Anogenital lichen sclerosus et atrophicus lesions in a case series of cancer patients on immunotherapy.

Lichenoid reactions are one of the most frequently observed toxicities with anticancer agents and, recently, a rapid emergence of immunotherapies in oncology has hastened the need to better characterize their unique toxicity profiles, particularly for less common skin toxicities, including anogenital lichen sclerosus et atrophicus (LSA). This case series describes four patients with advanced cancer (one melanoma, two lung cancers, and one kidney tumor) developing LSA lesions while receiving an immunotherapy. Medical records from 2017 to 2020 were retrospectively reviewed. Two patients received pembrolizumab, anti-programmed cell death-1 (PD-1), one nivolumab, anti-programmed cell death-1 (PD-1), and one ipilimumab, an immune checkpoint inhibitor. LSA emerged after a median of 3 months (range, 2-4 months) from starting immunotherapy. All LSA cases were grade 2. Three cases occurred on the penis and one case on the anus. All patients improved after a specific treatment for LSA, and no LSA-related antineoplastic treatment interruption/life-threatening condition were reported. To date, this is the first case series of LSA lesions associated with immunotherapy. Early LSA recognition and management is helpful in cancer patients on immunotherapy allowing a long survival and treatment response.

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

Integration of reflectance confocal microscopy in sequential dermoscopy follow-up improves melanoma detection accuracy.

BACKGROUND: Successful treatment of melanoma depends on early diagnosis, but its varied clinical presentation means that no single noninvasive method or criterion can provide reliable detection in all cases. OBJECTIVES: To determine whether combining sequential dermoscopy imaging with reflectance confocal microscopy (RCM) can improve melanoma detection and reduce the burden of unnecessary excisions. METHODS: We conducted a retrospective study with median follow-up of 25 months. We included equivocal pigmented lesions that lacked clear dermoscopy criteria for melanoma at baseline but were excised subsequently because of changes during digital monitoring. RCM imaging was performed before excision. Main melanoma dermoscopy features, seven-point checklist score at baseline, and changes in structure and/or colour, and development of new melanoma-specific criteria at follow-up (scored as major, moderate or minor) were considered. Main melanoma RCM criteria were evaluated and diagnosis was made. Histopathological diagnosis was the reference standard for defining parameter frequency and diagnostic accuracy. RESULTS: Seventy lesions were included. Major changes were more frequently correlated with melanoma diagnosis, although one-third (four of 12) of melanomas showed moderate or minor changes. Cytological atypia and architectural disarrangement on RCM were correlated with melanoma diagnosis. A correct melanoma diagnosis was achieved with RCM in almost all cases (11 of 12, 92%). Referring for excision only those lesions with RCM-positive features and/or presenting major changes at digital dermoscopy follow-up, theoretically 27 of 58 naevi could be saved from surgery. CONCLUSIONS: Integration of RCM in the clinical and instrumental strategy for managing difficult pigmented lesions provided additional diagnostic information useful in the decision-making process.

Sunbed use among subjects at high risk of melanoma: an Italian survey after the ban.

BACKGROUND: The World Health Organization classified the entire ultraviolet (UV) spectrum and artificial UV tanning devices as carcinogenic to humans. Italian law has prohibited the use of tanning equipment by children under 18 years of age and by high-risk populations. OBJECTIVES: The present large survey aimed to determine the prevalence of current sunbed use in Italy and to identify user characteristics. This study identifies starting points for future national interventions to reduce the health risks of exposure to artificial UV radiation. METHODS: In 2011 we conducted a survey of 4703 people in an area on the sunny Mediterranean coast in Italy. Through multivariate logistic models we investigated the associations of sunbed use with phenotypical factors. RESULTS: Overall prevalence of sunbed use was 20%, higher among women (22% vs. 16%; P < 0·0001), and young (22% vs. 17% for age < 35 years; P < 0·0001) and highly educated people (22% vs. 14%; P < 0·0001). Subjects at high risk of melanoma used sunbeds significantly more; i.e. people with freckles (25% vs. 18%; P < 0·0001), red hair (30% vs. 19%; P = 0·01) or fair eyes (22% vs. 19%; P = 0·006). Associations were confirmed in multivariate models. CONCLUSIONS: More skin cancer monitoring is needed at tanning centres, and educational campaigns should be promoted, especially for young women and subjects at high risk of melanoma.

Population genetic structure of the tropical tree species Aegiphila sellowiana (Lamiaceae).

The Tibagi River, located in southern Brazil, is associated with a significant degree of environmental heterogeneity, along its 550 km extension. There is concern about the integrity of this river's ecosystem, as human interference has been increasing. Aegiphila sellowiana (Lamiaceae) is an important pioneer tree species, commonly found near rivers; the fruit is consumed by avifauna. We studied this species along three ecological gradients, comprising the upper, middle, and lower regions of the Tibagi River basin. The genetic structure of nine subpopulations of A. sellowiana distributed along these gradients was investigated using RAPDs. Moderate levels of gene diversity (ranging from 0.091 to 0.132) were identified, inferred by a traditional approach and a Bayesian model-based method. The F-statistic, G(ST) parameters and molecular variance analysis showed high genetic differentiation among the three regions (39.5 to 50.26%). Analysis of molecular variance revealed high levels of genetic variation between populations (50.26%), while lower values of genetic variation (ranging from 9.56 to 16.35%) were seen between subpopulations within the upper, middle, and lower regions of the Tibagi River basin. The validity of these results was confirmed by principal coordinate analysis. Linear regression analysis showed significant correlations (r = 0.621, P = 0.0001) between the genetic and geographical distances. The differences observed in genetic variation between regions are probably due to habitat fragmentation; for conservation purposes, we recommend that at least one subpopulation from each region of the Tibagi River should be maintained.

Molecular, anatomical and physiological properties of a genetically modified soybean line transformed with rd29A:AtDREB1A for the improvement of drought tolerance.

We evaluated the molecular, anatomical and physiological properties of a soybean line transformed to improve drought tolerance with an rd29A:AtDREB1A construct. This construct expressed dehydration- responsive element binding protein DREB1A from the stress-inducible rd29A promoter. The greenhouse growth test included four randomized blocks of soybean plants, with each treatment performed in triplicate. Seeds from the non-transformed soybean cultivar BR16 and from the genetically modified soybean P58 line (T(2) generation) were grown at 15% gravimetric humidity for 31 days. To induce water deficit, the humidity was reduced to 5% gravimetric humidity (moderate stress) for 29 days and then to 2.5% gravimetric humidity (severe stress). AtDREB1A gene expression was higher in the genetically modified P58 plants during water deficit, demonstrating transgene stability in T(2) generations and induction of the rd29A promoter. Drought-response genes, including GmPI-PLC, GmSTP, GmGRP, and GmLEA14, were highly expressed in plants submitted to severe stress. Genetically modified plants had higher stomatal conductance and consequently higher photosynthetic and transpiration rates. In addition, they had more chlorophyll. Overexpression of AtDREB1A may contribute to a decrease in leaf thickness; however, a thicker abaxial epidermis was observed. Overexpression of AtDREB1A in soybean appears to enhance drought tolerance.

Genetic diversity and flooding survival in Aegiphila sellowiana (Lamiaceae), a typical tree species from upland riparian forests.

Saplings of Aegiphila sellowiana were submitted to flooding and analysis of genetic diversity in order to investigate flooding tolerance as well as its genetic determination. This response is important because it means that some lines could be planted in degraded riparian areas. Leaves were sampled from each plant, and they were submitted to different flooding periods. Mortality of saplings was 40, 80, 50, 53.3, 33.3, and 33.3% in flooding for 15, 18, 25, 50, 80 days, and flooding for 50 days followed by re-aeration for 30 days, respectively. From the total number of flooded plants, 46.7% died in the first seven days of treatment, while 53.3% survived the flooding. The percentage of polymorphic loci (P(p)), Nei's genetic diversity (H) and the Shannon index (I) were slightly higher for the group that survived the stress of flooding (surviving: P(p) (%) = 67.48, H = 0.184, I = 0.287; not surviving: P(p) (%) = 66.67, H = 0.165, I = 0.261). Analysis of molecular variance showed that 5.88% of the genetic variability was due to the differences between groups of plants surviving and not surviving flooding, while 94.12% was due to genetic differences between individuals within these groups. Similar results were obtained by principal coordinate analysis. Based on these results, we can assume the existence of environment-specific genotypes and the genetic determination of flooding tolerance in A. sellowiana. Thus, some lines of A. sellowiana could be used in the reforestation of riparian habitats, especially in uplands along riverbanks.

Anatomy and genetic diversity of two populations of Schinus terebinthifolius (Anacardiaceae) from the Tibagi River basin in Paraná, Brazil.

Knowledge of the effects of flooding on plant survival is relevant for the efficiency of management and conservation programs. Schinus terebinthifolius is a tree of economic and ecological importance that is common in northeast Brazil. Flooding tolerance and genetic variation were investigated in two riparian populations of S. terebinthifolius distributed along two different ecological regions of the Tibagi River basin. Flooding tolerance was evaluated through the investigation of young plants, submitted to different flooding intensities to examine the morphological and anatomical responses to this stress. The growth rate of S. terebinthifolius was not affected by flooding, but total submersion proved to be lethal for 100% of the plants. Morphological alterations such as hypertrophied lenticels were observed in both populations and lenticel openings were significantly higher in plants from one population. Genetic analysis using DNA samples obtained from both populations showed a moderate degree of genetic variation between populations (13.7%); most of the variation was found within populations (86.3%). These results show that for conservation purposes and management of degraded areas, both populations should be preserved and could be used in programs that intend to recompose riparian forests.

Soybean physiology and gene expression during drought.

Soybean genotypes MG/BR46 (Conquista) and BR16, drought-tolerant and -sensitive, respectively, were compared in terms of morphophysiological and gene-expression responses to water stress during two stages of development. Gene-expression analysis showed differential responses in Gmdreb1a and Gmpip1b mRNA expression within 30 days of water-deficit initiation in MG/BR46 (Conquista) plants. Within 45 days of initiating stress, Gmp5cs and Gmpip1b had relatively higher expression. Initially, BR16 showed increased expression only for Gmdreb1a, and later (45 days) for Gmp5cs, Gmdefensin and Gmpip1b. Only BR16 presented down-regulated expression of genes, such as Gmp5cs and Gmpip1b, 30 days after the onset of moisture stress, and Gmgols after 45 days of stress. The faster perception of water stress in MG/BR46 (Conquista) and the better maintenance of up-regulated gene expression than in the sensitive BR16 genotype imply mechanisms by which the former is better adapted to tolerate moisture deficiency.

Evidence of ecotypic differentiation between populations of the tree species Parapiptadenia rigida due to flooding.

The tree species Parapiptadenia rigida, native to southern South America, is frequently used in reforestation of riverbanks in Brazil. This tree is also a source of gums, tannins and essential oils, and it has some medicinal uses. We investigated flooding tolerance and genetic diversity in two populations of P. rigida; one of them was naturally exposed to flooding. Plants derived from seeds collected from each population were submitted to variable periods of experimental waterlogging and submergence. Waterlogging promoted a decrease in biomass and structural adjustments, such as superficial roots with aerenchyma and hypertrophied lenticels, that contribute to increase atmospheric oxygen intake. Plants that were submerged had an even greater reduction in biomass and a high mortality rate (40%). The two populations varied significantly in their RAPD marker profiles, in their ability to produce aerenchyma when waterlogged and to survive when submerged, suggesting ecotypic differentiation between them. Hence, the seasonal flooding that has been challenging the tropical riparian forest appears to be genetically modifying the P. rigida populations exposed to it by selecting individuals with increased ability to live under this condition.

Cloning and quantitative expression analysis of drought-induced genes in soybean.

We determined the expression levels of DREB transcription factor (Gmdreb1) and of the genes Gmgols, Gmpip1b, Gmereb, and Gmdefensin in drought-tolerant (MG/BR46-Conquista) and drought-sensitive (BR16) genotypes of soybean, during drought. The trial was carried out in a controlled-environment chamber, set up to provide drought conditions. Sequences of Arabidopsis thaliana DREB-family proteins were used to build a phylogenetic tree through the alignment of the conserved regions near the AP2 domain. We found that Gmdreb1 is similar to Atrap2.1, which is located near the AtDREB1 and AtDREB2 families. The amplified fragment was cloned and sequenced; alignment with the sequence available at Genbank showed total similarity. Expression analysis showed that under drought: a) Gmdreb1 expression increased in leaves and roots of both genotypes and expression level changes occurred that were correlated with the length of the water-deficit period; b) there were increased expression levels of Gmdefensin in roots of MG/BR46; c) expression of Gmgols increased in leaves and roots of the two genotypes; d) Gmpip1b expression generally increased, except in roots of BR16, and e) the same was found for Gmereb, except in roots of MG/BR46.

Childhood lichen sclerosus: a long-term follow-up.

Lichen sclerosus (LS) shows a predilection for the genital area and occurs mostly in postmenopausal women and in prepubertal girls. We conducted a retrospective review of 15 young girls whit genital LS with onset before the menarcheal age and treated with topical clobetasol propionate 0.05%. The mean duration of follow-up was 4.7 years with relapses in nine patients after approximately 1 year from the first clearing. At the end of the study we observed that (i) potent topical steroids are safe and effective in childhood, (ii) an early aggressive treatment gives the best therapeutic response, (iii) one follow-up visit a year is required to monitor for relapsing.

Use of textiles in atopic dermatitis: care of atopic dermatitis.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease which usually starts during the first years of life. In the management of AD, the correct approach requires a combination of multiple treatments to identify and eliminate trigger factors, and to improve the alteration of the skin barrier. In this article we try to explain the importance of skin care in the management of AD in relation to the use of textiles: they may be useful to improve disrupted skin but they are also a possible cause of triggering or worsening the lesions. Garments are in direct contact with the skin all day long, and for this reason it is important to carefully choose suitable fabrics in atopic subjects who have disrupted skin. Owing to their hygienic properties fabrics produced from natural fibres are preferential. Wool fibres are frequently used in human clothes but are irritant in direct contact with the skin. Wool fibre has frequently been shown to be irritant to the skin of atopic patients, and for this reason wool intolerance was included as a minor criterion in the diagnostic criteria of AD by Hanifin and Rajka in 1980. Cotton is the most commonly used textile for patients with AD; it has wide acceptability as clothing material because of its natural abundance and inherent properties like good folding endurance, better conduction of heat, easy dyeability and excellent moisture absorption. Silk fabrics help to maintain the body temperature by reducing the excessive sweating and moisture loss that can worsen xerosis. However, the type of silk fabric generally used for clothes is not particularly useful in the care and dressing of children with AD since it reduces transpiration and may cause discomfort when in direct contact with the skin. A new type of silk fabric made of transpiring and slightly elastic woven silk is now commercially available (Microair Dermasilk) and may be used for the skin care of children with AD. The presence of increased bacterial colonization has been demonstrated in patients with AD. Such colonization has been included in the group of trigger factors for eczema in AD. Silver products have recently been demonstrated to offer two advantages in the control of bacterial infections. Textiles may be used not only for clothes, but also to prevent dust mite sensitization in atopic patients. A marked clinical improvement of AD was observed in a group of adults and children with positive skin tests (not necessarily towards mites), after an intensive eradication programme for mite allergens. Skin treatment with acaricide and house dust mite control measures can decrease AD symptoms. Different textiles have various potential worsening links with allergies: e.g. clothing has been proposed as an additional source of exposure to mite and cat allergens. On the other hand, special textiles can be used to prevent dust mite sensitization.

Comparing human skeletal muscle architectural parameters of cadavers with in vivo ultrasonographic measurements.

The purpose of this study was to document and compare the architectural parameters (fibre bundle length, angle of pennation) of human skeletal muscle in cadaveric specimens and live subjects. The medial (MG) and lateral (LG) gastrocnemius, and posterior (PS) and anterior (AS) soleus were examined bilaterally in 5 cadavers (mean age 72.6, range 65-83 y) and 9 live subjects (mean age 76.3, range 70-92 y). Data were obtained from direct measurement of cadaveric specimens and from ultrasonographic scans of the live subjects. In cadaveric muscle, fibre bundles were isolated; their length was measured in millimetres and pennation angles were recorded in degrees. In live muscle, similar measurements were taken from ultrasonographic scans of relaxed and contracted muscle. For the scans of relaxed muscle, subjects were positioned prone with the foot at a 90 degrees angle to the leg, and for scans of contracted muscle, subjects were asked to sustain full plantarflexion during the scanning process. Fibre bundle length and angle of pennation were compared at matched locations in both groups. It was found that the relationship between cadaveric and in vivo values for fibre length and angle of pennation varied between muscle parts. The cadaveric architectural parameters did not tend to lie consistently towards either extreme of relaxation or contraction. Rather, within MG, PS and AS, cadaveric fibre bundle lengths lay between those for relaxed and contracted in vivo muscle. Similarly both the anterior and posterior cadaveric fibre angles of pennation lay between the in vivo values within LG and PS. In summary, architectural characteristics of cadaveric muscle differ from both relaxed and contracted in vivo muscle. Therefore, when developing models of skeletal muscle based on cadaveric studies, the architectural differences between live and cadaveric tissue should be taken into consideration.

Sonographic studies of human soleus and gastrocnemius muscle architecture: gender variability.

The purpose of this study was to establish if there are gender differences in muscle architecture in relaxed human soleus and gastrocnemius muscles of normal, live subjects. Ultrasonography was used to measure fiber bundle length, muscle thickness, and angles of pennation in a total of ten predetermined sites in the medial and lateral heads of gastrocnemius and the anterior and posterior soleus in 19 males and 16 females. Percentage differences between males and females for each parameter were recorded. Gender differences were statistically analyzed using multivariate analysis of variance. In the gastrocnemius and soleus muscles of males and females the differences between the overall fiber bundle length, angle of pennation and muscle thickness were statistically significant (P < 0.05). Overall, females were found to have longer average muscle fiber bundle length and males thicker muscles and larger angles of pennation. The greatest percentage differences of the architectural parameters between males and females were in the posterior soleus: 13% difference in fiber length and 26% difference in angle of pennation in the midline of posterior soleus and 26% difference in muscle thickness of the lateral part of posterior soleus. No correlation was found between leg length and fiber length, angle of pennation or muscle thickness. Fiber length (decreased), angle of pennation (greater) and muscle thickness (greater) of most parts of the gastrocnemius and soleus muscles were significantly different in males and females. Leg length of males and females did not correlate to these architectural parameters.

[The PAPNET system in the rescreening of negative cervical/vaginal smears. A study from the Imola cytology laboratory]. / Il sistema PAPNET nel rescreening degli strisci cervico/vaginali negativi. Uno studio del laboratorio di citologia di Imola.

The rescreening of negative cervical/vaginal smears is one of the potential areas of utilization of the systems for computer-assisted cytology diagnosis. In the Imola cytology laboratory, a random sample of 1309 conventionally prepared smears that had been originally reported as negative was rescreened with the PAPNET System (Neuromedical Systems, Inc., Suffern, NY). Smears with a PAPNET diagnosis other than negative were further and independently evaluated by the staff of the laboratory and classified according to the majority report. The PAPNET rescreening confirmed the original negative diagnosis for 1188 smears (907.6/1000) and led to the detection of 46 ASCUS/LGSIL cases (35.1/1000) and 2 AGUS/HGSIL cases (1.5/1000). Seventy-three smears (55.8/1000) were interpreted as unsatisfactory. The majority report confirmed the original negative diagnosis for 42 (91%) of the 46 PAPNET diagnoses of ASCUS/LGSIL and 50 (68%) of the 73 smears interpreted as unsatisfactory. The 2 cases of AGUS/HGSIL diagnosed by PAPNET were confirmed. The detection rate of ASCUS/LGSIL decreased from 35.1/1000 to 3.1/1000 (rate ratio 0.09, 95% confidence interval [95% CI] 0.02-0.22). The rate of unsatisfactory smears decreased from 55.8/1000 to 17.6/1000 (rate ratio 0.31, 95% CI 0.20-0.47). The rate of negative smears increased from 907.6/1000 to 977.9/1000 (rate ratio 1.08, 95% CI 1.02-1.14). In conclusion, the PAPNET rescreening of negative smears brought about a low detection rate of severe cellular changes. Though greater, the detection rate of low grade changes was substantially and significantly reduced by the majority reports. At our laboratory, the PAPNET rescreening does not appear to improve the performance of conventional cytodiagnosis.

Accuracy comparison between PAPNET diagnoses and conventional diagnoses in an Italian cervical cytology laboratory.

In a population-based cervical screening laboratory with a controlled workload, a retrospective PAPNET review of 1,654 Pap smears was performed. The series included a random sample of smears originally and conventionally classified as negative (no. 1,309) and unsatisfactory (no. 43), and 299 consecutive smears originally classified as abnormal. The PAPNET diagnoses and the original diagnoses were compared for accuracy. For smears with discordant classification, a majority diagnosis as obtained on manual review was used as a gold standard. The PAPNET testing showed a greater proportion of negative smears classified as unsatisfactory (3.7% vs. 0.2%; ratio, 16.7; 95% CI 12.4-22.0); a reduced proportion of ASCUS/LGSIL cases correctly identified as positive (i.e., a reduced sensitivity for such lesions) (76.3% vs. 97.9%; ratio, 0.78; 95% CI 0.66-0.91); an equal proportion (96.2%) of AGUS/HGSIL cases correctly identified as positive (i.e., an equal sensitivity for such lesions); and an equal proportion of negative smears correctly identified as such (i.e., an equal specificity). In conclusion, the PAPNET testing did not improve the diagnostic performance of the manual screening.