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Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity.

Introduction: The round window membrane (RWM) acts as a pressure-relieving membrane for incompressible cochlear fluid. The reinforcement of the RWM has been used as a surgical intervention for the treatment of superior semicircular canal dehiscence and hyperacusis. The aim of this study was to investigate how RWM reinforcement affects sound pressure variations in the cochlea. Methods: The intracochlear sound pressure (ICSP) was simultaneously measured in the scala tympani (ST) and scala vestibuli (SV) of cadaveric human temporal bones (HTBs) in response to acoustic stimulation for three RWM reinforcement materials (soft tissue, cartilage, and medical-grade silicone). Results: The ICSP in the ST was significantly increased after RWM reinforcement for frequencies below 2 kHz. Between 400 and 600 Hz, all three materials demonstrated the highest median pressure increase. The higher the RWM stiffness, the larger the pressure increase: silicone (7 dB) < soft tissue (10 dB) < cartilage (13 dB). The ICSP in the SV was less affected by reinforcement. The highest median pressure increase was 3 dB. The experimental findings can be explained with numerical models of cochlear mechanics. Discussion and conclusions: RWM reinforcement increases the sound pressure in ST at lower frequencies but only has a minor influence on the SV pressure.

Amaryllidaceae alkaloids (AAs) are plant specialized metabolites with therapeutic properties exclusively produced by the Amaryllidaceae plant family. The two most studied representatives of the family are galanthamine, an acetylcholinesterase inhibitor used as a treatment of Alzheimer’s disease, and lycorine, displaying potent in vitro and in vivo cytotoxic and antiviral properties. Unfortunately, the variable level of AAs’ production in planta restricts most of the pharmaceutical applications. Several biotechnological alternatives, such as in vitro culture or synthetic biology, are being developed to enhance the production and fulfil the increasing demand for these AAs plant-derived drugs. In this review, current biotechnological approaches to produce different types of bioactive AAs are discussed.

[This corrects the article DOI: 10.3389/fnagi.2021.647285.].[This corrects the article DOI: 10.3389/fnagi.2021.647285.].

Transition metal oxide nanoparticles contained in fly ash are known to catalyze the formation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) during the waste incineration process. The potential catalytic activity of silica-supported NiO, CuO, and NiO-CuO nanoparticles for the formation of PCDD/Fs will be discussed in this dissertation. The successful synthesis of silica-supported NiO, CuO, and NiO-CuO nanoparticles as surrogates of combustion-generated nanoparticles was important to this study. The synthesis was followed by the characterization of the nanoparticle surrogates by X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDS). Finally, the catalytic activity of these nanoparticle surrogates for the formation of PCDD/Fs was investigated.Silica-supported metal oxide nanoparticles were prepared by wetness impregnation of metal iondendrimer complexes (WI-D) and wetness impregnation of metal ion solutions (WIM), both followed by oxidative thermal treatment (calcination). NiO nanoparticles with low size dispersity (14%) and an average diameter of 3.6 ± 0.5 nm were formed by the WI-D method followed by calcination at 500 C for 5 h. NiO nanoparticles prepared by the WI-M method showed of low size dispersity (14%) and an average diameter 2.9 ± 0.4 nm followed by calcination at 500 C for 5 h. For the first time, mixed NiO-CuO nanoparticles were synthesized with the ability to control their Ni:Cu (1:1, 1:3, 1:10, 10:1, and 3:1) molar composition by altering the amounts of metal ions in the starting solutions.Catalytic activity of NiO, CuO, and NiO-CuO nanoparticles was investigated by reacting 2-monochlorophenol (2-MCP)a known PCDD/Fs precursoron their surface at cool-zone temperatures of waste incinerators (300–500 C with 50 C intervals). Results indicated nearly 85% of the 2-MCP was reacted at 300 C, while close to 100% conversion was achieved for 2- MCP at temperatures above 450 C. It is proposed that the reactions associated with PCDD/Fs formation were initiated by binding of 2-MCP to the metal-oxide sites on the silica support, followed by formation of surface-bound chlorinated phenol molecule. PCDD/Fs yields as a function of reaction temperature and the nature of the catalyst (NiO, CuO and NiO-CuO) will be discussed.

Amaryllidoideae produce specific specialized metabolites known as Amaryllidaceae alkaloids (AAs), extensively studied for their significant pharmacological potential. AAs’ spatial distribution and biosynthesis within plant tissues remain poorly understood. This study investigates organ- and tissue-specific localization in Hippeastrum papilio, from precursors to galanthamine and haemanthamine, using matrix-assisted laser desorption/ionization mass spectrometry imaging. Consistent accumulation of AAs was observed in epidermal and vascular tissues, with leaves exhibiting a uniform distribution across all ages and positions. Bulbs exhibited higher concentrations in the outer-scales and basal-plates, while roots displayed compartmentalized patterns, with galanthamine being uniquely abundant in the vascular bundles. Haemanthamine and galanthamine were detected in high quantities in the leaves’ and bulbs’ mucilage, while precursors were scarce. Multivariate analyses revealed that precursors clustered separately from end-products and were specifically enriched in the middle-scales and apical-leaves of the bulbs. Nonetheless, biosynthetic intermediates were observed in all tissues, indicating widespread AA biosynthesis across all organs. These findings suggest a coordinated metabolic network in H. papilio, which challenges existing hypotheses on organ-specific AA biosynthesis and hints at the transport of end-products. This study refines current models of alkaloid biosynthesis and underscore the value of H. papilio as a promising resource for sustainable production of therapeutic AAs. MALDI-MSI reveals widespread, tissue-specific alkaloid distribution in Hippeastrum papilio, challenging organ-specific biosynthesis and implicating epidermal and vascular tissues in Amaryllidaceae alkaloid production.

Background The United Nations Interagency Group for Child Mortality Estimation (UNIGME) indicates that child mortality is the death rate of children between age zero to five. The importance of this area of research is high where worldwide a number of studies have been led on infant and child mortality, despite limited research discoveries with regards to Sri Lanka. The aim of this study is to investigate the socio-economic and demographic characteristics associated with child mortality in Sri Lanka. Methods Using the context of Sri Lanka as a case study, this study carried out based on data gathered from the micro level national survey. Using the logit regression model through the step-wise technique, the study investigate the socio-economic and demographic characteristics associated with child mortality in Sri Lanka. Results According to the generated results, place of residence province-wise, household head’s education level and source of drinking water have negative effect (lower risk) on child mortality in Sri Lanka. Exceptionally, the Western province has the highest negative effect on child mortality which demonstrates it as the least harmful region in Sri Lanka in child endurance. Household heads who owns private entities and Sri Lankan Moors has a positive effect on child mortality as well. Conclusion This study is helpful to address the population health of local arena and results can be supportive to the government and policymakers to gain an overview of physical health status of the country and able to uplift their policies based on the new findings.

Knowledge of early clinical manifestations, people's perceptions and behaviours is crucial in preventing and controlling neglected tropical diseases (NTDs). Cutaneous leishmaniasis is an NTD that causes skin lesions and affects millions worldwide. Delayed healthcare-seeking behaviour leading to prolonged treatment periods and complications is rife among people with cutaneous leishmaniasis. This study examined the patient-reported early clinical manifestations of cutaneous leishmaniasis, local interpretations and associated health behaviours within the socio-cultural context of rural Sri Lanka. We conducted a qualitative study among people with cutaneous leishmaniasis in three rural communities in the Anuradhapura district, Sri Lanka. Participants' experiences were explored through a study-bespoke participant experience reflection journal and in-depth interviews. We analysed the data using a narrative-thematic approach. The study included 30 people with cutaneous leishmaniasis (12 females and 18 males) aged between 18 and 75 years. We identified four major themes during the analysis: 1) patient-reported early clinical manifestations of cutaneous leishmaniasis, 2) local interpretations of the early skin lesion(s), 3) associated actions and behaviours, and 4) the time gap between the initial notice of symptoms and seeking healthcare for cutaneous leishmaniasis. Early clinical manifestations differed among the participants, while the majority misinterpreted them as a mosquito/ant bite, pimple, wart, eczema, macule, or worm infestation. Participants undertook different context-specific self-management actions to cure cutaneous leishmaniasis. We identified an average time gap between the notice of symptoms and the first visit to the healthcare facility ranging from three to twelve months. Diverse early clinical manifestations, local interpretations, and associated behaviours of people with cutaneous leishmaniasis have led to a substantial delay in healthcare-seeking. The study sheds light on the importance of understanding the manifestations of NTDs within the social context. Our findings will inform designing context-specific health interventions to improve awareness and healthcare-seeking in cutaneous leishmaniasis in rural settings.