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1.
Cureus ; 16(4): e57614, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707180

RESUMEN

This case report details a complex case of parotid gland sialolithiasis with stones adherent to the facial nerve, a scenario that presents a significant surgical challenge. Traditional sialendoscopy failed to address the condition in a 23-year-old female patient, leading to the adoption of a combined endoscopic transcutaneous approach. This method successfully resolved the condition without intraoperative complications, maintaining intact facial nerve function postoperatively. The case emphasizes the importance of individualized surgical strategy and expert technique in advanced parotid surgery, advocating this approach for similarly complex sialolithiasis cases.

2.
J Med Chem ; 67(11): 9613-9627, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38776401

RESUMEN

The development of antibacterial drugs with new mechanisms of action is crucial in combating the rise of antibiotic-resistant infections. Bacterial carbonic anhydrases (CAs, EC 4.2.1.1) have been validated as promising antibacterial targets against pathogens such as Helicobacter pylori, Neisseria gonorrhoeae, and vancomycin-resistant enterococci. A multitarget strategy is proposed to design penicillin-based CA inhibitor hybrids for tackling resistance by targeting multiple bacterial pathways, thereby resensitizing drug-resistant strains to clinical antibiotics. The sulfonamide derivatives potently inhibited the CAs from N. gonorrhoeae and Escherichia coli with KI values in the range of 7.1-617.2 nM. Computational simulations with the main penicillin-binding protein (PBP) of N. gonorrhoeae indicated that these hybrid derivatives maintained the mechanism of action of the lead ß-lactams. A subset of derivatives showed potent PBP-related antigonococcal effects against multidrug-resistant N. gonorrhoeae strains, with several compounds significantly outperforming both the lead ß-lactam and CA inhibitor drugs (MIC values in the range 0.25 to 0.5 µg/mL).


Asunto(s)
Antibacterianos , Inhibidores de Anhidrasa Carbónica , Anhidrasas Carbónicas , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/enzimología , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Anhidrasas Carbónicas/metabolismo , Penicilinas/farmacología , Penicilinas/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Relación Estructura-Actividad , Humanos , Sulfonamidas/farmacología , Sulfonamidas/química , Sulfonamidas/síntesis química , Estructura Molecular , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología
3.
Materials (Basel) ; 17(7)2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38611995

RESUMEN

Researchers from all around the world have been paying close attention to particle-based power tower technologies. On the King Saud University campus in the Kingdom of Saudi Arabia, the first integrated gas turbine-solar particle heating hybrid system has been realized. In this study, two different types of experiments were carried out to examine how susceptible prospective liner materials for thermal energy storage tanks were to erosion. An accelerated direct-impact test with high particulate temperature was the first experiment. A low-velocity mass-flow test was the second experiment, and it closely mimicked the flow circumstances in a real thermal energy storage tank. The tests were conducted on bare insulating fire bricks (IFBs) and IFBs coated with Tuffcrete 47, Matrigun 25 ACX, and Tuffcrete 60 M. The latter three lining materials were high-temperature-resilient materials made by Allied Mineral Products Inc. (AMP) (Columbus, OH, USA). The results showed that although IFBs coated with AMP materials worked well in this test, the accelerated direct-impact test significantly reduced the bulk of the bare IFB. As a result, lining substances must be added to the surface of IFBs to increase their strength and protection because they cannot be used in situations where particles directly impact their surface. On the other hand, the findings of the 60 h cold-particle mass-flow test revealed that the IFBs were not significantly eroded. Additionally, it was discovered that the degree of erosion on the samples of bare IFB was unaffected by the height of the particle bed.

4.
J Craniovertebr Junction Spine ; 15(1): 92-98, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644915

RESUMEN

Objective: Metastatic spinal tumors represent a rare but concerning complication of primary thyroid carcinoma. We identified demographics, metastatic features, outcomes, and treatment strategies for these tumors in our institutional cohort. Materials and Methods: We retrospectively reviewed patients surgically treated for spinal metastases of primary thyroid carcinoma. Demographics, tumor characteristics, and treatment modalities were collected. The functional outcomes were quantified using Nurik, Modified Rankin, and Karnofsky Scores. Results: Twelve patients were identified who underwent 17 surgeries for resection of spinal metastases. The primary thyroid tumor pathologies included papillary (4/12), follicular (6/12), and Hurthle cell (2/12) subtypes. The average number of spinal metastases was 2.5. Of the primary tumor subtypes, follicular tumors averaged 2.8 metastases at the highest and Hurthle cell tumors averaged 2.0 spinal metastases at the lowest. Five patients (41.7%) underwent preoperative embolization for their spinal metastases. Seven patients (58.3%) received postoperative radiation. There was no significant difference in progression-free survival between patients receiving surgery with adjuvant radiation and surgery alone (P = 0.0773). Five patients (41.7%) experienced postoperative complications. Two patients (16.7%) succumbed to disease progression and two patients (16.7%) experienced tumor recurrence following resection. Postsurgical mean Nurik scores decreased 0.54 points, mean Modified Rankin scores decreased 0.48 points, and mean Karnofsky scores increased 4.8 points. Conclusion: Surgery presents as an important treatment modality in the management of spinal metastases from thyroid cancer. Further work is needed to understand the predictive factors for survival and outcomes following treatment.

5.
J Craniovertebr Junction Spine ; 15(1): 21-29, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644924

RESUMEN

Introduction: Atlas fractures often accompany traumatic dens fractures, but existing literature on the management of simultaneous atlantoaxial fractures is limited. Methods: We examined all patients with traumatic dens fractures at our institution between 2008 and 2018. We used multivariable logistic regression and ordinal logistic regression to identify factors independently associated with presentation with a simultaneous atlas fracture, as well myelopathy severity, fracture nonunion, and selection for surgery. Results: Two hundred and eighty-two patients with traumatic dens fractures without subaxial fractures were identified, including 65 (22.8%) with simultaneous atlas fractures. The distribution of injury mechanisms differed between groups (χ2 P = 0.0360). On multivariable logistic regression, dens nonunion was positively associated with type II fractures (odds ratio [OR] = 2.00, P = 0.038) and negatively associated with having surgery (OR = 0.52, P = 0.049), but not with having a C1 fracture (P = 0.3673). Worse myelopathy severity on presentation was associated with having a severe injury severity score (OR = 102.3, P < 0.001) and older age (OR = 1.28, P = 0.002), but not with having an atlas fracture (P = 0.2446). Having a simultaneous atlas fracture was associated with older age (OR = 1.29, P = 0.024) and dens fracture angulation (OR = 2.62, P = 0.004). Among patients who underwent surgery, C1/C2 posterior fusion was the most common procedure, and having a simultaneous atlas fracture was associated with selection for occipitocervical fusion (OCF) (OR = 14.35, P = 0.010). Conclusions: Among patients with traumatic dens, patients who have simultaneous atlas fractures are a distinct subpopulation with respect to age, mechanism of injury, fracture morphology, and management. Traumatic dens fractures with simultaneous atlas fractures are independently associated with selection for OCF rather than posterior cervical fusion alone.

6.
Cureus ; 16(3): e56540, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38646382

RESUMEN

Introduction Voice is a crucial tool for communication, and voice problems are more likely to occur in professionals who frequently use their voice for work. Teachers, whose profession requires sustained vocal use, are particularly susceptible to occupation-related voice disorders. This study aimed to quantify the prevalence of voice disorders among teachers in Saudi Arabia, with the general population serving as a control group, and to identify associated risk factors. Methods A cross-sectional study was conducted utilizing an online self-administered questionnaire, which was completed by both teachers and the general population in Saudi Arabia. The latter group acted as a control. The questionnaire included sections on sociodemographic data, teaching patterns, symptoms of voice issues, and the Voice Handicap Index-10 (VHI-10) for assessing voice disorders among participants. Results The study included 640 participants, with 438 (68.4%) being teachers, the majority of whom were females (N = 406; 63.4%). The most common voice-related symptoms reported by teachers were hoarseness (N = 210; 37.9%) and dry throat (N = 147; 26.9%). Voice disorders, as determined by the VHI, affected 355 (55.5%) of the teachers. A high VHI score was associated with a diagnosis of voice disorders and GERD. There was no significant difference in the VHI scores between teachers and the general population (p > 0.05). Conclusion Teachers in Saudi Arabia exhibited a higher prevalence of voice disorders compared to the general population. Risk factors, such as smoking, longer teaching experience, and more teaching hours per week, were more common among teachers with voice disorders. Further investigative studies are warranted to elucidate the causal relationships between these variables and voice disorders.

7.
Ann Case Rep ; 9(1)2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606301

RESUMEN

Immunoglobulin G4-related disease (IgG4-RD) is a rare autoimmune disorder with an unknown etiology. Using orthogonal immune profiling and automated sequential multiplexing, we found an enhanced frequency of activated circulating B cells, antigen-presenting myeloid cells in peripheral blood, and a distinct distribution of immune cells within the CNS lesions. Prohibitin-expressing CD138+ plasma B cells and CD11c+ dendritic cells have been found interacting with T cells resulting in irmnune cell activation within the lesion. The data implicate prohibitin as a potential triggering antigen in the pathogenesis of IgG4-RD and shed light on the cellular dynamics and interactions driving IgG4-RD in the central nervous system, emphasizing the need for further studies corroborating these findings.

8.
World Neurosurg ; 185: e1040-e1048, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38484967

RESUMEN

INTRODUCTION: The Coronavirus disease 2019 pandemic ushered a paradigm shift in medical education, accelerating the transition to virtual learning in select cases. The Virtual Global Spine Conference (VGSC), launched at the height of the pandemic, is a testament to this evolution, providing an independent educational series for spine care professionals worldwide. This study assesses VGSC's 3-year performance, focusing on accessibility, engagement, and educational value. METHODOLOGY: Through retrospective data analysis from April 2020 to August 2023, we examined our social media metrics to measure VGSC's reach and impact. RESULTS: Over the study period, VGSC's webinars successfully attracted 2337 unique participants, maintaining an average attendance of 47 individuals per session. The YouTube channel demonstrated significant growth, amassing over 2693 subscribers and releasing 168 videos. These videos collectively garnered 112,208 views and 15,823.3 hours of watch time. Viewer demographics reveal a predominant age group of 35-44 years, representing 56.81% of the audience, closely followed by the 25-34 age group at 40.2%. Male participants constituted 78.95% of the subscriber base. Geographically, the viewership primarily originates from the United States, with India, Canada, South Korea, and the United Kingdom also contributing substantial audience numbers. The VGSC's presence on the "X account" has grown to 2882 followers, significantly enlarging the digital community and fostering increased engagement. CONCLUSIONS: The VGSC has demonstrated significant value as a virtual educational tool in spine education. Its diverse content and ease of access will likely enable it to drive value well into the post-pandemic years. Maintaining and expanding engagement, beyond North America in particular, remains a priority.


Asunto(s)
COVID-19 , Congresos como Asunto , Humanos , Estudios Retrospectivos , Adulto , Masculino , Medios de Comunicación Sociales , Femenino , Educación a Distancia/métodos , Columna Vertebral/cirugía , Enfermedades de la Columna Vertebral
9.
Mar Pollut Bull ; 201: 116247, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38522340

RESUMEN

Ship recycling has gained significant importance in recent years due to the growing awareness of environmental concerns and the need for sustainable practices within the maritime industry. As vessels reach the end of their operational life, proper recycling methods are crucial to mitigate environmental impacts and promote resource conservation. With an increasing number of ships being decommissioned annually, there has been a growing interest and emphasis on developing efficient and eco-friendly ship recycling practices worldwide. This article presents a systematic literature review and bibliometric analysis of 228 studies on ship recycling indexed in Scopus. Employing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology for its robustness in comprehensive literature analysis, this review uncovers key insights into prominent countries, authors, journals, collaborations, topics, and historical trends in ship recycling research, thereby extending the scope of previous reviews. Notably, major contributions from Turkey, India, Bangladesh, the USA, and China focus on environmental impact studies, reflecting urgent global sustainability concerns. The review discusses commonly adopted methodologies such as Life Cycle Assessment and Elemental Analysis, shedding light on their application in this field. Through thematic analysis across 8 categories, future research pathways are identified, highlighting crucial areas such as continuous environmental monitoring, innovative renewable energy extraction from end-of-life vessels, and the need for human factors in ship recycling. This comprehensive synthesis of existing knowledge and identification of emergent research needs and opportunities serve as a foundational resource for impactful future research and informed policymaking, particularly in aligning with global environmental and sustainability goals. Researchers, policymakers and other stakeholders in maritime safety and environmental sustainability may find the knowledge gained from this systematic literature review insightful.


Asunto(s)
Reciclaje , Navíos , Humanos , Reciclaje/métodos , Monitoreo del Ambiente/métodos , Bibliometría , Investigación
10.
N Engl J Med ; 390(3): 203-211, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38231621

RESUMEN

BACKGROUND: Testosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed. METHODS: In a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.4 nmol per liter), in fasting plasma samples obtained at least 48 hours apart. Participants were randomly assigned to apply a testosterone or placebo gel daily. At every visit, participants were asked if they had had a fracture since the previous visit. If they had, medical records were obtained and adjudicated. RESULTS: The full-analysis population included 5204 participants (2601 in the testosterone group and 2603 in the placebo group). After a median follow-up of 3.19 years, a clinical fracture had occurred in 91 participants (3.50%) in the testosterone group and 64 participants (2.46%) in the placebo group (hazard ratio, 1.43; 95% confidence interval, 1.04 to 1.97). The fracture incidence also appeared to be higher in the testosterone group for all other fracture end points. CONCLUSIONS: Among middle-aged and older men with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo. The fracture incidence was numerically higher among men who received testosterone than among those who received placebo. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).


Asunto(s)
Fracturas Óseas , Hipogonadismo , Testosterona , Anciano , Humanos , Masculino , Persona de Mediana Edad , Densidad Ósea/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Método Doble Ciego , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Hipogonadismo/tratamiento farmacológico , Testosterona/administración & dosificación , Testosterona/efectos adversos , Testosterona/sangre , Testosterona/farmacología , Geles , Administración Tópica
11.
RSC Adv ; 14(2): 1513-1526, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38174234

RESUMEN

The structure-activity relationship of a new tert-butylphenylthiazole series, with a pyrimidine linker, was investigated. We wished to expand knowledge of this novel class of antibiotics by generating 21 new derivatives bearing ≥2 heteroatoms in their side chains. Their activity was examined against isolates of methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. Two compounds with 1,2-diaminocyclohexane as a nitrogenous side chain showed promising activity against the highly infectious MRSA USA300 strain, with a minimum inhibitory concentration (MIC) of 4 µg mL-1. One of these two compounds demonstrated potent activity against C. difficile, with a MIC of 4 µg mL-1. Moderate activities against a C. difficile strain with a MIC of 8 µg mL-1 were noted. Some new compounds possessed antifungal activity against a wild fluconazole-resistant C. albicans strain, with MIC values of 4-16 µg mL-1. ADME and metabolism-simulation studies were performed for the most promising compound and compared with lead compounds. Our results revealed that one compound possessed greater penetration of bacterial membranes and metabolic resistance, which aided a longer duration of action against MRSA.

13.
Clin Spine Surg ; 37(2): E97-E105, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-37941100

RESUMEN

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To calculate the magnitude of any increased risk of epidural hematoma (EDH) associated with chemoprophylactic anticoagulation (chemoprophylaxis), if any. SUMMARY OF BACKGROUND DATA: Chemoprophylaxis for the prevention of venous thromboembolic events may be associated with an increased risk of EDH after spine surgery. MATERIALS AND METHODS: A total of 6869 consecutive spine surgeries performed at our institution were identified, and clinical and demographic data were collected. We identified cases in which symptomatic EDHs were evacuated within 30 days postoperatively. Patients receiving chemoprophylaxis and controls were matched using K-nearest neighbor propensity score matching to calculate the effect of anticoagulation on the rate of postoperative EDH. RESULTS: After propensity score matching, 1071 patients who received chemoprophylaxis were matched to 1585 controls. Propensity scores were well balanced between populations (Rubin B=20.6, Rubin R=1.05), and an 89.6% reduction in bias was achieved, with a remaining mean bias of 3.2%. The effect of chemoprophylaxis on EDH was insignificant ( P =0.294). Symptomatic EDH was independently associated with having a transfusion [odds ratio (OR)=7.30 (1.15, 46.20), P =0.035], having thoracic-level surgery [OR=41.19 (3.75, 452.4), P =0.002], and increasing body mass index [OR=1.44 (1.04, 1.98), P =0.028] but was not associated with chemoprophylaxis. Five out of 13 patients who developed EDH (38.5%) were receiving some form of anticoagulation, including 1 patient on therapeutic anticoagulation, 1 concurrently on aspirin and chemoprophylaxis, and 2 who were also found to have developed thrombocytopenia postoperatively. The median time on anticoagulation before EDH was 8.1 days. A higher proportion of patients who developed EDH also developed venous thromboembolic events than the general population [38.5% vs. 2.4%, OR=25.34 (9.226, 79.68), P <0.0001], and 1 EDH patient died from pulmonary embolism while off chemoprophylaxis. CONCLUSIONS: Chemoprophylactic anticoagulation did not cause an increase in the rate of spinal EDH in our patient population.


Asunto(s)
Hematoma Espinal Epidural , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Hematoma Espinal Epidural/prevención & control , Anticoagulantes/efectos adversos , Factores de Riesgo
15.
Cureus ; 15(10): e46782, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37954752

RESUMEN

Objective This study examined the interaction between adolescent idiopathic scoliosis (AIS) and pregnancy, focusing on pregnancy outcomes, changes in back pain, and anesthesia use. Methods A retrospective analysis was conducted on adult patients with AIS who gave birth at our institution between 2006 and 2022. Results A total of 163 AIS patients with 263 pregnancies were included. The median age at delivery was 33 (range 18 to 50) years. Among 157 patients with information on prior scoliosis treatment, 66.9% had not received treatment, 20.4% had undergone spinal fusion, and 12.7% had received bracing. Of the 260 pregnancies with available data, 90.4% were delivered at term and 8.5% were preterm. Of the 257 pregnancies with information on anesthesia type, 35.0% received epidural anesthesia, 17.9% received spinal anesthesia, 37.7% received combined spinal and epidural anesthesia, 8.2% received no anesthesia, and 1.2% received intravenous or general anesthesia. Difficulty administering neuraxial anesthesia was reported in 6.1% of cases, and these patients were less likely to receive combined spinal and epidural anesthesia (6.3% versus 39.8%, p = 0.0123). Among 116 cases with recorded back pain during pregnancy, 67.2% reported increased pain, 31.9% reported similar pain, and one patient reported decreased pain. Of the 16 patients with pre and postpartum radiographs, eight showed a Cobb angle increase ≥ 3°, with five patients having an increase ≥ 5°. Conclusions Pregnancy can exacerbate back pain and pose challenges for neuraxial anesthesia in some AIS patients. Further large-scale, multi-institutional studies with standardized data collection are needed to fully understand the impact of pregnancy on AIS.

16.
J Enzyme Inhib Med Chem ; 38(1): 2284119, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37994421

RESUMEN

Carbonic anhydrases (CAs) from the pathogenic bacteria Nesseria gonorrhoeae and vancomycin-resistant enterococci (VRE) have recently been validated as antibacterial drug targets. Here we explored the inhibition of the α-CA from N. gonorrhoeae (α-NgCA), of α- and γ-class enzymes from Enterococcus faecium (α-EfCA and γ-EfCA) with a panel of aliphatic, heterocyclic and aryl-alkyl primary/secondary monothiocarbamates (MTCs). α-NgCA was inhibited in vitro with KIs ranging from 0.367 to 0.919 µM. The compounds inhibited the α-EfCA and γ-EfCA with KI ranges of 0.195-0.959 µM and of 0.149-1.90 µM, respectively. Some MTCs were also investigated for their inhibitory effects on the growth of clinically-relevant N. gonorrhoeae and VRE strains. No inhibitory effects on the growth of VRE were noted for all MTCs, whereas one compound (13) inhibited the growth N. gonorrhoeae strains at concentrations ranging from 16 to 64 µg/mL. This suggests that compound 13 may be a potential antibacterial agent against N. gonorrhoeae.


Asunto(s)
Anhidrasas Carbónicas , Enterococos Resistentes a la Vancomicina , Bacterias , Antibacterianos/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología
17.
RSC Med Chem ; 14(10): 2089-2099, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37859711

RESUMEN

Cryptococcal infections remain a major cause of mortality worldwide due to the ability of Cryptococci to pass through the blood-brain barrier (BBB) causing lethal meningitis. The limited number of available therapeutics, which exhibit limited availability, severe toxicity and low tolerability, necessitates the development of new therapeutics. Investigating the antifungal activity of a novel series of naphthylthiazoles provided trans-diaminocyclohexyl derivative 18 with many advantageous attributes as a potential therapeutic for cryptococcal meningitis. Briefly, the antimycotic activity of 18 against cryptococcal strains was highly comparable to that of amphotericin-B and fluconazole with MIC values as low as 1 µg mL-1. Moreover, compound 18 possessed additional advantages over fluconazole; it significantly reduced the intracellular burden of Cryptococci and markedly inhibited cryptococcal biofilm formation. Initial PK assessment of 18 indicated its ability to reach the CNS after oral administration with high permeability, and it maintained therapeutic plasma concentrations for 18 h. Its antifungal activity extended to other clinically relevant strains, such as fluconazole-resistant C. auris.

18.
J Craniovertebr Junction Spine ; 14(3): 221-229, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860027

RESUMEN

Objective: Venous thromboembolic event (VTE) after spine surgery is a rare but potentially devastating complication. With the advent of machine learning, an opportunity exists for more accurate prediction of such events to aid in prevention and treatment. Methods: Seven models were screened using 108 database variables and 62 preoperative variables. These models included deep neural network (DNN), DNN with synthetic minority oversampling technique (SMOTE), logistic regression, ridge regression, lasso regression, simple linear regression, and gradient boosting classifier. Relevant metrics were compared between each model. The top four models were selected based on area under the receiver operator curve; these models included DNN with SMOTE, linear regression, lasso regression, and ridge regression. Separate random sampling of each model was performed 1000 additional independent times using a randomly generated training/testing distribution. Variable weights and magnitudes were analyzed after sampling. Results: Using all patient-related variables, DNN using SMOTE was the top-performing model in predicting postoperative VTE after spinal surgery (area under the curve [AUC] =0.904), followed by lasso regression (AUC = 0.894), ridge regression (AUC = 0.873), and linear regression (AUC = 0.864). When analyzing a subset of only preoperative variables, the top-performing models were lasso regression (AUC = 0.865) and DNN with SMOTE (AUC = 0.864), both of which outperform any currently published models. Main model contributions relied heavily on variables associated with history of thromboembolic events, length of surgical/anesthetic time, and use of postoperative chemoprophylaxis. Conclusions: The current study provides promise toward machine learning methods geared toward predicting postoperative complications after spine surgery. Further study is needed in order to best quantify and model real-world risk for such events.

19.
Pathog Dis ; 812023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-37852672

RESUMEN

The rapid occurrence of gonococcal resistance to all classes of antibiotics could lead to untreatable gonorrhea. Thus, development of novel anti-Neisseria gonorrhoeae drugs is urgently needed. Neisseria gonorrhoeae FA1090 is the most used in gonococcal infection mouse models because of its natural resistance to streptomycin. Streptomycin inhibits the urogenital commensal flora that permits gonococcal colonization. However, this strain is drug-susceptible and cannot be used to investigate the efficacy of novel agents against multidrug-resistant N. gonorrhoeae. Hence, to test the in vivo efficacy of new therapeutics against N. gonorrhoeae resistant to the frontline antibiotics, azithromycin, or ceftriaxone, we constructed streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant). We identified the inoculum size needed to successfully colonize mice. Both mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, colonized the genital tract of mice for 14 days with 100% colonization observed for at least 7 days. CDC-181-rpsLA128G demonstrated better colonization of the murine genital tract compared to WHO-X-rpsLA128G. Lower inoculum of WHO-X-rpsLA128G (105 and 106 CFU) colonized mice better than higher inoculum. Overall, our results indicate that CDC-181-rpsLA128G and WHO-X-rpsLA128G can colonize the lower genital tract of mice and are suitable to be used in mouse models to investigate the efficacy of antigonococcal agents.


Asunto(s)
Gonorrea , Neisseria gonorrhoeae , Animales , Ratones , Femenino , Ceftriaxona , Azitromicina/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Estreptomicina , Modelos Animales de Enfermedad
20.
Sci Rep ; 13(1): 14468, 2023 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-37660222

RESUMEN

Drug-resistant Neisseria gonorrhoeae represents a major threat to public health; without new effective antibiotics, untreatable gonococcal infections loom as a real possibility. In a previous drug-repurposing study, we reported that salicylic acid had good potency against azithromycin-resistant N. gonorrhoeae. We now report that the anti-gonococcal activity in this scaffold is easily lost by inopportune substitution, but that select substituted naphthyl analogs (3b, 3o and 3p) have superior activity to salicylic acid itself. Furthermore, these compounds retained potency against multiple ceftriaxone- and azithromycin-resistant strains, exhibited rapid bactericidal activity against N. gonorrhoeae, and showed high tolerability to mammalian cells (CC50 > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria.


Asunto(s)
Gonorrea , Neisseria gonorrhoeae , Animales , Femenino , Ácido Salicílico/farmacología , Azitromicina , Gonorrea/tratamiento farmacológico , Bacterias , Mamíferos
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