Environmental Triggering Factors Research Articles

Tubulointerstitial Nephritis and Uveitis Syndrome During the COVID-19 Pandemic: A Case Series.

To report the ocular findings, laboratory results, and management of patients with tubulointerstitial nephritis and uveitis syndrome (TINU), whose numbers increased during the 2019 coronavirus disease (COVID-19) pandemic. Demographic characteristics, ophthalmic examination findings, laboratory results including polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serum SARS-CoV-2 immunoglobulin G (IgG) antibody, and treatment of patients diagnosed with TINU between March 2020 and March 2022 were evaluated retrospectively. The study included 19 eyes of 10 patients (6 female/4 male). The mean age was 13.5±2.4 years (range: 8-16 years). The mean follow-up duration was 13.5±6.1 months (range: 6-24 months). All patients presented with anterior uveitis. Anterior uveitis was bilateral in 9 patients (90%) and unilateral in 1 patient (10%). Posterior segment findings were normal in 8 patients (80%), and bilateral optic disc edema was observed in only 2 patients (20%). None of the patients had a previous SARS-CoV-2 infection and/or vaccination history. The SARS-CoV-2 PCR test was negative in all patients at presentation. The SARS-CoV-2 IgG antibody test was reactive in 7 patients (70%). Recurrent uveitis developed in 8 patients (80%) during follow-up. Systemic immunomodulatory therapy was required for the control of ocular inflammation in 7 patients (70%) with severe uveitis flare-ups. TINU is a multisystemic autoimmune disease, especially in response to environmental triggering factors such as viral infections. Although TINU is a rare disease, the number of cases increased during the COVID-19 pandemic. SARS-CoV-2 antibodies were detected at a significant rate of 70% in these patients, who did not have a history of SARS-CoV-2 infection and vaccination. Previous asymptomatic SARS-CoV-2 infection in children may be a triggering factor in the development of TINU.

Space-time data-driven modeling of precipitation-induced shallow landslides in South Tyrol, Italy

Shallow landslides represent potentially damaging processes in mountain areas worldwide. These geomorphic processes are usually caused by an interplay of predisposing, preparatory, and triggering environmental factors. At regional scales, data-driven methods have been used to model shallow landslides by addressing the spatial and temporal components separately. So far, few studies have explored the integration of space and time for landslide prediction. This research leverages generalized additive mixed models to develop an integrated approach to model shallow landslides in space and time. We built upon data on precipitation-induced landslide records from 2000 to 2020 in South Tyrol, Italy (7400 km2). The slope unit-based model predicts landslide occurrence as a function of static and dynamic factors while seasonal effects are incorporated. The model also accounts for spatial and temporal biases inherent in the underlying landslide data. We validated the resulting predictions through a suite of cross-validation techniques, obtaining consistent performance scores above 0.85. The analyses revealed that the best-performing model combines static ground conditions and two precipitation time windows: a short-term cumulative precipitation of 2 days before the landslide event and a medium-term cumulative precipitation of 14 days. We demonstrated the model's predictive capabilities by predicting the dynamic landslide probabilities over historical data associated with a heavy precipitation event on August 4th and August 5th, 2016, and hypothetical non-spatially explicit precipitation (what-if) scenarios. The novel approach shows the potential to integrate static and dynamic landslide factors for large areas, accounting for the underlying data structure and data limitations.

Environmental Factors Influencing Tobacco Usage among High School Children in Lucknow City: A Cross-sectional Study

Background: Evidence proves that the majority of adult tobacco users begin using tobacco as children or teens. Teenagers are drawn to tobacco products for a variety of reasons. Public health planners are gravely concerned about the current rapid trade and tobacco use among teenagers in a developing nation like India. Objective: The present paper focuses on the prevalence of tobacco use among children in the eighth to tenth grades and the various environmental factors that contribute to tobacco use among children. Material and Methods: Following ethical clearance, six government schools in Lucknow were chosen for this cross-sectional study, and data was gathered using the Global Youth Tobacco Survey (GYTS) to examine the relationship between tobacco use in children and other independent influencing factors. Logistic regression analysis was used. Results: 21.7% of the children used tobacco in some or the other way. Supari with tobacco was the most popular tobacco product consumed by children (48.3%). Statistical analysis showed that family members consuming tobacco at home and adults sending their kid to get tobacco had a high connection with tobacco use among children. The direct relationship between children watching individuals consuming tobacco on television and their arousal of interest for the same was also seen. Similarly, the presence of tobacco vendors outside the school and easy availability of tobacco products to children significantly influenced the tobacco consumption habit. Conclusion: Tobacco users in families, adults sending children to buy tobacco, children’s arousal of interest on seeing people using tobacco on media, tobacco vendors outside the school, and the easy availability of tobacco products have all been proven to be environmental triggering factors for tobacco consumption amongst high school students.

Morphea: a practical review of its diagnosis, classification and treatment.

Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with extracutaneous manifestations. Its etiology is not fully understood, but it is believed that there is genetic predisposition, in addition to environmental triggering factors. Classification of the disease is not simple due to its multiple presentations; however, it is useful in order to define the treatment, which should be individualized and started early to avoid cosmetic and functional complications. In this review, we summarize the most important practical aspects of the classification, diagnostic methods and evaluation of morphea activity, as well as available therapeutic options, with an emphasis on existing clinical evidence regarding their efficacy and safety.

Implementation of Nursing Care by Providing Nebulizers to Asthmatic Children with Ineffective Airway Clearance Problems

Asthma is one of the main non-communicable diseases and asthma is a chronic disease in which the airways of the lungs become inflamed and narrow. Asthma trigger factors are often found in the environment both inside and outside the home, but children with a family history of asthma have a greater risk of developing asthma. Apart from that, factors that trigger asthma are divided into two groups, namely genetic, including bronchial atopy/allergy, eczema; environmental trigger factors, such as motor vehicle fumes, cigarette smoke, burning rubbish, humidity in the house, and allergens such as house dust and animal dander. Method: The case study used in this research is descriptive in a case study design to explore the implementation of nursing care providing nebulizers with the problem of ineffective airway clearance in children with asthma at Bhayangkara Hospital, Palembang. The approach used is a nursing care approach which includes assessment, nursing diagnosis, nursing intervention, nursing implementation, and nursing evaluation. Results: The results of the research after the implementation of asthma management nursing with a Nebulizer in Asthma patients were proven to have an impact on improving breathing frequency because it had the effect of improving sputum production so that it was very influential in the process of improving breathing frequency/shortness of breath. Conclusion: Implementation of Nursing Care by Giving Nebulizers to asthmatic children with hygiene problems ineffective airway can be done because it is more effective for asthma patients and improves respiratory frequency.

In-silico Study of Phytoconstituents from Tribulus terrestris as potential Anti-psoriatic agent

Introduction: Psoriasis (Ps) is a well-known chronic non-infectious, inflammatory skin disease affecting about 2–3% of the worldwide Population. Pathogenesis includes the environmental trigger factors with other factors like genetic factors, trauma, chemicals, bacterial infection etc. Currently there is no drug which can permanently cure the skin lesions as well as completely eradicate this dermatosis. The purpose of this research is to investigate the anti-psoriatic activity of phytoconstituents of Tribulus terrestris by predicting the ligand-receptor binding and by predicting the ADMET parameters using Lipinski's rule. Methodology: The process of research work starts with protein and ligand structure preparation. Further docking was done using PyRxAutodock Vina. Afterward, analysis and visualisation of the interaction between protein-ligands was done, and ADMET profiling was carried out according to lipinski's rules using Swiss ADME. Result: we selected four phytoconstituents of Tribulus terrestris. Molecular docking simulation showed all four compounds had better binding affinities. Based on the results of prediction of ADMET values using the Lipinski rule, compound that are thought to have good activity. Conclusion: Based on results these molecules have discovered that they may be able to produce anti-psoriatic activity and found that they have a lower toxicity, and ADME analysis determined the easily absorbability to the tissue site. Hence, these compounds can be analysed by further in vitro studies and can be a leader in the designing of the potential drug for the psoriasis management.

Effects of rigid gas permeable contact lens on morphological parameters and vision-related quality of life in keratoconus patients.

To evaluate the effect of rigid gas permeable contact lens (RGP-CL) on corneal morphological parameters and vision-related quality of life in keratoconus (KC) patients. Totally 57 eyes of 30 KC patients who were followed-up for more than two years, including 17 RGP wearers (32 eyes) and 13 non-wearers (25 eyes) were retrospectively analyzed. Initial medical history and corneal topography were collected at baseline. Corneal topography, corneal aberration, optical coherence tomography, and vision-related quality of life questionnaires were performed at the last follow-up. According to corneal topography, increase of the flattest keratometric values was higher in RGP wearers than in non-wearers (P=0.038). The morphological parameters, including symmetry index of front corneal curvature (P=0.004) and Baiocchi-Calossi-Versaci index front (P=0.047), were lower in RGP wearers than in non-wearers. Vertical coma was smaller in RGP wearers than non-wearers in 3.0, 5.0, 6.0, and 7.0 mm pupil diameters, respectively (P<0.05). The environmental triggering domain of ocular surface disease index was worse in RGP wearers as compared to non-wearers (P=0.003). At the last follow-up, there were no significant differences in constituent ratios of KC progression, corneal thickness topography, epithelial thickness topography, morphological parameters of corneal topography, and other questionnaire scores between the two groups (all P>0.05). Long-term use of RGP does not worsen KC but may cause corneal epithelial remodeling to increase symmetry of corneal anterior surface, reduce corneal vertical coma and improve visual quality. However, RGP wearing causes a slight decrease in vision-related quality of life. The occurrence of ocular surface symptoms is mainly associated with environmental triggering factors.

Parasomnias during trans-meridian and long-distance travel: Critical literature review and clinical practice recommendations.

Parasomnias are undesirable events that occur during sleep. They can be classified into rapid eye movement parasomnias and non-rapid eye movement parasomnias. Those who experience parasomnias may be anxious about travel for many reasons, including the occurrence of unwanted events during the trip, increased exposure to environmental trigger factors, and the propensity for harm to occur due to unfamiliar surroundings while travelling. There is a paucity of literature examining this area. This review summarizes the relevant literature and the clinical experience of the authors to compile clinical practice recommendations. The clinical features of parasomnias and how they relate to trans-meridian and long-distance travel are described. Triggers for non-rapid eye movement parasomnias, particularly the use of sedative hypnotic drugs, alcohol, drug withdrawal, sleep deprivation, emotional stress and environmental stimulations, are described. Management of parasomnias whilst travelling is reviewed, with a particular focus on trigger minimalization. The role for clonazepam and melatonin is outlined. At the pre-travel health consultation, the physician is strongly advised to screen the traveller for co-morbid sleep conditions, which exacerbate parasomnias. Areas for further research are explored, including the extent to which these sleep disorders impact on the travel experience.

Neuroimmune communication regulating pruritus in atopic dermatitis

Atopic dermatitis (AD) is a common, chronic-relapsing inflammatory skin disease with significant disease burden. Genetic and environmental trigger factors contribute to AD, activating 2 of our largest organs, the nervous system and the immune system. Dysregulation of neuroimmune circuits plays a key role in the pathophysiology of AD, causing inflammation, pruritus, pain, and barrier dysfunction. Sensory nerves can be activated by environmental or endogenous trigger factors, transmitting itch stimuli to the brain. On stimulation, sensory nerve endings also release neuromediators into the skin, contributing again to inflammation, barrier dysfunction, and itch. In addition, dysfunctional peripheral and central neuronal structures contribute to neuroinflammation, sensitization, nerve elongation, and neuropathic itch, thus chronification and therapy resistance. Consequently, neuroimmune circuits in skin and central nervous system may be targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids, and ions excite/sensitize sensory nerve endings, which not only induces itch but further aggravates/perpetuates inflammation, skin barrier disruption, and pruritus as well. Thus, targeted therapies for neuroimmune circuits as well as pathway inhibitors (eg, kinase inhibitors) may be beneficial to control pruritus in AD either in systemic and/or in topical form. Understanding neuroimmune circuits and neuronal signaling will optimize our approach to control all pathological mechanisms in AD, inflammation, barrier dysfunction, and pruritus.

First Report on Microcystin-LR Occurrence in Water Reservoirs of Eastern Cuba, and Environmental Trigger Factors.

The factors related to cyanotoxin occurrence and its social impact, with comprehension and risk perception being the most important issues, are not yet completely understood in the Cuban context. The objectives of this research were to determine the risk extension and microcystin-LR levels, and to identify the environmental factors that trigger the toxic cyanobacteria growth and microcystin-LR occurrence in 24 water reservoirs in eastern Cuba. Samplings were performed in the early morning hours, with in situ determination and physicochemical analysis carried out in the laboratory. Microcystin-LR were determined in water and within the cells (intracellular toxins) using UPLC–MS analysis after solid phase extraction. The reservoirs studied were found to be affected by eutrophication, with high levels of TN:TP ratio and phytoplankton cell concentrations, high water temperatures and low transparency, which cause collateral effect such as cyanobacterial bloom and microcystin-LR occurrence. In Hatillo, Chalóns, Parada, Mícara, Baraguá, Cautillo, La Yaya, Guisa and Jaibo reservoirs, concentrations of MC-LR higher than the WHO limits for drinking water (1 µg·L−1), were detected.

Coinfections and Phenotypic Antimicrobial Resistance in Actinobacillus pleuropneumoniae Strains Isolated From Diseased Swine in North Western Germany-Temporal Patterns in Samples From Routine Laboratory Practice From 2006 to 2020.

Actinobacillus pleuropneumoniae (APP) is one major bacterial porcine respiratory tract pathogen causing disease outbreaks worldwide, although effective commercial vaccines are available. Due to frequent failure of this preventive measure, treatment with antimicrobials is indispensable to prevent animal losses within an outbreak situation. To preserve the effectivity of antimicrobial substances to fight APP should therefore be the primary aim of any interventions. In this study, the temporal development of antimicrobial resistance in APP was analyzed retrospectively in the time period 2006–2020 from a routine diagnostic database. In parallel, frequent coinfections were evaluated to identify most important biotic cofactors as important triggers for disease outbreaks in endemically infected herds. The proportion of APP serotype 2 decreased over time but was isolated most often from diseased swine (57% in 2020). In ~1% of the cases, APP was isolated from body sites outside the respiratory tract as brain and joints. The lowest frequencies of resistant isolates were found for cephalothin and ceftiofur (0.18%), florfenicol (0.24%), tilmicosin (2.4%), tiamulin (2.4%), enrofloxacin (2.7%), and spectinomycin (3.6%), while the highest frequencies of resistant isolates were found for gentamicin (30.9%), penicillin (51.5%), and tetracycline (78.2%). For enrofloxacin, tiamulin, tilmicosin, and tetracycline, significantly lower frequencies of resistant isolates were found in the time period 2015–2020 compared to 2006–2014, while gentamicin-resistant isolates increased. In summary, there is only a low risk of treatment failure due to resistant isolates. In maximum, up to six coinfecting pathogens were identified in pigs positive for APP. Most often pigs were coinfected with Porcine Circovirus 2 (56%), Streptococcus suis (24.8%), or the Porcine Reproductive and Respiratory Syndrome Virus (23.3%). Potential synergistic effects between these pathogens published from experimental findings can be hypothesized by these field data as well. To prevent APP disease outbreaks in endemically infected herds more efficiently in the future, next to environmental trigger factors, preventive measures must also address the coinfecting agents.

Neurodegenerative Disorders Tendency in Adult Cuban Population

Introduction: Neurodegenerative diseases have a multifactorial etiology, based on genetics and triggering environmental factors, associated with the aging process of the population. Objectives: To describe the mortality and trend of Amyotrophic Lateral Sclerosis, Alzheimer's dementia and Parkinson's disease in Cuba and other countries during the period from 2015 to 2020. Methods Longitudinal descriptive observational study was carried out, which it classifies as chronological or temporal series, on mortality and behavioral trend of Amyotrophic Lateral Sclerosis, Alzheimer's disease and Parkinson's disease in Cuba, during the period 2015 to 2020. Results: The data obtained show that Alzheimer's disease has a tendency to decrease mortality, unlike Parkinson's disease that is observed a slight increase, while in Amyotrophic Lateral Sclerosis the behavior is stable. Deaths in Parkinson's and Alzheimer's disease occurred between 75-79 years of age, while in Amyotrophic Lateral Sclerosis it was 65-69 years old. There was predominance of the male sex in Parkinson's and Amyotrophic Lateral Sclerosis. Women predominated in Alzheimer's disease. The three neurodegenerative diseases occurred in patients with white skin color. The highest number of deaths were shown in the provinces of Havana and Holguín. Conclusions: The prevalence and incidence of dementia and Alzheimer's disease increases exponentially, in relation with Parkinson´s disease the incidence vary widely throughout the world and the most significant risk factors are aging and men. Finally, the prevalence of Amyotrophic Lateral Sclerosis remains low due to high mortality, due to the lack of effective treatment at present.

Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Molecular and Environmental Triggering Factors of Pathogenicity of Fusarium oxysporum and F. solani Isolates Involved in the Coffee Corky-Root Disease.

Coffee corky-root disease causes serious damages to coffee crop and is linked to combined infection of Fusarium spp. and root-knot nematodes Meloidogyne spp. In this study, 70 Fusarium isolates were collected from both roots of healthy coffee plants and with corky-root disease symptoms. A phylogenetic analysis, and the detection of pathogenicity SIX genes and toxigenicity Fum genes was performed for 59 F. oxysporum and 11 F. solani isolates. Based on the molecular characterization, seven F. oxysporum and three F. solani isolates were assessed for their pathogenicity on coffee seedlings under optimal watering and water stress miming root-knot nematode effect on plants. Our results revealed that a drastic increment of plant colonization capacity and pathogenicity on coffee plants of some Fusarium isolates was caused by water stress. The pathogenicity on coffee of F. solani linked to coffee corky-root disease and the presence of SIX genes in this species were demonstrated for the first time. Our study provides evidence for understanding the pathogenic basis of F. oxysporum and F. solani isolates on coffee and revealed the presence of SIX and Fum genes as one of their pathogenicity-related mechanisms. We also highlight the relevance of chlorophyll, a fluorescence as an early and high-throughput phenotyping tool in Fusarium pathogenicity studies on coffee.

Comparison of Four Different Allergy Tests in Equine Asthma Affected Horses and Allergen Inhalation Provocation Test

Potential triggers for equine asthma are allergens from hay and straw dusts, mold spores and storage mites. The contribution of these environmental trigger factors to equine asthma is still largely uncertain. The aim of this study was to compare results of four allergy tests from healthy and asthma-affected horses, and to evaluate the clinical relevance of allergens tested positive via specific inhalation provocation test. Fifteen horses were classified using a clinical scoring system as asthmatic (n = 9) or control (n = 6). Four different allergy tests (functional in vitro test, intradermal test, Fc-epsilon receptor test, and ELISA for allergen-specific IgE) were compared. A histamine inhalation provocation test as positive control was performed in all horses and the interpleural pressure was measured. In addition, two individual allergens were chosen for the allergen inhalation provocation test based on the results of the allergy tests and inhaled in increasing concentrations, until signs of dyspnea occurred. None of the four allergy tests could differentiate reliably between controls and asthma-affected horses. There was no agreement among the results of the four allergy tests. The interpleural pressure results showed a large individual variability. A clear positive reaction on the allergen inhalation provocation test was only detected in two asthma-affected horses 6 hours after allergen inhalation with Aspergillus fumigatus and Cladosporium herbarum. In most cases a purely type I immediate reaction is unlikely to be involved in causing the clinical signs of equine asthma. Because of a delayed reaction after allergen provocation in two horses, the involvement of cell-mediated type III or IV hypersensitivity may be possible. As all allergy tests used in this study can only detect IgE-mediated hypersensitivity, these tests are probably not suitable for an etiological diagnosis of equine asthma.

A STUDY OF THE EFFECT OF NB-UVB PHOTOTHERAPY ON SERUM FOLATE LEVELS IN PATIENTS WITH CHRONIC PLAQUE PSORIASIS

Psoriasis is a chronic immune mediated disease characterized by abnormal proliferation and differentiation of epidermal keratinocytes. It is a multifactorial disease with genetic background, environmental triggering factors, and immunological mediators, there are multiple clinical types of psoriasis the most common type is chronic plaque psoriasis (psoriasis vulgaris) which characterized by sharply demarcated scaly erythematous cutaneous lesions. One of the most recent elements to be measured in psoriatic patients is the serum folate level, it is an essential water soluble vitamin naturally present in food that is required for biosynthesis of the DNA building units. Photolysis of folate may be significant, especially when serum is exposed in vitro to ultraviolet (UV) radiation, so the degradation effect of NB-UVB phototherapy in psoriatic patients is a matter of interest. Narrowband ultraviolet B (NB-UVB) is an important therapeutic tool of generalized psoriasis. can be used as a single monotherapy or combined with other topical or systemic agents in more generalized severe psoriatic patients, inducing more apoptosis of pathogenic T cells and highly proliferating keratinocytes.

Landslide Hazard Assessment Map as an Element Supporting Spatial Planning: The Flysch Carpathians Region Study

Landslides and rock falls are among the many phenomena that have an impact on sustainable construction and infrastructure safety. The main causes of landslides are natural meteorological and hydrological phenomena. In building design and construction, environmental monitoring by identifying geotechnical hazards must be taken into account, as appropriate hazard assessment contributes to ensuring future construction safety. The Carpathian region in southern Poland is particularly predisposed to landslide formation. This may be favored by the nature of the shapes associated with the high and steep slopes of the region’s valleys. Another reason for concern is the flysch geological structure, which is characterized by alternating layers of water-permeable sandstones and poorly permeable shales, clays, and marls. Furthermore, the presence of a quaternary weathering cover makes the geological structure more susceptible to landslide processes and tectonic formations. The paper presents the results of a study whose aim was to elaborate a detailed landslide hazard map for a selected area in the Polish Carpathians, using statistical methods. The approach is based on the Hellwig method, which seems particularly useful in the assessment of susceptibility and landslide hazards on a local scale for a relatively small area. A two-stage study was conducted. The first stage of the research involved the creation of a database associated with environmental parameters and triggering factors, whereas the second stage consisted of the adoption of weights for seven thematic sections and their special features on the basis of expert knowledge. The hazard map developed as a result was compared to the mapping made using the weight-of-evidence method. The proposed data normalization method allows the use and analysis of both qualitative and quantitative data collected from various sources. The advantage of this method is the simple calculation procedure. A large-scale (1:2000) map might be used to assess the landslide hazard for specific cadastral units. Such a map becomes the basis for municipal spatial planning and may be able to influence investment decisions. Detailed landslide hazard maps are crucial for more precise risk evaluation for specific cadastral units. This, in turn, allows one to reduce serious economic and social losses, which might be the future results of landslides.

Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic

BackgroundThe timing of puberty in girls is occurring at an increasingly early age. While a positive family history is recognised as a predisposing factor for early or precocious puberty, the role of environmental factors is not fully understood.Aims of the studyTo make a retrospective evaluation of the incidence of newly diagnosed central precocious puberty (CPP) and the rate of pubertal progression in previously diagnosed patients during and after the Italian lockdown for COVID-19, comparing data with corresponding data from the previous 5 years. To determine whether body mass index (BMI) and the use of electronic devices increased during lockdown in these patients.Patients and methodsThe study included 49 females with CPP. We divided the patients into two groups: group 1, patients presenting a newly diagnosed CPP and group 2, patients with previously diagnosed slow progression CPP whose pubertal progression accelerated during or after lockdown. We collected auxological, clinical, endocrinological and radiological data which were compared with data from two corresponding control groups (patients followed by our Unit, March to July 2015–2019). Patients’ families completed a questionnaire to assess differences in the use of electronic devices before and during lockdown.ResultsThirty-seven patients presented newly diagnosed CPP (group 1) and 12, with previously diagnosed but untreated slow progression CPP presented an acceleration in the rate of pubertal progression (group 2). The number of new CPP diagnoses was significantly higher than the mean for the same period of the previous 5 years (p < 0.0005). There were no significant differences between patients in group 1 and control group 1 regarding time between appearance of B2 and CPP diagnosis, although group 1 patients had a significantly earlier chronological age at B2, a more advanced Tanner stage at diagnosis (p < 0.005), higher basal LH and E2 levels, higher LH peak after LHRH test (p < 0.05) and increased uterine length (p < 0.005) and ovarian volume (p < 0.0005). The number of patients with previously diagnosed CPP whose pubertal development accelerated was also statistically higher compared to controls (p < 0.0005). In this group, patients’ basal LH (p < 0.05) and E2 levels (p < 0.0005) became more markedly elevated as did the LH peak after LHRH test (p < 0.05). These patients also showed a significantly accelerated progression rate as measured by the Tanner scale (p < 0.0005), uterine length (p < 0.005), and ovarian volume (p < 0.0005). In both group 1 and group 2, BMI increased significantly (p < 0.05) and patients’ families reported an increased use of electronic devices (p < 0.0005).ConclusionOur data show an increased incidence of newly diagnosed CPP and a faster rate of pubertal progression in patients with a previous diagnosis, during and after lockdown compared to previous years. We hypothesize that triggering environmental factors, such as the BMI and the use of electronic devices, were enhanced during lockdown, stressing their possible role in triggering/influencing puberty and its progression. However, more studies are needed to determine which factors were involved and how they interacted.

Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease

Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory angiogenesis. Mysterin mutations, together with exposure to environmental trigger factors, lead to an elevated stroke risk since childhood. Mysterin is induced during cell stress, to function as cytosolic AAA+ ATPase and ubiquitylation enzyme. Little knowledge exists, in which context mysterin is needed. Here, we found that genetic ablation of several mitochondrial matrix factors, such as the peptidase ClpP, the transcription factor Tfam, as well as the peptidase and AAA+ ATPase Lonp1, potently induces Rnf213 transcript expression in various organs, in parallel with other components of the innate immune system. Mostly in mouse fibroblasts and human endothelial cells, the Rnf213 levels showed prominent upregulation upon Poly(I:C)-triggered TLR3-mediated responses to dsRNA toxicity, as well as upon interferon gamma treatment. Only partial suppression of Rnf213 induction was achieved by C16 as an antagonist of PKR (dsRNA-dependent protein kinase). Since dysfunctional mitochondria were recently reported to release immune-stimulatory dsRNA into the cytosol, our results suggest that mysterin becomes relevant when mitochondrial dysfunction or infections have triggered RNA-dependent inflammation. Thus, MMD has similarities with vasculopathies that involve altered nucleotide processing, such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Furthermore, in MMD, the low penetrance of RNF213 mutations might be modified by dysfunctions in mitochondria or the TLR3 pathway.

Neutrophilic Asthma and Potentially Related Target Therapies.

Neutrophilic asthma is generally associated with the absence of eosinophils and activation of non- predominant type 2 immunological pathways. It involves bronchial inflammation followed by different degrees of airway remodeling. Neutrophilic inflammation activates specific cellular and molecular pathways due to inhalation of environmental trigger factors such as exhaust fumes, cigarette smoke, occupation-related agents, and infections. This review discusses the involvement of neutrophils in asthma and potentially related target therapies. Corticosteroid resistance is the hallmark of neutrophilic asthma which increases disease severity and leads to difficult-to-control asthma. Patients with neutrophil-dominant asthma are characterized by low levels of (or absence of) Th2 cytokines. Due to the shortage of effective treatments for neutrophilic asthma newer biologics are being developed that target type 2 asthma symptoms and phenotypes. Understanding different biomarkers, inflammatory pathways and treatment strategies involved in neutrophilic asthma will help to decrease adverse effects related to corticosteroid insensitivity. Better insight of targets involved in neutrophilic inflammation can lead to improved therapies. Further evaluation and clinical trials of emerging biologics involved in neutrophilic asthma needs to be performed before bringing them into clinical practice.