Structural basis of flagellar motility regulation by the MogR repressor and the GmaR antirepressor in Listeria monocytogenes.

The pathogenic Listeria monocytogenes bacterium produces the flagellum as a locomotive organelle at or below 30°C outside the host, but it halts flagellar expression at 37°C inside the human host to evade the flagellum-induced immune response. Listeria monocytogenes GmaR is a thermosensor protein that coordinates flagellar expression by binding the master transcriptional repressor of flagellar genes (MogR) in a temperature-responsive manner. To understand the regulatory mechanism whereby GmaR exerts the antirepression activity on flagellar expression, we performed structural and mutational analyses of the GmaR-MogR system. At or below 30°C, GmaR exists as a functional monomer and forms a circularly enclosed multidomain structure via an interdomain interaction. GmaR in this conformation recognizes MogR using the C-terminal antirepressor domain in a unique dual binding mode and mediates the antirepressor function through direct competition and spatial restraint mechanisms. Surprisingly, at 37°C, GmaR rapidly forms autologous aggregates that are deficient in MogR neutralization capabilities.

Impact of Norepinephrine and Dopamine Infusion on Renal Arterial Resistive Index during Pre-Emptive Living Donor Kidney Transplantation: Propensity Score Matching Analysis.

Background: Living donor kidney transplantation (LDKT) is a crucial treatment for end-stage renal disease, with pre-emptive LDKT (transplantation before dialysis initiation) offering significant benefits in graft function and patient survival. The selection of a vasopressor during LDKT, particularly between norepinephrine and dopamine, and its impact on renal arterial hemodynamics measured using the renal arterial resistive index (RARI) is poorly understood. Methods: This retrospective observational cohort study enrolled 347 eligible pre-emptive LDKT recipients from the Seoul St. Mary's Hospital between January 2019 and June 2023. Utilizing propensity score matching (PSM), the patients were categorized into dopamine and norepinephrine groups to compare the effects of these vasopressors on the intraoperative RARI, postoperative estimated glomerular filtration rate (eGFR), and hourly urine output. The RARI was measured via the Doppler ultrasonography of the renal hilum and parenchyma post-graft vascular and ureteral anastomoses. Results: The preoperative differences in the recipients' and donors' characteristics were mitigated following PSM. The dopamine group exhibited higher intraoperative RARI values at the renal hilum (0.77 ± 0.11 vs. 0.66 ± 0.13, p < 0.001) and parenchyma (0.71 ± 0.1 vs. 0.6 ± 0.1, p < 0.001) compared to those of the norepinephrine group. However, these differences were not statistically significant on postoperative day 7. The norepinephrine infusion adjusted for the propensity scores was associated with significantly lower odds of an RARI > 0.8 (hilum: OR = 0.214, 95% CI = 0.12-0.382, p < 0.001; parenchyma: OR = 0.1, 95% CI = 0.029-0.348, p < 0.001). The early postoperative outcomes showed a higher eGFR (day 1: 30.0 ± 13.3 vs. 25.1 ± 17.4 mL/min/1.73 m2, p = 0.004) and hourly urine output (day 1: 41.8 ± 16.9 vs. 36.5 ± 14.4 mL/kg/h, p = 0.002) in the norepinephrine group. Furthermore, the long-term outcomes were comparable between the groups. Conclusions: Norepinephrine infusion during pre-emptive LDKT is associated with more favorable intraoperative renal arterial hemodynamics, as evidenced by a lower RARI and improved early postoperative renal function compared to those of dopamine. These findings suggest a potential preferential role for norepinephrine in optimizing perioperative management and early graft functions in LDKT recipients. Given the retrospective nature of this study, further prospective studies are needed to confirm these observations. Additionally, the study limitations include the potential for unmeasured confounding factors and the inability to determine causality due to its observational design.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patients.

BACKGROUND: Transcutaneous oxygen pressure (TcPO2) is a noninvasive, nonradiological test to measure local oxygen released from capillaries through the skin. Since it reflects the metabolic state of the lower limb, it can predict wound healing in patients with critical limb threatening ischemia (CLTI). The purpose of this study was to determine the effectiveness of TcPO2 test in evaluating wound healing potential of patients with CLTI. METHODS: This was a retrospective, single-center, nonrandomized, and observational study. A prospectively registered database of patients who visited Vascular Surgery Department of St. Mary's Hospital for CLTI and underwent TcPO2 tests from October 1, 2015 to July 1, 2021 was reviewed. Patients were divided into 2 groups: (1) those who had amputation only; and (2) those who underwent revascularization procedures. Patients whose wound healing status could not be determined were excluded. The clinical characteristics of patients, patient characteristics related to lower TcPO2 value, treatment success rate, and time for the wound to be healed were analyzed. RESULTS: A total of 84 patients were included in this study. There was no difference in background patient characteristics between the 2 groups despite better survival within 12 months and shorter healing time in the revascularization group. A total of 76 patients survived 12 months after surgery, and 63 patients were healed. Higher HbA1c, higher serum creatinine, history of stroke, and history of coronary artery disease were related to lower TcPO2 value on multiple linear regression. The cutoff value of TcPO2 was determined to be 40 mm Hg for predicting wound healing. This value was similar to those of previous studies. In addition, there was a negative correlation between TcPO2 and wound healing time. Correlations among the anklebrachial index (ABI), toe-brachial index (TBI), and TcPO2 were not determined because ABI and TBI for some patients could not be obtained due to wound condition. CONCLUSIONS: The TcPO2 value can predict the wound healing process of ischemic lower extremity injury.

Contrast enhanced duplex ultrasound for early postoperative follow-up after endovascular aneurysm repair: Relation to patient's initial risk of complications.

OBJECTIVES: Current guidelines recommend initial postoperative follow-up with computed tomography angiography (CTA) after endovascular aneurysm repair (EVAR). However, CTA has risks associated with ionizing radiations and nephrotoxic contrast agents. We investigated possibilities to replace the initial postoperative CTA with contrast enhanced duplex ultrasound (CE-DUS) in selected patients. METHODS: Out of the 273 consecutive patients who underwent EVAR, 173 were excluded and the 100 patients who underwent CTA and CE-DUS imaging concurrently (≤1 month interval between CTA and CE-DUS imaging) within 60 days after EVAR were analyzed. Patients who underwent EVAR outside the manufacturer's instructions for use or who had endoleaks discovered on intraoperative angiography were classified as the high-risk group, otherwise, they were classified as the low-risk group. Measurements of diagnostic values of CE-DUS ​​related to the detection of complications were calculated using CTA as the gold standard. McNemar's test was performed to compare these values and Pearson correlation coefficient was derived to compare CE-DUS measurements of sac diameters with CTA. RESULTS: In the low-risk group, no difference was observed between CE-DUS and CTA in the detection of EVAR-related complications (sensitivity = 0.95, specificity = 0.93). In the high-risk group, CE-DUS was not as accurate as CTA for the detection of overall EVAR-related complications (sensitivity = 0.57, specificity = 0.86, p = 0.04) and for the detection of complications other than endoleaks (p = 0.02). Regarding sac diameter measurement, there was good agreement between CE-DUS and CTA (r = 0.92, p < 0.001). CONCLUSIONS: First postoperative CE-DUS was reliable for the evaluation of EVAR-related complications compared to CTA in selected patients. Individualized EVAR follow-up strategy using CE-DUS based on the initial risk of EVAR-related complications should be considered.

Structural analysis of carboxyspermidine dehydrogenase from Helicobacter pylori.

Spermidine is a cationic polyamine that plays key roles in diverse biological processes, including biofilm formation and cell viability in bacteria. In some human gastrointestinal bacteria, such as Helicobacter pylori and Campylobacter jejuni, spermidine is biosynthesized using carboxyspermidine dehydrogenase (CASDH) and carboxyspermidine decarboxylase through an alternative pathway rather than the classical pathway found in most bacteria and eukaryotes. CASDH condenses putrescine and aspartate ß-semialdehyde into carboxyspermidine in an NADPH-dependent manner. Because structural information on CASDH is not available, the exact enzymatic mechanism of CASDH has not been elucidated. To reveal the structural features of CASDH required for cofactor and substrate recruitment, we determined the crystal structures of the H. pylori CASDH protein alone and in complex with NADP. CASDH consists of three domains (D1, D2, and D3) and assembles into a homodimer exclusively using the D3 domain. The CASDH structure harbors a dent between the D1 and D3 domains. The NADP cofactor is inserted into the interdomain dent and induces structural rearrangements in CASDH, including dent closure and local structural changes in the D1 and D3 domains. A comparative analysis suggests that the substrate of CASDH binds in a cavity near the nicotinamide moiety of NADPH for the condensation reaction.

Structural analysis of the dNTP triphosphohydrolase PA1124 from Pseudomonas aeruginosa.

dNTP triphosphohydrolase (TPH) belongs to the histidine/aspartate (HD) superfamily and catalyzes the hydrolysis of dNTPs into 2'-deoxyribonucleoside and inorganic triphosphate. TPHs are required for cellular dNTP homeostasis and DNA replication fidelity and are employed as a host defense mechanism. PA1124 from the pathogenic Pseudomonas aeruginosa bacterium functions as a dGTP and dTTP triphosphohydrolase. To reveal how PA1124 drives dNTP hydrolysis and is regulated, we performed a structural study of PA1124. PA1124 assembles into a hexameric architecture as a trimer of dimers. Each monomer has an interdomain dent where a metal ion is coordinated by conserved histidine and aspartate residues. A structure-based comparative analysis suggests that PA1124 accommodates the dNTP substrate into the interdomain dent near the metal ion. Interestingly, PA1124 interacts with ssDNA, presumably as an allosteric regulator, using a positively charged intersubunit cleft that is generated via dimerization. Furthermore, our phylogenetic analysis highlights similar or distinct oligomerization profiles across the TPH family.

Real-Time Evaluation of Blood Flow Patterns Using AneurysmFlow for an in vivo Abdominal Aortic Aneurysm Model.

BACKGROUND: Many new tools for abdominal aortic aneurysm (AAA) rupture risk evaluation have been developed. These new tools need detailed hemodynamic information in AAA. However, hemodynamic data obtained from in vivo research are lacking. Thus, the objective of this study was to analyze blood flow patterns in an in vivo AAA model to acquire real-time hemodynamic information using AneurysmFlow, a novel flow evaluation system. METHODS: Digital subtraction angiography images of patients who underwent endovascular aneurysm repair were analyzed using the visualization function of the AneurysmFlow to classify blood flow patterns as laminar or turbulent flow. The presence of boundary layer separation was also evaluated. The time taken for contrast medium to travel from the infrarenal aortic neck to aortic bifurcation was acquired to calculate the flow velocity. Associations between characteristics of aneurysm including lumen occupying ratio of intraluminal thrombus (ILT) and the hemodynamic flow pattern were evaluated. RESULTS: A total of 37 AAA patients was enrolled. Their blood flow patterns were evaluated using the AneurysmFlow. Logistic regression analyses with lumen occupying ratio of ILT as an independent variable showed that the larger the lumen occupying ratio of ILT, the more likely the aneurysm was to show a laminar pattern (P = 0.03), and the more likely the boundary layer separation would not exist (P = 0.04). The flow velocity from the infrarenal aortic neck to the aortic bifurcation showed a positive association with the lumen occupying ratio of the ILT in linear regression analysis (P < 0.001). CONCLUSIONS: Hemodynamic analysis of AAA with the AneurysmFlow using real-time individual patient models showed different flow patterns and flow velocities depending on ILT. This novel analytic approach using AneurysmFlow has potential to play an important role in obtaining clinically meaningful hemodynamic information of AAA.

Kidney Transplantation From Deceased Donors With Bloodstream Infection: A Multicenter Retrospective Study.

BACKGROUND: The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). METHODS: A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. RESULTS: Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. CONCLUSION: Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.

Apo structure of the transcriptional regulator PadR from Bacillus subtilis: Structural dynamics and conserved Y70 residue.

PadR is a bacterial transcriptional regulator that controls the expression of phenolic acid decarboxylase (PadC) in response to phenolic acids to prevent their toxic effects. During transcriptional repression, PadR associates with the operator sequence at the promoter site of the padC gene. However, when phenolic acids are present, PadR directly binds the phenolic acids and undergoes an interdomain rearrangement to dissociate from the operator DNA. To further examine the structural dynamics of PadR, we determined the apo structure of Bacillus subtilis PadR. Apo-PadR exhibits significant interdomain flexibility and adopts structures that are similar to the phenolic acid-bound PadR structures but distinct from the DNA-bound structure, suggesting that apo-PadR can bind phenolic acids without substantial structural rearrangement. Furthermore, we identified the Y70 residue of PadR as the most conserved residue in the PadR family. PadR Y70 displays similar conformations irrespective of the associated partners, and its conformation is conserved in diverse PadR family members. The Y70 residue is surrounded by the key DNA-binding entities of PadR and is required to optimally arrange them for operator DNA recognition by PadR. PadR Y70 also plays a critical role in protein stability based on the results of a denaturation assay. These observations suggest that PadR Y70 is a canonical residue of the PadR family that contributes to protein stability and DNA binding.

Structural and DNA-binding studies of the PadR-like transcriptional regulator BC1756 from Bacillus cereus.

Transcription factors that belong to the PadR family play an essential role in the transcriptional regulation of diverse biological processes by recognizing their cognate palindromic DNA sequences. Bacillus cereus harbors a gene that encodes a PadR-like protein (bcPLP; BC1756). bcPLP has not been structurally characterized, and it remains unelucidated how bcPLP interacts with a specific DNA sequence to function as a transcription factor. To provide structural insights into DNA recognition by bcPLP, we performed a structural study and a DNA-binding analysis of bcPLP. The crystal structure of bcPLP was determined at 1.92 Šresolution. bcPLP consists of two domains, an N-terminal domain (NTD) and a C-terminal domain (CTD), and forms a homodimer mainly using the CTD. In the structure, bcPLP contains a highly positively charged elongated patch in the NTD that serves as a putative DNA-binding site. Indeed, an electrophoresis mobility shift assay and a fluorescence polarization assay showed that bcPLP specifically recognizes a palindromic DNA sequence upstream of the bcPLP-encoding region. Moreover, based on our mutagenesis and modeling studies, we demonstrate that bcPLP interacts with dsDNA primarily using the Y19, Y41, P64, and K66 residues in the NTD.

Venous Thromboembolism Following Abdominal Cancer Surgery in the Korean Population: Incidence and Validation of a Risk Assessment Model.

BACKGROUND: A cancer patient slated for abdominal surgery is considered to be at moderate to high risk for developing venous thromboembolism (VTE), but the incidence is quite low in Korean patients. Most risk assessment models and recommendations for VTE management are from Western reports, however they possibly overestimate the risk of VTE in the Korean population. METHODS: We retrospectively reviewed the medical records of 1966 patients who were diagnosed with abdominal organ cancer and required surgical treatment. RESULTS: Each patient was rated using the Caprini risk scoring model. The mean score was 7.5 ± 0.7 points; 98.4% of patients were classified as high risk for VTE. Symptomatic VTE occurred in eight patients, and the overall incidence was 0.4%. The mean Caprini score for VTE patients was 8.8 ± 1.9 points. In the group with scores between 5 and 9 points, the incidence was 0.3-0.5%, while in patients with scores > 10 points, the incidence of VTE was found to be 1.12%. CONCLUSIONS: The risk stratification system in the Caprini scoring model needs to be modified based on the actual incidence in the Korean population.

Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR.

The PadR family is a large group of transcriptional regulators that function as environmental sensors. PadR negatively controls the expression of phenolic acid decarboxylase, which detoxifies harmful phenolic acids. To identify the mechanism by which PadR regulates phenolic acid-mediated gene expression, we performed structural and mutational studies of effector and operator recognition by Bacillus subtilis PadR. PadR contains an N-terminal winged helix-turn-helix (wHTH) domain (NTD) and a C-terminal homodimerization domain (CTD) and dimerizes into a dolmen shape. The PadR dimer interacts with the palindromic sequence of the operator DNA using the NTD. Two tyrosine residues and a positively charged residue in the NTD provide major DNA-binding energy and are highly conserved in the PadR family, suggesting that these three residues represent the canonical DNA-binding motif of the PadR family. PadR directly binds a phenolic acid effector molecule using a unique interdomain pocket created between the NTD and the CTD. Although the effector-binding site of PadR is positionally segregated from the DNA-binding site, effector binding to the interdomain pocket causes PadR to be rearranged into a DNA binding-incompatible conformer through an allosteric interdomain-reorganization mechanism.

Structural and biochemical characterization of bacterial YpgQ protein reveals a metal-dependent nucleotide pyrophosphohydrolase.

The optimal balance of cellular nucleotides and the efficient elimination of non-canonical nucleotides are critical to avoiding erroneous mutation during DNA replication. One such mechanism involves the degradation of excessive or abnormal nucleotides by nucleotide-hydrolyzing enzymes. YpgQ contains the histidine-aspartate (HD) domain that is involved in the hydrolysis of nucleotides or nucleic acids, but the enzymatic activity and substrate specificity of YpgQ have never been characterized. Here, we unravel the catalytic activity and structural features of YpgQ to report the first Mn(2+)-dependent pyrophosphohydrolase that hydrolyzes (deoxy)ribonucleoside triphosphate [(d)NTP] to (deoxy)ribonucleoside monophosphate and pyrophosphate using the HD domain. YpgQ from Bacillus subtilis (bsYpgQ) displays a helical structure and assembles into a unique dimeric architecture that has not been observed in other HD domain-containing proteins. Each bsYpgQ monomer accommodates a metal ion and a nucleotide substrate in a cavity located between the N- and C-terminal lobes. The metal cofactor is coordinated by the canonical residues of the HD domain, namely, two histidine residues and two aspartate residues, and is positioned in close proximity to the ß-phosphate group of the nucleotide, allowing us to propose a nucleophilic attack mechanism for the nucleotide hydrolysis reaction. YpgQ enzymes from other bacterial species also catalyze pyrophosphohydrolysis but exhibit different substrate specificity. Comparative structural and mutational studies demonstrated that residues outside the major substrate-binding site of bsYpgQ are responsible for the species-specific substrate preference. Taken together, our structural and biochemical analyses highlight the substrate-recognition mode and catalysis mechanism of YpgQ in pyrophosphohydrolysis.

Structural and biochemical characterization of the Bacillus cereus 3-hydroxyisobutyrate dehydrogenase.

The 3-hydroxyisobutyrate dehydrogenase (HIBADH) family catalyzes the NAD(+)- or NADP(+)-dependent oxidation of various ß-hydroxyacid substrates into their cognate semialdehydes for diverse metabolic pathways. Because HIBADH group members exhibit different substrate specificities, the substrate-recognition mode of each enzyme should be individually characterized. In the current study, we report the biochemical and structural analysis of a HIBADH group enzyme from Bacillus cereus (bcHIBADH). bcHIBADH mediates a dehydrogenation reaction on S-3-hydroxyisobutyrate substrate with high catalytic efficiency in an NAD(+)-dependent manner; it also oxidizes l-serine and 3-hydroxypropionate with lower activity. bcHIBADH consists of two domains and is further assembled into a functional dimer rather than a tetramer that has been commonly observed in other prokaryotic HIBADH group members. In the bcHIBADH structure, the interdomain cleft forms a putative active site and simultaneously accommodates both an NAD(+) cofactor and a substrate mimic. Our structure-based comparative analysis highlights structural motifs that are important in the cofactor and substrate recognition of the HIBADH group.

Efficacy of Retrievable Inferior Vena Cava Filter Placement in the Prevention of Pulmonary Embolism during Catheter-Directed Thrombectomy for Proximal Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: Inferior vena cava (IVC) filter placement is not indicated for thrombolytic interventional treatment for deep vein thrombosis (DVT). We analyzed the efficacy and feasibility of retrievable IVC filter placement for the preventive management of embolic shedding during catheter-directed thrombectomy (CDT) for DVT of lower extremity. METHODS: Seventy patients (35 males and 35 females) who underwent retrievable IVC filter placement to prevent thrombus dislodgement during CDT in all symptomatic DVT with thrombus age suspected within 4 weeks of the lower extremity between March 2008 and January 2014 were included in this study. All patients underwent laboratory blood study, duplex ultrasound and/or computed tomography for diagnosis, treatment, and follow-up in accordance with treatment policy of our Uijeongbu St. Mary's hospital. Two types of retrievable IVC filters (OptEase Filter, Cordis, Roden, The Netherlands; Gunther Tulip Filter, Cook, Bloomington, IN) were used to prevent thromboembolic events during CDT. After filter placement, subcutaneous low-molecular-weight heparin and overlapped to warfarin or new oral anticoagulant tried to achieve a target international normalized ratio (INR) of 2.0-3.0 in warfarin patients. RESULTS: The thrombus was dislodged through the IVC filter during catheter-directed thrombolytic therapy in 22 patients (31.4%). In 22 cases, the thromboses were trapped by the retrievable IVC filter, and follow-up images showed thrombus capture. Thirty-four patients (48.6%) received percutaneous transluminal angioplasty (PTA). Additional stents were inserted in 23 patients (32.8%). Pulmonary embolism (PE) was not observed in patients implanted with retrievable IVC filters. CONCLUSIONS: Our study findings suggest that retrieval IVC filter placement during interventional treatments of DVT of lower extremity such as thrombectomy of vein thrombus with or without stent insertion at compressed deep vein is favorable and effective for protecting against PE or lethal complications. We recommend carefully that before the management of DVT thrombus of lower extremity, retrieval IVC filter placement should be considered for preventing morbidity related with the PE.

Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis.

OBJECTIVE: According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. DESIGN: Case-control study in Korean population. METHODS: We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. RESULTS: With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. CONCLUSIONS: The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown.

Pre-existing Arterial Micro-Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients.

Vascular access micro-calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro-calcification (AMiC) on the patency of vascular access in HD patients. One-hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan-Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.

Clinical Importance of Intraoperative Cephalic Vein Distensibility as a Predictor of Radiocephalic Arteriovenous Fistula Maturation.

Radiocephalic arteriovenous fistula (RCAVF) is the preferred vascular access, but the maturation failure rate is high. Poor vein distensibility is the main cause of maturation failure. There have been several studies regarding vein distensibility, but vein dilation protocol and the cut-off value predicting maturation failure were inconsistent. We were doubtful that the vein distensibility had been appropriately evaluated, and sought to determine a more clinically applicable parameter. The cephalic vein was dilated via intraluminal hydrostatic pressure during the surgery and the vein size was measured. Maturation failure occurred in 30 patients (22.4%) and was more common in females and in patients who had a previous history of arteriovenous access formation (p = 0.0095 and p = 0.014). The intraoperative postdilation diameter, and the difference between pre and postdilation diameters differed between the two groups (p = 0.0004 and p = 0.0004). The cut-off value of the postdilation diameter, which indicated a high probability of maturation success, was >4 mm, and the cut-off value which indicated a higher probability of maturation failure; that is, the difference between the pre and postdilation diameter, was ≤2.2 mm. The degree of distensibility of the cephalic vein may be an important determinant of RCAVF maturation.

Structural analysis of a putative SAM-dependent methyltransferase, YtqB, from Bacillus subtilis.

S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases) methylate diverse biological molecules using a SAM cofactor. The ytqB gene of Bacillus subtilis encodes a putative MTase and its biological function has never been characterized. To reveal the structural features and the cofactor binding mode of YtqB, we have determined the crystal structures of YtqB alone and in complex with its cofactor, SAM, at 1.9 Å and 2.2 Å resolutions, respectively. YtqB folds into a ß-sheet sandwiched by two α-helical layers, and assembles into a dimeric form. Each YtqB monomer contains one SAM binding site, which shapes SAM into a slightly curved conformation and exposes the reactive methyl group of SAM potentially to a substrate. Our comparative structural analysis of YtqB and its homologues indicates that YtqB is a SAM-dependent class I MTase, and provides insights into the substrate binding site of YtqB.