Engaging Leadership and Psychological Safety as Moderators of the Relationship between Strain and Work Recovery: A Cross-Sectional Study of HSS Employees.

Work in the health and social sector (HSS) is highly straining and therefore recovery from work needs to be promoted. Less is known on how job resources can be used to alleviate job strain and increase recovery from work. Thus, we analyzed the following: the association between job demands and work recovery; the connections of engaging leadership and psychological safety to recovery from work; and the moderating effects of engaging leadership and psychological safety on the relationship between strain and recovery from work.

3D Printed Cellulose-Based Filaments-Processing and Mechanical Properties.

Cellulose is an abundant and sustainable material that is receiving more and more attention in different industries. In the context of additive manufacturing, it would be even more valuable. However, there are some challenges to overcome in processing cellulose-based materials.

A Hands-On Exercise on Caries Diagnostics among Dental Students-A Qualitative Study.

According to current care practices, the aim is to prevent the onset of caries lesions and to stop the progression of incipient lesions. A visual lesion assessment system, International Caries Detection and Assessment System (ICDAS), has been developed to promote reliability and repeatability of assessment of different stage caries lesions. The aims of this study were to evaluate the experiences of a hands-on exercise with authentic teeth as an adjunct to lecturing among third-year dental students and to evaluate the learning process during the hands-on exercise measured by qualitative (inductive content) analysis of the given feedback.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway.

Thermoplastic Cellulose-Based Compound for Additive Manufacturing.

The increasing environmental awareness is driving towards novel sustainable high-performance materials applicable for future manufacturing technologies like additive manufacturing (AM). Cellulose is abundantly available renewable and sustainable raw material. This work focused on studying the properties of thermoplastic cellulose-based composites and their properties using injection molding and 3D printing of granules.

3D Printing High-Consistency Enzymatic Nanocellulose Obtained from a Soda-Ethanol-O Pine Sawdust Pulp.

Soda-ethanol pulps, prepared from a forestry residue pine sawdust, were treated according to high-consistency enzymatic fibrillation technology to manufacture nanocellulose. The obtained nanocellulose was characterized and used as ink for three-dimensional (3D) printing of various structures. It was also tested for its moisture sorption capacity and cytotoxicity, as preliminary tests for evaluating its suitability for wound dressing and similar applications.

Use of conventional surfactant media as surrogates for FaSSIF in simulating in vivo dissolution of BCS class II drugs.

The usefulness of selected conventional surfactant media to enhance dissolution of BCS class II drugs similarly to fasted state simulated intestinal fluid (FaSSIF) and to predict the absorption of drugs in vivo was evaluated. Dissolution behavior of danazol (Danol), spironolactone (Spiridon) and N74 (phase I compound) was compared between FaSSIF, containing physiological levels of sodium taurocholate (STC) and lecithin, and dissolution media containing various concentrations of anionic surfactant, sodium lauryl sulfate (SLS) or non-ionic surfactant, polysorbate (Tween) 80. Although these media differed largely in their solubilization ability, micelle size, diffusivity and surface tension, similar dissolution enhancing levels were achieved between FaSSIF and drug-specific concentrations of conventional surfactants.

Functional interaction of AIRE with PIAS1 in transcriptional regulation.

AIRE (autoimmune regulator) promotes the establishment of self-tolerance by regulating gene expression in the thymus. Mutations in AIRE lead to an autoimmune disease, APECED. Here we have identified PIAS proteins as novel AIRE interaction partners.

The monopartite nuclear localization signal of autoimmune regulator mediates its nuclear import and interaction with multiple importin alpha molecules.

Autoimmune regulator (AIRE) is a transcriptional regulator involved in establishing immunological self-tolerance. Mutations in the AIRE gene lead to the development of the autosomal, recessively inherited, organ-specific autoimmune disease, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). The AIRE protein is mainly localized in the cell nucleus where it is associated with nuclear bodies.

Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare disorder caused by mutations in the autoimmune regulator gene (AIRE) and characterized by a variable combination of organ-specific autoimmune diseases. Studies on AIRE-deficient mice suggest that AIRE is an important factor in the establishment and maintenance of self-tolerance. The AIRE protein contains several structural domains often found in transcriptional regulators and functions as a transcriptional transactivator in vitro.

APECED-causing mutations in AIRE reveal the functional domains of the protein.

A defective form of the AIRE protein causes autoimmune destruction of target organs by disturbing the immunological tolerance of patients with a rare monogenic disease, autoimmune polyendocrinopathy (APE)-candidiasis (C)-ectodermal dystrophy (ED), APECED. Recently, experiments on knockout mice revealed that AIRE controls autoimmunity by regulating the transcription of peripheral tissue-restricted antigens in thymic medullary epithelial cells. Thus, AIRE provides a unique model for molecular studies of organ-specific autoimmunity.

Gelsolin-related familial amyloidosis, Finnish type, in a Portuguese family: clinical and neurophysiological studies.

We report a Portuguese family with familial amyloid polyneuropathy related to gelsolin. There were no known Finnish ancestors, but the same mutation as described in Finnish patients (G654A) was carried. Clinical and neurophysiological investigations were performed in four patients.

N-in-one permeability studies of heterogeneous sets of compounds across Caco-2 cell monolayers.

Purpose: The purpose of the study was to evaluate several n-in-one cocktails of heterogeneous compounds to increase the throughput of permeability studies across Caco-2 monolayers, to investigate the reliability and applicability of the method, and to develop fast and sensitive analysis for the compounds. Compounds with potential interactions in efflux and/or active transport were chosen.

Methods: Permeability experiments with verapamil, propranolol, midazolam, hydroxyzine, timolol, buspirone, procaine, naproxen, ketoprofen, and antipyrine as single compounds and in cocktails of 5-10 compounds were performed at 50 microM concentration both in the apical-to-basolateral and basolateral-to-apical direction.

Role of proprotein convertases in the pathogenic processing of the amyloidosis-associated form of secretory gelsolin.

Familial amyloidosis of the Finnish type (FAF) is caused by two proteolytic cleavages of mutant gelsolin leading to the accumulation of FAF amyloid in the patients' tissues. Here, we demonstrate that, in mouse pituitary corticotropic AtT20 cells, the enzyme responsible for the first cleavage of mutant secretory FAF gelsolin to FAF amyloid precursor is present in reasonable amounts. Furthermore, in At T20 cells stably expressing alpha1-PDX a potent inhibitor of most proprotein convertases, this cleavage was inhibited The present data provide strong evidence that proprotein convertases, possibly furin or PC5, are involved in the initialpathological cleavage of mutant secretory FAF gelsolin leading ultimately to the amyloid disease.

The autoimmune regulator: a key toward understanding the molecular pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune disease with autosomal recessive inheritance. APECED is characterized by the breakdown of tolerance to several organ-specific selfantigens. The symptoms of APECED fall into three main categories: autoimmune polyendocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies.

N-in-one determination of retention factors for drugs by immobilized artificial membrane chromatography coupled to atmospheric pressure chemical ionization mass spectrometry.

Immobilized artificial membrane (IAM) chromatography is widely used in drug discovery for ranking the absorption properties of drug candidates. In this work an IAM chromatography method using atmospheric pressure chemical ionization mass spectrometric detection (IAM/APCI-MS) was developed for the determination of log k(IAM) values for a mixture of compounds (9-in-one). Values were calculated from isocratic runs (0, 10, 20, 30, 35% acetonitrile) in both positive and negative modes.

Effect of nitro groups and alkyl chain length on the negative ion tandem mass spectra of alkyl 3-hydroxy-5-(4'-nitrophenoxy) and alkyl 3-hydroxy-5-(2', 4'-dinitrophenoxy) benzoates.

Tandem mass spectrometric behaviour was studied for a small combinatorial library of alkyl 3-hydroxy-5-(4'-nitrophenoxy) benzoates (A1-A5) and alkyl 3-hydroxy-5-(2', 4'-dinitrophenoxy) benzoates (B1-B5). The spectra were recorded by negative ion electrospray low-energy collision induced dissociation (CID) tandem mass spectrometry. The product ion spectra of [M - H](-) of the benzoates A1-A5 are similar, as are those of benzoates B1-B5.

Functional consequences of amyloidosis mutation for gelsolin polypeptide -- analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts.

Gelsolin, an actin-modulating protein, derived from a single gene exists in intracellular and secreted forms. A point mutation at position 187 of both forms of gelsolin causes familial amyloidosis of the Finnish type (FAF). Here, we expressed both isoforms of the wild-type and FAF mutant gelsolin in mouse embryonic gelsolin-null fibroblasts.

Enzyme-assisted synthesis and structural characterization of nitrocatechol glucuronides.

Enzyme-assisted synthesis and characterization are described for 3-O-beta-D-glucuronides 1b-4b of the aglycons E- and Z-2-cyano-N, N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide (entacapone), 1a and 2a, respectively, 3-(3,4-dihydroxy-5-nitrobenzylidene)-2, 4-pentanedione (nitecapone) 3a and 4'-methyl-3, 4-dihydroxy-5-nitrobenzophenone (tolcapone) 4a, and 1-o- and 2-o-glucuronides 5b and 6b of the aglycon 1, 2-dihydroxy-4-nitrobenzene 5a. Liver microsomes from rats pretreated with Aroclor 1254 were used as catalyst in the synthesis. Glucuronidation was regio- and stereoselective in the case of 1a-4a; only one product was observed by HPLC, HPTLC, and NMR.

Cells of the neuronal lineage play a major role in the generation of amyloid precursor fragments in gelsolin-related amyloidosis.

Gelsolin-related amyloidosis or familial amyloidosis, Finnish type (FAF) (OMIM No105120) is a hereditary amyloid disease caused by a mutation in a precursor protein for amyloid (gelsolin) and characterized by corneal dystrophy and polyneuropathy. In vitro expression of the FAF-mutant (Asp187 --> Asn/Tyr) secretory gelsolin in COS cells leads to generation of an aberrant polypeptide presumably representing the precursor for tissue amyloid. Here, we provide evidence that this abnormal processing results from defective initial folding of the secreted FAF gelsolin due to the lack of the Cys188-Cys201 disulfide bond, normally formed next to the FAF mutation site.

Identification of the circulating amyloid precursor and other gelsolin metabolites in patients with G654A mutation in the gelsolin gene (Finnish familial amyloidosis): pathogenetic and diagnostic implications.

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant type of systemic amyloidosis caused by a G654A (Asn-187) or G654T (Tyr-187) mutation in the gelsolin gene. Herein we show that patients with the Asn-187 gelsolin mutation have, in addition to full-sized gelsolin, a series of lower-Mr C-terminal fragments of gelsolin (Mr of 70,000-45,000) in the circulation, and that a 50 to 55-kd fragment of gelsolin is excreted in the urine. In homozygous FAF (Asn-187), the 65-kd fragment, which contains the amyloid-forming region (Ala173-Met243), and the 55-kd fragment, which is devoid of that region, are the major gelsolin species in plasma; whereas normal gelsolin, as well as a 70-kd fragment identified as the C-terminal portion of gelsolin starting at Glu122, and a 45-kd fragment starting at Ser384, are minor components.

Tissue distribution and levels of gelsolin mRNA in normal individuals and patients with gelsolin-related amyloidosis.

We measured quantitatively the mRNA levels of intracellular and secretory forms of gelsolin, an actin-modulating protein, in human tissues from subjects of different ages. The intracellular gelsolin mRNA constituted the major type of gelsolin steady-state mRNA in all tissues analyzed. Both forms of gelsolin were expressed in most adult tissues, with particularly high mRNA levels in all types of muscle and interestingly in skin.

In vitro expression analysis shows that the secretory form of gelsolin is the sole source of amyloid in gelsolin-related amyloidosis.

Amyloidoses are a group of diseases where abnormal fibrillar protein deposits accumulate in patients' tissues. In familial amyloidosis of the Finnish type (FAF), or gelsolin-related amyloidosis, the amyloid subunit protein consists of gelsolin peptides of amino acids 173-243 with the disease causing substitution at Asp187. Gelsolin is an actin-modulating protein and exists in both secretory and intracellular forms both encoded by a single gene in chromosome 9.

Toward understanding the pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment.

Gelsolin-related amyloidosis, also called familial amyloidosis, Finnish type (FAF) is an autosomal dominantly inherited disorder characterized by progressive polyneuropathy and corneal lattice dystrophy. All the analyzed patients are found to carry a nucleotide substitution of A or T for G654 in their gelsolin gene, which at the protein level results in the conversion of the 187 amino acid residue, aspartic acid, to asparagine or tyrosine, respectively. In this study, we transfected mammalian mesenchymal COS-1 cells with a derivative of the expression vector pCD-X containing cDNA coding for the wild-type (D187) and mutant forms (N187 and Y187) of plasma gelsolin.