Loss of aPKCλ disrupts epidermal homeostasis and bulge stem cell maintenance by driving cell fate changes via a shift toward asymmetric division

The lifelong self‐renewal of the epidermis is driven by a progenitor cell population with high proliferative potential. To date, the upstream signals that determine this potential have remained largely elusive. Here, we find that insulin and insulin‐like growth factor receptors (IR and IGF‐1R) determine epidermal proliferative potential and cooperatively regulate interfollicular epidermal morphogenesis in a cell autonomous manner. Epidermal deletion of either IR or IGF‐1R or both in mice progressively decreased epidermal thickness without affecting differentiation or apoptosis. Proliferation was temporarily reduced at E17.5 in the absence of IGF‐1R but not IR. In contrast, clonogenic capacity was impaired in both IR‐ and IGF‐1R‐deficient primary keratinocytes, concomitant with an in vivo loss of keratin 15. Together with a reduction in label‐retaining cells in the interfollicular epidermis, this suggests that IR/IGF‐1R regulate progenitor cells. The expression of dominant active Rac rescued clonogenic potential of IR/IGF‐1R‐negative keratinocytes and reversed epidermal thinning in vivo. Our results identify the small GTPase Rac as a key target of epidermal IR/IGF‐1R signalling crucial for proliferative potential and interfollicular morphogenesis.

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ImportanceCancer screening deficits during the first year of the COVID-19 pandemic were found to persist into 2021. Cancer-related deaths over the next decade are projected to increase if these deficits are not addressed.ObjectiveTo assess whether participation in a nationwide quality improvement (QI) collaborative, Return-to-Screening, was associated with restoration of cancer screening.Design, Setting, and ParticipantsAccredited cancer programs electively enrolled in this QI study. Project-specific targets were established on the basis of differences in mean monthly screening test volumes (MTVs) between representative prepandemic (September 2019 and January 2020) and pandemic (September 2020 and January 2021) periods to restore prepandemic volumes and achieve a minimum of 10% increase in MTV. Local QI teams implemented evidence-based screening interventions from June to November 2021 (intervention period), iteratively adjusting interventions according to their MTVs and target. Interrupted time series analyses was used to identify the intervention effect. Data analysis was performed from January to April 2022.ExposuresCollaborative QI support included provision of a Return-to-Screening plan-do-study-act protocol, evidence-based screening interventions, QI education, programmatic coordination, and calculation of screening deficits and targets.Main Outcomes and MeasuresThe primary outcome was the proportion of QI projects reaching target MTV and counterfactual differences in the aggregate number of screening tests across time periods.ResultsOf 859 cancer screening QI projects (452 for breast cancer, 134 for colorectal cancer, 244 for lung cancer, and 29 for cervical cancer) conducted by 786 accredited cancer programs, 676 projects (79%) reached their target MTV. There were no hospital characteristics associated with increased likelihood of reaching target MTV except for disease site (lung vs breast, odds ratio, 2.8; 95% CI, 1.7 to 4.7). During the preintervention period (April to May 2021), there was a decrease in the mean MTV (slope, −13.1 tests per month; 95% CI, −23.1 to −3.2 tests per month). Interventions were associated with a significant immediate (slope, 101.0 tests per month; 95% CI, 49.1 to 153.0 tests per month) and sustained (slope, 36.3 tests per month; 95% CI, 5.3 to 67.3 tests per month) increase in MTVs relative to the preintervention trends. Additional screening tests were performed during the intervention period compared with the prepandemic period (170 748 tests), the pandemic period (210 450 tests), and the preintervention period (722 427 tests).Conclusions and RelevanceIn this QI study, participation in a national Return-to-Screening collaborative with a multifaceted QI intervention was associated with improvements in cancer screening. Future collaborative QI endeavors leveraging accreditation infrastructure may help address other gaps in cancer care.

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Summary A combination of surgical emphysema, bilateral pneumothorax, pneumomediastinum and pneumoperitoneum complicating anaesthesia using endotracheal intubation has been reported only once before. Its occurrence twice in a recent period of 4 months at one hospital suggests that it may not be rare. Recognition of the early signs should enable steps to be taken before irreversible cerebral damage has occurred.

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The presence of an isolated phlebolith in oral soft tissue is a rare entity. This case presents the finding of a tender calcified mass situated in the buccal sulcus, adjacent to where the lower wisdom tooth was situated 5 years prior. Histological diagnosis of the lesion confirmed a phlebolith; to the best of our knowledge this is the first reported case of an isolated oral phlebolith, with no associated vascular malformation, arising after the surgical extraction of a wisdom tooth. Here, we discuss the case of a 27 year old female complaining of soreness in the right posterior buccal mucosa, adjacent to where the lower right wisdom tooth (LR8) was extracted 5 years ago. Clinical examination revealed a small, mobile firm lump within the buccal soft tissue. Radiographically, a well‐defined round lesion of mixed radiodensity was detected, indicating a calcified lesion. This was excised and histology confirmed it to be a phlebolith. This may have been caused by trauma from the surgical extraction of the LR8 or long‐buccal infiltration, as it presented in that specific location. Oral phleboliths rarely occur without associated vascular malformations; there have only been four other similar lesions reported in the literature to date. This is a rare but interesting complication that likely arose from the uneventful surgical procedure 5 years previously, and should be included in a differential diagnosis for calcified lesions in buccal soft tissue.