A protocol for a randomised double-blind placebo-controlled feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing and remitting multiple sclerosis (RRMS).

BACKGROUND: Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis. METHODS: Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (< 10 years) of relapsing and remitting MS (RRMS) and who are over 18 years of age will be recruited from neurology clinics and throughout the Thames Valley community. During a 6-week nutrition intervention period, participants will consume the cocoa beverage, high flavonoid or low flavonoid content, at breakfast daily. At baseline, demographic factors and disease-related factors will be assessed. Fatigue, activity and quality of life, in addition to other measures, will be taken at three visits (baseline, week 3 and week 6) in a university setting by a researcher blinded to group membership. Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial.We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. DISCUSSION: We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. TRIAL REGISTRATION: Registered with ISRCTN Registry. Trial registration No: ISRCTN69897291; Date April 2016.

Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial.

CONTEXT: Current research suggests that dark cocoa may reduce fatigue; however, the effect on fatigue in people with MS (pwMS) has never been established. The objective of this feasibility study was to explore the acute effect of high flavonoid cocoa on measures of fatigue and glycaemic response. METHODS: This was a randomised crossover participant blind exploratory study in 12 participants (2 male and 10 female) with MS-related fatigue (>4 on the Fatigue Severity Scale; FSS). After fasting overnight, participants consumed the high flavonoid cocoa drink (350 mg gallic acid equivalents {GAE}/g) or a low flavonoid cocoa control (120 mg GAE/g), consuming the alternative drink on the next visit. Fatigue was self-reported on a 100 mm visual analogue scale at 30-min time intervals for 2 h post cocoa consumption and every 2 h for the rest of the day. Fatigability was monitored using a 6 min walk test (6MWT) at the end of the visit (2 h), and activity monitors worn for 24 h commencing at 12 noon on the day of testing. The feasibility of performing the trial including outcome measures was documented. RESULTS: A moderate effect was found in self-reported fatigue throughout the day in favour of the high flavonoid group (Cohen's d 0.32, 95% non-central t CI -0.57 to 1.20). Fatigability measures did not change. Participants consumed and enjoyed the cocoa, all participants completed the study and outcome measures were accepted. CONCLUSION: The results of this study support further trials to investigate the feasibility and efficacy of pure cocoa as a dietary supplement for fatigue in pwMS.

Porcine Acellular Dermal Matrix for Hernia Repair in Transplant Patients.

PURPOSE: The purpose of this study was to compare clinical outcomes of incisional hernia repair in solid organ transplant patients using non-cross-linked porcine acellular dermal matrix (PADM), human derived acellular dermal matrix (HADM) and synthetic mesh. METHODS: A retrospective review of patients who underwent hernia repair with PADM after pancreas and/or renal transplant at the University of Maryland Medical Center from 2008 to 2012 was conducted. Repair type, postoperative infection, hernia recurrence, mesh removal, and length of follow-up were recorded. Results were compared with our previously published data evaluating HADM and synthetic mesh used in transplant patients between 2000 and 2005. RESULTS: Twenty-seven patients underwent ventral hernia repair with PADM, 34 patients were repaired with HADM and 26 were repaired with synthetic mesh. The rate of wound infection in those repaired with PADM, HADM, and synthetic mesh were 14.8%, 14.7%, and 65.4%, respectively. Rates of recurrence were 13.3%, 23.5%, and 76.9%, respectively. Rate of mesh removal was found to be 7.4%, 11.8%, and 69.2%, respectively. These complication rates were significantly lower in patients who received HADM or PADM compared with patients repaired with synthetic mesh (P < 0.001). There was no statistically significant difference in the outcomes between the groups repaired with HADM or PADM. CONCLUSIONS: The use of PADM for incisional hernia repair after kidney and/or pancreas transplant significantly reduces the incidence of hernia recurrence, wound infection, and need for mesh removal compared to synthetic mesh. No difference in morbidity between HADM and PADM was observed in the study population; however, longer follow-up in the PADM group is warranted.

Utility of indocyanine green fluorescence lymphography in identifying the source of persistent groin lymphorrhea.

SUMMARY: Surgical manipulation of the groin can result in lymphatic injury in a significant number of patients leading to poor wound healing or infectious complications. Surgical repair of lymphatic injury is greatly aided by the precise and prompt intraoperative localization of the injured lymphatic vessels. We assessed and identified lymphatic leaks in 2 cases of surgical wound lymphorrhea occurring after instrumentation of the groin using laser-assisted indocyanine green lymphography paired with isosulfan blue injection. Both cases healed without complication, and no lymphatic leak recurrence was observed during postoperative follow-up. Laser-assisted indocyanine green lymphography is a useful adjunct in the management of lymphatic leaks after surgery of the groin and may have potential for prophylactic evaluation of high-risk groin wounds.

Novel technique for innervated abdominal wall vascularized composite allotransplantation: a separation of components approach.

OBJECTIVE: Applications for Abdominal Wall Vascularized Composite Allotransplantation may expand if a functional graft with decreased immunosuppressive requirements can be designed. We hypothesize that it is anatomically feasible to prepare a functional, innervated, and vascularized abdominal composite graft using a multilayered component separation technique. Including vascularized bone in the graft design may decrease the immunosuppressive requirements by inducing immunologic chimerism. METHODS: Two cadaver torsos were used. Adipocutaneous flaps were elevated from the midaxillary lines, preserving deep inferior epigastric artery perforators. A 2-layered component separation through the external and internal oblique fasciae was carried out, exposing segmental intercostal thoracolumbar nerves. Superiorly directed muscle release over the subcostal margin provided for a 3-rib segment with attached rectus abdominis muscle. The remainder of the full-thickness allograft was harvested with its vasculature. Flap inset into the recipient cadaver abdomen, with osteosynthesis fixation between donor and recipient ribs, was achieved. RESULTS: The harvested grafts had an average size of 845 ± 205 cm(2) with a total procurement time of 110 minutes. On one cadaver, 4 thoracolumbar nerves were isolated bilaterally, while the other cadaver yielded 3 nerves. The nerves were transected with an average length of 5.7 ± 1.2 cm. The graft vasculature was transected with a length of 4.40 ± 0.10 cm. CONCLUSION: Using the principles of component separation technique, we demonstrated a novel approach to harvest and transfer a neurotized osteomyofasciocutaneous abdominal wall allotransplant as a multipedicled, single functional unit.

Longitudinal outcomes for victims of child abuse.

Childhood abuse and neglect (child maltreatment) represent a common and significant public health burden. The consequences of maltreatment can be seen immediately, in the short term and in the long term. Determination of the exact prevalence of childhood maltreatment is difficult, as many cases go unreported; however in reported cases there is an estimated $124 billion annual burden on the US health-care system. The evaluation of potential maltreatment is difficult as many of the initial symptoms are subtle and can be explained with alternative illnesses or injuries. Potential immediate and short-term effects include brain injury, shaken baby syndrome and behavioral regression. The potential long-term sequelae of child maltreatment are explored in detail here and include increased risks of the development of mental health disorders, substance use disorders and chronic physical complaints during development and adulthood. Lastly, the review provides an overview of current treatment approaches for victims of childhood maltreatment.

Emergence of the acute-phase protein hemopexin in jawed vertebrates.

When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high-affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny as bony fish where it is called warm-temperature acclimation-related 65 kDa protein (WAP65), as serum protein levels are increased at elevated environmental temperatures as well as by infection. During analysis of nurse shark (Ginglymostoma cirratum) plasma we isolated a Ni(2+)-binding serum glycoprotein and characterized it as the APP Hx. We subsequently cloned Hx from nurse shark and another cartilaginous fish species, the little skate Leucoraja erinacea. Functional analysis showed shark Hx, like that of mammals, binds heme but is found at unusually high levels in normal shark serum. As an Hx orthologue could not be found in the genomes of jawless vertebrates or lower deuterostomes it appears to have arisen just prior to the emergence of jawed vertebrates, coincident with the second round of genome-wide duplication and the appearance of tetrameric hemoglobin (Hb).

Construction of a nurse shark (Ginglymostoma cirratum) bacterial artificial chromosome (BAC) library and a preliminary genome survey.

BACKGROUND: Sharks are members of the taxonomic class Chondrichthyes, the oldest living jawed vertebrates. Genomic studies of this group, in comparison to representative species in other vertebrate taxa, will allow us to theorize about the fundamental genetic, developmental, and functional characteristics in the common ancestor of all jawed vertebrates. AIMS: In order to obtain mapping and sequencing data for comparative genomics, we constructed a bacterial artificial chromosome (BAC) library for the nurse shark, Ginglymostoma cirratum. RESULTS: The BAC library consists of 313,344 clones with an average insert size of 144 kb, covering ~4.5 x 1010 bp and thus providing an 11-fold coverage of the haploid genome. BAC end sequence analyses revealed, in addition to LINEs and SINEs commonly found in other animal and plant genomes, two new groups of nurse shark-specific repetitive elements, NSRE1 and NSRE2 that seem to be major components of the nurse shark genome. Screening the library with single-copy or multi-copy gene probes showed 6-28 primary positive clones per probe of which 50-90% were true positives, demonstrating that the BAC library is representative of the different regions of the nurse shark genome. Furthermore, some BAC clones contained multiple genes, making physical mapping feasible. CONCLUSION: We have constructed a deep-coverage, high-quality, large insert, and publicly available BAC library for a cartilaginous fish. It will be very useful to the scientific community interested in shark genomic structure, comparative genomics, and functional studies. We found two new groups of repetitive elements specific to the nurse shark genome, which may contribute to the architecture and evolution of the nurse shark genome.

Recovery of nonbeating donor hearts.

BACKGROUND: Use of hearts from non-heart-beating donors could greatly increase the pool of cardiac homografts. This hypothesis was investigated in a model of traumatic death with New Zealand rabbits which were exsanguinated after 10 minutes of hypotension. METHODS: The hearts were left in situ at normothermia until just before the onset of contracture, were surgically exposed, given either blood cardioplegic, crystalloid cardioplegic, or University of Wisconsin cardioplegic solution, and then stored for 1 hour at 4 degrees C in the respective solutions. The hearts were reperfused for 20 minutes with a Langendorff apparatus. A balloon was placed in the left ventricle, and peak developed pressure and diastolic pressure-volume relationship data were collected over a range of balloon volumes. Control data was obtained from nonischemic rabbit hearts. RESULTS: Blood cardioplegic solution preserved peak developed pressure and the slope of diastolic pressure-volume relationship at control levels, whereas crystalloid cardioplegic and University of Wisconsin solutions showed significant deterioration in both of these indexes. The total adenine nucleotide pool was significantly improved with the use of blood cardioplegic solution compared with crystalloid cardioplegic and University of Wisconsin solutions although all groups were significantly depressed compared with control values. CONCLUSIONS: This study indicates that hearts harvested from non-heart-beating donors can have function that is not statistically different from controls if preserved with blood cardioplegic solution and that University of Wisconsin and crystalloid cardioplegic solutions are inadequate for preserving hearts harvested under these unique conditions.