Objectives: Epstein-Barr virus (EBV) infection is strongly associated with the development of nasopharyngeal carcinoma. However, existing diagnostic methods based on EBV antibodies and plasma DNA exhibit insufficient sensitivity and specificity for early detection. This study aimed to overcome this limitation by developing a highly sensitive and specific method for detecting the EBV-encoded biomarker microRNA miR-BART6-3p. Methods: We designed a probe (EB4) containing a C-rich sequence, a restriction endonuclease half-recognition site, a G-rich stem-loop structure, and a target recognition domain. Based on this probe, an isothermal fluorescence platform was developed by integrating target recycling amplification (TRA) with strand displacement amplification (SDA). The detection mechanism relies on miR-BART6-3p initiating a polymerase-endonuclease cycle, which generates G-quadruplex structures and target-like DNA. The fluorescence signal is produced when Thioflavin T (ThT) binds to these G-quadruplexes. The sensitivity, specificity, and anti-interference capability of the method were systematically evaluated. Results: The assay exhibited a broad linear detection range for miR-BART6-3p, spanning from 1 pM to 100 nM, with an ultra-low detection limit of 0.143 pM, thereby demonstrating significantly enhanced sensitivity compared to conventional methods. The assay also displayed high specificity, effectively differentiating targets with single-base mismatches. Clinical evaluation using serum samples revealed markedly elevated fluorescence signals in EBV-positive patients relative to healthy controls. Furthermore, the platform exhibited strong anti-interference capability, ensuring reliable performance under complex biological conditions. Conclusions: This study successfully developed a one-step, single-probe method for detecting EBV miRNA (miR-BART6-3p) with high sensitivity and specificity. The TRA-SDA platform provides operational simplicity, high interference resistance, and superior diagnostic performance. This innovative approach shows great clinical application prospects as a molecular diagnostic tool for the early detection of nasopharyngeal carcinoma.
<i>Background and Objectives</i>: The efficacy of newly synthesized water-soluble octa-mercaptopyridine-substituted oxotitanium (IV) phthalocyanine (oxo-TiPc) and copper (II) phthalocyanine (CuPc) compounds in photodynamic therapy (PDT) was investigated using human tongue squamous cell cancer cell line (SCC-9, ATCC) cultures. <i>Materials and Methods</i>: A laser light source with a wavelength of 635 nm was used for this study. The cytotoxic values of the cancerous (SCC-9) and healthy (L-929) cell samples to which different Pc concentrations were applied under laser light were evaluated spectroscopically with the XTT method. <i>Results</i>: The oxo-TiPc compound exhibited a significantly lower IC50 value (46.8 µM) for SCC-9 cells compared to the CuPc compound (286.2 µM), indicating higher anticancer activity. This cytotoxicity may be due to decreased aggregation and enhanced reactive oxygen species (ROS) formation. Double-staining tests confirmed that oxo-TiPc-induced cell death included both apoptosis and necrosis. <i>Conclusions</i>: The findings show that the oxo-TiPc compound, unlike the CuPc compound, exhibited more selective toxicity to the SCC-9 cell line and has a higher phototoxic effect.
Se Hwan Hwang, Hyesoo Shin, Gulnaz Stybayeva
et al.
Objectives. In this study, we evaluated the associations between birth-related exposures, postnatal factors, and the risk of allergic rhinitis and asthma in children and adolescents. Methods. We performed a comprehensive search of five literature databases up to May 2023. To quantify the associations of birth-related exposures (birth weight, delivery mode, prematurity, sex, maternal age, and parental allergy history) and postnatal factors (birth order, number of siblings, breastfeeding exclusivity, and breastfeeding duration) with allergic disease, we calculated pooled odds ratios and 95% confidence intervals. We conducted subgroup analyses for allergic disease type, birth order, number of siblings, and parental allergy history. The methodological quality of the identified studies was evaluated using the Newcastle-Ottawa Scale. Results. This meta-analysis included 31 studies, encompassing 218,899 patients in total. The birth-related exposures of low birth weight, maternal age, and prematurity (less than 37 weeks gestation) were not significantly associated with the risk of asthma or allergic rhinitis during childhood or adolescence. Male sex, family history of allergy, and cesarean delivery were linked to an elevated risk of asthma or allergic rhinitis. Among postnatal factors, exclusive breastfeeding, breastfeeding for longer than 6 months, second or later birth order, and having siblings exhibited protective effects against allergic diseases in offspring. Conclusion. The risks of allergic rhinitis and asthma were elevated in male patients, those delivered by cesarean section, and those with a family history of allergy. Conversely, exclusive breastfeeding, breastfeeding for longer than 6 months, and having siblings corresponded to a reduced risk of respiratory allergic diseases.
Abstract Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.
Abstract Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p < 0.001). The hazards of retinal vascular occlusion, RAO, and RVO were significantly greater in the migraine group (aHR, 1.69 [95% CI, 1.57, 1.83], 2.13 [95% CI, 1.84, 2.48] and 1.53 [95% CI, 1.40, 1.68], respectively). Risks of retinal vascular occlusion were significantly higher in migraine both with aura (MA) and without aura (MO) (aHR, 1.77 [95% CI, 1.58, 1.98], and 1.92 [95% CI, 1.64, 2.25]). Among patients with migraine, nonsteroidal anti-inflammatory drugs, propranolol, and flunarizine significantly reduce their risks of retinal vascular occlusion (aHR, 0.19 [95% CI, 0.16, 0.22], 0.73 [95% CI, 0.62, 0.86], 0.84 [95% CI, 0.76, 0.93]). Migraine, MA and MO are independently associated with higher risks of retinal vascular occlusion, RAO, and RVO.
Mette Niemann Johansen, Anna Handberg, Mohamed El Haddouchi
et al.
Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.
Tinnitus affects millions of people around the world and causes significant negative impacts on their quality of life (QoL). Tinnitus is rarely examined in Saudi Arabia. This study aimed to estimate the prevalence of tinnitus among adults, explore their experience with tinnitus, investigate the impact of tinnitus on their QoL, and discover their tinnitus management methods. A descriptive cross-sectional study design was performed utilizing a non-probability purposive sampling technique and a face-to-face in-person administered questionnaire. Descriptive statistics and a chi-square test were used to assess the data and find any correlation between the variables. Out of 4860 adults, 320 (males: <i>n</i> = 172; females: <i>n</i> = 148; age range = 18–90 years) had tinnitus, mainly described as a daily, gradual, continuous, whistling, and ringing tinnitus in both ears. Tinnitus prevalence was estimated at 6.54% with a slight predominance in males (6.9%) compared with females (6.2%). Most of the participants were unaware of the cause of their tinnitus. The modal value of the severity of tinnitus signals was severe for both genders. The modal value of the impact of tinnitus on the QoL was moderate for males and severe for females. Sleep, social activities, quiet settings, and concentration were largely affected by tinnitus. Significant associations (<i>p</i> < 0.05) between the impact of tinnitus on the QoL and risk factors, such as gender, age, hearing loss, and hyperacusis were determined. Also, the impact of tinnitus on the QoL was significantly associated (<i>p</i> < 0.05) with the duration of complaints and the severity of tinnitus signals. Approximately, 61% of the participants did not use any tinnitus treatment, while the remaining participants usually used hearing aids, medications, and counseling to manage their tinnitus. By increasing awareness, establishing standard practice, developing guidelines for managing tinnitus, expanding access to suitable interventions, and carrying out additional research, adults living with tinnitus in Saudi Arabia will have better support and, ultimately, an enhancement of their overall well-being.
Classical notion claims that a memory is implicit if has nothing to do with consciousness during the information retrieval from storage, or is otherwise explicit. Here, we demonstrate event-related potential evidence for involuntary consciousness during implicit memory retrieval. We designed a passive oddball paradigm for retrieval of implicit memory in which an auditory stream of Shepard tones with musical pitch interval contrasts were delivered to the subjects. These contrasts evoked a mismatch negativity response, which is an event-related potential and a neural marker of implicit memory, in the subjects with long-term musical training, but not in the subjects without. Notably, this response was followed by a salient P3 component which implies involvement of involuntary consciousness in the implicit memory retrieval. Finally, source analysis of the P3 revealed moving dipoles from the frontal lobe to the insula, a brain region closely related to conscious attention. Our study presents a case of involvement of involuntary consciousness in the implicit memory retrieval and suggests a potential challenge to the classical definition of implicit memory.
<i>Background and Objectives</i>: Many otologists face a dilemma in the decision-making process of surgical management of patients with cochlear nerve (CN) aplasia. The goal of this study is to provide fresh evidence on cochlear implantation (CI) results in patients with CN aplasia. <i>Materials and Methods</i>: We scrutinized functional outcomes in 37 ears of 21 children with bilateral CN aplasia who underwent unilateral or bilateral CI based on cross-sectional and longitudinal assessments. <i>Results</i>: The Categories of Auditory Performance (CAP) scores gradually improved throughout the 3-year follow-up; however, variable outcomes existed between individuals. Specifically, 90% of recipients with a 1-year postoperative CAP score ≤1 could not achieve a CAP score over 1 even at 3-year postoperative evaluation, while the recipients with a 1-year postoperative CAP score >1 had improved auditory performance, and 72.7% of them were able to achieve a CAP score of 4 or higher. Meanwhile, intraoperative electrically evoked compound action potential was not correlated with postoperative CAP score. <i>Conclusions</i>: Our results further refine previous studies on the clinical feasibility of CI as the first treatment modality to elicit favorable auditory performance in children with CN aplasia. However, special attention should be paid to pediatric patients with an early postoperative CAP score ≤1 for identification of unsuccessful cochlear implants and switching to auditory brainstem implants.
Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. Methods In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. Results We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). Conclusions TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Hair cell (HC) loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/β-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5, Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs. Our previous studies showed that Lgr6+ cells are a subpopulation of Lgr5+ progenitor cells and that both Lgr6+ and Lgr5+ progenitors can generate Myosin7a+ HCs in vitro. Thus we hypothesized that Lgr6+ cells are an enriched population of cochlear progenitor cells. However, the detailed distinctions between the Lgr5+ and Lgr6+ progenitors are unclear. Here, we systematically compared the proliferation, HC differentiation, and detailed transcriptome expression profiles of these two progenitor populations. We found that the same number of isolated Lgr6+ progenitors generated significantly more Myosin7a+ HCs compared to Lgr5+ progenitors; however, Lgr5+ progenitors formed more epithelial colonies and more spheres than Lgr6+ progenitors in vitro. Using RNA-Seq, we compared the transcriptome differences between Lgr5+ and Lgr6+ progenitors and identified a list of significantly differential expressed genes that might regulate the proliferation and differentiation of these HC progenitors, including 4 cell cycle genes, 9 cell signaling pathway genes, and 54 transcription factors. In conclusion, we demonstrate that Lgr6+ progenitors are an enriched population of inner ear progenitors that generate more HCs compared to Lgr5+ progenitors in the newborn mouse cochlea, and the our research provides a series of genes that might regulate the proliferation of progenitors and HC generation.
Mansour Moghimi, Mahmood Kazeminasab, Mohammad Reza Vahidi
et al.
Laryngeal chondrosarcoma is a rare tumor that involves head and neck region such as larynx in rare cases. This malignant tumor usually grows quite slowly. The patient may experience symptoms for several years before a diagnosis is made. The diagnosis is achieved by clinical, radiological and pathological features. Management is basically surgical. Prognosis is generally good, depending basically on histologic grade. Herein, we report a case of laryngeal chondrosarcoma presented with hoarseness. Spiral CT scan demonstrated an expansile mass with calcification originating from cricoid cartilage. The patient underwent surgery for open excisional biopsy, and postoperative histopathologic evaluations confirmed "laryngeal chondrosarcoma" as definite diagnosis. The patient denied total laryngectomy for complete removal of the tumor. Six months follow up showed no more growth.
Tobias Dombrowski, Christian Wrobel, Stefan Dazert
et al.
Abstract Background Curriculum design and specific topic selection for on-site practical courses in clinical disciplines with limited teaching time is challenging. An electronic learning supported curriculum based on the flipped classroom principle has a high potential to effectively gain knowledge and education along with improving practical experience. Here, we demonstrate the introduction of a flipped classroom curriculum for practical courses in Otorhinolaryngology (ORL) in real world practice to improve the on-site time management and students’ experience. Methods Educational aims of our practical curriculum were analysed and rearranged into a flipped classroom (FC) framework. Core knowledge was taught preliminary based on a moodle platform in predominantly interactive formats. Two quasi-randomized groups were formed with 212 participants either receiving or not receiving access to the e-learning program to reduce a potential allocation bias to the e-learning group. All students completed a questionnaire with learning related items. Focusing the study on the intervention group, we investigated if students using the flipped classroom more often felt better prepared for the practical course. Results The online learning platform was highly accepted and frequently used by 66% of participating students in the e-learning group. Students with frequent use of our e-learning platform significantly felt better prepared for the practical course (p = 0.001). The far majority of all students supports the idea of further development of e-learning. More than 70% were generally interested in ORL. Handouts were the overall most important learning resource and more than 50% relied solely on them. Conclusions Flipped classroom curricula can save time and help improving the on-site experience in practical courses especially in smaller surgical disciplines. The acceptance of digital learning is high, and most students rely on handouts for learning ORL, emphasizing the need for guidance by the teacher e.g. through electronic learning. Our results underline the high potential of FC to address teaching challenges for smaller medical disciplines with limited teaching time like ORL.
Felice Scasso, Andrea Elio Sprio, Luciano Canobbio
et al.
Oxidative stress exerts major role in the pathogenesis of side effects of many antineoplastic drugs, including ototoxicity of cisplatin. In particular, increased levels of reactive oxygen species (ROS) represent one of the molecular mechanisms underlying the apoptosis of different types of hearing cells. Antioxidants and ROS scavengers may thus represent potential therapeutic options to prevent platinum-associated ototoxicity.The aim of this preliminary case-control study was to explore the efficacy of a dietary antioxidant supplement, in order to hamper the occurrences of ototoxicity in patients undergoing cisplatin chemotherapy.As results, a significant protection against cochlear toxic damage was demonstrated in patients who took the antioxidant supplement, which furthermore prevented the occurrence of hearing disorders and tinnitus. These clinical evidences were corroborated by the oxidative status of patients. After cisplatin chemotherapy, the plasma derivatives of reactive oxygen metabolites (d-ROMs) content rapidly increased in control patients, but it was maintained in those under dietary supplementation, likely because of a higher anti-ROMs potential. Indeed, an increment in rapid anti-ROMs was detected in supplemented patients, though no differences were highlighted in terms of slow anti-ROMs.In conclusion, in this preliminary report we demonstrated the feasibility of a dietary antioxidant supplementation in order to prevent the cisplatin induced hearing damage.