During inflammation, the skin deploys antimicrobial peptides (AMPs) yet during allergic inflammation it becomes more susceptible to Staphylococcus aureus. To understand this contradiction, ...single-cell sequencing of Il4ra−/− mice combined with skin microbiome analysis reveals that lower production of AMPs from interleukin-4 receptor α (IL-4Rα) activation selectively inhibits survival of antibiotic-producing strains of coagulase-negative Staphylococcus (CoNS). Diminished AMPs under conditions of T helper type 2 (Th2) inflammation enable expansion of CoNS strains without antibiotic activity and increase Staphylococcus aureus (S. aureus), recapitulating the microbiome on humans with atopic dermatitis. This response is rescued in Camp−/− mice or after topical steroids, since further inhibition of AMPs enables survival of antibiotic-producing CoNS strains. In conditions of Th17 inflammation, a higher expression of host AMPs is sufficient to directly inhibit S. aureus survival. These results show that antimicrobials produced by the host and commensal bacteria each act to control S. aureus on the skin.
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•Skin colonization by Staphylococcus aureus exacerbates existing Th2 inflammation•IL-4Rα suppresses but does not eliminate antimicrobial peptide (AMP) expression•CoNS that express antibiotics are more sensitive to AMPs than S. aureus or other CoNS•Loss of antimicrobial defense from AMPs and CoNS enables S. aureus survival on skin
Nakatsuji et al. report how activation of IL-4Rα partially suppresses production of antimicrobial peptides from the skin so that they cannot kill Staphylococcus aureus (S. aureus) but do inhibit protective strains of Staphylococcus that produce bacteriocins. Their findings can explain why S. aureus expands on the skin of patients with atopic dermatitis.
In the liver, ductal cells rarely proliferate during homeostasis but do so transiently after tissue injury. These cells can be expanded as organoids that recapitulate several of the cell-autonomous ...mechanisms of regeneration but lack the stromal interactions of the native tissue. Here, using organoid co-cultures that recapitulate the ductal-to-mesenchymal cell architecture of the portal tract, we demonstrate that a subpopulation of mouse periportal mesenchymal cells exerts dual control on proliferation of the epithelium. Ductal cell proliferation is either induced and sustained or, conversely, completely abolished, depending on the number of direct mesenchymal cell contacts, through a mechanism mediated, at least in part, by Notch signaling. Our findings expand the concept of the cellular niche in epithelial tissues, whereby not only soluble factors but also cell-cell contacts are the key regulatory cues involved in the control of cellular behaviors, suggesting a critical role for cell-cell contacts during regeneration.
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•The numbers of mesenchyme-ductal cell contacts change during damage regeneration•Ductal-mesenchyme organoids recapitulate cell interactions and in vivo architecture•Mesenchymal cells induce ductal epithelium cell proliferation via soluble factors•Mesenchymal cells impair ductal epithelium cell proliferation via cell-cell contacts
Huch and colleagues describe that during liver regeneration, ductal and mesenchymal cells proliferate with different tempos, resulting in changes in the cellular contacts between both populations. By developing organoid co-cultures that recapitulate ductal-mesenchymal interactions, they provide proof that the number of cell contacts matters and either promotes or arrests epithelial proliferation.
C. difficile is an endospore-forming pathogen, which is becoming a common cause of microbial health-care associated gastrointestinal disease in the United States. Both healthy and symptomatic ...patients can shed C. difficile spores into the environment, which can survive for long periods, being resistant to desiccation, heat, and disinfectants. In healthcare facilities, environmental contamination with C. difficile is a major concern as a potential source of exposure to this pathogen and risk of disease in susceptible patients. Although hospital-acquired infection is recognized, community-acquired infection is an increasingly recognized health problem. Primary care clinics may be a significant source of exposure to this pathogen; however, there are limited data about presence of environmental C. difficile within clinics. To address the potential for primary care clinics as a source of environmental exposure to virulent C. difficile, we measured the frequency of environmental contamination with spores in clinic examination rooms and hospital rooms in Dallas-Fort Worth (DFW) area of Texas. The ribotypes and presence of toxin genes from some environmental isolates were compared. Our results indicate primary care clinics have higher frequencies of contamination than hospitals. After notification of the presence of C. difficile spores in the clinics and an educational discussion to emphasize the importance of this infection and methods of infection prevention, environmental contamination in clinics was reduced on subsequent sampling to that found in hospitals. Thus, primary care clinics can be a source of exposure to virulent C. difficile, and recognition of this possibility can result in improved infection prevention, potentially reducing community-acquired C. difficile infections and subsequent disease.
•Chinese environmental flows research was characterized based on bibliometric analysis for the period 1967–2019.•This body of research was compared to e-flows research trends within and outside of ...China.•Prominent Chinese authors and important ideas in e-flows research were identified.•This body of work helps identify prevailing trends in Chinese e-flows research.
Advances in water resources research in China has blossomed in recent decades. Although historically many Chinese scientific publications had been limited to regional, language-specific outlets, the more recent emergence of Chinese scholarship in water resources sustainability and engineering suggests that broader recognition within the scientific community is needed. In this study, we explore the recent evolution of Chinese environmental flows research through the bibliometric analysis of two prominent databases. This paper highlights trends in environmental flow publication rates, emerging areas of research, and citation networks for prominent authors in the Chinese context as compared to the global network of environmental flows research. Results indicate that China’s environmental flows research developed rapidly over the past two decades (2005–2019) and that Chinese authors are among the most productive in the field (60% of the top 20 authors). However, based on the number of citations, few Chinese articles are among the most highly cited (5 out of 800). The field of environmental flows research has identified the need to minimize parochial boundaries, and this analysis suggests a rich, yet untapped, literature to promote scientific integration. Differences in journal selection, keyword choice, and lesser-known authors to readers outside of China were identified as potential limitations to broader global integration. This approach to systematic bibliometric analysis can be used to identify prominent authors and important studies such that new ideas in environmental flows research can flow across continental boundaries, from East to West, to accelerate global understanding of prevailing trends and best practices in river management
Within the peri-portal region of the adult liver, portal fibroblasts exist in close proximity to epithelial ductal/cholangiocyte cells. However, the cellular interactions between them are poorly ...understood. Here, we provide two co-culture techniques to incorporate liver portal mesenchyme into ductal cell organoids, which recapitulate aspects of their cellular interactions in vitro. We integrate several techniques from mesenchyme isolation and expansion to co-culture by microfluidic cell co-encapsulation or 2D-Matrigel layer. The protocol is easily adaptable to other cells from other organs.
For complete information on the generation and use of this protocol, please refer to Cordero-Espinoza et al.1
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•Isolation, sorting, and in vitro expansion of primary liver portal mesenchyme•Production of microfluidic PDMS chips•Droplet microfluidic method for primary liver mesenchyme/ductal cell organoid co-culture•Cell self-aggregation method for primary liver mesenchyme/ductal cell organoid co-culture
Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Within the peri-portal region of the adult liver, portal fibroblasts exist in close proximity to epithelial ductal/cholangiocyte cells. However, the cellular interactions between them are poorly understood. Here, we provide two co-culture techniques to incorporate liver portal mesenchyme into ductal cell organoids, which recapitulate aspects of their cellular interactions in vitro. We integrate several techniques from mesenchyme isolation and expansion to co-culture by microfluidic cell co-encapsulation or 2D-Matrigel layer. The protocol is easily adaptable to other cells from other organs.
Background
Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Multiple risk factors are associated in the development of BCC, with ultraviolet light and genetics playing major roles.
...Aims
The departments of dermatology, medical oncology, ophthalmology, otorhinolaryngology, head and neck surgery, plastic surgery, and radiation oncology of the Jose R. Reyes Memorial Medical Center, Manila, Philippines, have convened and formulated consensus statements on the diagnosis and management of BCC patients seen in the institution.
Conclusion
The summary of the recommendations is: (1) Surgery is the treatment of choice for BCC. The range of margins (2–4 mm) depends on the type of BCC. (2) Mohs micrographic surgery (MMS) is indicated for high risk BCC. (3) Topical treatment with imiquimod or 5‐flourouracil (5‐FU) may be used for superficial BCC. (4) Destructive methods (cryotherapy, curettage and electrodessication, photodynamic therapy) may be used for low risk BCC. (5) Medical and/or radiation therapy is advised for cases where surgery is contraindicated or tumor is not amenable to surgery. Metastasis of this malignancy is rare. Follow‐up, which may continue up until 2 years, is recommended for high risk BCC.
We aimed to evaluate whether there is a significant association between a placental pathology diagnosis basal plate myofibers (BPMF) in an index pregnancy with placenta accreta spectrum (PAS) in the ...subsequent pregnancy.
We conducted a retrospective nested cohort study of all cases with a histopathological finding of BPMF between August 2012 and March 2020 at a single tertiary referral center. Data were collected for all subjects (cases and controls) with at least two consecutive pregnancies (the initial index pregnancy and at least one subsequent pregnancy) accompanied by a concomitant record of histopathological study of the placenta at our center. The primary outcome was pathologically confirmed PAS in the subsequent pregnancy. Data are presented as percentage or median, interquartile range accordingly.
A total of
= 1,344 participants were included, of which
= 119 (index cases) carried a contemporaneous histopathological diagnosis of BPMF during the index pregnancy and
= 1,225 did not (index controls). Among the index cases, patients with BPMF were older (31.0 20, 42 vs. 29.0 15, 43,
< 0.001), more likely to have undergone in vitro fertilization (IVF) for conception (10.9 vs. 3.8%,
= 0.001) and were of a more advanced gestational age at delivery (39.0 25, 41 vs. 38.0 20, 42,
= 0.006). In the subsequent pregnancy, the rate of PAS was significantly higher among the BPMF index cases (6.7 vs. 1.1%,
< 0.001). After adjusting for maternal age and IVF, a histopathological diagnosis of BPMF in an index pregnancy was shown to be a significant risk factor for PAS in the subsequent gestation (hazard ratio: 5.67 95% confidence interval: 2.28, 14.06,
< 0.001).
Our findings support that a histopathological diagnosis of BPMF is an independent risk factor for PAS in the subsequent pregnancy.
· BPMF may indicate morbid adherence of placenta.. · Patients with BPMF were older and more likely to have undergone IVF for conception.. · The BPMF in the current pregnancy is an independent risk factor for PAS in the subsequent pregnancy..
Older adults and caregivers play an essential role in medication safety; however, self-perception of their and health professionals’ roles in medication safety is not well-understood. The objective ...of our study was to identify the roles of patients, providers, and pharmacists in medication safety from the perspective of older adults. Semi-structured qualitative interviews were held with 28 community-dwelling older adults over 65 years who took five or more prescription medications daily. Results suggest that older adults’ self-perceptions of their role in medication safety varied widely. Older adults perceived that self-learning about their medications and securing them are critical to avoiding medication-related harm. Primary care providers were perceived as coordinators between older adults and specialists. Older adults expected pharmacists to inform them of any changes in the characteristics of medications to ensure medications were taken correctly. Our findings provide an in-depth analysis of older adults’ perceptions and expectations of their providers’ specific roles in medication safety. Educating providers and pharmacists about the role expectations of this population with complex needs can ultimately improve medication safety.
Preventable harms from medications are significant threats to patient safety in community settings, especially among ambulatory older adults on multiple prescription medications. Patients may partner ...with primary care professionals by taking on active roles in decisions, learning the basics of medication self-management, and working with community resources.
This study aims to assess the impact of a set of patient partnership tools that redesign primary care encounters to encourage and empower patients to make more effective use of those encounters to improve medication safety.
The study is a nonrandomized, cross-sectional stepped wedge cluster-controlled trial with 1 private family medicine clinic and 2 public safety-net primary care clinics each composing their own cluster. There are 2 intervention sequences with 1 cluster per sequence and 1 control sequence with 1 cluster. Cross-sectional surveys will be taken immediately at the conclusion of visits to the clinics during 6 time periods of 6 weeks each, with a transition period of no data collection during intervention implementation. The number of visits to be surveyed will vary by period and cluster. We plan to recruit patients and professionals for surveys during 405 visits. In the experimental periods, visits will be conducted with two partnership tools and associated clinic process changes: (1) a 1-page visit preparation guide given to relevant patients by clinic staff before seeing the provider, with the intention to improve communication and shared decision-making, and (2) a library of short educational videos that clinic staff encourage patients to watch on medication safety. In the control periods, visits will be conducted with usual care. The primary outcome will be patients' self-efficacy in medication use. The secondary outcomes are medication-related issues such as duplicate therapies identified by primary care providers and assessment of collaborative work during visits.
The study was funded in September 2019. Data collection started in April 2023 and ended in December 2023. Data was collected for 405 primary care encounters during that period. As of February 15, 2024, initial descriptive statistics were calculated. Full data analysis is expected to be completed and published in the summer of 2024.
This study will assess the impact of patient partnership tools and associated process changes in primary care on medication use self-efficacy and medication-related issues. The study is powered to identify types of patients who may benefit most from patient engagement tools in primary care visits.
ClinicalTrials.gov NCT05880368; https://clinicaltrials.gov/study/NCT05880368.
DERR1-10.2196/57878.
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