Nanosystems with potential application as carriers for skin depigmenting actives.

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.

Evaluation of the non-clinical toxicity of an antiparasitic agent: diminazene aceturate.

The diminazene aceturate (C14H15N7.2C4H7NO3) is a chemotherapeutic agent with more than six decades of use, however more studies regarding its toxicity still need to be performed. Thus, the present study determined the acute toxicity (14 days) of diminazene acetate (DIZE) in male and female swiss mice by changes in body mass, food consumption, biochemical and hematological parameters, locomotor activity and motor coordination. DIZE was administered at a single dose (1000 and 2000 mg/kg) orally. In addition, in vitro antioxidant capacity, hemolytic activity, toxicity in Artemia salina and in silico evaluation were also performed. The results obtained include several signs of toxicity (hypoactivity, loss of the straightening reflex and tachycardia), reduction of behavioral activity (locomotor activity and motor coordination) and significant changes (p < 0.05) in biochemical and hematological parameters. According to the in silico study, the DIZE can be classified based on the mean lethal dose (LD50) in category 4 (300 mg/kg < LD50 ≤ 2000 mg/kg, ProTox-II) or 3 (50 mg/kg < LD50 ≤ 300 mg/kg, AdmetSAR 1.0). Additionally, DIZE (30.3-969.9 nM) was not toxic to A. salina in the first 48 hours of treatment and was not cytotoxic to rat red blood cells after induced hemolysis. In vitro results indicated low antioxidant capacity against DPPH• and ABTS•+ radicals. Therefore, DIZE induces several adverse effects with influence on the central nervous system, changes in hematological and biochemical parameters and even mortality at the highest dose. However, absence of toxicity was observed in A. salina and rats red blood cells.

Perspectives of the International Society for Cell & Gene Therapy Gastrointestinal Scientific Committee on the Intravenous Use of Mesenchymal Stromal Cells in Inflammatory Bowel Disease (PeMeGi).

Inflammatory bowel disease (IBD), namely, Crohn's disease and ulcerative colitis, remains a grievous and recalcitrant problem incurring significant human and health care costs, even in consideration of the growing incidence. Initial goals of care aimed to achieve the induction and maintenance of clinical remission. The advent of novel treat-to-target approaches using patient stratification, early introduction of immunosuppressants and rapid escalation to biologics or early use of combination therapy has refocused the goals of care toward the achievement of mucosal healing. This is in an attempt to preserve intestinal function, decrease hospitalization and surgery rates and improve the quality of life of affected patients. Cellular therapeutics for the treatment of IBD offers an unprecedented opportunity to change the current paradigm from single-targeted to systems-targeted therapy, trying to dampen the whole inflammatory cascade instead of a only molecule. Therefore, as we move forward, the importance of designing informative and possibly adaptive trial designs, standardizing methodologies, harmonizing goals of therapy and evaluating methods cannot be underemphasized. In this article, we review the current literature on the application of mesenchymal stromal cells for the treatment of IBD in an effort to establish a consensus on designing efficient and consistent clinical trials for the intravenous use of this cellular therapy in IBD.

Modifiable vascular risk factors, white matter disease and cognition in early Parkinson's disease.

BACKGROUND AND PURPOSE: Dementia in Parkinson's disease (PD) is common and disabling. Identification of modifiable risk factors for it is essential. Vascular risk factors (VRFs) may be associated with cognitive decline in early PD. Biomarkers that serve as surrogates of the long-term effect of VRFs on PD are needed. To that end, we aimed to quantitate white matter hyperintensities (WMH) in early PD, measure associations with VRFs and examine relationships between WMH and longitudinal cognition. METHODS: Participants in the Parkinson's Progression Markers Initiative study (141 patients with PD, 63 healthy controls) with adequate baseline structural brain magnetic resonance imaging data were included. Hypertension and diabetes history, and body mass index were combined to create a vascular risk score. WMH were quantitated via automated methods. Cognition was assessed annually with a comprehensive test battery. RESULTS: In the PD group, vascular risk score was associated with WMH for total brain (ß = 0.210; P = 0.021), total white matter (ß = 0.214; P = 0.013), frontal (ß = 0.220; P = 0.002) and temporal (ß = 0.212; P = 0.002) regions. Annual rate of change in global cognition was greater in those with higher vascular risk score (ß = -0.040; P = 0.007) and greater WMH (ß = -0.029; P = 0.049). Higher temporal WMH burden was associated with great decline over time in verbal memory (ß = -0.034; P = 0.031). CONCLUSIONS: In early PD, modifiable VRFs are associated with WMH on brain magnetic resonance imaging. Temporal WMH burden predicts decline in verbal memory. WMH may serve as a surrogate marker for the effect of VRFs on cognitive abilities in PD.

Synthesis, characterization and applications of maghemite beads functionalized with rabbit antibodies.

Magnetic nanoparticles (NPs) have attracted great attention owing to their applications in the biomedical field. In the present work, maghemite (γFe2O3) NPs of 6.5 nm were prepared using a sonochemical method and used to prepare magnetic beads through silanization with 3-aminopropyltrimethoxysilane (APTS). Subsequently, amino groups in the resulting APTS-γFe2O3 beads were converted to carboxylic acid (CARB-γFe2O3) through the succinic anhydride reaction, as confirmed by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy and dynamic light scattering (DLS) measurements. The size of these beads was measured as 12 nm and their hydrodynamic diameter as 490 nm, using TEM analysis and DLS, respectively. The CARB-γFe2O3 beads were further functionalized by immobilizing rabbit antibodies on their surfaces; the immobilization was confirmed by flow cytometry and ionic strength. The samples were further characterized by Mössbauer spectroscopy and DC magnetization measurements. Studies on magnetic relaxivities showed that magnetic beads present great potential for application in MR imaging.

Non-clinical toxicity of ß-caryophyllene, a dietary cannabinoid: Absence of adverse effects in female Swiss mice.

ß-caryophyllene is a food additive that is found in food plants and has broad pharmacological potential. However, little toxicological information has been reported and its use is based on the fact that this bicyclic sesquiterpene is daily consumed as a plant food in much larger quantities than as a food additive. Thus, this study evaluated acute (14-day) and repeated-dose (28 days) oral ß-caryophyllene toxicity in female Swiss mice analyzing changes in body weight, food intake, water intake, hematological and biochemical parameters, organ weight after necropsy, oxidative stress markers and histopathology of various tissues. Acute (300 and 2000 mg/kg) and repeated-dose (300 and 2000 mg/kg) toxicity studies were performed according to the Organization for Economic Cooperation and Development (OECD) guideline 423 and 407, respectively. There was absence of adverse clinical signs and mortality in any animal subjected to acute and repeated-dose toxicity study. In addition, no significant changes in body weight, food and water intake, oxidative stress biomarkers, hematological and biochemical parameters were observed when compared to control group from single-dose and repeated-dose toxicity study. Therefore, the results of this study provide an understanding of the toxicity profile of ß-caryophyllene which can be considered a compound with toxicity at doses higher than 2000 mg/kg body weight.

Absence of toxicity in Swiss mice following treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin: Acute and repeated-dose toxicity study.

Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4-arylcoumarin and neoflavene, have been the subject of a number of studies with respect to their therapeutic potential and, despite promising in vitro, ex vivo and in vivo pharmacological activities, there is a lack of studies demonstrating their toxicological properties. Therefore, this study aims to evaluate the acute (14 days) and repeated-dose (28 days) toxicity of synthetic neoflavonoid 7-acetoxy-4-aryl-3,4-dihydrocoumarin in Swiss mice through parameters related to changes in body weight, food and water intake, hematological and biochemical parameters. Toxicity studies using acute doses (300 and 2000 mg/kg) and repeated doses (250, 500 and 1000 mg/kg) orally were carried out as per Organization for Economic Co-operation and Development (OECD) guidelines 423 and 407, respectively. Based on the results of this study, treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin was found to not cause clinical adverse symptoms and mortality in any animal used in the acute and repeated-dose toxicity study. In addition, no significant changes were observed in body weight and internal organs, food and water intake, hematological and biochemical parameters, compared to control group. Therefore, these results provide an initial understanding regarding the toxicity profile of 7-acetoxy-4-aryl-3,4-dihydrocoumarin, which can be considered a neoflavonoid with toxicity seen at doses higher than 2000 mg/kg in Swiss mice.

An AAVrh10-CAG-CYP21-HA vector allows persistent correction of 21-hydroxylase deficiency in a Cyp21-/- mouse model.

The treatment of severe forms of 21-hydroxylase deficiency (21OHD) remains unsatisfactory in many respects. As a monogenic disease caused by loss-of-function mutations, 21OHD is a potential candidate for a gene therapy (GT) approach. The first step of GT is to demonstrate positive effects of the therapeutic vector in the Cyp21-/- mouse model. Thus, we tested the adrenal tropism of an AAVrh10-CAG-GFP vector ('GFP vector') then attempted to correct the phenotypic and biochemical alterations in Cyp21-/- mice using an AAVrh10-CAG-humanCYP21A2-HA vector ('CYP21 vector'). Cyp21-/- mice had decreased body mass, high progesterone (4 ×), impaired stress response, increased adrenal expression of genes involved in steroidogenesis or ACTH signaling. Following injection of the GFP vector, Cyp21-/- mice showed abundant GFP expression in the adrenal cortex. Intravenous injection of the therapeutic CYP21 vector allowed 21OH expression in adrenal tissue, resulting in increased body weight and near normalization of urinary progesterone for more than 15 weeks, improved response to stress and restoration of near-normal expression of (several important genes) in the adrenal cortex. The adrenal tropism of AAVrh10 and the persistent correction of phenotypic and biochemical traits in Cyp21-/- mice pave a first step on the way to GT of 21OHD in humans.

Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.

Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV.

Hypercholesterolemia and Ecto-enzymes of Purinergic System: Effects of Paullinia cupana.

Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process.

Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.

An alien in the group: eusocial male bees sharing nonspecific reproductive aggregations.

Sexual selection predicts that individuals competing for access to sexual partners should maximize their chances of mating by looking for sites where the chances of finding partners are more likely to occur. However, males of stingless bees have been observed sharing nonspecific reproductive aggregations. This uncommon behavior appears to confer no obvious increase of individual fitness. It has been suggested that this reproductive strategy is due to the similarity between male odors common to different stingless bee species. Cuticular hydrocarbons (CHCs) are candidate odors of interest because their nonvolatile pheromone nature allows them to play an important role in sexual behavior and species recognition. Here, we review the literature to evaluate whether any phylogenetic patterns exist among male stingless bees that aggregate with closely or distantly related species. We also compared the CHC profiles of males of Neotropical stingless bee species (Plebeia sp. Schwarz, Trigona spinipes (F.), Tetragona clavipes (F.), Nannotrigona testaceicornis (Lepeletier), Scaptotrigona aff. depilis (Moure), Tetragonisca angustula (Latreille), and Melipona subnitida (Ducke) to reveal any chemical similarities among their male odors. We found males of 21 stingless bee species involved in interspecific interactions mainly from Neotropical and Indo-Malayan/Australasian regions. Alien males did not necessarily visit host aggregations of closely related species. Furthermore, the CHC profiles of different studied species were very distinct from each other and do not overlapped at all. It is unclear yet why this apparently nonadaptive behavior carried out by some stingless bee males.

A comparative study of five centrally acting drugs on the pharmacological treatment of obesity.

CONTEXT: No long-term studies have compared centrally acting drugs for treating obesity. OBJECTIVE: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. DESIGN AND SETTING: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. PATIENTS: A total of 174 obese premenopausal women. INTERVENTION: Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. MAIN OUTCOME MEASURES: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. RESULTS: Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.

Extreme thermopower anisotropy and interchain transport in the quasi-one-dimensional metal Li0.9Mo6O17.

Thermopower and electrical resistivity measurements transverse to the conducting chains of the quasi-one-dimensional metal Li0.9Mo6O17 are reported in the temperature range 5≤T≤500 K. For T≥400 K the interchain transport is determined by thermal excitation of charge carriers from a valence band ∼0.14 eV below the Fermi level, giving rise to a large, p-type thermopower that coincides with a small, n-type thermopower along the chains. This dichotomy-semiconductorlike in one direction and metallic in a mutually perpendicular direction-gives rise to substantial transverse thermoelectric effects and a transverse thermoelectric figure of merit among the largest known for a single compound.

Changes in the interbranchial lymphoid tissue of Atlantic salmon (Salmo salar) affected by amoebic gill disease.

The interbranchial lymphoid tissue (ILT) was recently described in the gills of salmonids. This study examined changes in the ILT during a parasitic infection in marine environment, using amoebic gill disease (AGD) as a model. Atlantic salmon (Salmo salar) experimentally infected with Neoparamoeba perurans were sampled at 0, 3, 7, 14 and 28 days post challenge. Transversal sections of three areas of the gills (dorsal, medial and ventral) were histologically assessed for morphological and cellular changes. AGD induced morphological changes and a cellular response in the ILT of affected fish. These changes included a significant increase in the ILT surface area in fish 28 days after AGD challenge, compared to control fish at the same time point. The length of the ILT increased significantly 28 days post exposure in the dorsal area of the gill arch in the fish affected by AGD. The lymphocyte density of the ILT increased after AGD challenge, peaking at 7 days post exposure; however, by 28 days post exposure, a reduction of lymphocyte density to values close to pre-infection levels was observed. PCNA immunostaining revealed that epithelial hyperplasia was the most likely factor contributing to the ILT enlargement in the affected fish.

Effects of delay sequence in a delay discounting task.

Delay discounting refers to the decrease in subjective value of a reward as the delay until its receipt increases. In the present study we assessed the effects of the sequence of delay blocks (increasing or decreasing) on discounting and the data systematicity using a titrating procedure with human participants. All participants completed the delay discounting task in both an increasing and decreasing sequence of delays. Delays ranged from one day to ten years. We found steeper discounting when the delays were presented in an increasing sequence compared with when they were presented in a decreasing sequence. We also found steeper discounting when participants completed the increasing sequence condition first. Our results agree with other findings reported in the literature and suggest that delay discounting may be affected by prior and subsequent experience.

Effect of calcination on minimally processed recycled zirconia powder derived from milling waste.

OBJECTIVE: To assess the influence of calcination process on the properties of minimally processed recycled 3Y-TZP, and to compare it with its commercial counterpart. METHODS: Non-milled 3Y-TZP waste was collected, fragmented and ball-milled to a granulometric < 5 µm. Half of the recycled powder was calcined at 900 °C. Recycled 3Y-TZP disks were uniaxially pressed and sintered to create two recycled groups: 1) Calcined and 2) Non-calcined to be compared with a commercial CAD/CAM milled 3Y-TZP. The microstructure of experimental groups was assessed through density (n = 6), scanning electron microscopy (n = 3) and energy-dispersive X-ray spectroscopy (n = 3); and the crystalline content was evaluated through X-ray diffraction (XRD) (n = 3). Optical and mechanical properties were investigated through reflectance tests (n = 10), and Vickers hardness, fracture toughness (n = 5), and biaxial flexural strength tests (n = 16), respectively. Fractographic analysis was performed to identify fracture origin and crack propagation. Statistical analyses were performed through ANOVA followed by Tukey´s test, and by Weibull statistics. RESULTS: Particle size distribution of recycled powder revealed an average diameter of ∼1.60 µm. The relative density of all experimental groups was > 98.15 % and XRD analysis exhibited a predominance of tetragonal-phase in both recycled groups, which were similar to the crystallographic pattern of the control group. Cross-section micrographs presented flaws on the non-calcined group, and a more homogeneous microstructure for the calcined and commercial groups. Commercial samples showed lower contrast-ratio and higher translucency-parameter than the recycled groups, where non-calcined presented higher translucency-parameter and lower contrast-ratio than its calcined counterpart. The commercial group presented higher fracture toughness and characteristic strength than the recycled groups. Moreover, the calcined group exhibited higher hardness, characteristic strength, and probability of survival at higher loads than the non-calcined group. Fractographic analysis depicted the presence of microstructural flaws in the non-calcined group, which may have acted as stress-raisers and led to failures at lower flexural strengths values. SIGNIFICANCE: The calcination process improved the microstructure, optical, and mechanical properties of the recycled 3Y-TZP.

Assessing nitrate groundwater hotspots in Europe reveals an inadequate designation of Nitrate Vulnerable Zones.

Monitoring networks show that the European Union Nitrates Directive (ND) has had mixed success in reducing nitrate concentrations in groundwater. By combining machine learning and monitored nitrate concentrations (1992-2019), we estimate the total area of nitrate hotspots in Europe to be 401,000 km2, with 47% occurring outside of Nitrate Vulnerable Zones (NVZs). We also found contrasting increasing or decreasing trends, varying per country and time periods. We estimate that only 5% of the 122,000 km2 of hotspots in 2019 will meet nitrate quality standards by 2040 and that these may be offset by the appearance of new hotspots. Our results reveal that the effectiveness of the ND is limited by both time-lags between the implementation of good practices and pollution reduction and an inadequate designation of NVZs. Substantial improvements in the designation and regulation of NVZs are necessary, as well as in the quality of monitoring stations in terms of spatial density and information available concerning sampling depth, if the objectives of EU legislation to protect groundwater are to be achieved.

Psychological profile (anxiety and depression) in patients with oral lichen planus: a controlled study.

AIM: The influence of psychological disturbances in oral lichen planus (OLP) still bears some controversy. This study aimed at assessing levels of anxiety and depression in OLP patients and control subjects, using a self-report scale questionnaire. METHODS: This cross-sectional study comprised 91 consecutive OLP patients (71 female and 20 male; mean age 52.9 years) and 87 subjects as a control group (69 female and 18 male; mean age 52.7 years). Data collected of both groups included age, sex, race, medical records and systemic disease. Anxiety and depression levels were assessed using, respectively, the State-Trait Anxiety Inventory (STAI-T) and Center for Epidemiologic Studies Depression Scale (CES-D). Data were analyzed by Chi-square and Fisher's exact tests as appropriate, and by Logistic regression analysis. RESULTS: No statistically significant difference was found when the level of anxiety and depression was compared between the OLP and control using Chi-square and Fisher's tests (P>0.05). Logistic regression analysis showed that the score in 2 out of 20 items of the STAI-T scale (but none of the CES-D) was significantly higher in OLP patients (P<0.05). The analysis by gender showed that the female and male OLP patients presented a significantly higher score for one item in the STAI-T scale (respectively question 4 and 20) but none in the CES-D scale, as compared with that of the control group (P<0.05). CONCLUSION: Our findings do not support that either anxiety or depression has any role in the development of OLP lesions.

Children's Physical Activity During the COVID-19 Lockdown: A Cross Cultural Comparison Between Portugal, Brazil and Italy.

The COVID-19 pandemic forced governments to implement measures that disrupted the daily routines of many families worldwide. We studied how the COVID-19 lockdown affected children's routines in Portugal (PT), Brazil (BR), and Italy (IT) to determine if children's age and country impacted their physical activity (PA) and sedentary time. We launched an anonymous online survey to assess how 3-12 years old children adjusted their daily routines to this situation. Parents reported the times each child was engaged in different activities throughout the day, and we used these data to calculate separately overall sedentary and physical activity time. We conducted separate analyses of variance for age and country on the percentage of time spent in the different activities. Results, based on the data from 3045 children in these three countries (PT n = 2044; BR n = 836; IT n = 165), showed that, during lockdown, most children spent most of their awake daily hours in sedentary activities. There was a clear age effect on the way their routines were organized. Percentages of time spent in intellectual activity, playful screen activity, and overall sedentary time were greater in the older age groups, whereas percentages of time spent in play (with and without PA) and in overall PA were greater in the younger groups. We found a main effect of country for all variables except play without PA. The country effect was mainly due to the difference between the routines in BR when compared to PT and IT. Values of playful screen time and overall sedentary activity were higher in BR than in the two European countries. Conversely, values for play with PA, PA, and overall PA (except in the older group) were lower in BR. Patterns of time spent in these activities were similar in IT and PT, but PA and overall PA times were higher in the two younger age groups in IT. In summary, percentage of PA time of confined children was low and decreased with age across all three countries and was particularly low for children in BR relative to those in PT and IT.