Modular Synthesis of Complex Benzoxaboraheterocycles through Chelation-Assisted Rh-Catalyzed [2 + 2 + 2] Cycloaddition.

Benzoxaboraheterocycles (BOBs) are moieties of increasing interest in the pharmaceutical industry; however, the synthesis of these compounds is often difficult or impractical due to the sensitivity of the boron moiety, the requirement for metalation-borylation protocols, and lengthy syntheses. We report a straightforward, modular approach that enables access to complex examples of the BOB framework through a Rh-catalyzed [2 + 2 + 2] cycloaddition using MIDA-protected alkyne boronic acids. The key to the development of this methodology was overcoming the steric barrier to catalysis by leveraging chelation assistance. We show the utility of the method through synthesis of a broad range of BOB scaffolds, mechanistic information on the chelation effect, intramolecular alcohol-assisted BMIDA hydrolysis, and linear/cyclic BOB limits as well as comparative binding affinities of the product BOB frameworks for ribose-derived biomolecules.

Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Allergic sensitization pattern as a marker of bronchial hyperresponsiveness in allergic rhinitis patients living in temperate continental climate zone.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but it may also appear in allergic rhinitis. The type of allergen, as well as regional characteristics, play an important role in the development of BHR. The aim of our study was to analyze allergen sensitization patterns and the factors that affect BHR in allergic rhinitis patients living in temperate continental climate zone. METHODS: This study retrospectively analyzed allergic rhinitis patients from Eastern Slovakia who underwent skin-prick tests to aeroallergens, spirometry, histamine and methacholine bronchial provocation tests for evaluation of lower airway symptoms. We analyzed the associations between BHR and the pattern of aeroallergen sensitization, lung function parameters, and the total IgE and eosinophil levels. RESULTS: Out of 365 allergic rhinitis patients (age range 16-64 years), 114 showed BHR. Sensitization to house dust mites (HDMs) and grass were the most common. BHR was significantly associated with sensitization to dogs (odds ratio, OR = 2.15, 95% confidence interval, CI: 1.13-4.11) and Alternaria (OR = 2.15, 95% CI: 1.06-4.35); however, BHR did not show a relationship with HDMs sensitization. The levels of total IgE and eosinophils were higher in the BHR-positive group. Sensitization to more than six allergens significantly increased the probability of BHR (p < 0.01). CONCLUSION: Dogs and Alternaria, but not HDMs, were the sensitizing agents most closely associated with BHR. High-grade sensitization and increased total IgE and eosinophil levels were characteristic clinical signs in BHR-positive allergic rhinitis patients in the temperate continental climatic zone.

Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.

Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed ß,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.

Burnout syndrome as an occupational disease in the European Union: an exploratory study.

The risk of psychological disorders influencing the health of workers increases in accordance with growing requirements on employees across various professions. This study aimed to compare approaches to the burnout syndrome in European countries. A questionnaire focusing on stress-related occupational diseases was distributed to national experts of 28 European Union countries. A total of 23 countries responded. In 9 countries (Denmark, Estonia, France, Hungary, Latvia, Netherlands, Portugal, Slovakia and Sweden) burnout syndrome may be acknowledged as an occupational disease. Latvia has burnout syndrome explicitly included on the List of ODs. Compensation for burnout syndrome has been awarded in Denmark, France, Latvia, Portugal and Sweden. Only in 39% of the countries a possibility to acknowledge burnout syndrome as an occupational disease exists, with most of compensated cases only occurring in recent years. New systems to collect data on suspected cases have been developed reflecting the growing recognition of the impact of the psychosocial work environment. In agreement with the EU legislation, all EU countries in the study have an action plan to prevent stress at the workplace.

Different clinical effect of several types of airborne allergens on the severity of bronchial hyperreactivity.

BACKGROUND: Atopic sensitization belongs to the most common risk factors for bronchial asthma. However, in clinical practice, it is not clear whether sensitization against pollen and perennial allergens is differently associated with the severity of bronchial hyperresponsiveness (BHR). AIM: To find out whether patients sensitized to perennial allergens differ in severity of bronchial hyperresponsiveness from patients sensitized to pollen allergens. METHODS: The study includes 109 patients. Based on the results of skin prick tests, patients were divided into three groups: sensitivity to pollen allergens - group A; sensitivity to perennial allergens - group B; sensitivity to both pollen and perennial allergens - group C. Based on the histamine bronchoprovocation test, we compared the values of histamine provocative concentration causing a 20% drop in FEV1 (PC20) among particular groups of patients. Mild bronchial hyperresponsiveness was determined if the value of PC20 was >4 mg/ml, while if the value of PC20 was <4 mg/ml, the bronchial hyperresponsiveness was considered as moderate/severe. RESULTS: A statistically significant difference was found in the degrees of bronchial hyperresponsiveness between the three groups of patients, namely, group A with the patients sensitized only to the pollen allergens, group B comprising patients sensitized to the perennial allergens only, and group C, involving patients sensitized to the combination of both pollen and perennial allergens. The PC20 values were higher among the patients from the group A (7.46 mg/ml) compared to group B (4.25 mg/ml) and C (4.52 mg/ml). The odds ratio for moderate/severe BHR was 5.21 and 5.04 in group B and group C, respectively. CONCLUSION: Severity of bronchial hyperresponsiveness shows differences according to sensitization to particular allergens. Perennial allergens are more often associated with serious forms of bronchial hyperresponsiveness which also have an impact on the severity and prognosis of bronchial asthma.

Effects of partially ionised medical oxygen, especially with O2•-, in vibration white finger patients.

A major symptom of hand-arm vibration syndrome is a secondary Raynaud's phenomenon-vibration white finger (VWF)-which results from a vasospasm of the digital arteries caused by work with vibration devices leading to occupational disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The aim of this work was to verify the influence of inhalation of partially ionized oxygen (O2•-) on peripheral blood vessels in the hands of patients with VWF. Ninety one (91)patients with VWF underwent four-finger adsorption plethysmography, and the pulse wave amplitude was recorded expressed in numeric parameters-called the native record. Next, a cold water test was conducted following with second plethysmography. The patients were divided in to the three groups. First and second inhaled 20-min of ionized oxygen O2•- or oxygen O2 respectively. Thirth group was control without treatment. All three groups a follow-up third plethysmography-the post-therapy record. Changes in the pulse wave amplitudes were evaluated. Inpatients group inhaling O2•- a modest increase of pulse wave amplitude was observed compared to the native record; patients inhaling medical oxygen O2 and the control showed a undesirable decline of pulse wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the group inhaling O2•- compare to O2 (p < 0.05). Peripheral vasodilatation achieved by inhalation of O2•- could be used for VWF treatment without undesirable side effect in hospital as well as at home environment.

Occupational rhinitis in the Slovak Republic--a long-term retrospective study.

BACKGROUND: Allergic and non-allergic rhinitis ranks among the common occupational health problems. However, data on the incidence of occupational rhinitis are lacking, since comprehensive studies are rare. METHODS: The study includes a group of patients in the Slovak Republic who were reported as having occupational rhinitis in the years 1990-2011. The following parameters were tracked in the investigated sample: age, gender, number of cases by individual years, occupations, causative factors and the length of exposure to the given agent. Possible progression of rhinitis to bronchial asthma was evaluated as well. The diagnostic algorithm was also analysed retrospectively, which included skin tests, the examination of specific IgE antibodies and nasal provocation tests. RESULTS: A total of 70 cases of occupational rhinitis were reported. The disease most often occurred in food industry workers (50% of cases). The most common aetiological factor was flour. Among other relatively common allergens were synthetic textile, wool, cotton and different types of moulds. Significant agents were also different chemical factors causing allergic and irritant rhinitis. The average length of exposure was 14.8 years. Exposure was shorter in men than in women (11 years vs. 16 years) (p = 0.04). Bronchial asthma as a comorbidity was diagnosed in 13 patients (19.7%). The critical diagnostic method on the basis of which the causal association between rhinitis and work environments was confirmed in 59% of cases was skin test; confirmation of the occupational cause using nasal provocation test was less frequent (18%). CONCLUSION: Food industry, textile industry and agriculture were the most risky occupational environments. Workers in these sectors require preventive intervention. In case of showing rhinitis symptoms it is necessary to confirm the occupational aetiology of the disease by the objective diagnostic methods. Since occupational rhinitis mostly precedes the occupational asthma, the elimination from the workplace is necessary.

Latent airway hyperresponsiveness: a phenomenon bordering bronchial asthma definition.

The basic features of bronchial asthma are dyspnea with wheezing and objectively confirmed obstructive respiratory disorder reversible after inhalation of bronchodilators. In stable intermittent bronchial asthma, these features are not present; therefore confirmation of asthma consists of the presence of bronchial hyperresponsiveness (BHR). In the present study, there were 902 bronchoprovocation tests performed for the verification of BHR. A significant criterium for BHR is a decrease of FEV(1) of 20% from the baseline level. Every test either positive or negative was finished with inhalation of four doses of salbutamol through a spacer. We obtained 675 bronchoprovocation tests negative and 227 positive. Among the 675 subjects with a negative test there were 49 subjects who after inhalation of salbutamol had an increase in FEV(1) of ≥20% above baseline. The bronchodilatatory response of these 49 subjects, makes one think about the so-called latent bronchospasm present already at baseline, limiting further constriction during bronchoprovocation tests. The detection of such latent bronchospasm in BHR increases the number of patients with an objectively confirmed bronchial asthma from 25.0% to 30.5%. Our results suggest that bronchodilation test be performed in all patients with suspected bronchial asthma to allow detecting latent bronchospasm as an initial stage of the disease.