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Background/Objective: Pudendal neuralgia is a distressing condition that presents with pain in the perineum. While a positive anesthetic pudendal nerve block is one of the essential criteria for diagnosing this condition, this block can also provide a therapeutic effect for those afflicted with pudendal neuralgia. There are multiple ways in which a pudendal nerve block can be performed. The objective of this study is to share our results and follow-up of fluoroscopy-guided transgluteal pudendal nerve blocks. Methods: This is a retrospective case series. Included were 101 patients who met four out of the five Nantes criteria (pain in the anatomical territory of the pudendal nerve, pain worsened by sitting, pain that does not wake the patient up at night, and no objective sensory loss on clinical examination) who did not respond to conservative treatment and subsequently underwent a fluoroscopy-guided transgluteal pudendal nerve block. Therapeutic success was defined as a 30% or greater reduction in pain. Success rates were calculated, and the duration over which that success was sustained was recorded. Results: For achieving at least 30% relief of pain, using worst-case analysis, the success rate at two weeks was 49.4% (95% CI: 38.5%, 60.3%). In addition to pain relief, patients experienced other therapeutic benefits, such as reductions in medication use and improvements in activities of daily living. Conclusions: Fluoroscopy-guided transgluteal pudendal nerve block appears to be effective in patients who have pudendal neuralgia that is resistant to conservative therapy, with good short-term success.
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BACKGROUND: The COVID-19 pandemic has imposed unprecedented hurdles on health care systems and medical faculties alike. Lecturers of practical courses at medical schools have been confronted with the challenge of transferring knowledge remotely. OBJECTIVE: We sought to evaluate the effects of a web-based medical microbiology course on learning outcomes and student perceptions. METHODS: During the summer term of 2020, medical students at Saarland University, Germany, participated in a web-based medical microbiology course. Teaching content comprised clinical scenarios, theoretical knowledge, and instructive videos on microbiological techniques. Test performance, failure rate, and student evaluations, which included open-response items, for the web-based course were compared to those of the on-site course from the summer term of 2019. RESULTS: Student performance was comparable between both the online-only group and the on-site comparator for both the written exam (n=100 and n=131, respectively; average grade: mean 7.6, SD 1.7 vs mean 7.3, SD 1.8; P=.20) and the oral exam (n=86 and n=139, respectively; average grade: mean 33.6, SD 4.9 vs mean 33.4, SD 4.8; P=.78). Failure rate did not significantly differ between the online-only group and the comparator group (2/84, 2.4% vs 4/120, 3.3%). While lecturer expertise was rated similarly as high by students in both groups (mean 1.47, SD 0.62 vs mean 1.27, SD 0.55; P=.08), students who took the web-based course provided lower scores for interdisciplinarity (mean 1.7, SD 0.73 vs mean 2.53, SD 1.19; P<.001), opportunities for interaction (mean 1.46, SD 0.67 vs mean 2.91, SD 1.03; P<.001), and the extent to which the educational objectives were defined (mean 1.61, SD 0.76 vs mean 3.41, SD 0.95; P<.001). Main critiques formulated within the open-response items concerned organizational deficits. CONCLUSIONS: Web-based courses in medical microbiology are a feasible teaching option, especially in the setting of a pandemic, leading to similar test performances in comparison to on-site courses. The lack of interaction and the sustainability of acquired manual skills warrant further research.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-ß (Aß) disease pathologies. Mice overexpressing both Aß and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aß accumulation in the brain and selectively increased the production of soluble Aß42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aß expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.
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CONTEXT: Comparisons of osteopathic physicians (ie, DOs) and allopathic physicians (ie, MDs) on interpersonal manner, including empathy and communication style, have been limited by such methodologic issues as self-assessment and a focus on medical students rather than practicing physicians. OBJECTIVE: To compare perceptions of the interpersonal manner, empathy, and communication style of DOs and MDs and corresponding clinical measures reported by their patients. METHODS: A cross-sectional study of adults with subacute or chronic low back pain was conducted within the PRECISION Pain Research Registry from April 2016 through December 2018. A total of 313 patients having their physician for 1 year or longer reported sociodemographic and clinical characteristics, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids for low back pain. Using validated research instruments, they also reported perceptions of their physician's interpersonal manner, empathy, and communication style and clinical measures of pain catastrophizing, pain self-efficacy, low back pain intensity, back-related disability, and deficits in quality of life relating to sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue. RESULTS: Patients treated by DOs were less likely to be using NSAIDs (odds ratio [OR], 0.60; 95% CI, 0.36-0.997) or opioids (OR, 0.57; 95% CI, 0.32-0.998) than patients treated by MDs. Patients treated by DOs reported lesser pain catastrophizing (mean, 12.5; 95% CI, 10.1-15.0 for DOs vs 18.1; 95% CI, 16.3-19.9 for MDs; P<.001) and greater pain self-efficacy (mean, 39.5; 95% CI, 36.3-42.8 for DOs vs 35.3; 95% CI, 33.4-37.3 for MDs; P=.03). Correspondingly, patients treated by DOs reported lesser back-related disability (mean, 11.2; 95% CI, 9.9-12.5 for DOs vs 13.5; 95% CI, 12.8-14.3 for MDs; P=.002) and a trend toward lesser deficits in quality of life. Patients reported more favorable perceptions of DOs on interpersonal manner (mean, 4.3; 95% CI, 4.2-4.5 for DOs vs 4.0; 95% CI, 3.9-4.2 for MDs; P=.01) and empathy (mean, 41.2; 95% CI, 39.1-43.3 for DOs vs 38.0; 95% CI, 36.5-39.5 for MDs; P=.02). CONCLUSION: The mechanisms underlying lesser use of NSAIDs and opioids, superior clinical status measures, and more favorable perceptions of physician interpersonal manner and empathy reported by patients treated by DOs warrant further investigation.
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Comunicación , Empatía , Dolor de la Región Lumbar/terapia , Medicina Osteopática , Médicos Osteopáticos/psicología , Relaciones Médico-Paciente , Adulto , Anciano , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Pharmaceutical companies often refer to 'screening their library' when performing high-throughput screening (HTS) on a corporate compound collection to identify lead structures for small-molecule drug discovery programs. Characteristics of such a library, including the size, chemical space covered, and physicochemical properties, often determine the success of a screening campaign. Therefore, strategies to maintain and enhance the overall quality of screening collections are crucial to stay competitive and to cope with the 'novelty erosion' that is observed gradually. The Next Generation Library Initiative (NGLI), the enhancement of Bayer's HTS collection by 500000 newly designed compounds within 5 years, is addressing exactly this challenge. Here, we describe this collaborative project, which involves all internal medicinal chemists in a crowd-sourcing approach, as well as selected external partners, to reach this ambitious goal.
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Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento , Bibliotecas de Moléculas Pequeñas , Industria Farmacéutica , Control de CalidadRESUMEN
This Article describes the generation and study of surfaces modified with custom-crafted poly(l-lysine) (PLL) coatings for use in the loading and delivery of single-stranded DNA (ssDNA). The experimental strategy utilizes bidentate dithiol adsorbates to generate stably bound azide-terminated self-assembled monolayers (SAMs) on gold possessing an oligo(ethylene glycol) (OEG) spacer. Consequent to the molecular assembly on gold, the azide termini are covalently attached to a maleimide linker moiety via a copper-catalyzed azide-alkyne "click" reaction. Functionalization with maleimide provides a platform for the subsequent attachment of cysteine-terminated poly(l-lysine) (PLL), thus forming a suitable surface for the loading of ssDNA via electrostatic interactions. In efforts to maximize DNA loading, we generate SAMs containing mixtures of short and long PLL segments and explore the DNA-loading capability of the various PLL SAMs. We then use thermal increases to trigger the release of the ssDNA from the surface. By examining the loading and release of ssDNA using these new two-dimensional systems, we gain preliminary insight into the potential efficacy of this approach when using three-dimensional gold nanostructure systems in future gene-delivery and biosensing applications.
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Polilisina/química , ADN , Oro , Polietilenglicoles , Propiedades de SuperficieRESUMEN
An efficient and convenient solution-phase synthesis of a 1H-1,2,4-triazole library with potential agrochemical activity is reported employing microwave-assisted organic synthesis (MAOS) and continuous-flow microfluidic synthetic methods starting from commercially available 3,5-dibromo-1H-1,2,4-triazole (1). MAOS was used for the synthesis of 5-amino-3-bromo-1,2,4-triazole analogs 3 and for their 3-aryl derivatives 4 via Suzuki-Miyaura coupling with polymer-supported catalyst. A microfluidic hydrogenation reactor integrated into an automated parallel synthesis platform was built and utilized for the reductive dehalogenation reactions providing 5-aminotriazoles (5).