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Summary: Background: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)‐1. Objectives: To determine whether anakinra (an IL‐1 receptor antagonist) delivers therapeutic benefit in PPP. Methods: This was a randomized (1 : 1), double‐blind, two‐staged, adaptive, UK multicentre, placebo‐controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015‐003600‐23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self‐administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Results: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention‐to‐treat analysis [–1·65, 95% confidence interval (CI) –4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI –26·44 to 32·33; favouring anakinra), total pustule count (–30·08, 95% CI –83·20 to 23·05; favouring placebo) and patient‐reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was –3·80 (95% CI –10·76 to 3·16; P = 0·285). No serious adverse events occurred. Conclusions: No evidence for the superiority of anakinra was found. IL‐1 blockade is not a useful intervention for the treatment of PPP. What is already known about this topic?Treatment options for palmoplantar pustulosis include superpotent corticosteroids, phototherapy, acitretin, methotrexate and ciclosporin. However, these have poor evidence for benefit and there is a risk of toxicity with long‐term use.Anakinra is a recombinant interleukin (IL)‐1 receptor antagonist that blocks the activity of IL‐1α and IL‐1β, two cytokines repeatedly linked to neutrophil activation and extravasation.A therapeutic benefit of anakinra has been shown in neutrophilic dermatoses and conditions that manifest with skin pustulation. What does this study add?Anakinra was not significantly superior to placebo at 8 weeks in objective investigator‐assessed and patient‐reported measures.A greater proportion of participants in the anakinra group strongly agreed that the treatment was worthwhile.The safety profile of anakinra was consistent with previous studies.This is one of the largest randomized controlled trials for this rare condition, providing important data on its natural history and change in disease severity over time. Linked Comment: S.N. Lo and J.F. Thompson. Br J Dermatol 2022; 186:205–206. Plain language summary available online [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?. SUMMARY ANSWER Our results suggest an association between in utero exposure to perfluorooctanoic acid (PFOA) and delay in age of menarche. WHAT IS KNOWN ALREADY Previous cross-sectional studies have reported possible effects of PFASs on female reproduction including reduced fecundity, delayed puberty and accelerated age at menopause. Only limited data exist from follow-up studies on long-term implications of prenatal exposure to PFASs. STUDY DESIGN, SIZE, DURATION In this study we used data from a Danish population-based cohort established in 1988–1989. Of 1212 eligible pregnant women, 965 participated. Follow-up was initiated in 2008 on the female offspring at ∼20 years of age. Three hundred and sixty seven (84%) daughters answered a questionnaire and 267 (61%) daughters furthermore attended clinical examinations which were conducted in 2008–2009. PARTICIPANTS/MATERIALS, SETTING, METHODS The final study population consisted of 343 daughters of which 254 had attended the clinical examinations and 89 had answered the questionnaire only. Levels of PFASs in maternal serum from pregnancy week 30 were used as a measure of prenatal exposure and related to age of menarche, menstrual cycle length, levels of reproductive hormones and follicle number of the daughters. Data were divided into three groups according to tertiles of maternal concentrations of PFASs (low, medium, high). MAIN RESULTS AND THE ROLE OF CHANCE In adjusted regression analyses, daughters exposed to higher levels of PFOA in utero had a 5.3 (95% confidence interval: 1.3; 9.3) months later age of menarche compared with the reference group of lower PFOA. Crude (P = 0.05) and adjusted (P = 0.01) trend tests also indicated a relationship between higher prenatal PFOA exposure and delay of menarche. LIMITATIONS, REASONS FOR CAUTION We did not measure the exact amount of PFASs to which the daughters had been exposed prenatally. Instead we used PFAS concentrations in maternal serum as surrogates. However, PFASs are efficiently transferred to the fetus via placenta. Information on age of menarche was collected retrospectively but the time interval for recall in our study was relatively short (2–10 years). The remaining outcome measures depended on participation in clinical examination which reduced the number of observations leading to limited statistical power and risk of selection bias. WIDER IMPLICATIONS OF THE FINDINGS Since PFASs can be detected in humans all over the world, effects of prenatal exposure on female reproductive function later in life may have wide health implications. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by the Danish Council for Independent Research (271-05-0296, 09-065631), the Danish Ministry of Interior and Health (0-302-02-18/5), the Danish Council for Strategic Research (09-067124 (Centre for Fetal Programming), 09-063072, 2101-06-0005), the Novo Nordisk Foundation, the Aarhus University Research Foundation, the Frimodt-Heineke Foundation, the Foundation of Maria Dorthea and Holger From, the Beckett-Foundation, the Research Grant of Organon and the Foundation of Lily Benthine Lund. There are no competing interests. Trial registration number Not applicable. [ABSTRACT FROM PUBLISHER]

Linked Article: Mahil et al. Br J Dermatol 2021; 185:80–90. [ABSTRACT FROM AUTHOR]

Background: The objective of the investigation was to test the hypothesis that exposure to nitrogen dioxide (NO2) has a causal influence on the occurrence of bronchial obstruction in children below 2 years of age.Methods: A nested case-control study with 153 one-to-one matched pairs was conducted within a cohort of 3754 children born in Oslo in 1992/93. Cases were children who developed > or = 2 episodes of bronchial obstruction or one episode lasting >4 weeks. Controls were matched for date of birth. Exposure measurements were performed in the same 14-day period within matched pairs. The NO2 exposure was measured with personal samplers carried close to each child and by stationary samplers outdoors and indoors.Results: Few children (4.6%) were exposed to levels of NO2 > or = 30 microg/m3 (average concentration during a 14-day period). In the 153 matched pairs, the mean level of NO2 was 15.65 microg/m3 (+/-0.60, SE) among cases and 15.37 (+/-0.54) among controls (paired t = 0.38, P = 0.71).Conclusions: The results suggest that NO2 exposure at levels observed in this study has no detectable effect on the risk of developing bronchial obstruction in children below 2 years of age. [ABSTRACT FROM AUTHOR]

Two samples of a typical Norwegian minced meat emulsion were fried at 215°C One had the regular composition while 4.2% creatine was added to the second sample prior to frying. Mutagens in both samples were purified using aqueous acid extraction, XAD-2 adsorption and a series of semipre-parative and analytical high performance liquid chromatography (HPLC) purification steps monitored by the Ames/ mutagenicity test. Mutagenic activity in the creatine-fortified product was enhanced 15-fold. Mutagenicity profiles from reverse-phase and normal-phase HPLC were qualitatively similar for both samples indicating no major production of new mutagens due to the presence of additional creatine. A total of 8 distinct mutagenic peaks could be separated after three additional HPLC steps. These compounds fall into a class of compounds called amino-imidazoazaarenes (AIA). The majority of mutagenic activity is made up by the known cooking mutagens 2-amino-3,8-dimethylimi-dazo[4,5-]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimi-dazo[4,5-]quinoxaline (DiMeIQx), 2-amino-3-methylimidazo [3,5-]quinoline (IQ) and 2-amino--trimethylimidazo-pyridine (TMIP). Smaller contributions are from 2-amino-3-methylimidazo- [4,5-]quinoxaline (IQx), 2-amino--dimethylimidazopyridine (DMIP), 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP) and two oxygen-containing AIA. With respect to mass, MeIQx and PhIP were the dominating mutagens. [ABSTRACT FROM PUBLISHER]

Linked Article: Ryan et al. Br J Dermatol 2018; 179:844–852. [ABSTRACT FROM AUTHOR]

The article describes a case of necrotizing eosinophilic folliculitis (NEF) in a 49-year-old man. Topics discussed include physical examination which showed multiple, tender, erythematous, subcutaneous nodules on the patient's forehead and limbs, and histological examination which revealed dense infiltration of neutrophils with abscess formation and eosinophils in the subcutaneous tissues.

The article discusses a case study of a 59-year-old man who was diagnosed with cutaneous scleroderma and malignant carcinoid syndrome. His physical examination reveals facial plethora, along with skin induration and marked leg oedema. Furthermore, high levels of urinary 5-hydroxyindoleacetic acid and serum gut hormones have been identified in laboratory investigations.

The authors discuss the use of methotreaxate (MTX) as the leading treatment for psoriasis due to its cost-effectiveness and efficacy. The authors say that the individual variability of MTX response and toxicity depend on the demographic factors, genetic variation in pharmacokinetics, and external influences. Moreover, the study by R. Woolf and colleagues on the relationship of clinical response of psoriatic patients with the intracellular concentrations of MTX polyglutamates (MTXPGs) is cited.

The article discusses the cases of patients demonstrating linear erythema of the right lower eyelid. Physical examination determined a linear lesion that extends from the right lateral to the mid infraorbital crease. Diagnosis of the patients was linear basal cell carcinoma (BCC) tumor. The study of the cases mention that the potential of the lower eyelid as the site of linear BCC.

j. wesche, e. hammer, d. becher, g. burchhardt and f. schauer. 2004.Biphenyl-degrading bacteria are able to metabolize dibenzofuran via lateral dioxygenation andmeta-cleavage of the dihydroxylated dibenzofuran produced. This degradation was considered to be incomplete because accumulation of a yellow-orange ring-cleavage product was observed. In this study, we want to characterize the 1,2-dihydroxydibenzofuran cleaving enzyme which is involved in dibenzofuran degradation in the bacteriumRalstoniasp. SBUG 290.In this strain, complete degradation of dibenzofuran was observed after cultivation on biphenyl. The enzyme shows a wide substrate utilization spectrum, including 1,2-dihydroxydibenzofuran, 2,3-dihydroxybiphenyl, 1,2-dihydroxynaphthalene, 3- and 4-methylcatechol and catechol. MALDI-TOF analysis of the protein revealed a strong homology to thebphCgene products. We therefore cloned a 3·2 kb DNA fragment containing thebphCgene ofRalstoniasp. SBUG 290. The deduced amino acid sequence ofbphCis identical to that of the corresponding gene inPseudomonassp. KKS102. ThebphCgene was expressed inEscherichia coliand themeta-fission activity was detected using either 2,3-dihydroxybiphenyl or 1,2-dihydroxydibenzofuran as substrate.These results demonstrate that complete degradation of dibenzofuran by biphenyl degraders can occur after initial oxidation steps catalysed by gene products encoded by thebph-operon. The ring fission of 1,2-dihydroxydibenzofuran is catalysed by BphC. Differences found in the metabolism of the ring fission product of dibenzofuran among biphenyl degrading bacteria are assumed to be caused by different substrate specificities of BphD.This study shows for the first time that the gene products of thebph-operon are involved in the mineralization of dibenzofuran in biphenyl degrading bacteria. [ABSTRACT FROM AUTHOR]

Background Most information on the comparative effectiveness and survival of methotrexate (MTX) and adalimumab (ADA) in the treatment of psoriasis is from randomized control trials and may not translate to the everyday clinical setting. Objectives To determine the real-world effectiveness and survival of MTX and ADA in patients with moderate-to-severe psoriasis registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Methods Eligible patients were registered in BADBIR, ≥ 16 years of age and receiving a first course of MTX or ADA between September 2007 and December 2021, with ≥ 6 months of follow-up. Effectiveness was defined as achieving an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 reported ≥ 13 weeks after the treatment start date until the stop date. The average treatment effect (ATE) was estimated using inverse probability of treatment weighting with propensity score, including baseline covariates. ATE results were presented as risk ratios (RR). A flexible parametric model was used to estimate adjusted standardized average survival, defined as treatment discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs) at 6, 12 and 24 months. Restricted mean survival time (RMST) at 2 years of treatment exposure was calculated. Results In total, 6575 patients (median age 44 years; 44% female) were analysed; 2659 (40.4%) were prescribed MTX and 3916 (59.5%) ADA. The proportion of patients achieving PASI ≤ 2 was higher in the ADA cohort (77.4%) than in the MTX cohort (37.4%). ADA was more effective than MTX [RR 2.20, 95% confidence interval (CI) 1.98–2.45]. Overall survival associated with ineffectiveness or AEs was lower in the MTX cohort than in the ADA cohort at 6 months [survival estimate 69.7 (95% CI 67.9–71.5) vs. 90.6 (95% CI 89.8–91.4)], 1 year [survival estimate 52.5 (95% CI 50.4–54.8) vs. 80.6 (95% CI 79.5–81.8)] and 2 years [survival estimate 34.8 (95% CI 32.5–37.2) vs. 68.6 (95% CI 67.2–70.0)]. The difference in RMST (years) overall, or when stratified by ineffectiveness and AEs, was 0.53 (95% CI 0.49–0.58), 0.37 (95% CI 0.33–0.42) and 0.29 (95% CI 0.25–0.33), respectively. Conclusions Patients on ADA were twice as likely to be clear or nearly clear of psoriasis and were less likely to discontinue their medication than patients on MTX. Findings from this real-world cohort provide important information to aid clinicians managing patients with psoriasis. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals that are persistent in the environment. They can be transferred across the placenta to fetuses and through human milk to infants. The American Academy of Pediatrics advises that the benefits of breastfeeding infants almost always outweigh the potential risks of harm from environmental chemicals. However, there are few chemical-specific summaries of the potential harms of exposure to PFAS during the neonatal period through breastfeeding. This systematic review explores whether exposure to PFAS through breastfeeding is associated with adverse health outcomes among infants and children using evidence from human and animal studies. Systematic searches identified 4297 unique records from 7 databases. The review included 37 total articles, including 9 animal studies and 1 human study measuring the direct contribution of exposure of the infant or pup through milk for any health outcome. Animal studies provided evidence of associations between exposure to PFOA through breastfeeding and reduced early life body weight gain, mammary gland development, and thyroid hormone levels. They also provided limited evidence of associations between PFOS exposure through breastfeeding with reduced early life body weight gain and cellular changes in the hippocampus. The direct relevance of any of these outcomes to human health is uncertain, and it is possible that many adverse health effects of exposure through breastfeeding have not yet been studied. This review documents the current state of science and highlights the need for future research to guide clinicians making recommendations on infant feeding. [ABSTRACT FROM AUTHOR]

Background Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited. Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis. Methods Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective, multicentre pharmacovigilance register of patients with moderate-to-severe psoriasis receiving biologic and/or conventional systemic therapies, were analysed. Eligible patients were ≥ 16 years of age receiving a first course of acitretin, ciclosporin, FAEs or methotrexate between 2007 and 2021 with ≥ 6 months' follow-up. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥ 4 weeks after treatment start date until date of cessation. To identify baseline clinical variables associated with treatment effectiveness, we used multivariable logistic regression models estimating the adjusted odds ratio (aOR) of achieving aPASI ≤ 2. To describe drug persistence associated with ineffectiveness, occurrence of adverse events or other reasons for discontinuation, survival estimates with 95% confidence intervals (CIs) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis. Overall, 1023 (19%) patients were receiving acitretin, 1401 (26%) patients were on ciclosporin, 347 (6%) patients were on FAEs, and 2659 (49%) patients were receiving methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower for those treated with acitretin [ n = 118 (21%)] compared with those receiving ciclosporin [ n = 233 (34%)], FAEs [ n = 43 (29%)] and methotrexate [ n = 372 (32%)]. Factors associated with ineffectiveness included prior experience to previous nonbiologic systemic therapies (acitretin) (aOR 0.64, 95% CI 0.42–0.96), male sex (methotrexate) (aOR 0.58, 95% CI 0.46–0.74), comorbidities (aOR 0.70, 95% CI 0.51–0.97) and alcohol consumption (≤ 14 units per week) (ciclosporin) (aOR 0.70, 95% CI 0.50–0.98). Persistence associated with all reasons for discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [survival estimate 46.1 (95% CI 44.0–48.3), 31.9 (95% CI 29.4–34.7), 30.0 (95% CI 27.5–32.4) and 35.0 (95% CI 29.9–40.9), respectively]. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous nonbiologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about mid-term survival after abdominal aortic aneurysm (AAA) surgery that has been predicted through cardiopulmonary exercise testing.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs. [ABSTRACT FROM AUTHOR]

We examined differences in the physiology and life history between dimorphs of the common pistachio psyllid, Agonoscena pistaciae (Burckhardt and Lauterer) (Hemiptera: Aphalaridae), and how they differ in elicitating host plant production of key metabolites and volatile compounds involved in the recruitment of herbivores and natural enemies. Summer morphs had higher activities of glutathione S-transferase, carboxylesterase, acetylcholinesterase, and cytochrome P450 monooxygenase, superoxide dismutase, catalase, peroxidase, phenoloxidase, and a higher total protein content compared to winter morphs, whereas the latter had higher amounts of lipid, carbohydrate, and glycogen. Winter morphs were heavier, with a higher chitin content and longer preoviposition period, but greater fecundity and longevity than summer morphs. A lower LC50 to thiamethoxam for winter morphs resulted in higher mortality following exposure to the recommended rate of this insecticide in a greenhouse trial. Feeding by winter morphs elicited more strongly the release of volatile compounds known to be attractive to other herbivores, whereas feeding by summer morphs elicited more strongly the release of volatiles implicated in the attraction of natural enemies. Feeding by psyllids increased the concentrations of nitrogenous compounds, carbohydrates, vitamins, and amino acids in plants, the winter morph eliciting larger changes and more improved host plant quality. We conclude that winter morphs are more vulnerable targets for chemical control in early spring, whereas management of summer morphs could rely more on conservation biological control. [ABSTRACT FROM AUTHOR]

Comment on 'Paradoxical hidradenitis suppurativa due to anti-interleukin-1 agents for mevalonate kinase deficiency successfully treated with the addition of ustekinumab' Google Scholar Crossref Search ADS PubMed WorldCat 8 Berman HS, Villa NM, Shi VY, Hsiao JL. Guselkumab in the treatment of concomitant hidradenitis suppurativa, psoriasis, and Crohn's disease. Paradoxical hidradenitis suppurativa induced by adalimumab biosimilar successfully treated with guselkumab in a patient with psoriasis. [Extracted from the article]

Brominated flame retardants (BFR) are molecules added to consumer products to reduce fire hazards. They were banned in North America and Europe because of their persistence and biomagnification. However, BFR are still released in the environment due to continued use of products manufactured before restriction, and from waste and recycling processes of those products. As a result, they remain sources of chronic environmental and human exposure worldwide. BFR are well-characterized endocrine disruptors. They have been associated with a wide range of alterations in endocrine and reproductive systems both in humans and experimental models in vivo and in vitro. Paradoxically, the effects of BFR on mammary glands, whose development and carcinogenesis are mainly under hormonal dependency are poorly known. There is increasing weight of evidence that exposure to endocrine disruptors promotes breast cancer, especially if the exposure occurs during sensitivity windows. For the mammary gland, these windows include the perinatal life, puberty, and pregnancy, as important remodeling of the organ happens during those periods. The peak of exposure to BFRs happened during late 1990s and beginning of 2000s in most countries. Women who were pregnant at that time are reaching menopause while their daughters are 20–30 years old. It is thus important to better understand the effects of BFRs on mammary gland development and breast cancer to determine whether these women are more at risk. Thus, this review aims to propose a comprehensive review of data reporting the effects of exposure to BFR on female endocrine and reproductive systems, with a particular focus on mammary gland development and of a potential increased risk of breast cancer. [ABSTRACT FROM AUTHOR]

Context: Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. Objective: To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. Materials and Methods: Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. Results: Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ΣPFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. Conclusions: These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences. [ABSTRACT FROM AUTHOR]

Summary: Background: Palmoplantar pustulosis (PPP) is a rare, chronic, inflammatory skin disease characterized by sterile pustules on palmar or plantar areas. Data on PPP are scarce. Aim: To investigate the clinical characteristics and risk factors for disease severity in a large cohort of Turkish patients with PPP. Methods: We conducted a cross‐sectional, multicentre study of patients with PPP recruited from 21 tertiary centres across Turkey. Results: In total, 263 patients (165 women, 98 men) were evaluated. Most patients (75.6%) were former or current smokers. The mean Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 8.70 ± 8.06 and the mean Dermatology Life Quality Index (DLQI) score was 6.87 ± 6.08, and these scores were significantly correlated (r = 0.52, P < 0.001). Regression analysis showed that current smoking was significantly associated with increased PPPASI (P = 0.03). Coexisting psoriasis vulgaris (PsV) was reported by 70 (26.6%) patients. Male sex prevalence, PPP onset incidence, disease duration, DLQI, and prevalence of nail involvement and psoriatic arthritis (PsA) were significantly increased among patients with PPP with PsV. Of the 263 patients, 18 (6.8%) had paradoxical PPP induced by biologic therapy, and these patients had significantly increased mean DLQI and prevalence of PsA (r = 0.03, P = 0.001). Conclusion: Our data suggest that smoking is a risk factor for both PPP development and disease severity. Patients with PPP with PsV present distinct clinical features and patients with biologic therapy‐induced paradoxical PPP have reduced quality of life and are more likely to have PsA. [ABSTRACT FROM AUTHOR]

Transformative Innovation Policies (TIPs) assert that addressing the key challenges currently facing our societies requires profound changes in current socio-technical systems. To leverage such 'socio-technical transitions' calls for a different, broad mix of research and innovation policies, with particular attention being paid to policy experiments. As TIPs diffuse and gain legitimacy they pose a substantial evaluation challenge: how can we evaluate these policy experiments with a narrow geographical and temporal scope, when the final objective is ambitiously systemic? How can we know whether a specific set of policy experiments is contributing to systemic transformation? Drawing on TIPs principles as developed by and applied in the activities of the Transformative Innovation Policy Consortium and on the concept of transformative outcomes, this article develops an approach to the evaluation of TIPs that is operational and adaptable to different contexts. [ABSTRACT FROM AUTHOR]

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003–2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose–response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di- n -butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed. [ABSTRACT FROM AUTHOR]

Background: Chromosomal mosaicism can be detected in different stages of early life: in cleavage stage embryos, in blastocysts and biopsied cells from blastocysts during preimplantation genetic testing for aneuploidies (PGT-A) and later during prenatal testing, as well as after birth in cord blood. Mosaicism at all different stages can be associated with adverse pregnancy outcomes. There is an onward discussion about whether blastocysts diagnosed as chromosomally mosaic by PGT-A should be considered safe for transfer. An accurate diagnosis of mosaicism remains technically challenging and the fate of abnormal cells within an embryo remains largely unknown. However, if aneuploid cells persist in the extraembryonic tissues, they can give rise to confined placental mosaicism (CPM). Non-invasive prenatal testing (NIPT) uses cell-free (cf) DNA released from the placenta in maternal blood, facilitating the detection of CPM. In literature, conflicting evidence is found about whether CPM is associated with fetal growth restriction (FGR) and/or other pregnancy outcomes. This makes counselling for patients by clinicians challenging and more knowledge is needed for clinical decision and policy making.Objective and Rationale: The objective of this review is to evaluate the association between CPM and prenatal growth and adverse pregnancy outcomes. All relevant literature has been reviewed in order to achieve an overview on merged results exploring the relation between CPM and FGR and other adverse pregnancy outcomes.Search Methods: The following Medical Subject Headings (MESH) terms and all their synonyms were used: placental, trophoblast, cytotrophoblast, mosaicism, trisomy, fetal growth, birth weight, small for gestational age and fetal development. A search in Embase, PubMed, Medline Ovid, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases was conducted. Relevant articles published until 16 July 2020 were critically analyzed and discussed.Outcomes: There were 823 articles found and screened based on their title/abstract. From these, 213 articles were selected and full text versions were obtained for a second selection, after which 70 publications were included and 328 cases (fetuses) were analyzed. For CPM in eight different chromosomes (of the total 14 analyzed), there was sufficient evidence that birth weight was often below the 5th percentile of fetal growth standards. FGR was reported in 71.7% of CPM cases and preterm birth (<37 weeks of delivery) was reported in 31.0% of cases. A high rate of structural fetal anomalies, 24.2%, in cases with CPM was also identified. High levels of mosaicism in CVS and presence of uniparental disomy (UPD) were significantly associated with adverse pregnancy outcomes.Wider Implications: Based on the literature, the advice to clinicians is to monitor fetal growth intensively from first trimester onwards in case of CPM, especially when chromosome 2, 3, 7, 13, 15, 16 and 22 are involved. In addition to this, it is advised to examine the fetuses thoroughly for structural fetal anomalies and raise awareness of a higher chance of (possibly extreme) premature birth. Despite prematurity in nearly a fifth of cases, the long-term follow-up of CPM life borns seems to be positive. More understanding of the biological mechanisms behind CPM will help in prioritizing embryos for transfer after the detection of mosaicism in embryos through PGT-A. [ABSTRACT FROM AUTHOR]

Background: Maternal seafood intake during pregnancy and prenatal mercury exposure may influence children's growth trajectories.Methods: This study, based on the Norwegian Mother, Father and Child Cohort Study (MoBa), includes 51 952 mother-child pairs recruited in pregnancy during 2002-08 and a subsample (n = 2277) with maternal mercury concentrations in whole blood. Individual growth trajectories were computed by modelling based on child's reported weight and length/height from 1 month to 8 years. We used linear mixed-effects regression analysis and also conducted discordant-sibling analysis.Results: Maternal lean fish was the main contributor to total seafood intake in pregnancy and was positively but weakly associated with child body mass index (BMI) growth trajectory. Higher prenatal mercury exposure (top decile) was associated with a reduction in child's weight growth trajectory, with the estimates ranging from -130 g [95% Confidence Intervals (CI) = -247, -12 g] at 18 months to -608 g (95% CI = -1.102, -113 g) at 8 years. Maternal fatty fish consumption was positively associated with child weight and BMI growth trajectory, but only in the higher mercury-exposed children (P-interaction = 0.045). Other seafood consumption during pregnancy was negatively associated with child weight growth compared with no intake, and this association was stronger for higher mercury-exposed children (P-interaction = 0.004). No association was observed between discordant maternal seafood intake and child growth in the sibling analysis.Conclusions: Within a population with moderate seafood consumption and low mercury exposure, we found that maternal seafood consumption in pregnancy was associated with child growth trajectories, and the direction of the association varied by seafood type and level of prenatal mercury exposure. Prenatal mercury exposure was negatively associated with child growth. Our findings on maternal seafood intake are likely non-causal. [ABSTRACT FROM AUTHOR]

Over the past two decades, several methods have been developed to evaluate the societal impact of research. Compared to the practical development of the field, the conceptual development is relatively weak. This review article contributes to the latter by elucidating the theoretical aspects of the dominant methods for evaluating societal impact of research, in particular, their presuppositions about the relationship between scientific and societal value of research. We analyse 10 approaches to the assessment of the societal impact of research from a constructivist perspective. The methods represent different understandings of knowledge exchange, which can be understood in terms of linear, cyclical, and co-production models. In addition, the evaluation methods use a variety of concepts for the societal value of research, which suggest different relationships with scientific value. While some methods rely on a clear and explicit distinction between the two types of value, other methods, in particular Evaluative Inquiry, ASIRPA, Contribution Mapping, Public Value Mapping, and SIAMPI, consider the mechanisms for producing societal value integral to the research process. We conclude that evaluation methods must balance between demarcating societal value as a separate performance indicator for practical purposes and doing justice to the (constructivist) science studies' findings about the integration of scientific and societal value of research. Our analytic comparison of assessment methods can assist research evaluators in the conscious and responsible selection of an approach that fits with the object under evaluation. As evaluation actively shapes knowledge production, it is important not to use oversimplified concepts of societal value. [ABSTRACT FROM AUTHOR]

Introduction: Social media provides a favorable space for health education. Among the available digital resources, WhatsApp message groups can serve as a source of information and a platform for discussions. Recent studies on sexual education through social media are more concentrated on interventions targeting STI prevention, sexual abuse mitigation, and contraception education. However, there are no reports of utilization of WhatsApp for education about paraphilias. The Brazilian Association for Studies in Medicine and Sexual Health (ABEMSS) utilizes WhatsApp as a tool to promote discussions of this often neglected topic. Nevertheless, more studies are needed to substantiate the validity of this resource. Objective: To review the literature and to share the experience of using WhatsApp to facilitate discussions and knowledge sharing about paraphilias. Methods: Narrative Review on the Use of Social Media in Sexual Education and an experience report on the Utilization of WhatsApp as an Educational Instrument for the study of paraphilias. Results: The WhatsApp paraphilia study group was created in 2020 and comprises 222 healthcare professionals (54% urologists, 9% endocrinologists, 8% psychiatrists, 18% psychologists, 7% physiotherapists). Its activities primarily occur in a scheduled manner, but they can also arise spontaneously. They include discussions of clinical cases, scientific studies and lay media. In the first half of 2023, there were 12 scheduled activities and 8 spontaneous ones. To mitigate the risk of stigmatizing comments, department members act as moderators. Conclusions: WhatsApp seems to be a valuable tool for disseminating information about neglected health topics, such as paraphilias. The use of specific groups with scheduled and spontaneous activities promotes the provision of scientific information while promotes a attitude towards the topic. Keywords: Paraphilias; Paraphilic disorders; Medical education; Social media Financing: No conflict. [ABSTRACT FROM AUTHOR]

Background: Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP).Objective and Rationale: Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research.Search Methods: We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies.Outcomes: The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP.Wider Implications: Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed. [ABSTRACT FROM AUTHOR]

In 1997, the first in vivo bisphenol A (BPA) study by endocrinologists reported that feeding BPA to pregnant mice induced adverse reproductive effects in male offspring at the low dose of 2 µg/kg/day. Since then, thousands of studies have reported adverse effects in animals administered low doses of BPA. Despite more than 100 epidemiological studies suggesting associations between BPA and disease/dysfunction also reported in animal studies, regulatory agencies continue to assert that BPA exposures are safe. To address this disagreement, the CLARITY-BPA study was designed to evaluate traditional endpoints of toxicity and modern hypothesis-driven, disease-relevant outcomes in the same set of animals. A wide range of adverse effects was reported in both the toxicity and the mechanistic endpoints at the lowest dose tested (2.5 µg/kg/day), leading independent experts to call for the lowest observed adverse effect level (LOAEL) to be dropped 20 000-fold from the current outdated LOAEL of 50 000 µg/kg/day. Despite criticism by members of the Endocrine Society that the Food and Drug Administration (FDA)'s assumptions violate basic principles of endocrinology, the FDA rejected all low-dose data as not biologically plausible. Their decisions rely on 4 incorrect assumptions: dose responses must be monotonic, there exists a threshold below which there are no effects, both sexes must respond similarly, and only toxicological guideline studies are valid. This review details more than 20 years of BPA studies and addresses the divide that exists between regulatory approaches and endocrine science. Ultimately, CLARITY-BPA has shed light on why traditional methods of evaluating toxicity are insufficient to evaluate endocrine disrupting chemicals. [ABSTRACT FROM AUTHOR]

2,4,6-Tribromophenol (TBP, CAS no. 118-79-6) is a brominated chemical used as a precursor, flame retardant, and wood antifungal agent. TBP is detected in environmental matrices and biota, including human breast milk, placenta, and serum. To address reports of TBP accumulation in human placenta and breast milk, studies were conducted to characterize TBP disposition and toxicokinetics in timed-pregnant or nursing Sprague Dawley rats following a single oral dose to the dam. Animals were administered [14C]-TBP (10 μmol/kg, 25 µCi/kg, 4 ml/kg) by gavage on gestation day 12 and 20, or postnatal day 12 and serially euthanized between 15 min and 24 h for collection of blood and tissues from the dam and fetuses/pups. Observed plasma TBP C max (3 and 7 nmol/ml) occurred at 15 min in both GD12 and GD20 dams while C max (3 nmol/ml) was observed at 30 min for PND12 dams. Concentrations in tissues followed plasma concentrations, with kidneys containing the highest concentrations at 30 min. GD12 litters contained a sustained 0.2%–0.3% of the dose (5–9 nmol/litter) between 15 min and 6 h while GD20 fetuses (2%–3%) and placentas (0.3%–0.5%) had sustained levels between 30 min and 12 h. The stomach contents (approx. 1 nmol-eq/g, 6–12 h), livers (0.04–0.1 nmol-eq/g) and kidneys (0.1–0.2 nmol-eq/g) of PND12 pups increased over time, indicating sustained exposure via milk. Systemic exposure to TBP and its metabolites occurs in both the directly exposed mother and the indirectly exposed offspring and is rapid and persistent after a single dose in pregnant and nursing rats. [ABSTRACT FROM AUTHOR]

The concept of a threshold of adversity in toxicology is neither provable nor disprovable. As such, it is not a scientific question but a theoretical one. Yet, the belief in thresholds has led to traditional ways of interpreting data derived from regulatory guideline studies of the toxicity of chemicals. This includes, for example, the use of standard "uncertainty factors" when a "No Adverse Effect Level" (or similar "benchmark dose") is either observed, or not observed. In the context of endocrine-disrupting chemicals (EDCs), this approach is demonstrably inappropriate. First, the efficacy of a hormone on different endpoints can vary by several orders of magnitude. This feature of hormone action also applies to EDCs that can interfere with that hormone. For this reason, we argue that the choice of endpoint for use in regulation is critical, but note that guideline studies were not designed with this in mind. Second, the biological events controlled by hormones in development not only change as development proceeds but are different from events controlled by hormones in the adult. Again, guideline endpoints were also not designed with this in mind, especially since the events controlled by hormones can be both temporally and spatially specific. The Endocrine Society has laid out this logic over several years and in several publications. Rather than being extreme views, they represent what is known about hormones and the chemicals that can interfere with them. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women's health.Objective and Rationale: This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function.Search Methods: A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors' knowledge of the topic and key terms.Outcomes: Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood-follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus.Wider Implications: The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality. [ABSTRACT FROM AUTHOR]

There is a growing need to understand the potential neurotoxicity of organophosphate flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial flame retardant mixture Firemaster 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters for the developing brain. We have shown in rats and humans that flame retardants accumulate in placental tissue, and induce functional changes, including altered neurotransmitter production. Here, we sought to establish if OPFRs (triphenyl phosphate and a mixture of isopropylated triarylphosphate isomers) alter placental function and fetal forebrain development, with disruption of tryptophan metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1000, or 2000 μg/day) or a serotonin (5-HT) agonist 5-methoxytryptamine for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine metabolic pathways were upregulated. In addition, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental tryptophan metabolism. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are used as industrial surfactants and chemical coatings for household goods such as Teflon. Despite regulatory efforts to phase out legacy PFAS, they remain detectable in drinking water throughout the United States. This is due to the stability of legacy PFAS and the continued use of replacement compounds. In humans, PFAS have been detected in placenta and cord blood and are associated with low birth weight and preeclampsia risk. Preeclampsia is a leading cause of maternal mortality and is driven by insufficient endometrial trophoblast invasion, resulting in poor placental blood flow. PFAS alter invasion of other cell types, but their impact on trophoblasts is not understood. We therefore assessed the effects of PFAS on trophoblast migration, invasion, and gene expression in vitro. Trophoblast migration and invasion were assessed using a modified scratch assay in the absence or presence of Matrigel, respectively. Treatment with perfluorooctanoic sulfate (PFOS), perfluorooctanoic acid (PFOA), and GenX (1000 ng/ml) each decreased trophoblast migration over 24 h. However, only GenX (1000 ng/ml) significantly inhibited trophoblast invasion. Treatment with PFOS, PFOA, and GenX also decreased trophoblast expression of chemokines (eg, CCL2), chemokine receptors (eg, CCR4), and inflammatory enzymes (eg, ALOX15) involved in migration. Inhibition of chemokine receptors with pertussis toxin (10 ng/ml), a G-protein inhibitor, inhibited trophoblast migration similar to the PFAS. Taken together, PFAS decrease trophoblast migration, invasion, and inflammatory signaling. By understanding the mechanisms involved, it may be possible to identify the biological and exposure factors that contribute to preeclampsia. [ABSTRACT FROM AUTHOR]

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size. [ABSTRACT FROM AUTHOR]

This paper reports on a detailed institutional study of the German technology transfer system using material from a survey of practitioners and observations of the system over a 2 year period. The purpose of this research was to understand the dynamics within the system which, despite heavy criticism over the past 10-15 years, has proved remarkably resilient, competitive and capable of change. It is argued that the dynamism lies within the funding and the institutional structures of the system which allow competition to exist alongside collaboration and networking, thus incorporating the best of a 'market-based' technology transfer system with the advantages of regulation and coordination. These inherent, but contradictory, pressures are termed 'symbiotic tension': it is argued that this is key to understanding the resilience of the system. [ABSTRACT FROM AUTHOR]

Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR). Drug survival associated with effectiveness and safety of treatment with guselkumab, ixekizumab, secukinumab, ustekinumab, and adalimumab in patients with psoriasis. Thus, methotrexate might be considered the best conventional treatment option - perhaps the only one still possible - in the era of biological therapy.[7] And this implies that the theoretical goals of treatment are not always met - or even expected to be met - by doctors and patients in daily practice. [Extracted from the article]

Viruses that affect humans, animals and plants are often dispersed and transmitted through airborne routes of infection. Due to current technological deficiencies, accurate determination of the presence of airborne viruses is challenging. This shortcoming limits our ability to evaluate the actual threat arising from inhalation or other relevant contact with aerosolized viruses. To improve our understanding of the mechanisms of airborne transmission of viruses, air sampling technologies that can detect the presence of aerosolized viruses, effectively collect them and maintain their viability, and determine their distribution in aerosol particles, are needed. The latest developments in sampling and detection methodologies for airborne viruses, their limitations, factors that can affect their performance and current research needs, are discussed in this review. Much more work is needed on the establishment of standard air sampling methods and their performance requirements. Sampling devices that can collect a wide size range of virus‐containing aerosols and maintain the viability of the collected viruses are needed. Ideally, the devices would be portable and technology‐enabled for on‐the‐spot detection and rapid identification of the viruses. Broad understanding of the airborne transmission of viruses is of seminal importance for the establishment of better infection control strategies. [ABSTRACT FROM AUTHOR]

Summary: Background: Palmoplantar pustulosis (PPP) is a chronic pustular skin condition on the palms and soles. The disease is often seen in combination with plaque psoriasis, and whether PPP is a variant of psoriasis has been debated. The disease prevalence of PPP and co‐occurring psoriasis is not yet established and the patient group remains understudied. Objectives: To estimate the prevalence of PPP and co‐occurring psoriasis in three population‐based cohorts and to provide information on patient demographics and characteristics. Methods: Administrative healthcare registries and insurance databases from the U.S.A., Denmark and Germany were used as data sources. Patients with PPP were defined by a single International Classification of Diseases 10th Revision code for PPP during a 1‐year period. Information regarding co‐occurring plaque psoriasis and other comorbidities was extracted. Furthermore, use of antipsoriatic medication was identified. Results: In total 1435, 751 and 1832 patients with PPP were identified in the U.S., Danish and German populations, with estimated 1‐year prevalences of 0·009%, 0·005% and 0·08%, respectively. Plaque psoriasis was present in 14·2–61·3% of patients with PPP. Patients with co‐occurring psoriasis had an overall higher prevalence of psoriatic arthritis. Similarly, medication use was more prevalent in patients with PPP with co‐occurring psoriasis, and especially pronounced was the use of biologic therapies. Conclusions: This large observational study on patients with PPP provides detailed information regarding patient demographics, comorbidities and medication use. The 1‐year prevalence of PPP varied in the three studied populations, possibly due to differences in diagnostics and recording practices. Psoriasis frequently co‐occurred in patients with PPP. What's already known about this topic? Palmoplantar pustulosis (PPP) is a skin disease of the palms of the hands and soles of the feet and is known to be related to psoriasis.Whether PPP is a distinct disease or a variant of psoriasis is not yet established.The condition is understudied in terms of disease prevalence, disease predictors, patient characteristics and comorbidity. What does this study add? In this study using data from three large population‐based cohorts we found low prevalence rates (< 0·1%) of PPP.The prevalence of psoriasis was estimated at between 14·2% and 61·3% in patients with psoriasis.Patients with PPP with co‐occurring psoriasis have a higher prevalence of psoriatic arthritis and use of antipsoriatic drugs. Respond to this article Linked Comment: Haidari and Feldman. Br J Dermatol 2019; 181:887–888. Plain language summary available online [ABSTRACT FROM AUTHOR]

Study Question: Are maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) during pregnancy associated with anogenital distance (AGD) in male infants at birth, 6, and 12 months of age?Summary Answer: Higher maternal plasma concentrations of some PFASs were associated with shorter AGD in male infants at birth and 6 months of age.What Is Known Already: Two animal studies have found that exposure to PFASs was associated with shorter AGD in male rat fetuses and wild male minks. There is only one human study on the topic that did not identify consistent patterns between maternal serum concentrations of PFASs during pregnancy and AGD in male infants.Study Design, Size, Duration: In the prospective cohort study, a total of 1292 eligible pregnant women were recruited at 12-16 weeks of gestation between April and December 2012 at the Maternal and Child Health Hospital of Minhang district in Shanghai, China. At delivery, 667 male singletons were born. They were then followed up at birth (n = 439) and at 6 (n = 411) and 12 months (n = 376) of age when anopenile distance (AGDAP) and anoscrotal distance (AGDAS) were measured.Participants/materials, Setting, Methods: A total of 500 male infants who had both maternal plasma concentrations of PFASs and at least one AGD measurement of at three time points were included in the present study. Multiple linear regression models were used to evaluate the potential linear associations between maternal concentrations of PFASs and AGD.Main Results and the Role Of Chance: Maternal plasma concentrations (ln-transformed) of perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were inversely associated with AGDAS or AGDAP at birth (AGDAS: per ln unit increase in PFAS concentrations: β (95% CI): -0.65 (-1.27 to -0.02) mm for PFOS; -0.58 (-1.11 to -0.06) mm for PFDA; and -0.57 (-1.09 to -0.06) mm for PFUdA; AGDAP: per ln unit increase in PFAS concentrations: β (95% CI): -0.63 (-1.24 to -0.01) mm for PFDA and - 0.76 (-1.36 to -0.16) mm for PFUdA). At 6 months of age, per unit increase in maternal ln concentrations of PFOS and perfluorotridecanoic acid (PFTrDA), AGDAS decreased on average by -2.21 (95% CI: -4.28 to -0.14) and -1.11 (95% CI: -2.17 to -0.06) mm, respectively. Additionally, ln-transformed perfluorooctanoic acid (PFOA) showed nonsignificant but inverse associations with both AGDAS and AGDAP at 6 months of age. We found no significant associations between ln-transformed maternal concentrations of PFASs and either AGDAS or AGDAP at 12 months of age. However, significantly inverse association of ln-transformed PFOA with AGDAP was observed in male infants who never or shortly breastfed (<3 months) at 12 months of age.Limitations, Reasons For Caution: AGD measurements were performed by different examiners at each follow-up visit, and the intra-examiner variation was not assessed, which might cause intra-rater and inter-rater measurement errors. Additionally, our study may have selection bias since a considerable number of participants withdrew from the cohort although the differences in demographic characteristics were not statistically significant between included mother-infant pairs and those excluded. No statistical correction was made for multiple comparisons.Wider Implications Of the Findings: Our findings may have important implications for the early development of genital health in male infants since PFASs can be detected in almost all pregnant women and infants worldwide.Study Funding/competing Interest(s): This study was supported by grants from the National Key Research and Development program of China (2018YFC1002801 and 2016YFC1000505), the Science and Technology Commission of Shanghai Municipality (16ZR1430100), the National Natural Science Foundation of China (81428011), and the Innovation-Oriented Science and Technology Grant from National Health Commission Key Laboratory of Reproduction Regulation (CX2017-06). The authors have no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with approximately 61% of the dose recovered after 4 h, and 89%–94% in 24 h; 5% was recovered in feces; and 1%–2% in blood/tissues. TBP administered to female SD rats (0.1–1000 µmol/kg) by gavage was well absorbed, with approximately 25% eliminated via urine after 4 h and approximately 88% after 24 h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin with between 55% and 85% of a 100 nmol/cm2 passing into or through skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP whereas bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23%–27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data, we conclude that humans are likely to have significant systemic exposure when TBP is ingested or dermal exposure occurs. [ABSTRACT FROM AUTHOR]

Specific mate recognition relies on the chemical senses in most animals, and especially in nocturnal insects. Two signal types mediate premating olfactory communication in terrestrial habitats: sex pheromones, which blend into an atmosphere of plant odorants. We show that host plant volatiles affect the perception of sex pheromone in males of the African cotton leafworm Spodoptera littoralis and that pheromone and plant volatiles are not perceived as independent messages. In clean air, S. littoralis males are attracted to single synthetic pheromone components or even the pheromone of a sibling species, oriental cotton leafworm S. litura. Presence of host plant volatiles, however, reduces the male response to deficient or heterospecific pheromone signals. That plant cues enhance discrimination of sex pheromone quality confirms the idea that specific mate recognition in noctuid moths has evolved in concert with adaptation to host plants. Shifts in either female host preference or sex pheromone biosynthesis give rise to new communication channels that have the potential to initiate or contribute to reproductive isolation. [ABSTRACT FROM AUTHOR]

Study Question: Is self-reported type of underwear worn associated with markers of testicular function among men at a fertility center?Summary Answer: Men who reported most frequently wearing boxers had higher sperm concentration and total count, and lower FSH levels, compared to men who did not.What Is Known Already: Elevated scrotal temperatures are known to adversely affect testicular function. However, the epidemiologic literature on type of underwear, as a proxy of scrotal temperature, and male testicular function is inconsistent.Study Design, Size, Duration: This is a cross-sectional study including 656 male partners of couples seeking infertility treatment at a fertility center (2000-2017).Participants/materials, Setting, Methods: Self-reported information on type of underwear worn was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone levels and neutral comet assays for sperm DNA damage. We fit linear regression models to evaluate the association between underwear type and testicular function, adjusting for covariates and accounting for multiple semen samples.Main Results and the Role Of Chance: Men had a median (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9) kg/m2. About half of the men (53%; n = 345) reported usually wearing boxers. Men who reported primarily wearing boxers had a 25% higher sperm concentration (95% CI = 7, 31%), 17% higher total count (95% CI = 0, 28%) and 14% lower serum FSH levels (95% CI = -27, -1%) than men who reported not primarily wearing boxers. Sperm concentration and total count were inversely related to serum FSH. Furthermore, the differences in sperm concentration and total count according to type of underwear were attenuated after adjustment for serum FSH. No associations with other measured reproductive outcomes were observed.Limitations, Reasons For Caution: Our results may not be generalizable to men from the general population. Underwear use was self-reported in a questionnaire and there may be misclassification of the exposure. The cross-sectional design limits causal inference, and residual confounding is still possible owing to lack of information on other modifiable life styles that can also modify scrotal heat (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was not limited to the morning and, as a result, we may have missed associations with testosterone or other hormones with significant circadian variation despite statistical adjustment for time of blood draw.Wider Implications Of the Findings: Certain styles of male underwear may impair spermatogenesis and this may result in a compensatory increase in gonadotrophin secretion, as reflected by higher serum FSH levels among men who reported most frequently wearing tight underwear. Confirmation of these findings, and in particular the findings on FSH levels suggesting a compensatory mechanism, is warranted.Study Funding/competing Interest(s): The project was financed by Grants (R01ES022955, R01ES009718, P30ES000002, and K99ES026648) from the National Institutes of Health. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD), the classic aryl hydrocarbon receptor (AhR) agonist, is a potent environmental toxicant and endocrine-disrupting chemical (EDC) with known developmental toxicity in humans, rodents, and fish. Early life exposure to some EDCs, including TCDD, is linked to the occurrence of adult-onset and multigenerational disease. Previous work exposing juvenile F0 zebrafish (Danio rerio) to 50 ppt (parts per trillion) TCDD during reproductive development has shown male-mediated transgenerational decreases in fertility (F0–F2) and histologic and transcriptomic alterations in F0 testes. Here, we analyzed male germline alterations in F1 and F2 adult fish, looking for changes in testicular histology and gene expression inherited through the male lineage that could account for decreased reproductive capacity. Testes of TCDD-lineage F1 fish displayed an increase in spermatogonia (immature germ cells) and decrease in spermatozoa (mature germ cells). No histological changes were present in F2 fish. Transcriptomic analysis of exposed F1 and F2 testes revealed alterations in lipid and glucose metabolism, oxidation, xenobiotic response, and sperm cell development and maintenance genes, all of which are implicated in fertility outcomes. Overall, we found that differential expression of reproductive genes and reduced capacity of sperm cells to mature could account for the reproductive defects previously seen in TCDD-exposed male zebrafish and their descendants, providing insight into the distinct multigenerational effects of toxicant exposure. [ABSTRACT FROM AUTHOR]

The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account. [ABSTRACT FROM AUTHOR]

A phase 1 dose-escalation trial assessed the chemotherapeutic potential of ammoniumperfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer patients who failed standard therapy received weekly APFO doses (50-1200mg) for 6 weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured predose and weekly thereafter. Several clinical measures including total cholesterol, high-density lipoproteins (HDLs), thyroid stimulating hormone (TSH), and free thyroxine (fT4), relative to PFOA concentrations were examined by: Standard statistical analyses using generalized estimating equations (GEE) and a probabilistic analysis using probability distribution functions (pdf) at various PFOA concentrations; and a 2-compartment pharmacokinetic/pharmacodynamic (PK/PD) model to directly estimatemean changes. Based on the GEE, the average rates of change in total cholesterol and fT4 associated with increasing PFOA were approximately -1.2x10-3mmol/l/lMand 2.8x10-3pmol/l/lM, respectively. The PK/PDmodel predictedmore closely the trends observed in the data as well as the pdfs of biomarkers. A decline in total cholesterol was observed, with a clear transition in shape and range of the pdfs, manifested by the maximum value of the Kullback-Leibler (KL) divergence, that occurred at plasma PFOA between 420 and 565lM (175 000- 230 000 ng/ml). High-density lipoprotein was unchanged. An increase in fT4 was observed at a higher PFOA transition point, albeit TSH was unchanged. Our findings are consistent with some animalmodels and maymotivate re-examination of the epidemiologic studies to PFOA at levels several orders of magnitude lower than this study. These observational studies have reported contrary associations, but currently understood biology does not support the existence of such conflicting effects. [ABSTRACT FROM AUTHOR]