Impact of COVID-19 & Response Measures on HIV-HCV Prevention Services and Social Determinants in People Who Inject Drugs in 13 Sites with Recent HIV Outbreaks in Europe, North America and Israel.

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.

RESUMEN: La prevención del VIH/VHC entre las personas que se inyectan drogas (PWID) es de vital importancia para la salud pública. Nuestro objetivo fue evaluar el impacto de COVID-19 y las medidas de respuesta asociadas en los servicios de prevención del VIH/VHC y el estado socioeconómico de las PWID en sitios de alto riesgo de VIH. Se contactó con sitios con brotes recientes (2011­2019) de VIH entre PWID en Europa, América del Norte e Israel, que habían sido previamente identificados, a principios de mayo de 2020. De los 17 sitios invitados a participar, 13 aceptaron. Se prepararon informes cualitativos semiestructurados del sitio que cubrían los datos de marzo a mayo de 2020, analizados/codificados y confirmados con un cuestionario estructurado, en el que todos los sitios respondieron explícitamente a los 103 asuntos reportados en los informes cualitativos. El tratamiento de mantenimiento con opiáceos, los programas de agujas/jeringas y el tratamiento antirretroviral/tratamiento de la hepatitis C continuaron, pero con importantes reducciones y cambios operativos. Se reportaron aumentos en las sobredosis, dificultades generalizadas con las necesidades alimentarias y de higiene, interrupciones en el suministro de medicamentos y aumento de personas sin hogar. Los programas de servicios reformaron rápidamente las políticas restrictivas de prestación de servicios, establecidas desde hace mucho tiempo y políticamente arraigadas. Las futuras medidas de control de epidemias deben incluir la mitigación de los efectos secundarios negativos en la prestación de servicios y los determinantes socioeconómicos en las PWID.

Mineral reaction kinetics constrain the length scale of rock matrix diffusion.

Mass transport by aqueous fluids is a dynamic process in shallow crustal systems, redistributing nutrients as well as contaminants. Rock matrix diffusion into fractures (void space) within crystalline rock has been postulated to play an important role in the transient storage of solutes. The reacted volume of host rock involved, however, will be controlled by fluid-rock reactions. Here we present the results of a study which focusses on defining the length scale over which rock matrix diffusion operates within crystalline rock over timescales that are relevant to safety assessment of radioactive and other long-lived wastes. Through detailed chemical and structural analysis of natural specimens sampled at depth from an active system (Toki Granite, Japan), we show that, contrary to commonly proposed models, the length scale of rock matrix diffusion may be extremely small, on the order of centimetres, even over timescales of millions of years. This implies that in many cases the importance of rock matrix diffusion will be minimal. Additional analyses of a contrasting crystalline rock system (Carnmenellis Granite, UK) corroborate these results.

Fe-oxide concretions formed by interacting carbonate and acidic waters on Earth and Mars.

Spherical Fe-oxide concretions on Earth, especially in Utah, USA, have been investigated as an analog of hematite spherules found in Meridiani Planum on Mars to support interpretations of water-rock interactions in early Mars. Although several formation mechanisms have been proposed for the Fe-oxide concretions on Earth, it is still unclear whether these mechanisms are viable because a precise formation process and precursor of the concretions are missing. This paper presents evidence that Fe-oxide concretions in Utah and newly found Fe-oxide concretions in Mongolia had spherical calcite concretions as precursors. Different formation stages of calcite and Fe-oxide concretions observed, both in Utah and Mongolia, indicate that calcite concretions initially formed within eolian sandstone strata and were dissolved by infiltrating Fe-rich acidic waters to form spherical FeO(OH) crusts due to pH buffering. The similarity between these Fe-oxide concretions on Earth and the hematite spherule occurrences in Meridiani Planum, combined with evidence of acid sulfate water influences on Mars, suggest that the hematite spherules also formed from dissolution of preexisting carbonate spherules possibly formed under a dense carbon dioxide early martian atmosphere.

Exercise training comprising of single 20-s cycle sprints does not provide a sufficient stimulus for improving maximal aerobic capacity in sedentary individuals.

PURPOSE: Sprint interval training (SIT) provides a potent stimulus for improving maximal aerobic capacity ([Formula: see text]), which is among the strongest markers for future cardiovascular health and premature mortality. Cycling-based SIT protocols involving six or more 'all-out' 30-s Wingate sprints per training session improve [Formula: see text], but we have recently demonstrated that similar improvements in [Formula: see text] can be achieved with as few as two 20-s sprints. This suggests that the volume of sprint exercise has limited influence on subsequent training adaptations. Therefore, the aim of the present study was to examine whether a single 20-s cycle sprint per training session can provide a sufficient stimulus for improving [Formula: see text]. METHODS: Thirty sedentary or recreationally active participants (10 men/20 women; mean ± SD age: 24 ± 6 years, BMI: 22.6 ± 4.0 kg m(-2), [Formula: see text]: 33 ± 7 mL kg(-1) min(-1)) were randomised to a training group or a no-intervention control group. Training involved three exercise sessions per week for 4 weeks, consisting of a single 20-s Wingate sprint (no warm-up or cool-down). [Formula: see text] was determined prior to training and 3 days following the final training session. RESULTS: Mean [Formula: see text] did not significantly change in the training group (2.15 ± 0.62 vs. 2.22 ± 0.64 L min(-1)) or the control group (2.07 ± 0.69 vs. 2.08 ± 0.68 L min(-1); effect of time: P = 0.17; group × time interaction effect: P = 0.26). CONCLUSION: Although we have previously demonstrated that regularly performing two repeated 20-s 'all-out' cycle sprints provides a sufficient training stimulus for a robust increase in [Formula: see text], our present study suggests that this is not the case when training sessions are limited to a single sprint.

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT).

PURPOSE: We have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves VO2max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT. METHODS: In Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m(-2), VO2max: 51 ± 11 ml kg(-1) min(-1)) performed a single 10-min REHIT cycling session (60 W and two 20-s 'all-out' sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4. In Study 2, eight men (21 ± 2 year; 25 ± 4 kg·m(-2); 39 ± 10 ml kg(-1) min(-1)) performed three trials (REHIT, 30-min cycling at 50 % of VO2max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise. RESULTS: Acutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1α. When compared to aerobic exercise, changes in VO2, RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected. CONCLUSIONS: Collectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise.

Shifting environmental baselines in the Red Sea.

The Red Sea is among the world's top marine biodiversity hotspots. We re-examined coastal ecosystems at sites surveyed during the 1980s using the same methodology. Coral cover increased significantly towards the north, mirroring the reverse pattern for mangroves and other sedimentary ecosystems. Latitudinal patterns are broadly consistent across both surveys and with results from independent studies. Coral cover showed greatest change, declining significantly from a median score of 4 (1000-9999 m(2)) to 2 (10-99m(2)) per quadrat in 2010/11. This may partly reflect impact from coastal construction, which was evident at 40% of sites and has significantly increased in magnitude over 30 years. Beach oil has significantly declined, but shore debris has increased significantly. Although substantial, levels are lower than at some remote ocean atolls. While earlier reports have suggested that the Red Sea is generally healthy, shifting environmental baselines are evident from the current study.

Assess and interpret the visual fields at the bedside.

Understanding and applying a bedside visual field assessment is an important skill for the neurologist. By appreciating some basic anatomical and physiological principles it is possible to target the examination appropriately, thus gaining important diagnostic information with the minimum of fuss. Specific patterns of visual loss are caused by damage at various sites within the visual pathway. This review focuses on techniques that can be used at the bedside to identify common visual field defects and cites examples by dividing the visual system into its component parts. We urge the use of an appropriately sized red pin and berate the well worn "waggling finger" technique.

Wall shear stress in intracranial self-expanding stents studied using ultra-high-resolution 3D reconstructions.

BACKGROUND AND PURPOSE: Imaging of intracranial stents is constrained by resolution limits of current clinical imaging techniques providing insufficient visualization of deployment details and impeding its use for computational hemodynamic (CHD) simulations. The purpose of our study was to evaluate whether ultra-high-resolution MicroCT scans can illuminate detailed aspects of realistic in vitro stent deployment and serve as a reliable basis for CHD simulations of blood flow through self-expanding intracranial stents. MATERIALS AND METHODS: A Neuroform Treo (NF) stent and an Enterprise (ENT) stent were deployed in identical straight polytetrafluoroethylene tubes filled with contrast agent. MicroCT scans were obtained at a spatial resolution of 14 mum and used for ultra-high-resolution 3D reconstructions. CHD simulations were performed, with particular emphasis on local flow behavior near the wall and struts. Flow differences between the geometrically different stents were studied. RESULTS: MicroCT data revealed strut prolapse near the markers for the closed-cell design (ENT) stent and at some of the unconnected vertices of the open-cell design (NF) stent, which also showed some misalignments. CHD simulations showed that reverse wall shear stress occurred near some of the strut vertices and markers for the NF but only near the markers for the ENT. CONCLUSIONS: This work demonstrates the feasibility of ultra-high-resolution MicroCT imaging in elucidating important details of intracranial stent deployment as a basis for accurate CHD simulations and in enabling a structural and hemodynamic study of realistically deployed stents with different geometry and design.

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

A rete mirabile of the posterior cerebral artery. Embryonic and phylogenetic remnant of choroidal artery origin.

SUMMARY: We present the case of a 41-year-old man with a vascular network associated with the left posterior cerebral artery (PCA). Although initially considered to be a brain AVM, further investigation showed no arteriovenous shunting and a rete mirabile of the PCA was diagnosed. A well known but rare occurrence mainly in the anterior circulation, rete mirabile has not previously been described in the PCA.The PCA is a composite vessel, developmentally. Its proximal portion derives from the posterior division of the ICA while its cortical territories are annexed from the anterior choroidal artery adjacent to the lateral geniculate body. We propose that this rete (or network) represents a persistence of the embryonic anastomosis betweenthe AChA and the PCA.

Hemodynamics in a cerebral artery before and after the formation of an aneurysm.

Using data obtained from 3D digital subtraction angiography acquisitions, computational fluid dynamics techniques were used first to assess hemodynamic factors in geometrically correct models of 3 paraclinoid aneurysms and then again for assessment after virtual removal of the aneurysms and reconstruction of the parent artery. Simulations revealed an area of relatively low and rotating wall shear stresses at the location at which each aneurysm had developed. This phenomenon, to our knowledge, has not been previously described.

New Zealand national incidence of bronchiectasis "too high" for a developed country.

AIMS: To prospectively estimate the incidence of bronchiectasis among New Zealand (NZ) children, to consider aetiology and severity, and to evaluate regional and ethnic variation. METHODOLOGY: NZ paediatricians were surveyed monthly for new cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance unit (with coverage of >94% of NZ paediatricians). Notified cases had their computed tomography scans reviewed and scored for severity. Confirmed cases were followed up by postal questionnaire one year after diagnosis. Demographic, aetiological, and severity data were collected. RESULTS: Ninety nine notifications were received. Sixty five cases were confirmed. An overall incidence of 3.7 per 100,000 under 15 year old children per year was estimated. Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori, 1.5 in NZ European, and 2.4 other per 100,000 per year. Incidence varied significantly by region. The median age at diagnosis was 5.2 years; the majority had symptoms for more than two years. Eighty three per cent had bilateral disease, with a median of three lobes affected, mean FEV1 of 77% predicted, and modified Bhalla HRCT score of 18. CONCLUSIONS: The incidence of bronchiectasis is high in NZ children, nearly twice the rate for cystic fibrosis and seven times that of Finland, the only other country reporting a childhood national rate. Incidence varied substantially between ethnicities. Most cases developed disease in early childhood and had delayed diagnosis.

Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical relationships.

Non cystic fibrosis (CF) bronchiectasis in children presents with a spectrum of disease severity. Our aims were to document the extent and severity of disease in children with non-CF bronchiectasis, to review the inter- and intraobserver agreement for the high-resolution computed tomography (HRCT) features examined, and to assess correlations between HRCT features and clinical measures of severity. We performed a retrospective review of 56 children from the Starship Children's Hospital. HRCT scans were scored by a modified Bhalla system, and the chest X-rays using the Brasfield score. Scores were correlated with demographics, number of hospitalizations, disease duration, pulmonary function, clinical examination, and chronic sputum infection. The bronchiectasis seen was widespread and severe, particularly in Maori and Pacific Island children. The kappa coefficient for intraobserver agreement was better than that for interobserver agreement. Comparisons between HRCT scan and lung function parameters showed that the strongest relationships were between forced expiratory volume in 1 sec (FEV(1)) and forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) with the extent of bronchiectasis, bronchial wall thickening, and air trapping. Children with digital clubbing and chest deformity showed significantly higher scores for extent of bronchiectasis, bronchial wall dilatation and thickness, and overall computed tomography (CT) score. No relationship was demonstrated between chronic sputum infection and CT score. The HRCT score demonstrated a stronger correlation between the extent and severity of bronchiectasis, and spirometry values, than the chest X-ray score. In conclusion, pediatric non-CF bronchiectasis in Auckland is extensive and severe. The good intraobserver ratings mean that consistency of scoring is possible on repeated scans. This study cannot comment on the relationships of CT and less severe disease.

HLA-G does not have a pathophysiological role in Graves' disease.

AIMS: It has been suggested that the non-classic HLA class I molecule HLA-G plays a role in autoimmune disease by protecting tissues from damage by infiltrating cytotoxic T cells. Such infiltration occurs in the thyroid of patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) and can eventually result in tissue destruction. The aim of the current study was to analyse thyroid tissue and thyrocytes obtained from individuals with autoimmune thyroid disease for the expression of HLA-G. METHODS: HLA-G expression was analysed in thyroid tissue taken from six patients with GD and one with HT by reverse transcriptase polymerase chain reaction. Thyroid tissue samples isolated from six patients with multinodular goitre (MNG) were used as non-autoimmune controls. HLA-G expression was also examined in cultured thyroid follicular cells (TFCs). RESULTS: The expression of HLA-G was not detected in the thyroid gland of patients with either GD, HT, or MNG. Furthermore, HLA-G expression could not be detected in cultured patient TFCs under basal conditions or after stimulation with the proinflammatory cytokines-interleukin 1alpha, interferon gamma, and tumour necrosis factor alpha. CONCLUSIONS: HLA-G expression does not occur in the thyroid of patients with GD, indicating that HLA-G does not play a pathophysiological role in this autoimmune disorder. Although the expression of HLA-G was not detected in the thyroid sample of the patient with HT, a greater sample size would be required to conclude that HLA-G does not have a part to play in this autoimmune thyroid disease.

High-dose leptin activates human leukocytes via receptor expression on monocytes.

Leptin is capable of modulating the immune response. Proinflammatory cytokines induce leptin production, and we now demonstrate that leptin can directly activate the inflammatory response. RNA expression for the leptin receptor (Ob-R) was detectable in human PBMCs. Ob-R expression was examined at the protein level by whole blood flow cytometry using an anti-human Ob-R mAb 9F8. The percentage of cells expressing leptin receptor was 25 +/- 5% for monocytes, 12 +/- 4% for neutrophils, and 5 +/- 1% for lymphocytes (only B lymphocytes). Incubation of resting PBMCs with leptin induced rapid expression of TNF-alpha and IL-6 mRNA and a dose-dependent production of TNF-alpha and IL-6 by monocytes. Incubation of resting PBMCs with high-dose leptin (250 ng/ml, 3-5 days) induced proliferation of resting cultured PBMCs and their secretion of TNF-alpha (5-fold), IL-6 (19-fold), and IFN-gamma (2.5-fold), but had no effect on IL-4 secretion. The effect of leptin was distinct from, and additive to, that seen after exposure to endotoxin or activation by the mixed lymphocyte reaction. In conclusion, Ob-R is expressed on human circulating leukocytes, predominantly on monocytes. At high doses, leptin induces proinflammatory cytokine production by resting human PBMCs and augments the release of these cytokines from activated PBMCs in a pattern compatible with the induction of Th1 cytokines. These results demonstrate that leptin has a direct effect on the generation of an inflammatory response. This is of relevance when considering leptin therapy and may partly explain the relationship among leptin, proinflammatory cytokines, insulin resistance, and obesity.

Hepatic hemangioendothelioma associated with production of humoral thyrotropin-like factor.

We report on 7 patients referred for treatment of hepatic hemangioendothelioma with increased thyrotropin levels. The serum thyroxine level was decreased in 4 and increased in 2. Immunohistochemistry showed positive staining of tumor, but not of normal liver tissue, for thyrotropin. We propose secretion by the tumor of a thyrotropin-like factor.