What you need to know about migraine in Hughes syndrome patients.

BACKGROUND: Headache, often migrainous, is common in patients with antiphospholipid antibodies, whether or not they meet Sydney criteria for a definite diagnosis of Hughes syndrome. Migraine may be a harbinger of stroke in this patient population and even refractory migraine may be highly responsive to antithrombotic therapy in this clinical context. PURPOSE: To summarize what is known to date about managing this important manifestation of the immune-mediated hypercoagulable Hughes syndrome. RESULTS: We provide a suggested management algorithm for refractory headache in this unique patient population. CONCLUSION: Most neurologists don't see or recognize many aPL-positive patients in their practice, so hematologists and rheumatologists who see these patients should recognize that refractory headache may be a manifestation of their immune-mediated hypercoagulable disorder and understand that the potential risks of not addressing this issue may be high.

Liver function tests in primary care provide a key opportunity to diagnose and engage patients with hepatitis C.

Since the advent of direct-acting antiviral therapy, the elimination of hepatitis c virus (HCV) as a public health concern is now possible. However, identification of those who remain undiagnosed, and re-engagement of those who are diagnosed but remain untreated, will be essential to achieve this. We examined the extent of HCV infection among individuals undergoing liver function tests (LFT) in primary care. Residual biochemistry samples for 6007 patients, who had venous blood collected in primary care for LFT between July 2016 and January 2017, were tested for HCV antibody. Through data linkage to national and sentinel HCV surveillance databases, we also examined the extent of diagnosed infection, attendance at specialist service and HCV treatment for those found to be HCV positive. Overall HCV antibody prevalence was 4.0% and highest for males (5.0%), those aged 37-50 years (6.2%), and with an ALT result of 70 or greater (7.1%). Of those testing positive, 68.9% had been diagnosed with HCV in the past, 84.9% before the study period. Most (92.5%) of those diagnosed with chronic infection had attended specialist liver services and while 67.7% had ever been treated only 38% had successfully cleared infection. More than half of HCV-positive people required assessment, and potentially treatment, for their HCV infection but were not engaged with services during the study period. LFT in primary care are a key opportunity to diagnose, re-diagnose and re-engage patients with HCV infection and highlight the importance of GPs in efforts to eliminate HCV as a public health concern.

Cardiovascular Risk Management in Type 1 Diabetes.

PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is associated with increased mortality, with premature cardiovascular disease (CVD) a major factor. To date, research has identified multiple risk factors for this excess CVD liability. However, gaps remain in our understanding of the underlying mechanisms. RECENT FINDINGS: T1DM is generally diagnosed at a young age. Since cardiovascular complications often only manifest at a later stage of life, there is generally less focus in earlier years on reducing CVD risk for affected individuals. This is an area that requires improvement as risk factors might be managed from earlier age to reduce later development of CVD. In this review, we discuss the evidence for cardiovascular risk factors, risk prediction models, candidate surrogate measurements and CVD risk management.

Palynological evidence for pre-agricultural reindeer grazing and the later settlement history of the Lycksele region, northern Sweden.

Analyses of high-resolution pollen data, coprophilous fungal spores, microscopic charcoal and sedimentology, combined with radiocarbon dating, allow the assessment of the impact of Sami and Nordic land use in the region surrounding the winter market town of Lycksele in northern Sweden. Such winter markets were established by the Crown during the seventeenth century AD to control the semi-nomadic movements of the Sami who traded here with Finnish settlers and were also taxed and educated. Little is known about Sami and Nordic co-existence beyond these market places, mainly due to a lack of archaeological evidence relating to Sami activity. Vegetation and land-use changes in the region between ~ AD 250 and 1825 reveal no signal for pre-seventeenth century agricultural activity, but the coprophilous fungal spore records suggest the increased regional presence of grazing herbivores (possibly reindeer) between ~ AD 800 and 1100. Sami activity in the parish of Lycksele has been suggested by rich metal finds dated to ~ AD 1000-1350 and they may have been attracted by an abundance of reindeer.

Trends in HbA1c and other biochemical outcomes of individuals with newly diagnosed type 1 diabetes.

BACKGROUND: There is limited data on glycaemic control and cardiovascular risk factor management in newly diagnosed individuals with type 1 diabetes in the first 2 years. METHODS: Retrospective, single centre study from the North West of England, newly diagnosed with type 1 diabetes between 2014 and 2018 (n = 58). HbA1c, blood pressure, lipids and body mass index (BMI) data were collected from electronic patient records from the time of diagnosis until the end of 2 years, stratified by age 16-24 years or ≥ 25 years at presentation. RESULTS: For those aged 16-24 years (n = 31), median (IQR), HbA1c improved at 6 months from 83 (63-93) to 51.5 (46-75) mmol/mol (p = 0.001) and remained stable 6-24 months. For those ≥ 25 years (n = 27), HbA1c declined from 91 (70-107) to 65 (50-89) mmol/mol, (p < 0.01) at 6 months and declined further to 52 mmol/mol (44-70) at 24 months. At 24 months, 27.8% of all individuals had an HbA1c ≥ 69 mmol/mol. Approximately, a third met LDL (< 2 mmol/L) and total cholesterol (< 4 mmol/L) targets. A total of 58.6% of individuals were overweight/obese (BMI > 25 kg/m2) at 24 months compared to 45.8% at baseline. There were no significant blood pressure changes during the follow-up. CONCLUSIONS: In both age groups, significant improvement of HbA1c occurred within the first 6 months of diagnosis with no statistical difference between the two groups at any of the time points up to 24 months. Despite significant improvements in HbA1c, majority had levels > 53 mmol/mol at 24 months. Alongside the high incidence of obesity and dyslipidaemia, our data support the need for further intensification of therapy from diagnosis of type 1 diabetes.

Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasizing. Proteomic analysis of cSCCs can provide insight into the biological processes responsible for metastasis, as well as future therapeutic targets and prognostic biomarkers. OBJECTIVES: To identify proteins associated with development of metastasis in cSCC. METHODS: A proteomic-based approach was employed on 105 completely excised, primary cSCCs, comprising 52 that had metastasized (P-M) and 53 that had not metastasized at 5 years post-surgery (P-NM). Formalin-fixed, paraffin-embedded cSCCs were microdissected and subjected to proteomic profiling after one-dimensional (1D), and separately two-dimensional (2D), liquid chromatography fractionation. RESULTS: A discovery set of 24 P-Ms and 24 P-NMs showed 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P-Ms and P-NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. The findings were verified by multiple reaction monitoring on six peptides from two proteins, annexin A5 (ANXA5) and dolichyl-diphosphooligosaccharide-protein glycosyltransferase noncatalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n = 57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve of 0·93 (confidence interval 0·83-1·00), an accuracy of 91·2% and higher sensitivity and specificity than cSCC staging systems currently in clinical use. CONCLUSIONS: This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.

Exciton effect in new generation of carbon nanotubes: graphdiyne nanotubes.

Graphdiyne-based nanotubes (GDNTs) are a novel type of carbon nanotubes. While conventional carbon nanotubes (CNTs) are generated by rolling graphene sheets, GDNTs are generated by rolling sheets that are similar to graphene but where the edges are elongated by the introduction of additional acetylene bonds between vertices (C6 aromatic rings). Such nanotubes are predicted to have many useful practical applications, but a thorough understanding of the relationship between their structure and their physical properties is still missing. We present a theoretical study of the electronic and optical properties of GDNTs. The structural, electronic, and optical properties of GDNTs with different diameters (i.e., 2-10 additional acetylene bonds) have been studied systematically by using density function theory (DFT) and self-consistent charge density functional tight-binding (SCC-DFTB) and by solving the Bethe-Salpeter equation (BSE), with and without considering the electron-hole interactions. The results indicate that the GDNTs are semiconductors with the direct band gap in close range, which is beneficial for photoelectronic devices and applications. Moreover, the absorption spectra of the GDNTs with different edge structures, (armchair, and zigzag) revealed little differences between the optical spectra of armchair and zigzag GDNTs, which could mean that fine separation between those structures (a process that is likely difficult and expensive in practice) will not be necessary. Importantly, the nanotubes were highly stable based on their cohesive energies, and their exciton binding energies were as large as about ~ 1 eV. From a methodological point of view, SCC-DFTB was found to be in agreement with more elaborate DFT calculations for most systems. Graphical abstract.

Synthesis of a Vocal Sound from the 3,000 year old Mummy, Nesyamun 'True of Voice'.

The sound of a 3,000 year old mummified individual has been accurately reproduced as a vowel-like sound based on measurements of the precise dimensions of his extant vocal tract following Computed Tomography (CT) scanning, enabling the creation of a 3-D printed vocal tract. By using the Vocal Tract Organ, which provides a user-controllable artificial larynx sound source, a vowel sound is synthesised which compares favourably with vowels of modern individuals.

Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

Influences of salinity on the physiology and distribution of the Arctic coralline algae, Lithothamnion glaciale (Corallinales, Rhodophyta).

In Greenland, free-living red coralline algae contribute to and dominate marine habitats along the coastline. Lithothamnion glaciale dominates coralline algae beds in many regions of the Arctic, but never in Godthåbsfjord, Greenland, where Clathromorphum sp. is dominant. To investigate environmental impacts on coralline algae distribution, calcification and primary productivity were measured in situ during summers of 2015 and 2016, and annual patterns of productivity in L. glaciale were monitored in laboratory-based mesocosm experiments where temperature and salinity were manipulated to mimic high glacial melt. The results of field and cold-room measurements indicate that both L. glaciale and Clathromorphum sp. had low calcification and photosynthetic rates during the Greenland summer (2015 and 2016), with maximum of 1.225 ± 0.17 or 0.002 ± 0.023 µmol CaCO3  · g-1  · h-1 and -0.007 ±0.003 or -0.004 ± 0.001 mg O2  · L-1  · h-1 in each species respectively. Mesocosm experiments indicate L. glaciale is a seasonal responder; photosynthetic and calcification rates increase with annual light cycles. Furthermore, metabolic processes in L. glaciale were negatively influenced by low salinity; positive growth rates only occurred in marine treatments where individuals accumulated an average of 1.85 ± 1.73 mg · d-1 of biomass through summer. These results indicate high freshwater input to the Godthåbsfjord region may drive the low abundance of L. glaciale, and could decrease species distribution as climate change increases freshwater input to the Arctic marine system via enhanced ice sheet runoff and glacier calving.

Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome.

WHAT IS KNOWN AND OBJECTIVES: At least four prospective trials have been initiated investigating the direct oral anticoagulants in the antiphospholipid syndrome. Preliminary reports have supported their use in patients with a history of venous thrombosis and a target INR of 2-3, but there have also been reports of failure of these agents in the antiphospholipid syndrome. The objective is to present a case report that illustrates there may be important dosing issues when considering the use of these agents in patients with the antiphospholipid syndrome. CASE SUMMARY: A 50-year-old woman with the antiphospholipid syndrome, manifesting clinically with recurrent pyoderma gangrenosum-like leg ulcers, was treated with apixaban, resulting in improved ulcer healing. For insurance purposes, she was switched to rivaroxaban with worsening of the ulcers which again improved when apixaban was resumed. WHAT IS NEW AND CONCLUSION: Despite a similar half-life, pharmacokinetics and pharmacodynamics, the manufacturer-recommended maintenance dosing of apixaban is twice daily and rivaroxaban once daily. We believe this difference in recommended dose accounts for the differential clinical response noted in the present case report and that twice daily dosing and a larger daily dose of these agents may be more efficacious in potent hypercoagulable disorders, such as the antiphospholipid syndrome.

Industrial-era lead and mercury contamination in southern Greenland implicates North American sources.

To study the long-range transport of atmospheric pollutants from lower latitude industrial areas to the Arctic, we analysed a peat core spanning the last ~700cal.yr (~1300-2000CE) from southern Greenland, an area sensitive to atmospheric pollution from North American and Eurasian sources. A previous investigation conducted in the same location recorded atmospheric lead (Pb) pollution after ~1845, with peak values recorded in the 1970s, and concluded that a North American source was most likely. To confirm the origin of the lead, we present new Pb isotope data from Sandhavn, together with a high-resolution record for mercury (Hg) deposition. Results demonstrate that the mercury accumulation rate has steadily increased since the beginning of the 19th century, with maximum values of 9.3µgm-2yr-1 recorded ~1940. Lead isotopic ratios show two mixing lines: one which represents inputs from local and regional geogenic sources, and another that comprises regional geogenic and pollution sources. Detrending the Pb isotopic ratio record (thereby extracting the effect of the geogenic mixing) has enabled us to reconstruct a detailed chronology of metal pollution. The first sustained decrease in Pb isotope signals is recorded as beginning ~1740-1780 with the lowest values (indicating the highest pollution signature) dated to ~1960-1970. The 206Pb/207Pb ratio of excess Pb (measuring 1.222, and reflecting pollution-generated Pb), when compared with the Pb isotopic composition of the Sandhavn peat record since the 19th century and the timing of Pb enrichments, clearly points to the dominance of pollution sources from North America, although it did not prove possible to further differentiate the emissions sources geographically.

High-resolution palynology reveals the land use history of a Sami renvall in northern Sweden.

The limited availability of historical and archaeological evidence means that much is still unknown about the development of Sami reindeer herding in Fennoscandia in both the recent and more distant past. To address this problem, high-resolution palynological analyses, 14C and 210Pb dating were undertaken on two adjacent (<25 m apart) peat profiles collected at a recently abandoned reindeer gathering pen (renvall) near Jokkmokk (~66.6°N, 19.8°E) in the boreal forest of northern Sweden. The aim was to assess the impact of Sami reindeer herding on the local environment through a study of pollen, coprophilous fungal spores, microscopic charcoal and sedimentology. The samples collected from within an annex to the renvall indicate cycles of use and abandonment of the pen on a multi-decadal timescale between ~ad 1800-2008, most obviously in the coprophilous fungal spore archive. The pattern and timing of these cycles confirm events previously known only from oral histories. Although the local pollen assemblage zones associated with the phasing of activity were reproducible in a second peat core beyond the boundary of the renvall, the coprophilous fungal spore signal in this paired profile was much less distinctive, possibly due to the typically shorter dispersal distances for these microfossils in comparison to pollen grains.

A matched comparison study of hepatitis C treatment outcomes in the prison and community setting, and an analysis of the impact of prison release or transfer during therapy.

Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.

Simulating backspatter of blood from cranial gunshot wounds using pig models.

Few studies have examined the biomechanical basis for backspatter from cranial gunshot wounds. Backspatter is material which travels against the direction of fire following ejection from a gunshot entrance wound. Our paper focuses on the use of animals for reconstructing this phenomenon. Five live pigs and several slaughtered pigs were shot using either 9 × 19 mm, 115 grain, full metal jacketed ammunition or .22 long rifle, 40 grain, lead, round-nose ammunition. A high-speed camera was used to record the entrance wound formation and backspatter. A small amount of backspattered material was produced with all targets, and blood backspatter was seen in a few cases. However, we conclude that our model provides an understanding of the phenomenon of backspatter and the physical mechanisms associated with it. The various components of the mechanism of backspatter formation are complex and overlap. The principle mechanism observed in pig cranial gunshots was the high-speed impact response of the skin overlying the skull bone. This study has also produced evidence supporting the view that backspatter can result from the splashing of superficial blood if it is already present on the skin. Subcutaneous gas effects have been demonstrated for backspatter from contact shots. There has been no clear evidence of the role of the collapse of a temporary cavity within the brain.

The histopathological mimics of inflammatory bowel disease: a critical appraisal.

The pathological diagnosis of inflammatory bowel disease (IBD) is often difficult because biopsy material may not contain pathognomonic features, making distinction between Crohn's disease, ulcerative colitis and other forms of colitides a truly challenging exercise. The problem is further complicated as several diseases frequently mimic the histological changes seen in IBD. Successful diagnosis is reliant on careful clinicopathological correlation and recognising potential pitfalls. This is best achieved in a multidisciplinary team setting when the full clinical history, endoscopic findings, radiology and relevant serology and microbiology are available. In this review, we present an up-to-date evaluation of the histopathological mimics of IBD.

A novel imaging approach to periocular basal cell carcinoma: in vivo optical coherence tomography and histological correlates.

PURPOSE: Optical coherence tomography (OCT) is a non-invasive imaging method widely used in ophthalmology. Recent developments have produced OCT devices for imaging the skin. The purpose of this study was to investigate Fourier Domain OCT morphological features of periocular basal cell carcinoma (BCC) in correlation with conventional histopathology. METHODS: Consecutive patients with periocular nodular BCC were prospectively examined with VivoSight OCT (Michelson Ltd) prior to surgical excision. OCT slice mode images were analysed using criteria defined for conventional and HD-OCT; the images were correlated to haematoxylin and eosin stained histology sections. RESULTS: A total of 15 patients with periocular BCC were recruited. Three categories of BCC morphological features were identified from slice mode OCT images: (1) Epidermal changes included epidermal thinning (15/15; 100%), ulceration and crusting (5/15, 33.3%) and decreased density of hair follicles (8/15; 53.3%); (2) Intralesional features included hyporeflective nodules (15/15; 100%), hyper-reflective edges (15/15; 100%) and hyporeflective central necrosis (3/15; 20%) (3) Perilesional features included hyporeflective borders (11/15; 73%), hypereflective margins (15/15; 100%) and dilated blood vessels (5/15; 33%). CONCLUSIONS: This study demonstrated that Fourier Domain OCT imaging offers additional information in the identification of morphological features of nodular BCC compared to conventional OCT diagnostic criteria. VivoSight produced fast, non-invasive imaging of skin lesions in the periocular region and high correlation with histology. Further studies are necessary to investigate OCT features of different histological subtypes of BCC.