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MedRxiv : the Preprint Server For... Jun 2024Advances in the development of neurotechnologies have the potential to revolutionize treatment of brain-based conditions. However, a critical concern revolves around the...
BACKGROUND
Advances in the development of neurotechnologies have the potential to revolutionize treatment of brain-based conditions. However, a critical concern revolves around the willingness of the public to embrace these technologies, especially considering the tumultuous histories of certain neurosurgical interventions. Therefore, examining public attitudes is paramount to uncovering potential barriers to adoption ensuring ethically sound innovation.
METHODS
In the present study, we investigate public attitudes towards the use of four neurotechnologies (within-subjects conditions): deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), pills, and MRI-guided focused ultrasound (MRgFUS) as potential treatments to a person experiencing either mood, memory, or motor symptoms (between-subjects conditions). US-based participants (N=1052; stratified to be nationally representative based on sex, race, age) were asked about their perceptions of risk, benefit, invasiveness, acceptability, perceived change to the person, and personal interest in using these neurotechnologies for symptom alleviation.
RESULTS
Descriptive results indicate variability between technologies that the U.S. public is willing to consider if experiencing severe mood, memory, or motor symptoms. The main effect of neurotechnology revealed DBS was viewed as the most invasive and risky treatment and was perceived to lead to the greatest change to who someone is as a person. DBS was also viewed as least likely to be personally used and least acceptable for use by others. When examining the main effects of symptomatology, we found that all forms of neuromodulation were perceived as significantly more beneficial, acceptable, and likely to be used by participants for motor symptoms, followed by memory symptoms, and lastly mood symptoms. Neuromodulation (averaging across neurotechnologies) was perceived as significantly riskier, more invasive, and leading to a greater change to person for mood versus motor symptoms; however, memory and motor symptoms were perceived similarly with respect to risk, invasiveness, and change to person.
CONCLUSION
These results suggest that the public views neuromodulatory approaches that require surgery (i.e., DBS and MRgFUS) as riskier, more invasive, and less acceptable than those that do not. Further, findings suggest individuals may be more reluctant to alter or treat psychological symptoms with neuromodulation compared to physical symptoms.
PubMed: 38946963
DOI: 10.1101/2024.06.09.24308176 -
Cancer Innovation Apr 2024Synovial sarcoma (SS) is an fusion gene-driven soft tissue sarcoma with mesenchymal characteristics, associated with a poor prognosis due to frequent metastasis to a...
BACKGROUND
Synovial sarcoma (SS) is an fusion gene-driven soft tissue sarcoma with mesenchymal characteristics, associated with a poor prognosis due to frequent metastasis to a distant organ, such as the lung. Histone deacetylase (HDAC) inhibitors (HDACis) are arising as potent molecular targeted drugs, as HDACi treatment disrupts the SS oncoprotein complex, which includes HDACs, in addition to general HDACi effects. To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells, we examined cellular responses to HDACi treatment in combination with two-dimensional (2D) and 3D culture conditions.
METHODS
Using several SS cell lines, biochemical and cell biological assays were performed with romidepsin, an HDAC1/2 selective inhibitor. SN38 was concomitantly used as an ameliorant drug with romidepsin treatment. Cytostasis, apoptosis induction, and MHC class I polypeptide-related sequence A/B (MICA/B) induction were monitored to evaluate the drug efficacy. In addition to the conventional 2D culture condition, spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.
RESULTS
By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells, we observed that responsiveness is diverse in each cell line. In the apoptotic inducible cells, co-treatment with SN38 enhanced cell death. In nonapoptotic inducible cells, cytostasis and MICA/B induction were observed, and SN38 improved MICA/B induction further. As a novel efficacy of SN38, we revealed TWIST1 suppression in SS cells. In the spheroid (3D) condition, romidepsin efficacy was severely restricted in TWIST1-positive cells. We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form, and concomitant SN38 treatment along with romidepsin reproduced the reaction.
CONCLUSIONS
The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.
PubMed: 38946933
DOI: 10.1002/cai2.113 -
BME Frontiers 2024: We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release. : This design is inspired by the skin baroreceptors, which are...
: We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release. : This design is inspired by the skin baroreceptors, which are mechanosensitive elements of the peripheral nervous system. We adopt the finger touching to trigger the electric stimulation, ensuring a fast-response and user-friendly administration with potentially minimal off-target effects. : Chronic skin diseases bring about large, recurrent skin damage and often require convenient and timely transdermal treatment. Traditional methods lack spatiotemporal controllable dosage, leaving a risk of skin irritation or drug resistance issues. : The patch consists of drug-containing microneedles and stretchable electrode array. The electrode array, integrated with the piezoconductive switch and flexible battery, provides a mild electric current only at the spot that is pressed. Drugs in microneedles will then flow along the current into the skin tissues. The stretchable feature also provides the mechanical robustness and electric stability of the device on large skin area. : This device delivers Cy3 dye in pig skin with spatiotemporally controlled dosage, showing ~8 times higher fluorescence intensity than the passive delivery. We also deliver insulin and observe the reduction of the blood glucose level in the mouse model upon pressing. Compared with passive delivery without pressing, the dosage of drugs released by the simulation is 2.83 times higher. : This baroreceptor-inspired microneedle skin patch acts as a good example of the biomimicking microneedle device in the precise control of the drug release profile at the spatiotemporal resolution.
PubMed: 38946867
DOI: 10.34133/bmef.0044 -
World Journal of Gastrointestinal... Jun 2024At present, laparoscopic cholecystectomy (LC) is the main surgical treatment for gallstones. But, after gallbladder removal, there are many complications. Therefore, it...
BACKGROUND
At present, laparoscopic cholecystectomy (LC) is the main surgical treatment for gallstones. But, after gallbladder removal, there are many complications. Therefore, it is hoped to remove stones while preserving the function of the gallbladder, and with the development of endoscopic technology, natural orifice transluminal endoscopic surgery came into being.
AIM
To compare the quality of life, perioperative indicators, adverse events after LC and transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery (EGPS) in patients with gallstones.
METHODS
Patients who were admitted to The First Affiliated Hospital of Xinjiang Medical University from 2020 to 2022 were retrospectively collected. We adopted propensity score matching (1:1) to compare EGPS and LC patients.
RESULTS
A total of 662 cases were collected, of which 589 cases underwent LC, and 73 cases underwent EGPS. Propensity score matching was performed, and 40 patients were included in each of the groups. In the EGPS group, except the gastrointestinal defecation ( = 0.603), the total score, physical well-being, mental well-being, and gastrointestinal digestion were statistically significant compared with the preoperative score after surgery ( < 0.05). In the LC group, except the mental well-being, the total score, physical well-being, gastrointestinal digestion, the gastrointestinal defecation was statistically significant compared with the preoperative score after surgery ( < 0.05). When comparing between groups, gastrointestinal defecation had significantly difference ( = 0.002) between the two groups, there was no statistically significant difference in the total postoperative score and the other three subscales. In the surgery duration, hospital stay and cost, LC group were lower than EGPS group. The recurrence factors of gallstones after EGPS were analyzed: and recurrence was not correlated with gender, age, body mass index, number of stones, and preoperative score.
CONCLUSION
Whether EGPS or LC, it can improve the patient's symptoms, and the EGPS has less impact on the patient's defecation. It needed to, prospective, multicenter, long-term follow-up, large-sample related studies to prove.
PubMed: 38946854
DOI: 10.4253/wjge.v16.i6.318 -
Biomedical Engineering Letters Jul 2024As silicon photomultiplier (SiPM)-based time-of-flight (TOF) positron emission tomography (PET) becomes popular, the need for sophisticated PET data acquisition (DAQ)...
As silicon photomultiplier (SiPM)-based time-of-flight (TOF) positron emission tomography (PET) becomes popular, the need for sophisticated PET data acquisition (DAQ) systems is increasing. One promising solution to this challenge is the adoption of a field-programmable gate array (FPGA)-only signal digitization method. In this paper, we propose a new approach to efficiently implement an FPGA-only digitizer. We configured the input/output (IO) port of the FPGA to function as a dual-threshold voltage comparator through the use of simple passive circuitry and heterogeneous IO standards. This configuration overcomes the limitations of existing methods by allowing different threshold voltages for adjacent IO pins, effectively reducing routing complexity and lowering manufacturing costs. An FPGA-only digitizer was implemented by integrating the dual-threshold voltage comparator and FPGA-based time-to-digital converter. By combining the dual-threshold time-over-threshold (TOT) method and curve fitting, precise energy information could be obtained. The performance of the FPGA-only digitizer was assessed using a detector setup comprising a 3 × 3 × 20 mm LYSO scintillation crystal and a single pixel SiPM. Using the configured evaluation setup, an energy resolution of 12.5% and a time resolution of 146 ± 9 ps were achieved for a 20 mm scintillation crystal. The dual-threshold TOT implemented using the proposed method showed consistent linearity across an energy range of 100 keV to 600 keV. The proposed method is well-suited for the development of cost-effective DAQ systems in highly integrated TOF PET systems.
PubMed: 38946816
DOI: 10.1007/s13534-024-00380-5 -
PRiMER (Leawood, Kan.) 2024According to self-determination theory (SDT), fulfillment of three basic psychological needs-autonomy, competence, and relatedness-positively impacts people's health and...
BACKGROUND AND OBJECTIVES
According to self-determination theory (SDT), fulfillment of three basic psychological needs-autonomy, competence, and relatedness-positively impacts people's health and well-being. Amid the COVID-19 pandemic, an accelerated adoption of virtual care practices coincided with a decline in the well-being of physicians. Taking into account the frequency of virtual care use, we examined the relationship between workplace need fulfillment and physician well-being.
METHODS
Using online survey methodology, in March through June 2022, we collected data from 156 family physicians (FPs) in Alberta, Canada. The survey contained scales that measured workplace need satisfaction and frustration, subjective well-being (physical, psychological, and relational), and frequency of virtual care use. We performed correlational and regression analyses of the data.
RESULTS
More frequent use of virtual care was associated with lower relatedness satisfaction among FPs. Controlling for the frequency of virtual care use, frustration of autonomy and competence needs negatively related to FPs' physical well-being; frustration of competence and relatedness needs negatively related to their psychological and relational well-being.
CONCLUSIONS
Findings from this study align with SDT and underscore the importance of supporting FPs' basic psychological needs, while we work to integrate virtual care into clinical practice. In their day-to-day work, we encourage physicians to reflect on their own sense of autonomy, competence, and relatedness, and consider how using virtual care aligns with these basic needs.
PubMed: 38946752
DOI: 10.22454/PRiMER.2024.690812 -
Journal of Indian Prosthodontic Society Jul 2024Assessment of occlusion changes during laboratory phase of relining is essential to evaluate the occlusal discrepancies that could get incorporated in the denture with...
AIM
Assessment of occlusion changes during laboratory phase of relining is essential to evaluate the occlusal discrepancies that could get incorporated in the denture with the use of different relining materials. Since the long term stability and functional success of the denture is heavily influenced by occlusion, an In-vitro study to assess these changes after relining is warranted. The aim of the study is to evaluate the changes in occlusion during laboratory phase of relining procedure.
SETTINGS AND DESIGN
This is an in vitro study with a total of 30 specimen.
MATERIALS AND METHODOLOGY
A total of 30 maxillary standardized dentures were fabricated after mounting on a semi adjustable articulator. These samples will be divided into three groups based on the relining material used (Autopolymerizing resin, Heat-cure resin, Tissue conditioner). The vertical dimension, Centric contact points and eccentric contact points were measured before and after relining.
STATISTICAL ANALYSIS USED
The variables were tested to see if they had a normal distribution using the Shapiro-Wilk test. Parametric distribution was seen for ECP leading to further comparison using one way analysis of variance (ANOVA). Non-parametric distribution was found while testing the VD, CCP leading to adoption of Kruskal-wallis test for comparison of groups. Dunn Bonferroni test was done for VD since results were significant.
RESULTS
The results of this in-vitro study showed statistically significant difference with respect to change in vertical dimension in all groups pre and post relining (P = 0.005). The centric contact points showed lesser variation in position when comparing the pre to the post relining phase with the use of autopolymerising resins, whereas heat cure resins and tissue conditioners showed statistically significant difference in the centric point contacts post relining. No statistically significant changes were seen in eccentric occlusion post relining in all groups. Tissue conditioners showed minimum mean changes in eccentric contacts.
CONCLUSION
Within the limitations of this study, the use of autopolymerising resins depicted the most stable results with respect to occlusion, for relining of dentures.
Topics: Humans; In Vitro Techniques; Dental Occlusion; Denture Retention; Dental Materials; Denture Liners
PubMed: 38946509
DOI: 10.4103/jips.jips_363_23 -
Orthopaedic Surgery Jun 2024Periprosthetic femoral fractures (PPFFs) following total hip arthroplasty (THA) present a significant clinical challenge due to their increasing incidence with an aging... (Review)
Review
Periprosthetic femoral fractures (PPFFs) following total hip arthroplasty (THA) present a significant clinical challenge due to their increasing incidence with an aging population and evolving surgical practices. Historically, classifications were primarily based on anatomical fracture location, the stability of the implant, and bone quality surrounding the implant. We critically analyzed 25 classification systems, highlighting the emergence and adaptations of key systems such as the Vancouver classification system (VCS) and the Unified classification system (UCS), which are lauded for their simplicity and effectiveness yet require further refinement. VCS, developed in 1995, categorizes fractures based on the site, implant stability, and bone quality, and remains widely used due to its robust applicability across different clinical settings. Introduced in 2014, UCS expands the VCS to encompass all periprosthetic fractures with additional fracture types, aiming for a universal application. Despite their widespread adoption, these systems exhibit shortcomings, including the incomplete inclusion of all PPFF types and the imprecise assessment of implant stability and surrounding bone loss. These gaps can result in misclassification and suboptimal treatment outcomes. This paper suggests the necessity for ongoing improvements in classification systems to include emerging fracture types and refined diagnostic criteria, ensuring that they remain relevant to contemporary orthopedic practices and continue to facilitate the precise tailoring of treatment to patient-specific circumstances. This comprehensive historical review serves as a foundation for future innovations in classification systems, ultimately aiming to standardize PPFF treatment and improve patient prognosis.
PubMed: 38946014
DOI: 10.1111/os.14149 -
Chemical & Pharmaceutical Bulletin 2024In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry...
In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.
Topics: Tablets; Particle Size; Drug Compounding; Powders; Stearic Acids; Tensile Strength; Excipients; Solubility
PubMed: 38945947
DOI: 10.1248/cpb.c23-00801 -
The Journal of Biological Chemistry Jun 2024The CD1 family of antigen-presenting molecules adopt a Major Histocompatibility Complex class I (MHC-I) fold. Whereas MHC molecules present peptides, the CD1 family has... (Review)
Review
The CD1 family of antigen-presenting molecules adopt a Major Histocompatibility Complex class I (MHC-I) fold. Whereas MHC molecules present peptides, the CD1 family has evolved to bind self- and foreign-lipids. The CD1 family of antigen-presenting molecules comprises four members, CD1a, CD1b, CD1c, CD1d, that differ in their architecture around the lipid-binding cleft, thereby enabling diverse lipids to be accommodated. These CD1-lipid complexes are recognised by T cell receptors (TCRs) expressed on T cells, either through dual recognition of CD1 and lipid or in a new model whereby the TCR directly contacts CD1, thereby triggering an immune response. Chemical syntheses of lipid antigens, and analogues thereof, have been crucial in understanding the underlying specificity of T cell-mediated lipid immunity. This review will focus on our current understanding of how TCRs interact with CD1-lipid complexes, highlighting how it can be fundamentally different from TCR-MHC-peptide co-recognition.
PubMed: 38945451
DOI: 10.1016/j.jbc.2024.107511