A time differentiated dietary intervention effect on the biomarkers of exposure to pyrethroids and neonicotinoids pesticides.

Tailoring medical models to the right person or risk subgroups delivered at the right time is important in personalized medicine/prevention initiatives. The CIRCA-CHEM randomized 2x2 crossover pilot trial investigated whether the consumption of fruits/vegetables within a time-restricted daily window would affect urinary biomarkers of exposure to neonicotinoids (6-chloronicotinic acid, 6-CN) and pyrethroids (3-phenoxybenzoic acid, 3-PBA) pesticides, a biomarker of oxidative damage (4-hydroxynonenal, 4-HNE) and the associated urinary NMR metabolome. A statistically significant difference (p < 0.001) in both creatinine-adjusted 6-CN and 3-PBA levels was observed between the two-time dietary intervention windows (morning vs. evening). In the evening intervention period, pesticides biomarker levels were higher compared to the baseline, whereas in the morning period, pesticide levels remained unchanged. Positive associations were observed between pesticides and 4-HNE suggesting a diurnal chrono-window of pesticide toxicity. The discovery of a chronotoxicity window associated with chrono-disrupted metabolism of food contaminants may find use in personalized medicine initiatives.

Assessment of indoor and outdoor air quality in primary schools of Cyprus during the COVID-19 pandemic measures in May-July 2021.

Combined pollutant effects from indoor and outdoor sources on children's health, while being at school have not been holistically tackled. The aim of the School Temperature and Environmental Pollutants Study (STEPS) was to perform a school population representative assessment of indoor air quality (IAQ) in primary schools of densely and intermediate populated areas of Cyprus (n = 42). The study took place during May-July 2021 when a school-specific COVID-19 protocol was in place. Questionnaire-based characteristics of schools/classrooms were collected along with 24/48-h long IAQ monitoring of air temperature, relative humidity (RH), particulate matter (PM), carbon dioxide (CO2) and volatile organic compounds (VOCs), using low-cost sensors. Mixed effect models assessed the IAQ determinants during school hours. Indoor PM, temperature, RH and VOCs increased with progressing school periods in the day, while indoor CO2 decreased. Indoor RH and CO2 were negatively associated with % open windows, while indoor PM2.5 was positively associated. Most of school time (85%), indoor air temperature exceeded the recommended upper limit (27 °C), while a third of indoor PM2.5 (24-h) measurements exceeded 15 µg/m3. The interplay of clean indoor air with adequate ventilation and adaptation to heat stress in schools is important and its comprehensive characterization requires holistic methodological approaches and tools.

[Frontal fibrosing alopecia-update]. / Frontal fibrosierende Alopezie ­ aktuelles Wissen.

The number of patients presenting with frontal fibrosing alopecia (FAA) is increasing not only in hair clinics. The recognition of the peculiar clinical pattern and associated symptoms is an important prerequisite to ensure adequate counseling and therapeutic management of the patients. Experimental studies and a range of case series give first insights into the pathogenesis, possible trigger factors, clinical course of disease and treatment options. The clinical spectrum of FFA extends beyond the typical recession of the frontal hair line initially observed in postmenopausal women. Younger women, men and rarely adolescents may also be affected. Band-like extension to the occiput, diffuse bitemporal hair thinning, eyebrow and body hair involvement as well as facial papules are part of the clinical spectrum. Similar to lichen planopilaris, inflammation and fibrosis with involvement of the stem cell region result in permanent loss of hair follicles. Which additional factors contribute to the characteristic pattern remains to be elucidated. Currently, therapeutic management largely relies on anti-inflammatory treatment with combined topical, intralesional and systemic administration depending on disease activity. The chronic progressive course, sometimes even in the absence of pronounced inflammation remains a challenge for both the affected individuals and the treating physicians. Controlled studies are required to develop evidence-based recommendations and to explore novel treatment strategies.

Alopecia areata - Current understanding and management.

Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute or chronic non-scarring hair loss, with a heterogeneity in clinical manifestations ranging from patchy hair loss to complete scalp and body hair loss. An overview of the up-to-date pathophysiology and the underlying signaling pathways involved in AA together with diagnostic and therapeutic recommendations will be provided. Current treatments, including topical, systemic and injectable interventions show varying response and frequent relapses reflecting the unmet clinical need. Thus, the new emerging concepts and therapeutic approaches, including Janus kinase inhibitors are eagerly awaited. Traditional and emerging therapies of AA will be discussed, in order to provide physicians with guidance for AA management. Since the latter is so challenging and often tends to take a chronic course, it can have an enormous psychosocial burden on patients, compromising their quality of life and often causing depression and anxiety. Therefore, the psychosocial aspects of the disease need to be evaluated and addressed, in order to implement appropriate psychological support when needed.

Stakeholders' Perceptions of Environmental and Public Health Risks Associated with Hydrocarbon Activities in and around the Vasilikos Energy Center, Cyprus.

The Vasilikos Energy Center (VEC) is a large hydrocarbon industrial hub actively operating in Cyprus. There is strong public interest by the communities surrounding VEC to engage with all stakeholders towards the sustainable development of hydrocarbon in the region. The methodological framework of the exposome concept would allow for the holistic identification of all relevant environmental exposures by engaging the most relevant stakeholders in industrially contaminated sites. The main objectives of this study were to: (i) evaluate the stakeholders' perceptions of the environmental and public health risks and recommended actions associated with the VEC hydrocarbon activities, and (ii) assess the stakeholders' understanding and interest towards exposome-based technologies for use in oil and gas applications. Methods: Six major groups of stakeholders were identified: local authorities, small-medium industries (SMIs) (including multi-national companies), small-medium enterprises (SMEs), academia/professional associations, government, and the general public residing in the communities surrounding the VEC. During 2019-2021, a suite of stakeholder engagement initiatives was deployed, including semi-structured interviews (n = 32), a community survey for the general public (n = 309), technical meetings, and workshops (n = 4). Results from the semi-structured interviews, technical meetings and workshops were analyzed through thematic analysis and results from the community survey were analyzed using descriptive statistics. Results: Almost all stakeholders expressed the need for the implementation of a systematic health monitoring system for the VEC broader area and its surrounding residential communities, including frequent measurements of air pollutant emissions. Moreover, stricter policies by the government about licensing and monitoring of hydrocarbon activities and proper communication to the public and the mass media emerged as important needs. The exposome concept was not practiced by the SMEs, but SMIs showed willingness to use it in the future as part of their research and development activities. Conclusions: The sustainable development of hydrocarbon exploitation and processing prospects for Cyprus involves the VEC. Continuous and active collaboration and mutual feedback among all stakeholders involved with the VEC is essential, as this may allow future environmental and occupational health initiatives to be formalized.

A randomized cross-over trial investigating differences in 24-h personal air and skin temperatures using wearable sensors between two climatologically contrasting settings.

The influence of elevated air temperatures recorded in various urban microenvironments in adversely impacting biologically relevant disease end points has not yet been extensively tackled. This study is a post hoc analysis of the TEMP pilot trial, a randomized 2 × 2 cross-over trial that examined changes in metabolic and stress hormonal profiles of healthy adults in two settings (urban vs. rural) with distinctly different climatological characteristics during the Mediterranean summer. This analysis aimed to study the association between the 24-h personal air or skin temperature sensor measurements and the diary-based location type (indoors vs. outdoors) in urban (seaside) vs. rural (higher in altitude) microenvironments. Out of 41 eligible participants, a total of 37 participants were included in this post-hoc TEMP trial analysis. Wearable sensors recorded personal air temperature, skin temperature, and activity (as a surrogate marker of physical activity) in each setting, while a time-stamped personal diary recorded the types of indoor or outdoor activities. Temperature peaks during the 24-h sampling period were detected using a peak finding algorithm. Mixed effect logistic regression models were fitted for the odds of participant location (being indoors vs. outdoors) as a function of setting (urban vs. rural) and sensor-based personal temperature data (either raw temperature values or number of temperature peaks). During the study period (July-end of September), median [interquartile range, IQR] personal air temperature in the rural (higher altitude) settings was 1.5 °C lower than that in the urban settings (27.1 °C [25.4, 29.2] vs. 28.6 °C [27.1, 30.5], p < 0.001), being consistent with the Mediterranean climate. Median [IQR] personal air temperature in indoor (micro)environments was lower than those in outdoors (28.0 °C [26.4, 30.3] vs 28.5 °C [26.8, 30.7], p < 0.001). However, median [IQR] skin temperature was higher in indoor (micro)environments vs. outdoors (34.8 °C [34.0, 35.6] and 33.9 °C [32.9, 34.8], p < 0.001) and the number of both personal air and skin temperature peaks was higher indoors compared to outdoors (median [IQR] 3.0 [2.0,4.0] vs 1.0 [1.0,1.3], p < 0.007, for the skin sensors). A significant association between the number of temperature peaks and indoor location types was observed with either the personal air sensor (OR 3.1; 95% CI 1.2-8.2; p = 0.02) or the skin sensor (OR 3.7; 95% CI 1.4-9.9; p = 0.01), suggesting higher number of indoor air temperature fluctuations. Amidst the global climate crisis, more population health studies or personalized medicine approaches that utilize continuous tracking of individual-level air/skin temperatures in both indoor/outdoor locations would be warranted, if we were to better characterize the disease phenotype in response to climate change manifestations.

Dysbiosis and Enhanced Beta-Defensin Production in Hair Follicles of Patients with Lichen Planopilaris and Frontal Fibrosing Alopecia.

Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this exploratory study, we investigate the bacterial composition of scalp skin and plucked hair follicles (HF) of patients with FFA, LPP and alopecia areata circumscripta (AAc), as well as healthy individuals, in relation to cellular infiltrates and the expression of defense mediators. The most abundant genus in lesional and non-lesional HFs of LPP and FFA patients was Staphylococcus, while Lawsonella dominated in healthy individuals and in AAc patients. We observed statistically significant differences in the ratio of Firmicutes to Actinobacteria between healthy scalp, lesional, and non-lesional sites of FFA and LPP patients. This marked dysbiosis in FFA and LPP in compartments close to the bulge was associated with increased HßD1 and HßD2 expression along the HFs from lesional sites, while IL-17A was increased in lesional HF from AAc patients. The data encourage further studies on how exogenous factors and molecular interactions across the HF epithelium could contribute to disease onset and propagation.

Exposome changes in primary school children following the wide population non-pharmacological interventions implemented due to COVID-19 in Cyprus: A national survey.

BACKGROUND: Non-pharmacological interventions (NPI), including lockdowns, have been used to address the COVID-19 pandemic. We describe changes in the environment and lifestyle of school children in Cyprus before the lockdown and during school re-opening, and assess compliance to NPI, using the exposome concept. METHODS: During June 2020, parents completed an online questionnaire about their children's lifestyle/behaviours for two periods; school re-opening (May 21-June 26) following the population-wide lockdown, and the school period before lockdown (before March). FINDINGS: Responses were received for 1509 children from over 180 primary schools. More than 72% of children complied with most NPI measures; however, only 48% decreased the number of vulnerable contacts at home. Sugary food consumption was higher in the post-lockdown period with 37% and 26% of the children eating sugary items daily and 4-6 times/week, compared to 33% and 19%, respectively, for the pre-lockdown period (p<0.001). Children's physical activity decreased compared to pre-lockdown (p<0.001), while screen time increased in the post-lockdown period, with 25% of children spending 4-7 hours/day in front of screens vs. 10% in the pre-lockdown period (p<0.001). About half of the children washed their hands with soap 4-7 times/day post-lockdown vs. 30% in the pre-lockdown period (p<0.001). INTERPRETATION: This national survey showed a high degree of compliance to NPI measures among school children. Furthermore, the exposome profile of children may be affected in the months following NPI measures due to alterations in diet, physical activity, sedentary behaviour, and hand hygiene habits. FUNDING: Partial funding by the EXPOSOGAS project, H2020 Research and Innovation Programme (grant #810995).

The Potential Relevance of the Microbiome to Hair Physiology and Regeneration: The Emerging Role of Metagenomics.

Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses by controlling the local inflammatory milieu, the breakdown of which can result in chronic inflammatory disorders. Follicular microbiome shifts described in some inflammatory cutaneous diseases suggest a link between their development or perpetuation and dysbiosis. Though the hair follicle infundibulum is an area of intense immunological interactions, bulb and bulge regions represent immune-privileged niches. Immune privilege maintenance seems essential for hair growth and regeneration, as collapse and inflammation characterize inflammatory hair disorders like alopecia areata and primary cicatricial alopecia. Current research largely focuses on immunological aberrations. However, studies suggest that external stimuli and interactions across the follicular epithelium can have profound effects on the local immune system, homeostasis, and cycling. Herein, we review hair follicle bacterial colonization, its possible effects on the underlying tissue, and links to the pathogenesis of alopecia, beyond the pure investigation of specific species abundance. As skin microbiology enters the metagenomics era, multi-dimensional approaches will enable a new level of investigations on the effects of microorganisms and metabolism on host tissue.

Identification of anti-microbial peptides and traces of microbial DNA in infrainfundibular compartments of human scalp terminal hair follicles.

BACKGROUND: The upper follicular compartment, a well-known reservoir of cutaneous microbiota, constitutes a space for intensive cross-barrier dialogue. The lower follicle comprises the bulb and bulge, structures with relative immune-privileged status, crucial for physiological cycling, and widely considered to be microbial-free. OBJECTIVES: Following our initial immunohistochemical screening for regulatory cytokines and defensin expression in anagen hair follicles, we aimed to confirm our results with a follow-up ELISA investigation. We postulated that exposure to microbial components may trigger expression, and thus opted to investigate microbial presence in this area. MATERIALS & METHODS: We performed immunohistochemical staining for selected cytokines and antimicrobial peptides, and Gram and Giemsa staining on tissue sections from healthy individuals. Based on ELISA analyses, we confirmed a marked presence of IL-17A- and HBD2 in infrainfundibular compartments from plucked anagen hair follicles of 12 individuals (six females, six males; frontal and occipital scalp sites). 16S rRNA sequencing on microbial DNA extracted from lower follicles, as well as fluorescence in situ hybridization (FISH) were applied to explore bacterial presence in the infrainfundibular compartments. RESULTS: 16S rRNA sequencing yielded reproducible data of bacterial presence in infrainfundibular compartments of plucked scalp follicles; Lawsonella clevelandensis, Staphylococcaceae and Propionibacteriaceae were the most abundant bacteria. Also, FISH revealed biofilm structures formed by Cutibacterium acnes (formerly Propionibacterium acnes) and Staphylococcus sp. below the infundibulum. CONCLUSION: As the skin microbiome largely influences the local immune system, the presence of bacteria in proximity to follicular immune-privileged areas may be of relevance to hair cycling in health and disease.

A niche in the spotlight: Could external factors critically disturb hair follicle homeostasis and contribute to inflammatory hair follicle diseases?

The anatomy of the hair follicle and the dynamics of its barrier provide a special space for interactions between macromolecules and the underlying tissue. Translocation across the hair follicle epithelium and immune recognition have been confirmed for proteins, nucleic acids, engineered particles, virus particles and others. Tissue responses can be modulated by pro-inflammatory stimuli as demonstrated in penetration and transcutaneous immunization studies. Even under physiological conditions, hair follicle openings are filled with exogenous material ranging from macromolecules, engineered particles to natural particles including diverse communities of microbes. The exposed position of the infundibulum suggests that local inflammatory insults could disturb the finely tuned balance and may trigger downstream responses that initiate or facilitate local outbreaks of inflammatory hair diseases typically occurring in close spatial association with the infundibulum as observed in cicatricial alopecia. The question as to how microbial colonization or deposition of contaminants on the surface of the hair follicle epithelium interact with the barrier status under the influence of individual predisposition, may help us understand local flare-ups of inflammatory hair diseases. Specifically, learning more about skin barrier alterations in the different types of inflammatory hair diseases and cross-talk with exogenous compounds could give new insights in this less explored aspect of hair follicle homeostasis. Such knowledge may not only be used to develop supportive measures to maintain a healthy scalp. It may have wider implications for our understanding on how external factors influence inflammation and immunological responses in the skin.