The skin is the first line of defense against the environment, with the epidermis as the outermost tissue providing much of the barrier function. Given its direct exposure to and encounters with the ...environment, the epidermis must evolve to provide an optimal barrier for the survival of an organism. Recent advances in genomics have identified a number of genes for the human skin barrier that have undergone evolutionary changes since humans diverged from chimpanzees. Here, we highlight a selection of key and innovative genetic findings for skin barrier evolution in our divergence from our primate ancestors and among modern human populations.
In the 20 years since the American College of Surgeons outlined the first research agenda for surgical palliative care, there has been immense growth in the evidence. In this article, we briefly ...review the state of the science and priority research areas in surgical palliative care.
The genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in ...diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.
ABSTRACT
BACKGROUND
Leaders in academic medicine are often selected from the ranks of physician-researchers, whose demanding careers involve multiple professional commitments that must also be ...balanced with demands at home.
OBJECTIVE
To gain a more nuanced understanding of work–life balance issues from the perspective of a large and diverse group of faculty clinician-researchers and their mentors.
DESIGN
A qualitative study with semi-structured, in-depth interviews conducted from 2010 to 2011, using inductive analysis and purposive sampling.
PARTICIPANTS
One hundred former recipients of U.S. National Institutes of Health (NIH) K08 or K23 career development awards and 28 of their mentors.
APPROACH
Three researchers with graduate training in qualitative methods conducted the interviews and thematically coded verbatim transcripts.
KEY RESULTS
Five themes emerged related to work–life balance: (1) the challenge and importance of work–life balance for contemporary physician-researchers, (2) how gender roles and spousal dynamics make these issues more challenging for women, (3) the role of mentoring in this area, (4) the impact of institutional policies and practices intended to improve work–life balance, and (5) perceptions of stereotype and stigma associated with utilization of these programs.
CONCLUSIONS
In academic medicine, in contrast to other fields in which a lack of affordable childcare may be the principal challenge, barriers to work–life balance appear to be deeply rooted within professional culture. A combination of mentorship, interventions that target institutional and professional culture, and efforts to destigmatize reliance on flexibility (with regard to timing and location of work) are most likely to promote the satisfaction and success of the new generation of clinician-researchers who desire work–life balance.
Nomenclature in Palliative Surgery Kopecky, Kimberly E.; Strong, Erin A.; Pellizzeri, Katherine F.
The American surgeon,
05/2023, Letnik:
89, Številka:
5
Journal Article
Recenzirano
Surgical palliative care, palliative care interventions, and palliative surgery all reference a blend of these 2 sub-specialty fields. Despite prior published definitions, use of these phrases both ...clinically and in the literature is varied and can lead to confusion and misunderstanding. Herein, we proposed the adoption of standardized nomenclature to guide the consistent use of these phrases.
To understand frontline ICU clinician's perceptions of end-of-life care delivery in the ICU.
Qualitative observational cross-sectional study.
Seven ICUs across three hospitals in an integrated ...academic health system.
ICU clinicians (physicians critical care, palliative care, advanced practice providers, nurses, social workers, chaplains).
None.
In total, 27 semi-structured interviews were conducted, recorded, and transcribed. The research team reviewed all transcripts inductively to develop a codebook. Thematic analysis was conducted through coding, category formulation, and sorting for data reduction to identify central themes. Deductive reasoning facilitated data category formulation and thematic structuring anchored on the Systems Engineering Initiative for Patient Safety model identified that work systems (people, environment, tools, tasks) lead to processes and outcomes. Four themes were barriers or facilitators to end-of-life care. First, work system barriers delayed end-of-life care communication among clinicians as well as between clinicians and families. For example, over-reliance on palliative care people in handling end-of-life discussions prevented timely end-of-life care discussions with families. Second, clinician-level variability existed in end-of-life communication tasks. For example, end-of-life care discussions varied greatly in process and outcomes depending on the clinician leading the conversation. Third, clinician-family-patient priorities or treatment goals were misaligned. Conversely, regular discussion and joint decisions facilitated higher familial confidence in end-of-life care delivery process. These detailed discussions between care teams aligned priorities and led to fewer situations where patients/families received conflicting information. Fourth, clinician moral distress occurred from providing nonbeneficial care. Interviewees reported standardized end-of-life care discussion process incorporated by the people in the work system including patient, family, and clinicians were foundational to delivering end-of-life care that reduced both patient and family suffering, as well as clinician moral distress.
Standardized work system communication tasks may improve end-of life discussion processes between clinicians and families.
Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the ...roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC.
A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival.
Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5).
Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection.
•Advanced peritoneal carcinomatosis (PC) can cause debilitating symptoms.•To benefit patients, palliative surgery must be safe in terms of morbidity and mortality and effective in terms of symptom relief.•In highly selected patients, palliative CRS and/or HIPEC can offer durable symptom relief.•Important factors in patient selection include patient factors, disease characteristics, and operative approach.
Screening guidelines in patients with inherited endocrine syndromes and others at high risk for developing endocrine cancers have significant implications as early tumor detection is associated with ...improved outcomes. Given the unique challenges in diagnosis and treatment, patients at high risk for developing endocrine cancers require multidisciplinary care. The complexity of decision making and rarity of these syndromes support referral to high‐volume centers with the experience and knowledge to treat these at‐risk patients.
Management of multisite colorectal metastases is expanding to make curative resection possible for more patients who present with advanced disease. Patient selection, tumor biology, meticulous ...surgical technique, and thoughtful perioperative care are essential to extending the benefit to patients previously treated with palliative goals of care.
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