Cosmetic Products with Potential Photoprotective Effects Based on Natural Compounds Extracted from Waste of the Winemaking Industry.

Grape marc is a by-product resulting from the winemaking industry that still contains beneficial compounds that can be valorized. Thus, we report here the possibility of using polyphenolic extracts of grape marc origin to obtain sun protection creams. The extractions were performed in ethanol and acetone solutions using pomace from different grape varieties (Merlot, Bläufrankisch, Feteasca Neagra, Isabella) as a raw material. The obtained extracts were analyzed in order to determine the total phenolic content, the antioxidant activity, and the sun protection factor (SPF) via Mansur spectrophotometric assay. The best results were achieved using 70% ethanol in water as a solvent. The extracts with the highest potential photoprotective effects are from the Merlot variety (SPFspectrophotometric = 7.83 ± 0.76). The sunscreens were prepared using the 70% ethanolic extract of the Merlot variety evaporated to dryness, redissolved in either distilled water or ethanol. The SPF estimated in vitro via the COLIPA method showed values of 14.07 ± 1.50 and 11.46 ± 1.32 for the aqueous and ethanolic extracts, respectively, when working with a cream to polyphenolic extract a ratio of 1/1 (w/w). At the same time, the use of aqueous polyphenolic extracts ensures the better stability of creams compared with the ethanolic ones.

Green Extraction Techniques of Phytochemicals from Hedera helix L. and In Vitro Characterization of the Extracts.

Hedera helix L. contains phytochemicals with good biological properties which are beneficial to human health and can be used to protect plants against different diseases. The aim of this research was to find the most suitable extraction method and the most favorable parameters for the extraction of different bioactive compounds from ivy leaves. Different extraction methods, namely microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and conventional heating extraction (CHE), were used. The most suitable method for the extraction of saponins is MAE with an extraction efficiency of 58%, while for carbohydrates and polyphenols, the best results were achieved via UAE with an extraction efficiency of 61.7% and 63.5%, respectively. The antioxidant activity (AA) of the extracts was also determined. The highest AA was obtained via UAE (368.98 ± 9.01 µmol TR/gDM). Better results were achieved at 50 °C for 10 min of extraction, using 80% ethanol in water as solvent. In order to evaluate their in vitro cytotoxicity, the extracts richest in bioactive compounds were tested on NCTC fibroblasts. Their influence on the DNA content of RAW 264.7 murine macrophages was also tested. Until 200 µg/mL, the extracts obtained via UAE and MAE were cytocompatible with NCTC fibroblasts at 48 h of treatment. Summarizing the above, both MAE and UAE can be employed as green and efficient methods for producing extracts rich in bioactive compounds, exhibiting strong antioxidant properties and good noncytotoxic activity.

Snijders Blok-Campeau Syndrome: Description of 20 Additional Individuals with Variants in CHD3 and Literature Review.

Snijders Blok-Campeau syndrome (SNIBCPS, OMIM# 618205) is an extremely infrequent disease with only approximately 60 cases reported so far. SNIBCPS belongs to the group of neurodevelopmental disorders (NDDs). Clinical features of patients with SNIBCPS include global developmental delay, intellectual disability, speech and language difficulties and behavioral disorders like autism spectrum disorder. In addition, patients with SNIBCPS exhibit typical dysmorphic features including macrocephaly, hypertelorism, sparse eyebrows, broad forehead, prominent nose and pointed chin. The severity of the neurological effects as well as the presence of other features is variable among subjects. SNIBCPS is caused likely by pathogenic and pathogenic variants in CHD3 (Chromodomain Helicase DNA Binding Protein 3), which seems to be involved in chromatin remodeling by deacetylating histones. Here, we report 20 additional patients with clinical features compatible with SNIBCPS from 17 unrelated families with confirmed likely pathogenic/pathogenic variants in CHD3. Patients were analyzed by whole exome sequencing and segregation studies were performed by Sanger sequencing. Patients in this study showed different pathogenic variants affecting several functional domains of the protein. Additionally, none of the variants described here were reported in control population databases, and most computational predictors suggest that they are deleterious. The most common clinical features of the whole cohort of patients are global developmental delay (98%) and speech disorder/delay (92%). Other frequent features (51-74%) include intellectual disability, hypotonia, hypertelorism, abnormality of vision, macrocephaly and prominent forehead, among others. This study expands the number of individuals with confirmed SNIBCPS due to pathogenic or likely pathogenic variants in CHD3. Furthermore, we add evidence of the importance of the application of massive parallel sequencing for NDD patients for whom the clinical diagnosis might be challenging and where deep phenotyping is extremely useful to accurately manage and follow up the patients.

Case Report. Diagnostic Challenges: Liver Metastases from Mammary Gland Origin or Cholangiocarcinoma?

Liver metastases are secondary malignant tumor formations due to the dissemination of primary malignant tumors, which are often the first clinical manifestation of mammary cancer. We present the case of a 52-year-old female patient from an urban area who came to the walk-in service at the "Sf. Ap. Andrei" Emergency County Hospital, Galati, for laboratory investigations. These revealed a significant increase in CA 15-3 tumor markers and a slight increase in CA 125 and CA 19-9 markers; however, clinical examination did not reveal tumors in the breast and there were no axillary adenopathies. CT exam revealed a large tumor formation in the hepatic right lobe and, close to it, a smaller one. The mammograph showed millimetric lesions at the level of the left mammary gland and bilateral axillary adenopathies. Subsequently, the patient underwent two liver biopsies in two different hospitals, which produced different histological and immunohistochemical results. PET-CT drew attention to a lung tumor and disclosed a different origin of metastases. In the end, correlating all investigations, the final diagnosis was cholangiocarcinoma with liver metastases and lung tumor with lung and bone metastases.

NPC1 plays a role in the trafficking of specific cargo to melanosomes.

Niemann-Pick type C1 (NPC1) protein is a multimembrane spanning protein of the lysosome limiting membrane that facilitates intracellular cholesterol and sphingolipid transport. Loss-of-function mutations in the NPC1 protein cause Niemann-Pick disease type C1, a lysosomal storage disorder characterized by the accumulation of cholesterol and sphingolipids within lysosomes. To investigate whether the NPC1 protein could also play a role in the maturation of the endolysosomal pathway, here, we have investigated its role in a lysosome-related organelle, the melanosome. Using a NPC1-KO melanoma cell model, we found that the cellular phenotype of Niemann-Pick disease type C1 is associated with a decreased pigmentation accompanied by low expression of the melanogenic enzyme tyrosinase. We propose that the defective processing and localization of tyrosinase, occurring in the absence of NPC1, is a major determinant of the pigmentation impairment in NPC1-KO cells. Along with tyrosinase, two other pigmentation genes, tyrosinase-related protein 1 and Dopachrome-tautomerase have lower protein levels in NPC1 deficient cells. In contrast with the decrease in pigmentation-related protein expression, we also found a significant intracellular accumulation of mature PMEL17, the structural protein of melanosomes. As opposed to the normal dendritic localization of melanosomes, the disruption of melanosome matrix generation in NPC1 deficient cells causes an accumulation of immature melanosomes adjacent to the plasma membrane. Together with the melanosomal localization of NPC1 in WT cells, these findings suggest that NPC1 is directly involved in tyrosinase transport from the trans-Golgi network to melanosomes and melanosome maturation, indicating a novel function for NPC1.

Ultrasound Assisted Extraction of Saponins from Hedera helix L. and an In Vitro Biocompatibility Evaluation of the Extracts.

The aim of this study was to establish the best ultrasound assisted extraction (UAE) conditions of saponins from Hedera helix L. leaves and to evaluate the in vitro biocompatibility of the extracts richest in saponins. Different parameters, such as extraction time, temperature, ultrasound power, solvent to plant material ratio, and solvent concentration, were investigated. The most efficient extraction conditions were a temperature of 50 °C, an ultrasound amplitude of 40%, an extraction time of 60 min, a plant material to solvent ratio of 1:20 (w:v), and 80% ethanol as solvent. In vitro cytotoxicity of the extracts richest in saponins and their influence on the DNA content of L929 (NCTC) fibroblasts were tested. Until 200 µg/mL, the studied extracts were cytocompatible with L929 fibroblast cell lines at 48 h of treatment. These in vitro cell culture results provide useful information for further applications of Hedera helix extracts in a pharmaceutical field.

Artificial Intelligence-Based Medical Data Mining.

Understanding published unstructured textual data using traditional text mining approaches and tools is becoming a challenging issue due to the rapid increase in electronic open-source publications. The application of data mining techniques in the medical sciences is an emerging trend; however, traditional text-mining approaches are insufficient to cope with the current upsurge in the volume of published data. Therefore, artificial intelligence-based text mining tools are being developed and used to process large volumes of data and to explore the hidden features and correlations in the data. This review provides a clear-cut and insightful understanding of how artificial intelligence-based data-mining technology is being used to analyze medical data. We also describe a standard process of data mining based on CRISP-DM (Cross-Industry Standard Process for Data Mining) and the most common tools/libraries available for each step of medical data mining.

Major Hepatectomy En Bloc with Cava Vein Resection for Locally Invasive Caudate Lobe Hepatocarcinoma.

BACKGROUND/AIM: Locally advanced liver tumours with vascular invasion have been considered for a long period of time as unresectable lesions, so the patient was further deferred to oncology services for palliation. However, improvement of the surgical techniques and the results reported so far came to demonstrate that extended hepatic and vascular resections might be safely performed in such cases and might significantly improve the long-term outcomes. MATERIALS AND METHODS: A 61-year-old patient was diagnosed with a caudate lobe tumour invading the inferior cava vein and the right hepatic pedicle. RESULTS: The patient was successfully submitted to surgery, and an extended right hepatectomy en bloc with cava vein resection was performed; the continuity of the cava vein was re-established by the placement of a synthetic graft. The postoperative outcome was uneventful. CONCLUSIONS: Although initially considered as a formal contraindication for resection, vascular invasion of the greater vessels should not preclude surgery if complete resection is achievable.

Testicular-sparing excision for benign paratesticular IgG4-related disease.

A 28-year-old male was referred by his local general practitioner due to recurrence of painful right scrotal mass, first noted 8 years prior. The mass was further characterised with ultrasound and then was locally excised via an inguinal approach, sparing the testicle, without any postoperative complication. Immunoperoxidase staining of the excised lesion confirmed paratesticular IgG4-related disease.

Internationalized science and human rights activism during the late Cold War: The French Committee of Mathematicians.

This article examines the ties between an internationalised science and transnational activism, in particular for causes considered universal, such as defending human rights, during the late Cold War. It focuses on a scientific network that supported mathematicians persecuted for their political views by both left- and right-wing undemocratic regimes. The Committee of Mathematicians was founded in 1974 and was active for a decade, built incrementally as a transnational advocacy network located in several Western countries. Focussing primarily on the Committee's French component, this article investigates the social and organisational underpinnings of its transnational action and defence of universal principles. It examines the modes of action and how they were shaped by scientists' professional and even disciplinary affiliations. These focal points allow an interrogation of the place the committee occupied within the space of human rights activism. The article aims to contribute to a historical sociology of the ties between science and politics and of the transnational trends that strained national frameworks, while moving away from an approach focussed solely on political macrotrends that fuelled the Cold War.

Actual Weight, Perceived Weight and Desired Weight of Romanian School Children by Parents and Children.

Background and Objectives: The perception of the body weight by children and parents influences the consequent actions undertaken for children's body weight management. This study investigated the correspondence between objective evaluations of Romanian school children (actual weight) and perceptions about weight (perceived weight), preoccupation with body weight management (desired weight) and parents' perceptions on children's weight. Materials and Methods: A cross sectional study was performed among 344 children aged 11 to 14 and 147 parents from Cluj-Napoca, Romania. We made anthropometric measurements of children, and short questionnaires were completed by the children and the parents. Results: The results show that 3.8% of children were underweight, 68.3% had a normal weight and 27.9% were overweight. Of this sample, 61.5% of underweight children, 20% of normal weight children and 43.7% of overweight children had misperceptions about their weight. The percentage of parents who did not estimate their children's weight correctly was 50%, 11.9% and 41.5%, respectively, for each of the three weight groups. The results of the logistic regression analyses showed that several factors were associated with the misclassification of their own body weight by the children, such as body mass index, gender, weight management practices, misclassification by the parents as well as parent-child discussions on these issues. Conclusions: Education for both Romanian parents and children is needed with regard to correctly identifying and managing children' body weight.

Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania.

This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C > G, c.502G > A, c.1618G > A mutations in exon 2, exon 4, exon 11, and exon 13-15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations.

Incidence and Mortality of Prostate Cancer in Canada during 1992-2010.

In Canada, prostate cancer is the most common reportable malignancy in men. We assessed the temporal trends of prostate cancer to gain insight into the geographic incidence and mortality trends of this disease. Three independent population-based cancer registries were used to retrospectively analyze demographic data on Canadian men diagnosed with prostate cancer and men who died of prostate cancer between the years of 1992 and 2010. The incidence and mortality rates were calculated at the provincial, city, and forward sortation area (FSA) postal code levels by using population counts that were obtained from the Canadian Census of Population. The Canadian average incidence rate was 113.57 cases per 100,000 males. There has been an overall increasing trend in crude prostate cancer incidence between 1992 and 2010 with three peaks, in 1993, 2001, and 2007. However, age-adjusted incidence rates showed no significant increase over time. The national mortality rate was calculated to be 24.13 deaths per 100,000 males per year. A decrease was noted in crude and age-adjusted mortality rates between 1992 and 2010. Several provinces, cities, and FSAs had higher incidence/mortality rates than the national average. Several of the FSA postal codes with the highest incidence/mortality rates were adjacent to one another. Several Canadian regions of high incidence for prostate cancer have been identified through this study and temporal trends are consistent with those reported in the literature. These results will serve as a foundation for future studies that will seek to identify new regional risk factors and etiologic agents.

Penile Invasive Squamous Cell Carcinoma: Analysis of Incidence, Mortality Trends, and Geographic Distribution in Canada.

BACKGROUND: Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends. OBJECTIVE: Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors. METHODS: Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels. RESULTS: The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status. CONCLUSION: This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.

Bicycle helmet use patterns in Italy. A description and analysis of survey data from an Italian friends of cycling association.

Cycling is becoming one of the most popular forms of recreation and transport the world over, but cyclists still have a high level of vulnerability. A bicycle helmet is an important safety device available to cyclists, but little is known regarding possible determinants of helmet use among adults. This study aims at providing information on helmet usage patterns in Italy and identifying the factors associated with bicycle helmet use. Data on 2072 bicycle riders from an Italian friends of cycling association aged 18 years or older who had ridden a bicycle in the last month were collected using an ad-hoc questionnaire via the web. The sample was equally distributed among subjects who always, most of the time, sometimes, rarely, or never use a helmet. To evaluate the association among socio-demographic and bicycle use characteristics and helmet use, a multinomial logistic regression model was performed. The results show a higher propensity to use a helmet among males, riders coming from Central and Southern Italy, people who cycles more than 60kilometres in a week, cyclists who have already had a crash, people who do not cycle daily or almost daily, riders of sport bikes. Moreover, the propensity to use a helmet increases with age. The survey provided a first step in approaching the lack of data on cycling behaviour and the wearing of a helmet in Italy.

Area-Level Deprivation and Adverse Consequences in People With Substance Use Disorders: Findings From the Psychiatric and Addictive Dual Disorder in Italy (PADDI) Study.

BACKGROUND: Environmental factors may operate with individual ones to influence the risk of substance use. Research has focused on severe adverse consequences influenced by contextual variables. However, the literature on community level factors influencing substance use behaviors is relatively limited across Europe so far. OBJECTIVE: We capitalized on data from a National survey, exploring individual and contextual characteristics, to study adverse consequences among people with substance use disorders. METHODS: The impact of area-level deprivation on nonfatal overdose, hepatitis C or B infections, and major involvement with the criminal justice system, was explored. Logistic regression models with cluster-robust errors, modeling subject-level and area-level effects, were used. RESULTS: Living in deprived and intermediate areas, as compared with affluent ones, was associated with greater likelihood of both nonfatal overdose and jail sentences longer than 6 months, though not of active viral hepatitis. CONCLUSIONS: Area-level deprivation may play an important role in determining adverse consequences in people with substance use disorders, also after controlling for individual-level characteristics. More research is needed to understand the aspects of social and physical environments that matter for drug outcomes before effective policy and research interventions can be developed.

Use of adjuvant chemotherapy in radical cystectomy patients aged >65 years: a population-based study from the surveillance epidemiology and end results (SEER)-medicare database.

BACKGROUND: The role of adjuvant chemotherapy (AC) within urothelial carcinoma of the urinary bladder (UCUB) patients after radical cystectomy (RC) is under debate. We assessed contemporary AC utilization rates. We also examined the rates of AC according to patient disease and sociodemographic characteristics. METHODS: We relied on the SEER-Medicare database for non-organ-confined, muscle-invasive T2 N+ -T4a UCUB patients who underwent RC between 1991 and 2009 without neoadjuvant chemotherapy delivery. Multivariable logistic regression analyses tested predictors of AC use; T-stage, N-stage, year of diagnosis, age, gender, race, radiotherapy (RT) administration, marital urban and socioeconomic status, tumor grade and Charlson Comorbidity Index (CCI). RESULTS: Overall, 2681 patients were identified. Of those, 667 (24.9%) received AC. The rate of AC were 21.4%, 23.5%, 24.6% and 29.9% over time (1991-1999 vs. 2000-2002 vs. 2003-2005 vs. 2006-2009) (P=0.002). In multivariable analyses stages pT2N+ (odds ratio (OR): 4.7; P<0.001) and pT3/4aN+ (OR: 4.0; P<0.001), year of diagnosis (OR: 1.9; P<0.001), RT (OR: 1.7; P<0.001), married status (OR: 1.4; P=0.001) and advanced age (OR: 0.3; P<0.001) were independent predictors of AC. Neither race nor CCI demonstrated significance. CONCLUSIONS: In conclusion, we report lower than anticipated overall (24.9%) use of AC. Nonetheless, the rate increased from 13.6% (1991) to 24.1% (2009). Presence of lymph node invasion at RC regardless of T2 or T3/4a stage was the most important variable that increased AC use. Older and unmarried individuals were less likely to receive AC. AC rates were higher in T2N+ UCUB patients than in T3-T4a individuals.

Suboptimal use of neoadjuvant chemotherapy in radical cystectomy patients: A population-based study.

INTRODUCTION: We aimed to assess contemporary rates of neoadjuvant chemotherapy (NC) use. METHODS: We relied on the Surveillance, Epidemiology and End Results (SEER)-Medicare database for non-metastatic, muscle-invasive (T2-T4a) urothelial carcinoma of the urinary bladder (UCUB) patients who underwent radical cystectomy (RC) between 1991 and 2009. Multivariable logistic regression analyses tested predictors of NC use, such as: T-stage, N-stage, year of diagnosis, age at diagnosis, gender, race, use of radiotherapy (RT), marital status, urban status, socioeconomic status, tumour grade, and Charlson comorbidity index (CCI). RESULTS: Overall, 5207 patients treated with RC were identified. Of those, 332 (6.4%) received NC. The rate of NC increased over time from 6.1% (1991) to 15.0% (2009) (p<0.001). In multivariable analyses, year of diagnosis (odds ratio [OR]: 4.7; p<0.001), lower T-stage (T3 vs. T2: OR: 0.7; p=0.003), married status (OR: 1.5; p=0.006), and younger age at diagnosis (≥80 vs. 66-69: OR: 0.6; p=0.006) were associated with a higher odds of NC; all represented independent predictors of NC use. Neither race nor CCI demonstrated statistical significance. CONCLUSIONS: We reported lower than anticipated overall (6.4%) use of NC. Nonetheless, the rate increased from 6.1% (1991) to 15.0% (2009). Older and unmarried individuals were less likely to receive NC. NC rates were higher in T2 UCUB patients. Some of the observed discrepancies, such as lower use in unmarried individuals, may require correction. Better adherence to guidelines should be encouraged and implemented, especially based on the confirmed benefits of NC according to randomized, controlled trials. The study is limited by a retrospective design and limited variables.

Cross-talk between Dopachrome Tautomerase and Caveolin-1 Is Melanoma Cell Phenotype-specific and Potentially Involved in Tumor Progression.

l-Dopachrome tautomerase (l-DCT), also called tyrosinase-related protein-2 (TRP-2), is a melanoma antigen overexpressed in most chemo-/radiotherapeutic stress-resistant tumor clones, and caveolin-1 (CAV1) is a main regulator of numerous signaling processes. A structural and functional relationship between DCT and CAV1 is first presented here in two human amelanotic melanoma cell lines, derived from vertical growth phase (MelJuSo) and metastatic (SKMel28) melanomas. DCT co-localizes at the plasma membrane with CAV1 and Cavin-1, another molecular marker for caveolae in both cell phenotypes. Our novel structural model proposed for the DCT-CAV1 complex, in addition to co-immunoprecipitation and mass spectrometry data, indicates a possible direct interaction between DCT and CAV1. The CAV1 control on DCT gene expression, DCT post-translational processing, and subcellular distribution is cell phenotype-dependent. DCT is a modulator of CAV1 stability and supramolecular assembly in both cell phenotypes. During autocrine stimulation, the expressions of DCT and CAV1 are oppositely regulated; DCT increases while CAV1 decreases. Sub-confluent MelJuSo clones DCT(high)/CAV1(low) are proliferating and acquire fibroblast-like morphology, forming massive, confluent clusters as demonstrated by immunofluorescent staining and TissueFAXS quantitative image cytometry analysis. CAV1 down-regulation directly contributes to the expansion of MelJuSo DCT(high) subtype. CAV1 involved in the perpetuation of cell phenotype-overexpressing anti-stress DCT molecule supports the concept that CAV1 functions as a tumor suppressor in early stages of melanoma. DCT is a regulator of the CAV1-associated structures and is possibly a new molecular player in CAV1-mediated processes in melanoma.

Methods for obtaining and determination of squalene from natural sources.

Squalene is a natural dehydrotriterpenic hydrocarbon (C30H50) with six double bonds, known as an intermediate in the biosynthesis of phytosterol or cholesterol in plants or animals. We have briefly reviewed the natural sources for squalene and focused on the main methods and techniques to obtain and to determine it. Some of its applications in different fields of human activity are also mentioned.