Radiographic Cone Zone Classification of Metaphyseal Cone Fixation in Revision Total Knee Arthroplasty.

Background: No objective radiographic scoring system exists to classify metaphyseal cone stability. Our purpose was to create a novel, systematic method to radiographically evaluate metaphyseal cone fixation based on radiographic findings suggestive of cone stability. Methods: A retrospective analysis was conducted of revision total knee arthroplasty patients (6/2015-12/2017) using porous titanium femoral or tibial metaphyseal cones in conjunction with short cemented stems (50 mm-75 mm). Minimum follow-up was 2 years. Survivorship free of aseptic loosening and reoperation, as well as radiographic evaluation using a novel cone zone scoring system were analyzed. Results: Forty-nine revision total knee arthroplasties were included in the study (12 femoral, 48 tibial cones), the majority, performed for aseptic loosening (25/49, 51%). Median follow-up was 39 months (range 25-58). Using the radiographic cone zone scoring method, >90% of all femoral cones were classified as likely stable or stable with strong, statistically significant intraclass correlations between all 3 reviewers. Similarly, >97% of all tibial cones were classified as likely stable or stable, with moderate, statistically significant intraclass correlations between all 3 reviewers. Only 1 femoral and 1 tibial cone were considered at risk of loosening. The study sample demonstrated 100% survivorship free of revision for aseptic loosening without evidence of radiographic loosening in any case. Conclusions: Using a novel systematic cone zone scoring and classification method, the overwhelming majority of femoral and tibial cones were classified as likely stable or stable, with no identified cases of aseptic loosening or related revision. Further studies are needed to validate this objective classification method.

Thermometry and velocimetry in a ramjet using dual comb spectroscopy of the O2 A-band.

Dual comb spectroscopy (DCS) of near-infrared H2O absorption has been demonstrated in the past for low-uncertainty flow measurements in ground test ramjets. However, H2O is scarce at actual ramjet flight altitudes, so oxygen is a preferable absorption target. Here, we demonstrate DCS of the O2 A-band (13000-13200 cm-1) and fit temperature and velocity across different flow conditions in a ground-test ramjet, demonstrating precisions of 3-5% and 7-11% respectively in five minutes and total uncertainty estimates of 7-9% and 8-12% respectively. The DCS measurements and uncertainty estimates are compared to predicted values for the test facility.

Associations between Dietary Fatty Acid Profile and Milk Fat Production and Fatty Acid Composition in Dairy Cows: A Meta-Analysis.

This meta-analysis aimed to investigate the effect of dietary fatty acid (FA) profile on milk fat production and FA profile in dairy cows. The study also aimed to develop prediction models using a meta-regression approach. The database included 217 peer-reviewed articles on lactating dairy cows (n = 12,892), consisting of 515 treatment means. Effect size was assessed using the raw mean differences between diets with supplementary lipid sources and those without. Subgroup analyses were employed to assess heterogeneity. Diets rich in saturated FA (SFA) increased milk fat production and proportion, while reducing de novo FA in milk. Diets high in monounsaturated FA and polyunsaturated FA decreased mixed FA in milk. Most lipid-supplemented diets increase preformed FA in milk, except those rich in SFA. Prediction models were developed using meta-regression. Key predictors of milk fat production included neutral detergent fiber (NDF), dietary myristic acid, and milk production. Milk fat proportion was best predicted by dietary unsaturated FA, NDF, and forage. De novo FA in milk was predicted by dry matter intake (DMI) and dietary FA, while preformed FA was predicted by DMI, dietary oleic and linoleic acids. In conclusion, this study emphasizes the importance of the dietary FA profile in evaluating the effects of lipids on milk fat production and FA profile. Accurate and precise predictions of milk fat production, proportion, and FA profile can be achieved by considering cow production and dietary characteristics.

Choline Regulates SOX4 through miR-129-5p and Modifies H3K27me3 in the Developing Cortex.

Choline availability regulates neural progenitor cell proliferation and differentiation in the developing cerebral cortex. Here, we investigated the molecular mechanism underlying this process and demonstrated that choline regulates the transcription factor SOX4 in neural progenitor cells. Specifically, we found that low choline intake during neurogenesis reduces SOX4 protein levels, causing the downregulation of EZH2, a histone methyltransferase. Importantly, we demonstrate that low choline is not involved in SOX4 protein degradation rate and established that protein reduction is caused by aberrant expression of a microRNA (miR-129-5p). To confirm the role of miR-129-5p, we conducted gain-of-function and loss-of-function assays in neural progenitor cells and demonstrated that directly altering miR-129-5p levels could affect SOX4 protein levels. We also observed that the reduction in SOX4 and EZH2 led to decreased global levels of H3K27me3 in the developing cortex, contributing to reduced proliferation and precocious differentiation. For the first time, to our knowledge, we demonstrate that a nutrient, choline, regulates a master transcription factor and its downstream targets, providing a novel insight into the role of choline in brain development.

Seven-year Outcomes of Adolescent Forearm Fractures Treated With Plate Fixation.

BACKGROUND: Pediatric forearm fractures are common injuries and can sometimes require surgical treatment. Few studies have evaluated the long-term outcomes of pediatric forearm fracture plating. We evaluated long-term functional outcomes and satisfaction in children with forearm fractures treated with plate fixation. METHODS: We performed a single-institution case series at a pediatric level 1 trauma center. Inclusion criteria were: patients with radius and/or ulna diaphyseal fractures, index surgery at 18 years of age or younger, plate fixation, and a minimum of 2 years follow-up. We surveyed patients with the QuickDASH outcome measure and supplemented this with functional outcomes and satisfaction questions. Demographics and surgery characteristics were obtained from the electronic medical record. RESULTS: A total of 41 patients met the eligibility criteria, of whom 17 completed the survey with a mean follow-up of 7.2 ± 1.4 years. The mean age at index surgery was 13.1 ± 3.6 years (range, 4 to 17), with 65% males. All patients reported at least one symptom, with aching (41%) and pain (35%) occurring most frequently. There were 2 complications (12%), including one infection and one compartment syndrome treated with fasciotomy. Hardware removal occurred in 29% of patients. There were no refractures. The mean QuickDASH score was 7.7 ± 11.9, with an occupation module score of 1.6 ± 3.9 and a sports/performing arts module score of 12.0 ± 19.7. The mean surgery satisfaction was 92% and scar satisfaction was 75%. All patients returned to prior activities and 88% reported a return to their preoperative baseline level of function. CONCLUSIONS: Plate fixation for pediatric forearm fractures achieves osseous union but not without the potential for long-term sequelae. All patients reported residual symptoms 7 years later. Scar satisfaction and return to baseline function were imperfect. Patient education for long-term outcomes of surgery is essential, especially in the transition to adulthood. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Exercise-based cardiac rehabilitation in women with heart failure: a review of enrollment, adherence, and outcomes.

Exercise-based cardiac rehabilitation (CR) is an evidence-based recommendation for patients with stable heart failure (HF). Less clear is how effective exercise-based CR is for women with HF. The aim of this review was to synthesize the evidence for the effects of exercise-based CR on mortality, hospitalizations, exercise capacity, and quality of life (QOL) among women with HF. We identified 18 studies comprising 4917 patients, of which 1714 were women. The interventions evaluated consisted of various combinations of supervised in-hospital and out-patient sessions as well as home-based programs that included aerobic (walking, treadmill, bicycle) and resistance training. The interventions ranged from 12 to 54 weeks, with a frequency of 2-7 sessions per week, lasting from 30 to 105 min per session. Because of a paucity of sex-specific analyses of the outcomes, it was not possible to draw conclusions for women. There was limited evidence for mortality benefit for men or women participating in exercise-based CR. There was more substantial evidence for reductions in hospitalizations for the participants. Generally, exercise training improved exercise capacity. The effects of exercise-based CR on QOL were mixed with most studies favoring CR at 3 months but not at 4, 5, and 12 months. Moreover, generally, the physical dimension of QOL but not the mental dimensions improved. Recommendations for future research to reduce the gap in knowledge about the effects of exercise-based CR for women are offered.

Homocysteine-induced endoplasmic reticulum stress activates FGF21 and is associated with browning and atrophy of white adipose tissue in Bhmt knockout mice.

Betaine-homocysteine methyltransferase (BHMT) catalyzes the transfer of methyl groups from betaine to homocysteine (Hcy), producing methionine and dimethylglycine. In this work, we characterize Bhmt wild type (Bhmt-WT) and knockout (Bhmt-KO) mice that were fully backcrossed to a C57Bl6/J background. Consistent with our previous findings, Bhmt-KO mice had decreased body weight, fat mass, and adipose tissue weight compared to WT. Histological analyses and gene expression profiling indicate that adipose browning was activated in KO mice and contributed to the adipose atrophy observed. BHMT is not expressed in adipose tissue but is abundant in liver; thus, a signal must originate from the liver that modulates adipose tissue. We found that, in Bhmt-KO mice, homocysteine-induced endoplasmic reticulum (ER) stress is associated with activation of the hepatic transcription factor cyclic AMP response element binding protein (CREBH), and an increase in hepatic and plasma concentrations of fibroblast growth factor 21 (FGF21), which is known to induce adipose browning. Our data indicate that the deletion of a single gene in one-carbon metabolism modifies adipose biology and energy metabolism. Future studies could focus on identifying if functional polymorphisms in BHMT result in a similar adipose atrophy phenotype.

Drought impairs herbivore-induced volatile terpene emissions by ponderosa pine but not through constraints on newly assimilated carbon.

Volatile terpenes serve multiple biological roles including tree resistance against herbivores. The increased frequency and severity of drought stress observed in forests across the globe may hinder trees from producing defense-related volatiles in response to biotic stress. To assess how drought-induced physiological stress alters volatile emissions alone and in combination with a biotic challenge, we monitored pre-dawn water potential, gas-exchange, needle terpene concentrations and terpene volatile emissions of ponderosa pine (Pinus ponderosa) saplings during three periods of drought and in response to simulated herbivory via methyl jasmonate application. Although 3-, 6- and 7-week drought treatments reduced net photosynthetic rates by 20, 89 and 105%, respectively, the magnitude of volatile fluxes remained generally resistant to drought. Herbivore-induced emissions, however, exhibited threshold-like behavior; saplings were unable to induce emissions above constitutive levels when pre-dawn water potentials were below the approximate zero-assimilation point. By comparing compositional shifts in emissions to needle terpene concentrations, we found evidence that drought effects on constitutive and herbivore-induced volatile flux and composition are primarily via constraints on the de novo fraction, suggesting that reduced photosynthesis during drought limits the carbon substrate available for de novo volatile synthesis. However, results from a subsequent 13CO2 pulse-chase labeling experiment then confirmed that both constitutive (<3% labeled) and herbivore-induced (<8% labeled) de novo emissions from ponderosa pine are synthesized predominantly from older carbon sources with little contribution from new photosynthates. Taken together, we provide evidence that in ponderosa pine, drought does not constrain herbivore-induced de novo emissions through substrate limitation via reduced photosynthesis, but rather through more sophisticated molecular and/or biophysical mechanisms that manifest as saplings reach the zero-assimilation point. These results highlight the importance of considering drought severity when assessing impacts on the herbivore-induced response and suggest that drought-altered volatile metabolism constrains induced emissions once a physiological threshold is surpassed.

Mid-term Follow Up of a Highly Porous Acetabular Component for Primary Total Hip Arthroplasty.

INTRODUCTION: As implant technology has continued to improve over the past decade, there has been an increase in the utilization of highly porous metal substrate acetabular components for primary total hip arthroplasty (THA). These implants have several theoretical benefits including a lower modulus of elasticity, which may result in a reduction in stress shielding, a higher coefficient of friction, which may enable better initial implant fixation, as well as higher porosity that may facilitate improved biological fixation. Although these components are implanted frequently, there are some studies that have posed concerns regarding radiographic evidence of loosening. Therefore, the purpose of this study was to assess: 1) The quality of fixation of porous metal acetabular components based on radiographs; 2) clinical outcomes; and 3) revision rates. MATERIALS AND METHODS: A total of 159 patients (169 hips) who had undergone a primary THA utilizing a porous metal primary acetabular cup with minimum two-year follow up were assessed. The study cohort consisted of 51% women, had a mean age of 65 years (range, 30 to 92 years), a mean body mass index (BMI) of 29kg/m2 (range, 15 to 54), and a mean follow up of approximately four years (range, three to six years). Acetabular revision for component failure was documented. Radiographic assessments were independently performed by two fellowship-trained arthroplasty surgeons to determine implant stability and radiolucencies. Clinical evaluations were made by assessing the hip disability and osteoarthritis outcome score (HOOS-Jr) survey scores. Failure was defined as the need to revise the acetabular component, for either septic or aseptic pathology. RESULTS: At final follow up, one patient had definitive loosening, one had probable loosening, and three patients had possible loosening. Only 3.0% had radiolucencies or radiosclerotic lesions in at least one zone. Of these patients, three developed progressive radiolucencies. All patients achieved excellent postoperative HOOS-Jr scores, and no significant differences were noted between patients who did not have loosening compared to patients who had possible or probable loosening. Only two patients underwent revision for aseptic loosening of the cup (success rate for this implant was 98.8% [2/169]). DISCUSSION: There is a paucity of studies focused on the results of this porous metal substrate acetabular component, with some of the current literature reporting conflicting outcomes. Our study reported a low acetabular revision rate of only 1.2% at an approximate mean follow up of four years. The incidence of radiolucencies and progressive radiolucencies were lower (3.0%) than has been found in some studies. Overall, the results of this study support the utilization of this acetabular component in appropriately indicated patients. CONCLUSION: These data show a low rate of acetabular revision at mean four-year follow up.

Impact of Mental Health on General Surgery Patients and Strategies to Improve Outcomes.

Mental Health Disorders (MHD) are a growing concern nationwide. The significant impact MHD have on surgical outcomes has only recently started to be understood. This literature review investigated how mental health impacts the outcomes of general surgery patients and what can be done to make improvements. Patients with schizophrenia had the poorest surgical outcomes. Mental health disorders increased post-surgical pain, hospital length of stay, complications, readmissions, and mortality. Mental health disorders decreased wound healing and quality of care. Optimizing outcomes will be best accomplished through integrating more effective perioperative screening tools and interventions. Screenings tools can incorporate artificial intelligence, MHD data, resilience and its biomarkers, and patient mental health questionnaires. Interventions include cognitive behavioral therapy, virtual reality, spirituality, pharmacology, and resilience training.

Projections from the five divisions of the orbital cortex to the thalamus in the rat.

The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we describe the efferent projections from the five divisions of the ORB to the thalamus in the rat. We demonstrated that, with some overlap, each division of the ORB distributed in a distinct (and unique) manner to nuclei of the thalamus. Overall, ORB projected to a relatively restricted number of sites in the thalamus, and strikingly distributed entirely to structures of the medial/midline thalamus, while completely avoiding lateral regions or principal nuclei of the thalamus. The main termination sites in the thalamus were the paratenial nucleus (PT) and nucleus reuniens (RE) of the midline thalamus, the medial (MDm) and central (MDc) divisions of the mediodorsal nucleus, the intermediodorsal nucleus, the central lateral, paracentral, and central medial nuclei of the rostral intralaminar complex and the submedial nucleus (SM). With some exceptions, medial divisions of the ORB (MO, VO) mainly targeted "limbic-associated" nuclei such as PT, RE, and MDm, whereas lateral division (VLO, LO, DLO) primarily distributed to "sensorimotor-associated" nuclei including MDc, SM, and the rostral intralaminar complex. As discussed herein, the medial/midline thalamus may represent an important link (or bridge) between the orbital cortex and the hippocampus and between the ORB and medial prefrontal cortex. In summary, the present results demonstrate that each division of the orbital cortex projects in a distinct manner to nuclei of the thalamus which suggests unique functions for each division of the orbital cortex.

Entero-Urachal Fistula: An Unusual Initial Presentation of Penetrating and Stricturing Crohn's Disease.

Crohn's disease (CD) has a wide variety of clinical presentations, ranging from abdominal pain to stricture and fistula. Fistulas involving the genitourinary tract can be severe and often require surgical intervention. Given the array of presenting symptoms, a delay in diagnosis can occur. We present the case of a healthy active duty soldier, with no previous medical history, found to have CD through an initial presentation of isolated umbilical drainage. Imaging workup identified an entero-uracho-cutaneous fistula with involvement of the transverse colon. Urachal anomalies are uncommon, and entero-urachal fistula as an initial presentation of CD is exceedingly rare. This case highlights the need to consider CD in the differential for patients with umbilical drainage despite a lack of concurrent more frequent presenting symptoms (abdominal pain, bloody diarrhea, and perianal fistula). Maintaining awareness of uncommon initial presentations of CD can minimize delay in diagnosis and thereby mitigate the risk of severe complications.

Association of Type of Vaccination Center With Time to Emergency Department Presentation for Acute COVID-19 Infection: An Exploratory Analysis.

Objective The objective of this study was to identify potential associations between coronavirus disease 2019 (COVID-19) vaccination center reception location and time to presentation to the emergency department for acute COVID-19 infection. The a priori hypothesis was that there are significant differences in the outcome based on vaccination administration center type. Methods This was a cross-sectional, observational study conducted within a hospital in Lakeland, Florida, between October 2021 and May 2022. Participants were at least 18 years old with confirmed severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection and at least two COVID-19 symptoms at enrollment. Patients with prior confirmed COVID-19 diagnosis and hospitalization within 10 days of screening were excluded. Participants were sampled from within the emergency department of the institution. The primary outcome was time to presentation to the emergency department for acute COVID-19 infection since the last vaccination dose from each sampled COVID-19 vaccination center location. Results A total of 93 participants were analyzed. Of these, 48 (52%) participants received COVID-19 vaccination. Participants vaccinated at vaccine clinics demonstrated a significantly longer mean survival time (288.2 (29.9)) compared to other sites. Significant predictors of hospitalization were age (aOR, 1.09, 95%CI 1.02-1.16, p < 0.01), sex (aOR: 10.05, 95%CI 1.52-66.54, p < 0.05), physical function (aOR, 0.90, 95%CI 0.83-0.97, p < 0.01) and number of medications (aOR, 1.34, 95%CI 1.14-1.58, p < 0.001).  Conclusions This exploratory analysis highlights the need for further investigation into both characteristics of healthcare institutions and individual-level factors that may play a role in the prolonged prevention of emergency department presentations due to COVID-19 infection. Increased transparency of data regarding practices related to the administration of COVID-19 vaccines across various institutions may be beneficial in further understanding the role of COVID-19 vaccinations in preventing symptomatic disease across local and global communities.

Nutrient additions to seagrass seed planting improve seedling emergence and growth.

To maximize the opportunities of seagrass as a nature-based solution requires restoration to occur on a large scale. New methods and knowledge are required that can solve ecological bottlenecks, improving its reliability and effectiveness. Although there is increasing interest in the use of seeds for seagrass restoration there exists a limited understanding of how best to plant them with the most knowledge on germination and seedling emergence coming from laboratory studies. Here we present the results of a novel field study on the emergence success of seeds of the seagrass Zostera marina when subjected to varied planting treatments. Seeds were planted into hessian bags according to a factorial design of three treatments (sediment type, detritus addition, and nutrient addition). By adding nutrients to natural sediment, the present study provides some evidence of seagrass shoot emergence and maximum shoot length doubling. The present study provides evidence that even in heavily nutrient-rich environments, seagrass sediments may require additional nutrients to improve seedling emergence and growth. It also highlights the highly variable nature of planting seagrass seeds in shallow coastal environments. Critically this study provides increasing levels of evidence that small subtleties in the method can have large consequences for seagrass restoration and that for restoration to scale to levels that are relevant for nature-based solutions there remain many unknowns that require consideration.

Pyoderma Gangrenosum Affecting the Dorsal Hand: A Case Report.

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis characterized by an ulcerative lesion with a violaceous border. Most frequently, these lesions present in the lower extremity and are associated with underlying immune-mediated comorbidities. Infrequently, these lesions may present in the upper extremity, which presents difficult challenges for upper extremity surgeons as the lesions are frequently misdiagnosed as an infectious process. This often leads to inappropriate surgical debridement and antibiotic administration. Local trauma to the lesion can lead to a process of pathergy and worsening of the lesion. Here, we report on a case of cutaneous pyoderma gangrenosum affecting the dorsal hand, originally misidentified as an atypical infection with subsequent unsuccessful surgical debridement. After involvement of a multidisciplinary team, appropriate diagnosis was made, and treatment with local immunosuppressive agents achieved resolution of the lesion.

Method development for the determination of seven ginsenosides in three Panax ginseng reference materials via liquid chromatography with tandem mass spectrometry.

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of ginsenosides in three Panax ginseng reference materials (RMs). Extraction procedures were optimized to recover neutral and malonyl-ginsenosides using a methanol-water extraction under basic conditions. Optimized mass fragmentation transitions were obtained for the development of a multiple reaction monitoring (MRM) detection method with electrospray ionization in negative and positive ion mode. Mass fraction values were determined for ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the three ginseng materials (rhizomes, extract, and an oral dosage form). Quantitation of these seven compounds was accomplished with 4-methylestradiol and SRM 3389 Ginsenoside Calibration Solution serving as an internal standard (IS) and calibration standards, respectively. Mass fraction values for the seven ginsenosides ranged from 1.27 mg/g to 21.42 mg/g, 3.25 mg/g to 35.81 mg/g, and 0.56 mg/g to 2.51 mg/g for SRM 3384, SRM 3385, and RM 8664, respectively.

Biophysical quantification of reorganization dynamics of human pancreatic islets during co-culture with adipose-derived stem cells.

Islet transplantation is a potential therapy for type 1 diabetes, but it is expensive due to limited pancreas donor numbers and the variability in islet quality. The latter is often addressed by co-culture of harvested islets with stem cells to promote in vitro remodeling of their basement membrane and enable expression of angiogenic factors for enhancing vascularization. However, given the heterogeneity in islet size, shape and function, there is a need for metrics to assess the reorganization dynamics of single islets over the co-culture period. Based on shape-evolution of individual multi-cell aggregates formed during co-culture of human islets with adipose derived stem cells and the pressures required for their bypass through microfluidic constrictions, we present size-normalized biomechanical metrics for monitoring the reorganization. Aggregates below a threshold size exhibit faster reorganization, as evident from rise in their biomechanical opacity and tightening of their size distribution, but this size threshold increases over culture time to include a greater proportion of the aggregates. Such biomechanical metrics can quantify the subpopulation of reorganized aggregates by distinguishing them versus those with incomplete reorganization, over various timepoints during the co-culture.

Aging-Related Behavioral, Adiposity, and Glucose Impairments and Their Association following Prenatal Alcohol Exposure in the C57BL/6J Mouse.

People that experience prenatal alcohol exposure (PAE) may have behavioral and metabolic impairments, and it is unclear whether these remain stable or change with age. We assessed behavioral and metabolic endpoints across the lifespan in a mouse model of fetal alcohol spectrum disorder (FASD). Pregnant C57BL/6J mice received alcohol (ALC; 3 g/kg) or maltose-dextrin (control, CON) daily from embryonic day 8.5 to 17.5. Offspring were tested on accelerating rotarod, Y-maze, novel object recognition, and fear conditioning at 6 weeks and 10 and 17 months; females were also tested at 24 months. Body composition, fasting glucose, and glucose clearance were assessed at 18 months. Female but not male ALC mice had greater adiposity than age-matched CON from 7 months onward. At 18 months, male but not female ALC mice had reduced glucose clearance and ALC mice were more likely to have elevated fasting glucose. In the rotarod training session, ALC females performed worse than CON. In the Y-maze, significant exposure-age interactions affected ALC performance in both sexes versus age-match CON. For fear conditioning, all animals acquired the task and froze more at older ages. In both the context and cued tasks, there were exposure-age interactions and ALC animals frozen less than CON at 10 months. Correlation analysis revealed that fasting glucose and glucose clearance correlated with % of body fat in ALC but not in CON mice. Additionally, glucose intolerance and % body fat negatively correlated with performance in the rotarod, context learning, and novel object recognition tasks in ALC but not CON mice. All mice exhibit worsening of behavioral performance as they age, and PAE did not further exacerbate this. ALC but not CON mice displayed adiposity and glucose intolerance that correlate with their cognitive impairments, suggesting that these may be mechanistically related in PAE. Findings emphasize that FASD should be considered a whole-body disorder.

Serum anti-Müllerian hormone concentration as a diagnostic tool to identify testicular tissue in canine disorders of sexual development.

Disorders of sexual development (DSD) may have their origin in alterations of the chromosomal, gonadal or phenotypic sex. Affected animals are usually presented because of ambiguous external genitalia, seldom because of reproductive disorders. Anti-Müllerian hormone (AMH) is secreted in the gonads with higher amounts in males than in females and can be used to identify gonadal tissue in sexually normally developed dogs. The aim of this study was to examine the diagnostic potential of serum AMH to identify testicular tissue in 11 dogs with DSD. The diagnostic procedures applied were: determination of the phenotypic sex (n = 11), genital ultrasound (n = 9), determination of the SRY gene (n = 11), karyogram (n = 6), gonadectomy (n = 11), pathohistology of the gonads (n = 10), serum AMH measurement (n = 11). 39 female dogs described in a previous study and 19 male dogs with a normal spermiogram served as controls for the AMH serum concentrations in sexually intact dogs. The 11 dogs with DSD were classified as 7 XY DSD and 4 XX DSD. Presumptive testes were obtained in 10 dogs and 1 dog had an ovotestis combined with a testis. Mean serum AMH values of the dogs with DSD were significantly higher (P < 0.001) than in male and female controls. The upper limit of the AMH test (≥ 23ng/ml) was reached in 6 dogs. High AMH concentrations have been described previously in cryptorchid dogs. 1 dog with a male phenotype and 2 with a female phenotype had AMH values within the range of the male controls, although all of them had cryptorchid testes. A Poodle, in which epididymis were identified but no definitive gonads, had an AMH concentration of the lower limit of the test (≤ 0.01 ng/ml), comparable to previously described castrated dogs. This study indicates that serum AMH levels are a useful diagnostic tool to identify testicular tissue in dogs with DSD and suggests the possible use of AMH to diagnose testicular dysgenesis.

Perfusable cell-laden micropatterned hydrogels for delivery of spatiotemporal vascular-like cues to tissues.

The integration of vasculature at physiological scales within 3D cultures of cell-laden hydrogels for the delivery of spatiotemporal mass transport, chemical and mechanical cues, is a stepping-stone towards building in vitro tissue models that recapitulate in vivo cues. To address this challenge, we present a versatile method to micropattern adjoining hydrogel shells with a perfusable channel or lumen core, for enabling facile integration with fluidic control systems, on one hand, and to cell-laden biomaterial interfaces, on the other hand. This microfluidic imprint lithography methodology utilizes the high tolerance and reversible nature of the bond alignment process to lithographically position multiple layers of imprints within a microfluidic device for sequential filling and patterning of hydrogel lumen structures with single or multiple shells. Through fluidic interfacing of the structures, the ability to deliver physiologically relevant mechanical cues for recapitulating cyclical stretch on the hydrogel shell and shear stress on endothelial cells in the lumen are validated. We envision application of this platform for recapitulation of the bio-functionality and topology of micro-vasculatures, alongside the ability to deliver transport and mechanical cues, as needed for 3D culture to construct in vitro tissue models.