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Dementia care is a major public health issue worldwide. The management of behavioral and psychological symptoms (BPSD) is one of the hardest challenges in this context. Non-pharmacological strategies, like music-based interventions (Mbi), seem promising options, being considered low-risk, widely available and inclusive. This scoping review aimed at mapping all Mbi used in dementia care, targeting BPSD, and debriefing its components, structure and rationale. Music therapy and other therapeutic music activities were included.

The Arksey and O'Malley framework, Cochrane recommendations and PRISMA checklist were followed. Embase, PubMed, PsycINFO, ASSIA and Humanities Index were searched from first records until the 31

of March 2020. Snowballing process and screening of relevant journals were also undertaken. A panel of experts critically guided the evidence synthesis.

Overall, 103 studies (34 RCT; 12 NRT; 40 Before/After studies and 17 Case Studies) met inclusion criteria. Basic elements of the Mbi, the rationale supporting its development and hypothesis tested were mostly underreported, thus hampering cross-study comparisons and generalizations. Despite this, available evidence indicates that it is feasible to deliver Mbi to PwD at very different stages and in different settings - from community to the acute setting - even for non-music therapists; positive or neutral effects in BPSD are often reported but not without exception; individualization seems a critical factor mediating Mbi effects.

Detailed intervention and research reporting are essential to interpretation, replication and translation into practice. Ten years after the publication of specific reporting guidelines, this goal is not yet fully achieved in music in dementia care.

Detailed intervention and research reporting are essential to interpretation, replication and translation into practice. Ten years after the publication of specific reporting guidelines, this goal is not yet fully achieved in music in dementia care.Early life adversity can disrupt development leading to emotional and cognitive disorders. This study investigated the effects of social isolation after weaning on anxiety, body weight and locomotion, and on extracellular dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) and their modulation by corticotropin releasing factor receptor 1. On the day of weaning, male rats were housed singly or in groups for 10 consecutive days. Anxiety-like behaviors were assessed by an elevated plus maze (EPM) and an open field test (OF). Neurotransmitter levels were measured by in vivo microdialysis. Single-housed rats spent less time, and entered more, into the closed arms of an EPM than group-housed rats. They also spent less time in the center of an OF, weighed more and showed greater locomotion. In the NAc, no differences in CRF, or in basal extracellular DA or GLU between groups, were observed. A depolarizing stimulus increased DA release in both groups but to higher levels in isolated rats, whereas GLU increased only in single-housed rats. selleckchem Blocking CRF-R1 receptors with CP-154,526 decreased DA release in single-housed but not in group-housed rats. The corticotropin releasing factor receptor type 1 receptor antagonist also decreased GLU in group-housed animals. These results show that isolating adolescent rats increases anxiety, body weight and ambulation, as well as the sensitivity of dopaminergic neurons to a depolarizing stimulus. This study provides further evidence of the detrimental effects of social isolation during early development and indicates that dysregulation of the CRF system in the NAc may contribute to the pathologies observed.During normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS-induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA-induced checkpoint. We find that YneA C-terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA-enforced DNA damage checkpoint. With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.The total synthesis of long proteins requires the assembly of multiple fragments through successive ligations. The need for intermediate purification steps is a strong limitation, particularly in terms of overall yield. One solution to this problem would be solid-supported chemical ligation (SPCL), for which a first peptide segment must be immobilized on a SPCL-compatible solid support through a linker that can be cleaved under very mild conditions to release the assembled protein. The cleavage of SPCL linkers has previously required chemical conditions sometimes incompatible with sensitive protein targets. Herein, we describe an alternative enzymatic approach to trigger cleavage under extremely mild and selective conditions. Optimization of the linker structure and use of a small enzyme able to diffuse into the solid support were key to the success of the strategy. We demonstrated its utility by the assembly of three peptide segments on the basis of native chemical ligation to afford a 15 kDa polypeptide.

Tebipenem pivoxil (TBPM-PI) has been developed as the first oral carbapenem drug in the world to treat otolaryngological and respiratory infections in pediatric patients. Due to its structural properties and external factors, some related impurities, which may cause side effects in patients, might be formed during the synthesis and storage of TBPM-PI. It was vital to rapidly separate and identify the related impurities to guarantee the safe use of TBPM-PI.

A method using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) was developed to separate and detect TBPM-PI and related impurities in an oral pharmaceutical formulation. LC/MS and MS/MS spectra of these compounds in the formulation were acquired to confirm their elemental compositions and propose their structures based on LC/MS data and fragmentation pathways of available reference substances.

LC/MS parameters and MS/MS fragmentation pathways of reference substances of TBPM-PI and related impurities were summarized in detail.