Host response to cholestyramine can be mediated by the gut microbiota.

The gut microbiota has been implicated as a major factor contributing to metabolic diseases and the response to drugs used for the treatment of such diseases. In this study, we tested the effect of cholestyramine, a bile acid sequestrant that reduces blood cholesterol, on the murine gut microbiota and metabolism. We also explored the hypothesis that some effects of this drug on systemic metabolism can be attributed to alterations in the gut microbiota.

Transkingdom Network Analysis (TkNA): a systems framework for inferring causal factors underlying host-microbiota and other multi-omic interactions.

We present Transkingdom Network Analysis (TkNA), a unique causal-inference analytical framework that offers a holistic view of biological systems by integrating data from multiple cohorts and diverse omics types. TkNA helps to decipher key players and mechanisms governing host-microbiota (or any multi-omic data) interactions in specific conditions or diseases. TkNA reconstructs a network that represents a statistical model capturing the complex relationships between different omics in the biological system.

Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH.

Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome.

Background: The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice.

Secondary Autologous Fat Grafting as a Novel Method to Improve Pain and Appearance of the Residual Fingertip After Amputation.

Background: Adequate soft tissue coverage following distal phalanx amputation remains challenging. The purpose of this study was to evaluate patient-reported outcomes following secondary autologous fat grafting after reconstruction of distal phalanx amputations with tissue flaps.

Methods: A retrospective review of patients who underwent autologous fat grafting to reconstructed fingertips following distal phalanx amputation with flaps from January 2018 to December 2020 was conducted.

Transkingdom Network Analysis (TkNA): a systems framework for inferring causal factors underlying host-microbiota and other multi-omic interactions.

Technological advances have generated tremendous amounts of high-throughput omics data. Integrating data from multiple cohorts and diverse omics types from new and previously published studies can offer a holistic view of a biological system and aid in deciphering its critical players and key mechanisms. In this protocol, we describe how to use Transkingdom Network Analysis (TkNA), a unique causal-inference analytical framework that can perform meta-analysis of cohorts and detect master regulators among measured parameters that govern pathological or physiological responses of host-microbiota (or any multi-omic data) interactions in a particular condition or disease.

GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA.

Enriched dietary saturated fatty acids induce trained immunity via ceramide production that enhances severity of endotoxemia and clearance of infection.

Trained immunity is an innate immune memory response that is induced by a primary inflammatory stimulus that sensitizes monocytes and macrophages to a secondary pathogenic challenge, reprogramming the host response to infection and inflammatory disease. Dietary fatty acids can act as inflammatory stimuli, but it is unknown if they can act as the primary stimuli to induce trained immunity. Here we find mice fed a diet enriched exclusively in saturated fatty acids (ketogenic diet; KD) confer a hyper-inflammatory response to systemic lipopolysaccharide (LPS) and increased mortality, independent of diet-induced microbiome and hyperglycemia.

Safety and Efficacy of Third-Generation Ultrasound-Assisted Liposuction: A Series of 261 Cases.

Background: The introduction of third-generation ultrasound-assisted liposuction (3rd UAL) allows for a less invasive modality of both deep and superficial lipectomy while offering improved skin retraction and reduced rate of complications. This study examined the efficacy and safety profile of this technology over 15 years of clinical experience.

Methods: A consecutive series of patients treated from 2005-2020 by the senior author were reviewed for demographic and anthropometric measurements, intraoperative settings, surgical outcomes, and complications via retrospective chart review.

Fecal Implants From and Donor Mice Sufficient to Induce Behavioral Phenotypes in Germ-Free Mice.

The gut microbiome and the gut brain axis are potential determinants of Alzheimer's disease (AD) etiology or severity and gut microbiota might coordinate with the gut-brain axis to regulate behavioral phenotypes in AD mouse models. Using 6-month-old human amyloid precursor protein (hAPP) knock-in (KI) mice, which contain the Swedish and Iberian mutations [APP NL-F ( )] or the Arctic mutation as third mutation [APP NL-G-F ( )], behavioral and cognitive performance is associated with the gut microbiome and APP genotype modulates this association. In this study, we determined the feasibility of behavioral testing of mice in a biosafety cabinet and whether stool from 6-month-old mice or crossed with human apoE4 targeted replacement mice is sufficient to induce behavioral phenotypes in 4-5 month-old germ-free C57BL/6J mice 4 weeks following inoculation.

Pathological Evaluation of Breast Specimens in Transgender Chest Masculinization: Incidental Findings and Effect of Prior Chest Binding and Androgen Therapy in 74 Consecutive Patients.

The rate of masculinizing chest surgery for gender affirmation continues to increase. With a paucity of literature on pathological evaluation of breast specimens in this patient population, there is a need for these data and for protocols on the handling of these specimens. A retrospective chart review was performed between 2015 and 2020 on all patients who underwent chest masculinization surgery for gender dysphoria by the senior author (J.

Effect of Nimodipine and Botulinum Toxin A on Peripheral Nerve Regeneration in Rats: A Pilot Study.

Background: Peripheral nerve damage is a frequent problem, with an estimated 2.8%-5.0% of trauma admissions involving peripheral nerve injury.

Chest Masculinization Technique and Outcomes in 72 Double-incision Chest-contouring Procedures with Free Nipple Grafting.

Unlabelled: Chest masculinization for gender affirmation is the removal of breast tissue and excess skin, often with repositioning of the nipple areola complexes to achieve a male-appearing chest. A double-incision technique with free nipple grafting (FNG) is the preferred method for trans men with large, ptotic breasts. The authors present the outcomes of 72 consecutive chest masculinization cases using this technique.

Dietary Indole-3-Carbinol Activates AhR in the Gut, Alters Th17-Microbe Interactions, and Exacerbates Insulitis in NOD Mice.

The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice.

Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes.

Western diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes (T2D) with gut microbiota playing an important role in modulating effects of the diet. Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism. Interrogation of this network pointed to taxa with potential beneficial or harmful effects on host's metabolism.

The Effect of Perforator Skeletonization on Pedicled Fasciocutaneous Flaps of the Lower Extremity: A Systematic Review.

Background:  Lower extremity defects often require free tissue transfer due to a paucity of local donor sites. Locoregional perforator-based flaps offer durable, single-stage reconstruction while avoiding the pitfalls of microsurgery. Multiple harvest techniques are described, yet few studies provide outcome comparisons.

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia.

A calorie-dense diet is a well-established risk factor for obesity and metabolic syndrome (MetS), whereas the role of the intestinal microbiota (IMB) in the development of diet-induced obesity (DIO) is not completely understood. To test the hypothesis that Swiss Webster (Tac:SW) mice can develop characteristics of DIO and MetS in the absence of the IMB, we fed conventional (CV) and germ-free (GF) male Tac:SW mice either a low-fat diet (LFD; 10% fat derived calories) or a high-fat diet (HFD; 60% fat derived calories) for 10 weeks. The HFD increased feed conversion and body weight in GF mice independent of the increase associated with the microbiota in CV mice.

Cuff and sieve electrode (CASE): The combination of neural electrodes for bi-directional peripheral nerve interfacing.

Background: A number of peripheral nerve interfaces for nerve stimulation and recording exist for the purpose of controlling neural prostheses, each with a set of advantages and disadvantages. The ultimate goal of neural prostheses is a seamless bi-directional communication between the peripheral nervous system and the prosthesis. Here, we developed an interfacing electrode array, the "cuff and sieve electrodes" (CASE), integrating microfabricated cuff and sieve electrodes to a single unit, to decrease the weaknesses faced by these electrode designs in isolation.

Role of gut microbiota in type 2 diabetes pathophysiology.

A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes. However, reports vary regarding the association of particular taxonomic groups with disease. In this systematic review, we focused on the potential role of different bacterial taxa affecting diabetes.