Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.     

Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp

Three new sterol sulfates, spheciosterol sulfates A-C (1-3), and the known sterol sulfate topsentiasterol sulfate E (4) have been isolated from the sponge Spheciospongia sp., collected in the Philippines. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-4 inhibited PKCzeta with IC50 values of 1.59, 0.53, 0.11, and 1.21 microM, respectively. In a cell-based assay, 1-4 also inhibited NF-kappaB activation with EC50 values of 12-64 microM.     

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update

BackgroundA previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts’ opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives.ConclusionMonoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01431-x.     

Free-Ranging Chickens in Households in a Periurban Shantytown in Peru—Attitudes and Practices 10 Years after a Community-Based Intervention Project

Free-ranging chickens are often found in periurban communities in developing countries, and their feces can pose a significant public health sanitation problem. Corralling chickens raised in these periurban areas in chicken coops has been proposed previously as an intervention to address this problem. Aims of this study were to revisit households in a corralling intervention study conducted in 2000–2001 to compare poultry-raising practices and investigate current attitudes regarding the impact of raising chickens in a periurban environment. Sociobehavioral questionnaires were given sequentially to all study participants; 30 families (58%) ceased raising poultry of any kind, whereas 42 (81%) do not raise chickens in their home. This finding indicates a significant reduction in poultry-raising in our study population since 2000–2001, possibly because of acculturation and/or change in socioeconomic status. However, attitudes about corral use for raising poultry were overwhelmingly positive, and the most common reason cited was cleanliness of the home.     

A potential role for mast cells in the of bFGF from normal myocytes during angiogenesis in vivo.

Basic fibroblast growth factor (bFGF) is a potent angiogenic factor produced by cells of mesodermal and neuroectodermal origin. Despite numerous advances, the precise mechanism of bFGF release from cells still remains unknown. Upon release from cells, the protein is stored and protected in the extracellular matrix by binding to heparan sulfate proteoglycans. A number of reports suggest that degrading enzymes secreted by mast cells may play a role in the release of bFGF from connective tissue stores. Additionally, mast cells are believed to play a role in the formation of new blood vessels. In this report, we studied the events involved in neovascularization using a well-characterized model of angiogenesis in rabbits where neovascularization is induced by transfer of a well-perfused rectus abdominis muscle flap to an ischemic limb. Using this model, we demonstrate that bFGF expression is induced in normal myofibers and bFGF is released in the wound fluid at the ischemic/nonischemic interface. The highest concentrations of bFGF were detected on days 14 and 21 postoperation. We also show that the number of mast cells and their degranulation correlate with the release of bFGF from adjacent muscle tissue and the appearance of the growth factor in the wound fluid. There appears to exist a temporal correlation between number of mast cells, their degranulation, and the release of bFGF during angiogenesis in vivo.     

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.     

Growth impairment shows an age-dependent pattern in boys with chronic kidney disease

The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3–21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.     

Amygdala volume and depressive symptoms in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a high prevalence of comorbid psychiatric disorders, including major depression (MD). The aim of this study was to examine whether a co-occurrence of MD is associated with structural changes in the amygdala of BPD patients. METHODS: Twenty-five right-handed, female patients with BPD and 25 matched healthy control subjects were examined. Diagnoses of BPD and MD were made according to DSM IV. Depressive symptomatology was determined with the Hamilton Depression Scale (HAMD). Magnetic resonance imaging scans were performed with 1.5 T Magnetom Vision (Siemens, Erlangen, Germany). The software program "BRAINS" was applied for brain volumetry and segmentation. The amygdala was delineated as "region of interest." RESULTS: Comparison of amygdala volumes between the whole group of BPD patients and control subjects revealed no significant difference. Amygdala volumes in both hemispheres were significantly larger in BPD patients with MD compared with those without MD. There was a significant correlation in BPD patients between left amygdala volume and depressive symptoms as measured by HAMD. CONCLUSIONS: Correlation of amygdala volume with depression in BPD patients might indicate a causal relationship. Future studies should clarify whether amygdala enlargement is a risk factor for MD in BPD patients or a consequence of the affective disorder.     

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

Renal allograft function in matched pediatric and adult recipient pairs of the same donor

BACKGROUND: To study the effect of donor age on kidney function, the authors investigated matched pairs from the same kidney donor given to a pediatric or an adult recipient. METHODS: Fifteen matched pairs of an adult and a pediatric patient, selected from the Eurotransplant registry, receiving the renal graft from the same cadaveric donor were selected for analysis of graft function over 7 years. Nine matched pairs were from adult donors (mean age, 40 years; range, 23-60 years) and six from pediatric donors (mean age, 11 years; range, 4-15 years). All recipients had comparable immunosuppression with cyclosporine A, prednisolone, and azathioprine and comparable numbers of acute rejection, cytomegalovirus reactivation, and antihypertensive therapy. Mean age of pediatric and adult recipients at transplantation was 5 years (range, 1-9 years) and 38 years (range, 25-60 years), respectively. RESULTS: The calculated glomerular filtration rate (GFR) corrected to body surface area was not different in adult and pediatric recipients. Initial absolute GFR was significantly lower in pediatric recipients (27 mL/ min; range, 17-38 mL/min) than in adult recipients (54 mL/min; range, 25-74 mL/min) (P <0.05) and remained lower in the following years. Initially, pediatric donor kidneys transplanted into pediatric recipients showed a lower absolute GFR than those transplanted into adults, however, approaching the GFR in adult recipients later. Adult donor kidneys transplanted into pediatric recipients showed a persistently lower absolute GFR in children compared with those transplanted into adult recipients. CONCLUSIONS: The authors conclude that adult donor kidneys in pediatric recipients decrease GFR in the early stages and lack an increase in GFR with growth of the child.