Oncoplastic Breast Reconstruction in Morbidly Obese Patients: An Acceptable Practice.

Background: Breast cancer is the most common noncutaneous malignancy amongst women. Lumpectomy with adjuvant radiation is a mainstay of surgical treatment. Oncoplastic breast reconstruction reduces the resultant breast deformity. Obesity is a risk factor for the development of complications after breast reconstruction. This study's purpose was to determine if oncoplastic breast reconstruction is a safe procedure in obese patients. Methods: A single institution retrospective chart review was performed on women undergoing oncoplastic breast reduction from 2009 to 2021. Patients were then divided into groups based on body mass index (BMI). A statistical analysis was performed comparing rates of complications and time to adjuvant therapy. Results: An estimated 340 patients were identified with an average age of 56.2 years (140 with BMI <30 kg/m2, 87 with BMI 30-34.9 kg/m2, 62 with BMI 35-39.9 kg/m2, and 51 with BMI >40 kg/m2). There was a significant difference between the BMI greater than 40 kg per m2 and BMI less than 30 kg per m2 group in the number of returns to the operating room (P = 0.0096), major complications (P = 0.0002), and minor complications (P = 0.0051). Average time to adjuvant treatment was 47 days and there was no statistically significant difference between the groups (P = 0.1691). Conclusions: There was a significant difference in major and minor complications between the BMI groups; however, there was no delay in the time to adjuvant therapy. Therefore, we conclude that with appropriate counseling on surgical risks, oncoplastic breast reduction is an acceptable option for breast cancer patients after lumpectomy, regardless of BMI.

Longitudinal Olfactory Patterns in Multiple Sclerosis: A Scoping Review and Implication for Use in Management of Disease.

BACKGROUND: Although studies regarding multiple sclerosis (MS) and olfactory dysfunction (OD) have been previously described and summarized, there is not a sole review of longitudinal studies regarding the matter. This review examines the existing literature investigating MS and its effect on olfaction. In addition, the role of OD in the diagnosis and prognosis of MS is explored. METHODS: A scoping review of the literature was performed covering longitudinal studies investigating MS and OD. Systematic searches of PubMed, Google Scholar, Web of Science, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, AgeLine, and MEDLINE were performed using terms that encompassed MS and olfaction. The aim of this review was to build on the existing literature by summarizing only findings that were demonstrated longitudinally. RESULTS: Of 6938 articles identified from the search, 9 met the inclusion criteria: longitudinal observation of relapsing-remitting or progressive MS. Olfaction was measured and scored using various testing arrays, and these scores were then correlated with a multitude of clinical markers. Across all studies, patients with MS demonstrated increased OD. Longitudinally, 2 contrasting patterns were identified: (1) clinical markers of acute inflammation correlated with an increased odor threshold and (2) clinical markers of neurodegeneration, or progression of disease, correlated with a decreased ability to discriminate and identify odors. CONCLUSIONS: These studies suggest that olfaction is a dynamic, dependent variable of neurodegeneration, correlating with inflammation and clinical markers. This opens the door for future exploration of olfaction's relationship with MS diagnosis, characterization, and therapeutic response.

The amphibian invitrome: Past, present, and future contributions to our understanding of amphibian immunity.

Many amphibian populations are declining worldwide, and infectious diseases are a leading cause. Given the eminent threat infectious diseases pose to amphibian populations, there is a need to understand the host-pathogen-environment interactions that govern amphibian susceptibility to disease and mortality events. However, using animals in research raises an ethical dilemma, which is magnified by the alarming rates at which many amphibian populations are declining. Thus, in vitro study systems such as cell lines represent valuable tools for furthering our understanding of amphibian immune systems. In this review, we curate a list of the amphibian cell lines established to date (the amphibian invitrome), highlight how research using amphibian cell lines has advanced our understanding of the amphibian immune system, anti-ranaviral defence mechanisms, and Batrachochytrium dendrobatidis replication in host cells, and offer our perspective on how future use of amphibian cell lines can advance the field of amphibian immunology.

The effects of school gardens on fruit and vegetable consumption at school: A randomized controlled trial with low-income elementary schools in four U.S. states.

This randomized controlled trial examines the effects of a school garden intervention on children's fruit and vegetable (FV) consumption at school over two years. We randomly assigned schools to the intervention group that received gardens and related curriculum (n = 24) or to the waitlist control group that received gardens and curriculum at the conclusion of the study (n = 22). Children in second, fourth, and fifth grade at baseline (n = 2767) in low-income schools (n = 46) in four U.S. States (Arkansas, Iowa, New York, and Washington) participated. The intervention comprised gardens for each classroom; a curriculum focused on nutrition, plant science, and horticulture, including activities and FV tasting sessions; resources for the school that addressed topics such as soil contamination and food safety; an implementation guide focused on issues related to planning, planting, and maintaining the garden through the year, engaging volunteers, summer gardening, building community capacity, and sustaining the gardening program. FV consumption was measured by photographing lunches before and after children ate, for 2-3 days, at baseline and at each of 3 subsequent periods of data collection during the intervention. FV consumption was calculated using Digital Food Image Analysis. Among children in the intervention, fruit consumption and low-fat vegetable consumption increased from pre-garden baseline to post-garden more than among control group children. Garden intervention fidelity (GIF) also predicted changes in dietary intake, with more robust interventions showing a stronger effect than weaker interventions. GIF-lessons was a particularly potent predictor of change in dietary intake. School gardens modestly increase children's FV consumption at school.

So, you want to create a frog cell line? A guide to establishing frog skin cell lines from tissue explants.

Skin is an important interface with the external environment and investigating amphibian skin cell biology will improve our understanding of how environmental factors such as pathogens and pollutants are contributing to global amphibian declines. There is a critical need for in vitro systems to facilitate conservation research in model and non-model amphibians and the creation of new amphibian cell lines will play a significant role in reducing or even replacing the use of live animals for in vivo studies by providing an in vitro alternative. Here, we detail an adapted protocol for the generation of spontaneously arising cell lines from frog skin tissues, without the need for immortalization steps. Expanding the amphibian invitrome will foster and expedite new research in amphibian gene function, cellular responses, host-pathogen interactions, and toxicology. The following customizations to traditional tissue explant generation procedures have facilitated the successful generation of adherent skin epithelial-like cell lines from Xenopus laevis and can be further adapted for use with different frog species, such as Rana sylvatica, and different tissues:•Osmotic adjustment of culture medium and solutions for different amphibian species.•Use of small tissue explants, instead of enzymatic digestion of tissues, and gentle spotting of these tissue explants onto the growth surface of tissue culture flasks to promote better tissue adherence.•Partial replacement of medium to allow accumulation of potential endogenous growth factors in cultures.

Magic angle spinning NMR of G protein-coupled receptors.

G protein-coupled receptors (GPCRs) have a simple seven transmembrane helix architecture which has evolved to recognize a diverse number of chemical signals. The more than 800 GPCRs encoded in the human genome function as receptors for vision, smell and taste, and mediate key physiological processes. Consequently, these receptors are a major target for pharmaceuticals. Protein crystallography and electron cryo-microscopy have provided high resolution structures of many GPCRs in both active and inactive conformations. However, these structures have not sparked a surge in rational drug design, in part because GPCRs are inherently dynamic and the structural changes induced by ligand or drug binding to stabilize inactive or active conformations are often subtle rearrangements in packing or hydrogen-bonding interactions. NMR spectroscopy provides a sensitive probe of local structure and dynamics at specific sites within these receptors as well as global changes in receptor structure and dynamics. These methods can also capture intermediate states and conformations with low populations that provide insights into the activation pathways. We review the use of solid-state magic angle spinning NMR to address the structure and activation mechanisms of GPCRs. The focus is on the large and diverse class A family of receptors. We highlight three specific class A GPCRs in order to illustrate how solid-state, as well as solution-state, NMR spectroscopy can answer questions in the field involving how different GPCR classes and subfamilies are activated by their associated ligands, and how small molecule drugs can modulate GPCR activation.

Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.

Hormones and growth factors (GFs) are signaling molecules implicated in the regulation of a variety of cellular processes. They play important roles in both healthy and tumor cells, where they function by binding to specific receptors on target cells and activating downstream signaling cascades. The stages of tumor progression are influenced by hormones and GF signaling. Hypoxia, a hallmark of cancer progression, contributes to tumor plasticity and heterogeneity. Most solid tumors contain a hypoxic core due to rapid cellular proliferation that outgrows the blood supply. In these circumstances, hypoxia-inducible factors (HIFs) play a central role in the adaptation of tumor cells to their new environment, dramatically reshaping their transcriptional profile. HIF signaling is modulated by a variety of factors including hormones and GFs, which activate signaling pathways that enhance tumor growth and metastatic potential and impair responses to therapy. In this review, we summarize the role of hormones and GFs during cancer onset and progression with a particular focus on hypoxia and the interplay with HIF proteins. We also discuss how hypoxia influences the efficacy of cancer immunotherapy, considering that a hypoxic environment may act as a determinant of the immune-excluded phenotype and a major hindrance to the success of adoptive cell therapies.

Improving CAR T-Cell Persistence.

Over the last decade remarkable progress has been made in enhancing the efficacy of CAR T therapies. However, the clinical benefits are still limited, especially in solid tumors. Even in hematological settings, patients that respond to CAR T therapies remain at risk of relapsing due to several factors including poor T-cell expansion and lack of long-term persistence after adoptive transfer. This issue is even more evident in solid tumors, as the tumor microenvironment negatively influences the survival, infiltration, and activity of T-cells. Limited persistence remains a significant hindrance to the development of effective CAR T therapies due to several determinants, which are encountered from the cell manufacturing step and onwards. CAR design and ex vivo manipulation, including culture conditions, may play a pivotal role. Moreover, previous chemotherapy and lymphodepleting treatments may play a relevant role. In this review, the main causes for decreased persistence of CAR T-cells in patients will be discussed, focusing on the molecular mechanisms underlying T-cell exhaustion. The approaches taken so far to overcome these limitations and to create exhaustion-resistant T-cells will be described. We will also examine the knowledge gained from several key clinical trials and highlight the molecular mechanisms determining T-cell stemness, as promoting stemness may represent an attractive approach to improve T-cell therapies.

Prior induction of cellular antiviral pathways limits frog virus 3 replication in two permissive Xenopus laevis skin epithelial-like cell lines.

Frog virus 3 (FV3) causes mortality in a range of amphibian species. Despite the importance of the skin epithelium as a first line of defence against FV3, the interaction between amphibian skin epithelial cells and FV3 remains largely uncharacterized. Here, we used newly established Xenopus laevis skin epithelial-like cell lines, Xela DS2 and Xela VS2, to study the susceptibility and permissiveness of frog skin epithelial cells to FV3, and the innate immune antiviral and proinflammatory gene regulatory responses of these cells to FV3. Both cell lines are susceptible and permissive to FV3, yet do not exhibit appreciable transcript levels of scavenger receptors thought to be used by FV3 for cellular entry. Xela DS2 and Xela VS2 upregulate antiviral and proinflammatory cytokine transcripts in response to poly(I:C) but not to FV3 or UV-inactivated FV3. Poly(I:C) pretreatment limits FV3 replication and FV3-induced cytopathic effects in both cell lines. Thus, Xela DS2 and Xela VS2 can support FV3 replication, represent in vitro systems to investigate antiviral responses of frog skin epithelial cells, and can serve as novel tools for screening compounds that initiate effective antiviral programs to limit FV3 replication.

Limited Shared Variance among Measures of Cognitive Performance Used in Nutrition Research: The Need to Prioritize Construct Validity and Biological Mechanisms in Choice of Measures.

BACKGROUND: The literature on correlates of nutrition has seen an increase in studies focused on functional consequences at the levels of neural, perceptual, and cognitive functioning. A range of measurement methodologies have been used in these studies, and investigators and funding agencies have raised the questions of how and if these various methodologies are at all comparable. OBJECTIVE: The aim was to determine the extent to which 3 different sets of cognitive measures provide comparable information across 2 subsamples that shared culture and language but differed in terms of socioeconomic status (SES) and academic preparation. METHODS: A total of 216 participants were recruited at 2 US universities. Each participant completed 3 sets of cognitive measures: 1 custom-designed set based on well-understood laboratory measures of cognition [cognitive task battery (COGTASKS)] and 2 normed batteries [Cambridge Neuropsychological Test Automated Battery (CANTAB), Weschler Adult Intelligence Scale, fourth edition (WAIS-IV)] designed for assessing general cognitive function. RESULTS: The 3 sets differed with respect to the extent to which SES and educational preparation affected the results, with COGTASKS showing no differences due to testing location and WAIS-IV showing substantial differences. There were, at best, weak correlations among tasks sharing the same name or claiming to measure the same construct. CONCLUSIONS: Comparability of measures of cognition cannot be assumed, even if measures have the same name or claim to assess the same construct. In selecting and evaluating different measures, construct validity and underlying biological mechanisms need to be at least as important as population norms and the ability to connect with existing literatures.

RNA-cDNA hybrids mediate transposition via different mechanisms.

Retrotransposons can represent half of eukaryotic genomes. Retrotransposon dysregulation destabilizes genomes and has been linked to various human diseases. Emerging regulators of retromobility include RNA-DNA hybrid-containing structures known as R-loops. Accumulation of these structures at the transposons of yeast 1 (Ty1) elements has been shown to increase Ty1 retromobility through an unknown mechanism. Here, via a targeted genetic screen, we identified the rnh1Δ rad27Δ yeast mutant, which lacked both the Ty1 inhibitor Rad27 and the RNA-DNA hybrid suppressor Rnh1. The mutant exhibited elevated levels of Ty1 cDNA-associated RNA-DNA hybrids that promoted Ty1 mobility. Moreover, in this rnh1Δ rad27Δ mutant, but not in the double RNase H mutant rnh1Δ rnh201Δ, RNA-DNA hybrids preferentially existed as duplex nucleic acid structures and increased Ty1 mobility in a Rad52-dependent manner. The data indicate that in cells lacking RNA-DNA hybrid and Ty1 repressors, elevated levels of RNA-cDNA hybrids, which are associated with duplex nucleic acid structures, boost Ty1 mobility via a Rad52-dependent mechanism. In contrast, in cells lacking RNA-DNA hybrid repressors alone, elevated levels of RNA-cDNA hybrids, which are associated with triplex nucleic acid structures, boost Ty1 mobility via a Rad52-independent process. We propose that duplex and triplex RNA-DNA hybrids promote transposon mobility via Rad52-dependent or -independent mechanisms.

The carry-over effects of school gardens on fruit and vegetable availability at home: A randomized controlled trial with low-income elementary schools.

This group-randomized controlled trial examines the effects of a school garden intervention on availability of fruits and vegetables (FV) in elementary school children's homes. Within each region, low income U.S. schools in Arkansas, Iowa, New York, and Washington State were randomly assigned to intervention group (n = 24) or waitlist control group (n = 22). Children were in grades 2, 4, and 5 at baseline (n = 2768). The garden intervention consisted of both raised-bed garden kits and a series of grade-appropriate lessons. FV availability at home was measured with a modified version of the GEMS FJV Availability Questionnaire. The instrument was administered at baseline (Fall 2011) and throughout the intervention (Spring 2012, Fall 2012, Spring 2013). Analyses were completed using general linear mixed models. The garden intervention led to an overall increase in availability of low-fat vegetables at home. Among younger children (2nd grade at baseline), the garden intervention led to greater home availability of vegetables, especially, low-fat vegetables. Moreover, for the younger group, garden intervention fidelity (GIF) or robustness predicted home availability of fruit, vegetables, and low-fat vegetables. School gardens have potential to affect FV availability in the home environment.

Effect of default menus on food selection and consumption in a college dining hall simulation study.

OBJECTIVE: To test an obesity prevention strategy derived from behavioural economics (optimal defaults plus delay), focused on changing the college dining hall service method. DESIGN: After a uniform pre-load, participants attended an experimental lunch in groups randomized to one of three conditions: a nutrient-dense, lower-fat/energy lunch as an optimal default (OD); a less-nutrient-dense, higher-fat/energy lunch as a suboptimal default (SD); or a free array (FA) lunch. In the OD condition, students were presented a menu depicting healthier vegetarian and omnivore foods as default, with opt-out alternatives (SD menu) available on request with a 15 min wait. In the SD condition, the same menu format was used with the positioning of food items switched. In the FA condition, all choices were presented in uniform fonts and were available immediately. SETTING: Private rooms designed to provide a small version of a college dining hall, on two campuses of a Northeastern US university. SUBJECTS: First-year college students (n 129). RESULTS: There was a significant main effect for condition on percentage of optimal choices selected, with 94 % of food choices in the OD condition optimal, 47 % in the FA condition optimal and none in the SD condition optimal. Similarly, energy intake for those in the SD condition significantly exceeded that in the FA condition, which exceeded that in the OD condition. CONCLUSIONS: Presenting menu items as optimal defaults with a delay had a significant impact on choice and consumption, suggesting that further research into its long-term applicability is warranted.