Disorder-to-order transition of long fibers contained in evaporating sessile drops.

A liquid drop containing a long fiber is a complex system whose configuration is determined by an interplay of elastic stresses in the fiber and capillary forces due to the liquid. We study the morphological evolution of fibers that are much longer than the drop diameter in evaporating sessile drops. After insertion, the fibers are either found in an ordered or disordered state, with increasing disorder for increasing fiber length. Upon evaporation, the order increases, in such a way that the final configuration deposited on the solid surface is either a circle, an ellipse, or 8-shaped. The morphology of the deposit depends on the fiber length and the elastocapillary length, both non-dimensionalized with the characteristic drop size, which we classify in a morphology regime map. The disorder-to-order transition allows depositing ordered fiber structures on solid surfaces even in cases of a strongly disordered state after fiber insertion. Combined with technologies such as inkjet printing, this process could open new avenues to decorate surfaces with filamental structures whose morphology can be controlled by varying the fiber length.

Recommendations for return to sports after total hip arthroplasty are becoming less restrictive as implants improve.

INTRODUCTION: Total hip arthroplasty (THA) surgeries are expected to exponentially increase in the upcoming years, likely because of the overall broader indication of THAs. With these developments, an increasing number of younger (< 50 years) and active patients will receive surgical interventions, and expectations for an active lifestyle will accordingly increase. In addition, surgeons now have a growing array of techniques and implant materials to choose from. Despite these developments, evidence to provide the best standard-of-care to patients with high expectations for return to sports (RTS) is scarce and urgently needed. What recommendations do arthroplasty surgeons currently make to patients with high return to sports expectations, what factors may influence their recommendations and what surgical techniques and implant specifications are considered favorable in the treatment of patients with a more active lifestyle? This study was conducted to analyze the current recommendations, patient assessment, and patient counseling after THA to identify trends and relevant factors for surgical decision-making in patients with high-RTS expectations. MATERIAL AND METHODS: We designed a questionnaire comprising five general items and 19 specific items that included 46 sub-items for hip arthroplasty and conducted a survey among 300 German surgeons specialized in arthroplasty at the German Arthroplasty Society (AE) to assess expert opinions, recommendations, surgical decision-making, and patient counseling for patients with high expectations for RTS after THA. RESULTS: The majority of surgeons (81.9%) were in favor of RTS after THA. Risks associated with sports after THA were considered minimal (1%), with periprosthetic fractures ranking highest, followed by hip dislocation and polyethylene wear. Some surgical decision-making was influenced by high-RTS expectations in regard to implant fixation, stem type, femoral head diameter, and bearing-surface tribology. We observed an increasingly liberal counseling of patients for high-impact sports. CONCLUSION: With the improvement of implants and surgical techniques, surgeons are more willing to encourage patients to adopt a more active lifestyle. However, the true long-term limitations need further investigation in future studies. LEVEL OF EVIDENCE: 5 Expert opinions.

Detachment of particles and particle clusters from liquid/liquid interfaces.

The detachment of microspheres from a liquid/liquid interface triggered by body forces is studied experimentally, both for the case of single particles and for particle clusters. The values of the critical force required to detach particles from the interface are in agreement with the maximum values of the wetting force keeping a particles at the interface. In the case of particle clusters, a rearrangement of the cluster configuration from a raft to a more compact structure is observed when the body force is increased. Clusters detach from the liquid/liquid interface at smaller acceleration values than single particles. The critical accelerations required to detach particle clusters are consistent with models assuming that the wetting force acts at the circumference of a spherical or hemispherical densely packed particle cluster. These models predict that the critical acceleration for particle clusters scales as n(-2/3), where n is the number of particles in a cluster.

[Periprosthetic infection after hip arthroplasty]. / Periprothetische Infektion nach Hüftendoprothetik.

BACKGROUND: Periprosthetic infections (PPI) represent one of the most complex complications in arthroplasty concerning both, diagnosis and therapy. The incidence of PPI of the hip is approximately 1 % after primary procedures and 4 % after revision surgery. About two thirds of PPIs occur via intraoperative contamination and the remaining PPIs are acquired by hematogenous seeding. AIM: This article presents an overview of up to date evidence-based diagnostics and therapy of PPI of the hip with the establishment of a clear algorithm. METHODS: A selective literature search was carried out with the inclusion of own work. RESULTS: A PPI must be actively excluded in cases of a painful prosthesis or signs of loosening within the first years after implantation. Measurement of C-reactive protein (CRP) can be normal especially in cases of chronic (low grade) PPI and cannot be used as an exclusion criterion. The standard diagnostic procedure includes preoperative joint aspiration with culture and leukocyte counts as well as culture and histology of periprosthetic tissue. Imaging techniques, such as magnetic resonance imaging (MRI) and scintigraphy are of inferior significance. Newer methods, such as sonication of removed implants have revolutionized the diagnostics and several cases which had previously been considered aseptic loosening failures have now been reclassified as PPI. Essential parameters for the treatment algorithm are maturity of the biofilm, stability of the prosthesis, the causative organism and the state of the soft tissue. Retention of the prosthesis can only be considered when the biofilm is still immature (acute PPI). In chronic (low grade) PPI eradication of the infection can only be achieved by exchanging the prosthesis. This has to be performed either as a one-stage procedure or as a two-stage exchange with a short (2-4 weeks) or a long (> 6 weeks) interval. Biofilm active antibiotics play an essential role in the treatment of PPI and have to be used as targeted therapy. DISCUSSION: Successful therapy and diagnostics of PPI require following an exact algorithm. The interdisciplinary cooperation between specialists for infectious diseases and microbiologists represents a decisive factor.

Isotachophoresis with emulsions.

An experimental study on isotachophoresis (ITP) in which an emulsion is used as leading electrolyte (LE) is reported. The study aims at giving an overview about the transport and flow phenomena occurring in that context. Generally, it is observed that the oil droplets initially dispersed in the LE are collected at the ITP transition zone and advected along with it. The detailed behavior at the transition zone depends on whether or not surfactants (polyvinylpyrrolidon, PVP) are added to the electrolytes. In a system without surfactants, coalescence is observed between the droplets collected at the ITP transition zone. After having achieved a certain size, the droplets merge with the channel walls, leaving an oil film behind. In systems with PVP, coalescence is largely suppressed and no merging of droplets with the channel walls is observed. Instead, at the ITP transition zone, a droplet agglomerate of increasing size is formed. In the initial stages of the ITP experiments, two counter rotating vortices are formed inside the terminating electrolyte. The vortex formation is qualitatively explained based on a hydrodynamic instability triggered by fluctuations of the number density of oil droplets.

Liquefaction necrosis of mitral annulus calcification in a patient with chronic renal failure: an unrecognized diagnosis.

Mitral annulus calcification is one of the most common cardiac calcifications. In patients with end-stage renal disease undergoing echocardiography, it can be detected in more than 40%. A specific form of mitral annulus calcification is liquefaction necrosis. It is often not adequately recognized by echocardiographers or clinicians and can be mistaken for cardiac tumor or infective vegetation. Here we report a case of liquefaction necrosis of mitral annulus calcification, mimicking an infective vegetation of the mitral valve apparatus in a patient with chronic renal failure.

Electrophoretic partitioning of proteins in two-phase microflows.

This work reports on protein transport phenomena discovered in partitioning experiments with a novel setup for continuous-flow two-phase electrophoresis consisting of a microchannel in which a phase boundary is formed in flow direction. Proteins can be partitioned exploiting their affinity to different aqueous phases in two-phase systems. This separation process may be enhanced or extended by applying an electric field perpendicular to the phase boundary. In this context, microsystems offer new possibilities, as interfacial forces usually dominate over volume forces, thus allowing a superior control of the formation and arrangement of liquid/liquid phase boundaries. The two immiscible phases which are injected separately into the microchannel are taken from a polyethylene glycol (PEG)-dextran system. The side walls of the channel are partially made of gel material which serves as an ion conductor and decouples the channel from the electrodes, thus preventing bubble generation inside the separation channel. The experiments show that the electrophoretic transport of proteins between the laminated liquid phases is characterized by a strong asymmetry. When bovine serum albumin (BSA) is introduced into the PEG-rich phase, it can easily be transferred into the dextran-rich phase via an applied electric field of low strength or just by diffusion. In the reverse case, up to a certain field strength the transfer to the opposing phase is strongly inhibited. Only if the field strength is further increased will the BSA molecules leave the dextran-rich phase almost completely.

Real-time contrast-enhanced sonography of renal transplant recipients predicts chronic allograft nephropathy.

Real-time contrast-enhanced sonography (RT-CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The study was performed to evaluate the feasibility of RT-CES in detecting chronic allograft nephropathy (CAN) in comparison to color Doppler ultrasonography (CDUS). A total of 26 consecutive renal transplant recipients were prospectively studied using RT-CES and conventional CDUS. Transplant tissue perfusion imaging was performed by low-power imaging during i.v. administration of the sonocontrast Optison. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow A *beta (A = peak signal intensity, beta= slope of signal intensity rise). In contrast to conventional CDUS resistance and pulsatility indices, renal blood flow estimated by CES was highly significant related to S-creatinine (r =-0.62, p = 0.0004). Determination of renal blood flow by CES reached a higher sensitivity (91% vs. 82%, p < 0.05), specificity (82% vs. 64%, p < 0.05) and accuracy (85% vs. 73%, p < 0.05) for the diagnosis of CAN as compared to conventional CDUS resistance indices. Perfusion parameters derived from RT-CES significantly improve the early detection of CAN compared to conventional CDUS. RT-CES using low-power real-time perfusion imaging is a feasible method to evaluate microvascular perfusion in renal allograft recipients.

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

OBJECTIVE: To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. METHODS AND RESULTS: Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). CONCLUSION: MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

Electroosmotic flow patterning using microfluidic delay loops.

A theoretical and experimental investigation of alternating electroosmotic flow patterns by means of specially designed delay loops is presented. Using elementary methods of compact network modeling and detailed FEM simulations the flow behavior and, in particular, the rearrangement of sample plugs is modeled. The proposed designs rely on flow splitting in combination with electroosmotic delay loops leading to a runtime difference or phase shift between two sub-streams. Due to this phase shift, a new fluid interface is generated at the merging point. The approach is experimentally validated by injection of a Rhodamine 6G solution into an aqueous sodium tetraborate buffer.

Real-time myocardial contrast echocardiography for the detection of stress-induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon emission computed tomography.

BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising technique for assessing myocardial perfusion. The purpose of this study was to test whether realtime MCE can be used to detect functionally significant coronary artery stenosis in patients with known or suspected coronary artery disease. Myocardial contrast echocardiographic studies were compared with nearly simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT) as a clinical standard reference to evaluate regional myocardial perfusion defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10 ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56 mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber views, each divided into 6 segments. Tracer uptake and myocardial opacification were visually analyzed for each segment by two pairs of blinded observers and graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial segments, myocardial opacification by MCE was uninterpretable in 143 (18%) segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments. Interobserver variability for MCE was good with concordance rates of 83% (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental level. In the diagnosis of fixed and reversible defects, and of normal perfusion, concordance rates were 73, 65 and 83%, respectively. When analysis was performed at the regional level, we found comparable levels of concordance rates for LAD (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion territories. CONCLUSIONS: These findings suggest that realtime MCE is a clinically acceptable method to evaluate myocardial perfusion defects during dipyridamole stress testing.

Is the "candy-wrapper" effect of (32)P radioactive beta-emitting stents due to remodeling or neointimal hyperplasia? Insights from intravascular ultrasound.

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Echocardiographic quantification of left ventricular asynergy in coronary artery disease with Fourier phase imaging.

BACKGROUND: Visual evaluation of wall motion is subjective and may be difficult in patients with impaired left ventricular function. Current algorithms used to analyze wall motion usually neglect motion asynchrony that may be profoundly altered in coronary artery disease. This study was to investigate whether the extent of left ventricular asynergy can be used to quantify the severity of regional myocardial dysfunction by the use of Fourier phase imaging. METHODS: Echocardiographic cine loops of 21 patients with ischemic cardiomyopathy (EF < or = 40%) were mathematically transformed using a first-harmonic Fourier algorithm displaying the sequence of wall motion as phase angles in parametric images and regional phase histograms. Segmental fractional area shortening (FAC) and qualitative assessment of regional wall motion based on visual inspection served as reference method. RESULTS: There was an inverse linear relationship between FAC and phase angles (r = -0.75, p < 0.01). Normal endocardial motion yielded low phase angles (mean 16 +/- 15 degrees SD). With an increase in wall motion abnormalities, phase angles were progressively delayed by 56 +/- 38 degrees in hypokinetic, by 88 +/- 38 degrees in akinetic, and by 143 +/- 33 degrees (p < 0.001) in dyskinetic segments. CONCLUSIONS: These results demonstrate that left ventricular asynchrony is an indicator of regional myocardial dysfunction in coronary artery disease. Echocardiographic Fourier phase imaging can be used to quantify wall motion displaying contraction sequence in a simple and objective format.

[Psychological satiation: a new experimental study of an old construct]. / Psychische Sättigung: Eine neue experimentelle Untersuchung zu einem alten Konstrukt.

The present experiment on the phenomenon of psychic satiation expands on the work of Karsten (1928) and Lewin (1928). Psychic satiation denotes a loss of intrinsic motivation when the same action is performed repeatedly. Although many studies have shown the high theoretical and practical relevance of this phenomenon, the conditions which lead to or reinforce psychic satiation have rarely been investigated empirically. Based on the concept of psychic satiation as formulated by Karsten and Lewin and refined by Schulz-Hardt, Rott, Meinken, and Frey (in press), we predicted that psychic satiation will increase if the task does not lend itself to being carried out "peripherally" (i.e., as an almost unconscious incidental action) and if it has high personal relevance. These predictions were investigated in an experiment with 66 high-school students who performed different versions of the "Konzentrations-Leistungs-Test" (concentration-performance-test, KLT). The results are largely in line with our predictions. In addition, the results indicate that the relation between satiation and performance is moderated by personal relevance and the induced task characteristic.

[Confirmatory information search in simultaneous vs. sequential information presentation]. / Konfirmatorische Informationssuche bei simultaner vs. sequentieller Informationsvorgabe.

After having made a preliminary or final decision, people prefer information that supports their chosen alternative to information that conflicts with their choice. Jonas, Schulz-Hardt, Frey, and Thelen (in press) found that sequential presentation of information leads to an even stronger preference for supporting information than the traditional form of simultaneous presentation. Their proposed explanation for this effect was that sequential presentation induces a focus on the prior decision, thereby increasing commitment to this decision. The present experiment was designed to rule out an alternative explanation: Being repeatedly confronted with pieces of information to select from could induce the participants to search for more information than they consider to be necessary, and because less effort is required to process supporting information the additional information requests are predominantly for these supporting pieces of information. To test this alternative explanation, in the present experiment--as in the Jonas et al. (in press) experiments--simultaneous vs. sequential information presentation following a preliminary decision was manipulated. In contrast to the former experiments, this time the number of information requests was fixed: Participants in both conditions had to choose 8 out of 16 pieces of information. The results show that once again a stronger preference for supporting information arises when the information is presented sequentially compared to simultaneously. The alternative explanation mentioned above could thus be ruled out.

Differential value of adenosine myocardial contrast echocardiography and dobutamine stress echocardiography in evaluating functional significance of coronary artery stenosis in a porcine model.

AIM: Myocardial contrast echocardiography (MCE) during adenosine induced hyperemia is an experimental method that detects flow limiting coronary artery stenosis by visualizing myocardial perfusion defects. Noninvasive detection of flow limiting coronary artery stenosis in clinical routine is a frequent domaine of dobutamine stress echocardiography (DSE) visualizing ischemia related regional wall motion abnormalities. This study investigated the values of adenosine MCE and DSE in the detection of functionally significant coronary artery stenosis in an experimental open chest pig model. METHODS: A total of 28 proximal LAD stenoses were instrumented in 12 animals. Reduction of coronary blood flow reserve (delta CFR [%] ) was calculated as a marker of functional significance of coronary artery stenosis (mild to moderate stenosis: delta CFR < or = 50%; severe stenosis: delta CFR > 50%). Fractional area shortening (FAS) and wall thickening (WT) were calculated to evaluate regional wall motion. Peak myocardial contrast intensities (PCI) were measured following aortic root injections of Levovist' to detect mocardial perfusion defects. RESULTS: As a group, severe stenosis significantly reduced wall motion response to dobutamine (delta FAS: 12.0 +/- 3.0%, vs. 20 +/- 3.0% without stenosis, p < 0.05; delta WT: 2.2 +/- 0.9 mm vs. 0.0 +/- 0.8 mm without stenosis, p < 0.05) and diminished myocardial opacification during hyperemia (PCI: 59 +/- 8 units vs. 143 +/- 16 units without stenosis, p < 0.05). Mild to moderate stenosis did not influence wall motion but reduced myocardial opacification (PCI 89 +/- 14 units vs. 143 +/- 16 units). PCI correlated more closely with alterations in CFR (r = -0.7, p < 0.0001) than did FAS (r = -0.5, p < 0.002) or WT (r = -0.2, p = 0.3). CONCLUSION: Adenosine myocardial contrast echocardiography detects flow limiting coronary artery stenosis and compares favorably to regional wall motion analysis during dobutamine infusion.

Glycogen synthase kinase 3beta regulates GATA4 in cardiac myocytes.

Inactivation of glycogen synthase kinase 3beta (GSK3beta) is critical for transcription of atrial natriuretic factor (ANF) by beta-adrenergic receptors in cardiac myocytes. We examined the mechanism by which GSK3beta regulates ANF transcription. Stimulation of beta-adrenergic receptors induced nuclear accumulation of GATA4, whereas beta-adrenergic ANF transcription was suppressed by dominant negative GATA4, suggesting that GATA4 plays an important role in beta-adrenergic ANF transcription. Interestingly, GATA4-mediated transcription was markedly attenuated by GSK3beta. GSK3beta physically associates with GATA4 and phosphorylates GATA4 in vitro. Overexpression of GSK3beta suppressed both basal and beta-adrenergic increases in nuclear expression of GATA4, whereas inhibition of GSK3beta by LiCl caused nuclear accumulation of GATA4, suggesting that GSK3beta negatively regulates nuclear expression of GATA4. The nuclear exportin Crm1 reduced nuclear expression of GATA4, and the reduction was enhanced by GSK3beta but not by kinase-inactive GSK3beta. Leptomycin B, an inhibitor for Crm1, increased basal nuclear GATA4 and suppressed GSK3beta-induced decreases in nuclear GATA4. These results suggest that GSK3beta negatively regulates nuclear expression of GATA4 by stimulating Crm1-dependent nuclear export. Inhibition of GSK3beta by beta-adrenergic stimulation abrogates GSK3beta-induced nuclear export of GATA4, causing nuclear accumulation of GATA4, which may represent an important signaling mechanism mediating cardiac hypertrophy.

Confirmation bias in sequential information search after preliminary decisions: an expansion of dissonance theoretical research on selective exposure to information.

Research on selective exposure to information consistently shows that, after having made a decision, people prefer supporting over conflicting information. However, in all of these experiments participants were given an overview of all available pieces of information, selected them simultaneously, and did not process the requested information during the selection phase. In the present research the authors show that an even stronger preference for supporting information arises if information is presented and processed sequentially instead of simultaneously (Experiment 1), and they demonstrate that this stronger confirmation bias is due to sequential presentation and not to sequential processing of information (Experiment 2). The authors provide evidence that the increase in confirmation bias under sequential presentation is caused by heightened commitment due to the participants' increased focusing on their decision (Experiments 3 and 4).

Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.

One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.

A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.

Gephyrin was originally identified as a membrane-associated protein that is essential for the postsynaptic localization of receptors for the neurotransmitters glycine and GABA(A). A sequence comparison revealed homologies between gephyrin and proteins necessary for the biosynthesis of the universal molybdenum cofactor (MoCo). Because gephyrin expression can rescue a MoCo-deficient mutation in bacteria, plants, and a murine cell line, it became clear that gephyrin also plays a role in MoCo biosynthesis. Human MoCo deficiency is a fatal disease resulting in severe neurological damage and death in early childhood. Most patients harbor MOCS1 mutations, which prohibit formation of a precursor, or carry MOCS2 mutations, which abrogate precursor conversion to molybdopterin. The present report describes the identification of a gephyrin gene (GEPH) deletion in a patient with symptoms typical of MoCo deficiency. Biochemical studies of the patient's fibroblasts demonstrate that gephyrin catalyzes the insertion of molybdenum into molybdopterin and suggest that this novel form of MoCo deficiency might be curable by molybdate supplementation.