Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona.

BACKGROUND: There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) and chemical elements (including some metals, essential trace elements, rare earth elements, and minority elements), are immunomodulatory and cause a range of adverse clinical events. There are no prospective studies on the effects of such substances on the incidence of SARS-CoV-2 infection and COVID-19. OBJECTIVE: To investigate the influence of blood concentrations of POPs and elements measured several years before the pandemic on the development of SARS-CoV-2 infection and COVID-19 in individuals from the general population. METHODS: We conducted a prospective cohort study in 154 individuals from the general population of Barcelona. POPs and elements were measured in blood samples collected in 2016-2017. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or by antibody serology using eighteen isotype-antigen combinations measured in blood samples collected in 2020-2021. We analyzed the associations between concentrations of the contaminants and SARS-CoV-2 infection and development of COVID-19, taking into account personal habits and living conditions during the pandemic. RESULTS: Several historically prevalent POPs, as well as arsenic, cadmium, mercury, and zinc, were not associated with COVID-19, nor with SARS-CoV-2 infection. However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), and ruthenium (5.0 [1.8-14]) were associated with COVID-19, as were tantalum, benzo(b)fluoranthene, DDD, and manganese. Thallium (3.8 [1.6-8.9]), and ruthenium (2.9 [1.3-6.7]) were associated with SARS-CoV-2 infection, and so were lead, gold, and (protectively) iron and selenium. We identified mixtures of up to five substances from several chemical groups, with all substances independently associated to the outcomes. CONCLUSIONS: Our results provide the first prospective and population-based evidence of an association between individual concentrations of some contaminants and COVID-19 and SARS-CoV-2 infection. POPs and elements may contribute to explain the heterogeneity in the development of SARS-CoV-2 infection and COVID-19 in the general population. If the associations are confirmed as causal, means are available to mitigate the corresponding risks.

Effect of Different Chemical Surface Treatments on the Shear Bond Strength of Acrylic Teeth With Different High-Impact Denture Base Resins.

Introduction The debonding of acrylic teeth from the denture base, particularly in cases of prominent ridges, is a common problem faced by clinicians and patients. The present study was conducted to assess the effects of various chemical treatments on the shear bond strength (SBS) of acrylic teeth bonded to different high-impact denture base materials. Materials and methods The present in vitro study was conducted on 80 wax specimens with acrylic teeth bonded to two high-impact denture base materials (DPI Tuff (DPI Dental Products of India Ltd, Mumbai) and Trevalon HI (Trevalon HI, Dentsply, Karnataka)). The two main groups were further divided into four subgroups of 10 specimens each, depending on the chemical treatment at the ridge lap area of the tooth: control group without any chemical treatment, chemical surface treatment (CST) with dichloromethane and monomer mix, CST with ethyl acetate, and CST with acrylic adhesive cyanoacrylate. The SBS was tested using a universal testing machine (UTM). Analysis of variance (ANOVA) and post-hoc Tukey tests were used for statistical analyses. Results The mean SBS of Group A (DPI Tuff) was 111.75 N as compared to 118 N in Group B (Trevalon HI). The differences were statistically significant (p<0.05). ANOVA and post-hoc Tukey's tests revealed significant differences between subgroups. The highest mean SBS was noted with a dichloromethane and monomer mix (1:1 volume), followed by the ethyl acetate, control, and cyanoacrylate subgroups. Conclusion The cross-linked acrylic teeth treated with a dichloromethane and monomer mixture (1:1 by volume), processed with Trevalon HI high-impact denture base resin had the highest SBS and thus were indicated for bonding teeth with the suggested denture base.

The effect of low-magnitude, high-frequency vibration on poly(ethylene glycol)-microencapsulated mesenchymal stem cells.

Low-magnitude, high-frequency vibration has stimulated osteogenesis in mesenchymal stem cells when these cells were cultured in certain types of three-dimensional environments. However, results of osteogenesis are conflicting with some reports showing no effect of vibration at all. A large number of vibration studies using three-dimensional scaffolds employ scaffolds derived from natural sources. Since these natural sources potentially have inherent biochemical and microarchitectural cues, we explored the effect of low-magnitude, high-frequency vibration at low, medium, and high accelerations when mesenchymal stem cells were encapsulated in poly(ethylene glycol) diacrylate microspheres. Low and medium accelerations enhanced osteogenesis in mesenchymal stem cells while high accelerations inhibited it. These studies demonstrate that the isolated effect of vibration alone induces osteogenesis.

Isolated lower limb hypoplasia secondary to congenital varicella syndrome: a rare occurrence and management of its complications.

Isolated lower limb hypoplasia is a rare consequence of maternal congenital varicella syndrome (CVS). The hypoplastic limb is susceptible to multiple injuries, including fractures, especially if there is associated muscle weakness and lack of sensation. We describe a unique index case of a woman aged 26 years with a background of CVS who presented with a distal femur fracture following a fall onto her insensate, hypoplastic right leg. This report highlights the complexities involved in the diagnosis and management of fractures in patients with an anaesthetic limb, and in particular describes limb amputation as a successful treatment modality for distal femur fractures.

Effects of retinoic acid on retinal pigment epithelium from excised membranes from proliferative vitreoretinopathy.

It has been reported that retinoic acid (RA) may inhibit the growth of RPE and be used in the treatment of proliferative vitreoretinopathy (PVR). However, previous reports in this field have been conflicting. The main reason for these contradictory findings is that different methods for evaluating the effects of RA on RPE from different species have been used. In human specimens, only RPE from the donor eye (stationary) but not RPE from the PVR membrane (already at active proliferation status) have been tested. This study tested the effects of RA on the growth of RPE using a novel in vitro model: RPE from the PVR membranes, which simulates the in vivo situation of PVR patients better than RPE from the donor eyes. This study also used various methods to solve the conflicting results reported previously. We found that both all transretinoic acid (all-RA) and 13-cis-retinoic acid (cis-RA) can promptly (though not completely) inhibit proliferation of RPE (inhibition rate of 89%-90%) over a very wide range of concentrations (10(-9)-10(-5) M) and various lengths of periods (2-12 days) in a dose-dependent and time-dependent manner and without evident cytotoxic effects. Previously reported disadvantages discovered from the study of RPE from donor eyes, e.g., the absence of inhibitory effects on the early passages of cultured cells and inhibition occurring only after long-term treatment, do not present in RPE cells from the PVR membrane. The proliferation of RPE recovered from the inhibition by RA rapidly after the discontinuation of treatment, indicating that a continuous supply of the drug over a long period, i.e., until the breakdown of the blood-retinal barrier has been repaired, is essential for the success of drug treatment of PVR.

Self-compassionate reactions to health threats.

Four studies investigated the relationship between self-compassion, health behaviors, and reactions to illness. Participants completed measures of self-compassion, health-related thoughts and feelings, reactions to actual and hypothetical illnesses, and self-regulation. Study 1 revealed that self-compassion was related to health-related cognitions and affect for healthy and unhealthy participants. In Study 2, self-compassion predicted participants' reactions to actual illnesses beyond the influence of illness severity and other predictors of health behaviors. Self-compassionate people also indicated they would seek medical attention sooner when experiencing symptoms than people lower in self-compassion. Study 3 demonstrated that self-compassion is related to health-promoting behaviors even after accounting for self-regulatory capabilities and illness cognitions. Study 4 revealed that the relationship between self-compassion and health reactions is partially explained by a proactive approach to health, benevolent self-talk, and a motivation toward self-kindness. Overall, these studies demonstrate that self-compassion has important implications for health-promoting behaviors and reactions to illness.

Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Genetic analysis is commonly performed in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. STUDY OBJECTIVE: The objective of the study was to describe comprehensive CYP21A2 mutation analysis in a large cohort of CAH patients. METHODS: Targeted CYP21A2 mutation analysis was performed in 213 patients and 232 parents from 182 unrelated families. Complete exons of CYP21A2 were sequenced in patients in whom positive mutations were not identified by targeted mutation analysis. Copy number variation and deletions were determined using Southern blot analysis and PCR methods. Genotype was correlated with phenotype. RESULTS: In our heterogeneous U.S. cohort, targeted CYP21A2 mutation analysis did not identify mutations on one allele in 19 probands (10.4%). Sequencing identified six novel mutations (p.Gln262fs, IVS8+1G>A, IVS9-1G>A, p.R408H, p.Gly424fs, p.R426P) and nine previously reported rare mutations. The majority of patients (79%) were compound heterozygotes and 69% of nonclassic (NC) patients were compound heterozygous for a classic and a NC mutation. Duplicated CYP21A2 haplotypes, de novo mutations and uniparental disomy were present in 2.7% of probands and 1.9 and 0.9% of patients from informative families, respectively. Genotype accurately predicted phenotype in 90.5, 85.1, and 97.8% of patients with salt-wasting, simple virilizing, and NC mutations, respectively. CONCLUSIONS: Extensive genetic analysis beyond targeted CYP21A2 mutational detection is often required to accurately determine genotype in patients with CAH due to the high frequency of complex genetic variation.

Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families.

OBJECTIVE: To comprehensively phenotype parents identified with nonclassic congenital adrenal hyperplasia (NCCAH) by family genetic studies, termed here as cryptic NCCAH and to define the incidence of cryptic NCCAH in the parents of a large cohort of patients with 21-hydroxylase deficiency. DESIGN: Genotyping was performed on 249 parents of 145 unrelated congenital adrenal hyperplasia (CAH) patients. Parents with two CYP21A2 mutations underwent extensive evaluation. RESULTS: Of the 249 parents, ten (4%; seven females and three males) were identified as having cryptic NCCAH. The majority was of ethnicities previously reported to have a higher incidence of NCCAH. Cosyntropin stimulation performed in eight parents provided biochemical confirmation (17-hydroxyprogesterone range 56-364 nmol/l) and cortisol response was ≤500 nmol/l in three parents (38%). Of the seven women (27-54 years) with cryptic NCCAH, four had prior infertility, two reported irregular menses, two had treatment for hirsutism, one had androgenic alopecia. Men were asymptomatic. All cryptic NCCAH parents reported normal puberty and had normal height. Adrenal hypertrophy and a small adrenal myelolipoma were observed in two parents; testicular adrenal rest tissue was not found. CONCLUSIONS: Parents diagnosed with NCCAH by genetic testing are mostly asymptomatic. Temporary female infertility and suboptimal cortisol response were commonly observed. Ongoing glucocorticoid therapy is not indicated in adults with CAH identified by family genotype studies unless symptomatic, but glucocorticoid stress coverage should be considered in select cases. Parents of a child with CAH have a 1:25 risk of having NCCAH; if the mother of a child with CAH has infertility, evaluation for NCCAH is indicated.