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Introduction: Cholesteatoma usually harbors a poly-microbial infection. As the diversity of bacterial pathogens in the Indian COM is unknown, we set out to identify the bacteria associated with cholesteatoma disease in different patients of North India using targeted metagenomic analysis of the 16 S rRNA gene. Methods: We recruited 15 patients of cholesteatomatous chronic otitis media (COM), who underwent surgical disease clearance. We divided these patients into four groups based on the four clinic-radiological stages categorized as per the EAONO/JOS joint consensus statement classification. Representative samples were extracted during the surgery and sent for bacterial culture and sensitivity and 16 S rRNA gene metagenomic analysis. Results: While 12 (80%) of the patients belonged to clinical Stage I/II; one patient had an extracranial complication (stage III) and two patients had an intracranial complication (stage IV). Our detailed bacterial metagenomics analyses showed that while phylum Proteobacteria was most abundant (reads up to ⼠95%) in specimens from nine patients, phylum Firmicutes was most abundant (up to ⼠80%) in specimens from four patients. Gamma (γ) Proteobacteria and Epsilon (ε) Proteobacteria were the most abundant class amongst Proteobacteria. Class Tissierellia stood out as the most abundant Firmicutes (40-60%), followed by Clostridia (20%) and Bacilli (10%). There was negligible difference in the bacterial profiles across all four clinical stages. Conclusion: Cholesteatoma is primarily associated with Proteobacteria and Firmicutes phyla, even in complicated disease. Further studies with a larger sample size are required to validate our findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04678-9.
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Speech and hearing impairments are among the most common problems in Indian societies. It can affect anyone, whether children, adults, or more. Many different treatments can help to overcome hearing problems. Different types of hearing aids and cochlear implants help amplify sounds for better hearing. The type of language known as sign language is very scientific and has its grammar and syntax. Still, due to a need for more awareness among hard-of-hearing persons, they need to be made familiar with the institutions where they can learn and equip themselves for communication. This paper describes an approach to aid speech and hard-of-hearing persons so that they are free to communicate with persons who do not have speech and hearing disabilities based on the Indian Sign Language System. To find an appropriate solution, there is a need to develop a system that can act as an interpreter for speech and hard-of-hearing persons. The interpreter system is designed with the help of the Robotic hand model and is programmed using Raspberry Pi 4. Based on the experimental results, it can be observed that the robotic hands generated different signs of the alphabet corresponding to the speech commands uttered by an individual. Several experimental trials were conducted by ten persons who do not have any hearing disabilities. The results of the five experimental trials are shown in this paper. The estimation of performance parameters and statistical analysis are also carried out to analyze better and interpret the experimental results. Based on the experimental results, the proposed robotic hand interpreter system model accurately generates gestures corresponding to different alphabets used in the Indian Sign Language system, yielding an overall accuracy of 94 percent.
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Tissue ablation techniques have long been used in clinical settings to treat various oncologic diseases. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is a noninvasive, nonionizing, nonthermal tissue ablation technique that has the potential to replace surgical interventions in various clinical settings. Histotripsy works by delivering high-intensity focused ultrasound waves to target tissue. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tissue into acellular debris that is subsequently absorbed by the body's immune system. Preclinical and clinical studies have demonstrated the efficacy of histotripsy in treating a range of diseases, including liver, pancreatic, renal, and prostate tumors. Safety outcomes of histotripsy have been generally favorable, with minimal adverse effects reported. However, further studies are needed to optimize the technique and understand its long-term effects. This review aims to discuss the importance of histotripsy as a noninvasive tissue ablation technique, the preclinical and clinical literature on histotripsy and its safety, and the potential applications of histotripsy in clinical practice. Keywords: Tumor Microenvironment, Ultrasound-High-Intensity Focused (HIFU), Ablation Techniques, Abdomen/GI, Genital/Reproductive, Nonthermal Tissue Ablation, Histotripsy, Clinical Trials, Preclinical Applications, Focused Ultrasound © RSNA, 2024.
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Técnicas de Ablación , Neoplasias de la Próstata , Masculino , Humanos , Técnicas de Ablación/métodos , Hígado/cirugía , Ultrasonografía , Riñón , Microambiente TumoralRESUMEN
Histotripsy, a non-thermal ultrasound technique, holds significant promise in various applications within the realm of brain interventions. While its use for treating brain tumors is somewhat limited, focused ultrasound technology has been extensively investigated for a wide range of purposes within the brain, including disrupting the blood-brain barrier, supporting immunotherapy, addressing conditions like essential tremor, Parkinson's disease, Alzheimer's disease, epilepsy, and neuropathic pain. Research findings indicate that histotripsy can reduce tumor cells with fewer pulses, minimizing the risk of bleeding and cellular injury. The use of MRI sequences such as T2 and T2* enhances the evaluation of the effects of histotripsy treatment, facilitating non-invasive assessment of treated areas. Furthermore, histotripsy displays promise in creating precise brain lesions with minimal edema and inflammation, particularly in porcine models, suggesting considerable progress in the treatment of brain lesions. Moreover, studies confirm its feasibility, safety, and effectiveness in treating intracerebral hemorrhage by safely liquefying clots without causing significant harm to surrounding brain tissue., opening exciting possibilities for clinical applications. The development of transcranial MR-guided focused ultrasound systems based on histotripsy represents a significant breakthrough in overcoming the limitations associated with thermal ablation techniques. Histotripsy's ability to efficiently liquefy clots, minimize skull heating, and target shallow lesions near the skull establishes it as a promising alternative for various brain treatments. In conclusion, histotripsy offers diverse potential in the field of brain interventions, encompassing applications ranging from tumor treatment to the management of intracerebral hemorrhage. While challenges such as accurate monitoring and differentiation of treatment effects persist, ongoing research efforts and technological advancements continue to expand the role of histotripsy in both neurology and neurosurgery.
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Técnicas de Ablación , Neoplasias Encefálicas , Humanos , Animales , Porcinos , Ultrasonografía/métodos , Neoplasias Encefálicas/cirugía , Hemorragia Cerebral , Encéfalo/diagnóstico por imagen , Encéfalo/cirugíaRESUMEN
Histotripsy, an innovative ultrasonic technique, is poised to transform the landscape of cardiovascular disease management. This review explores the multifaceted applications of histotripsy across various domains of cardiovascular medicine. In thrombolysis, histotripsy presents a non-invasive, drug-free, and precise method for recanalizing blood vessels obstructed by clots, minimizing the risk of vessel damage and embolism. Additionally, histotripsy showcases its potential in congenital heart defect management, offering a promising alternative to invasive procedures by creating intracardiac communications noninvasively. For patients with calcified aortic stenosis, histotripsy demonstrates its effectiveness in softening calcified bioprosthetic valves, potentially revolutionizing valve interventions. In the realm of arrhythmias, histotripsy could play an important role in scar-based ventricular tachycardia ablation, eliminating channel-like isthmuses of slowly conducting myocardium. Histotripsy`s potential applications also extend to structural heart interventions, enabling the safe sectioning of basal chordae and potentially addressing mitral regurgitation. Furthermore, it showcases its versatility by safely generating ventricular septal defects, providing a non-invasive means of creating intracardiac communications in neonates with congenital heart disease. Yet, most supporting studies are in-vitro or animal studies and there are possible challenges in translating experimental data on cardiac histotripsy to the clinical level. As histotripsy continues to evolve and mature, its remarkable potential in cardiovascular disease management holds promise for improving patient outcomes and reducing the burden of invasive procedures in the field of cardiology.
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Background and Objective: Osteomyelitis, a severe bone infection caused mainly by pyogenic organisms, poses diagnostic challenges due to its non-specific magnetic resonance imaging (MRI) manifestations. Conventional MRI, though the imaging modality of choice, often exhibits signal abnormalities with overlapping differential diagnoses, potentially leading to overestimation of infection extent and duration. To address these limitations, advanced MRI sequences, including dynamic contrast-enhanced (DCE) MRI, 1H magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and Dixon techniques have emerged as promising alternatives. This narrative review explores the potential role of these sequences in aiding the differential diagnosis of osteomyelitis. Methods: We used the PubMed database to search for relevant articles using the MeSH keywords: (osteomyelitis) AND (advanced MRI sequences) and we manually selected the most suitable studies to include in our review. Articles outside of original studies were also included. Only records in English or French were considered. Key Content and Findings: In particular, DWI is useful for characterizing fluid collections, distinguishing bone infarcts, and bacterial skull base osteomyelitis from neoplastic lesions. Moreover, DWI assists in differentiating diabetic foot osteomyelitis (DFO) from Charcot neuro-osteoarthropathy, facilitates the diagnosis of pediatric acute osteoarticular infections, and aids in distinguishing osteomyelitis from Modic I degenerative changes. Additionally, DWI proves valuable in monitoring spinal infections and distinguishing pedal osteomyelitis from other conditions, even in patients with renal impairment. DCE-MRI enhances MRI specificity by assessing contrast uptake over time, providing valuable insights into inflammatory microenvironments. It aids in detecting DFO, differentiating it from acute Charcot arthropathy, and distinguishing osteomyelitis from neuropathic arthropathy. Moreover, DCE-MRI shows potential in assessing response to antibiotic therapy in spinal infections. Dixon acquisition improves image quality and facilitates the detection of bone marrow abnormalities, aiding in the differentiation of diabetic foot from osteomyelitis. It also assists in distinguishing osteomyelitis from neuropathic arthropathy and provides valuable information in evaluating the diabetic foot. Proton MR spectroscopy, a well-established modality, offers metabolic information that can differentiate malignant from benign lesions. Conclusions: The role of advanced MRI techniques in evaluating osteomyelitis remains to be fully defined, and further research is required to explore its potential utility in this context. In conclusion, the incorporation of advanced MRI sequences has shown promise in improving the differential diagnosis of osteomyelitis. Future investigations exploring combinations of these techniques and their clinical applications hold significant potential to enhance diagnostic accuracy and patient outcomes.
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BACKGROUND: The relative motion (RM) orthosis was introduced over 40 years ago for extensor tendon rehabilitation and more recently applied to flexor tendon repairs. PURPOSE: We systematically reviewed the evidence for RM orthoses following surgical repair of finger extensor and flexor tendon injuries including indications for use, configuration and schedule of orthosis wear, and clinical outcomes. STUDY DESIGN: Systematic review. METHODS: A PRISMA-compliant systematic review searched eight databases and five trial registries, from database inception to January 7, 2022. The protocol was registered prospectively (CRD42020211579). We identified studies describing patients undergoing rehabilitation using RM orthoses after surgical repair of acute tendon injuries of the finger and hand. RESULTS: For extensor tendon repairs, ten studies, one trial registry and five conference abstracts met inclusion criteria, reporting outcomes of 521 patients with injuries in zones IV-VII. Miller's criteria were predominantly used to report range of motion; with 89.6% and 86.9% reporting good or excellent outcomes for extension lag and flexion deficit, respectively. For flexor tendon repairs, one retrospective case series was included reporting outcomes in eight patients following zones I-II repairs. Mean total active motion was 86%. No tendon ruptures were reported due to the orthosis not protecting the repair for either the RME or RMF approaches. DISCUSSION: Variation was seen in use of RME plus or only, use of night orthoses and orthotic wear schedules, which may be the result of evolution of the RM approach. Since Hirth et al's 2016 scoping review, there are five additional studies, including two RCTs reporting the use of the RM orthosis in extensor tendon rehabilitation. CONCLUSIONS: There is now good evidence that the RM approach is safe in zones V-VI extensor tendon repairs. Limited evidence currently exists for zones IV and VII extensor and for flexor tendon repairs. Further high-quality clinical studies are needed to demonstrate its safety and efficacy.
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Traumatismos de los Dedos , Traumatismos de los Tendones , Humanos , Estudios Retrospectivos , Aparatos Ortopédicos , Traumatismos de los Tendones/cirugía , Traumatismos de los Tendones/rehabilitación , Tendones , Dedos , Traumatismos de los Dedos/cirugía , Traumatismos de los Dedos/rehabilitación , Rango del Movimiento ArticularRESUMEN
BACKGROUND AND OBJECTIVES: Cholesteatomatous chronic otitis media acquires epithelial proliferation and differentiation characteristics, which render it able to erode the underlying bone and cause complications. We attempt to characterize the cholesteatoma epithelium by observing the expression of cytokeratins (such as 34ße12, CK17, and CK13) and Ki67 among patients with cholesteatoma with different aggressiveness as compared to disease-free controls. Subjects and. METHODS: In this prospective study (2017-2021), we enrolled all consenting consecutive patients with cholesteatomatous chronic otitis media. They were staged in accordance with the staging guidelines of the European Academy of Otology and Neurotology and the Japanese Otological Society. Bony external auditory canal (EAC) skin specimens of the patients undergoing tympanoplasty were chosen as controls. We did an immunohistochemical analysis of the cholesteatoma specimens and normal bony EAC controls by observing the expression of 34ße12, CK17, CK13, and Ki67 across the layers of the epithelium. Fisher's exact test and chi-square test were used to evaluate any statistical significance between the cases and the controls, and the subgroups were made based on the clinical stage. RESULTS: An increased expression of CK17 (p<0.001), CK13 (p<0.03), and Ki67 (p<0.001) was observed in cholesteatoma specimens when compared to normal bony EAC controls. Also, there was a loss of expression of 34ße12 in a subset of cholesteatoma specimens, all of which showed full-thickness expression of CK13. There was no difference in the expression of cytokeratin among specimens from patients belonging to different subgroups based on clinical stage, age, sex, duration of ear symptoms, or type of hearing loss (conductive vs. sensorineural). CONCLUSIONS: The majority of cholesteatoma specimens significantly overexpressed CK17, CK13, and Ki67 when compared to normal bony EAC skin controls, while a subset showed loss of expression of 34ße12, which provides some insight into its pathogenesis.
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Purpose. To revise the current literature on FIL SSF (Carlevale) intraocular lens, previously known as Carlevale lens, and to compare their outcomes with those from other secondary IOL implants. Methods. We performed a peer review of the literature regarding FIL SSF IOLs until April 2021 and analyzed the results only of articles with a minimum of 25 cases and a follow-up of at least 6 months. The searches yielded 36 citations, 11 of which were abstracts of meeting presentations that were not included in the analysis because of their limited data. The authors reviewed 25 abstracts and selected six articles of possible clinical relevance to review in full text. Of these, four were considered to be sufficiently clinically relevant. Particularly, we extrapolated data regarding the pre- and postoperative best corrected visual acuities (BCVA) and the complications related to the procedure. The complication rates were then compared with those from a recently published Ophthalmic Technology Assessment by the American Academy of Ophthalmology (AAO) on secondary IOL implants. Results. Four studies with a total of 333 cases were included for results analysis. The BCVA improved in all cases after surgery, as expected. Cystoid macular edema (CME) and increased intraocular pressure were the most common complications, with an incidence of up to 7.4% and 16.5%, respectively. Other IOL types from the AAO report included anterior chamber IOLs, iris fixation IOLs, sutured iris fixation IOLs, sutured scleral fixation IOLs, and sutureless scleral fixation IOLs. There was no statistically significant difference in the rates of postoperative CME (p = 0.20), and vitreous hemorrhage (p = 0.89) between other secondary implants and the FIL SSF IOL, whereas the rate of retinal detachment was significantly less with FIL SSF IOLs (p = 0.04). Conclusion. The results of our study suggest the implantation of FIL SSF IOLs is an effective and safe surgical strategy in cases where there is a lack of capsular support. In fact, their outcomes seem to be comparable to those obtained with the other available secondary IOL implants. According to published literature, the FIL SSF (Carlevale) IOL provides favorable functional results with a low rate of postoperative complications.
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Background: Propensity score matching (PSM), a statistical technique that estimates a treatment effect by accounting for predictor covariates, has been used to evaluate biologics for inflammatory bowel disease (IBD). Financial conflicts of interest are prevalent in the marketing of biologic medications. It is unclear whether this burden of conflicts is present among authors of PSM studies comparing IBD biologics and biosimilars. Objective: This study was aimed to determine the prevalence of financial conflicts of interest among authors of PSM studies evaluating IBD biologics and biosimilars. Methods: We conducted a systematic search for PSM studies comparing biologics and biosimilars in IBD treatment. We identified 21 eligible studies. Two independent authors extracted self-declared conflicts from the disclosures section. Each participating author was searched on the Centers for Medicare & Medicaid Services Open Payments to identify payment amounts and undisclosed conflicts. Primary outcome was the prevalence of author conflicts. Secondary analyses assessed for an association between conflict prevalence and reporting of positive outcomes. Results: Among 283 authors, conflicts were present among 41.0% (116 of 283). Twenty-three per cent (27 of 116) of author conflicts involved undisclosed payments. Studies with positive outcomes were significantly more likely to include conflicted authors than neutral studies (relative risk = 2.34, 95% confidence interval: 1.71 to 3.21, P < 0.001). Conclusions: Overall, we found a high burden of undisclosed conflicts among authors of PSM studies comparing IBD biologics and biosimilars. Given the importance of PSM studies as a means for biologic comparison and the potential for undue industry influence from these payments, authors should ensure greater transparency with reporting of industry relationships.
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Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.
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Curcumina , Enfermedades de la Retina , Apoptosis , Curcumina/farmacología , Curcumina/uso terapéutico , Humanos , Enfermedades de la Retina/tratamiento farmacológicoRESUMEN
The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multisubunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress, has not been sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8, is a bona fide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that the requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that GTPBP8, the human orthologue, complements the loss of cellular respiration in Δmrx8 cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggests a universal role of the MRX8 family of proteins in regulating mitochondrial function.
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Complejo IV de Transporte de Electrones/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , GTP Fosfohidrolasas/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismo , Ribosomas Mitocondriales/metabolismo , Fosforilación Oxidativa , Biosíntesis de Proteínas , ARN de Hongos/metabolismo , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Saccharomyces cerevisiae/metabolismo , Temperatura , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Since 2008, the Canadian Institutes of Health Research (CIHR) has mandated that studies it funds either in whole or in part are required to publish their results as open access (OA) within 12 months of publication using either online repositories and/or OA journals. Yet, there is evidence that authors are poorly compliant with this mandate. Specifically, there has been an apparent decrease in OA publication after 2015, which coincides with a change in the OA policy during the same year. One particular policy change that may have contributed to this decline was lifting the requirement that authors deposit their article in an OA repository immediately upon publication. We investigated the proportion of OA compliance of CIHR-funded studies in the period before and after the policy change of 2015 with manual confirmation of both CIHR funding and OA status. METHODS AND FINDINGS: We identified CIHR-funded studies published between the years 2014 to 2017 using a comprehensive search in the Web of Science (WoS). We took a stratified random sample from all four years (i.e. 2014 to 2017), with 250 studies from each year. Two authors independently reviewed the final full-text publications retrieved from the journal web page to determine to confirm CIHR funding, as indicated in the acknowledgements or elsewhere in the paper. For each study, we also collected bibliometric data that included citation count and Altmetric attention score Statistical analyses were conducted using two-tailed Fisher's exact test with relative risk (RR). Among the 851 receiving CIHR funding published from 2014 to 2017, the percentage of CIHR-funded studies published as OA significantly decreased from 79.6% in 2014 to 70.3% in 2017 (RR = 0.88, 95% CI: 0.79-0.99, P = 0.028). When considering all four years, there was no significant difference in the percentage of CIHR-funded studies published as OA in both 2014 and 2015 compared to both 2016 and 2017 (RR = 0.97, 95% CI: 0.90-1.05, P = 0.493). Additionally, OA publications had significantly higher citation count (both in year of publication and in total) and higher attention scores (P<0.05). CONCLUSIONS: Overall, we found that there was a significant decrease in the proportion of CIHR funded studies published as OA from 2014 compared to 2017, though this difference did not persist when comparing both 2014-2015 to 2016-2017. The primary limitation was the reliance of self-reported data from authors on CIHR funding status. We posit that this decrease may be attributable to CIHR's OA policy change in 2015. Further exploration is warranted to both validate these studies using a larger dataset and, if valid, investigate the effects of potential interventions to improve the OA compliance, such as use of a CIHR publication database, and reinstatement of a policy for authors to immediately submit their findings to OA repositories upon publication.
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Investigación Biomédica/economía , Publicación de Acceso Abierto , Canadá , Bases de Datos Factuales , Publicación de Acceso Abierto/tendencias , Apoyo a la Investigación como AsuntoRESUMEN
The future of robotic ophthalmologic surgery looks promising. Innovations in robotic technology and artificial intelligence may provide an ideal machine-human interface with planned and precise movements minimizing unwanted tissue damage and improving clinical outcomes.