Ear Inflammation Research Articles

P022 Luliconazole—a novel potent imidazole activity against Aspergillus niger and Aspergillus flavus causing otomycosis

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background and ObjectivesSuppurative otitis media (SOM) is characterized by the inflammation of the middle ear and mastoid, tympanic membrane perforation as well as discharge. The tympanic membrane perforation may result in increased exposure of the middle ear to pathogens. Aspergillus niger and Aspergillus flavus, are the most common causative agents of otomycosis with worldwide distribution, when it spreads from the external auditory canal to adjacent anatomical structures, it is classified as Aspergillus invasive otitis externa. Aspergillus otomycosis treatment is initiated by thorough cleaning of the ear canal, accomplished with suction, and drying with cotton swabs. In developing countries, SOM is a major cause of preventable hearing loss, its incidence ranges from 7% to 46% and is common amongst children of lower socioeconomic status. Treatment of SOM is directed at debridement and drying the ear with topical antifungal agents. Extensive surgical debridement and systemic antifungal therapy are needed in cases of refractory otomycosis or Aspergillus invasive otitis externa. Despite this management, treatment failure may result from suboptimal therapeutic management caused by antifungal agent toxicity. Luliconazole is currently confirmed for the topical therapy of dermatophytosis. Moreover, it is found that luliconazole has in vitro activity against some molds and yeast species. The aim of the present study was to evaluate the efficacy of luliconazole in comparison to routinely used antifungals on clinical isolates of A. niger and A. flavus.MethodsThe study was carried out in the Department of Microbiology, SRIHER, Chennai. A total of 55 (29 A. niger and 26 A. flavus) strains of Aspergillus isolates obtained from clinical otomycosis cases were confirmed based on macroscopic and microscopic identification by Lacto Phenol Cotton Blue mount and slide culture technique. Antifungal susceptibility patterns of all the Aspergillus isolates to itraconazole, voriconazole, posaconazole, and luliconazole were determined by broth microdilution method as per Clinical Laboratory Standards Institute (CLSI) M38-A2 guidelines.ResultsThe lowest minimum inhibitory concentration (MIC) geometric mean (GM) (0.00309 μg/ml) was attributed to luliconazole followed by posaconazole (0.18409 μg/ml), voriconazole (1.02727 μg/ml) and itraconazole (11.0091 μg/ml). Also, among the azoles tested, luliconazole had the lowest MIC50 and MIC90 values of 0.00098 μg/ml and 0.00781 μg/ml respectively. Among the triazoles tested posaconazole had a lower MIC50 and MIC90 values of 0.125 μg/ml and 0.25 μg/ml. Being the drug of choice for invasive aspergillosis voriconazole had a slightly higher MIC50 and MIC90 value of 1 μg/ml and 2 μg/ml. Luliconazole was found to be more effective even for pan azole-resistant isolates (n = 3) with lower MIC values.ConclusionThe results of this study showed that luliconazole had an excellent in vitro activity against all Aspergillus isolates with a lower MIC GM, MIC50, and MIC90 values than the triazoles tested. Hence, this novel imidazole antifungal agent can be regarded as appropriate Candidate for the treatment of otomycosis caused by A. niger and A. flavus strains. Also, luliconazole showed better efficacy with lower MIC values for pan azole resistant isolates, suggesting that it could be a potential antifungal for treating aspergillosis caused by pan azole-resistant isolates.

Exopolysaccharides of Bacillus amyloliquefaciens Amy-1 Mitigate Inflammation by Inhibiting ERK1/2 and NF-κB Pathways and Activating p38/Nrf2 Pathway.

Bacillus amyloliquefaciens is a probiotic for animals. Evidence suggests that diets supplemented with B. amyloliquefaciens can reduce inflammation; however, the underlying mechanism is unclear and requires further exploration. The exopolysaccharides of B. amyloliquefaciens amy-1 displayed hypoglycemic activity previously, suggesting that they are bioactive molecules. In addition, they counteracted the effect of lipopolysaccharide (LPS) on inducing cellular insulin resistance in exploratory tests. Therefore, this study aimed to explore the anti-inflammatory effect and molecular mechanisms of the exopolysaccharide preparation of amy-1 (EPS). Consequently, EPS reduced the expression of proinflammatory factors, the phagocytic activity and oxidative stress of LPS-stimulated THP-1 cells. In animal tests, EPS effectively ameliorated ear inflammation of mice. These data suggested that EPS possess anti-inflammatory activity. A mechanism study revealed that EPS inhibited the nuclear factor-κB pathway, activated the mitogen-activated protein kinase (MAPK) p38, and prohibited the extracellular signal-regulated kinase 1/2, but had no effect on the c-Jun-N-terminal kinase 2 (JNK). EPS also activated the anti-oxidative nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Evidence suggested that p38, but not JNK, was involved in activating the Nrf2 pathway. Together, these mechanisms reduced the severity of inflammation. These findings support the proposal that exopolysaccharides may play important roles in the anti-inflammatory functions of probiotics.

Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

The ear is a complex structure consisting of the outer, middle and inner ear. For the proper function of the auditory system, the development of all these parts needs to be highly organized. Any alterations in this chain of events can lead to hearing loss or other impairments, such as dizziness, tinnitus and loss of balance. Of note, several external and internal elements, including noise exposure, ototoxic drugs, aging, as well as environmental or genetic factors, have been widely associated with hearing loss. Over the years, a growing body of evidence has indicated that microRNAs (miRNAs/miRs) play a critical role in ear development and auditory function, suggesting that an altered pattern of miRNA expression may be involved in the progression of these pathological conditions. On these bases, the present review article aimed to summarize the role of miRNAs in inner ear development and hearing disorders. Although further studies are warranted to provide more in‑depth knowledge of the implicated mechanisms of action, according to the current data, miRNAs may be used as novel diagnostic biomarkers for the early detection of hearing loss. In addition, miRNAs and related signaling pathways may represent novel potential therapeutic targets for the treatment of hearing loss, ear inflammation and vestibular schwannoma.

Functional Outcomes of Single-Stage Ossiculoplasty in Chronic Otitis Media With or Without Cholesteatoma.

Background:Two-stage ossiculoplasty has been widely used for hearing improvement in chronic otitis media with or without cholesteatoma. However, the outcomes of single-stage ossiculoplasty have not been fully clarified.The aim of this study is to determine whether the outcomes of single-stage ossiculoplasty are comparable with those of 2-stage ossiculoplasty in chronic otitis media with or without cholesteatoma.Methods:Medical records of 191 cases (187 patients) who underwent single-stage ossiculoplasty from January 2011 to May 2018 at our hospital were retrospectively reviewed.Results:Polycel and titanium were used in 56 and 135 cases, respectively. In chronic otitis media without cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 80.7% and 81.6%, respectively. In chronic otitis media with cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 63.6% and 64.6%, respectively, while that of polycel and titanium total ossicular replacement prosthesis was 45.9% and 47.8%, respectively.Conclusion:These results suggest that single-stage ossiculoplasty is a suitable option for recovering postoperative hearing in chronic otitis media with or without cholesteatoma. Thus, if middle ear inflammation can be sufficiently treated in the first stage, single-stage ossiculoplasty is a suitable option for chronic otitis media with or without cholesteatoma.

Otological Manifestations in Adults with Primary Ciliary Dyskinesia: A Controlled Radio-Clinical Study.

Primary ciliary dyskinesia (PCD) is a rare genetical disease characterized by an abnormal structure or function of the cilia, causing sinusitis, otitis, and bronchiectasis. Hearing loss affects 60% of PCD patients, but data are lacking concerning hearing and temporal bone imaging in adults. Our aim was to describe clinical and radiological ear disease in adults with genetically confirmed PCD. Data were recorded from January 2018 to December 2019. PCD patients were compared with controls with bronchiectasis without PCD. Clinical examination included otomicroscopy and auditory tests. A temporal bone CT scan (TBCT) was systematically performed. Seventeen patients (34 ears) were included in each group. The eardrums were abnormal in 25 (74%) PCD ears versus 8 (24%) ears in the controls (p < 0.05). Conductive hearing loss was more frequent in the PCD group (24% vs. 12% in controls). TBCT were abnormal in 94% PCD patients vs. 32% in the controls (p < 0.05). The Main CT-scan images in PCD were middle ear inflammation (65%), mastoid condensation (62%), or ossicular anomalies (35%). With its excellent sensitivity, TBCT gives typical arguments for PCD diagnosis, adding otological signs to the usual sinus CT signs (hypoplasia, aplasia). Systematic TBCT could be useful in the initial evaluation of patients with suspicion of PCD.

An in-depth discussion of cholesteatoma, middle ear Inflammation, and langerhans cell histiocytosis of the temporal bone, based on diagnostic results.

ObjectiveThis study aimed to conduct an in-depth investigation of the learning framework used for deriving diagnostic results of temporal bone diseases, including cholesteatoma and Langerhans cell histiocytosis (LCH). In addition, middle ear inflammation (MEI) was diagnosed by CT scanning of the temporal bone in pediatric patients.DesignA total of 119 patients were included in this retrospective study; among them, 40 patients had MEI, 38 patients had histology-proven cholesteatoma, and 41 patients had histology-proven LCH of the temporal bone. Each of the 119 patients was matched with one-third of the disease labels. The study included otologists and radiologists, and the reference criteria were histopathology results (70% of cases for training and 30% of cases for validation). A multilayer perceptron artificial neural network (VGG16_BN) was employed and classified, based on radiometrics. This framework structure was compared and analyzed by clinical experts according to CT images and performance.ResultsThe deep learning framework results vs. a physician’s diagnosis, respectively, in multiclassification tasks, were as follows. Receiver operating characteristic (ROC) (cholesteatoma): (0.98 vs. 0.91), LCH (0.99 vs. 0.98), and MEI (0.99 vs. 0.85). Accuracy (cholesteatoma): (0.99 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Sensitivity (cholesteatoma): (0.96 vs. 0.97), LCH (0.99 vs. 0.98), and MEI (1 vs. 0.69). Specificity (cholesteatoma): (1 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89).ConclusionThis article presents a research and learning framework for the diagnosis of cholesteatoma, MEI, and temporal bone LCH in children, based on CT scans. The research framework performed better than the clinical experts.

Acute otitis media in children 6 months to 2 years of age.

Acute otitis media (AOM) is one of the most common findings among children in our family medicine office, and we frequently see this illness during seasons with high rates of upper respiratory tract infections. With more widespread pneumococcal immunization, has the rate of AOM declined? What are the current recommendations for antibiotic treatment? Although rates of the infection have declined over time with better uptake of vaccines against Streptococcus pneumoniae, AOM is still prevalent in the pediatric population and may be associated with serious complications that affect hearing and quality of life. Once a diagnosis has been made (based on a combination of acute onset of symptoms, signs of middle ear inflammation, and effusion), treatment of children 6 months to 2 years of age depends on physical examination findings. Children with perforated tympanic membranes and purulent discharge should receive 10 days of systemic antibiotics. For children with more mild symptoms or early AOM, primary care providers should consider either treatment or watchful waiting.

Phenolic profile, safety, antioxidant and anti-inflammatory activities of wasted Bunium ferulaceum Sm. aerial parts

The pharmaceutical and nutraceutical industries benefit greatly from recycling and transforming non-utilized parts of medicinal plants from agro-industrial operations into value added products. Hence, the aim of this work was to study the potential nutraceutical and pharmaceutical applications of Bunium ferulaceum Sm. aerial parts, in order to maximize their value. The phenolic profile of their hydromethanolic extract was determined and its antioxidant activity was evaluated in vitro and in vivo alongside with its anti-inflammatory activity and safety profile. The extract exerted an in vitro antioxidant activity mainly through radical scavenging (DPPH IC50: 14.0 ± 0.3 µg/ml) and iron chelating ability (24 ± 2 µg/ml), while, in vivo, the extract did not cause any mortality or visible signs of acute toxicity at high dose (2000 mg/kg body weight). The supplementation of the extract at different doses improved mice liver redox state by increasing catalase and reduced glutathione levels and reducing lipid peroxidation, without causing any toxicity. Moreover, the extract efficiently inhibited xylene induced ear inflammation (62 %). These different bioactivities were linked to the phenolic compounds present in the extract, particularly, chlorogenic acid (78 ± 6 mg/g extract), rutin (44 ± 2 mg/g extract) and hesperidin (56 ± 9 mg/g extract). However, further studies should be carried out on the isolated major compounds found in the extract to correlate the activity with these compounds or their mixture. The wasted aerial parts of Bunium ferulaceum Sm. proved to be a valuable source of polyphenols and exhibited interesting health promoting effects with no toxicity. Thus, Bunium ferulaceum Sm. aerial parts can be included in nutraceutical formulations or used as functional food and the extracted compounds may be used as an alternative food preservative.

A multicenter study to investigate the positive rate of SARS-CoV-2 in middle ear and mastoid specimens from otologic surgery patients

ObjectiveSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19). Otologic surgeries with drilling by powered instruments induce significant aerosols, which may induce SARS-CoV-2 transmission to medical staff if SARS-CoV-2 exists in the middle ear and mastoid cavity. During a COVID-19 pandemic, therefore, confirming a negative COVID-19 test prior to otologic surgery is recommended. However, previous coronavirus studies demonstrated that coronavirus was detected in the middle ear in some patients even though the polymerase chain reaction (PCR) test using their nasopharyngeal swab was negative. This study aimed to elucidate the probability of a positive SARS-CoV-2 PCR test in the middle ear or mastoid specimens from otologic surgery patients in whom SARS-CoV-2 was not detected by preoperative PCR test using a nasopharyngeal swab. MethodsWe conducted a prospective, multicenter clinical study. Between April 2020 and December 2021, during the COVID-19 pandemic, 251 ears of the 228 participants who underwent otologic surgery were included in this study. All participants had no symptoms suggesting COVID-19 or close contact with a confirmed COVID-19 patient two weeks prior to the surgery. They were also negative in the SARS-CoV-2 PCR tests using a nasopharyngeal swab before surgery. We collected mucosa, granulation, bone dust with mucosa or fluid from the middle ear or mastoid for the SARS-CoV-2 PCR tests during each otologic surgery. ResultsThe median age of the participants at surgery was 31.5 years old. Mastoidectomy using a powered instrument was conducted in 180 of 251 otologic surgeries (71.8%). According to intraoperative findings, active inflammation in the middle ear or mastoid cavities was evident in 20 otologic surgeries (8.0%), while minor inflammation was observed in 77 (30.7%). All SARS-CoV-2 PCR tests of otologic specimens showed a negative result. No patient suffered from COVID-19 within two months after otologic surgery. Furthermore, no hospital-acquired infections associated with otologic surgery occurred in our institutions ConclusionsOur results showed that PCR testing did not detect SARS-CoV-2 in middle ear and mastoid specimens, suggesting that the risk of transmission of SARS-CoV-2 is not high in otologic surgeries even using powered instruments when both clinical and laboratory tests are confirmed to be negative for COVID-19.

Organs-at-risk dose constraints in head and neck intensity-modulated radiation therapy using a dataset from a multi-institutional clinical trial (JCOG1015A1)

BackgroundJCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015.MethodsIndividual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities.ResultsThe 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less).ConclusionsThe dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Modern trends in the treatment of otitis media in children and adults

Otitis media, which is an inflammatory process in the middle ear cavity, is a fairly common disease. Its incidence is up to 30 % of all otolaryngological pathology. The main route of transmission is tubogenic, in which the pathogen migrates from the nasopharynx into the middle ear cavity through the pharyngeal pouch of the auditory tube. The main causative agents of acute otitis media are S. pneumoniae and nontypeable strains of H. influenzae, less often — M. catarrhalis. Otitis media of viral etiology occurs in no more than 6 % of cases. Most often, otitis media affects children, mostly under the age of 3 years. The course of the disease is characterized by a pronounced staging of the pathological process: the catarrhal stage is replaced by the purulent one, which turns into the reparative one during recovery. In adult patients, inflammation of the middle ear is relatively rare; the older age group is characterized by an atypical course without otorrhea and pain in the mastoid process. The main complications of otitis media include the spread of infection into the intracranial space, the occurrence of the facial nerve paresis, and the development of mastoiditis and sepsis. One of the main problems in the treatment of otitis media is the resistance of the microflora that caused it to β-lactam drugs.

Pneumatization Pattern and Status of the Mastoid Antrum in Chronic Otitis Media: A Review.

Chronic otitis media is generally more prevalent in individuals with a weakly pneumatized temporal bone, whereas acute otitis media has a propensity for pneumatized temporal bone. Antimicrobial drugs are thought to have influenced the incidence and progression of middle ear infections. The mastoid air cell system, a part of the middle ear cleft, has recently been recognized as a crucial factor in the genesis, behaviour, course, and outcome of middle ear inflammatory conditions. Epithelium infiltrates the growing bone and produces epithelium-lined air cell chambers, a process known as pneumatization.Conventional temporal bone radiography, i.e. X-ray mastoid, has not kept up with recent otology breakthroughs. Detailed visualization of the aural structures has advanced significantly with the introduction of high-resolution computed tomography (HRCT). HRCT has a clear edge in the assessment of the temporal bone, especially when thin-section, high-resolution methods are used, resulting in a more precise description of the pneumatization pattern and the anatomical extent of middle ear pathology.Our results of the review indicated that persistent inflammation of the middle ear in children inhibits pneumatization of the temporal bone. Due to its potential to exert a greater negative middle ear pressure, the middle ear volume is insufficient to generate a retraction pocket; thus, the size and state of the antrum is also a significant factor in the establishment of a COM-like retraction pocket in inactive squamosal disease. Numerous factors, including the number of patients, regional, genetic, ethnic and hereditary characteristics, as well as the cellularity of the mastoid, which is impacted by a multitude of factors, may account for the variable reports and inter-study variation in this regard.

Electrospun nanofibrous membrane functionalized with dual drug-cyclodextrin inclusion complexes for the potential treatment of otitis externa

External ear canal infections and inflammation (called otitis externa) represent considerable health and psychological problem. It is commonly treated via an ointment combination of ciprofloxacin (CIP) and dexamethasone (DEX). The ointment application has a shorter residence time, could fail to reach the target area, and their uncontrolled use could perforate the eardrum and promote superbugs infections. Therefore, current studies aimed to modulate drug release, drug performance, targeted drug delivery, and optimized single application of dual drugs based β-cyclodextrin (βCD) inclusion complex. Herein, polymer-free (βCD-CIP and βCD-DEX) and polymer-based (βCD-CIP/polycaprolactone and βCD-DEX/polycaprolactone) nanofibers were fabricated via electrospinning in multilayered form. The surface of the inclusion complex entrapped nanofibers was coated with catechol-functionalized adhesive nanofibers. The morphological, physicochemical, thermo-mechanical, crystalline, and contact angle studies confirm the entrapment of inclusion complex in nanofibers. The studied polymer-based nanofibers were mechanically stable, convenient for storage, integrated and ensured amorphous distribution of both drugs, possessed initial burst, and then sustained drug release, and better inhibited bacterial growth. The surface adhesiveness and tunable biophysical properties could prolong drug residence and expand nanocomposite applicability. Overall, the designed nanofibrous system could enable single application-based dual drug delivery to treat ear canal infections.

Association of otitis media with dental caries in children: a systematic review

Introduction: Otitis media, also known as middle ear infection, refers to any inflammation of the middle ear. It may be attributable to bacteria like Streptococcus pneumoniae and Hemophilus influenzae (most commonly involved), though viruses can also cause middle ear infection. It affects the pediatric group during the first three years of life, with 80% youngsters having had one otitis media episode at the minimum by age three years, 50% having had at least three episodes, while a smaller number experience their first episode after age three years. This phenomenon has also been linked to an increased presence of Streptococcus mutans which in turn raises the risk of acquiring dental caries.&#x0D; Objective: To determine whether an association exists between middle ear infection and the high occurrence of Streptococcus mutans that ultimately leads to dental caries in children and causes poor oral hygiene problems.&#x0D; Materials &amp; Methods: A comprehensive and well-organized search of published articles was conducted in February 2022. The investigation was conducted using the Reporting Items for Systematic Reviews. Articles that fulfilled the predefined inclusion and exclusion criteria were appraised with respect to the key objectives of the review.&#x0D; Results: Based on the findings of the studies highlighted in this systematic review, not only was there a positive correlation between middle ear infection and dental caries, but some data were also supplied on the nature of the link between early childhood caries and middle ear infection.&#x0D; Conclusion: Increased Streptococcus mutans levels in early childhood together with other contributory risk factors such as middle ear infection could enhance the incidence of early childhood dental caries.

CoCl2 -simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived fromtympanosclerosis by upregulating the expression of BMP-2.

Tympanosclerosis (TS) is a result of long-standing middle ear inflammation characterized by fibroblasts ossification. Fibrosis is the last revertible stage in the progress of middle ear inflammation to TS. It was hypothesized that chronic hypoxia could be modulating fibrosis, which in turn additionally further aggravated hypoxia via decreasing oxygen diffusion. However, the effects of hypoxia on osteoinductive activity of fibroblasts have not been explored. Herein, we purposed to explore the role of hypoxia in osteogenic differentiation of fibroblasts derived from TS. The expression of bone morphogenetic protein-2 (BMP-2), hypoxia-inducible factor-1α (HIF-1α), and Vimentin in the human surgical specimens of tympansclerosis was investigated by immunofluorescent staining. Furthermore, cultured fibroblasts were stratified into the following study groups: control, 25, 50, and 100 μM cobaltous chloride (CoCl2 ) group. BMP-2, as well as HIF-1α levels of expression were detected via western blotting and immunofluorescence analysis. We found that the expression of BMP-2 and HIF-1α was significantly upregulated in TS tissues and these fibroblasts, which was vimentin positive surrounding sclerotic plaques, were also expressing HIF-1α positive. The results also demonstrated that CoCl2 treatment increased nuclear HIF-1α protein level in the fibroblast. Furthermore, treatment with CoCl2 significantly increased BMP-2 expression and remarkably elevated alkaline phosphatse activity and the mineralized nodules area. These data illustrate that hypoxia may play an osteogenic role in TS fibroblasts via the elevated expression of a possible osteogenic factor, BMP-2.

Otitis media in children: Risk factors &amp; causative organisms

Otitis media is inflammation of the middle ear and the tympanic membrane, which often occurs as a result of an acute upper respiratory tract infection. Generally, it is caused by a viral infection that is then complicated by a secondary bacterial infection. However, the initial infection may also be bacterial.Otitis media is very common in children and there is a high rate of spontaneous recovery. It has been suggested that it is an unavoidable illness of childhood and part of the natural maturation of a child’s immune system. Despite this, supportive complications can occur, such as perforation of the tympanic membrane, otitis externa and mastoiditis, as well as other sequelae affecting balance, motor control and hearing.

Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies

Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E2, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable ( ∗ ∗ ∗ P &lt; 0.001 ) till the 5th hour of test sample injection. Compound D also exhibited excellent percent inhibition (63.81 ± 2.24%) at the highest dose in arachidonic acid-induced ear inflammation. On the basis of in vivo and in vitro results, compound D was subjected to various inflammation-causing agents such as histamine, prostaglandins E2, bradykinin, and leukotriene via the mouse paw edema test. Compound D revealed moderate effect (28.10 ± 1.64%) against histamine-induced paw edema while nonsignificant result (9.72 ± 3.125%) was marked for the bradykinin pathway. Compound D showed significance against edematogenic consequence of prostaglandin E2 (56.28–72.03%) and leukotriene (55.13 ± 2.25%) induced inflammation. In summary, our findings recommended that compound D possesses double acting anti-inflammatory properties inhibiting both COX and LOX pathways. Binding orientations and energy values computed via docking simulations support the results of the experimental in vitro evaluation.

A Small Molecule Selected from a DNA‐Encoded Library of Natural Products That Binds to TNF‐α and Attenuates Inflammation In Vivo (Adv. Sci. 21/2022)

nDEL in Reversable Pharmacology Natural product DNA-encoded library (nDEL) has great value in reverse pharmacology. In article number 2201258, Peixiang Ma, Hongtao Xu, Guang Yang, and co-workers applied nDEL in a reverse pharmacology study targeting tumor necrosis factor α (TNF-α). Several natural products, particularly kaempferol are identified to recognize and attenuate the TNF-α signaling as that of adalimumab, and reduce mice ear inflammation.

Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging

BackgroundTherapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far.ResultsPenetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSCCxcr3). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSCCxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSCCxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis.ConclusionsTAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy.Graphical

Otitis media with effusion in children aged 2–12 years attending the paediatric clinic at Mulago National Referral Hospital, a Ugandan tertiary hospital: a cross-sectional study

BackgroundOtitis media with effusion (OME) is common in children aged between 6 months to 4 years, and it is one of the causes of hearing loss (HL) in children worldwide. OME is a type of inflammation of the middle ear in which there is a collection of fluid. The latter causes HL which interferes with speech and language development, communication skills, school performance, psychosocial skills, and quality of life of children.MethodsThis was a prospective cross-sectional study on 246 children aged 2 -12 years, attending the Mulago National Referral Hospital (MNRH). A consecutive sampling procedure was used to reach each participant under ethical considerations until the sample size was reached. All children aged 2–12 years who meet inclusion criteria were examined first by the Pediatrician and then by the Principal Investigator. Patients with tympanogram type B (flat curve) were diagnosed to have OME. The prevalence of OME was summarized as a proportion and multivariate analysis was used to determine the factors associated with OME. Data were analyzed using the STATA version 13.0.ResultsA total of 246 children were recruited for the study. Of the 246 children, 60% were male. The median age of the participants was 4.8 ± 2.8 years. The prevalence of OME was found to be 11%. Upper respiratory tract infections (URTI), recurrent AOM (p = 0.005, OR:5.14, 95% CI: 1.66–15.96), and snoring (p = 0.000, OR: 6.32, 95% CI: 2.32–17.26) were found to be strongly associated with OME in children aged 2–12 years attending the Mulago National Referral Hospital.ConclusionsThe prevalence of OME among children aged 2–12 years attending MNRH was found to be 11%. There is an association between OME and URTI, recurrent AOM, and snoring in children aged 2–12 years attending MNRH.