Low-molecular-weight heparin for the prevention and treatment of venous thromboembolism in pregnancy

PURPOSE OF REVIEW: Low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparins for both prophylaxis and treatment of venous thromboembolism in nonpregnant patients. However, until recently, evidence in pregnant women was lacking, despite the increasing use of LMWHs during pregnancy in clinical practice. This review covers recent literature on the use of LMWHs in relation to pregnancy. RECENT FINDINGS: The main areas covered in this review are the use of LMWHs in both prophylaxis and treatment of venous thromboembolism in pregnancy. The review also considers issues relating to monitoring of LMWHs in pregnancy, and safety from both a maternal and a fetal perspective. SUMMARY: The available evidence demonstrates that LMWHs are of at least equivalent efficacy but have a better safety profile compared with unfractionated heparins in both prophylaxis and treatment of maternal venous thromboembolism, and are more convenient to administer. There is no consensus with respect to whether these agents require monitoring during pregnancy other than periodic checking of the platelet count. The clinical implication from the available evidence is that LMWHs should now be regarded as the anticoagulant agents of choice for both prophylaxis and treatment of maternal venous thromboembolism.     

Microstructure provides insights into evolutionary design and resilience of Coscinodiscus sp. frustule

We conducted in situ three-point bending experiments on beams with roughly square cross-sections, which we fabricated from the frustule of Coscinodiscus sp. We observe failure by brittle fracture at an average stress of 1.1 GPa. Analysis of crack propagation and shell morphology reveals a differentiation in the function of the frustule layers with the basal layer pores, which deflect crack propagation. We calculated the relative density of the frustule to be ∼30% and show that at this density the frustule has the highest strength-to-density ratio of 1,702 kN⋅m/kg, a significant departure from all reported biologic materials. We also performed nanoindentation on both the single basal layer of the frustule as well as the girdle band and show that these components display similar mechanical properties that also agree well with bending tests. Transmission electron microscopy analysis reveals that the frustule is made almost entirely of amorphous silica with a nanocrystalline proximal layer. No flaws are observed within the frustule material down to 2 nm. Finite element simulations of the three-point bending experiments show that the basal layer carries most of the applied load whereas stresses within the cribrum and areolae layer are an order of magnitude lower. These results demonstrate the natural development of architecture in live organisms to simultaneously achieve light weight, strength, and exceptional structural integrity and may provide insight into evolutionary design.Diatoms are single-cell algae that form a hard cell wall made of a silica/organic composite. The ability to produce a functional biosilica shell presents several natural precedents that fascinate and inspire scientists and engineers. One fascinating aspect of such silica glass shells is their intricate, varied, and detailed architecture. Diatoms are generally classified based on the symmetry of their shells: Centric diatoms display radial symmetry whereas pennate diatoms have bilateral symmetry. Fig. 1A shows a schematic of a typical centric diatom and reveals that the shells are composed of two halves, called frustules, that fit together in a Petri-dish configuration. The frustules are attached to each other around the perimeter of the shell by one or several girdle bands. The frustules are usually porous with pore size and density varying between species. The frustule shell can also be composed of multiple layers with a cellular structure within the shell.Open in a separate windowFig. 1.(A) Schematic of the diatom frustule shell. (B) Cross-section of shell demonstrating the honeycomb sandwich plate configure of the silica shell. (C) Cribrum, the outer layer of the frustule shell, displays hexagonal arrangements of pores. (D) The basal plate, the inner layer of the frustule shell, is punctuated by reinforced pores called foramen.The proposed evolutionary functions for these intricate shell designs include nutrient acquisition, control of diatom sinking rate, control of turbulent flow around the cell, and protection from grazing and viral attack (1). Evidence in favor of a protective function is that the degree of shell silification depends on the environment, with greater amounts of silica found in shells grown in a predatory environment (2). As a deterrent to predation, the frustule makes use of an inherently brittle glass as a structurally protective material while balancing other evolutionary pressures. A denser shell may provide greater protection but will cause the diatom to sink beyond depths suitable for photosynthesis. A solid shell might also prevent exchange of resources and waste between the diatom cell and its environment. This requires adaption through control of the frustule micromorphology or modification of the constituent silica/organic composite material (3). The protective aspects of the frustule shell are clear; what remains an open question is how much the intricate pore structure and cellular design contribute to the amplified structural resilience vs. biological function.The size of most diatom species ranges from 2 to 200 µm (4, 5), which renders most of the traditional mechanical testing methods inadequate to characterize such complex materials; a few mechanical studies on diatoms have been reported (6–11). The majority of studies perform atomic force microscopy (AFM) indentation (6–9) on a full frustule of centric or pennate diatoms. Reported values of hardness ranged from 0.06–12 GPa and values of elastic modulus from 0.35–22.4 GPa. Differences in local pore structure and the nonplanar geometry of the frustule were often cited for the variance in mechanical properties. Three-point bending tests on beams that were extracted from the diatom frustule reported failure strengths of 336 ± 73 MPa but were complicated by local penetration of the indenter tip and tilting of the frustule during testing (10, 11).This overview demonstrates a wide range in the reported hardnesses and elastic moduli for biosilica shells. Most of these experiments were performed on full diatom shells, which in some instances contained organic cellular material; it is unclear whether the measured mechanical data represent the deformation of the constituent biosilica or the overall deformation of the shell through bending, local twisting, pivoting, and so on. Indentation using AFM can introduce inaccuracies such as tip sliding, and the resulting uncertainty in compliance within a single set of experiments, as well as among the data obtained with different instruments, makes it challenging to compare mechanical properties of the diatoms across the reported experiments. Within a single species, these mechanical data may provide qualitative trends in the structural response of the diatom shells; it is difficult to make any conclusions on the mechanical properties of the constituent biosilica. The mechanisms of silica biogenesis likely varies among the species (12), but it is unclear to what extent these differences reflect the variation in elastic modulus and hardness between species and within an individual frustule.To investigate the mechanical properties of the diatom frustule and constituent biosilica as decoupled from the full-shell structural response, we conducted in situ three-point bending experiments on beams with roughly 3.5-µm-square cross-sections fabricated from the frustule of Coscinodiscus sp. performed in a scanning electron microscope (SEM) equipped with a nanoindenter, as well as ex situ nanoindentation on an individual basal plate that had been isolated from a frustule and the girdle band. We determined the elastic modulus to be 36.4 ± 8.3 GPa and the failure strength to be 1.1 ± 0.3 GPa. We discuss these results, as well as deformation and failure mode of the diatoms, in the context of their atomic-level microstructure obtained from transmission electron microscopy (TEM) and finite element method (FEM) simulations of the three-point bending tests.     

The contribution of primary care practitioners to interventions reducing loneliness and social isolation in older people—An integrative review

Background

Social connection is a fundamental human need. Its absence can lead to loneliness and social isolation, adversely impacting health and well-being. Given their regular contact and trusted relationships with older people, practitioners delivering community-based primary care are well-positioned to address this issue. However, their contribution to addressing loneliness and social isolation is unclear.

Aim

This integrative review explores the contribution of the primary care workforce to interventions aimed at reducing loneliness and social isolation in community-dwelling older people.

Method

Using an integrative review method, Scopus, Web of Science, CINAHL and PubMed were searched for original research published between 2000 and 2022. Fourteen papers reporting 13 primary studies were appraised for methodological quality and included in the review. Data were extracted into a summary table and analysed using thematic analysis.

Results

Included studies came from over six countries. Internationally, primary care services have diverse structures, funding and workforces influencing their response to loneliness and social isolation. All but one intervention was multi-component, with ten studies including a group-based activity and three providing primarily individual-level activities. Only six studies reported reductions in loneliness following the intervention. Three themes were identified: characteristics of interventions; implementation context, barriers and facilitators; and differing contributions of primary care practitioners in addressing loneliness and social isolation of older people.

Conclusion

There is increasing demand and scope for primary care practitioners to assist lonely and socially isolated older people. It is important to understand how to equip and incentivise these practitioners to routinely identify, assess and respond to lonely and socially isolated older people despite varying implementation contexts. There is a need for further research that explores how the primary care team can be better utilised to deliver effective interventions that reduce the health impacts of loneliness and social isolation.     

Occurrence of BMAA Isomers in Bloom-Impacted Lakes and Reservoirs of Brazil,Canada, France,Mexico, and the United Kingdom

The neurotoxic alkaloid β-N-methyl-amino-l-alanine (BMAA) and related isomers, including N-(2-aminoethyl glycine) (AEG), β-amino-N-methyl alanine (BAMA), and 2,4-diaminobutyric acid (DAB), have been reported previously in cyanobacterial samples. However, there are conflicting reports regarding their occurrence in surface waters. In this study, we evaluated the impact of amending lake water samples with trichloroacetic acid (0.1 M TCA) on the detection of BMAA isomers, compared with pre-existing protocols. A sensitive instrumental method was enlisted for the survey, with limits of detection in the range of 5–10 ng L⁻¹. Higher detection rates and significantly greater levels (paired Wilcoxon’s signed-rank tests, p < 0.001) of BMAA isomers were observed in TCA-amended samples (method B) compared to samples without TCA (method A). The overall range of B/A ratios was 0.67–8.25 for AEG (up to +725%) and 0.69–15.5 for DAB (up to +1450%), with absolute concentration increases in TCA-amended samples of up to +15,000 ng L⁻¹ for AEG and +650 ng L⁻¹ for DAB. We also documented the trends in the occurrence of BMAA isomers for a large breadth of field-collected lakes from Brazil, Canada, France, Mexico, and the United Kingdom. Data gathered during this overarching campaign (overall, n = 390 within 45 lake sampling sites) indicated frequent detections of AEG and DAB isomers, with detection rates of 30% and 43% and maximum levels of 19,000 ng L⁻¹ and 1100 ng L⁻¹, respectively. In contrast, BAMA was found in less than 8% of the water samples, and BMAA was not found in any sample. These results support the analyses of free-living cyanobacteria, wherein BMAA was often reported at concentrations of 2–4 orders of magnitude lower than AEG and DAB. Seasonal measurements conducted at two bloom-impacted lakes indicated limited correlations of BMAA isomers with total microcystins or chlorophyll-a, which deserves further investigation.