ResearchPad - research-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Food insecurity in females with phenylketonuria]]> https://www.researchpad.co/article/elastic_article_10773 Phenylketonuria (PKU) is a genetic disorder characterized by insufficient metabolism of phenylalanine. Depending on severity, patients follow a low‐phenylalanine diet and may consume medical food (MF) and low‐protein modified foods; dietary and medical treatment can be expensive. This study assessed prevalence of food insecurity (FI), the lack of resources to access enough nutritious food to have an active, healthy life, in females with PKU and examined associations with diet and metabolic control. Participants were recruited from a research‐based camp in 2018. Adult and adolescent modules of the USDA Household Food Security survey were utilized to categorize participants as food secure [high food security (FS) or marginal FS] or food insecure (low FS or very low FS); results were compared to the general U.S. population. Dietary intake via three‐day food records and plasma amino acids were also assessed. Thirty females 11‐58 years of age (mean = 21.4 years) participated. Twelve (40%), including seven adolescents (44%) and five adults (36%), were FI compared to the U.S. prevalence of 11.1%. MF protein intake was significantly lower in those with very low FS compared to high FS and low FS (P = .04). Age and intact protein intake were significantly higher in those with very low FS compared to high FS (P < .05). Our study suggests adolescent and adult females with PKU have a higher prevalence of FI than the general U.S. population. Those with very low FS were older, consumed more dietary phenylalanine and intact protein, and less MF protein. Clinicians should consider screening for FI in patients with PKU.

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<![CDATA[A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care]]> https://www.researchpad.co/article/elastic_article_10772 Alkaptonuria (AKU) is an ultrarare and multifaceted disease characterized by the absence of functional homogentisate 1,2‐dioxygenase activity, the enzyme responsible for breakdown of homogentisic acid—a tyrosine‐degradation product. The presymptomatic phase of the disease makes diagnosis difficult, with many patients unidentified or diagnosed late in life.ObjectiveTo date, no study has analyzed the perceived impact of different symptoms or the experiences of individuals through the patient journey in the context of AKU. This study aimed to examine patients' perceptions of AKU symptoms and their impact on quality of life as well as patients' experiences of being diagnosed and living with the disease.MethodsData for this study were collected using a quantitative self‐report questionnaire administered online to people with AKU.ResultsData from 45 participants indicate that symptoms with the highest impact for patients are those related to pain and ruptures, disability and inability to perform normal routines, emotional/mental health issues, and heart complications. Findings also revealed significant delays in contact with healthcare services and time to diagnosis. Furthermore, patients reported difficulty in receiving information about AKU, treatment and care, and long‐term disease management support.ConclusionsTime to diagnosis and care of AKU is significantly delayed. Symptoms of AKU with the highest impact on quality of life for patients are those related to pain and disability and the inability to perform normal routines. Bridging any gaps between patients with AKU and healthcare professionals through education could help improve patients' experiences with AKU through the patient journey. ]]> <![CDATA[Interaction of MOPS buffer with glass–ceramic scaffold: Effect of (PO<sub>4</sub>)<sup>3−</sup> ions in SBF on kinetics and morphology of formatted hydroxyapatite]]> https://www.researchpad.co/article/elastic_article_8265 The international standard ISO 23317:2014 for the in vitro testing of inorganic biomaterials in simulated body fluid (SBF) uses TRIS buffer to maintain neutral pH. In our previous papers, we investigated the interaction of a glass–ceramic scaffold with TRIS and HEPES buffers. Both of them speeded up glass–ceramic dissolution and hydroxyapatite (HAp) precipitation, thereby demonstrating their unsuitability for the in vitro testing of highly reactive biomaterials. In this article, we tested MOPS buffer (3‐[N‐morpholino] propanesulfonic acid), another amino acid from the group of “Goods buffers”. A highly reactive glass–ceramic scaffold (derived from Bioglass®) was exposed to SBF under static–dynamic conditions for 13/15 days. The kinetics and morphology of the newly precipitated HAp were studied using two different concentrations of (PO4)3− ions in SBF. The pH value and the SiIV, Ca2+, and (PO4)3− concentrations in the SBF leachate samples were measured every day (AAS, spectrophotometry). The glass–ceramic scaffold was monitored by SEM/EDS, XRD, WD‐XRF, and BET before and after 1, 3, 7, 11, and 13/15 days of exposure. As in the case of TRIS and HEPES, the preferential dissolution of the glass–ceramic crystalline phase (Combeite) was observed, but less intensively. The lower concentration of (PO4)3− ions slowed down the kinetics of HAp precipitation, thereby causing the disintegration of the scaffold structure. This phenomenon shows that the HAp phase was predominately generated by the presence of (PO4)3− ions in the SBF, not in the glass–ceramic material. Irrespective of this, MOPS buffer is not suitable for the maintenance of pH in SBF.

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<![CDATA[Porous titanium fiber mesh with tailored elasticity and its effect on stromal cells]]> https://www.researchpad.co/article/elastic_article_7113 Porous titanium fiber mesh (TFM) is considered a suitable scaffold material for bone reconstruction. Also, TFM can be used to cover the surface of bone‐anchored devices, that is, orthopedic or dental implants. The titanium fiber size has an effect of the stiffness as well as porosity of the titanium mesh, which can influence the behavior of bone forming cells. Therefore, the aim of this study was to vary TFM composition, in order to achieve different stiffness, and to assess the effects of such variation on the behavior of bone marrow‐derived stromal cells (BMSCs). With that purpose, nine types of TFM (porosities 60–87%; fiber size 22–50 μm), were examined for their mechanical properties as well as their effect on the proliferation and differentiation of rat bone marrow‐derived stromal cells (rBMSCs) up to 21 days. Dynamic mechanical analysis revealed that the stiffness of TFM were lower than of solid titanium and decreased with larger fiber sizes. The stiffness could effectively be tailored by altering fiber properties, which altered the pore simultaneously. For the 22 and 35 μm size fiber meshes with the highest porosity, the stiffness closely matched the value found in literature for cortical bone. Finally, all tested TFM types supported the growth and differentiation of rBMSCs. We concluded that TFM material has been proven cytocompatible. Further preclinical studies are needed to assess which TFM type is most suitable as clinical use for bone ingrowth and bone regeneration.

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<![CDATA[Investigation of multiphasic 3D‐bioplotted scaffolds for site‐specific chondrogenic and osteogenic differentiation of human adipose‐derived stem cells for osteochondral tissue engineering applications]]> https://www.researchpad.co/article/elastic_article_6993 Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.

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<![CDATA[Computational characterization of the porous‐fibrous behavior of the soft tissues in the temporomandibular joint]]> https://www.researchpad.co/article/elastic_article_6864

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<![CDATA[ATP6AP1‐CDG: Follow‐up and female phenotype]]> https://www.researchpad.co/article/N54951b0f-6a9e-42eb-90e8-88471912692b In 2016, 11 male patients were reported with immunodeficiency and hepatic, gastric and (in some) neurological disease due to X‐linked ATP6AP1 deficiency (ATP6AP1‐CDG). In 2018, three other patients were reported with additional features: connective tissue abnormalities, sensorineural hearing loss, hyperopia, glomerular and tubular dysfunction, exocrine pancreatic insufficiency and altered amino acid and lipid metabolism. We here present a follow‐up of three reported siblings showing progression of deafness to total hearing loss, progressive loss of hair up to alopecia, chestnut skin and, at last follow‐up, in some of them proteinuria. Three female carriers showed a normal serum transferrin isoelectrofocusing but in two of them there was a persistent proteinuria.

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<![CDATA[Simplified Diet for nutrition management of phenylketonuria: A survey of U.S. metabolic dietitians]]> https://www.researchpad.co/article/Nb1d2ecff-4363-4bc2-85f6-61fcd527b664 Phenylketonuria (PKU) is an inherited metabolic disorder affecting the conversion of phenylalanine (Phe) to tyrosine. Medical nutrition therapy, consisting of a Phe‐restricted diet with medical formula, is the primary treatment for PKU. The Simplified Diet is an approach to PKU nutrition management that allows certain fruits, vegetables, and low‐protein foods to be eaten without measuring or tracking, referred to as free/uncounted foods. There is no consensus on how to implement this approach in metabolic centers in the United States (U.S.), and clinical practice varies.AimThis study describes the clinical experience of metabolic dietitians in U.S.‐based metabolic centers related to the use and implementation of the Simplified Diet.MethodsA survey was developed and sent out to metabolic dietitians to query current clinical practices related to the Simplified Diet. Descriptive statistics were used to analyze responses.ResultsSixty‐three dietitians managing ≥5 patients with PKU in U.S.‐based metabolic centers responded to the survey. Ninety‐eight percent of survey respondents reported using some version of the Simplified Diet in clinical practice. The survey identified areas of strong agreement, including introduction of the Simplified Diet at 6 to 12 months of age. The survey also identified areas of widespread variability, including specific Phe or protein thresholds for free/uncounted foods, and whether or not to set daily quantity limits on these foods.ConclusionsSignificant variability related to implementation of the Simplified Diet exists across U.S.‐based metabolic centers. This practice variability may contribute to differences in the patient experience across centers and may indicate a need for development of clinical guidelines. ]]> <![CDATA[Inter‐laboratory analytical improvement of succinylacetone and nitisinone quantification from dried blood spot samples]]> https://www.researchpad.co/article/Nce3d29fe-f306-4444-8005-c7c04e90c1b0 Nitisinone is used to treat hereditary tyrosinemia type 1 (HT‐1) by preventing accumulation of toxic metabolites, including succinylacetone (SA). Accurate quantification of SA during newborn screening is essential, as is quantification of both SA and nitisinone for disease monitoring and optimization of treatment. Analysis of dried blood spots (DBS) rather than plasma samples is a convenient method, but interlaboratory differences and comparability of DBS to serum/plasma may be issues to consider.MethodsEight laboratories with experience in newborn screening and/or monitoring of patients with HT‐1 across Europe participated in this study to assess variability and improve SA and nitisinone concentration measurements from DBS by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Quantification of nitisinone from both DBS and plasma was performed to assess sample comparability. In addition, efforts to harmonize laboratory procedures of SA and nitisinone quantifications during 5 rounds of analysis are described.ResultsNitisinone levels measured from DBS and plasma strongly correlated (R 2 = 0.93). Due to partitioning of nitisinone to the plasma, levels were higher in plasma by a factor of 2.34. In the initial assessment of laboratory performance, all had linear calibrations of SA and nitisinone although there was large inter‐laboratory variability in actual concentration measurements. Subsequent analytical rounds demonstrated markedly improved spread and precision over previous rounds, an outcome confirmed in a final re‐test round.ConclusionThe study provides guidance for the determination of nitisinone and SA from DBS and the interpretation of results in the clinic. Inter‐laboratory analytical harmonization was demonstrated through calibration improvements. ]]> <![CDATA[Longitudinal metabolomics in dried bloodspots yields profiles informing newborn screening for succinic semialdehyde dehydrogenase deficiency]]> https://www.researchpad.co/article/N821b990d-29bd-4b67-a2a2-4628595a94ce Analyses of 19 amino acids, 38 acylcarnitines, and 3 creatine analogues (https://clir.mayo.edu) were implemented to test the hypothesis that succinic semialdehyde dehydrogenase deficiency (SSADHD) could be identified in dried bloodspots (DBS) using currently available newborn screening methodology. The study population included 17 post‐newborn SSADHD DBS (age range 0.8‐38 years; median, 8.2 years; 10 M; controls, 129‐353 age‐matched individuals, mixed gender) and 10 newborn SSADHD DBS (including first and second screens from 3 of 7 patients). Low (informative) markers in post‐newborn DBS included C2‐ and C4‐OH carnitines, ornithine, histidine and creatine, with no gender differences. For newborn DBS, informative markers included C2‐, C3‐, C4‐ and C4‐OH carnitines, creatine and ornithine. Of these, only creatine demonstrated a significant change with age, revealing an approximate 4‐fold decrease. We conclude that quantitation of short‐chain acylcarnitines, creatine, and ornithine provides a newborn DBS profile with potential as a first tier screening tool for early detection of SSADHD. This first tier evaluation can be readily verified using a previously described second tier liquid chromatography‐tandem mass spectrometry method for γ‐hydroxybutyric acid in the same DBS. More extensive evaluation of this first/second tier screening approach is needed in a larger population.

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<![CDATA[Sjögren‐Larsson syndrome: The mild end of the phenotypic spectrum]]> https://www.researchpad.co/article/N896ec964-7ba0-4b6b-8ce2-28f4764ee3c1 Sjögren‐Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype‐phenotype correlation nor an alternative explanation for the strikingly mild phenotypes was found. New biochemical techniques to study the underlying metabolic defect in SLS, like lipidomics, may in the future help to unravel the reasons for the exceptionally mild phenotypes. In the meantime, it is important to recognize these mildly affected patients to provide them with appropriate care and genetic counseling, and to increase our insights in the true disease spectrum of SLS.

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<![CDATA[Hepatic glycogen synthase (GYS2) deficiency: seven novel patients and seven novel variants]]> https://www.researchpad.co/article/N196df857-cf8d-4c90-867f-6e39b6abf406 GYS2 gene manifesting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting, and postprandial hyperglycemia and hyperlactatemia. GSD 0 is a rare form of hepatic glycogen storage disease with less than 30 reported patients in the literature so far.DNA samples of 93 Russian patients with clinical diagnoses of hepatic GSDs were collected and analyzed by next‐generation sequencing custom target panel and by direct sequencing. Seven new GSD 0 patients with variable phenotypes were found showing 10 variants. Seven variants are novel.We present seven new GSD 0 patients with variable phenotypes. Overall, 10 different mutant alleles of the GYS2 gene were found. Seven of them are novel: c.214delC, c.845delT, c.1644C>A, c.205T>A, c.929G>T, c.1169G>C and c.1703C>A. Three of the novel variants were annotated as pathogenic and likely pathogenic; four other variants have an uncertain significance.The current results expand the spectrum of known mutations in GYS2 and suggest that phenotypes of GSD 0 are more variable and less specific than the reported ones.SynopsisSeven new patients with glycogen storage disease type 0 were found using next‐generation sequencing and seven novel variants of GYS2 gene were annotated. ]]> <![CDATA[The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma]]> https://www.researchpad.co/article/N0f868948-9fb9-47b7-bc1b-ba4f1e23c00f Alkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross‐sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning.MethodSeventy‐four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7‐day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25‐hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti‐inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)—a validated measure of disease progression stratified by age.ResultsFifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid‐upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as “clinically undernourished.” Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti‐inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score.ConclusionAKU patients are at risk of protein depletion associated with a “perfect storm” of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated. ]]> <![CDATA[The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis]]> https://www.researchpad.co/article/Nf8af308d-bc43-4383-b942-85d641f31224

Rheumatoid arthritis (RA), a chronic inflammatory disease affecting primarily the joints, is frequently characterized by the presence of autoimmune anticitrullinated protein antibodies (ACPA) during preclinical stages of disease and accumulation of hypercitrullinated proteins in arthritic joints. A strong association has been reported between RA and periodontal disease, and Porphyromonas gingivalis, a known driver of periodontitis, has been proposed as the microbial link underlying this association. We recently demonstrated P. gingivalis–mediated gut barrier breakdown and exacerbation of joint inflammation during inflammatory arthritis. In the present study, we investigated another potential role for P. gingivalis in RA etiopathogenesis, based on the generation of ACPA through the activity of a unique P. gingivalis peptidylarginine deiminase (PPAD) produced by this bacterium, which is capable of protein citrullination. Using a novel P. gingivalis W50 PPAD mutant strain, incapable of protein citrullination, and serum from disease-modifying antirheumatic drug–naïve early arthritis patients, we assessed whether autocitrullinated proteins in the P. gingivalis proteome serve as cross-activation targets in the initiation of ACPA production. We found no evidence for patient antibody activity specific to autocitrullinated P. gingivalis proteins. Moreover, deletion of PPAD did not prevent P. gingivalis–mediated intestinal barrier breakdown and exacerbation of disease during inflammatory arthritis in a murine model. Together, these findings suggest that the enzymatic activity of PPAD is not a major virulence mechanism during early stages of inflammatory arthritis.

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<![CDATA[Effect of heat shock protein 70 modulators on the development of morphine analgesic tolerance in rats]]> https://www.researchpad.co/article/N2fe3e0f9-44af-4436-8f7e-5690a73a33c5

The clinical use of opioid analgesics, such as morphine, is limited by analgesic tolerance, molecular mechanism of which is not well understood. Recently, molecular chaperone heat shock protein 70 (Hsp70) has been demonstrated to play important roles in morphine-induced neuroadaptation. Here, we focused on the involvement of Hsp70 in the development of analgesic tolerance to morphine. Rats were treated with morphine (5, 10, 20 mg/kg, subcutaneously) or saline once daily for 10 consecutive days. Hsp70 modulator N-formyl-3, 4-methylenedioxybenzylidine-γ-butyrolactam [KNK437, 100 mg/kg, intraperitoneally (i.p.)], geranylgeranylacetone (500 mg/kg, i.p.) or pifithrin-μ (20 mg/kg, i.p.) was administered before morphine (10 mg/kg, subcutaneously)/saline treatment. Analgesic effect of morphine was measured using the tail-flick latency test, and Hsp70 protein expression was examined by western blot. Analgesic effect of morphine decreased gradually with the increase in the number of days of morphine injection, indicating development of analgesic tolerance. A significant increase of Hsp70 expression in the periaqueductal gray was observed during the development of analgesic tolerance after repeated morphine injections. The development of morphine analgesic tolerance was suppressed by pre-treatment with Hsp70 transcriptional inhibitor KNK437 or functional antagonist pifithrin-μ, while promoted by pre-treatment with Hsp70 transcriptional inducer geranylgeranylacetone. Our results demonstrated that the development of morphine analgesic tolerance was dual regulated by Hsp70 modulators, suggesting Hsp70 as an interesting and new target for preventing the development of opioid analgesic tolerance.

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<![CDATA[Effects of dose on acquisition and persistence of a new response for a remifentanil-associated stimulus]]> https://www.researchpad.co/article/Nf39a981b-4739-4359-9ea3-c8ca76b97b9f

Previous research demonstrated that a remifentanil-associated stimulus facilitated the acquisition of a previously unlearned response; however, it is unclear how long a remifentanil-associated stimulus maintains conditioned reinforcing properties under conditions of daily testing. To address this gap, we exposed adult male rats to response-independent stimulus presentations and deliveries of remifentanil (1.0, 3.2, or 10.0 μg/kg/infusion). Rats either received the stimulus presentations and remifentanil deliveries together (Paired Pavlovian conditioning) or according to separate clocks (Random control group). In the sessions following Pavlovian conditioning, we allowed rats to emit nose-poke responses for the presentation of the stimulus alone and measured the extent to which the stimulus facilitated and maintained a previously unlearned response. We tested responding for the stimulus presentations across 28 daily sessions to assess the Pavlovian extinction (degradation of the drug-stimulus association) of the conditioned reinforcing properties of the remifentanil-associated stimulus. We observed the highest and most persistent levels of responding in rats with a Paired Pavlovian conditioning history at 3.2 and 10.0 μg/kg/infusion. In addition, we included analyses of the variability in responding for each group, which revealed individual differences in the susceptibility of the remifentanil-associated stimulus acting as a conditioned reinforcer. These findings demonstrate that a remifentanil-associated stimulus has the ability to sustain drug-seeking behavior and underscores the importance of Pavlovian conditioning in promoting drug abuse.

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<![CDATA[Use of tendon to produce decellularized sheets of mineralized collagen fibrils for bone tissue repair and regeneration]]> https://www.researchpad.co/article/Nca30ee92-97dd-43b4-806b-795bc6182a61

Abstract

With demand for alternatives to autograft and allograft materials continuing to rise, development of new scaffolds for bone tissue repair and regeneration remains of significant interest. Engineered collagen‐calcium phosphate (CaP) constructs can offer desirable attributes, including absence of foreign body response and possession of inherent osteogenic potential. Despite their promise, current collagen‐CaP constructs are limited to nonload‐bearing applications. In this article, we describe a process for creating decellularized sheets of highly aligned, natively cross‐linked, and mineralized collagen fibrils, which may be useful for developing multilaminate collagen‐CaP constructs with improved mechanical properties. Decellularized bovine tendons were cryosectioned to produce thin sheets of aligned collagen fibrils. Mineralization of the sheets was then performed using an alternate soaking method incorporating a polymer‐induced liquid precursor (PILP) process to promote intrafibrillar mineralization, along with incorporation of physiologically relevant amounts of citrate, Mg, and carbonate. Characteristics of the produced scaffolds were assessed using energy‐dispersive X‐ray spectroscopy (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Scaffolds were also compared with both native bovine cortical bone and pure hydroxyapatite using X‐ray powder diffraction (XRD), and Fourier transform infrared spectroscopy attenuated total reflection (FTIR‐ATR). Structural and chemical analyses show that the scaffold preparation process that we described is successful in creating mineralized collagen sheets, possessing a mineral phase similar to that found in bone as well as a close association between collagen fibrils and mineral plates.

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<![CDATA[Hybrid cardiovascular sourced extracellular matrix scaffolds as possible platforms for vascular tissue engineering]]> https://www.researchpad.co/article/Nf7f07d14-0570-4b41-b786-912e294b8099

Abstract

The aim when designing a scaffold is to provide a supportive microenvironment for the native cells, which is generally achieved by structurally and biochemically imitating the native tissue. Decellularized extracellular matrix (ECM) possesses the mechanical and biochemical cues designed to promote native cell survival. However, when decellularized and reprocessed, the ECM loses its cell supporting mechanical integrity and architecture. Herein, we propose dissolving the ECM into a polymer/solvent solution and electrospinning it into a fibrous sheet, thus harnessing the biochemical cues from the ECM and the mechanical integrity of the polymer. Bovine aorta and myocardium were selected as ECM sources. Decellularization was achieved using sodium dodecyl sulfate (SDS), and the ECM was combined with polycaprolactone and hexafluoro‐2‐propanol for electrospinning. The scaffolds were seeded with human umbilical vein endothelial cells (HUVECs). The study found that the inclusion of aorta ECM increased the scaffold's wettability and subsequently lead to increased HUVEC adherence and proliferation. Interestingly, the inclusion of myocardium ECM had no effect on wettability or cell viability. Furthermore, gene expression and mechanical changes were noted with the addition of ECM. The results from this study show the vast potential of electrospun ECM/polymer bioscaffolds and their use in tissue engineering.

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<![CDATA[New psychoactive substances (NPS) in the Netherlands: occurrence in forensic drug samples, consumer drug samples and poisons center exposures between 2013 and 2017]]> https://www.researchpad.co/article/Nd42d5f6a-37ed-4452-b402-0d1e0aa63301 ]]> <![CDATA[Women's perspective on life after total laryngectomy: a qualitative study]]> https://www.researchpad.co/article/N55c0a9cf-c8ec-424f-8962-3c85363b5413

Abstract

Background

Physical and psychosocial challenges are common after total laryngectomy. The surgery leads to lifelong changes in communication, airway, swallowing and appearance. As we move towards health models driven by patient‐centred care, understanding the differential impacts of surgical procedures on subgroups of patients can help improve our care models, patient education and support systems. This paper discusses the experiences of women following total laryngectomy.

Aims

To gain an insight into the impact of total laryngectomy on women's daily life while identifying their specific rehabilitation needs.

Methods & Procedures

This paper is based on in‐depth, semi‐structured interviews with eight women who had undergone total laryngectomy. These interviews were conducted with women at least 1 year after they had undergone total laryngectomy, and the participants did not have recurrent disease. Using an interview guide, participants were encouraged to discuss their everyday experiences, while also focusing on issues typical to women. The transcribed interview data were analysed by thematic analysis, taking interpretative phenomenological analysis as a lead.

Outcomes & Results

The interviews revealed three main themes: disease and treatment as a turning point, re‐establishing meaningful everyday activities, and persistent vulnerability. Participants reported experiencing challenges in their rehabilitation process due to physical disabilities, dependency on others and experienced stigma. Women‐specific challenges arose in dealing with the altered appearance and voice, performing care activities, and the spousal relationship (including intimacy).

Conclusions & Implications

Women who undergo total laryngectomy are likely to experience issues in returning to work, the performance of informal care‐work, the spousal relationship, intimacy and social interaction due to stigmatization. Medical pretreatment counselling and multidisciplinary rehabilitation programmes should help patients form realistic expectations and prepare them for the changes they will face. A gender‐ and age‐matched laryngectomized patient visitor can contribute to this process. Rehabilitation programmes should incorporate the partner and offer psychosocial support for women following total laryngectomy to return to their former roles in family life, social life and work‐related activities.

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