Dissemination of meticillin-resistant Staphylococcus aureus sequence type 8 (USA300) in Taiwan.

BACKGROUND: In Taiwan, sequence type (ST) 239 and ST59 were two major clones among meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates in the past two decades. USA300 (ST8) prevailed in the Americas but not in outside areas. Recently USA300 (ST8) emerged and was increasingly identified in Taiwan; we thus conducted an island-wide study to explore the role of USA300 among MRSA isolates. METHODS: One hundred MRSA bloodstream isolates identified in 2020 from each of the six participating hospitals in Taiwan were collected and characterized. The first 10 ST8 isolates from each hospital were further analysed by whole-genome sequencing. RESULTS: Of the 590 confirmed MRSA isolates, a total of 22 pulsotypes and 21 STs were identified. The strain of pulsotype AI/ST8 was the most common lineage identified, accounting for 187 isolates (31.7%) and dominating in five of six hospitals, followed by pulsotype A/ST239 (14.7%), pulsotype C/ST59 (13.9%) and pulsotype D/ST59 (9.2%). Of the 187 pulsotype AI/ST8 isolates, 184 isolates were characterized as USA300 and clustered in three major sub-pulsotypes, accounting for 78%. Ninety per cent of the 60 ST8 isolates for whole-genome sequencing were clustered in three major clades. CONCLUSIONS: In 2020, USA300 became the most common clone of MRSA in Taiwan, accounting for >30% of MRSA bloodstream isolates island wide. Most of USA300 isolates circulating in Taiwan might have been imported on multiple occasions and evolved into at least three successful local clades. MRSA USA300 has successfully established its role in Taiwan, an area outside of the Americas.

J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine.

There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST4) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70 mg/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8-12-weeks (morphine-sensitive phase; Phase 1) and 16-18-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30 mg/kg), gabapentin (100 mg/kg i.p.), subcutaneous morphine (1 mg/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156 at 30 mg/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5 h compared with 1 h for gabapentin and morphine. The durations of action for all three compounds were greater than 3 h. The corresponding mean (±SEM) extent and duration of anti-allodynia (ΔPWT AUC) for gabapentin did not differ significantly from that for J-2156 (30 mg/kg) or morphine. However, in Phase 2, the ΔPWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (±SEM) ΔPWT AUC for J-2156 (30 mg/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (±SEM) ΔPWT AUCs did not differ significantly (p > 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST4 receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.

The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

Maternal and Child Health Pipeline Training Programs: A Description of Training Across 6 Funded Programs.

PURPOSE: The HRSA-funded maternal and child health pipeline training programs (MCHPTPs) are a response to the critical need to diversify the MCH workforce, as a strategy to reduce health disparities in MCH populations. These MCHPTPs support students from undergraduate to graduate education and ultimately into the MCH workforce. DESCRIPTION: The models and components of training across the six MCHPTPs funded in 2016-2021 are summarized, to examine the design and delivery of undergraduate pipeline training and the insights gained across programs. ASSESSMENT: Strategies that emerged across training programs were organized into three themes: recruitment, support for student persistence (in education), and pipeline-to-workforce intentionality. Support for student persistence included financial support, mentoring, creating opportunity for students to develop a sense of belonging, and the use of research as a tool to promote learning and competitiveness for graduate education. Finally, the link to Maternal and Child Health Bureau (MCHB) long-term training and other MCHB opportunities for professional development contributed significant nuance to the pipeline-to-workforce objectives of these programs. CONCLUSIONS: The MCHPTPs not only increase the diversity of the MCH workforce, they also actively prepare the next generation of MCH leaders. The intentional connection of undergraduates to the infrastructure and continuum of MCH training, underscores the comprehensive impact of this funding.

Mechanical work accounts for most of the energetic cost in human running.

The metabolic cost of human running is not well explained, in part because the amount of work performed actively by muscles is largely unknown. Series elastic tissues such as tendon can save energy by performing work passively, but there are few direct measurements of the active versus passive contributions to work in running. There are, however, indirect biomechanical measures that can help estimate the relative contributions to overall metabolic cost. We developed a simple cost estimate for muscle work in humans running (N = 8) at moderate speeds (2.2-4.6 m/s) based on measured joint mechanics and passive dissipation from soft tissue deformations. We found that even if 50% of the work observed at the lower extremity joints is performed passively, active muscle work still accounts for 76% of the net energetic cost. Up to 24% of this cost compensates for the energy lost in soft tissue deformations. The estimated cost of active work may be adjusted based on assumptions of multi-articular energy transfer, elasticity, and muscle efficiency, but even conservative assumptions yield active work costs of at least 60%. Passive elasticity can reduce the active work of running, but muscle work still explains most of the overall energetic cost.

Stepping onto the unknown: reflexes of the foot and ankle while stepping with perturbed perceptions of terrain.

Unanticipated variations in terrain can destabilize the body. The foot is the primary interface with the ground and we know that cutaneous reflexes provide important sensory feedback. However, little is known about the contribution of stretch reflexes from the muscles within the foot to upright stability. We used intramuscular electromyography measurements of the foot muscles flexor digitorum brevis (FDB) and abductor hallucis (AH) to show for the first time how their short-latency stretch reflex response (SLR) may play an important role in responding to stepping perturbations. The SLR of FDB and AH was highest for downwards steps and lowest for upwards steps, with the response amplitude for level and compliant steps in between. When the type of terrain was unknown or unexpected to the participant, the SLR of AH and the ankle muscle soleus tended to decrease. We found significant relationships between the contact kinematics and forces of the leg and the SLR, but a person's expectation still had significant effects even after accounting for these relationships. Motor control models of short-latency body stabilization should not only include local muscle dynamics, but also predictions of terrain based on higher level information such as from vision or memory.

Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.

For the two proteins myoglobin and fluoroacetate dehalogenase, we present a systematic comparison of crystallographic diffraction data collected by serial femtosecond (SFX) and serial synchrotron crystallography (SSX). To maximize comparability, we used the same batch of micron-sized crystals, the same sample delivery device, and the same data analysis software. Overall figures of merit indicate that the data of both radiation sources are of equivalent quality. For both proteins, reasonable data statistics can be obtained with approximately 5000 room-temperature diffraction images irrespective of the radiation source. The direct comparability of SSX and SFX data indicates that the quality of diffraction data obtained from these samples is linked to the properties of the crystals rather than to the radiation source. Therefore, for other systems with similar properties, time-resolved experiments can be conducted at the radiation source that best matches the desired time resolution.

Cardiac magnetic resonance imaging: insights into developmental programming and its consequences for aging.

Cardiovascular diseases (CVD) are important consequences of adverse perinatal conditions such as fetal hypoxia and maternal malnutrition. Cardiac magnetic resonance imaging (CMR) can produce a wealth of physiological information related to the development of the heart. This review outlines the current state of CMR technologies and describes the physiological biomarkers that can be measured. These phenotypes include impaired ventricular and atrial function, maladaptive ventricular remodeling, and the proliferation of myocardial steatosis and fibrosis. The discussion outlines the applications of CMR to understanding the developmental pathways leading to impaired cardiac function. The use of CMR, both in animal models of developmental programming and in human studies, is described. Specific examples are given in a baboon model of intrauterine growth restriction (IUGR). CMR offers great potential as a tool for understanding the sequence of dysfunctional adaptations of developmental origin that can affect the human cardiovascular system.

101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species.

Clostridium innocuum is a vancomycin-resistant pathogen that may cause antibiotic-associated diarrhoea.

OBJECTIVES: Clostridium innocuum can cause extraintestinal infection in patients with underlying diseases. The role of C. innocuum in antibiotic-associated diarrhoea (AAD) remains unknown. METHODS: Clinical information of 103 patients from whom C. innocuum was isolated was reviewed. We carried out cellular and animal experiments to examine the pathogenic potential of C. innocuum in AAD. RESULTS: Eighty-eight per cent (91/103) of the 103 patients received antibiotics within 2 weeks of diarrhoea onset. Patients were further classified into two groups, severe colitis and diarrhoea, according to clinical severity level. The mortality rate was 13.6% (14/103) among the patients from whom C. innocuum was isolated. The lowest concentrations at which 90% of the isolates were inhibited for metronidazole and vancomycin were 0.5 and 16 mg/L, respectively. All isolates tested were susceptible to metronidazole but resistant to vancomycin. Nineteen randomly selected isolates (ten from severe colitis group, nine from diarrhoea group) were subjected to further in vitro cellular examinations. The level of cytotoxicity to Vero cells was significantly higher in isolates from the severe colitis group at both 24 and 48 hours after inoculation (24 and 48 hours, p 0.042 and 0.033, respectively). We observed apoptotic changes that subsequently led to cell death in C. innocuum-infected Vero cells. Tissue damages, necrotic changes and oedema were observed in the mouse ileal loop infected by C. innocuum. CONCLUSIONS: Vancomycin-resistant C. innocuum may play a potential role as a causative agent of AAD. The clinical manifestations of AAD caused by C. innocuum were diarrhoea or severe colitis, including pseudomembranous colitis.

Poor perinatal growth impairs baboon aortic windkessel function.

The ability of the aorta to buffer blood flow and provide diastolic perfusion (Windkessel function) is a determinant of cardiovascular health. We have reported cardiac dysfunction indicating downstream vascular abnormalities in young adult baboons who were intrauterine growth restricted (IUGR) at birth as a result of moderate maternal nutrient reduction. Using 3 T MRI, we examined IUGR offspring (eight male, eight female; 5.7 years; human equivalent 25 years) and age-matched controls (eight male, eight female; 5.6 years) to quantify distal descending aortic cross-section (AC) and distensibility (AD). ANOVA showed decreased IUGR AC/body surface area (0.9±0.05 cm2/m2 v. 1.2±0.06 cm2/m2, M±s.e.m., P<0.005) and AD (1.7±0.2 v. 4.0±0.5×10-3/mmHg, P<0.005) without sex difference or group-sex interaction, suggesting intrinsic vascular pathology and impaired development persisting in adulthood. Future studies should evaluate potential consequences of these changes on coronary perfusion, afterload and blood pressure.

A shared neural integrator for human posture control.

Control of standing posture requires fusion of multiple inputs including visual, vestibular, somatosensory, and other sensors, each having distinct dynamics. The semicircular canals, for example, have a unique high-pass filter response to angular velocity, quickly sensing a step change in head rotational velocity followed by a decay. To stabilize gaze direction despite this decay, the central nervous system supplies a neural "velocity storage" integrator, a filter that extends the angular velocity signal. Similar filtering might contribute temporal dynamics to posture control, as suggested by some state estimation models. However, such filtering has not been tested explicitly. We propose that posture control indeed entails a neural integrator for sensory inputs, and we test its behavior with classic sensory perturbations: a rotating optokinetic stimulus to the visual system and a galvanic vestibular stimulus to the vestibular system. A simple model illustrates how these two inputs and body tilt sensors might produce a postural tilt response in the frontal plane. The model integrates these signals through a direct weighted sum of inputs, with or without an indirect pathway containing a neural integrator. Comparison with experimental data from healthy adult subjects (N = 16) reveals that the direct weighting model alone is insufficient to explain resulting postural transients, as measured by lateral tilt of the trunk. In contrast, the neural integrator, shared by sensory signals, produces the dynamics of both optokinetic and galvanic vestibular responses. These results suggest that posture control may involve both direct and indirect pathways, which filter sensory signals and make them compatible for sensory fusion.NEW & NOTEWORTHY Control of standing posture requires fusion of multiple inputs including visual, vestibular, somatosensory, and other sensors, each having distinct dynamics. We propose that postural control also entails a shared neural integrator. To test this theory, we perturbed standing subjects with classic sensory stimuli (optokinetic and galvanic vestibular stimulation) and found that our proposed shared filter reproduces the dynamics of subjects' postural responses.

Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons.

Developmental programming studies indicate that glucocorticoids modify fetal development. We hypothesized that administration of the synthetic glucocorticoid (sGC) betamethasone to pregnant baboons at doses and stages of fetal life equivalent to human obstetric practice to decrease premature offspring morbidity and mortality, programs lipid metabolism. In 10-year-old male baboons (human equivalent 40) exposed in fetal life to betamethasone or saline, we quantified pericardial fat and hepatic lipid content with magnetic resonance imaging and spectroscopy. sGC offspring delivered at term as do most sGC-exposed human neonates. Pericardial fat thickness (7.7±3.6 mm vs 3.1±1.1 mm, M±s.d.; P=0.022; n=5) and hepatic fatty acids (13.3±11.0% vs 2.5±2.2%; P=0.046; n=5) increased following sGC without birth weight or current body morphometric differences. Our results indicate that antenatal sGC therapy caused abnormal fat deposition and adult body composition in mid-life primate offspring. The concern raised is that this degree of pericardial and hepatic lipid accumulation can lead to harmful local lipotoxicity. In summary, developmental programing by sGC produces a mid-life metabolically obese but normal weight phenotype. Prior studies show sexually dimorphic responses to some programming challenges thus female studies are necessary.

Comparative genomics of Mortierella elongata and its bacterial endosymbiont Mycoavidus cysteinexigens.

Endosymbiosis of bacteria by eukaryotes is a defining feature of cellular evolution. In addition to well-known bacterial origins for mitochondria and chloroplasts, multiple origins of bacterial endosymbiosis are known within the cells of diverse animals, plants and fungi. Early-diverging lineages of terrestrial fungi harbor endosymbiotic bacteria belonging to the Burkholderiaceae. We sequenced the metagenome of the soil-inhabiting fungus Mortierella elongata and assembled the complete circular chromosome of its endosymbiont, Mycoavidus cysteinexigens, which we place within a lineage of endofungal symbionts that are sister clade to Burkholderia. The genome of M. elongata strain AG77 features a core set of primary metabolic pathways for degradation of simple carbohydrates and lipid biosynthesis, while the M. cysteinexigens (AG77) genome is reduced in size and function. Experiments using antibiotics to cure the endobacterium from the host demonstrate that the fungal host metabolism is highly modulated by presence/absence of M. cysteinexigens. Independent comparative phylogenomic analyses of fungal and bacterial genomes are consistent with an ancient origin for M. elongata - M. cysteinexigens symbiosis, most likely over 350 million years ago and concomitant with the terrestrialization of Earth and diversification of land fungi and plants.

Comparative genomics and expression levels of hydrophobins from eight mycorrhizal genomes.

Hydrophobins are small secreted proteins that are present as several gene copies in most fungal genomes. Their properties are now well understood: they are amphiphilic and assemble at hydrophilic/hydrophobic interfaces. However, their physiological functions remain largely unexplored, especially within mycorrhizal fungi. In this study, we identified hydrophobin genes and analysed their distribution in eight mycorrhizal genomes. We then measured their expression levels in three different biological conditions (mycorrhizal tissue vs. free-living mycelium, organic vs. mineral growth medium and aerial vs. submerged growth). Results confirmed that the size of the hydrophobin repertoire increased in the terminal orders of the fungal evolutionary tree. Reconciliation analysis predicted that in 41% of the cases, hydrophobins evolved from duplication events. Whatever the treatment and the fungal species, the pattern of expression of hydrophobins followed a reciprocal function, with one gene much more expressed than others from the same repertoire. These most-expressed hydrophobin genes were also among the most expressed of the whole genome, which suggests that they play a role as structural proteins. The fine-tuning of the expression of hydrophobin genes in each condition appeared complex because it differed considerably between species, in a way that could not be explained by simple ecological traits. Hydrophobin gene regulation in mycorrhizal tissue as compared with free-living mycelium, however, was significantly associated with a calculated high exposure of hydrophilic residues.

All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.

Soft tissues store and return mechanical energy in human running.

During human running, softer parts of the body may deform under load and dissipate mechanical energy. Although tissues such as the heel pad have been characterized individually, the aggregate work performed by all soft tissues during running is unknown. We therefore estimated the work performed by soft tissues (N=8 healthy adults) at running speeds ranging 2-5 m s(-1), computed as the difference between joint work performed on rigid segments, and whole-body estimates of work performed on the (non-rigid) body center of mass (COM) and peripheral to the COM. Soft tissues performed aggregate negative work, with magnitude increasing linearly with speed. The amount was about -19 J per stance phase at a nominal 3 m s(-1), accounting for more than 25% of stance phase negative work performed by the entire body. Fluctuations in soft tissue mechanical power over time resembled a damped oscillation starting at ground contact, with peak negative power comparable to that for the knee joint (about -500 W). Even the positive work from soft tissue rebound was significant, about 13 J per stance phase (about 17% of the positive work of the entire body). Assuming that the net dissipative work is offset by an equal amount of active, positive muscle work performed at 25% efficiency, soft tissue dissipation could account for about 29% of the net metabolic expenditure for running at 5 m s(-1). During running, soft tissue deformations dissipate mechanical energy that must be offset by active muscle work at non-negligible metabolic cost.

Successful combined liver/kidney transplantation from a donor with Pompe disease.

Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. This case demonstrates co-operative transplant surgery and genetic medicine evaluation and risk estimation for donors with inherited metabolic disorders some of which may be suitable for donation of selected organs for transplantation.