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Institutional ethnography (IE), a term coined by sociologist Dorothy Smith, explores the nuances of institutions and their complex relationships in sociology. IE is an approach to studying and analysing social organization, and it provides a more holistic understanding of 'invisible' relationships that govern institutions and how those relationships interact with each other. Health sciences researchers in patient care, patient experience, and allied health professionals have recently become more interested in the use of this methodology and how to incorporate it into their research. However, in health professions education (HPE) there is little use of IE. We hypothesize this may be because of limited practical knowledge of this methodology. This paper serves as an introduction to the use of IE in HPE, describing the differences between IE and traditional ethnographies, recognizing the common pitfalls when utilising IE, and incorporating texts into IE. While ethnographies may be daunting to researchers less familiar with these approaches, the tips in this paper will provide an introduction and help educators and researchers successfully navigate the use of IE in health profession scholarship and education. [ABSTRACT FROM AUTHOR]

This pilot study assesses barriers to obtaining healthy affordable food and the early-stage acceptability of a novel subsidized healthy frozen meal product designed to address food insecurity and nutritional status among corner store customers in rural North Carolina. A convenience sample of 50 customers were surveyed to examine the perceived availability of healthy food options, barriers to maintaining healthy diets, food shopping and consumption habits, and reception of the product. Findings confirmed barriers to obtaining healthy foods that the product seeks to address, the validity of corner stores as the intervention site, and approval of the product's taste and concept. [ABSTRACT FROM AUTHOR]

Excess suprapubic adiposity can have negative consequences for patients, including concerns related to physical comfort, sexual function, hygiene, and esthetics. Historically, treatment options for pubic contouring have been limited to surgical methods. The purpose of this article is to review the literature investigating the use of minimally invasive fat reduction treatments for suprapubic adiposity including cryolipolysis, injection lipolysis, radiofrequency, and ultrasound. A thorough search of the PubMed database was conducted to search for studies evaluating the use of cryolipolysis, injection lipolysis, radiofrequency, and ultrasound for suprapubic adiposity. The literature search did not yield any publications that evaluated the use of cryolipolysis, injection lipolysis, radiofrequency, or ultrasound for treatment of suprapubic adiposity. Minimally invasive treatments for fat reduction, including cryolipolysis, injection lipolysis, radiofrequency, and ultrasound, have clinically demonstrated safety and efficacy in various anatomic locations. However, clinical studies evaluating these procedures for suprapubic adiposity are noticeably absent. These options may confer benefits such as decreased recovery time, risk, and cost to patients. Future clinical studies evaluating these potential treatment modalities for suprapubic fat reduction are warranted. [ABSTRACT FROM AUTHOR]

Gut microbiota imbalance (dysbiosis) is increasingly associated with pathological conditions, both within and outside the gastrointestinal tract. Intestinal Paneth cells are considered to be guardians of the gut microbiota, but the events linking Paneth cell dysfunction with dysbiosis remain unclear. We report a three-step mechanism for dysbiosis initiation. Initial alterations in Paneth cells, as frequently observed in obese and inflammatorybowel diseases patients, cause a mild remodeling of microbiota, with amplification of succinate-producing species. SucnR1 -dependent activation of epithelial tuft cells triggers a type 2 immune response that, in turn, aggravates the Paneth cell defaults, promoting dysbiosis and chronic inflammation. We thus reveal a function of tuft cells in promoting dysbiosis following Paneth cell deficiency and an unappreciated essential role of Paneth cells in maintaining a balanced microbiota to prevent inappropriate activation of tuft cells and deleterious dysbiosis. This succinate--tuft cell inflammation circuit may also contribute to the chronic dysbiosis observed in patients. [ABSTRACT FROM AUTHOR]

Graduate medical education is refocusing on the reconciliation process with Indigenous peoples and integrating Indigenous healing practices, cultural humility training, and courses on Indigenous health issues in their curricula. Physicians and all health care workers must be able to recognize, respect, and address the distinct health needs of all Indigenous peoples. The aim of this scoping review was to explore and describe what exists in the current literature on the impact and challenges associated with Indigenous curricula developed for resident physicians. The search was conducted using 9 bibliographic databases from inception until April 19, 2021. Two reviewers independently screened for inclusion using Covidence. Three reviewers extracted data and all 3 checked for completeness and accuracy. Eleven reports were included. Our included reports consisted of qualitative research (n=2), commentaries (n=1), special articles (n=3), systematic reviews (n=1), innovation reports (n=1), published abstracts (n=1), and program evaluation papers (n=2). Findings are presented by 3 themes: (1) Misunderstandings and cultural bias toward Indigenous people; (2) Increasing community-driven Indigenous partnerships to create a safe environment; and (3) Challenges in implementing Indigenous health curricula. Themes identified related to Indigenous involvement, culturally competent care, common misconceptions about Indigenous peoples, as well as challenges and barriers to implementing Indigenous curricula for residency programs. A collaborative approach involving stakeholders with training in the community is a viable path forward. But comprehensive program evaluation, a source of stable funding, and further research focusing on effective Indigenous curricula for residents are needed. [ABSTRACT FROM AUTHOR]

Objective: To explore International Medical Graduates residents' experiences and perspectives of their residency training program. Methods: This qualitative study was conducted at a large research-intensive University. Purposeful sampling was used to recruit 14 International medical graduates. The residents recruited for this study were at different levels in their training ranging from Postgraduate year one to five. Residents interviewed represented seven unique specialties. Each trainee was interviewed, and the data were recorded and transcribed verbatim. A thematic analysis framework was used to conduct the data analysis, resulting in the development of study themes. Results: Our analysis generated six main themes. These themes were related to costly decisions, unspoken expectations, the stigma associated with being an IMG, fears of being an IMG, the strength and resilience of IMGs, and recommendations proposed by IMGs for program improvement. Conclusions: In this study, we wanted to explore international residents' experiences with their programs. The experience of each individual international resident is unique. However, in this study, we were able to provide firsthand perceptions of IMGs from a research-intensive university and identified common themes experienced and perceived by our residents. This study's findings may help educate, reduce stigma, and guide the implementation of effective individual and systemic support for these trainees. Which in turn will enhance the overall educational experiences for IMGs trainees. Our study found that themes seem to be recurring, hence, an urgency to bring about appropriate changes, equitable opportunities, and support for IMGs. [ABSTRACT FROM AUTHOR]

Introduction: During the SARS-CoV-2 pandemic, Canadian postsecondary institutions were forced to rely on online teaching to comply with physical distancing recommendations. This sole reliance on virtual methods to deliver synchronous teaching sessions in medical education was novel. We found little empirical research examining pediatric educators' experiences. Hence, the objective of our study was to describe and gain a deeper understanding of pediatric educators' perspectives, focusing on the research question, "How is synchronous virtual teaching impacting and transforming teaching experiences of pediatricians during a pandemic?" Methods: A virtual ethnography was conducted guided by an online collaborative learning theory. This approach used both interviews and online field observations to obtain objective descriptions and subjective understandings of the participants' experiences while teaching virtually. Pediatric educators (clinical and academic faculty) from our institution were recruited using purposeful sampling and invited to participate in individual phone interviews and online teaching observations. Data were recorded and transcribed, and a thematic analysis was conducted. Results: Fifteen frontline pediatric teachers from our large Canadian research-intensive university were recruited. Four main themes, with subthemes, emerged: (1) the love/hate relationship with the virtual shift; (2) self-imposed pressure to increase virtual engagement; (3) looking back, moving forward; (4) accelerated adaptation and enhanced collaboration. Conclusion: Pediatricians adopted new delivery methods quickly and found many efficiencies and opportunities in this shift. Continued use of virtual teaching will lead to increased collaboration, enhanced student engagement strategies, and blending the advantages of virtual and face-to-face learning. [ABSTRACT FROM AUTHOR]

Background: Foot orthoses (FOs) are used to manage foot pathologies such as plantar fasciopathy. 3D printed custom-made FOs are increasingly being manufactured. Although these 3D-printed FOs look like traditionally heat-moulded FOs, there are few studies comparing FOs made using these two different manufacturing processes.Research Question: How effective are 3D-printed FOs (3D-Print) compared to traditionally-made (Traditional) or no FOs (Control), in changing biomechanical parameters of flat-footed individuals with unilateral plantar fasciopathy?Methods: Thirteen participants with unilateral plantar fasciopathy walked with shoes under three conditions: Control, 3D-print, and Traditional. 2 × 3 repeated measures analysis of variance (ANOVAs) with Bonferroni post-hoc tests were used to compare discrete kinematic and kinetic variables between limbs and conditions. Waveform analyses were also conducted using statistical parametric mapping (SPM).Results: There was a significant condition main effect for arch height drop (p = 0.01; ηp2 =0.54). There was 0.87 mm (95% CI [-1.84, -0.20]) less arch height drop in 3D-print compared to Traditional. The SPM analyses revealed condition main effects on ankle moment (p < 0.001) and ankle power (p < 0.001). There were significant differences between control condition and both 3D-print and Traditional conditions. For ankle moment and power, there were no differences between 3D-print and Traditional conditions.Significance: 3D-printed FOs are more effective in reducing arch height drop, whist both FOs lowered ankle plantarflexion moment and power compared to no FOs. The results support the use of 3D-printed FOs as being equally effective as traditionally-made FOs in changing lower limb biomechanics for a population of flat-footed individuals with unilateral plantar fasciopathy. [ABSTRACT FROM AUTHOR]

Background: Powerful constitutive and inducible transgenic / bitransgenic / tritransgenic murine models of breast cancer have been used over the past two decades to shed light on the molecular mechanisms by which the given transgenic oncogenes have interacted with other cellular genes and set in motion breast cancer initiation and progression. However, these transgenic models, as in vivo models only, are expensive and restrictive in the opportunities they provide to manipulate the experimental variables that would enable a better understanding of the molecular events related to initial transformation and the target cell being transformed. Methods: To overcome some of these limitations, we derived oncogene-containing induced pluripotent stem cell (iPSC) clones from tail vein fibroblasts of these transgenic mice and manipulated them both in vitro and in vivo in non-transgenic background mice. We created the iPSC clones with a relatively low M.O.I, producing retroviral integrations which averaged only 1 to 2 sites per retroviral plasmid construct used. Results: Most iPSC clones derived from each group displayed an essentially normal murine karyotype, strong expression of the exogenous reprogrammable genes and significant expression of characteristic endogenous murine surface stem cell markers including SSEA-1 (CD15), PECAM-1 (CD31), Ep-Cam (CD326), and Nectin (CD112), but no expression of their transgene. A majority (75%) of iPSC clones displayed a normal murine karyotype but 25% exhibited a genomically unstable karyotype. However, even these later clones exhibited stable and characteristic iPSC properties. When injected orthotopically, select iPSC clones, either constitutive or inducible, no longer expressed their exogenous pluripotency reprogramming factors but expressed their oncogenic transgene (PyVT or ErbB2) and participated in both breast ontogenesis and subsequent oncogenesis. When injected non-orthotopically or when differentiated in vitro along several different non-mammary lineages of differentiation, the iPSC clones failed to do so. Although many clones developed anticipated teratomas, select iPSC clones under the appropriate constitutive or inducible conditions exhibited both breast ontogenesis and oncogenesis through the same stages as exhibited by their transgenic murine parents and, as such, represent transgenic surrogates. Conclusions: The iPSC clones offer a number of advantages over transgenic mice including cost, the ability to manipulate and tag in vitro, and create an in vitro model of breast ontogeny and oncogenesis that can be used to gain additional insights into the differentiated status of the target cell which is susceptible to transformation. In addition, the use of these oncogene-containing iPSC clones can be used in chemopreventive studies of breast cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND Melasma is a common acquired disorder of hyperpigmentation, classically manifesting as symmetric brown patches on the face. Although the exact pathogenesis is not fully understood, vascular abnormalities have been implicated in melasma. OBJECTIVE To evaluate the laboratory and clinical evidence regarding the safety and efficacy of antivascular agents for the treatment of melasma. METHODS A systematic review of PubMed, EMBASE, and Cochrane was conducted on May 13, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Original research articles investigating the role of vascularity and/or evaluating the use of antivascular therapeutics in melasma were included. Clinical recommendations were based on the American College of Physicians guidelines. RESULTS A total of 34 original research articles as follows were identified: 4 laboratory studies, 15 diagnostic studies, and 15 therapeutic studies. CONCLUSION There is promising evidence supporting the use of tranexamic acid and laser/light therapies to treat the vascular component of melasma, and more rigorous clinical trials are needed to validate their efficacy. Clinicians may consider treatment with one or more antivascular therapeutics in patients with melasma. Further research is warranted to characterize the role of cutaneous vascularization in melasma and may provide insights for novel therapies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Light-emitting diodes (LEDs) may be used as an activating light source for photosensitizers in photodynamic therapy (PDT), a form of noninvasive phototherapy. Photodynamic therapy for aesthetic dermatologic conditions has demonstrated skin rejuvenating effects. OBJECTIVE: To evaluate the safety and efficacy of PDT using LEDs to treat aesthetic dermatologic conditions including photoaged skin, scarring, and dyspigmentation. MATERIALS AND METHODS: A search of PubMed and EMBASE databases was conducted through May 31, 2019, to identify studies that used LEDs as a light source for PDT and evaluated cosmetic improvements as the primary outcome measure. RESULTS: A total of 24 original articles were included in the authors' systematic review. The available evidence supports methyl aminolevulinate or 5-aminolevulinic acid incubation followed by LED treatment for global improvement of skin quality, including smoother texture, reduction of rhytides, and improvement of scars. Histologic analysis for global skin improvement demonstrated increased collagen fibers and decreased elastin fibers after LED-mediated PDT. CONCLUSION: Light-emitting diode-based PDT seems to have beneficial effects for photoaging, scars and dyspigmentation. A paucity of high-quality studies using LED-based PDT for aesthetic outcomes was found, highlighting the need for well-designed randomized control trials on this topic. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL. [ABSTRACT FROM AUTHOR]

Real-time intraoperative assessment of anastomotic perfusion with indocyanine green fluorescence angiography (ICG-FA) is a recent technique that is found to assist intraoperative decision-making and decrease risk of anastomotic leak in the General Surgery literature. No studies to date evaluate its use in Gynecologic Oncology. Our objectives were to assess the safety and feasibility of ICG-FA use and to describe the intraoperative assessment of anastomotic perfusion with ICG-FA. A retrospective study of a prospectively-collected database of patients with a gynecologic malignancy who underwent a bowel resection at Princess Margaret Cancer Centre in Toronto, Canada, between November 1, 2017 and December 15, 2019 was conducted. ICG-FA was administered intravenously, and a near infrared imaging system (Pinpoint, Novadaq, Canada; SPY-PHI, Stryker, USA) was used to objectively assess bowel perfusion. ICG-FA was used to assess a total of 100 bowel anastomoses in 82 consecutive surgeries: 56 low anterior resections, 19 small bowel resections, 15 right hemi-colectomies, 6 left hemi-colectomies, 3 transverse colectomies, and 1 total colectomy. Fifty-five end-to end, 44 side-to-side and 1 end-to-side anastomoses were assessed. ICG angiography was successful in all patients, allowing complete visualization of anastomotic perfusion in all cases. Hypoperfusion detected by ICG-FA resulted in change in operative plan for three patients (two anastomotic revisions and one diverting ileostomy). There were no adverse reactions to ICG. In this cohort, there was one postoperative anastomotic leak. ICG-FA enables objective and accurate intraoperative evaluation of anastomotic perfusion in surgeries for gynecologic malignancies. Its implementation and routine use were found to be safe and well-tolerated without side effects in our study cohort. ICG-FA can be used with other risk-assessment strategies to guide operative decision-making in Gynecologic Oncology. • This is the first study describing the use of indocyanine green angiography for bowel anastomoses in Gynecologic Oncology. • We report prospectively its use in 100 consecutive small and large bowel anastomoses. • Indocyanine green angiography can be used with other risk-assessment strategies to guide intraoperative decision-making. [ABSTRACT FROM AUTHOR]

Background: Cosmeceuticals are commonly used in skincare regimens to maintain healthy skin and improve visible signs of aging. In recent years, South Korean skincare has gained prominence in the global beauty industry by introducing innovative cosmeceutical products and aesthetic trends. Objectives: To describe the global impact of Korean skincare and to review the current research evidence for bioactive ingredients commonly found in Korean cosmeceuticals. Methods: A review of the biomedical literature was conducted using PubMed to identify laboratory, animal, and clinical studies that evaluated the biological properties and potential dermatologic uses of ingredients found in Korean cosmeceuticals. Results: Bioactive ingredients in Korean cosmeceutical products are increasingly undergoing scientific validation and are derived from various sources including animals (eg, bee venom and snail mucin), plants (eg, dragon's blood and tiger grass extract), and biotechnology (eg, synthetic snake venom). Their bioactive components and pharmacologic activities have been shown to provide dermatologic benefits with potential applications for skin rejuvenation, photoprotection, wound healing, and more. Conclusion: Further research studies are warranted to elucidate any biological or therapeutic mechanisms of action of these ingredients, which may translate into clinical practice. With the rising public awareness and interest in Korean cosmeceuticals, patients may seek advice from dermatologists about how to incorporate these bioactive ingredients into their skincare regimens to improve skin health and aesthetics. [ABSTRACT FROM AUTHOR]

Skin fibrosis, characterized by excessive fibroblast proliferation and extracellular matrix deposition in the dermis, is the histopathologic hallmark of dermatologic diseases such as systemic sclerosis, hypertrophic scars, and keloids. Effective anti-scarring therapeutics remain an unmet need, underscoring the complex pathophysiologic mechanisms of skin fibrosis. The Th2 cytokines interleukin (IL)-4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders. The goal of this article is to summarize the current understanding of the role of the IL-4/IL-13 axis in wound healing and skin fibrosis. We conducted a literature search to identify research studies investigating the roles of IL-4 and IL-13 in fibrotic skin diseases. While transforming growth factor-beta has long been regarded as the main driver of fibrotic processes, research into the cellular and molecular biology of wound healing has revealed other pathways that promote scar tissue formation. IL-4 and IL-13 are important mediators of skin fibrosis, supported by evidence from in vitro data, animal models of fibrosis, and clinical studies. Overactive signaling of the IL-4/IL-13 axis contributes to the initiation and perpetuation of fibrotic skin diseases. Further insights into the IL-4/IL-13 axis may reveal potential targets for the development of novel therapies that prevent or treat fibrotic skin diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND Dermatologists routinely perform office-based surgical procedures that result in cutaneous wounds. Wound care instructions are an important resource for postoperative patients. As there is no consensus on the ideal wound care regimen after dermatologic procedures, recommendations may vary. OBJECTIVE To evaluate the current recommendations for wound care following dermatologic procedures. METHODS The authors conducted a cross-sectional assessment of dermatology wound care handouts available online. The handouts were evaluated based on predefined parameters: topical agent recommendations for wound healing, caution against topical antibiotic use, and discussion of scarring, infection, bleeding, analgesia, and lifestyle considerations. RESULTS A total of 169 handouts were evaluated. The majority (84%) recommended the application of petrolatum-based products, specifically Vaseline (75%) and Aquaphor (43%). Nearly half (43%) recommended the use of topical antibiotics, whereas 24% advised patients to avoid antibiotic ointments. Handouts variably addressed scarring (36%), infection (72%), bleeding (69%), pain (66%), and lifestyle modifications (64%). CONCLUSION The instructions provided in dermatology patient handouts are highly variable, with various topical agents being recommended for wound healing. Topical antibiotics are not indicated for prophylaxis in clean dermatologic procedures but are still widely used. Greater efforts should be made to ensure that patients receive consistent and evidence-based wound care guidance. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea (OSA) and perioperative respiratory adverse events are significant risks for anaesthesia in children undergoing adenotonsillectomy. Upper airway collapse is a crucial feature of OSA that contributes to respiratory adverse events. A measure of upper airway collapsibility to identify undiagnosed OSA can help guide perioperative management. We investigated the utility of pharyngeal closing pressure (P CLOSE) for predicting OSA and respiratory adverse events. Children scheduled for elective adenotonsillectomy underwent in-laboratory polysomnography 2–12 weeks before surgery. P CLOSE measurements were obtained while the child was anaesthetised and breathing spontaneously just before surgery. Logistic regression was used to assess the predictive performance of P CLOSE for detecting OSA and perioperative respiratory adverse events after adjusting for potential covariates. In 52 children (age, mean [standard deviation] 5.7 [1.8] yr; 20 [38%] females), airway collapse during P CLOSE was observed in 42 (81%). Of these, 19 of 42 (45%) patients did not have OSA, 15 (36%) had mild OSA, and eight (19%) had moderate-to-severe OSA. All 10 children with no evidence of airway collapse during the P CLOSE measurements did not have OSA. P CLOSE predicted moderate-to-severe OSA (odds ratio [OR] 1.71; 95% confidence interval [CI]: 1.2–2.8; P =0.011). All children with moderate-to-severe OSA could be identified at a P CLOSE threshold of –4.0 cm H 2 O (100% sensitivity), and most with no or mild OSA were ruled out (64.7% specificity; receiver operating characteristic/area under the curve=0.857). However, there was no significant association between respiratory adverse events and P CLOSE (OR 1.0; 95% CI: 0.8–1.1; P =0.641). Measurement of P CLOSE after induction of anaesthesia can reliably identify moderate or severe OSA but not perioperative respiratory adverse events in children before adenotonsillectomy. ANZCTR ACTRN 12617001503314. [ABSTRACT FROM AUTHOR]

Various strategies exist to promote hemostasis and minimize bleeding complications after dermatologic procedures.[[1]] The choice of hemostatic method depends on the type of surgery, anatomic location, patient characteristics, maintenance requirements, and cost. Here, we present a novel technique that repurposes a medical examination glove to act as an effective pressure dressing on surgical wounds. The "balloon glove" was placed in the groin on top of the surgical wound on the scrotum (covered by a patch of hydrocolloid dressing) and held securely beneath the patient's undergarment. [Extracted from the article]

Background: Antibiotic resistance is a well‐known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains and might lead to underestimating antimicrobial resistance. This study aims to evaluate the susceptibility profile, the frequency of heteroresistance of H. pylori strains, and their effect on eradication success in a pediatric population. Materials and Methods: Children aged 2–17 years who underwent an upper gastrointestinal endoscopy from 2011 to 2019 with positive H. pylori status were included. Susceptibility was measured by disk diffusion and E‐test. The difference in susceptibility profiles between isolates from the antrum and the corpus was used to detect heteroresistance. For those who received eradication treatment, we evaluated eradication rate and factors affecting treatment success. Results: Inclusion criteria were met by 565 children. Strains susceptible to all antibiotics were detected in 64.2%. Primary resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), tetracyclin (TET), and amoxicillin (AMO) were 11%, 22.9%, 6.9%, 0.4%, and 0% and secondary resistance rates were 20.4%, 29.4%, 9.3%, 0%, and 0%. Heteroresistance was present in untreated children in 2%, 7.1%, 0.7%, 0.7%, and 0% for CLA, MET, LEV, TET, and AMO. First‐line eradication rates were 78.5% in intention‐to‐treat (ITT), 88.3% in full‐analysis‐set (FAS), and 94.1% in per‐protocol (PP). Factors affecting eradication success were the duration of treatment when the triple‐tailored treatment was used, the number of daily doses of amoxicillin administered, and the patient's adherence to treatment. Conclusions: This study shows the presence of relatively low primary resistance rates for H. pylori isolates but demonstrates the presence of heteroresistance in our population. Routine biopsies from the antrum and corpus must be considered for susceptibility testing to allow tailored treatments and increase eradication rates. Treatment success is affected by treatment choice, correct dosing of medications, and adherence. All these factors should be considered when evaluating the efficacy of an eradication regimen. [ABSTRACT FROM AUTHOR]

Objectives: Bowel resection is an important component of surgical management of women with advanced gynecologic malignancies. Real-time intraoperative assessment of anastomotic perfusion with indocyanine green fluorescence angiography (ICG-FA) is a recent technique that has been shown to effectively evaluate perfusion of large and small bowel anastomoses. The objective of this study was to capture national practice patterns, characterize facilitators and barriers to ICG-FA utilization for bowel perfusion assessment, and identify opportunities for further education across Canada. Methods: A needs assessment survey was developed with a focus group of key stakeholders in the field, as well as a methodologist, and piloted in advance to distribution. The survey captured basic sociodemographics, work history, facilitators and barriers to use of ICG-FA for bowel perfusion assessment, and modalities for further education (e.g., peer-reviewed article, surgical video, national/ international conference, local grand rounds, and invited experts for practical training). On July 1, 2021, the survey was distributed to 115 gynecologic oncologists registered through the Society of Gynecologic Oncology of Canada. Responses were collected until September 1, 2021. Results: The response rate was 31% (n =37), with respondents from all Canadian provinces. Approximately three-quarters (78%) of respondents identified as women, and the majority (60%) have been practicing gynecologic oncology for less than ten years. Of the respondents, 81% (n =30) performed bowel resection, and 67% (n =20) used ICG-FA for anastomotic perfusion assessment after bowel surgery. The three most reported barriers to integrating ICG-FA into routine clinical practice were the lack of training (30%), knowledge (27%), and equipment (27%). Surgical videos were the highest-ranked educational modality, followed by national/international conferences and peer- reviewed articles. Conclusions: ICG-FA for bowel perfusion assessment is a valuable tool that can be used with other risk-assessment strategies to guide operative decision-making in gynecologic oncology. However, further training across multiple educational modalities is needed to build knowledge among the Canadian gynecologic oncologic community, with surgical videos serving as the preferred educational modality. Additionally, more funding for necessary equipment will facilitate the uptake of this tool. This represents a national practice improvement opportunity. [ABSTRACT FROM AUTHOR]

Cannabis use by adolescents is widespread, but its effects on the ovaries remain largely unknown. Δ9-tetrahydrocannabinol (THC) exerts its pharmacological effects by activating, and in some conditions hijacking, cannabinoid receptors (CBRs). We hypothesized that adolescent exposure to THC affects ovarian function in adulthood. Peripubertal female C57BL/6N mice were given THC (5 mg/kg) or its vehicle, once daily by intraperitoneal injection. Some mice received THC from postnatal day (PND) 30–33 and their ovaries were harvested PND34; other mice received THC from PND30–43, and their ovaries were harvested PND70. Adolescent treatment with THC depleted ovarian primordial follicle numbers by 50% at PND70, 4 weeks after the last dose. The treatment produced primordial follicle activation, which persisted until PND70. THC administration also caused DNA damage in primary follicles and increased PUMA protein expression in oocytes of primordial and primary follicles. Both CB1R and CB2R were expressed in oocytes and theca cells of ovarian follicles. Enzymes involved in the formation (N-acylphosphatidylethanolamine phospholipase D) or deactivation (fatty acid amide hydrolase) of the endocannabinoid anandamide were expressed in granulosa cells of ovarian follicles and interstitial cells. Levels of mRNA for CBR1 were significantly increased in ovaries after adolescent THC exposure, and upregulation persisted for at least 4 weeks. Our results support that adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Relevance of these findings to women who frequently used cannabis during adolescence warrants investigation. [ABSTRACT FROM AUTHOR]

L8004 --> 925.15 --> INTRODUCTION: Stanford's Division of Clinical Anatomy offered a virtual, week‐long Clinical Anatomy Summer Program (CASP) to pre‐health students interested in learning clinical anatomy, enabling the exploration of Virtual Reality (VR) as a supplemental teaching and learning modality. Students attended lectures, clinical case presentations, and hour‐long VR lab demonstrations featuring anatomical models via Engage platform. Students were provided support with setup, operation, and troubleshooting of Oculus Quest 1 headsets and the Engage application. The goal of this study is to evaluate the effectiveness of VR in anatomy teaching, understand the impact VR may have on the overall quality of the learning experience, and assess potential drawbacks to the usage of VR technology as a teaching tool. METHODS: Data was collected from anonymous survey responses of CASP 2020 students via Qualtrics. VR specific questions asked the students to rate various aspects of their VR experience using the 7‐point Likert scale with answers ranging from "Strongly Disagree" to "Strongly Agree." A series of short answer questions were also asked to obtain further insight on the overall VR experience. RESULTS: The CASP 2020 survey yielded a response rate of 68.75% (n=44). A Chi‐Square Goodness of Fit Test, X2(6, n=44) = 9.76, p=.045, confirmed expectations that the majority of respondents would agree that VR was an overall positive experience. 57% of students strongly agreed that VR was a positive learning experience. 62% of students found VR to overall be somewhat good, with 34% of respondents specifically mentioning they liked the 3D spatial visualization benefit of VR. Some students experienced negative symptoms upon use of the technology, with 20% reporting nausea, motion sickness, and/or headache. 46% chose VR as the element of the program that contributed least to their learning, with other programmatic elements garnering more favor, like surgical demonstration videos and hands‐on activities. CONCLUSIONS: The majority of CASP 2020 respondents had a positive experience with VR and recognized its benefits as a virtual learning modality, with specific mention of the ability to spatially visualize and interact with VR anatomical models. Our survey results show that VR may not contribute any more understanding of the material than traditional resources such as lectures and live demonstrations. The first iteration of this VR technology in CASP highlighted the need for improvements related to connectivity, audio, graphics, and setup instructions. Major improvements to VR were made for CASP 2021, and we expect to see this reflected in the CASP 2021 survey results. SIGNIFICANCE: VR technology has strong potential as a supplemental teaching and learning tool in anatomy education. Immersion in the VR space lends itself well to the spatial visualization of anatomical structures because models can be manipulated to become larger than life, rotated to any angle, and peered into to show internal structures. Further evaluation of VR technology in anatomy education will illuminate the improvements necessary for implementation in higher education and its effectiveness in improving students' ability to identify structures on cadaveric specimens. [ABSTRACT FROM AUTHOR]

R2027 --> 837.8 --> Adrenocorticotropic hormone (ACTH) is secreted from the pituitary gland and selectively activates the melanocortin type 2 receptor (MC2R) in the adrenal glands, where it modulates steroidal hormone (e.g., cortisol) synthesis and secretion. Excess ACTH contributes to the pathophysiology of Cushing's disease (CD), ectopic ACTH syndrome (EAS), and congenital adrenal hyperplasia (CAH). ACTH‐secreting tumors cause CD (in pituitary) and EAS (outside pituitary) and lead to hypercortisolemia and various metabolic comorbidities. CAH is caused by inactivating mutations in adrenal steroid synthesis pathway proteins leading to low levels of cortisol that are insufficient to provide negative feedback on ACTH production. Chronic ACTH elevation can lead to life‐threatening salt wasting and significant virilization. We hypothesize that blocking the ACTH‐MC2R interaction with a selective MC2R antagonist may provide a key new therapeutic option for these patients. We initiated an iterative medicinal chemistry program to identify potent and selective nonpeptide MC2R antagonists suitable for evaluation in clinical trials. Initial assessment consisted of equilibrium radioligand binding competition assays using [125I]ACTH(1‐39) to determine Ki and EC50 shift functional assays using ACTH(1‐24) to determine ΔpEC50 values. Select compounds were then characterized using a full Schild regression analysis to determine KB values and gain insight into mechanism. There was a strong correlation between the Ki and KB values for this class of small molecule. Our efforts identified CRN04894 as a highly potent MC2R antagonist (Ki = 2.1 nM, KB = 0.34 nM). The Schild regression data for CRN04894 was consistent with a competitive, orthosteric interaction with ACTH. The individual ACTH dose‐response curves with the addition of different concentrations of CRN04894 showed the same maximum response and slopes near unity, and the Schild plot had a slope not statistically different than unity. Furthermore, CRN04894 did not affect the dissociation rate of [125I]ACTH(1‐39) initiated by a saturating concentration of ACTH(1‐39), also consistent with an orthosteric interaction. Because CRN04894 appeared to bind the orthosteric site on MC2R, it was further tested in a kinetic radioligand binding competition assay using [125I]ACTH(1‐39) to determine its binding rate constants. CRN04894 rate constants are comparable to published values for other GPCR ligands with kon = 1.2 e7 M‐1 min‐1 and koff = 0.018 min‐1, corresponding to a dissociation t1/2of 39 min. The kinetic Ki (1.5 nM) calculated from the kon and koff is in accordance with the equilibrium competition binding Ki and Schild analysis KB. In addition, CRN04894 selectively blocks the ACTH‐MC2R interaction, showing no binding to MC1R, MC3R, MC4R, and MC5R at concentrations ≥ 1 µM. To our knowledge, this class of molecule represents the first reported potent nonpeptide MC2R antagonists, and CRN04894 is currently being evaluated in a first‐in‐human phase 1 clinical trial evaluating pharmacokinetics, pharmacodynamics, and tolerability in healthy subjects. [ABSTRACT FROM AUTHOR]

Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged 1 to 12 months. In this article, we review risk factors that may predispose infants to increased vulnerability. Maternal characteristics, including nonmodifiable and modifiable factors, antenatal medical conditions, labor and delivery events, and infant characteristics, are reviewed, with the purpose of helping obstetric care providers target risk reduction efforts. We have reviewed over 85 case-control, retrospective, and prospective cohort studies published between 1975 and 2011. Major modifiable risk factors include maternal and paternal smoking, drug use, alcohol use, and insufficient prenatal care. Infants at increased risk include males, premature infants, infants of low birth weight or growth-restricted infants, and infants in multiple gestations. By targeting modifiable and nonmodifiable risk factors, it may be possible to decrease the incidence of SIDS. Efforts should be put on decreasing high-risk behaviors and encouraging sufficient antenatal follow-up. In view of recent increases in ethnic and social disparity with SIDS, it is essential that risk reduction guidelines, which have recently been expanded by the American Association of Pediatrics, be explained in a culturally sensitive manner. [ABSTRACT FROM AUTHOR]

This study examined the relationship between academic preparation and post-secondary educational outcomes. To uncover the factors that influence secondary-level school course-taking patterns and outcomes, multi-level modelling was conducted using data from a nationally representative sample of US secondary-level school students from the Education Longitudinal Study of 2002. Results indicated (1) significant effects from student, family and school predictors on course-taking patterns and (2) significant effects from course-taking patterns on enrollment in post-secondary institution types with math course-taking pattern having the largest impact. Implications for educators and administrators are discussed. [ABSTRACT FROM AUTHOR]

Highlights from the article: The ability of anti-HLA antibodies to recognize their cognate antigen involves several physiological properties. Antibody (Ab) binding can be influenced by small sequence alterations within an epitope as well as motifs distant to the perceived epitope binding site. Since the peptide composition of HLA molecules present on the vasculature is unknown, our preliminary data suggest that some anti-HLA antibodies may be non-reactive with SABs leading to a false assumption of HLA Ab-Negative AMR.

In response to COVID-19, mental health clinics transitioned to telehealth to maintain psychotherapy delivery. Community mental health (CMH) settings, which are often under-resourced, likely experienced many barriers. This study examined CMH clinicians' experiences transitioning to telehealth. Data came from a state-funded initiative training CMH clinicians in cognitive behavioral therapy. Participants (N = 197) completed pre-training and post-consultation surveys which included questions about their experiences with telehealth. Most clinicians found telehealth beneficial and effective. Clinicians strongly endorsed wanting telehealth as an option even after in-person services resume. CMH clinicians rated "engaging younger children" as the most significant barrier to telehealth. Despite some telehealth barriers, clinicians generally viewed telehealth favorably and prefer having it as a long-term option. Future work should continue to understand when telehealth may be advantageous and for whom in order to improve the accessibility and quality of behavioral health services. [ABSTRACT FROM AUTHOR]

Myocardial injury after noncardiac surgery (MINS) is a common occurrence, with an estimated incidence of 12% to 24%. The majority of patients do not exhibit symptoms or electrocardiographic changes, making the condition difficult to detect without measuring troponin levels. MINS is associated with increased morbidity and mortality, and within 16 months, 1 in 6 patients with MINS will experience a major vascular complication. High-risk patients undergoing noncardiac surgery should have routine troponin measurement, and early identification allows for prompt management. All patients with MINS, regardless of symptoms, should receive secondary prevention, including acetylsalicylic acid, statin, and lifestyle modification. [Extracted from the article]

Patients with a propensity for upper airway obstruction, including those with obstructive sleep apnea (OSA), are vulnerable in the perioperative period. The P SB CLOSE sb measurement method and its potential clinical utility in adults have been described.[3] However, the feasibility of obtaining perioperative measurement of P SB CLOSE sb in children under anesthesia is unknown. P SB CLOSE sb measurements were performed at two separate perioperative phases: following anesthesia induction (Pre-procedure P SB CLOSE sb ) and emergence from anesthesia (Post-procedure P SB CLOSE sb ). [Extracted from the article]

Abstract: Trichosporonosis is a rare, life‐threatening, opportunistic fungal infection that affects immunocompromised individuals with neutropenia, particularly those with underlying hematologic malignancies. We present the case of a 10‐year‐old boy with acute lymphoblastic leukemia who developed a diffuse, morbilliform eruption in the setting of fever and pancytopenia. He was found to have Trichosporon asahii fungemia with widespread visceral dissemination, and his condition rapidly deteriorated despite treatment. It is important to consider trichosporonosis in the evaluation of a critically ill individual with neutropena and a rash, because the initial cutaneous presentation may appear benign and delayed therapy results in death. [ABSTRACT FROM AUTHOR]

Young women in Australia disproportionately experience unintended pregnancy and sexually transmissible infections (STIs). As the promotion of highly effective pregnancy prevention methods such as long-acting reversible contraception (LARC) increases, concurrent use of condoms with LARC remains optimal for pregnancy and STI prevention. There is little data exploring condom use behaviour in young Australian women using LARC. In this qualitative study we interviewed twenty women using LARC about their experiences of making decisions regarding condom use. We used inductive thematic analysis to identify factors influencing participant decision-making. We found that while LARC had an impact on condom use and sexual practices, decisions regarding condom use were influenced by multiple factors including mood, menstrual changes related to LARC, and relationship dynamics. Participants' views of 'safe sex' extended beyond pregnancy and STI protection, to include desired outcomes such as pleasure, consent and communication. Access to STI testing and treatment was key to how participants managed STI risk. Findings highlight the need for a more comprehensive approach to safer sex health promotion, and the importance of ensuring STI testing and treatment services continue to be available and accessible to all young people. [ABSTRACT FROM AUTHOR]

Immune-stimulatory ligands, such as major histocompatibility complex molecules and the T-cell costimulatory ligand CD86, are central to productive immunity. Endogenous mammalian membrane-associated RING-CHs (MARCH) act on these and other targets to regulate antigen presentation and activation of adaptive immunity, whereas virus-encoded homologs target the same molecules to evade immune responses. Substrate specificity is encoded in or near the membraneembedded domains of MARCHs and the proteins they regulate, but the exact sequences that distinguish substrates from nonsubstrates are poorly understood. Here, we examined the requirements for recognition of the costimulatory ligand CD86 by two different MARCH-family proteins, human MARCH1 and Kaposi's sarcoma herpesvirus modulator of immune recognition 2 (MIR2), using deep mutational scanning. We identified a highly specific recognition surface in the hydrophobic core of the CD86 transmembrane (TM) domain (TMD) that is required for recognition by MARCH1 and prominently features a proline at position 254. In contrast, MIR2 requires no specific sequences in the CD86 TMD but relies primarily on an aspartic acid at position 244 in the CD86 extracellular juxtamembrane region. Surprisingly, MIR2 recognized CD86 with a TMD composed entirely of valine, whereas many different single amino acid substitutions in the context of the native TM sequence conferred MIR2 resistance. These results show that the human and viral proteins evolved completely different recognition modes for the same substrate. That some TM sequences are incompatible with MIR2 activity, even when no specific recognition motif is required, suggests a more complicated mechanism of immune modulation via CD86 than was previously appreciated. [ABSTRACT FROM AUTHOR]

Background: Skin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/design: CURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.Discussion: LED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial Registration: ClinicalTrials.gov, NCT03795116 . Registered on 20 December 2018. [ABSTRACT FROM AUTHOR]

Home-based photobiomodulation is a popular treatment modality for patients seeking non-invasive aesthetic treatment. Studies demonstrate that photobiomodulation is effective for skin rejuvenation, which is aimed at improving the overall appearance of the skin by reducing fine lines and wrinkles and improving skin texture, skin tone, and dyspigmentation. Most current skin rejuvenation research focuses on treatments in women. However, men's aesthetics remains an underserved market. A combined red light (RL) and near-infrared (NIR) light-emitting diode (LED) has been designed specifically to target male skin, which may have different physiological and biophysical properties compared to female skin. Herein, the safety and efficacy of a commercially available RL and NIR (633, 830, and 1072 nm) LED array designed to be worn as a face mask was assessed. Primary outcomes included adverse events and facial rejuvenation as determined by participant-reported satisfaction scales and quantitative digital skin photography and computer analysis after 6 weeks of treatment. The participants reported overall favorable results and improvements in all individual categories, were satisfied with the treatment, and would recommend the product to others. The participants perceived the greatest improvement in fine lines and wrinkles, skin texture, and youthful appearance. Photographic digital analysis demonstrated favorable improvements in wrinkles, UV spots, brown spots, pores, and porphyrins. These results support the use of RL and NIR to treat male skin. Advantages of the LED facemask include its safety, efficacy, convenient home-based use, minimal associated downtime, simple operation, non-invasiveness, and appreciable results in as few as 6 weeks. [ABSTRACT FROM AUTHOR]

This article from the Canadian Medical Association Journal discusses the use of hormone therapy in menopausal patients with a history of gynecologic cancer. It highlights the potential benefits of hormone therapy for managing vasomotor symptoms and the increased risks of cardiovascular disease, osteoporosis, and mood and cognition difficulties associated with loss of ovarian function due to cancer treatment. The article recommends systemic estrogen therapy for patients with non-hormone-sensitive cancers, with consultation with the oncology team, and suggests local hormone therapy options for select patients. It also provides guidelines for the use of hormone therapy in patients with specific types of gynecologic cancer, such as cervical and endometrial cancer, and emphasizes the importance of individualized treatment duration. [Extracted from the article]

Hepatitis B virus (HBV) infection is endemic in West Africa. There has been a significant increase in the Bronx West African (WA) community. To achieve HBV elimination, vaccination of non-immune individuals is important. Unfortunately, vaccine uptake in immigrant populations is at this time very limited. An educational program was conducted by medical providers of WA origin in collaboration with local faith-based organizations, after which free HBV screening was offered. Non-immune individuals were initially recommended to contact their medical provider or referred to the Department of Health for vaccination. Beginning in 2021, the program offered vaccination. A questionnaire including reasons for vaccination in the program was offered. Among the first 500 individuals screened, 34.6 % required vaccination. Among those screened before program vaccine availability, 72.2 % initiated the vaccination series, with 38.2 % obtaining it at an outside setting and 34 % returning when available through the program. Among patients screened after program vaccine availability, 92.1 % initiated the series. Of those receiving vaccination in the program and completing the questionnaire, 70.7 % had access to care but chose vaccination by the program because of the trust instilled by WA personnel. Our findings demonstrate the effectiveness of integrating vaccination into an HBV screening program for an immigrant population. It emphasizes the importance of timeliness and cultural sensitivity. [ABSTRACT FROM AUTHOR]

People are widely exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP). Prior studies showed that prenatal exposure to BaP depletes germ cells in ovaries, causing earlier onset of ovarian senescence post-natally; developing testes were affected at higher doses than ovaries. Our primary objective was to determine if prenatal BaP exposure results in transgenerational effects on ovaries and testes. We orally dosed pregnant germ cell-specific EGFP-expressing mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5–11.5 (F1 offspring) or E6.5–15.5 (F2 and F3). Ovarian germ cells at E13.5 and follicle numbers at postnatal day 21 were significantly decreased in F3 females at all doses of BaP; testicular germ cell numbers were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Next, we compared the ovarian effects of 2 mg/kg-day BaP dosing to wild type C57BL/6J F0 dams from E6.5–11.5 or E12.5–17.5. We observed no effects on F3 ovarian follicle numbers with either of the shorter dosing windows. Our results demonstrate that F0 BaP exposure from E6.5–15.5 decreased the number of and partially disrupted transcriptomic sexual identity of female germ cells transgenerationally. [ABSTRACT FROM AUTHOR]

Historically, children and adolescents who identify as Black, Indigenous, and other people of Color (BIPOC) have had inequitable access to mental healthcare, and research shows that they are significantly less likely than their white American counterparts to utilize available services. Research identifies barriers that disproportionately impact racially minoritized youth; however, a need remains to examine and change systems and processes that create and maintain racial inequities in mental health service utilization. The current manuscript critically reviews the literature and provides an ecologically based conceptual model synthesizing previous literature relating to BIPOC youth barriers for service utilization. The review emphasizes client (e.g. stigma, system mistrust, childcare needs, help seeking attitudes), provider (e.g. implicit bias, cultural humility, clinician efficacy), structural/organizational (clinic location/proximity to public transportation, hours of operation, wraparound services, accepting Medicaid and other insurance-related issues), and community (e.g. improving experiences in education, the juvenile criminal-legal system, medical, and social service systems) factors that serve as barriers and facilitators contributing to disparities in community mental health service utilization for BIPOC youth. Importantly, we conclude with suggestions for dismantling inequitable systems, increasing accessibility, availability, appropriateness, and acceptability of services, and ultimately reducing disparities in efficacious mental health service utilization for BIPOC youth. [ABSTRACT FROM AUTHOR]

A moving porous media (MPM) modeling methodology was developed for reactor-scale CFD simulations of continuous spatial particle atomic layer deposition (ALD). The continuous vibrating reactor process for particle atomic layer deposition (CVR-ALD) was modeled by treating the powder bed as a porous media which conveys as a sliding and layering dynamic mesh zone inside the vibrating reactor zone. Candidate porous reactor baseplates were experimentally characterized using x-ray computed tomography (XRCT), porometry, porosimetry, and atomic force microscopy (AFM) before permeabilities from flow tests were used as inputs to the MPM model. Parameter sweeps over vibration magnitude, powder bed convection speed, and precursor mass fraction revealed the dependence of surface titration uniformity and residual gas breakthrough on operating conditions and powder properties. Parasitic chemical vapor deposition (CVD) reactions were observed in the first precursor zone when dose start times and inlet gas compositions were not optimized. [Display omitted] • A moving porous media model was developed for continuous spatial particle ALD. • Powder bed convection was simulated using the dynamic mesh method. • Optimal inlet precursor mass fraction was quantified using excess number. • CVD reactions were observed in the first precursor zone. [ABSTRACT FROM AUTHOR]

Docosahexaenoic acid (DHA, 22:6n-3) is exclusively utilized in fast signal processing tissues such as retinal, neural and cardiac. N-3 docosapentaenoic acid (n-3DPA, 22:5n-3), with just one less double bond, is also found in the marine food chain yet cannot substitute for DHA. Gradient temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry (DSC) to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS and both conventional and modulated DSC to n-3DPA and DHA from −100 to 20 °C. Three-dimensional data arrays with 0.2 °C increments and first derivatives allowed complete assignment of solid, liquid and transition state vibrational modes. Melting temperatures n-3DPA (−45 °C) and DHA (−46 °C) are similar and show evidence for solid-state phase transitions not seen in n-6DPA (−27 °C melt). The C6H2 site is an elastic marker for temperature perturbation of all three lipids, each of which has a distinct three dimensional structure. N-3 DPA shows the spectroscopic signature of saturated fatty acids from C1 to C6. DHA does not have three aliphatic carbons in sequence; n-6DPA does but they occur at the methyl end, and do not yield the characteristic signal. DHA appears to have uniform twisting from C6H2 to C12H2 to C18H2 whereas n-6DPA bends from C12 to C18, centered at C15H2. For n-3DPA, twisting is centered at C6H2 adjacent to the C2-C3-C4-C5 aliphatic moiety. These molecular sites are the most elastic in the solid phase and during premelting. [ABSTRACT FROM AUTHOR]

Cancer cells survive chemotherapy and cause lethal relapse by entering a senescent state that facilitates expression of many phagocytosis/macrophage-related genes that engender a novel cannibalism phenotype. We used biosensors and live-cell imaging to reveal the basic steps and mechanisms of engulfment by senescent human and mouse tumor cells. We show filamentous actin in predator cells was localized to the prey cell throughout the process of engulfment. Biosensors to various phosphoinositide (PI) species revealed increased concentration and distinct localization of predator PI(4) P and PI(4,5)P2 at the prey cell during early stages of engulfment, followed by a transient burst of PI(3) P before and following internalization. PIK3C2B, the kinase responsible for generating PI(3)P, was required for complete engulfment. Inhibition or knockdown of Clathrin, known to associate with PIK3C2B and PI(4,5)P2, severely impaired engulfment. In sum, our data reveal the most fundamental cellular processes of senescent cell engulfment, including the precise localizations and dynamics of actin and PI species throughout the entire process. This study shows that in response to chemotherapy treatment, breast cancer cells that enter a state of cellular senescence employ specific phosphoinositide kinases, actin networks and clathrin to cannibalize and digest neighboring cells, thus accessing nutrients and promoting survival. [ABSTRACT FROM AUTHOR]

Frailty is increasingly recognized as a predictor of postoperative morbidity and oncologic outcomes. Evidence of the predictive value of frailty assessment in gynecologic oncology remains sparse. To evaluate the National Surgical Quality Improvement Program (NSQIP) comorbidity-based modified Frailty Index-5 (mFI-5) as predictor of severe postoperative complications, non-completion of chemotherapy and other patient-centered outcomes in gynecologic oncology patients >70 years-old undergoing surgery. Prospectively-collected NSQIP data and retrospective chart review of patients undergoing elective laparotomies for gynecologic malignances at a tertiary academic center in Ontario, Canada, between 01/2016–09/2020 were reviewed. Primary outcome was rate of 30-day Clavien-Dindo (Clavien) grade III-V complications. Secondary outcomes included Clavien II-V complications, postoperative length of stay (LOS), non-home discharge and non-completion of chemotherapy. Logistic regression analyses and receiver-operator curves were performed. Two-hundred and fifty-nine patients were included; 103 were planned to receive adjuvant chemotherapy. Fifty-three patients (20.5%) had an mFI ≥ 2 and were categorized as frail. On multivariable analyses, frailty independently predicted grade III-V complications (OR 24.49, 95%CI 9.72–70.67, p < 0.0001), grade II-V complications (OR 4.64, 95%CI 2.31–9.94, p < 0.0001), non-home discharge (OR 7.37, 95%CI 2.81–20.46, p < 0.0001), LOS ≥ 7d (OR 3.6, 95% CI 1.54–8.6, p = 0.003) and non-completion of chemotherapy (OR 8.42, 95%CI 2.46–32.79, p = 0.001). Adjusted C-statistics demonstrated strong predictive value of the mFI-5 for grade III-V (0.92, 95%CI 0.86–0.97) and grade II-V (0.74, 95%CI 0.68–0.8) complications as well as non-home discharge (0.86, 95%CI 0.78–0.95) and chemotherapy non-completion (0.87, 95%CI 0.8–0.95). Frailty as assessed with the mFI-5 predicted adverse postoperative and chemotherapy outcomes in gynecologic oncology patients aged ≥70 undergoing a laparotomy. The mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification. • The mFI-5 predicts postoperative morbidity, chemotherapy non-completion, and non-home discharge in Gynecologic Oncology. • The mFI-5 is brief, objective and easily applied in a clinical setting. • Early frailty assessment may support tailored risk assessment and clinical decision-making. [ABSTRACT FROM AUTHOR]

De novo-designed receptor transmembrane domains (TMDs) present opportunities for precise control of cellular receptor functions. We developed a de novo design strategy for generating programmed membrane proteins (proMPs): single-pass α-helical TMDs that self-assemble through computationally defined and crystallographically validated interfaces. We used these proMPs to program specific oligomeric interactions into a chimeric antigen receptor (CAR) that we expressed in mouse primary T cells and found that both in vitro CAR T cell cytokine release and in vivo antitumor activity scaled linearly with the oligomeric state encoded by the receptor TMD, from monomers up to tetramers. All programmed CARs stimulated substantially lower T cell cytokine release relative to the commonly used CD28 TMD, which we show elevated cytokine release through lateral recruitment of the endogenous T cell costimulatory receptor CD28. Precise design using orthogonal and modular TMDs thus provides a new way to program receptor structure and predictably tune activity for basic or applied synthetic biology. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of a 10‐day quadruple therapy containing colloidal bismuth sub‐citrate (CBS), esomeprazole (ESO), amoxicillin (AMO), and metronidazole (MET) for Helicobacter pylori (H. pylori) eradication in children. Methods: Monocentric, open‐label, prospective, single‐arm clinical trial in children aged 6–17 years with H. pylori infection. The study was carried out on consecutive patients with upper gastrointestinal symptoms and H. pylori infection confirmed by histology and culture of gastric biopsies. The outcome was evaluated using a 13C‐urea breath test 8–10 weeks post‐therapy. Adverse events and compliance were evaluated by daily journal and pill counting. Results: A total of 36 children fulfilling the inclusion criteria were enrolled. Eight (22.2%) of them had a prior H. pylori eradication treatment. Thirteen (36.1%) patients were infected by a strain resistant to MET and 8 (22.2%) by a strain resistant to both MET and Clarithromycin (CLA). In the intention‐to‐treat population (ITT), eradication was achieved in35/36patients (95%CI: 85%−99%). Twenty‐three children reported at least one adverse event (63.8%), mostly mild (nausea, vomiting, abdominal pain, diarrhea, dark stool, metallic taste, headache, and rash). The compliance rate was high, with 30 (83.3%) patients taking >90% of the treatment. Conclusion: 10‐day quadruple therapy containing CBS, ESO, AMO, and MET for H. pylori eradication in children is a safe and very effective solution, especially for previously treated patients and those infected with double resistant strains. [ABSTRACT FROM AUTHOR]

The mechanism of helix stabilization or destabilization by different amino acids has been the subject of several experimental and theoretical studies; these studies suggest that large or bulky side chains may modulate helix stability by altering the hydration of the helix backbone. In this paper, we report a spectroscopic study to determine the effect of alanine to leucine substitutions on the conformation and solvation of specific segments of a model helical peptide. A 25-residue, alanine-rich, helical peptide [Ac-(AAAAK)[sub 4]-AAAAY-NH[sub 2] (AKA)] and its two leucine variants [Ac-LLLLK-(AAAAK)[sub 3]-AAAAYNH[sub 2] (LKA) and Ac-(AAAAK)[sub 4]-LLLLY-NH[sub 2] (AKL)] were characterized by infrared (IR) and electronic circular dichroism (ECD) spectroscopies. Introduction of [sup l3]C isotopes into specific, consecutive, backbone carbonyls for certain blocks of each of the peptides mentioned above allows the IR spectra to be interpreted in terms of the conformation and solvation of specific residues within the helix. These isotope-edited IR spectra of the leucine peptides do not show evidence of a decrease in the degree of backbone solvation compared to the alanines, but suggest that the peptide may adopt a distorted conformation to accommodate the larger leucine side chains at the N-terminus. These experiments demonstrate the power of isotopeedited IR in dissecting subtle changes in helix conformation at the residue level. [ABSTRACT FROM AUTHOR]

SUMMARY: Sex differences and evolutionary differences are critical biological issues. Ginkgo is an ancient lineage of dioecious gymnosperms with special value for studying the mechanism of sex determination in plants. However, the major genetic basic underlying sex chromosomes remains to be uncovered. In this study, we identify the sex‐determining region of Ginkgo and locate it to the area from megabases 48 to 75 on chromosome 2. We find that the male sex‐determining region of Ginkgo contains more than 200 genes, including four MADS‐box genes, demonstrating that the Ginkgo sex determination system is of the XY type. We also find that genetic sex differences result in specialized flavonoid metabolism and regulation in each sex. These findings establish a foundation for revealing the molecular mechanism of sexual dimorphism and promoting the development of the Ginkgo industry. [ABSTRACT FROM AUTHOR]