Nerve Blocks Prior to Microfocused Ultrasound Treatment are Safe and Reduce Patient Discomfort.

BACKGROUND: Microfocused ultrasound with visualization has become one of the more popular nonsurgical facial rejuvenation therapies available. Although the treatment has gained wide acceptance, providing adequate pain relief during the procedure can be challenging. OBJECTIVES: The aim of this study was to test our hypothesis that nerve blocks prior to treatment would be well tolerated and significantly reduce patient discomfort. METHODS: Subjects undergoing microfocused ultrasound were offered the choice of participating in a split face nerve block, bilateral block, or a control group. Nerves targeted included infraorbital, supratrochlear, supraorbital, zygomaticofrontal, mental, great auricular, and cervical plexus. Pain assessment was based on a 10-point Wong-Backer FACES Pain score. RESULTS: A total of 65 patients were included in the study: 28 in the split face group, 19 in the bilateral block group, and 18 without a block. The mean [standard deviation] pain score of the bilateral block cohort was 3.9 [1.2], and that of the control group was 5.1 [1.7] (P = 0.001). Patients in the split face cohort reported a higher pain score on the unblocked side of the face (7.5 [1.3]) than on the blocked side (2.9 [1.0]) (P < 0.001). The mean pain score for local anesthetic injection was 2.7 and 1.4 for the split face and the bilateral groups, respectively. There were no adverse events. CONCLUSIONS: Nerve blocks are well tolerated and significantly improve patient comfort during microfocused ultrasound treatment without compromising outcomes or increasing adverse events.

Geometric Three-Dimensional End-to-Side Microvascular Anastomosis: A Simple and Reproducible Technique.

BACKGROUND: End-to-side (ETS) anastomoses are useful when preservation of distal vascularity is critical. The ideal ETS microanastomosis should maintain a wide aperture and have a smooth take-off point to minimize turbulence, vessel spasm, and thrombogenicity of the suture line. We have developed a unique, dependable, and reproducible geometric technique for ETS anastomoses, and analyze its efficacy in our series of patients. METHODS: The geometric ETS technique involves creating a three-dimensional (3D) diamond-shaped defect on the recipient vessel wall, followed by a slit incision of the donor vessel to create a "spatula" fitting this defect. This technique removes sutures from the point of most turbulent blood flow while holding the recipient vessel open with a patch vesselplasty effect. We perform a retrospective review of a single surgeon's experience using this technique. RESULTS: The geometric 3D ETS technique was used in 87 free flaps with a total of 102 ETS anastomoses in a wide range of cases including head and neck, trunk and genitourinary, and extremity reconstruction. Overall, free flap success rates were 98%. CONCLUSIONS: The geometric 3D ETS technique creates a wide anastomosis, minimizes turbulence-inducing thrombogenicity, and mechanically holds the recipient vessel open. It is reliable and reproducible, and when performed properly has been shown to have high rates of success in a large group of free tissue transfer patients.

Muscle mass and physical recovery in ICU: innovations for targeting of nutrition and exercise.

PURPOSE OF REVIEW: We have significantly improved hospital mortality from sepsis and critical illness in last 10 years; however, over this same period we have tripled the number of 'ICU survivors' going to rehabilitation. Furthermore, as up to half the deaths in the first year following ICU admission occur post-ICU discharge, it is unclear how many of these patients ever returned home or a meaningful quality of life. For those who do survive, recent data reveals many 'ICU survivors' will suffer significant functional impairment or post-ICU syndrome (PICS). Thus, new innovative metabolic and exercise interventions to address PICS are urgently needed. These should focus on optimal nutrition and lean body mass (LBM) assessment, targeted nutrition delivery, anabolic/anticatabolic strategies, and utilization of personalized exercise intervention techniques, such as utilized by elite athletes to optimize preparation and recovery from critical care. RECENT FINDINGS: New data for novel LBM analysis technique such as computerized tomography scan and ultrasound analysis of LBM are available showing objective measures of LBM now becoming more practical for predicting metabolic reserve and effectiveness of nutrition/exercise interventions. 13C-Breath testing is a novel technique under study to predict infection earlier and predict over-feeding and under-feeding to target nutrition delivery. New technologies utilized routinely by athletes such as muscle glycogen ultrasound also show promise. Finally, the role of personalized cardiopulmonary exercise testing to target preoperative exercise optimization and post-ICU recovery are becoming reality. SUMMARY: New innovative techniques are demonstrating promise to target recovery from PICS utilizing a combination of objective LBM and metabolic assessment, targeted nutrition interventions, personalized exercise interventions for prehabilitation and post-ICU recovery. These interventions should provide hope that we will soon begin to create more 'survivors' and fewer victim's post-ICU care.

Facial Aesthetic Surgery: The Safe Use of Oral Sedation in an Office-Based Facility.

BACKGROUND: The desire for efficient and safe office-based facial plastic surgery procedures has continued to rise. Oral sedation is a safe and effective method to provide anesthesia for facial aesthetic surgery. OBJECTIVES: This study reviewed private practice anesthesia-related outcomes using oral sedation combined with local anesthesia for office-based facial aesthetic surgery procedures. METHODS: A retrospective chart review was performed on all patients who underwent office-based facial plastic surgery procedures from July 2008 to July 2014. Patient demographic data including age, gender, body mass index (BMI), past medical history, social history, surgical history, allergies, and medications were collected. Anesthesia-related data were also collected including: American Society of Anesthesia (ASA) class, type of procedure, medications administered, and major complications related to sedation were assessed. RESULTS: There were 199 patients (23 males and 176 females) who underwent 283 facial aesthetic surgical procedures. Mean age was 49.8 years (range, 29 to 80 years). There were 195 patients in ASA class I and 4 patients were in ASA class II. Patients underwent 44 upper blepharoplasty procedures, 35 lower blepharoplasty procedures, 5 browlifts, 43 upper blepharoplasty-browpexy, 46 facelifts, 38 neck lifts/lower facelifts, 54 fat grafting, 3 tip rhinoplasties, and 15 minor revision cases. During the study period, there were no major complications and no sedation issues. CONCLUSIONS: Facial aesthetic surgical procedures can be performed safely and comfortably in the office-based setting under oral sedation in appropriately selected patients. LEVEL OF EVIDENCE 4: Therapeutic.

NMR Metabolomics Show Evidence for Mitochondrial Oxidative Stress in a Mouse Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is associated with metabolic and endocrine disorders in women of reproductive age. The etiology of PCOS is still unknown. Mice prenatally treated with glucocorticoids exhibit metabolic disturbances that are similar to those seen in women with PCOS. We used an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach to understand the metabolic changes occurring in the plasma and kidney over time in female glucocorticoid-treated (GC-treated) mice. There are significant changes in plasma amino acid levels (valine, tyrosine, and proline) and their intermediates (2-hydroxybutyrate, 4-aminobutyrate, and taurine), whereas in kidneys, the TCA cycle metabolism (citrate, fumarate, and succinate) and the pentose phosphate (PP) pathway products (inosine and uracil) are significantly altered (p < 0.05) from 8 to 16 weeks of age. Levels of NADH, NAD(+), NAD(+)/NADH, and NADH redox in kidneys indicate increased mitochondrial oxidative stress from 8 to 16 weeks in GC-treated mice. These results indicate that altered metabolic substrates in the plasma and kidneys of treated mice are associated with altered amino acid metabolism, increased cytoplasmic PP, and increased mitochondrial activity, leading to a more oxidized state. This study identifies biomarkers associated with metabolic dysfunction in kidney mitochondria of a prenatal gluococorticoid-treated mouse model of PCOS that may be used as early predictive biomarkers of oxidative stress in the PCOS metabolic disorder in women.

Application of 3-dimensional printing in hand surgery for production of a novel bone reduction clamp.

Three-dimensional printing is being rapidly incorporated in the medical field to produce external prosthetics for improved cosmesis and fabricated molds to aid in presurgical planning. Biomedically engineered products from 3-dimensional printers are also utilized as implantable devices for knee arthroplasty, airway orthoses, and other surgical procedures. Although at first expensive and conceptually difficult to construct, 3-dimensional printing is now becoming more affordable and widely accessible. In hand surgery, like many other specialties, new or customized instruments would be desirable; however, the overall production cost restricts their development. We are presenting our step-by-step experience in creating a bone reduction clamp for finger fractures using 3-dimensional printing technology. Using free, downloadable software, a 3-dimensional model of a bone reduction clamp for hand fractures was created based on the senior author's (M.V.M.) specific design, previous experience, and preferences for fracture fixation. Once deemed satisfactory, the computer files were sent to a 3-dimensional printing company for the production of the prototypes. Multiple plastic prototypes were made and adjusted, affording a fast, low-cost working model of the proposed clamp. Once a workable design was obtained, a printing company produced the surgical clamp prototype directly from the 3-dimensional model represented in the computer files. This prototype was used in the operating room, meeting the expectations of the surgeon. Three-dimensional printing is affordable and offers the benefits of reducing production time and nurturing innovations in hand surgery. This article presents a step-by-step description of our design process using online software programs and 3-dimensional printing services. As medical technology advances, it is important that hand surgeons remain aware of available resources, are knowledgeable about how the process works, and are able to take advantage of opportunities in order to advance the field.

Effects of dietary sulfur amino acid levels on growth performance and intestinal immunity in broilers vaccinated and subsequently infected with coccidiosis.

Coccidia vaccination is a common practice in the poultry industry. However, research is lacking regarding the optimal nutritional support for coccidia vaccinated broilers. In this study, broilers were vaccinated with coccidia oocyst at hatch and were fed with a common starter diet from 1 to 10 d. On d 11, the broilers were randomly assigned to groups in a 4 × 2 factorial arrangement. Briefly, the broilers were fed one of four diets containing 0.6, 0.8, 0.9, and 1.0% of standardized ileal digestible methionine plus cysteine (SID M+C), respectively, from 11 to 21 d. On d 14, the broilers from each diet group were orally gavaged with either PBS (Mock challenge) or Eimeria oocysts. Compared to PBS-gavaged broilers and regardless of dietary SID M+C levels, the Eimeria-gavaged broilers had 1) decreased gain-to-feed ratio (15-21 d, P = 0.002; 11-21 d, P = 0.011); 2) increased fecal oocysts (P < 0.001); 3) increased plasma anti-Eimeria IgY (P = 0.033); and 4) increased intestinal luminal interleukin-10 (IL-10; duodenum, P = 0.039; jejunum, P = 0.018) and gamma interferon (IFN-γ; duodenum, P < 0.001; jejunum, P = 0.017). Regardless of Eimeria gavage, broilers fed 0.6% SID M+C had decreased (P<0.001) body weight gain (15-21 and 11-21 d) and gain-to-feed ratio (11-14, 15-21, and 11-21 d) when compared to those fed ≥ 0.8% SID M+C. Eimeria challenge increased (P < 0.001) duodenum lesions when the broilers were fed with 0.6, 0.8, and 1.0% SID M+C, and increased (P = 0.014) mid-intestine lesions when the broilers were fed with 0.6 and 1.0% SID M+C. An interaction between the two experimental factors was detected on plasma anti-Eimeria IgY titers (P = 0.022), as coccidiosis challenge increased plasma anti-Eimeria IgY titers only when the broilers were fed with 0.9% SID M+C. In summary, the dietary SID M+C requirement for grower (11-21 d) broilers vaccinated with coccidiosis was ranged from 0.8 to 1.0% for optimal growth performance and intestinal immunity, regardless of coccidiosis challenge.

Dietary supplementation of sulfur amino acids improves intestinal immunity to Eimeria in broilers treated with anti-interleukin-10 antibody.

Oral antibody to interleukin-10 (anti-IL-10) enhances the intestinal immune defense against Eimeria. The sulfur amino acids methionine and cysteine (M+C) play essential roles in inducing and maintaining protective immune responses during intestinal infections. Hence, increased dietary M+C may support the anti-IL-10-induced intestinal immunity to Eimeria. Broilers (n = 640) were arranged in a 2 × 2 × 2 factorial design with 2 levels of each of the 3 main factors: dietary standardized ileal digestible (SID) M+C levels (0.6% or 0.8%), dietary anti-IL-10 supplementation (with or without), and coccidiosis challenge (control or challenge). Briefly, the broilers were supplied with either 0.6% or 0.8% SID M+C, each with or without anti-IL-10 (300 µg/kg), from d 10 to 21. On d 14, broilers from each diet were gavaged with either PBS or Eimeria. The resulting Eimeria infection induced fecal oocyst shedding and intestinal lesions. Broilers fed 0.8% SID M+C (main effects, P ≤ 0.05) had decreased feed-to-gain ratio, increased duodenum and cecum luminal anti-Eimeria IgA titers, and decreased fecal oocyst counts, when compared to 0.6% SID M+C. The supplementation of anti-IL-10 (main effects, P ≤ 0.05) increased cecum luminal total IgA concentration and decreased cecum lesions. Interactions (P ≤ 0.05) were detected for growth performance and cecum luminal IFN-γ. Briefly, the highest body weight gain and feed intake were reached in PBS-gavaged broilers fed 0.8% SID M+C with no anti-IL-10 and in Eimeria-challenged broilers fed 0.8% SID M+C with anti-IL-10. In Eimeria-infected broilers, anti-IL-10 increased intestinal luminal IFN-γ and body weight gain only at 0.8% SID M+C. Collectively, anti-IL-10 increased intestinal luminal IFN-γ levels, decreased cecum lesions and restored growth only when fed with adequate amounts of sulfur amino acids. Our findings underscore the importance of providing sufficient essential nutrients to support the anti-IL-10 induced immunity against coccidiosis.

Individual isomers of conjugated linoleic acid reduce inflammation associated with established collagen-induced arthritis in DBA/1 mice.

Previously, dietary conjugated linoleic acid [(CLA), an equal mixture of cis-9, trans-11 (c9t11) and trans-10, cis-12 (t10c12) CLA isomers], was found to reduce inflammation in the murine collagen antibody-induced arthritis model, but less so in the murine collagen-induced arthritis (CIA) model, an arthritic model dependent upon acquired immunity. Because CLA is known to alter the acquired immune response, it was hypothesized that feeding CLA after the establishment of arthritis would reduce paw swelling in the CIA model. In this study, upon the establishment of arthritic symptoms, mice were randomized to the following dietary treatments: corn oil (CO) control (n = 6), 0.5% c9t11-CLA (n = 8), 0.5% t10c12-CLA (n = 6), or 1% combined CLA (1:1 c9t11:t10c12-CLA, n = 6). Paws were scored for severity of arthritis and measured for changes in thickness during an 84-d study period. Dietary c9t11- and combined-CLA similarly decreased the arthritic score (29%, P = 0.036, P = 0.049, respectively, when normalized to initial score) and paw thickness (0.11 mm, P = 0.027, P = 0.035, respectively) compared with CO. Dietary t10c12-CLA reduced the arthritic score (41%, P = 0.007 when normalized) and paw thickness (0.12 mm, P = 0.013) relative to CO. Reduced interleukin-1beta on d 7 and 21 for all CLA treatments (n = 3) relative to CO suggested that antiinflammatory effects of CLA isomers might work by common mechanisms of known pathways involved in chronic inflammation. In conclusion, dietary CLA reduced inflammation associated with CIA, and both c9t11-CLA and t10c12-CLA exhibited antiinflammatory effects.

Effects of dietary methionine plus cysteine levels on growth performance and intestinal antibody production in broilers during Eimeria challenge.

Research has shown that methionine+ cysteine (M+C) requirements may be higher when chickens are infected with Eimeria app. In a 4 × 2 factorial design, broilers (11 to 21 D) were fed one of 4 corn-soybean meal-based diets containing either 0.6, 0.8, 0.9, or 1.0% standardized ileal digestible (SID) M+C; on day 14, broilers from each diet were gavaged with either phosphate-buffered saline (PBS) or a commercial coccidiosis vaccine (at 100 × vaccine dose) which provide a mixture of live Eimeria acervulina, Eimeria maxima, and Eimeria tenella oocysts. Growth performance was recorded from day 11 to 21. Plasma and intestinal luminal samples were collected on days 14 and 21. Intestine lesion scores and fecal oocyst counts were conducted on day 21. Regardless of dietary SID M+C levels, compared to PBS gavaged broilers, the Eimeria-challenged broilers had (1) decreased (P < 0.05) body weight gain (BWG), feed intake (FI), and gain-to-feed ratio (G:F); (2) increased (P < 0.05) intestinal lesion scores and fecal oocyst counts; (3) increased (P < 0.05) plasma anti-Eimeria IgG, and intestinal luminal total IgA and anti-Eimeria IgA concentrations; and (4) increased (P < 0.05) levels of duodenum luminal gamma interferon (IFN-γ) and interleukin-10 (IL-10), as well as jejunum and cecum luminal IFN-γ concentrations. Regardless of Eimeria challenge, when compared to 0.6% SID M+C, broilers fed ≥0.8% SID M+C had (1) increased (P < 0.05) BWG, FI, and G:F and (2) increased (P < 0.05) levels of jejunum luminal total IgA. After Eimeria challenge, broilers fed 0.8% SID M+C had increased (P < 0.05) levels of jejunum luminal anti-Eimeria IgA compared to broilers fed diets containing 0.6 and 1.0% SID M+C. Collectively, in 11- to 21-D broilers, the growth suppression caused by Eimeria infection could not be mitigated by further increasing dietary M+C alone ≥0.8%. Further research should investigate interactions between dietary M+C and other nutrients for support of immune function and growth in pathogen-challenged broilers.

Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase response.

The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3 h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4-5 delta values lower than those of the control animals by 2.5 h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia.

Changes in exhaled 13CO2/12CO2 breath delta value as an early indicator of infection in intensive care unit patients.

BACKGROUND: We have developed a new, noninvasive predictive marker for onset of infection in surgical intensive care unit (ICU) patients. The exhaled CO2/CO2 ratio, or breath delta value (BDV), has been shown to be an early marker for infection in a proof of concept human study and in animal models of bacterial peritonitis. In these studies, the BDV changes during onset and progression of infection, and these changes precede physiological changes associated with infection. Earlier diagnosis and treatment will significantly reduce morbidity, mortality, hospitalization costs, and length of stay. The objective of this prospective, observational, multicenter study was to determine the predictive value of the BDV as an early diagnostic marker of infection. METHODS: Critically ill adults after trauma or acute care surgery with an expected length of stay longer than 5 days were enrolled. The BDV was obtained every 4 hours for 7 days and correlated to clinical infection diagnosis, serum C-reactive protein, and procalcitonin levels. Clinical infection diagnosis was made by an independent endpoint committee. This trial was registered at the US National Institutes of Health (ClinicalTrials.gov) NCT02327130. RESULTS: Groups were demographically similar (n = 20). Clinical infection diagnosis was confirmed on day 3.9 ± 0.63. Clinical suspicion of infection (defined by SIRS criteria and/or new antibiotic therapy) was on day 2.1 ± 0.5 in all infected patients. However, 5 (56%) of 9 noninfected subjects also met clinical suspicion criteria. The BDV significantly increased by 1‰ to 1.7‰ on day 2.1 after enrollment (p < 0.05) in subjects who developed infections, while it remained at baseline (± 0.5‰) for subjects without infections. CONCLUSION: A BDV greater than 1.4‰ accurately differentiates subjects who develop infections from those who do not and predicts the presence of infection up to 48 hours before clinical confirmation. The BDV may predict the onset of infection and aid in distinguishing SIRS from infection, which could prompt earlier diagnosis, earlier appropriate treatment, and improve outcomes. LEVEL OF EVIDENCE: Diagnostic test, level III.

Effect of anti-fibroblast growth factor receptor 1 antibodies on phosphorus metabolism in laying hens and their progeny chicks.

Targeting fibroblast growth factor 23 (FGF-23) signaling pathway is of interest in controlling body phosphate metabolism. This study investigated the effect of anti-fibroblast growth factor receptor 1 (FGFR1, major FGF-23 receptor in the kidney) antibodies on phosphate metabolism. White Leghorn laying hens (65-wk-old) were vaccinated with either a FGFR1 peptide vaccine (five 8-amino-acid peptides were selected, CrZ-1:LPEDPRWE, CrZ-2:LDKDKPNR, CrZ-3:RRPPGMEY, CrZ-4:GSPYPGVP, and CrZ-5:RMDKPSNC) or adjuvant control. At peak antibody titer, hens were artificially inseminated. Chicks from control-vaccinated hens were fed either a non-phytate phosphorus (nPP) sufficient (nPP = 0.45%, positive control) or deficient (nPP = 0.20%, negative control) diet, while chicks from each of the FGFR1 peptide vaccinated hens were fed with the above nPP-deficient diet, for 14 D. When compared to control hens, plasma phosphate in CrZ-1, CrZ-2, CrZ-3, CrZ-4, and CrZ-5 vaccinated hens were decreased by 33, 30, 24, 20, and 26%, respectively (P < 0.05); egg weight in CrZ-2 and CrZ-5 vaccinated hens were increased by 6 and 7%, respectively (P < 0.05); egg production in CrZ-3, CrZ-4, and CrZ-5 vaccinated hens tended to decrease (P = 0.085; decreased by 14, 15, and 13%, respectively). When compared to positive control, chicks from all other groups had decreased body weight gain (BWG) and feed intake (FI) during 1 to 14 D, and had decreased plasma phosphate, tibiotarsus ash, and 24-h phosphorus excretion on day 14. When compared to negative control, BWG of CrZ-1, CrZ-2, CrZ-3, and CrZ-4 antibody chicks were decreased by 23, 28, 26, and 20%, respectively (P < 0.05); FI of CrZ-1, CrZ-2, and CrZ-3 antibody chicks were decreased by 15, 15, and 18%, respectively (P < 0.05); plasma phosphate of CrZ-5 antibody chicks were decreased by 26% (P < 0.05); plasma FGF-23 levels of CrZ-4 antibody chicks were increased by 18% (P < 0.05); tibiotarsus ash content of CrZ-2, CrZ-3, and CrZ-4 antibody chicks were decreased by 20, 20, and 21%, respectively (P < 0.05). In conclusion, anti-FGFR1 peptide antibodies decreased egg production of hens and growth performance of their progeny chicks probably by activating FGF-23 signaling and stimulating FGF-23 production.

Re-introducing the delto-acromial perforator flap: Clinical experience and cadaver dissection.

BACKGROUND: Although perforator flaps from the pectoral branch of the thoraco-acromial (TA) axis have been well-described, there are few reports of perforator flaps based on the delto-acromial (DA) branches. We have found a reliable perforator coming off the DA branch of the TA axis, and have named a flap based on this vessel the delto-acromial perforator (DAP) flap. We describe our experience with the DAP flap together with a fresh cadaver anatomical study. METHODS: A retrospective review of all DAP flaps performed between December 2012 and January 2015 at our institution, with analysis of operative details, flap characteristics and surgical outcomes. We performed fresh cadaver dissection on 5 hemi-chest walls. RESULTS: The main cutaneous perforator from the deltoid and/or acromial branches is found at the delto-pectoral groove, 8 cm lateral to the TA axis and 8 cm inferior to the acromio-clavicular joint. Five patients underwent DAP flap reconstruction. Three were pedicled and 2 were free flaps. Average pedicle length from the origin of the DA branch was 8 cm, with an arterial diameter of at least 1 mm and vein diameter 1.5 mm. All flaps survived completely. Cadaver dissection showed a consistent perforator arising from the common delto-acromial branch in 4 cadavers, and from the deltoid branch in 1 cadaver. CONCLUSIONS: The DAP flap is a good addition to the armamentarium of reconstructive surgeons when a relatively thin fasciocutaneous flap with minimal hair is desired. It may be used for free tissue or locoregional transfer.

NF-kappaB independent inhibition of lipopolysaccharide-induced cyclooxygenase by a conjugated linoleic acid cognate, conjugated nonadecadienoic acid.

10t, 12c-CLA was shown to inhibit COX-2 expression through the NF-kappaB pathway. In the current study, conjugated nonadecadienoic acid (CNA) was shown to decrease inducible COX-2 protein and mRNA and PGE(2) release to the similar extent as 10t, 12c-CLA in Raw264.7 macrophage. However, unlike 10t, 12c-CLA, inhibition of COX-2 mRNA/protein by CNA was independent of the NF-kappaB pathway. The data indicate the regulation of COX-2 by select conjugated fatty acids and hence their anti-inflammatory actions could operate through different signal transduction pathways.

Maternally derived anti-fibroblast growth factor 23 antibody as new tool to reduce phosphorus requirement of chicks.

Novel means to reduce phosphate input into poultry feeds and increase its retention would preserve world phosphate reserves and reduce environmental impact of poultry production. Here we show that a maternally derived antibody to a fibroblast growth factor-23 (FGF-23) peptide (GMNPPPYS) alleviated phosphorus deficiency in chicks fed low non-phytate phosphorus (nPP) diets. White Leghorn laying hens were vaccinated with either an adjuvant control or the synthetic FGF-23 peptide, and chicks with control or anti-FGF-23 maternal antibodies were fed a diet containing either 0.13 or 0.45% nPP (experiment 1), and 0.20 or 0.45% nPP (experiment 2) for 14 d. In both experiments, decreasing nPP from 0.45 to 0.13 or 0.20% decreased BW gain, G:F, excreta phosphorus, plasma phosphate, and plasma FGF-23 at all time periods examined (nPP main effect, P < 0.05). In experiment 1, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and decreased excreta phosphate (d 7, 14) and plasma intact parathyroid hormone (d 7) when compared to chicks with control antibody (antibody main effect, P < 0.05). Mortality (d 7 to 14, 1 to 14), posture scores (d 7, 14) and bone lesion scores (d 14) decreased and plasma phosphate (d 14) increased in anti-FGF-23 chicks fed 0.13% nPP, compared to those with control antibody on the same diet (P < 0.05). In experiment 2, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and plasma phosphate (d 14) and 1,25(OH)2D3 (d 14) levels, compared to chicks with control antibody (antibody main effect, P < 0.05). BW gain and G:F were increased in chicks with anti-FGF-23 antibody fed 0.20% nPP, compared to control antibody chicks on the same diet, at all time periods examined (P < 0.05). In conclusion, maternally-derived anti-FGF-23 antibody increased phosphorus retention in chicks fed diets containing either 0.13 or 0.20% nPP and thereby, reduced signs of phosphorus deficiency.

Antibody to fibroblast growth factor 23-peptide reduces excreta phosphorus of laying hens.

Novel strategies to minimize the excretion of phosphorus in swine and poultry are critical in minimizing environmental degradation. We have developed a synthetic peptide vaccine to produce autoantibodies to fibroblast growth factor 23 (FGF-23), a bone-derived hormone that blocks kidney phosphate resorption and indirectly reduces intestinal phosphate absorption. Single Comb White Leghorn laying hens, fed a standard diet (inorganic phosphorus, Pi = 0.4%), were immunized over the course of 4 weeks with either a FGF-23 peptide vaccine or adjuvant control (without FGF-23 peptide). At peak antibody titer to the peptide (week 5), 24-h excreta were collected and hens were blood sampled (represents 0.4% Pi treatment). Hens were then fed a 0.8% Pi diet and blood was sampled at 24 and 72 h and 24-h excreta were collected at 12 to 36 and 60 to 84 h (represents 0.8% Pi treatment). Increasing Pi from 0.4 to 0.8% increased (P < 0.05) percent excreta phosphorus, total 24-h phosphorus excretion, and plasma levels of FGF-23 and phosphate in either control or FGF-23 peptide vaccinated hens as early as the first sampling period. FGF-23 peptide vaccinated hens fed 0.4% Pi had reduced (P < 0.05) percent excreta phosphorus, total 24 h phosphorus excretion, and plasma levels of FGF-23 and iPTH, and increased (P < 0.05) plasma levels of phosphate and 1,25(OH)2D3 when compared to control vaccinated hens fed 0.4% Pi. In the first collection period post 0.8% Pi feeding, FGF-23 peptide vaccinated hens had reduced (P < 0.05) plasma levels of FGF-23 and iPTH, and increased (P < 0.05) plasma levels of phosphate and 1,25(OH)2D3, and tended to have reduced percent excreta phosphorus (P = 0.085) and total 24 h phosphorus excretion (P = 0.078) when compared to control vaccinated hens. Results during the second collection period post 0.8% Pi feeding were similar to that at the first collection period. These results are the first to show that the inhibition of FGF-23 action by a peptide vaccine (via neutralizing antibody) reduced phosphorus excretion. The approach presented provides new information on phosphorus metabolism in the laying hen.

Dietary Conjugated Linoleic Acid-c9t11 Prevents Collagen-Induced Arthritis, Whereas Conjugated Linoleic Acid-t10c12 Increases Arthritic Severity.

Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

Parental leave policies in graduate medical education: A systematic review.

BACKGROUND: A thorough understanding of attitudes toward and program policies for parenthood in graduate medical education (GME) is essential for establishing fair and achievable parental leave policies and fostering a culture of support for trainees during GME. METHODS: A systematic review of the literature was completed. Non-cohort studies, studies completed or published outside of the United States, and studies not published in English were excluded. Studies that addressed the existence of parental leave policies in GME were identified and were the focus of this study. RESULTS: Twenty-eight studies addressed the topic of the existence of formal parental leave policies in GME, which was found to vary across time and ranged between 22 and 90%. Support for such policies persisted across time. CONCLUSIONS: Attention to formal leave policies in GME has traditionally been lacking, but may be increasing. Negative attitudes towards parenthood in GME persist. Active awareness of the challenges faced by parent-trainees combined with formal parental leave policy implementation is important in supporting parenthood in GME.