Women who seek help for fear of childbirth are a vulnerable group. Because the counseling received by the women in this study did not accord them the same positive experience of childbirth as the average parturient at the unit, more effective forms of treatment may be necessary. However, as most of the women were very satisfied with their care and with the outcome, one may assume that the care given had improved their situation to some degree.

It is widely accepted that disruption of the hedgehog-patched pathway is a key event in development of basal cell cancer. In addition to patched gene alterations, p53 gene mutations are also frequent in basal cell cancer. We determined loss of heterozygosity in the patched and p53 loci as well as sequencing the p53 gene in tumors both from sporadic and hereditary cases. A total of 70 microdissected samples from tumor and adjacent skin were subjected to PCR followed by fragment analysis and DNA sequencing. We found allelic loss in the patched locus in 6/8 sporadic basal cell cancer and 17/19 hereditary tumors. All sporadic and 7/20 hereditary tumors showed p53 gene mutations. Loss of heterozygosity in the p53 locus was rare in both groups. The p53 mutations detected in hereditary tumors included rare single nucleotide deletions and unusual double-base substitutions compared to the typical ultraviolet light induced missense mutations found in sporadic tumors. Careful microdissection of individual tumors revealed genetically linked subclones with different p53 and/or patched genotype providing an insight on time sequence of genetic events. The high frequency and co-existence of genetic alterations in the patched and p53 genes suggest that both these genes are important in the development of basal cell cancer.

The available evidence on the effects of ambient air pollution on cardiovascular diseases (CVDs) has increased substantially. In this umbrella review, we summarized the current epidemiological evidence from systematic reviews and meta‐analyses linking ambient air pollution and CVDs, with a focus on geographical differences and vulnerable subpopulations. We performed a search strategy through multiple databases including articles between 2010 and 31 January 2021. We performed a quality assessment and evaluated the strength of evidence. Of the 56 included reviews, the most studied outcomes were stroke (22 reviews), all‐cause CVD mortality, and morbidity (19). The strongest evidence was found between higher short‐ and long‐term ambient air pollution exposure and all‐cause CVD mortality and morbidity, stroke, blood pressure, and ischemic heart diseases (IHD). Short‐term exposures to particulate matter <2.5 μm (PM2.5), <10 μm (PM10), and nitrogen oxides (NOx) were consistently associated with increased risks of hypertension and triggering of myocardial infarction (MI), and stroke (fatal and nonfatal). Long‐term exposures of PM2.5 were largely associated with increased risk of atherosclerosis, incident MI, hypertension, and incident stroke and stroke mortality. Few reviews evaluated other CVD outcomes including arrhythmias, atrial fibrillation, or heart failure but they generally reported positive statistical associations. Stronger associations were found in Asian countries and vulnerable subpopulations, especially among the elderly, cardiac patients, and people with higher weight status. Consistent with experimental data, this comprehensive umbrella review found strong evidence that higher levels of ambient air pollution increase the risk of CVDs, especially all‐cause CVD mortality, stroke, and IHD. These results emphasize the importance of reducing the alarming levels of air pollution across the globe, especially in Asia, and among vulnerable subpopulations.

Epidermal clones of p53-mutated keratinocytes are abundant in chronically sun-exposed skin and may play an important role in early development of skin cancer. Advanced laser capture microdissection enables genetic analysis of targeted cells from tissue sections without contamination from neighboring cells. In this study p53 gene mutations were characterized in single cells from normal, chronically sunexposed skin. Biopsies were obtained from skin subjected to daily summer sun and skin totally protected from the sun by blue denim fabric. Using laser capture microdissection, 172 single-cell samples were retrieved from four biopsies and analyzed using single-cell polymerase chain reaction and direct DNA sequencing. A total of 14 different mutations were identified in 26 of 99 keratinocytes from which the p53 gene could be amplified. Mutations displayed a typical UV signature and were detected in both scattered keratinocytes and in a small cluster of p53-immunoreactive keratinocytes. This minute epidermal p53 clone had a diameter of 10 to 15 basal cells. Two missense mutations were found in all layers of epidermis within the p53 clone. The presented data show that p53 mutations are common in normal skin and that a clone of keratinocytes with a mutated p53 gene prevailed despite 2 months of total protection from ultraviolet light. 1 Ultraviolet (UV) radiation from the sun is accepted as a major risk factor and tumor cells exhibit mutations with typical UV signature in cancerrelated genes.2 Skin carcinogenesis is a multistep process, in which the early clandestine events, preceding malignant transformation are primarily unknown. In chronically sun-damaged skin SCC develops through stages of actinic keratosis and SCC in situ, whereas no such precursor lesions are known for BCC. Although several genes and pathways are important for development of skin cancer, the genetic events underlying the different steps from a normal cell to SCC or BCC are virtually unknown. Mutation of the p53 gene is one frequent, known genetic alteration found in SCC and BCC. In addition, activation of the sonic hedgehog/patched signaling pathway seems essential for development of BCC. 4,5 In human skin there exists a multitude of p53-immunoreactive clusters of morphologically normal epidermal keratinocytes.6 -8 These p53 clones are predominantly found in chronically sun-exposed skin. Microdissection followed by polymerase chain reaction (PCR) and direct DNA sequencing has shown an underlying p53 mutation in at least 70% of analyzed cases. Epidermal p53 clones and adjacent cancers have never been shown to share the same p53 mutation and thus there is no solid evidence of a genetic link between p53 clones and any specific type of skin cancer.9,10 However, the incidence and location of p53 clones suggest a role for p53 mutations in skin cancer. Mutations in the p53 gene have also been detected in UV-irradiated mouse skin months before the gross appearance of skin tumors, suggesting that p53 mutations are an early event for the development of skin ...

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