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British Medical Bulletin Dec 2023Osteoporosis results in reduced bone mass and consequent bone fragility. Small interfering RNAs (siRNAs) can be used for therapeutic purposes, as molecular targets or as... (Review)
Review
BACKGROUND
Osteoporosis results in reduced bone mass and consequent bone fragility. Small interfering RNAs (siRNAs) can be used for therapeutic purposes, as molecular targets or as useful markers to test new therapies.
SOURCES OF DATA
A systematic search of different databases to May 2023 was performed to define the role of siRNAs in osteoporosis therapy. Fourteen suitable studies were identified.
AREAS OF AGREEMENT
SiRNAs may be useful in studying metabolic processes in osteoporosis and identify possible therapeutic targets for novel drug therapies.
AREAS OF CONTROVERSY
The metabolic processes of osteoporosis are regulated by many genes and cytokines that can be targeted by siRNAs. However, it is not easy to predict whether the in vitro responses of the studied siRNAs and drugs are applicable in vivo.
GROWING POINTS
Metabolic processes can be affected by the effect of gene dysregulation mediated by siRNAs on various growth factors.
AREAS TIMELY FOR DEVELOPING RESEARCH
Despite the predictability of pharmacological response of siRNA in vitro, similar responses cannot be expected in vivo.
Topics: Humans; Osteoporosis; RNA, Small Interfering
PubMed: 37675799
DOI: 10.1093/bmb/ldad023 -
MethodsX Dec 2023The Broadband Internet industry is highly competitive, with service providers investing heavily in network development to meet customer demands and competing on pricing....
The Broadband Internet industry is highly competitive, with service providers investing heavily in network development to meet customer demands and competing on pricing. Effective cost management is crucial for profitability in this market. This work proposes a model for classifying broadband network devices based on text mining techniques applied to a device list from a leading broadband network company in Thailand. The device descriptions are used to generate a feature vector, which is then employed by a classification algorithm to categorize devices into core, access, and last mile hierarchies. Various algorithms including decision tree, naïve Bayes, Bayesian network, k-nearest neighbor, support vector machine, and deep neural network are compared, with support vector machine achieving the highest accuracy of 90.35%. The results are visualized to provide insights into network hierarchy, device replacement dates, and budget requirements, enabling support for cost management, budget planning, maintenance, and investment decision-making. The methodology outline includes,•Obtaining a device list from a major broadband network company and extracting device descriptions through text mining and generating a feature vector.•Using a support vector machine for classification and comparing algorithm performances.•Visualizing the results for actionable insights in cost management, budget planning, and investment decisions.
PubMed: 37674865
DOI: 10.1016/j.mex.2023.102346 -
Blood Advances Jul 2023Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the... (Clinical Trial)
Clinical Trial
Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the heterogeneity of these diseases has limited our understanding of these domains. The National Heart, Lung, and Blood Institute-sponsored MDS Natural History Study is a prospective cohort enrolling patients undergoing workup for suspected MDS in the setting of cytopenias. Untreated patients undergo bone marrow assessment with central histopathology review for assignment as MDS, MDS/myeloproliferative neoplasm (MPN), idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with <30% blasts, or "At-Risk." HRQoL data are collected at enrollment, including the MDS-specific Quality of Life in Myelodysplasia Scale (QUALMS). Vulnerability is assessed with the Vulnerable Elders Survey. Baseline HRQoL scores from 449 patients with MDS, MDS/MPN, AML <30%, ICUS or At-Risk were similar among diagnoses. In MDS, HRQoL was worse for vulnerable participants (eg, mean Patent-Reported Outcomes Management Information Systems [PROMIS] Fatigue of 56.0 vs 49.5; P < .001) and those with worse prognosis (eg, mean Euroqol-5 Dimension-5 Level [EQ-5D-5L] of 73.4, 72.7, and 64.1 for low, intermediate, and high-risk disease; P = .005). Among vulnerable MDS participants, most had difficulty with prolonged physical activity (88%), such as walking a quarter mile (74%). These data suggest that cytopenias leading to MDS evaluation are associated with similar HRQoL, regardless of eventual diagnosis, but with worse HRQoL among the vulnerable. Among those with MDS, lower-risk disease was associated with better HRQoL, but the relationship was lost among the vulnerable, showing for the first time that vulnerability trumps disease risk in affecting HRQoL. This study is registered at www.clinicaltrials.gov as NCT02775383.
Topics: Aged; Humans; Anemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Prospective Studies; Quality of Life
PubMed: 37146263
DOI: 10.1182/bloodadvances.2022009000 -
Physical Review. E Mar 2024Our understanding of the three basic states of matter (solids, liquids, and gases) is based on temperature and pressure phase diagrams with three phase transition lines:...
Our understanding of the three basic states of matter (solids, liquids, and gases) is based on temperature and pressure phase diagrams with three phase transition lines: solid-gas, liquid-gas, and solid-liquid lines. There are analytical expressions P(T) for the first two lines derived on a purely general-theoretical thermodynamic basis. In contrast, there exists no similar function for the third, melting, line (ML). Here, we develop a general two-phase theory of MLs and their analytical form. This theory predicts the parabolic form of the MLs for normal melting, relates the MLs to thermal and elastic properties of liquid and solid phases, and quantitatively agrees with experimental MLs in different system types. We show that the parameters of the ML parabola are governed by fundamental physical constants. In this sense, parabolic MLs possess universality across different systems.
PubMed: 38632732
DOI: 10.1103/PhysRevE.109.034122 -
Military Medicine Jul 2023Transgender individuals have served openly in the U.S. Military since 2016. Official policies for transgender servicemembers continue to evolve, including approaches to...
INTRODUCTION
Transgender individuals have served openly in the U.S. Military since 2016. Official policies for transgender servicemembers continue to evolve, including approaches to physical fitness testing of transgender servicemembers. There is a paucity of scientific data regarding the effects of gender affirming hormone therapy (GAHT) on athletic performance for the past 24 months of treatment. Identification of expected trends in performance during and after gender transition is essential to allow for the development of appropriate military policy regarding when to assess servicemembers' fitness by standards of their affirmed gender.
MATERIALS AND METHODS
We identified Department of the Air Force transgender patients using the Transgender Health Medical Evaluation Unit database and recorded dates of GAHT initiation through a retrospective chart review. We recorded performance values for the Air Force physical fitness test components 1 year before and up to 4 years after GAHT initiation. Performance measures were maximum sit-ups in 1 minute, push-ups in 1 minute, and 1.5-mile run time. Pre- and post-GAHT scores were compared using one-sample T-test to mean scores of Air Force-wide cisgender averages to assess for significant difference between affirmed transgender and cisgender airmen. We then performed the two one-sided test (TOST) procedure for equivalence with upper and lower bounds set at 1 SD from the means for cisgender airmen. Finally, using Z-scores, average transgender group scores were assigned a percentile rank with their respect to affirmed gender throughout the transition process.
RESULTS
Following initiation of GAHT, transgender males demonstrated statistically significant worse performance than cisgender males in all events until 3 years of GAHT. Their average scores would have attained a comfortable passing score within 1 year of GAHT. Transgender females' performance showed statistically significantly better performance than cisgender females until 2 years of GAHT in run times and 4 years in sit-up scores and remained superior in push-ups at the study's 4-year endpoint. TOST confirmed equivalence at all points where statistical difference was not demonstrated. Servicemembers approximate their pre-GAHT assigned gender percentile ranking in their affirmed gender in a manner consistent with hypothesis and TOST testing in the push-up event for both transgender males and females and in the 1.5-mile run event for transgender males.
CONCLUSIONS
In a sample of Air Force adult transgender patients, athletic performance measures demonstrate variable rates of change depending on the patients' affirmed gender and differ by physical fitness test component. Based on this study, transgender females should begin to be assessed by the female standard no later than 2 years after starting GAHT, while transgender males could be assessed by their affirmed standard no earlier than 3 years after initiating GAHT.
Topics: Humans; Transgender Persons; Male; Female; Retrospective Studies; Military Personnel; Adult; Physical Fitness; Exercise Test; United States
PubMed: 36271916
DOI: 10.1093/milmed/usac320 -
Reports on Progress in Physics.... Oct 2023Viewed as one of the grandest questions in modern science, understanding fundamental physical constants has been discussed in high-energy particle physics, astronomy and... (Review)
Review
Viewed as one of the grandest questions in modern science, understanding fundamental physical constants has been discussed in high-energy particle physics, astronomy and cosmology. Here, I review how condensed matter and liquid physics gives new insights into fundamental constants and their tuning. This is based on two observations: first, cellular life and the existence of observers depend on viscosity and diffusion. Second, the lower bound on viscosity and upper bound on diffusion are set by fundamental constants, and I briefly review this result and related recent developments in liquid physics. I will subsequently show that bounds on viscosity, diffusion and the newly introduced fundamental velocity gradient in a biochemical machine can all be varied while keeping the fine-structure constant and the proton-to-electron mass ratio intact. This implies that it is possible to produce heavy elements in stars but have a viscous planet where all liquids have very high viscosity (for example that of tar or higher) and where life may not exist. Knowing the range of bio-friendly viscosity and diffusion, we will be able to calculate the range of fundamental constants which favour cellular life and observers and compare this tuning with that discussed in high-energy physics previously. This invites an inter-disciplinary research between condensed matter physics and life sciences, and I formulate several questions that life science can address. I finish with a conjecture of multiple tuning and an evolutionary mechanism.
PubMed: 37811635
DOI: 10.1088/1361-6633/acfd3e -
Journal of Orthopaedic Surgery and... Sep 2023Percutaneous repair is a safe and reliable method to restore continuity after acute Achilles tendon ruptures, with a lower incidence of wound complications compared to...
Percutaneous repair is a safe and reliable method to restore continuity after acute Achilles tendon ruptures, with a lower incidence of wound complications compared to open techniques. We describe a novel percutaneous cruciate suture performed through 5 stab skin incisions, four of which are longitudinal and parallel to the course of the sural nerve to minimize the risk of injury and one transverse incision at the site of rupture, with a total of 16 suture threads and the knot outside the tendon body, increasing the tensile strength of the suture and minimizing the risk of re-rupture. Clinical studies are necessary to ascertain whether the theoretical advantages of the cruciate suture technique translate into better clinical outcomes compared to established percutaneous techniques.
Topics: Humans; Achilles Tendon; Tendon Injuries; Ankle Injuries; Dermatologic Surgical Procedures; Neurosurgical Procedures
PubMed: 37700324
DOI: 10.1186/s13018-023-04167-9 -
BioRxiv : the Preprint Server For... Aug 2023The extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular...
The extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular smooth muscle cells (VSMCs) are essential for vessel repair and, via their secretome, are able to invade from the vessel media into the intima to mediate ECM remodelling. Accumulation of fibronectin (FN) is a hallmark of early vascular repair and atherosclerosis and here we show that FN stimulates VSMCs to secrete small extracellular vesicles (sEVs) by activating the β1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. Spatially, sEV were secreted via filopodia-like cellular protrusions at the leading edge of migrating cells. We found that sEVs are trapped by the ECM and colocalise with FN in symptomatic atherosclerotic plaques . Functionally, ECM-trapped sEVs induced the formation of focal adhesions (FA) with enhanced pulling forces at the cellular periphery. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI. assays identified collagen VI as playing the key role in cell adhesion and invasion. Taken together our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collage VI enriched sEVs by VSMCs. These sEVs stimulate migration and invasion by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction forces to enable VSMC movement within the complex vascular ECM network.
PubMed: 37645762
DOI: 10.1101/2023.08.17.551257 -
Sensors (Basel, Switzerland) Oct 2023To study and monitor the adverse health consequences of using electronic cigarettes, a user's puff topography, which are quantification parameters of the user's vaping...
To study and monitor the adverse health consequences of using electronic cigarettes, a user's puff topography, which are quantification parameters of the user's vaping habits, plays a central role. In this work, we introduce a topography sensor to measure the mass of total particulate matter generated in every puff and to estimate the nicotine yield. The sensor is compact and low-cost, and is integrated into the electronic cigarette device to promptly and conveniently monitor the user's daily puff topography. The topography sensor is comprised of a photometric sensor and a pressure sensor. The photometric sensor measures the mass concentration of the aerosol, based on scattering of near-infrared light from airborne particles, while the pressure sensor measures the flow rate. The topography sensor was tested under various conditions including a wide range of atomizer power, puff duration, and inhalation pressure. The sensor's accuracy was validated by comparing the sensor's readings with reference measurements, and the results matched closely with the trends reported by existing studies on electronic cigarettes. An example application for tracking a user's puff topography was also demonstrated. Our topography sensor holds great promise in mitigating the health risks of vaping, and in promoting quality control of electronic cigarette products.
Topics: Electronic Nicotine Delivery Systems; Nicotine; Vaping; Aerosols; Nebulizers and Vaporizers
PubMed: 37837050
DOI: 10.3390/s23198220 -
Ophthalmic Plastic and Reconstructive...Plexiform schwannoma of the lacrimal gland of the palpebral lobe has not been previously described. This 41-year-old male presented with a 2-year history of a left upper...
Plexiform schwannoma of the lacrimal gland of the palpebral lobe has not been previously described. This 41-year-old male presented with a 2-year history of a left upper eyelid mass and associated regional irritation. MRI of the head and orbits confirmed a left superolateral multinodular mass centered on the palpebral lobe of the left lacrimal gland. Excision revealed a schwannoma of the plexiform subtype.
Topics: Male; Humans; Adult; Neurilemmoma; Eyelids; Lacrimal Apparatus; Magnetic Resonance Imaging; Inflammation
PubMed: 38133625
DOI: 10.1097/IOP.0000000000002572