86 novel HLA-E alleles discovered through full-gene sequencing of 6227 hematopoietic cell transplant patients and unrelated donors.

Until recently the number of alleles of the nonclassical HLA class I gene HLA-E documented in the IPD-IMGT/HLA Database was small and as a result, the gene was often not considered to be notably polymorphic. Here, we describe our work in identifying and submitting 86 novel HLA-E alleles after full-gene single-molecule real-time (SMRT) DNA sequencing of 6227 DNA samples. These samples were comprised of 2468 patients undergoing hematopoietic cell transplantation and 3759 unrelated potential donors. A total of 111 unique HLA-E alleles were detected in this cohort. The majority of novel alleles (79.1%) contained polymorphisms in intronic regions, highlighting the significant undiscovered variation present in the noncoding regions of the HLA-E gene.

The IPD-IMGT/HLA Database.

It is 24 years since the IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The database now contains over 35 000 alleles of the human Major Histocompatibility Complex (MHC) named by the WHO Nomenclature Committee for Factors of the HLA System. This complex contains the most polymorphic genes in the human genome and is now considered hyperpolymorphic. The IPD-IMGT/HLA Database provides a stable and user-friendly repository for this information. Uptake of Next Generation Sequencing technology in recent years has driven an increase in the number of alleles and the length of sequences submitted. As the size of the database has grown the traditional methods of accessing and presenting this data have been challenged, in response, we have developed a suite of tools providing an enhanced user experience to our traditional web-based users while creating new programmatic access for our bioinformatics user base. This suite of tools is powered by the IPD-API, an Application Programming Interface (API), providing scalable and flexible access to the database. The IPD-API provides a stable platform for our future development allowing us to meet the future challenges of the HLA field and needs of the community.

Widespread non-coding polymorphism in HLA class II genes of International HLA and Immunogenetics Workshop cell lines.

As the primary genetic determinant of immune recognition of self and non-self, the hyperpolymorphic HLA genes play key roles in disease association and transplantation. The large, variably sized HLA class II genes have historically been less well characterized than the shorter HLA class I genes. Here, we have used Pacific Biosciences Single Molecule Real-Time (SMRT®) DNA sequencing to perform four-field resolution HLA typing of HLA-DRB1/3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 from a panel of 181 B-lymphoblastoid cell lines from the International HLA and Immunogenetics Workshops. By interrogating all exons, introns, and the untranslated regions of these important reference cells, we have improved their HLA typing resolution on the IPD-IMGT/HLA database. We observed widespread non-coding polymorphism, with over twice as many unique genomic sequences identified compared with coding sequences (CDS). We submitted 263 unique sequences to the IPD-IMGT/HLA Database, often from multiple cell lines, including 114 confirmations of existing alleles, of which 30 were also extensions to full-length genomic sequences where only CDS was available previously. A total of 149 novel alleles were identified, largely differing from their closest reference allele sequences by a single nucleotide polymorphism (SNP). However, some highly divergent alleles were deemed to be recombinants, only detectable by full-length sequencing with long, phased reads. The fourth-field variation we observed allowed fine mapping of linkage disequilibrium patterns and haplotypes to particular ancestries. This study has highlighted the under-appreciated non-coding diversity in HLA class II genes, with potential implications for population genetic and clinical studies.

Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations.

Lipin 1 is a bifunctional protein that is a transcriptional regulator and has phosphatidic acid (PA) phosphohydrolase activity, which dephosphorylates PA to generate diacylglycerol. Human lipin 1 mutations lead to episodic rhabdomyolysis, and some affected patients exhibit cardiac abnormalities, including exercise-induced cardiac dysfunction and cardiac triglyceride accumulation. Furthermore, lipin 1 expression is deactivated in failing heart, but the effects of lipin 1 deactivation in myocardium are incompletely understood. We generated mice with cardiac-specific lipin 1 KO (cs-Lpin1-/-) to examine the intrinsic effects of lipin 1 in the myocardium. Cs-Lpin1-/- mice had normal systolic cardiac function but mild cardiac hypertrophy. Compared with littermate control mice, PA content was higher in cs-Lpin1-/- hearts, which also had an unexpected increase in diacylglycerol and triglyceride content. Cs-Lpin1-/- mice exhibited diminished cardiac cardiolipin content and impaired mitochondrial respiration rates when provided with pyruvate or succinate as metabolic substrates. After transverse aortic constriction-induced pressure overload, loss of lipin 1 did not exacerbate cardiac hypertrophy or dysfunction. However, loss of lipin 1 dampened the cardiac ionotropic response to dobutamine and exercise endurance in association with reduced protein kinase A signaling. These data suggest that loss of lipin 1 impairs cardiac functional reserve, likely due to effects on glycerolipid homeostasis, mitochondrial function, and protein kinase A signaling.

IPD-IMGT/HLA Database.

The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.

Reduced mitochondrial reactive oxygen species production in peripheral nerves of mice fed a ketogenic diet.

NEW FINDINGS: What is the central question of this study? Do peripheral sensory neurons metabolize fat-based fuel sources, and does a ketogenic diet modify these processes? What is the main finding and its importance We show that peripheral axons from mice fed a ketogenic diet respond to fat-based fuel sources with reduced respiration and H2 O2 emission compared with mice fed a control diet. These results add to our understanding of the responses of sensory neurons to neuropathy associated with poor diet, obesity and metabolic syndrome. These findings should be incorporated into current ideas of axonal protection and might identify how dietary interventions may change mitochondrial function in settings of sensory dysfunction. ABSTRACT: Metabolic syndrome and obesity are increasing epidemics that significantly impact the peripheral nervous system and lead to negative changes in sensation and peripheral nerve function. Research to understand the consequences of diet, obesity and fuel usage in sensory neurons has commonly focused on glucose metabolism. Here, we tested whether mouse sensory neurons and nerves have the capacity to metabolize fat-based fuels (palmitoyl-CoA) and whether these effects are altered by feeding of a ketogenic (90% kcal fat) diet compared with a control diet (14% kcal fat). Male C57Bl/6 mice were placed on the diets for 10 weeks, and after the mice were killed, the dorsal root ganglion (DRG) and sciatic nerve (SN) were placed in an Oroboros oxygraph-2K to examine diet-induced alterations in metabolism (respiration) of palmitoyl-CoA and H2 O2 emission (fluorescence). In addition, RNAseq was performed on the DRG of mice fed a control or a ketogenic diet for 12 weeks, and genes associated with mitochondrial respiratory function were analysed. Our results suggest that the sciatic nerves from mice fed a ketogenic diet display reduced O2 respiration and H2 O2 emission when metabolizing palmitoyl-CoA compared with mice fed a control diet. Assessments of changes in mRNA gene expression reveal alterations in genes encoding the NADH dehydrogenase complex and complex IV, which could alter production of reactive oxygen species. These new findings highlight the ability of sensory neurons and axons to oxidize fat-based fuel sources and show that these mechanisms are adaptable to dietary changes.

Intrinsic Activity of C57BL/6 Substrains Associates with High-Fat Diet-Induced Mechanical Sensitivity in Mice.

Pain is significantly impacted by the increasing epidemic of obesity and the metabolic syndrome. Our understanding of how these features impact pain is only beginning to be developed. Herein, we have investigated how small genetic differences among C57BL/6 mice from 2 different commercial vendors lead to important differences in the development of high-fat diet-induced mechanical sensitivity. Two substrains of C57BL/6 mice from Jackson Laboratories (Bar Harbor, ME; C57BL/6J and C57BL/6NIH), as well as C57BL/6 from Charles Rivers Laboratories (Wilmington, MA; C57BL/6CR) were placed on high-fat diets and analyzed for changes in metabolic features influenced by high-fat diet and obesity, as well as measures of pain-related behaviors. All 3 substrains responded to the high-fat diet; however, C57BL/6CR mice had the highest weights, fat mass, and impaired glucose tolerance of the 3 substrains. In addition, the C57BL/6CR mice were the only strain to develop significant mechanical sensitivity over the course of 8 weeks. Importantly, the C57BL/6J mice were protected from mechanical sensitivity, which may be based on increased physical activity compared with the other 2 substrains. These findings suggest that activity may play a powerful role in protecting metabolic changes associated with a high-fat diet and that these may also be protective in pain-associated changes as a result of a high-fat diet. These findings also emphasize the importance of selection and transparency in choosing C57BL/6 substrains in pain-related research. PERSPECTIVE: Obesity and the metabolic syndrome play an important role in pain. This study identifies key differences in the response to a high-fat diet among substrains of C57BL/6 mice and differences in intrinsic physical activity that may influence pain sensitivity. The results emphasize physical activity as a powerful modulator of obesity-related pain sensitivity.

A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice.

Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction.

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain.

INTRODUCTION: Diet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females. METHODS: Here, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high-capacity runners; HCR) or low endurance exercise capacity (low-capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions. RESULTS: LCR female rats have reduced mechanical sensitivity, higher intraepidermal nerve fiber density and TrkA-positive epidermal axons, increased numbers of Langerhans and mast cells in cutaneous tissues, and a higher fat content despite similar overall body weights compared to female HCR rats. Sensory and motor nerve conduction velocities, thermal sensitivity, and mRNA expression of selected genes relevant to peripheral sensation were not different. CONCLUSIONS: These results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.

Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation.

Dietary-associated diseases have increased tremendously in our current population, yet key molecular changes associated with high-fat diets that cause clinical pre-diabetes, obesity, hyperglycemia, and peripheral neuropathy remain unclear. This study examines molecular and metabolic aspects altered by voluntary exercise and a high-fat diet in the mouse dorsal root ganglion. Mice were examined for changes in mRNA and proteins encoding anti-inflammatory mediators, metabolic-associated molecules, and pain-associated ion channels. Proteins involved in the synaptosomal complex and pain-associated TRP ion channels decrease in the dorsal root ganglion of high-fat exercise animals relative to their sedentary controls. Exercise reversed high-fat diet induced mechanical allodynia without affecting weight gain, elevated blood glucose, and utilization of fat as a fuel source. Independent of weight or fat mass changes, high-fat exercised mice display reduced inflammation-associated mRNAs. The benefits of exercise on abnormal peripheral nerve function appear to occur independent of systemic metabolic changes, suggesting that the utilization of fats and inflammation in the peripheral nervous system may be key for diet-induced peripheral nerve dysfunction and the response to exercise.

Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain.

The utilization of physical activity as a therapeutic tool is rapidly growing in the medical community and the role exercise may offer in the alleviation of painful disease states is an emerging research area. The development of neuropathic pain is a complex mechanism, which clinicians and researchers are continually working to better understand. The limited therapies available for alleviation of these pain states are still focused on pain abatement and as opposed to treating underlying mechanisms. The continued research into exercise and pain may address these underlying mechanisms, but the mechanisms which exercise acts through are still poorly understood. The objective of this review is to provide an overview of how the peripheral nervous system responds to exercise, the relationship of inflammation and exercise, and experimental and clinical use of exercise to treat pain. Although pain is associated with many conditions, this review highlights pain associated with diabetes as well as experimental studies on nerve damages-associated pain. Because of the global effects of exercise across multiple organ systems, exercise intervention can address multiple problems across the entire nervous system through a single intervention. This is a double-edged sword however, as the global interactions of exercise also require in depth investigations to include and identify the many changes that can occur after physical activity. A continued investment into research is necessary to advance the adoption of physical activity as a beneficial remedy for neuropathic pain. The following highlights our current understanding of how exercise alters pain, the varied pain models used to explore exercise intervention, and the molecular pathways leading to the physiological and pathological changes following exercise intervention.

Muscle-related differences in mechanomyography frequency-force relationships are model dependent.

The purpose of this study was to examine the surface mechanomyographic mean power frequency (MMG MPF)-force relationships with linear regression models applied to the absolute and log-transformed values for the first dorsal interosseous (FDI), vastus lateralis (VL) and rectus femoris (RF) muscles. Thirteen healthy males performed isometric ramp contractions of the leg extensors and index finger from 10 to 80% of their maximal voluntary contraction with MMG sensors positioned on the VL, RF, and FDI. Simple linear regression models were fit to the absolute and log-transformed MMG MPF-force relationships. Skinfold thickness measurements were taken at each sensor site. There were significant differences for the slopes from the log-transformed MMG MPF-force relationships between the FDI and the leg extensors (P < 0.001) but not the absolute model (P = 0.168). The Y-intercepts were greater for the FDI than the leg extensors for the absolute (P < 0.001) and log-transformed models (P < 0.001), which reflected similar muscle-related differences (P < 0.001) for skinfold thickness. However, there were no significant correlations between Y-intercepts and skinfold thicknesses. Differences in the patterns of response between the FDI and leg extensors were only quantified with the log-transformed model.

Motor unit control strategies of endurance- versus resistance-trained individuals.

INTRODUCTION: We examined motor unit (MU) control properties of resistance-trained (RT) and endurance-trained (ET) individuals. METHODS: Five RT (age 25 ± 4 years) and 5 ET (age 19 ± 1 years) subjects participated. Surface electromyography (EMG) data were recorded from the vastus lateralis during isometric trapezoid muscle actions at 40% and 70% of maximal voluntary contraction. Decomposition and wavelet transform techniques were applied to the EMG signals to extract the firing events of single MUs and EMG intensity across the frequency spectrum. RESULTS: There were significant differences between RT and ET for the mean MU firing rate and derecruitment threshold versus recruitment threshold relationships and EMG intensity at various wavelet bands during the linearly increasing, steady force, and linearly decreasing segments of the trapezoid contraction. CONCLUSIONS: MU behavior is altered as a function of training status and is likely the result of differences in the physical properties of the MU.

The effects of poliomyelitis on motor unit behavior during repetitive muscle actions: a case report.

BACKGROUND: Acute paralytic poliomyelitis is caused by the poliovirus and usually results in muscle atrophy and weakness occurring in the lower limbs. Indwelling electromyography has been used frequently to investigate the denervation and innervation characteristics of the affected muscle. Recently developed technology allows the decomposition of the raw surface electromyography signals into the firing instances of single motor units. There is limited information regarding this electromyographic decomposition in clinical populations. In addition, regardless of electromyographic methods, no study has examined muscle activation parameters during repetitive muscle actions in polio patients. Therefore, the purpose of this study was to examine the motor unit firing rates and electromyographic amplitude and center frequency of the vastus lateralis during 20 repetitive isometric muscle actions at 50% maximal voluntary contraction in healthy subjects and one patient that acquired acute paralytic poliomyelitis. CASE PRESENTATION: One participant that acquired acute type III spinal poliomyelitis (Caucasian male, age = 29 yrs) at 3 months of age and three healthy participants (Caucasian females, age = 19.7 ± 2.1 yrs) participated in this study. The polio participant reported neuromuscular deficiencies as a result of disease in the hips, knees, buttocks, thighs, and lower legs. None of the healthy participants reported any current or ongoing neuromuscular diseases or musculoskeletal injuries. CONCLUSION: An acute bout of poliomyelitis altered motor unit behavior, such as, healthy participants displayed greater firing rates than the polio patient. The reduction in motor unit firing rates was likely a fatigue protecting mechanism since denervation via poliomyelitis results in a reduction of motorneurons. In addition, the concurrent changes in motor unit firing rates, electromyography amplitude and frequency for the polio participant would suggest that the entire motorneuron pool was utilized in each contraction unlike for the healthy participants. Finally, healthy participants exhibited changes in all electromyographic parameters during the repetitive muscle actions despite successfully completing all contractions with only a slight reduction in force. Thus, caution is warranted when quantifying muscular fatigue via motor unit firing rates and other electromyographic parameters since the parameters changed despite successful completing of all contractions with only a moderate reduction in strength in healthy subjects.

Examination of motor unit control properties of the vastus lateralis in an individual that had acute paralytic poliomyelitis.

The purpose of the study was to examine motor unit (MU) recruitment and derecruitment thresholds and firing rates of the vastus lateralis between 2 healthy (HE) individuals (women, ages = 19 and 23 years) and 1 individual (man, age = 22 years) who acquired acute poliomyelitis (PO). Each participant performed submaximal isometric trapezoid muscle actions of the leg extensors from 20% to 90% maximal voluntary contraction in 10% increments with a sensor placed on the vastus lateralis to record electromyography. Electromyographic signals were decomposed into the firing events of single MUs. Linear regressions were performed on the firing rates at recruitment and peak firing rates versus the recruitment thresholds and the derecruitment versus recruitment thresholds. In addition, data were pooled together from all contractions to examine differences between PO and HE with independent samples t-tests calculated for firing rates at recruitment, peak firing rates, recruitment thresholds, derecruitment thresholds, and duration of MU activity. The results demonstrated systematic differences in MU control strategies between the PO and HE. There were differences in the recruitment thresholds (P < 0.001; HE = 30.5% ± 22.2% maximal voluntary contraction; PO = 14.5% ± 5.0% maximal voluntary contraction), firing rates at recruitment (P < 0.001; HE = 7.4 ± 2.5 pulses per second; PO = 6.2 ± 1.7 pulses per second) and peak firing rates across the force spectrum (P = 0.001; HE = 22.2 ± 5.8 pulses per second; PO = 20.3 ± 2.3 pulses per second), altered derecruitment versus recruitment relationships (HE slope = 0.82 derec/rec, PO slope = 1.78 derec/rec), and duration of MU activity (P < 0.001) between the PO (18.6 ± 2.4 seconds) and HE (15.3 ± 3.0 seconds). Future research should examine the possible differences in MU behavior between PO and HE as a result of fatigue to further elucidate disease-related changes in MU properties.

Relationships between skinfold thickness and electromyographic and mechanomyographic amplitude recorded during voluntary and non-voluntary muscle actions.

INTRODUCTION: The purpose of this study was to examine possible correlations between skinfold thicknesses and the a terms from the log-transformed electromyographic (EMGRMS) and mechanomyographic amplitude (MMGRMS)-force relationships, EMG M-Waves, and MMG gross lateral movements (GLM). METHODS: Forty healthy subjects performed a 6-s isometric ramp contraction from 5% to 85% of their maximal voluntary contraction with EMG and MMG sensors placed on the vastus lateralis (VL) and rectus femoris (RF). A single electrical stimulus was applied to the femoral nerve to record the EMG M-waves and MMG GLMs. Skinfold thickness was assessed at the site of each electrode. Pearson's product correlation coefficients were calculated comparing skinfold thicknesses with the a terms from the log-transformed EMGRMS-and MMGRMS-force relationships, EMG M-waves, and MMG GLMs. RESULTS: There were no significant cor1relations (p>0.05) between the a terms and skinfold thicknesses for the RF and VL from the EMGRMS and MMGRMS-force relationships. However, there were significant correlations (p<0.05) between skinfold thicknesses and the EMG M-waves and MMG GLMs for the RF (r=-0.521, -0.376) and VL (r=-0.479, -0.484). DISCUSSION: Relationships were only present between skinfold thickness and the amplitudes of the EMG and MMG signals during the non-voluntary muscle actions.

Muscle-related differences in mechanomyography­force relationships are model-dependent.

INTRODUCTION: In this study we examined the mechanomyographic amplitude (MMG(RMS))­force relationships with log-transform and polynomial regression models for the vastus lateralis (VL), rectus femoris (RF), and first dorsal interosseous (FDI) muscles. METHODS: Twelve healthy (age 23 ± 3 years) men performed isometric ramp contractions of the leg extensors and index finger from 10% to 80% of their maximal voluntary contraction (MVC) with MMG sensors positioned on the VL, RF, and FDI. Log-transform and polynomial regression models were fitted to the relationships. RESULTS: There were differences for the a terms (intercepts) and b terms (slopes) from the log-transform model between the FDI, VL, and RF; however, there were no consistent differences identified with the polynomial regression models. CONCLUSIONS: The log-transform model quantified differences in the patterns of responses between the FDI and the leg extensors, but polynomial regression could not distinguish such differences.

Relationships between the mechanomyographic amplitude patterns of response and concentric isokinetic fatiguing tasks of the leg extensors.

The purpose of the present study was to examine possible correlations between the b terms (slopes) form the log-transformed mechanomyographic amplitude (MMGRMS)-force relationships and the fatigue index calculated from 50 maximal concentric contractions. Forty healthy subjects (age = 21 ± 2 yr) performed isometric ramp contractions from 5% to 85% of their maximal voluntary contraction followed by a 50-repetition concentric fatigue protocol of the leg extensors, fatigue index (%) was calculated from the 50-repetitions. MMG was recorded during the ramp contractions from the vastus lateralis (VL) and rectus femoris (RF). The b terms (slopes) were calculated from the log-transformed MMGRMS-force relationships. Correlations were performed comparing the b terms from the MMGRMS-force relationships for the VL and RF with the fatigue index. Significant positive correlations were found among the b terms from the MMGRMS-force relationships for the VL (p = 0.007, r = 0.417) and RF (p = 0.014, r = 0.386) with the fatigue index. The b terms from the log-transformed MMGRMS-force relationships for the VL and RF may have reflected muscle fiber type composition and, thus, correlated with the fatigue index. This adds further support that the MMGRMS-force relationships may reflect muscle fiber type composition.

Peri-operative challenges and long-term outcomes in liver transplantation for polycystic liver disease.

BACKGROUND: The purpose of this study was to determine peri-operative mortality and long-term outcomes in patients undergoing liver transplantation in the US using the United Network for Organ Sharing (UNOS) database. METHODS: This study is a retrospective review of liver transplantations (LT) recorded in the UNOS database performed between 1988 and 2010. In total, 107 411 LT were performed in the US, 357 (0.3%) were for adult polycystic liver disease (PLD). A random group of 9416 adult patients transplanted for other diagnoses was created for comparison (10% of the adult non-PLD database). RESULTS: Two hundred and seventy-one patients in the adult PLD group were females (75.9%), the mean age was 52.3 ± 8.2 [standard deviation (SD)] years. The median length of transplantation hospital stay was 11 days (interquartile range 8-21). Patients from the PLD group versus the comparison group (9416 patients) consisted of more females, lower Model for End-Stage Liver Disease (MELD) scores (17 versus 21 points), more multi-organ transplants (41% versus 4 %), chronic renal failure (creatinine 2.7 versus 1.5) and fewer patients with chronic hepatitis C (1.4% versus 32%). Peri-operative mortality (≤30 days) was 9% in the PLD versus 6% in the comparison group; however, at 1 year PLD survival was similar (85% versus 85%) to other diagnoses and better at 3 (81% versus 77%) and 5 years (77% versus 71%, overall Log Rank P = 0.006). A similar PLD survival advantage was observed in isolated initial transplants (P = 0.019). CONCLUSION: In spite of early technical challenges and mortality, transplantation should be considered an option for selected patients with PLD as excellent long-term outcomes can be achieved.

The reliability of the interpolated twitch technique during submaximal and maximal isometric muscle actions.

The reliability of the interpolated twitch technique during submaximal and maximal isometric muscle actions. J Strength Cond Res 27(10): 2909-2913, 2013-The purpose of this study was to examine the test-retest reliability of the percent voluntary activation (%VA) vs. force relationships. Fourteen healthy men (mean ± SD age = 21 ± 2.6 years) and 8 women (age = 21 ± 1.8 years) completed 4 maximal voluntary contractions (MVCs) and 9 randomly ordered submaximal isometric plantar flexions from 10 to 100% of the MVC. Transcutaneous electrical stimuli were delivered to the tibial nerve using a high-voltage constant-current stimulator (DS7AH; Digitimer, Herthfordshire, United Kingdom). The %VA was calculated for each maximal and submaximal MVC. Paired-samples t-tests were used to quantify systematic variability, whereas the intraclass correlation coefficients (ICCs), standard error of the mean (%SEM), and minimum differences (%MD; expressed as a percentage of the means) were used for test-retest reliability. Systematic variability was not present at any of the contraction intensities (p > 0.05). The ICCs ranged from 0.52 to 0.84, whereas the %SEM ranged from 6.75 to 38.45%, and the %MD ranged from 18.71 to 106.58%. The ICCs were ≥0.74 at contraction intensities ranging from 40 to 100% MVC (6.75-16.78% SEM), whereas the ICCs were ≤0.65 (20.95-38.45% SEM) for the contraction intensities ≤30% MVC. Although not statistically tested, the ICCs tended to be higher, whereas the %SEMs lower for contractions ≥40% MVC. Future research using %VA during submaximal contraction intensities to predict a true maximal force may want to exclude contraction intensities <40% MVC. In addition, caution is warranted when interpreting the changes in the %VA during MVCs after an experimental intervention.