Computational Dehydration of Crystalline Hydrates Using Molecular Dynamics Simulations

Molecular dynamics (MD) simulations have evolved to an increasingly reliable and accessible technique and are today implemented in many areas of biomedical sciences. We present a generally applicable method to study dehydration of hydrates based on MD simulations and apply this approach to the dehydration of ampicillin trihydrate. The crystallographic unit cell of the trihydrate is used to construct the simulation cell containing 216 ampicillin and 648 water molecules. This system is dehydrated by removing water molecules during a 2200 ps simulation, and depending on the computational dehydration rate, different dehydrated structures were observed. Removing all water molecules immediately and removing water relatively fast (10 water molecules/10 ps) resulted in an amorphous system, whereas relatively slow computational dehydration (3 water molecules/10 ps) resulted in a crystalline anhydrate. The structural changes could be followed in real time, and in addition, an intermediate amorphous phase was identified. The computationally identified dehydrated structure (anhydrate) was slightly different from the experimentally known anhydrate structure suggesting that the simulated computational structure could represent a kinetically trapped dehydration intermediate.     

Associations between the dimensions of perceived togetherness,loneliness, and depressive symptoms among older Finnish people

ABSTRACT

Objectives: We studied the associations between perceived togetherness, depressive symptoms, and loneliness over a six-month period among 222 people aged 75–79 who reported loneliness or depressive mood at baseline.

Method: The present cross-lagged models utilized baseline and six-month follow-up data of a randomized controlled trial that examined the effects of a social intervention on loneliness and depression (ISRCTN78426775). Dimensions of perceived togetherness, i.e. attachment, social integration, guidance, alliance, nurturance, and reassurance of worth, were measured with the Social Provisions Scale, depressive symptoms with a short form of the Geriatric Depression Scale, and loneliness with a single item.

Results: After controlling for baseline loneliness and depressive symptoms, baseline higher attachment in all participants and baseline higher opportunity for nurturance in the social intervention group predicted lower depressive mood at follow-up. No cross-lagged associations between the dimensions of perceived togetherness at baseline and loneliness at follow-up were observed. In addition, depressive symptoms and loneliness at baseline tended to negatively predict the dimensions of perceived togetherness at follow-up.

Discussion: Depressive symptoms and loneliness appear to be precursor for perceived togetherness, rather than dimensions of perceived togetherness to be antecedents of loneliness and depressiveness among older people.     

Validity of a single question to assess habitual physical activity of community‐dwelling older people

The aim is to determine concurrent validity of a single self‐report habitual physical activity (PA) question against accelerometer‐based PA and mobility variables, and corresponding changes in self‐reported PA and mobility. Cross‐sectional and longitudinal data of the “Life‐space mobility in old age” (LISPE) cohort and its substudy on PA were utilized. At baseline, 848 community‐dwelling, 75‐ to 90‐year‐old people living independently in central Finland participated in home‐based interviews. One and 2 years later, 816 and 761 of them were reassessed by phone, respectively. Tri‐axial accelerometer data over 7 days were collected following the baseline assessments in a subsample of 174. Self‐reported habitual PA was assessed based on intensity and duration using a single question with seven response options (range: mostly resting to competitive sports). Mobility variables were as follows: life‐space mobility, walking difficulty over 500 m, and short physical performance battery. Statistically significant correlations were found between self‐reported habitual PA and mobility (Spearman correlation coefficient Rs = 0.40–0.61) and accelerometer‐based PA variables [step counts (Rs = 0.49), time in moderate (Rs = 0.49) and low intensity (Rs = 0.40) PA, and time in sedentary behavior (Rs = ?0.28)]. A decline in self‐reported habitual PA over time was associated with 5–10p decline in life‐space mobility (PA improvement with 0–3p increase) and with developing a higher degree of walking difficulty (in 35–44% of participants). In conclusion, based on these results, the self‐report question to assess habitual PA is valid and responsive to change and thus useful for epidemiological research in community‐dwelling older people, also in follow‐up studies.     

Human sex chromosomes in oral and craniofacial growth

Studies on tooth crown size and structure in families and in individuals with various sex chromosome anomalies have demonstrated differential direct effects of the human X and Y chromosome genes on growth. The Y chromosome promotes both tooth crown enamel and dentin growth, whereas the effect of the X chromosome on crown growth seems to be restricted to enamel formation. Enamel growth is decisively influenced by cell secretory function and dentin growth by cell proliferation. It is suggested that these differential effects of the X and Y chromosomes on growth explain the expression of sexual dimorphism in various somatic features. These include tooth crown and root size, crown shape and the number of the teeth, and under the assumption of genetic pleiotropy, torus mandibularis, statural growth, and sex ratio. It is of interest that molecular studies have shown that the gene loci for human amelogenin, the major protein component of the organic matrix in enamel are on both the X and Y chromosomes. Future questions include the role of the Y chromosome in the mineralization process, the concentric control of enamel and dentin growth, and gene expression.     

Stabilization of liposomes during drying

INTRODUCTION: During the past 40 years, liposomes have been investigated intensively as drug carriers for anticancer drugs and as the adjuvant components of vaccines, for example. In this context, the development of dry formulations of liposomes is important to ensure a more stable drug product and to avoid the use of the 'cold chain' during distribution. AREAS COVERED: This review provides an overview of the technologies commonly used for the drying of liposomal formulations and the significance of formulation and processing parameters for the drying process. In addition, a review is provided of the protective mechanisms proposed to be responsible for stabilization during processing and in the dry state, with special emphasis on the techniques used for the characterization of the mechanisms. Parameters are discussed that critically influence the liposomal stability during drying and the underlying stabilization mechanisms, including the water replacement theory, vitrification and kosmotropic effects. EXPERT OPINION: Drying of liposomal formulations has contributed to the development of more stable products because liposomes can be dehydrated in the presence of appropriate stabilizing excipients, without affecting the size or the drug encapsulation efficiency. The key to the successful design and preparation of optimal liposomal dry powder formulations is an understanding of the significance of the drying process parameters, and the mechanisms responsible for the stabilization of liposomes during drying and in the dry state.     

Genetic architecture of circulating lipid levels

Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.     

Women's perceptions of caesarean birth: a Roy international study

The purpose of this Roy adaptation model-based multi-site international mixed method study was to examine the relations of type of caesarean birth (unplanned/planned), number of caesarean births (primary/repeat), and preparation for caesarean birth to women's perceptions of and responses to caesarean birth. The sample included 488 women from the United States (n = 253), Finland (n = 213), and Australia (n = 22). Path analysis revealed direct effects for type of and preparation for caesarean birth on responses to caesarean birth, and an indirect effect for preparation on responses to caesarean birth through perception of birth the experience.