Knowledge of appropriate acetaminophen use: A survey of college-age women

Objectives

To evaluate college-age women’s knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen.

Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: impact on 6-year survival

International Urology and Nephrology - The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and...     

Pineal cysts without hydrocephalus: microsurgical resection via an infratentorial-supracerebellar approach—surgical strategies,complications, and their avoidance

Neurosurgical Review - Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of...     

Virtual implantations to transition from porcine to bovine animal models for a total artificial heart

Realheart total artificial heart (TAH) is a novel, pulsatile, four-chamber total artificial heart which had been successfully tested acutely in a porcine animal model. However, the bovine model is better suited for long-term testing and thus an evaluation of how the design would fit the bovine anatomy was required. Virtual implantation is a method that enables a computer simulated implantation based on anatomical 3D-models created from computer tomography images. This method is used clinically, but not yet adopted for animal studies. Herein, we evaluated its suitability in the redesign of the outer dimensions and vessel connections of Realheart TAH to transition from the porcine to the bovine animal model. Virtual implantations in combination with bovine cadaver studies enabled a series of successful acute bovine implantations. Virtual implantations are a useful tool to replace the use of animals in early device development and refine subsequent necessary in vivo experiments. The next steps are to carry out human virtual implantations and cadaver studies to ensure the design is optimized for all stages of testing as well as the final recipient.     

No Association Between NRG1 and ErbB4 Genes and Psychopathological Symptoms of Schizophrenia

Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizophrenia symptom dimensions as evaluated by the Positive and Negative Syndrome Scale (PANSS). We then followed up nominally significant results in a second cohort of 439 schizophrenia subjects recruited in Germany. Using linear regression, we observed two different groups of polymorphisms in NRG1 gene: one showing a nominal association with higher scores of the PANSS positive dimension and the other one with higher scores of the PANSS negative dimension. Regarding ErbB4, a small cluster located in the 5′ end of the gene was detected, showing nominal association mainly with negative, general and total dimensions of the PANSS. These findings suggest that some regions of NRG1 and ErbB4 are functionally involved in biological processes that underlie some of the phenotypic manifestations of schizophrenia. Because of the lack of significant association after correction for multiple testing, our analyses should be considered as exploratory and hypothesis generating for future studies.     

Peptidoglycan-binding protein TsaP functions in surface assembly of type IV pili

Type IV pili (T4P) are ubiquitous and versatile bacterial cell surface structures involved in adhesion to host cells, biofilm formation, motility, and DNA uptake. In Gram-negative bacteria, T4P pass the outer membrane (OM) through the large, oligomeric, ring-shaped secretin complex. In the β-proteobacterium Neisseria gonorrhoeae, the native PilQ secretin ring embedded in OM sheets is surrounded by an additional peripheral structure, consisting of a peripheral ring and seven extending spikes. To unravel proteins important for formation of this additional structure, we identified proteins that are present with PilQ in the OM. One such protein, which we name T4P secretin-associated protein (TsaP), was identified as a phylogenetically widely conserved component of the secretin complex that co-occurs with genes for T4P in Gram-negative bacteria. TsaP contains an N-terminal carbohydrate-binding lysin motif (LysM) domain and a C-terminal domain of unknown function. In N. gonorrhoeae, lack of TsaP results in the formation of membrane protrusions containing multiple T4P, concomitant with reduced formation of surface-exposed T4P. Lack of TsaP did not affect the oligomeric state of PilQ, but resulted in loss of the peripheral structure around the PilQ secretin. TsaP binds peptidoglycan and associates strongly with the OM in a PilQ-dependent manner. In the δ-proteobacterium Myxococcus xanthus, TsaP is also important for surface assembly of T4P, and it accumulates and localizes in a PilQ-dependent manner to the cell poles. Our results show that TsaP is a novel protein associated with T4P function and suggest that TsaP functions to anchor the secretin complex to the peptidoglycan.Type IV pili systems (T4PSs) are involved in the assembly of long, thin fibers, which are found on the surfaces of many bacteria and archaea (1). Type IV pili (T4P) function in host cell adhesion, twitching motility, virulence, DNA uptake, and biofilm formation and are evolutionary related to type II secretion systems (T2SSs), bacterial transformation systems, and the archaellum (2–4). T4PSs can be divided into T4aPSs and T4bPSs that are distinguished based on pilin size and assembly systems (5, 6). T4aPSs form the most abundant class, and the T4P formed by these systems can undergo cycles of extension, adhesion, and retraction, which is a feature that distinguishes them from the other bacterial surface structures (7, 8). T4aP retract at rates up to 1 μm/s and can generate forces up to 150 pN (9, 10). Generally, T4bPSs are not associated with retraction. Here, we focus on T4aPSs and refer to these as T4PSs unless specifically indicated. T4PSs have been studied extensively in many bacteria but are especially well characterized in Neisseria and Pseudomonas spp. and in Myxococcus xanthus. Different nomenclature is used for different T4PSs (Table S1). Here, the Neisseria gonorrhoeae nomenclature is used.T4P are composed of major (e.g., PilE) and minor (in N. gonorrhoeae; e.g., PilV, PilX, ComP) pilins that are synthesized as preproteins with a type III signal peptide. After cleavage of the signal peptide by the prepilin peptidase PilD (11, 12), the T4P are assembled by a multiprotein complex (13). In Gram-negative bacteria, the proteins of T4PSs can be divided into three subcomplexes: the inner membrane (IM) motor complex, the alignment complex, and the outer membrane (OM) pore complex (6). The IM motor complex drives both the assembly and the retraction of T4P. Pilin subunits are extruded from the IM by the platform protein PilG (14) and the hexameric ATPase PilF (15). Disassembly of T4P with retraction occurs when PilF is replaced by the hexameric ATPase PilT (7, 16). PilU, a PilT paralog, is involved in retraction to a lesser extent (17). The alignment complex consisting of PilM, PilN, PilO, and PilP is proposed to connect the IM motor complex and the OM pore complex, and it is also thought to be involved in the stability and/or gating of the OM complex (18–20). In the OM, PilQ forms a homooligomeric ring that serves as a conduit for T4P (21–23).PilQ is a member of the secretin protein family. Proteins belonging to this family are present in many Gram-negative bacteria and are components of T4PSs, T2SSs, type III secretion systems (T3SSs), and extrusion systems of filamentous phages (24). Secretins are multidomain proteins with a signal sequence and a conserved C-terminal OM-spanning domain. Most secretins contain multiple copies of an N-terminal α/β domain (the N domains). PilQ proteins are integral OM proteins and form large gated channels. Oligomeric secretin complexes with different symmetries have been identified. Structural characterization by EM of purified PilQ from Neisseria meningitidis showed a dodecameric structure with a chamber sealed at both ends (25, 26), whereas the T2SS secretins PulD (27) and GspD (28) of the Klebsiella oxytoca pullanase and Vibrio cholerae toxin secretion systems, respectively, showed dodecameric structures with a chamber open at the periplasmic side and closed at the OM side. The structure of the InvG secretin complex of the T3SS of the Salmonella typhimurium needle complex showed 15-fold symmetry and is open at both ends (29), and the phage pIV secretin showed 14-fold symmetry (30). The structure of the C-terminal OM-spanning domain involved in multimer formation is currently not known. Crystal structures of the periplasmic N domains of GspD of the T2SS of enterotoxigenic Escherichia coli (31), of EscC of the T3SS of S. typhimurium (32), and of N. meningitidis PilQ (25) showed that these domains consist of α-helices packed against three-stranded β-sheets. Secretins of T4P systems also contain B domains, which are not present in other secretins and are located N-terminal to the N domains. The structure of the B2 domain of N. meningitidis PilQ consists of several β-strands (25). Remarkably, when the sequence conservation of the B2 domain was mapped to the structure of the B2 domain of N. meningitidis PilQ, a highly conserved patch was identified that was proposed to form the binding site for a currently unidentified T4PS protein (25).Secretins interact with several other proteins. Pilotin proteins are small lipoproteins that interact with the extreme C terminus of secretins and are responsible for OM targeting and oligomerization of secretins (33–38). Secretins of T4PSs also interact with the alignment complex. For N. meningitidis, Pseudomonas aeruginosa, and M. xanthus PilQ, a direct interaction was demonstrated between the respective PilPs and the N0 domains of the PilQs (25, 39, 40). Recently, ExeA of the T2SS of Aeromonas hydrophila (41) and FimV of the T4PS of P. aeruginosa (42) were also implicated in secretin assembly. They contain, respectively, PF01471 and LysM peptidoglycan (PG)-binding domains that might attach them to the PG. However, neither of these two proteins is ubiquitously conserved in bacteria assembling T4P.We have previously shown that the PilQ secretin of N. gonorrhoeae embedded in OM sheets is surrounded by a peripheral structure, which is formed by an additional peripheral ring as well as spikes (43). The proteins that make up these structures are not known. Here, we identify a widely conserved protein, which we name T4P secretin-associated protein (TsaP), that is important for the formation of the peripheral structure. Phylogenomic analysis of 450 genomes of Proteobacteria showed that the presence of the tsaP gene is strongly linked to the presence of genes for T4aPSs. We characterize the TsaP protein and demonstrate the importance of TsaP for T4aP assembly in the two phylogenetically widely separated model organisms N. gonorrhoeae and M. xanthus.     

Interaction of Different Antidepressants with Acute and Chronic Methadone in Mice,and Possible Clinical Implications

We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p?<?0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone’s antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone’s analgesic effect. Further studies are needed before possible clinical implications can be drawn.     

Lifelong learning in community healthcare: Testing competence after learning activities in a blended learning space

Aims and Objectives

This study reports from a municipality in Norway that implemented a competence enhancement programme for all its institutional nursing staff during the COVID-19 pandemic to fill identified competence gaps.

Background

Many Norwegian municipalities are experiencing a demand for expanded community healthcare services due to an increase in elderly patients and patients with extensive and complex needs. At the same time, most municipalities are striving to recruit and keep competent health personnel. New ways of organising and increasing the competence of the workforce may help ensure that the healthcare delivered corresponds to patients' changing needs.

Design and Methods

Nursing staff were encouraged to complete targeted competence enhancing activities with the aim of enhancing their competence in identified areas. The learning activities were blended and consisted of e-learning courses, lectures, supervision, vocational training and meetings with a superior. Competence was measured before and after the competence enhancing activities (n = 96). The STROBE checklist was applied.

Results

The results provide insight into the competence development of registered nurses and assistant nurses in institutional community health services. They show that the implementation of a workplace-based blended learning programme improved competence significantly, especially for assistant nurses.

Conclusions

Offering workplace-based competence enhancing activities seems to be a sustainable way of facilitating lifelong learning among nursing staff. Facilitation of learning activities in a blended learning space may enhance accessibility and increase the potential for participation. A combination of reorganisation of roles and simultaneous competence enhancing activities can ensure that both managers and nursing staff prioritise filling competence gaps.