the target site. These positive features are also coupled with high biocompatibility. However, liposomes still present some unsolved drawbacks, such as poor colloidal stability, short shelf-life, restricted and expensive conditions of preparation because of the inherent nature of their fundamental constituents (phospholipids). The new tools available in the self-assembly of controlled molecules have significantly advanced the field of L-NV design and synthesis, and non-liposomal L-NVs have been recently developed; this new generation of nanovesicles can represent a paradigm shift in nanomedicine: they may complement liposomes, showing their advantages and overcoming most of their drawbacks. Clearly, being still young, their rocky way to the clinic first and then to the market has just started and it is still long, but they have all the potentialities to reach their objective target. The purpose of this review is to first present the large plethora of L-NVs available, focusing on this new generation of non-liposomal L-NVs and showing their similarities and differences with respect to their ancestors (liposomes). Since the overspread of a nanomaterial to the market is also strongly dependent on the availability of technological-scale preparation methods, we will also extensively review the current approaches exploited for L-NV production. The most cutting-edge approaches based on compressed fluid (CF) technologies will be highlighted here since they show the potential to represent a game-change in the production of L-NVs, favouring their step from the bench to the market. Finally, we will briefly discuss L-NV applications in nanomedicine, looking also for their future perspectives.

Gist-based illusions within and across stimulus modalities in autism spectrum disorder.

Some studies have reported a low rate of false recognition (FR) in individuals with autism spectrum disorder (ASD) relative to non-autistic comparison participants (CPs). This finding, however, has not always been replicated and the source of the discrepancy remains unknown. We hypothesised that poor episodic memory functions may account for this finding. We used an adapted version of the Deese, Roediger and McDermott paradigm which presents lists of words, pictures or word-picture pairs to obtain measures of performance which reflect episodic [hits and false alarms (FAs)] and semantic (FR) memory functions. Results showed a decreased rate of FR in ASD individuals with lists of words which rose above the rate seen in non-autistic CPs with lists of word-picture pairs. This increased rate of FR in ASD was accompanied by a parallel increase in hits and a decrease in FA which reached a similar level in the two groups. Poor episodic memory functions may prevent individuals with ASD from acquiring item information which in turn precludes the formation of semantic links between items. This could render them less prone to FR.

Morphometric analysis and lymph node yield in laparoscopic complete mesocolic excision performed by supervised trainees.

BACKGROUND: Complete mesocolic excision with central vascular ligation (CME) produces an optimal colonic cancer specimen. The ability of expert laparoscopic surgeons to produce equivalent specimens is unknown. METHODS: Fresh specimen photographs and clinicopathological data from patients undergoing laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for independent pathological review. Surgery was performed by a mixture of consultant specialists and trainees under consultant specialist supervision, between February 2010 and July 2011. The planes of surgery were graded and tissue morphometry was performed using standard methods. The results were compared with published data from open CME and non-CME surgery. RESULTS: In total, 69 patients were identified, and in 96 per cent resection was performed completely or partially by surgical trainees. Laparoscopic CME produced a similar specimen to open CME. The laparoscopic mesocolic plane resection rate was similar to that for open surgery (90 versus 88 per cent). The distance between the bowel wall and site of vascular division was similar for laparoscopic and open right-sided CME (92 versus 95 mm respectively). The corresponding values for left-sided CME were also similar (103 versus 107 mm). Compared with values from two non-CME series, laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per cent), and resected more tissue between the bowel wall and the vascular division (right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The lymph node yield remained low following laparoscopic CME compared with open CME (median 18 versus 32; P < 0·001) and identical to that of non-CME surgery (median 18). CONCLUSION: Laparoscopic CME can be performed to the same standard as open surgery by supervised trainees. However, this did not increase the lymph node yield.

Randomized controlled trial of percutaneous versus transcutaneous posterior tibial nerve stimulation in faecal incontinence.

BACKGROUND: Percutaneous, transcutaneous and sham transcutaneous posterior tibial nerve stimulation was compared in a prospective blinded randomized placebo-controlled trial. METHODS: Patients who had failed conservative treatment for faecal incontinence were randomized to one of three groups: group 1, percutaneous; group 2, transcutaneous; group 3, sham transcutaneous. Patients in groups 1 and 2 received 30-min sessions of posterior tibial nerve stimulation twice weekly for 6 weeks. In group 3, transcutaneous electrodes were placed in position but no stimulation was delivered. Symptoms were measured at baseline and after 6 weeks using a bowel habit diary and St Mark's continence score. Response to treatment was defined as a reduction of at least 50 per cent in weekly episodes of faecal incontinence compared with baseline. RESULTS: Thirty patients (28 women) were enrolled. Nine of 11 patients in group 1, five of 11 in group 2 and one of eight in group 3 had a reduction of at least 50 per cent in weekly episodes of faecal incontinence at the end of the 6-week study phase (P = 0·035). Patients undergoing percutaneous nerve stimulation had a greater reduction in the number of incontinence episodes and were able to defer defaecation for a longer interval than those undergoing transcutaneous and sham stimulation. These improvements were maintained over a 6-month follow-up period. CONCLUSION: Posterior tibial nerve stimulation has short-term benefits in treating faecal incontinence. Percutaneous therapy appears to have superior efficacy to stimulation applied by the transcutaneous route. REGISTRATION NUMBER: NCT00530933 (http://www.clinicaltrials.gov).

Coherent molecule formation in anharmonic potentials near confinement-induced resonances.

We perform a theoretical and experimental study of a system of two ultracold atoms with tunable interaction in an elongated trapping potential. We show that the coupling of center-of-mass and relative motion due to an anharmonicity of the trapping potential leads to a coherent coupling of a state of an unbound atom pair and a molecule with a center of mass excitation. By performing the experiment with exactly two particles we exclude three-body losses and can therefore directly observe coherent molecule formation. We find quantitative agreement between our theory of inelastic confinement-induced resonances and the experimental results. This shows that the effects of center-of-mass to relative-motion coupling can have a significant impact on the physics of quantum systems near center-of-mass to relative-motion coupling resonances.

High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.

The first 3 years of national bowel cancer screening at a single UK tertiary centre.

AIM: St Mark's Bowel Cancer Screening Centre commenced screening in October 2006 as a contributor to the national programme. The first 35 months' experience is reported. METHOD: Individuals with a positive faecal occult blood test (FOBT) were offered colonoscopy or alternatives if they had significant comorbidity. All screening data were collected prospectively. RESULTS: Of the 98 815 FOBT kits issued, 42 523 were returned (43% uptake; 20.79% men). In total, 1339/1488 (90%) FOBT-positive participants attended the nurse clinic (57% men). Of these, 1057 had an index colonoscopy, 115 had a computed tomography colonoscopy (CTC) and eight had a flexible sigmoidoscopy. Five hundred and seventeen (44%) procedures were 'normal' (no polyps/cancers). Eighty (6%) individuals had colorectal cancer. The polyp detection rate in index procedures, including colonoscopy, CTC and flexible sigmoidoscopy, was 50%. The adenoma detection rate of all colonoscopies was 62.8%. The median polyp size was 5 (1-80) mm. In total, 1200 colonoscopies were performed by five accredited colonoscopists (96% completion rate). There were 13 (1%) adverse events with < 1 in 500 patients undergoing polypectomy requiring a transfusion. There was one 30-day postsurgical mortality, one perforation and no colonoscopy-related mortality. Almost all 39/40 (97%) patients in the BCS programme felt that the findings were adequately explained compared with 21/32 (64%) elective patients (P < 0.001) within the same unit. CONCLUSIONS: At this bowel cancer screening single centre, colonoscopy completion rates were high (unadjusted caecal intubation rate of 96%) and complication rates were low. In contrast to other published data, the uptake and cancer-detection rates were lower.

Sensorimotor functional connectivity changes in amyotrophic lateral sclerosis.

We investigated whether the functional connections to the primary sensorimotor cortex (SMC) at rest are abnormal in 26 patients with amyotrophic lateral sclerosis (ALS) and whether such changes are related to the corticospinal tract (CST) damage, measured using diffusion tensor magnetic resonance imaging (DT MRI). ALS patients versus controls showed a significantly increased functional connectivity between the left SMC and the right cingulate cortex, parahippocampal gyrus, and cerebellum-crus II. No right SMC connectivity changes were found. The pattern of increased functional connectivity to the left SMC was more widespread when considering only patients with no CST DT MRI abnormalities than the whole group of patients. In this patient group, functional connectivity was also increased between the right SMC and the right parahippocampal gyrus. On the contrary, in ALS patients with CST damage (as assessed using DT MRI) versus controls, functional connectivity was increased between the left SMC and the right cingulate cortex only, while it was decreased between the right SMC and the right cerebellum-lobule VI. In ALS patients, disease severity correlated with reduced SMC functional connectivity. Functional brain changes do occur in ALS with mild disability. These changes might have a role in compensating for (limited) structural damage and might exhaust with increasing burden of disease pathology.

A new procedure for extraction of collagen from modern and archaeological bones for 14C dating.

Bones are potentially the best age indicators in a stratigraphic study, because they are closely related to the layer in which they are found. Collagen is the most suitable fraction and is the material normally used in radiocarbon dating. Bone contaminants can strongly alter the carbon isotopic fraction values of the samples, so chemical pretreatment for (14)C dating by accelerator mass spectrometry (AMS) is essential. The most widespread method for collagen extraction is based on the Longin procedure, which consists in HCl demineralization to dissolve the inorganic phase of the samples, followed by dissolution of collagen in a weak acid solution. In this work the possible side effects of this procedure on a modern bone are presented; the extracted collagen was analyzed by ATR-IR spectroscopy. An alternative procedure, based on use of HF instead of HCl, to minimize unwanted degradation of the organic fraction, is also given. A study by ATR-IR spectroscopic analysis of collagen collected after different demineralization times and with different acid volumes, and a study of an archaeological sample, are also presented.

A novel hepatocyte nuclear factor-1ß (MODY 5) gene mutation in a Romanian boy with pancreatic calcifications, renal and hepatic dysfunction.

We report a 12-years-old Romanian boy with a diagnosis of diabetes and renal insufficiency. Mutations in homeodomain-containing transcription factor hepatocyte nuclear factor (HNF-1ß) have been reported in association with maturity-onset diabetes of the young (MODY 5) and early maturity-onset diabetes, progressive non-diabetic renal dysfunction and bilateral renal cysts. We found a new heterozygous mutation in HFN-1ß located in the exon 3 (c.715 G>C; p.239R) associated to pancreatic calcifications. The importance of molecular diagnosis of MODY patients is reinforced and the need for a careful follow-up is stressed in order to monitor the progression of clinical manifestations and its correlation with the gene mutation.

Cervical cord functional MRI changes in relapse-onset MS patients.

OBJECTIVE: To investigate whether (1) the tactile-associated cord functional MRI (fMRI) changes vary in the different clinical stages of relapse-onset multiple sclerosis (MS), and (2) the pattern of cord fMRI changes relates to severity of MS clinical disability. METHODS: Cervical cord fMRI was acquired from 49 MS patients (30 relapsing-remitting (RR), 19 secondary progressive (SP)), and 19 controls, during a tactile stimulation of the right hand. Task-related cord mean signal change and occurrence of fMRI activity at each cord quadrant and level were measured. MRI quantities were compared between groups using an univariate analysis. Between-group differences in topographical distribution of fMRI activity were evaluated using random-effect logistic regression models. RESULTS: Compared with controls, both RRMS (p=0.05) and secondary progressive multiple sclerosis (p=0.02) patients showed a higher cord fMRI activity, whereas no difference was found between patient groups. Severely disabled patients (26/49) showed a cord overactivation relative to controls (p=0.004) and patients with mild disability (p=0.04). Both controls and MS patients showed a functional lateralisation of cord activity, which was predominant in the cord side ipsilateral to the stimulus, and a more frequent activation of the posterior than of the anterior cord quadrants. DISCUSSION: This study shows that tactile-associated cervical cord fMRI activity is increased in relapse-onset MS patients. Such an overactivation is more prominent in patients with more severe locomotor disability. This suggests that an abnormality of cord functional properties may be among the factors associated with the clinical status of MS patients.

[Etanercept and chronic infection by HCV and HBV]. / Etanercept e infecci (R)n cr (R)nica por los virus de la hepatitis C y B.

Both psoriasis and chronic infections by HBV and HCV have high prevalence. Thus, it is relatively easy for them to coincide in the same patient. If the psoriasis requires systemic treatment, the dermatologist should consider the hepatic comorbidity when selecting an appropriate treatment. Cyclosporine, in addition to other well-known side effects, is an immunosuppressant that may condition worse evolution of the viral hepatitis. On the other hand, retinoids, psoralens and, above all, methotrexate may worsen the liver function. The anti-TNF-|A biological agents are not hepatotoxic and their theoretical contraindication in this context would be because of their action on the immune response and risk of reactivation of the hepatic infection. However, several studies have demonstrated that neither the viral load nor the hepatic inflammation parameters are generally modified negatively when they are used in hepatitis due to HCV. Their use in this context, with correct monitoring, seems, therefore, very reasonable. On the contrary, in chronic hepatitis B virus, there are cases of worsening, even with fatal outcome in some cases, and the use of these biological agents should be reserved for cases having greater need, and always be associated to antiviral treatment and strict monitoring. The review of the recent literature seems to allow the conclusion that the concomitant use of lamivudine would greatly reduce the risk of viral reactivation and, with this condition, the use of etanercept in some HBV+ patients may also be contemplated.

A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients.

OBJECTIVE: To define the temporal evolution of intrinsic tissue damage and atrophy in the cervical cord and the brain portion of the corticospinal tracts (CST) from patients with amyotrophic lateral sclerosis (ALS). METHODS: Conventional and diffusion tensor (DT) magnetic resonance imaging (MRI) of the cervical cord and brain were obtained from 17 ALS patients and 20 controls, at baseline and after a mean follow-up of 9 months. The following measurements were assessed: (a) cervical cord cross-sectional area, average mean diffusivity (MD) and average fractional anisotropy (FA); and (b) CST T2-visible hyperintensities, average MD and FA. RESULTS: During the follow-up, ALS patients showed a significant decrease in cord area (p = 0.003) and cord average FA (p = 0.01), and a significant increase in cord average MD (p = 0.01). In ALS patients, longitudinal changes of diffusivity measurements were not associated with cord area changes. At baseline, brain CST average MD was significantly higher in ALS patients compared with controls (p = 0.001). Brain CST diffusivity measurements remained stable over time in ALS patients and did not correlate with cord damage. CONCLUSIONS: This study shows that progressive tissue loss and injury to the remaining tissue occur in the cervical cord of ALS patients and that these two features of ALS-related pathology are not strictly interrelated. Cord pathology in ALS patients is likely to be independent of brain changes, indicating that imaging the cervical cord may be a useful adjunctive tool to monitor ALS evolution.