Multiple cerebral aneurysms in an adult with autosomal recessive polycystic kidney disease

[Extract] Autosomal recessive polycystic kidney disease(ARPKD) is a rare form offibrocystic kidneydisease that affects approximately 1 in 20,000 live births. The classic presentation is with prominenthepatic impairment caused by hepatic fibrosis in addition to renal impairment that is more aggressive than that seen in autosomal dominant polycystic kidney disease (ADPKD). Caroli syndrome is the eponymgiven to the combination of ARPKD, hepatic fibrosis, portal hypertension, and intrahepatic bile duct dilatation. It is seen in ≤50% of cases of ARPKD

The variability of the sediment plume and ocean circulation features of the Nass River Estuary, British Columbia

The Nass River discharges into Nass Bay and Iceberg Bay, which are adjoining tidal inlets located within the northern inland waters of British Columbia, Canada. After the Skeena River, the Nass River is the second longest river within northern British Columbia, which discharges directly into Canadian waters of the Pacific Ocean. It is also supports one of the most productive salmon fisheries in northern British Columbia. The Nass River discharges into the eastern end of Nass Bay. Nass Bay, in turn feeds into Portland Canal and the fresh surface waters then flows westward to the Pacific Ocean via Dixon Entrance. The tides in Northern British Columbia are very large with a tidal height range of just over 7 m. Nass Bay is a shallow inlet of less than 10 km in length with typical water depths of than 10 m or less. The existing knowledge of oceanographic processes in Nass and Iceberg Bays was rudimentary until three years ago, when the first modern oceanographic measurements were obtained. In this study, the seasonal and tidal variability of the lateral extent of the Nass River surface plume is mapped from analyses of Landsat satellite data spanning the period from 2008 to 2015. A high resolution coupled three dimensional (3D) hydrodynamic model was developed and implemented, within the widely used and accepted Delft3D modeling framework, which was forced and validated using recent 2013-2016 in-situ oceanographic measurements. The combined satellite and numerical modeling methods are used to study the physical oceanographic and sediment transport regime of Nass and Iceberg Bays and the adjoining waters of Portland Inlet and Observatory Inlet. The ocean circulation of Nass and Iceberg Bays was found to be dominated by tidal currents, and by the highly seasonal and variable Nass River freshwater discharges. Complex lateral spatial patterns in the tidal currents occur due to the opening of the southwestern side of Nass Bay onto the deeper adjoining waters of Iceberg Bay. Surface winds are limited to a secondary role in the circulation variability. The sediment dynamics of the Nass Bay system features a very prominent surface sediment plume present from the time of freshet in mid-spring through to large rainfall runoff events in the fall. The time-varying turbidity distribution and transport paths of the Nass River sediment discharges in the study area were characterized using the model results combined with an analysis of several high-resolution multi-year Landsat satellite data sets

Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass

Aneuploidy has been well-documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening in a 24-h protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy and distinguishes certain meiotic from mitotic errors. In this study, our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from 17 couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e. one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of 51 (96.1%) ICM samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that TE karyotype is an excellent predictor of ICM karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations

CSF-1–dependant donor-derived macrophages mediate chronic graft-versus-host disease

Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin and lung. Here, we used multiple murine models of cGVHD to investigate the contribution of macrophage populations in the development of cGVHD. Using an established IL-17–dependent sclerodermatous cGVHD model, we confirmed that macrophages infiltrating the skin are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS–). Cutaneous cGVHD developed in a CSF-1/CSF-1R–dependent manner, as treatment of recipients after transplantation with CSF-1 exacerbated macrophage infiltration and cutaneous pathology. Additionally, recipients of grafts from Csf1r–/– mice had substantially less macrophage infiltration and cutaneous pathology as compared with those receiving wild-type grafts. Neither CCL2/CCR2 nor GM-CSF/GM-CSFR signaling pathways were required for macrophage infiltration or development of cGVHD. In a different cGVHD model, in which bronchiolitis obliterans is a prominent manifestation, F4/80+ macrophage infiltration was similarly noted in the lungs of recipients after transplantation, and lung cGVHD was also IL-17 and CSF-1/CSF-1R dependent. Importantly, depletion of macrophages using an anti–CSF-1R mAb markedly reduced cutaneous and pulmonary cGVHD. Taken together, these data indicate that donor macrophages mediate the development of cGVHD and suggest that targeting CSF-1 signaling after transplantation may prevent and treat cGVHD

Heterobimetallic Complexes That Bond Vanadium to Iron, Cobalt, and Nickel

Zero-valent iron, cobalt, and nickel were installed into the metalloligand V­[N­(<i>o</i>-(NCH₂P­(ⁱPr)₂)­C₆H₄)₃] (<b>1</b>, VL), generating the heterobimetallic trio FeVL (<b>2</b>), CoVL (<b>3</b>), and NiVL (<b>4</b>), respectively. In addition, the one-electron-oxidized analogues [FeVL]­X ([<b>2</b>^<b>ox</b>]­X, where X^– = BPh₄ or PF₆) and [CoVL]­BPh₄ ([<b>3</b>^<b>ox</b>]­BPh₄) were prepared. The complexes were characterized by a host of physical methods, including cyclic voltammetry, X-ray crystallography, magnetic susceptibility, electronic absorption, NMR, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies. The CoV and FeV heterobimetallic compounds have short M–V bond lengths that are consistent with M–M multiple bonding. As revealed by theoretical calculations, the M–V bond is triple in <b>2</b>, <b>2</b>^<b>ox</b>, and <b>3</b>^<b>ox</b>, double in <b>3</b>, and dative (Ni → V) in <b>4</b>. The (d–d)¹⁰ species, <b>2</b> and <b>3</b>^<b>ox</b>, are diamagnetic and exhibit large diamagnetic anisotropies of −4700 × 10^–36 m³/molecule. Complexes <b>2</b> and <b>3</b>^<b>ox</b> are also characterized by intense visible bands at 760 and 610 nm (ε > 1000 M^–1 cm^–1), respectively, which correspond to an intermetal (M → V) charge-transfer transition. Magnetic susceptibility measurements and EPR characterization establish <i>S</i> = ¹/₂ ground states for (d–d)⁹ <b>2</b>^<b>ox</b> and (d–d)¹¹ <b>3</b>, while (d–d)¹² <b>4</b> is <i>S</i> = 1 based on Evans’ method

Heterobimetallic Complexes That Bond Vanadium to Iron, Cobalt, and Nickel

Zero-valent iron, cobalt, and nickel were installed into the metalloligand V­[N­(<i>o</i>-(NCH₂P­(ⁱPr)₂)­C₆H₄)₃] (<b>1</b>, VL), generating the heterobimetallic trio FeVL (<b>2</b>), CoVL (<b>3</b>), and NiVL (<b>4</b>), respectively. In addition, the one-electron-oxidized analogues [FeVL]­X ([<b>2</b>^<b>ox</b>]­X, where X^– = BPh₄ or PF₆) and [CoVL]­BPh₄ ([<b>3</b>^<b>ox</b>]­BPh₄) were prepared. The complexes were characterized by a host of physical methods, including cyclic voltammetry, X-ray crystallography, magnetic susceptibility, electronic absorption, NMR, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies. The CoV and FeV heterobimetallic compounds have short M–V bond lengths that are consistent with M–M multiple bonding. As revealed by theoretical calculations, the M–V bond is triple in <b>2</b>, <b>2</b>^<b>ox</b>, and <b>3</b>^<b>ox</b>, double in <b>3</b>, and dative (Ni → V) in <b>4</b>. The (d–d)¹⁰ species, <b>2</b> and <b>3</b>^<b>ox</b>, are diamagnetic and exhibit large diamagnetic anisotropies of −4700 × 10^–36 m³/molecule. Complexes <b>2</b> and <b>3</b>^<b>ox</b> are also characterized by intense visible bands at 760 and 610 nm (ε > 1000 M^–1 cm^–1), respectively, which correspond to an intermetal (M → V) charge-transfer transition. Magnetic susceptibility measurements and EPR characterization establish <i>S</i> = ¹/₂ ground states for (d–d)⁹ <b>2</b>^<b>ox</b> and (d–d)¹¹ <b>3</b>, while (d–d)¹² <b>4</b> is <i>S</i> = 1 based on Evans’ method

Eudaimonic well-being: Its importance and relevance to occupational therapy for humanity

Contemporary critique of the philosophy and theory of occupational therapy has asserted that the mainstream of the profession holds a westernized view of the world and that occupational therapy has been shackled to notions of health/illness and the medical establishment for too long, hampering movement into social and political spheres. Strategies and developments have been proposed to combat these biases, which have included increased cultural relativism and a re-focus on the subjective experience of occupation. The value placed on "being" in occupational therapy philosophy is described alongside the related terms of occupational integrity and spirituality. Drawing on theory and research from psychology, this paper proposes the construct of eudaimonic well-being as both relevant and valuable to occupational therapy in re-conceptualizing the profession, countering some of the central tensions in the identity of the profession and re-asserting that well-being through occupation is for all and for humanity. Finally, the paper proposes that well-being, in a eudaimonic sense, should be advertised and evidenced as a routine outcome of occupational therapy and consolidated into occupational therapy models as a relevant and meaningful concept

Non-Hfe iron overload: Is Phlebotomy the answer?

Iron is an essential factor for life, however a physiologically optimal balance is critical. In this article we explore the role of iron as a co-factor in a range of chronic liver diseases and how it may contribute to the development of liver injury, fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Whilst iron depletion therapy through phlebotomy is the most effective method of reducing iron stores, it is unclear whether this offers utility in the therapy of liver diseases in which iron is not the primary insult resulting in tissue injury. Here we examine the emerging evidence in the field of non-HFE hereditary haemochromatosis conditions associated with iron overload – is phlebotomy the answer