Study of Angiogenic, Pro-Apoptotic, and Pro-Inflammatory Factors in Congenital and Acquired Cholesteatomas.

OBJECTIVES: Despite recent advances in biomolecular research that have improved our knowledge of cholesteatoma pathogenesis, the reasons behind its highly variable clinical course are still not clarified. It has been proposed that biological signaling between peri-matrix and matrix cells could play a critical role in disease homeostasis. The aim of our study was to analyze the expression of inflammatory (IL-1ß), hyper-proliferative (STAT-3, TGF-ß), and angiogenic (VEGF-C, PDGFr) factors in congenital and acquired cholesteatomas (both in adults and children), which might correlate with the clinical features observed. We performed an experimental study on 37 patients (29 males and 8 females, ranging from 4 to 66 years of age) who were diagnosed with cholesteatoma between 2020 and 2021 in our institution. All patients underwent clinical, audiologic, and radiologic assessments. Bone erosion grading and staging of cholesteatoma growth were assessed through preoperative evaluation and intraoperative middle ear findings, according to the PTAM System proposed by the Japan Otological Society (2016). Retro-auricular skin specimens were intraoperatively collected in all patients. Skin and cholesteatoma samples were analyzed through histopathological, western blot, and immunohistochemical evaluations. The expression rate was measured to find out the differences between congenital and acquired cholesteatomas as well as between the adult and pediatric populations. Expression of angiogenic, inflammatory, and proliferative biomarkers is significantly increased in acquired cholesteatomas in children as compared to congenital and acquired forms in adults, in accordance with the higher stage of disease shown by imaging, surgical, and histological features. Our data suggest that pathways already supposed to be involved in the pathogenesis of cholesteatomas could be differently activated in more destructive forms, typically found in children. The identification of potential biomarkers of cholesteatoma aggressiveness could lead to more personalized management (timing of intervention, recurrence prevention) and the future identification of anti-growth/anti-proliferative agents as non-surgery therapeutic options.

Diagnosing acute mastoiditis in a Pediatric Emergency Department: a retrospective review.

Background and aim Acute mastoiditis (AM) is a common complication of acute otitis media in children. There is currently no consensus on criteria for diagnosis. Head CT is the most frequent diagnostic tool used in the ED although the increasing awareness on the use of ionized radiations in children has questioned the use of CT imaging versus solely using clinical criteria. Our research aimed to understand if CT imaging was essential in making a diagnosis of AM. Methods We retrospectively analyzed medical records from pediatric patients who accessed our Pediatric Emergency Department (ED) between January 2014 and December 2020, with a clinical suspicion of AM. We reviewed clinical symptoms upon presentation, head CT and lab values (white blood cell count or WBC, C-Reactive Protein or CRP) when done, presence of complications and discharge diagnosis. A multilogistic regression model was specified to establish the role of clinical features and of CT in the diagnosis of AM based on 77 patients. Results Otalgia (OR= 5.01; 95% CI= 1.52-16.51), protrusion of the auricle (OR= 8.42; 95% CI= 1.37-51.64) and hyperemia (OR= 4.07; 95% CI= 1.09-15.23) of the mastoid were the symptoms strongly associated with a higher probability of AM. In addition to clinical features, the adjusted OR conferred by head CT was 3.09 (95% CI = 0.92-10.34). Conclusions Clinical signs were most likely predictive of AM in our sample when compared to Head CT. Most common symptoms were protrusion of the auricle, hyperemia or swelling behind the ear and otalgia.

Factors Influencing Personalized Management of Vestibular Schwannoma: A Systematic Review.

Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or microsurgical resection or wait and scan (WS). The aim of the review was to clarify which patient and tumor parameters may lead to different therapeutic choices, with a view to a personalized VS approach. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between February and March 2022. The authors defined six parameters that seemed to influence decision-making in VS management: 1-incidental VS; 2-tumor size; 3-tumor regrowth after sRT; 4-subtotal resection; 5-patients' age; 6-symptoms. The initial search yielded 3532 articles, and finally, 812 articles were included. Through a qualitative synthesis of the included studies, management strategies were evaluated and discussed. An individualized proposal of procedures is preferable as compared to a single gold-standard approach in VS decision-making. The most significant factors that need to be considered when dealing with a VS diagnosis are age, tumor size and hearing preservation issues.

The triple helix in developed countries: when knowledge meets innovation?

This paper deals with innovation viewed through the triple helix model as a milestone in the contemporary society of knowledge-based economies. Our goal is to empirically investigate the (in)efficient utilisation of academia, industry and government as three helices in order to boost innovations. Therefore, we construct a sample of 30 developed OECD countries with data covering the period from 2006 to 2018 and set up an input-oriented BCC data envelopment analysis that employs variables with non-negative average values over the entire period to calculate their efficiency scores. Our estimates from the radial models show that countries could reduce their inputs by a mean value of 11.9 per cent and keep their level of innovations in the triple helix model and by a mean of 5.8 per cent on average in the extended quintuple helix model. We find higher total inefficiencies in the non-radial models, which amount to 25.3 per cent on average in the triple helix model and 21.8 per cent on average in the quintuple helix model. The breakdown of the inefficiency score for different inputs reveals that countries have the largest potential for reducing CO2 emissions and the least room to reduce the Education Index and Civil Society Participation.

Is conservatism good news? The case of stocks of Jakarta Islamic index.

This study examines the role of Sharia stocks to affect the association between conservatism and crash risk. Sharia stocks are represented by the Jakarta Islamic Index (JII) stocks. We use Sharia stocks as a moderating variable to provide contextual issues in discussing conservatism and crash risk. Our findings show that conservatism reduces the crash risk for Sharia stocks. The test also suggests that conservatism cannot affect crash risk for non-Sharia stocks. The examinations are also consistent with the belief that Sharia, as a set of religious norms, helps minimize future risk. This paper contributes to the literature on religion and corporate behaviors by adding a contextual factor, Sharia stocks in Indonesia.

Towards a 'wide' role for venture capital in OECD countries' industry 4.0.

This paper focuses on the current theoretical views of venture capital that predetermines a "narrow" treatment. In the light of the existing "narrow" treatment, venture investors seek private commercial interests in financial support for Industry 4.0, ignoring other interests that fall beyond the limits of the current "narrow" treatment of venture capital. A "wide" treatment of venture capital 4.0 proposed in this paper allows for improving venture investors' market strategies. Implementing this treatment, they will strive for providing a whole range of advantages for society. Due to this novel approach, venture capital 4.0 might become a tool of corporate social responsibility. To substantiate this novel approach, this paper considers data for 2020 that reflect the influence of venture capital 4.0 on the economy in the period of its stability for 33 countries of the OECD, including developed and developing countries. Econometric modelling based on the official statistics data proves that Industry 4.0 venture capital will help achieve such growth goals as innovative development, global competitiveness, and increasing digital competitiveness. The limitations of this research are due to the impossibility of achieving such goals as sustainable development, economic growth, and implementation of human potential; what's more, the specifics of developing countries have not been studied sufficiently. The conclusions are oriented mainly at developed countries and could merely partially be applied to developing countries. During further research, it is expedient to explore - more thoroughly - the experience of the influence of Industry 4.0 venture capital on emerging economies.

Long-term auditory follow-up in the management of pediatric platinum-induced ototoxicity.

PURPOSE: Irreversible bilateral sensorineural hearing loss is a common side effect of platinum compounds. Because of the extended overall survival, a prolonged hearing surveillance and management of hearing impairments are emerging concerns for pediatric oncology. METHODS: In this retrospective observational study, we enrolled 38 children out of 116 treated at our institution by chemotherapy (cisplatin and/or carboplatin) with or without irradiation between 2007 and 2014, submitted to hearing monitoring before every cycle of chemotherapy, and who completed a 5-year long-term audiological follow-up. Chemotherapy regimens, demographic findings, cumulative doses, and cranial irradiation were compared. RESULTS: At the end of 5-year follow-up, ototoxicity was significantly increased compared to that observed at the end of chemotherapy (52.5% vs 39.5%, p < 0.001). A late onset of hearing loss was experienced in 13.1% of children, while in 26.3% progressive hearing loss was measured. Deafness at the end of chemotherapy and irradiation were significant prognostic factors for late ototoxicity outcomes (Odds Ratio 7.2-CI 1.67-31.1-p < 0.01 and 5.25-CI 1.26-21.86-p < 0.01 respectively). No significant differences were found between cisplatin and combined treatment (i.e., cisplatin shifted to carboplatin during monitoring for the onset of ototoxicity) and ototoxicity was not associated with platinum compounds cumulative dose (p > 0.05). 13.1% of children needed hearing aids at the end of follow-up. CONCLUSION: Long-term monitoring of at least 5 years prevents the harmful effects of hearing deprivation identifying late onset/progressive hearing loss after platinum compound chemotherapy in children thanks to early hearing rehabilitation, especially in those who underwent multimodal therapy or subjected to irradiation.

Customer engagement in innovative smart grid deployment projects: evidence from Russia.

In recent years, Russian power grid companies have significantly intensified their planning and implementing innovative projects to introduce various elements of smart grid technology. The global experience shows that the best potential outcome from smart grid technologies largely relies on the customers' readiness and adoption. To this end, we assess the Russian consumers' awareness and readiness regarding smart grid technologies by conducting a comprehensive survey. Our empirical study showed that, in general, Russian consumers are unaware of the various aspects of smart grid technologies. On the contrary, a significant share of respondents believes that smart grid technologies can reduce their energy consumption burden through gaining efficiency. The low level of awareness would be detrimental to accrue smart grid innovative projects' potential socio-economic and environmental benefits. We propose several recommendations for policymakers and managers of grid companies for the elimination of the identified risks.

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board.

BACKGROUND: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. METHODS: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. RESULTS: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). CONCLUSIONS: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy.

Multiplexing efficiency of environmental taxes in ensuring environmental, energy, and economic security.

This paper assesses the multiplexing efficiency of environmental taxes in ensuring environmental, energy, and economic security which is an integral part of sustainability in six European countries that are leaders in the Environmental Performance Index. This study aims to confirm the hypothesis that environmental taxes and payments could simultaneously affect changes in important environmental, energy, and economic security as well as sustainability parameters. Not all the previously selected taxes, which affect the parameters of all three areas of environmental, energy, and economic sustainability and security can ensure their simultaneous growth. Calculations made for the period 1994-2019 showed that in the system of environmental taxation of Denmark, five environmental taxes and fees provide an increase in the integrated level of environmental, economic, and energy security and sustainability; in Belgium, two environmental taxes are characterized by multiplex efficiency; in France, seven environmental taxes and payments; in Austria, four; in Finland, one; and in the UK, four. The paper's findings could create the basis for improving environmental taxation systems in the countries to increase comprehensive national security growth and ensure sustainable development path of the countries.

Do stock markets love misery? Evidence from the COVID-19.

This study examines the impact of the change in the Barro Misery Index (BMI) and the novel coronavirus (COVID-19) cases and deaths on the stock markets' returns and volatility. Based on a sample of 76 different countries, we find that an increase in BMI adversely affects the stock returns and increases stock volatility. We also find that an increase in BMI coupled with an increase in percentage cases of COVID-19 adversely affect stock returns and increases volatility. We find that the impacts of BMI on stock returns and volatility are driven by real GDP changes, unemployment rate, and long-term interest rate instead of inflation rates, especially for the developed countries. Our findings are consistent with Barro (1999), which indicates that the BMI represents a better measure relative to the original misery index in predicting the economic outcome, especially during the COVID-19 pandemic. We also find that the impacts of BMI components on stock returns and volatility for the developed countries are different from the emerging markets.

Benign Paroxysmal Positional Vertigo (BPPV) in COVID-19.

OBJECTIVE: The purpose of this article is to describe BPPV in COVID-19 patients by discussing the possible mechanisms underlying the onset of this vertigo. METHODS: We studied eight patients (4 F, 4 M, aged between 44 and 69 years) with COVID-19 infections complaining of vertigo. Patients were evaluated at the end of infection with an accurate clinical history, and the investigation of spontaneous, positional and positioning nystagmus. RESULTS: The vestibular findings showed benign paroxysmal positional vertigo (BPPV) in all the patients. Three patients had a mild phenotype of the COVID infection, whereas five subjects were hospitalized for the COVID infection and in three cases intensive care was required. Vestibular evaluation showed an involvement of posterior semicircular canals in five patients and horizontal in three. Three patients were treated with the Epley maneuver, two with Semont, one with Lempert and two with Gufoni maneuvers. CONCLUSIONS: We hypothesize that BPPV in COVID-19 infections can be relate to drugs, prolonged bed rest and to direct damage by viral infection on the peripheral vestibular system and in particular on the otolitic membrane due to the cytopathic effect of the virus and to the inflammatory response. Studies on large series of patients are needed to confirm our preliminary observation and to better evaluate the pathophysiological mechanisms underlying BPPV in these patients.

The evaluation of global cognitive and emotional status of older patients with chronic tinnitus.

OBJECTIVES: Tinnitus is a common symptom largely impactful on quality of life, especially in the elderly. Our aim was to evaluate the efficacy of self-administered screening tests to correlate the severity of subjective perception of tinnitus with emotional disorders and the overall cognitive status. METHODS: Patients aged ≥ 55 years with chronic tinnitus were recruited and submitted to a complete audiological evaluation; Tinnitus Handicap inventory (THI); Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and Mini-Mental State Examination (MMSE). Demographic and audiological features of patients with and without cognitive impairment (MMSE score cut-off of 24/30) were analyzed in order to reveal the relationship among tinnitus, emotional disorders, and cognitive dysfunction. RESULTS: 102 patients were recruited (mean age: 70.4 ± 9.6). THI score was directly related to HADS-A score (r = .63) HADS-D score (r = .66), whereas there was no relationship between tinnitus severity and MMSE (r = .13). CI and n-CI groups did not differ in the characteristics of tinnitus (p > .05), however, hearing threshold (p = .049) and anxious depressive traits measured with HADS-A (p = .044) and HADS-D (p = .016) were significantly higher in the group with cognitive impairment. Furthermore, age ≥ 75 years (p = .002, OR = 13.8), female sex (p = .032; OR = 6.5), severe hearing loss (p = .036; OR = 2.3), and anxiety (p = .029; OR = 9.2) resulted risk factors for CI. Therefore, in CI group MMSE score was inversely related to age (r = -.84). CONCLUSIONS: Cognitive impairment and psychiatric discomfort should be considered in tinnitus patients, related to increasing age, female sex, and severe hearing loss. Thus, self-administered questionnaires can be useful in addressing clinical approach.

Corporate Social Responsibility Amid Social Distancing During the COVID-19 Crisis: BRICS vs. OECD Countries.

This paper compares today's corporate management in developing markets (BRICS countries) vs. developed markets (the OECD countries). The influence of determining a new social corporate management season considering social distancing amid the COVID-19 pandemic on emerging markets' economic growth is ascertained and set apart from corporate management in developing markets. This paper helps clarifying and better understanding the role of corporate social responsibility in the conditions of an economic crisis against the background of the COVID-19 pandemic. This work provides scientific arguments that allow solving critical discussions regarding the advantages (growth of quality of life, an increase of business's competitiveness) and costs (limitation of economic growth, non-commercial use of profit, and increased price for goods and services) of domestic production and consumption. In the long-term, responsible financial practices return all investments and allow countries to better cope with a crisis. The research supplies a new view of corporate social responsibility as a measure of crisis management. It reflects its advantages at a time of social distancing in the conditions of the COVID-19 pandemic. The institutionalization of corporate social responsibility in emerging countries is not predetermined by internal factors (approach to doing business or organizational culture), if not by external factors (market status, state regulation, and consumer awareness). These circumstances prove the high complexity of strengthening corporate social responsibility in developing countries. In the conditions of social distancing - due to the COVID-19 pandemic - corporate social responsibility goes to a new level. In both developing and developed countries, one of the most widespread manifestations of corporate social responsibility is the entrepreneurship's transition to the remote form of activities. This envisages the provision of remote employment for workers and the online purchase of goods and services for consumers.

How do equity markets react to COVID-19? Evidence from emerging and developed countries.

Based on the supply of stock market returns hypothesis, we argue that the unprecedented adverse shock of COVID-19 on the countries' economic growth translates into a negative shock to the stock markets. According to the institutional theory, we also argue that the impact of COVID-19 in emerging countries is different from developed countries. Based on the overreaction hypothesis, we expect that the market reaction during the stabilizing period of COVID-19 spread is different from the market reaction during the infection period. Using high-frequency daily data across 53 emerging and 23 developed countries from January 14 to August 20, 2020, we find that COVID-19 cases and deaths adversely affect stock returns and increase volatility and trading volume. Cases and deaths affected stock returns and volatility in the emerging markets, while only cases of COVID-19 affected stock returns, volatility, and trading volume in the developed markets. COVID-19 cases and deaths are related to returns, volatility, and trading volume for emerging countries during the rising infection of COVID-19 (pre-April 2020), while cases and mortality rates are related to returns, volatility, and trading volume in developed countries during the stabilizing spread (post-April 2020). Therefore, the emerging markets' investors seem to react to COVID-19 cases and mortality rates differently from those in the developed markets across two different periods of COVID-19 infection.

Otitis media in children: Which phenotypes are most linked to allergy? A systematic review.

BACKGROUND: Allergic rhinitis is a common childhood disease responsible for a major impact on quality of life and healthcare resources. Many hypotheses have been proposed to explain the link between allergy and otitis media, although a definitive mechanism has not been identified yet. One of the major critical points is that authors failed in distinguishing among different phenotypes of middle ear inflammation. This review pointed out literature evidence from the laboratory and clinical experience linking allergy to different phenotypes of otitis media in children. METHODS: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 3010 articles that were finally screened. This resulted in 20 manuscripts of which the full texts were included in a qualitative analysis. We paid particular attention in distinguishing among phenotypes of otitis media. RESULTS: Clinical evidence and analyses of biomarkers suggested that allergy may be linked to some phenotypes of otitis media and, in particular, to otitis media with effusion (OME) and acute re-exacerbations in children with middle ear effusion. It was not possible to perform the analysis for allergy and acute and chronic otitis media because of paucity and heterogeneity of data. CONCLUSION: Allergy should be considered in the diagnostic workup of children with OME as well as OME should be excluded in children with persistent moderate to severe AR. In these cases, clinicians should evaluate prompt and accurate treatment of allergy in improving outcomes, although futures studies are required to increase evidence supporting that anti-allergy treatment may be effective in the recovery and outcome of otitis media with effusion.

Traumatic benign paroxysmal positional vertigo: personal experience and comparison with idiopathic BPPV.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vestibular vertigo, with post-traumatic origin in about 15% of cases. Management and prognosis of traumatic BPPV (T-BPPV) are still debated, especially about recurrence. The aim was to compare T-BPPV to idiopathic (I-BPPV). DESIGN AND STUDY SAMPLE: We analysed data about 795 BPPV patients: 716 idiopathic (90%) and 79 post-traumatic (10%), evaluating clinical history and bedside-examination, treating all patients with repositioning manoeuvres and reassessing them until the resolution of symptoms and nystagmus. RESULTS: Persistence rate in T-BPPV and I-BPPV patients was significantly different (p = 0.0074, OR = 2.31), respectively 12.6% and 5%. Also the rate of bilateral disease (p = 0.0063, OR = 4.72) and multicanalar involvement (p = 0.0183; OR = 4.67) were significantly higher in T-BPPV patients . There were no significant differences in age and sex distribution, side and canal interested. In T-BPPV group, the resolution rate with one manoeuvre was lower than I-BPPV (p = 0.0132: OR: 0,56). Recurrence rate was 38% in the T-BPPV group and 30.6% in the I-BPPV group, without significant difference. CONCLUSIONS: T-BPPV resulted different from I-BPPV in the resolution rate, bilateral or multiple canal involvement and persistence rate. T-BPPV and I-BPPV does not differ for recurrence rate, suggesting that, after resolution, the natural course of post-traumatic and idiopathic BPPV is similar.

How Long Is Otosclerosis Surgery Effective? Hearing Results after a 22-Year Follow-Up.

INTRODUCTION: Stapes surgery is a safe procedure, with favourable hearing outcome. The objective of the study is to assess the long-term hearing results, addressing the bone conduction (BC) decay and the need for hearing aids in otosclerosis patients. METHODS: We enrolled patients who underwent stapes surgery by means of stapedectomy or stapedotomy between 1991 and 2001. All enrolled patients underwent pure-tone audiometry (PTA) between September 2017 and June 2018. A set of questions was administered to record the prevalence of subjective symptoms and the need for hearing aids. RESULTS: Seventy patients were enrolled for a long-term evaluation; 37 patients underwent bilateral surgery; therefore, 107 ears were included in the analysis. The average follow-up period was 22 years. No statistically significant difference was found between early and late post-operative air conduction (AC) PTA (41 vs. 49 dB; p > 0.05) nor between early and late post-operative BC-PTA (29 vs. 37 dB; p > 0.05). A significant difference was observed for AC at 8 kHz (65 vs. 78 dB; p < 0.05) and BC at 2 and 4 kHz (28 vs. 40 dB and 45 vs. 58 dB, respectively; p < 0.05). CONCLUSIONS: This is, to our knowledge, the longest mean follow-up time in the literature. A mild decrease in both AC and BC threshold can be expected and the sensorineural decay is more pronounced on the high frequencies. The subjective hearing symptoms and overall sound perception are satisfactory.

Let's lessen conditionality in times of force majeure events. The archaic righteousness of the policy of conditionality of international Institutions amid COVID-19.

This article investigates how international decision-making's conditionality aids countries during strenuous economic conditions imposed by the COVID-19 pandemic. It examines and contrasts the European Union's conditionality policies, the International Monetary Fund, and the World Bank as the more influential and leading groups of institutions. The article reveals notable policy differences. As opposed to that of the IMF and WB, the EU's approach is more comprehensive and not confined to economic considerations. Those variations aside, the article draws on the same premise: expectations of compliance with the set conditions. While in-depth, structural requirements could guide ordinary decision-making and build up resilient national institutions and policies, this article questions the merits of large-scale comprehensive terms in the face of a situation created by a force majeure or a humanly uncontrollable event such as the COVID-19 pandemic. With no more initial research addressing the specific question of the application and adequacy of conditionality to force majeure emergencies or pandemic situations of the scale of COVID-19, this article argues in favor of a measured and targeted response limited to the development, design, or determination of policy choices that tackle the intended purpose. Also, for validly practical considerations that search for to ensure the better use of aid and avoid distracting or overburdening the recipient countries to the point of risking losses of devastating proportions, the article proposes to revise and limit conditionality during force majeure events to the essential aspects of transparent management of funds for the sole intended purpose. This in itself is a distinct democratic exercise of efficient and accountable public management decision-making.

Evaluation of the Italian transport infrastructures: A technical and economic efficiency analysis.

•The deregulation process played a key role in terms of airport efficiency.•The technical efficiency of 32 Italian airports has been evaluated•The methodological approach has been twofold: DEA and Tobit model•The main results show that efficiency is independent of an airport's size.•The findings highlight the decisive role of public shareholders in small airports.