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Cureus Aug 2023Osteoporosis is a disease of global concern, with significant implications for mortality, morbidity, strain on national health resources, and the negative impact on the... (Review)
Review
Osteoporosis is a disease of global concern, with significant implications for mortality, morbidity, strain on national health resources, and the negative impact on the quality of life associated with the condition. As we witness a primarily aging population, future predictions indicate that risk factors for osteoporosis will be more prevalent, leading to an increase in the number of individuals suffering from the condition and associated fractures. However, the future of osteoporosis in terms of diagnosis and treatment is optimistic. Understanding of bone quality and examination of it has improved with the onset of magnetic resonance imaging (MRI) and other imaging techniques such as micro-computer tomography. Innovative therapies specifically targeting osteoporotic bone metabolism on a microscopic level hold promise. This narrative review provides details on the background, prognosis, and future treatment strategies of osteoporosis.
PubMed: 37674960
DOI: 10.7759/cureus.43031 -
Biophysical Reviews Aug 2023Over the past decade, myriads of studies have highlighted the central role of protein condensation in subcellular compartmentalization and spatiotemporal organization of... (Review)
Review
Over the past decade, myriads of studies have highlighted the central role of protein condensation in subcellular compartmentalization and spatiotemporal organization of biological processes. Conceptually, protein condensation stands at the highest level in protein structure hierarchy, accounting for the assembly of bodies ranging from thousands to billions of molecules and for densities ranging from dense liquids to solid materials. In size, protein condensates range from nanocondensates of hundreds of nanometers (mesoscopic clusters) to phase-separated micron-sized condensates. In this review, we focus on protein nanocondensation, a process that can occur in subsaturated solutions and can nucleate dense liquid phases, crystals, amorphous aggregates, and fibers. We discuss the nanocondensation of proteins in the light of general physical principles and examine the biophysical properties of several outstanding examples of nanocondensation. We conclude that protein nanocondensation cannot be fully explained by the conceptual framework of micron-scale biomolecular condensation. The evolution of nanocondensates through changes in density and order is currently under intense investigation, and this should lead to the development of a general theoretical framework, capable of encompassing the full range of sizes and densities found in protein condensates.
PubMed: 37681092
DOI: 10.1007/s12551-023-01105-1 -
Journal of Controlled Release :... Jun 2024The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have... (Review)
Review
The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.
Topics: Humans; Drug Delivery Systems; Gels; Animals; Aerosols; Administration, Inhalation; Particle Size; Pharmaceutical Preparations
PubMed: 38641021
DOI: 10.1016/j.jconrel.2024.04.021 -
The Journal of Physical Chemistry. A Nov 2023While CCSD(T) is often considered the "gold standard" of computational chemistry, the scaling of its computational cost as N limits its applicability for large and...
While CCSD(T) is often considered the "gold standard" of computational chemistry, the scaling of its computational cost as N limits its applicability for large and complex molecular systems. In this work, we apply the density-based many-body expansion [ 2020, 120, e26228] in combination with CCSD(T). The accuracy of this approach is assessed for neutral, protonated, and deprotonated water hexamers, as well as (HO) and (HO) clusters. For the neutral water clusters, we find that already with a density-based two-body expansion, we are able to approximate the supermolecular CCSD(T) energies within chemical accuracy (4 kJ/mol). This surpasses the accuracy that is achieved with a conventional, energy-based three-body expansion. We show that this accuracy can be maintained even when approximating the electron densities using Hartree-Fock instead of using coupled-cluster densities. The density-based many-body expansion thus offers a simple, resource-efficient, and highly parallelizable approach that makes CCSD(T)-quality calculations feasible where they would otherwise be prohibitively expensive.
PubMed: 37871170
DOI: 10.1021/acs.jpca.3c04591 -
Ecology and Evolution Oct 2023The western honey bee, , lives worldwide in approximately 102 million managed hives but also wild throughout much of its native and introduced range. Despite the... (Review)
Review
The western honey bee, , lives worldwide in approximately 102 million managed hives but also wild throughout much of its native and introduced range. Despite the global importance of as a crop pollinator, wild colonies have received comparatively little attention in the scientific literature and basic information regarding their density and abundance is scattered. Here, we review 40 studies that have quantified wild colony density directly ( = 33) or indirectly using genetic markers ( = 7) and analyse data from 41 locations worldwide to identify factors that influence wild colony density. We also compare the density of wild and managed colonies at a regional scale using data on managed colonies from the Food and Agriculture Organization (FAO). Wild colony densities varied from 0.1 to 24.2/km and were significantly lower in Europe (average of 0.26/km) than in Northern America (1.4/km), Oceania (4.4/km), Latin America (6.7/km) and Africa (6.8/km). Regional differences were not significant after controlling for both temperature and survey area, suggesting that cooler climates and larger survey areas may be responsible for the low densities reported in Europe. Managed colony densities were 2.2/km in Asia, 1.2/km in Europe, 0.2/km, in Northern America, 0.2/km in Oceania, 0.5/km in Latin America and 1/km in Africa. Wild colony densities exceeded those of managed colonies in all regions except Europe and Asia. Overall, there were estimated to be between two and three times as many wild colonies as managed worldwide. More wild colony surveys, particularly in Asia and South America, are needed to assess the relative density of wild and managed colonies at smaller spatial scales.
PubMed: 37841222
DOI: 10.1002/ece3.10609 -
Proceedings of the National Academy of... Dec 2023Establishing the fundamental chemical principles that govern molecular electronic quantum decoherence has remained an outstanding challenge. Fundamental questions such...
Establishing the fundamental chemical principles that govern molecular electronic quantum decoherence has remained an outstanding challenge. Fundamental questions such as how solvent and intramolecular vibrations or chemical functionalization contribute to the decoherence remain unanswered and are beyond the reach of state-of-the-art theoretical and experimental approaches. Here we address this challenge by developing a strategy to isolate electronic decoherence pathways for molecular chromophores immersed in condensed phase environments that enables elucidating how electronic quantum coherence is lost. For this, we first identify resonance Raman spectroscopy as a general experimental method to reconstruct molecular spectral densities with full chemical complexity at room temperature, in solvent, and for fluorescent and non-fluorescent molecules. We then show how to quantitatively capture the decoherence dynamics from the spectral density and identify decoherence pathways by decomposing the overall coherence loss into contributions due to individual molecular vibrations and solvent modes. We illustrate the utility of the strategy by analyzing the electronic decoherence pathways of the DNA base thymine in water. Its electronic coherences decay in [Formula: see text]30 fs. The early-time decoherence is determined by intramolecular vibrations while the overall decay by solvent. Chemical substitution of thymine modulates the decoherence with hydrogen-bond interactions of the thymine ring with water leading to the fastest decoherence. Increasing temperature leads to faster decoherence as it enhances the importance of solvent contributions but leaves the early-time decoherence dynamics intact. The developed strategy opens key opportunities to establish the connection between molecular structure and quantum decoherence as needed to develop chemical strategies to rationally modulate it.
PubMed: 38015846
DOI: 10.1073/pnas.2309987120 -
Investigative Ophthalmology & Visual... Sep 2023Hydroxychloroquine is an effective treatment for rheumatic diseases; however, retinal damage is a possible side effect. We aimed to identify the retinal area and related...
PURPOSE
Hydroxychloroquine is an effective treatment for rheumatic diseases; however, retinal damage is a possible side effect. We aimed to identify the retinal area and related risk factors associated with cone density reduction caused by hydroxychloroquine.
METHODS
We recorded the retinal images of patients with rheumatic diseases taking hydroxychloroquine (n = 44) and compared them with images of healthy controls (n = 107). Cone density was obtained in vertical and horizontal axes. Regions of decreased cone density and associations between age, rheumatic disease type, dosage for ideal body weight, and cone density were evaluated.
RESULTS
Cone densities were significantly lower in hydroxychloroquine-treated patients than in sex- and age-matched controls in the vertical axis (P < 0.001), with no significant difference in the horizontal axis (P = 0.120); in healthy elderly than in healthy young people in the horizontal axis (P < 0.001), with no significant difference in the vertical axis (P = 0.100); in hydroxychloroquine-treated elderly than in hydroxychloroquine-treated young patients in both axes (both P < 0.05); among patients with different rheumatic disease types, with no significant difference in the vertical axis (P = 0.294). The daily dose was negatively correlated with cone density in the vertical axis and inferior quadrant.
CONCLUSIONS
Hydroxychloroquine reduces retinal cone cell density in the vertical axis. Cone density loss in the horizontal axis increases with age; further, hydroxychloroquine dosage is negatively correlated with cone density in the vertical axis and inferior quadrant. Early screening of hydroxychloroquine-related retinal injury should consider changes in cone density in the vertical axis.
Topics: Aged; Humans; Adolescent; Hydroxychloroquine; Retinal Cone Photoreceptor Cells; Rheumatic Diseases; Retina; Eye Injuries; Retinal Diseases
PubMed: 37713205
DOI: 10.1167/iovs.64.12.29 -
CNS Neuroscience & Therapeutics Dec 2023We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We...
AIMS
We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We also investigated the association between clinical parameters and retinal changes in IH patients.
METHODS
Intracranial hypertension patients were divided into eyes with papilledema (IH-P) and eyes without papilledema (IH-WP). IH patients underwent lumbar puncture to measure intracranial pressure (ICP); visual acuity was performed using the Snellen chart. Optical coherence tomography (OCT) was used to image and measure the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) while OCT angiography was used to image and measure the superficial vascular complex (SVC) and deep vascular complex (DVC).
RESULTS
Intracranial hypertension patients showed reduced microvascular densities and thinner retinal thicknesses compared with the control group (all p < 0.001). Compared with the control group, IH-P showed reduced microvascular densities and thinner retinal thicknesses (all p < 0.001). IH-P showed reduced SVC density and thinner retinal thicknesses when compared with IH-WP (p = 0.008 for SVC, p = 0.025 for RNFL, and p = 0.018 for GCIPL). ICP correlated with the microvascular densities and GCIPL thickness in IH patients (p = 0.025 for GCIPL, p = 0.004 for SVC, and p = 0.002 for DVC). A significant association of ICP with SVC (p = 0.010) and DVC (p = 0.005) densities were also found in IH-P.
CONCLUSIONS
Given the observed differences in these noninvasive retinal imaging markers, further research into their clinical utility in IH is needed.
Topics: Humans; Papilledema; Intracranial Pressure; Retinal Ganglion Cells; Nerve Fibers; Intracranial Hypertension; Tomography, Optical Coherence
PubMed: 37287365
DOI: 10.1111/cns.14298 -
APL Bioengineering Dec 2023Safe and long-term electrical stimulation of neurons requires charge injection without damaging the electrode and tissue. A common strategy to diminish adverse effects...
Safe and long-term electrical stimulation of neurons requires charge injection without damaging the electrode and tissue. A common strategy to diminish adverse effects includes the modification of electrodes with materials that increases the charge injection capacity. Due to its high capacitance, the conducting polymer PEDOT:PSS is a promising coating material; however, the neural stimulation performance in terms of stability and safety remains largely unexplored. Here, PEDOT:PSS-coated platinum (Pt-PEDOT:PSS) microelectrodes are examined for neural stimulation and compared to bare platinum (Pt) electrodes. Microelectrodes in a bipolar configuration are used to deliver current-controlled, biphasic pulses with charge densities ranging from 64 to 255 C cm. Stimulation for 2 h deteriorates bare Pt electrodes through corrosion, whereas the PEDOT:PSS coating prevents dissolution of Pt and shows no degradation. Acute stimulation of primary cortical cells cultured as neurospheres shows similar dependency on charge density for Pt and Pt-PEDOT:PSS electrodes with a threshold of 127 C cm and increased calcium response for higher charge densities. Continuous stimulation for 2 h results in higher levels of cell survival for Pt-PEDOT:PSS electrodes. Reduced cell survival on Pt electrodes is most profound for neurospheres in proximity of the electrodes. Extending the stimulation duration to 6 h increases cell death for both types of electrodes; however, neurospheres on Pt-PEDOT:PSS devices still show significant viability whereas stimulation is fatal for nearly all cells close to the Pt electrodes. This work demonstrates the protective properties of PEDOT:PSS that can be used as a promising approach to extend electrode lifetime and reduce cell damage for safe and long-term neural stimulation.
PubMed: 38075207
DOI: 10.1063/5.0153094 -
Medical Physics Oct 2023Dosimetry in radionuclide therapy often requires the calculation of average absorbed doses within and between spatial regions, for example, for voxel-based dosimetry...
BACKGROUND
Dosimetry in radionuclide therapy often requires the calculation of average absorbed doses within and between spatial regions, for example, for voxel-based dosimetry methods, for paired organs, or across multiple tumors. Formation of such averages can be made in different ways, starting from different definitions.
PURPOSE
The aim of this study is to formally specify different averaging strategies for absorbed doses, and to compare their results when applied to absorbed dose distributions that are non-uniform within and between regions.
METHODS
For averaging within regions, two definitions of the average absorbed dose are considered: the simple average over the region (the region average) and the average when weighting by the mass density (density-weighted region average). The latter is shown to follow from the definition of mean absorbed dose according to the ICRU, and to be consistent with the MIRD formalism. For averaging between different spatial regions, three definitions follow: the volume-weighted, the mass-weighted, and the unweighted average. With respect to characterizing non-uniformity, the different average definitions lead to the use of dose-volume histograms (DVHs) (region average), dose-mass histograms (DMHs) (density-weighted region average), and unweighted histograms (unweighted average). Average absorbed doses are calculated for three worked examples, starting from the different definitions. The first, schematic, example concerns the calculation of the average absorbed dose between two regions with different volumes or mass densities. The second, stylized, example concerns voxel-based dosimetry, for which the average absorbed-dose rate within a region is calculated. The geometries studied include three Lu-filled voxelized spheres, where the sphere masses are held constant while the material compositions, densities, and volumes are varied. For comparison, the mean absorbed-dose rates obtained using unit-density sphere S-values are also included. The third example concerns SPECT/CT-based tumor dosimetry for five patients undergoing therapy with Lu-PSMA and six patients undergoing therapy with Lu-DOTA-TATE, for which the average absorbed-dose rates across multiple tumors are calculated. For the second and third examples, analyses also include representations by histograms.
RESULTS
Example 1 shows that the average absorbed doses, calculated using different definitions, can differ considerably if the masses and absorbed doses for two regions are markedly different. From example 2 it is seen that the density-weighted region average is stable under different activity and density distributions and is also in line with results using S-values. In contrast, the region average varies as function of the activity distribution. In example 3, the absorbed dose rates for individual tumors differ by (1.1 ± 4.3)% and (-0.1 ± 0.4)% with maximum deviations of +34.4% and -1.4% for Lu-PSMA and Lu-DOTA-TATE, respectively, when calculated as region averages or density-weighted region averages, with largest deviations obtained when the density is non-uniform. The average absorbed doses calculated across all tumors are similar when comparing mass-weighted and volume-weighted averages but these differ substantially from unweighted averages.
CONCLUSION
Different strategies for averaging of absorbed doses within and between regions can lead to substantially different absorbed-dose estimates. At reporting of radionuclide therapy dosimetry, it is important to specify the averaging strategy applied.
Topics: Humans; Radiopharmaceuticals; Radiometry; Single Photon Emission Computed Tomography Computed Tomography; Radioisotopes; Neoplasms
PubMed: 37272586
DOI: 10.1002/mp.16528