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1.
J Orthop ; 59: 30-35, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39351268

ABSTRACT

Introduction: The prevalence of total shoulder arthroplasties is on the rise annually. Improvements in implant quality, construct stability, and surgical techniques have notably enhanced post-operative results, prompting an expansion of indications for shoulder arthroplasty. Despite its high success rate, opportunities for enhancement remain, especially in preoperative planning and intraoperative execution. Advanced imaging technologies offer significant potential in optimizing implant placement, thus improving the longevity of the procedure. To our knowledge, a comprehensive review examining the impact of advanced imaging on shoulder arthroplasty has yet to be conducted. This systematic review aims to investigate the benefits of advanced imaging technologies in this context, focusing on their application in preoperative planning, osteoarthritis assessment, intraoperative adjustments, patient-specific instrumentation, and navigational aids. Methods: This review utilized a comprehensive search of PubMed to identify relevant studies published from 2000 to 2024, focusing on the application of various imaging techniques in shoulder arthroplasty. The search was conducted by two authors and centered on plain radiography, CT scans, and MRI. The selection criteria included availability of full-text articles, English language, direct comparison of imaging techniques, and a focus on patient outcomes, including discussions on broader applications such as intraoperative navigation and patient-specific instrumentation development. Results: Enhanced imaging techniques, particularly CT scans and MRIs, have been shown to significantly improve outcomes in shoulder arthroplasty. While plain radiographs remain standard, CT scans provide superior bony detail, crucial for evaluating glenoid wear and determining augmentation needs. Preoperative CT imaging has been demonstrated to enhance implant placement accuracy. Moreover, intraoperative technologies based on CT imaging, such as patient-specific instrumentation and navigation systems, contribute to better surgical results. Conclusion: The benefits of CT imaging in shoulder arthroplasty significantly outweigh the associated costs. Current literature strongly supports the adoption of CT imaging in these procedures, particularly when used alongside modern operative technologies.

2.
Angew Chem Int Ed Engl ; : e202408704, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39388344

ABSTRACT

Ultra-fast magic-angle spinning (100+ kHz) has revolutionized solid-state NMR of biomolecular systems but has so far failed to gain ground for the analysis of paramagnetic organic and inorganic powders, despite the potential rewards from substantially improved spectral resolution. The principal blockages are that the smaller fast-spinning rotors present significant barriers for sample preparation, particularly for air/moisture-sensitive systems, and are associated with lower sensitivity from the reduced sample volumes. Here these difficulties are overcome by improvements in rotor ceramics and handling methods that enable the routine use of this setup for repetitive, high-throughput analysis of sensitive samples. Furthermore, we demonstrate that the sensitivity penalty is less severe than expected for highly paramagnetic solids and is more than offset by the associated improved resolution. While previous approaches employing slower MAS are often unsuccessful in providing sufficient resolution, we show that ultra-fast 100+ kHz MAS allows site-specific assignments of all resonances from complex paramagnetic solids. This opens the way to routine characterisation of geometry and electronic structures of functional paramagnetic systems in chemistry, including catalysts and battery materials. We benchmark this approach on a hygroscopic luminescent Tb3+ complex, an air-sensitive homogeneous high-spin Fe2+ catalyst, and a series of mixed Fe2+/Mn2+/Mg2+ olivine-type cathode materials.

3.
ACS Omega ; 9(38): 39564-39572, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39346869

ABSTRACT

Interferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain and is a conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins through a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 has been crystallized in both monomeric and dimeric forms, but its functional state remains unclear. Here, we used a combined approach of small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy to characterize UbcH8's oligomeric state in solution. SAXS revealed a dimeric UbcH8 structure that could be dissociated when fused N-terminally to glutathione S-transferase. NMR spectroscopy validated the presence of a concentration-dependent monomer-dimer equilibrium and suggested a back-side dimerization interface. Chemical shift perturbation and peak intensity analysis further suggest dimer-induced conformational dynamics at the E1 and E3 interfaces, providing hypotheses for the protein's functional mechanisms. Our study highlights the power of combining NMR and SAXS techniques to provide structural information about proteins in solution.

4.
J Am Heart Assoc ; 13(18): e035859, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39248259

ABSTRACT

BACKGROUND: Direct oral anticoagulants (DOACs) have complex dosing regimens and are often incorrectly prescribed. We evaluated a nationwide DOAC population management dashboard rollout whose purpose includes pharmacist review and correction of off-label dosing prescriptions. METHODS AND RESULTS: Using data from Veterans Health Affairs, we identified all patients prescribed DOACs for atrial fibrillation or venous thromboembolism between August 2015 and December 2019. Sites were grouped on the basis of the timing of moderate-high usage of the DOAC population management tool dashboard. Effectiveness was defined as the monthly rate of off-label DOAC prescribing and the rate of clinical adverse events (bleeding, composite of stroke or venous thromboembolism). Implementation was evaluated as the percentage of off-label DOAC prescriptions changed within 7 days. Among the 128 652 patients receiving DOAC therapy at 123 centers, between 6.9% and 8.6% had off-label DOAC prescriptions. Adoption of the DOAC population management tool dashboard before July 2018 was associated with a decline in off-label dosing prescriptions (8.7%-7.6%). Only 1 group demonstrated a significant reduction in monthly rates of bleeding following implementation. All sites experienced a reduction in the composite of venous thromboembolism or stroke following dashboard adoption. There was no difference in the implementation outcome of DOAC prescription change within 7 days in any of the adoption groups. CONCLUSIONS: Early adoption of the DOAC population management tool dashboard was associated with decreased rates of off-label DOAC dosing prescription and reduced bleeding. Following adoption of the DOAC population management tool dashboard, all sites experienced reductions in venous thromboembolism and stroke events.


Subject(s)
Atrial Fibrillation , Off-Label Use , Pharmacists , Venous Thromboembolism , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , United States , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control , Venous Thromboembolism/epidemiology , Female , Male , Aged , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Stroke/prevention & control , Stroke/epidemiology , Administration, Oral , Anticoagulants/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Factor Xa Inhibitors/administration & dosage , Practice Patterns, Physicians'/standards , Drug Prescriptions/statistics & numerical data , United States Department of Veterans Affairs
5.
World J Mens Health ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39344113

ABSTRACT

There is a natural balance between the major sex steroids, testosterone and estradiol, controlled by gonadal secretion and peripheral conversion by aromatase. This balance is impacted by a variety of inborn and acquired conditions, and, more recently, by a growing use of exogenous testosterone therapy and off-label aromatase use under the guise of "men's health." We summarize reported testosterone:estradiol ratios, both naturally occurring and with pharmacologic manipulation and consider the ramifications of significant changes in these ratios. However, significant limitations exist in terms of steroid separation and measurement techniques, timing of samples, and lack of consistency from one assay to another, as well as definition of normative data. Limited data on the testosterone:estradiol ratio in men exists, particularly due to the scan data on concurrent estradiol values in men receiving testosterone therapy or aromatase inhibitors. Nonetheless, there seems to be a range of apparently beneficial values of the testosterone: estradiol radio at between 10 and 30, calculated as: testosterone in ng/dL/estradiol in pg/mL. Higher values appear to be associated with improved spermatogenesis and reduced bone density while lower values are associated with thyroid dysfunction. While there is growing awareness of the significance of the testosterone:estradiol ratio, and a sense of a desired range, the optimal value has not yet been determined. Further work is needed to clarify the measurement strategies and clearly-defined outcome measures related to the testosterone:estradiol ratio.

6.
Ther Adv Urol ; 16: 17562872241281574, 2024.
Article in English | MEDLINE | ID: mdl-39345303

ABSTRACT

Background: Artificial urinary sphincter (AUS) placement remains the gold-standard treatment for post-prostatectomy urinary incontinence (PPUI), despite their need for periodic surgical revision. Objective: To understand the experiences of patients who undergo repeat AUS revisions. Design: Mixed design including quantitative surveys and qualitative interviews for thematic analysis. Methods: Men with ⩾2 revisions were collected from a single-institution, retrospective database of AUS patients. Participants were interviewed about their prostatectomy, incontinence, AUS placement, and revisions. A survey was administered utilizing validated tools (e.g., Decision Regret Scale (DRS), Incontinence Impact Questionnaire-7) for quantitative analysis. Interview transcripts were used for qualitative thematic analysis. Results: Of 26 respondents, 20 completed the interview. Twenty-three men completed the survey. The mean DRS score for prostatectomy was 24 (standard deviation (SD) = 27), indicating low regret. Median Incontinence Impact Questionnaire score was 54 (SD = 27), with 70% of participants describing their PPUI as "severe." Participants experienced a significant decrease in daily pad usage with AUS placement (5.5 pre-AUS vs 1.4 post-AUS, p < 0.0001). Qualitative analysis revealed themes involving prostatectomy urgency, physician-patient relationships, expectation setting, and quality of follow-up. Most participants (96%) were satisfied with their initial AUS placement and endorsed a positive relationship with their urologist. However, 22% of participants were unaware of device limitations, including the need for revision. Some participants (26%) were uncertain of the status of their AUS, while some participants (35%) desired improved follow-up. Conclusions: Initial improvement and positive experiences with urologists motivate patients to undergo AUS repeat revision. Urologists should emphasize the limitations of the AUS before placement and follow up with patients to evaluate their needs for future care.

7.
Bone Jt Open ; 5(9): 758-765, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39260450

ABSTRACT

Aims: Patient dissatisfaction following primary total knee arthroplasty (TKA) with manual jig-based instruments has been reported to be as high as 30%. Robotic-assisted total knee arthroplasty (RA-TKA) has been increasingly used in an effort to improve patient outcomes, however there is a paucity of literature examining patient satisfaction after RA-TKA. This study aims to identify the incidence of patients who were not satisfied following RA-TKA and to determine factors associated with higher levels of dissatisfaction. Methods: This was a retrospective review of 674 patients who underwent primary TKA between October 2016 and September 2020 with a minimum two-year follow-up. A five-point Likert satisfaction score was used to place patients into two groups: Group A were those who were very dissatisfied, dissatisfied, or neutral (Likert score 1 to 3) and Group B were those who were satisfied or very satisfied (Likert score 4 to 5). Patient demographic data, as well as preoperative and postoperative patient-reported outcome measures, were compared between groups. Results: Overall, 45 patients (6.7%) were in Group A and 629 (93.3%) were in Group B. Group A (vs Group B) had a higher proportion of male sex (p = 0.008), preoperative chronic opioid use (p < 0.001), preoperative psychotropic medication use (p = 0.01), prior anterior cruciate ligament (ACL) reconstruction (p < 0.001), and preoperative symptomatic lumbar spine disease (p = 0.004). Group A was also younger (p = 0.023). Multivariate analysis revealed preoperative opioid use (p = 0.012), prior ACL reconstruction (p = 0.038), male sex (p = 0.006), and preoperative psychotropic medication use (p = 0.001) as independent predictive factors of patient dissatisfaction. Conclusion: The use of RA-TKA demonstrated a high rate of patient satisfaction (629 of 674, 93.3%). Demographics for patients not satisfied following RA-TKA included: male sex, chronic opioid use, chronic psychotropic medication use, and prior ACL reconstruction. Patients in these groups should be identified preoperatively and educated on realistic expectations given their comorbid conditions.

8.
Mayo Clin Proc ; 99(9): 1500-1517, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39115509

ABSTRACT

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs.


Subject(s)
Cardiovascular Diseases , Erectile Dysfunction , Phosphodiesterase 5 Inhibitors , Humans , Male , Erectile Dysfunction/drug therapy , Erectile Dysfunction/therapy , Erectile Dysfunction/etiology , Erectile Dysfunction/diagnosis , Phosphodiesterase 5 Inhibitors/therapeutic use , Consensus
9.
Front Physiol ; 15: 1369120, 2024.
Article in English | MEDLINE | ID: mdl-39100273

ABSTRACT

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-ß-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD.

10.
Braz J Microbiol ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39155341

ABSTRACT

The objective of this study was to determine the prevalence of Streptococcus equi (S. equi subsp equi and S. equi subsp zooepidemicus) in the state of Santa Catarina and evaluate the antimicrobial susceptibility of the isolates. For this, 420 nasal swab samples were collected from randomly selected horses. Isolation and phenotypic characterization of the bacteria were performed by sowing on 5% sheep blood agar, followed by analysis of morphotinctorial characteristics and biochemical analysis. To differentiate the main beta-hemolytic Streptococcus in horses, the fermentation profiles of the sugar's lactose, maltose, sorbitol, and trehalose were used, which were confirmed at the subspecies level by the PCR technique. The antimicrobial susceptibility panel was defined by the disk diffusion method, testing 13 antimicrobials from ten different classes, all regularly used in equine medical clinics, followed by the calculation of the multiple antimicrobial resistance index. Ten strains of S. equi were isolated, with a prevalence of 2.38% (10/420). Of the total positive samples, 3% (3/10) were confirmed as belonging to S. equi subsp equi and 70% (7/10) were confirmed as belonging to S. zooepidemicus. Multidrug resistance was observed in 60% (6/10) of isolates. The antimicrobial with the greatest resistance was clindamycin with 70% (7/10), followed by beta-lactams, with 40% (4/10) resistance to penicillin and 30% (3/10) to ceftiofur. The isolates were 100% (10/10) sensitive to gentamicin, chloramphenicol, levofloxacin, and vancomycin. This was the first study carried out in the state, and based on these data, it can be said that Santa Catarina has a low prevalence of S. equi and the presence of multi-resistant strains of S. equi was confirmed in the equine herd in Santa Catarina.

12.
Front Psychiatry ; 15: 1432864, 2024.
Article in English | MEDLINE | ID: mdl-39045548

ABSTRACT

Objective: In order to gain a better understanding of the individual and joint impact of testosterone and cortisol on behavior, the present study was developed to test the differences in each hormone alone and conjointly between perpetrators of IPV and non-violent controls. Method: Perpetrators of IPV on probation were compared to a control group of non-aggressive males from Hidalgo County in the Rio Grande Valley on baseline testosterone and cortisol, as well as several relevant questionnaires measuring aggression and trait anger. Differences in cortisol following exposure to a stressful event were also examined. Procedures included two laboratory visits consisting of questionnaires, a number of salivary testosterone and cortisol collections, and exposure to a stressor. Results: Perpetrators had higher basal testosterone and post stressor cortisol levels than non- violent controls as well as a higher T/C ratio. In addition, trait anger moderated the relationship between both testosterone alone, and the testosterone/cortisol ratio and perpetration of IPV. Conclusion: Results are consistent with the hypothesis that testosterone leads to antisocial behavior, including perpetration of violence. The results are also consistent with the dual hormone hypothesis, i.e., that testosterone and cortisol work together to jointly regulate social dominance and aggression. Both the increased freestanding testosterone and the increased cortisol following exposure to stress places these men at risk for perpetrating violence. Clinical implications are discussed.

14.
bioRxiv ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38948796

ABSTRACT

Rationale: Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication. Objectives: Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV. Methods: Male and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM). Results: Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV1-Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes. Conclusions: Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.

15.
Urology ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972393

ABSTRACT

OBJECTIVE: To evaluate predictors of implant length for men undergoing primary IPP placement. METHODS: A multicenter, retrospective cohort study was performed for men undergoing primary IPP placement at 16 high-volume surgical centers. Patient demographics, comorbidities, operative approach, and implanted cylinder and rear-tip extender length were recorded. Associations between potential preoperative and intraoperative predictors of total device length were tested using non-parametric correlation and Kruskal-Wallis tests, followed by multiple regression. RESULTS: Of 3951 men undergoing primary IPP placement from July 2016 to July 2021, the median implant length was 20 cm (IQR: 19-22). Shorter implant length was associated with increasing age in years (ß = -0.01, P = .009), Asian ethnicity (ß = -2.34, P = .008), history of radical prostatectomy (ß = -0.35, P = .001), and use of an infrapubic surgical approach (ß = -1.02, P <.001). Black or African American ethnicity was associated with the implantation of longer devices (ß = 0.35, P <.001). No significant associations were recorded with BMI, history of intracavernosal injections, diabetes mellitus, tobacco use, radiation therapy, Peyronie's disease, priapism, or cavernosal dilation technique. CONCLUSION: The length of an implanted penile prosthesis was found to be associated with preoperative and intraoperative factors including history of radical prostatectomy and operative approach. The knowledge of these associations may assist in the preoperative counseling of patients receiving IPP and help create accurate postoperative expectations.

16.
Surg Technol Int ; 442024 07 09.
Article in English | MEDLINE | ID: mdl-38981600

ABSTRACT

Hinged knee arthroplasties are commonly used in scenarios where there are major ligament deficiencies or bone loss around the knee. They are applicable in native knees with major deformities and during revisions. They can also be used as a salvage procedure after distal femoral resection. The new modular hinged device system, namely the Triathlon Hinge Knee (THK) System (Stryker, Mahwah, New Jersey), reflects the advancements of third-generation design and enhances surgical flexibility by allowing streamlined integration with the Triathlon Total Stabilized (TS) System (Stryker, Mahwah, New Jersey) and the Global Modular Replacement System (GMRS, Stryker, Mahwah, New Jersey). Additionally, the Triathlon Revision Tibial Baseplate (Stryker, Mahwah, New Jersey) has been launched as part of THK and is compatible with the Modular Rotating Hinge (MRH , Stryker, Mahwah, New Jersey) femur, which allows the Revision Baseplate to replace the existing tibial component while leaving the existing MRH Femoral Component in place. The Triathlon Revision Tibial Baseplate enables orthopaedic surgeons to use constrained or hinged prostheses, including both distal and total femoral replacement options, without changing the Tibial Baseplate. This is because the TS, MRH, THK, and GMRS femurs are compatible with the new Triathlon Revision Tibial Baseplate. Additionally, the system can be augmented with metaphyseal cone constructs to help provide a stable foundation for reconstruction. This report explores the application of a new modular hinged device system in various scenarios, starting with (1) complex primary hinged knee arthroplasty, followed by revision hinged knee arthroplasty cases including (2) failed TKA with medial collateral ligament (MCL) dysfunction, (3) severe arthrofibrosis post-TKA, (4) revisions for prosthetic joint infection, (5) extensor mechanism deficiency, and (6) arthrofibrosis with extensor mechanism disruption, concluding with a case of (7) distal femoral arthroplasty for periprosthetic fracture post-failed TKA.

17.
bioRxiv ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39026703

ABSTRACT

Type-I interferons (IFN) induce cellular proteins with antiviral activity. One such protein is Interferon Stimulated Gene 15 (ISG15). ISG15 is conjugated to proteins during ISGylation to confer antiviral activity and regulate cellular activities associated with inflammatory and neurodegenerative diseases and cancer. Apart from ISGylation, unconjugated free ISG15 is also released from cells during various conditions, including virus infection. The role of extracellular ISG15 during virus infection was unknown. We show that extracellular ISG15 triggers ISGylation and acts as a soluble antiviral factor to restrict virus infection via an IFN-independent mechanism. Specifically, extracellular ISG15 acts post-translationally to markedly enhance the stability of basal intracellular ISG15 protein levels to support ISGylation. Furthermore, extracellular ISG15 interacts with cell surface integrin (α5ß1 integrins) molecules via its RGD-like motif to activate the integrin-FAK (Focal Adhesion Kinase) pathway resulting in IFN-independent ISGylation. Thus, our studies have identified extracellular ISG15 protein as a new soluble antiviral factor that confers IFN-independent non-canonical ISGylation via the integrin-FAK pathway by post-translational stabilization of intracellular ISG15 protein.

18.
Lung Cancer ; 194: 107861, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39003938

ABSTRACT

Asbestos, a group of class I (WHO) carcinogenic fibers, is the main cause of mesothelioma. Asbestos inhalation also increases the risk to develop other solid tumours with lung cancer as the most prominent example [91]. The incidence of asbestos-related lung cancer (ARLC) is estimated to be to six times larger than the mesothelioma incidence thereby becoming an important health issue [86]. Although the pivotal role of asbestos in inducing lung cancer is well established, the precise causal relationships between exposures to asbestos, tobacco smoke, radon and 'particulate' (PM2.5) air pollution remain obscure and new knowledge is needed to establish appropriate preventive measures and to tailor existing screening practices[22,61,65]. We hypothesize that a part of the increasing numbers of lung cancer diagnoses in never-smokers can be explained by (historic and current) exposures to asbestos as well as combinations of different forms of air pollution (PM2.5, asbestos and silica).


Subject(s)
Asbestos , Lung Neoplasms , Humans , Lung Neoplasms/etiology , Lung Neoplasms/epidemiology , Asbestos/adverse effects , Environmental Exposure/adverse effects , Incidence , Air Pollution/adverse effects , Occupational Exposure/adverse effects , Particulate Matter/adverse effects
19.
J Sex Med ; 21(8): 716-722, 2024 08 01.
Article in English | MEDLINE | ID: mdl-38971577

ABSTRACT

BACKGROUND: Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear. AIM: To explore clinical associations between DM characteristics and PD complications. METHODS: We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45 years), average (45-65 years), and late (>65 years). OUTCOMES: Outcomes included effects of DM characteristics on PD development, progression, and severity. RESULTS: In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006). CLINICAL IMPLICATIONS: These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges. STRENGTHS AND LIMITATIONS: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables. CONCLUSIONS: This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD.


Subject(s)
Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Penile Induration , Humans , Penile Induration/complications , Male , Middle Aged , Retrospective Studies , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Aged , Age of Onset , Adult , Disease Progression , Penis/diagnostic imaging , Risk Factors
20.
J Sex Med ; 21(8): 723-728, 2024 08 01.
Article in English | MEDLINE | ID: mdl-38971576

ABSTRACT

BACKGROUND: Major ischemic priapism (IP) is defined as a persistent penile erection for >4 hours. IP may cause serious complications, especially if prompt resolution is not achieved. Therefore, selecting the most effective and usable shunt technique is crucial in IP cases that are refractory to medical therapy. AIM: To compare the effectiveness and complication risks of distal corporoglanular shunt procedures with and without the Burnett "snake" maneuver. METHODS: We conducted a retrospective study of patients who presented with IP and underwent surgical treatment at our institution between 2005 and 2021. The patients were categorized into 2 groups: group 1 (n = 26) underwent distal shunt + Burnett snake maneuver, and group 2 (n = 56) underwent distal shunt-only. Clinical history, parameters of IP, details of medical and surgical treatments, and follow-up information were evaluated. OUTCOMES: Outcomes included differences in IP resolution and recurrence, functional erections, and complications between corporoglanular shunt procedures with and without the Burnett snake maneuver. RESULTS: In group 1, 24 of 26 patients (92.3%) experienced priapism resolution with a single surgical intervention, while this outcome was observed in 30 of 56 patients (53.6%) in group 2 (P < .001). Notably, priapism recurrence was significantly lower in group 1, occurring in 1 of 24 patients (4.2%), as opposed to 8 of 30 patients (26.6%) in group 2 (P < .001). Of the patients with documented sexual function status at follow-up, functional erections (capable of penetration with or without phosphodiesterase 5 inhibitors) were noted in 6 of 14 patients (42.8%) in group 1 and 13 of 26 patients (50%) in group 2 (P = .66). CLINICAL IMPLICATIONS: This study provides valuable insights regarding technical aspects of distal shunt procedures with and without the Burnett snake maneuver for treating major IP episodes. These results can help surgeons with clinical decision making for patients who present with IP. STRENGTH AND LIMITATIONS: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, challenges in controlling confounding variables, and the lack of validated questionnaire scores for erectile function evaluation. CONCLUSION: Our study demonstrates that modifying distal shunt procedures using the Burnett snake maneuver significantly improves priapism resolution and effectively prevents further priapism episodes without introducing additional complications or erectile function loss, thereby distinguishing it from distal shunt-only procedures.


Subject(s)
Ischemia , Penis , Priapism , Humans , Male , Priapism/surgery , Priapism/etiology , Retrospective Studies , Adult , Penis/blood supply , Penis/surgery , Ischemia/surgery , Middle Aged , Treatment Outcome , Penile Erection/physiology
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