Nicotinamide mononucleotide inhibits oxidative stress-induced damage in a SIRT1/NQO-1-dependent manner.

Oxidative stress causes endothelial dysfunction, which is associated with vascular cellular aging and is causally related to cardiovascular disease pathogenesis. Preclinical studies indicate that a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide mononucleotide (NMN), alleviates oxidative stress in aged vessels, granting vasoprotective effects. However, the associated cellular mechanism remains largely unclear. In this study, we used human umbilical vein endothelial cells (HUVECs) to demonstrate that NMN inhibits oxidative stress-induced damage by activating the sirtuin 1 (SIRT1)/NAD(P)H: quinone oxidoreductase 1 (NQO-1) axis. We found that NMN inhibited H2O2-induced cytotoxicity and senescence-associated protein expression, such as p16 and p21. Furthermore, NMN prevented H2O2-induced actin cytoskeletal disorganization via inhibiting reactive oxygen species (ROS) production. NMN increased NQO-1 mRNA and protein expression that in turn was abrogated by SIRT1 inhibition, suggesting that NMN-inducible NQO-1 was associated with SIRT1 activity. SIRT1 and NQO-1 inhibition attenuated the inhibitory effect of NMN on H2O2-inducible cytotoxicity, senescence-related protein upregulation, and actin cytoskeletal disorganization. Our findings provide new insights into the mechanism by which NMN exerts protective effects against vascular oxidative stress.

Arthroscopic treatment of scaphoid nonunion with humpback deformity and DISI with corticocancellous bone grafting: Technical note.

For two decades, scaphoid nonunion has been treated arthroscopically. However, compressed cancellous bone graft does not have the same mechanical properties as corticocancellous bone graft for reducing the scaphoid humpback deformity and DISI tilt. Here, we describe an arthroscopic technique to treat Alnot stage IIB scaphoid nonunion. We treated a 27-year-old male patient for scaphoid waist nonunion with humpback deformity and DISI. A 8×8×10 mm cylindrical corticocancellous bone graft was harvested from the dorsal aspect of the radius using a single-use osteochondral autograft transfer system (OATS®, Arthrex Inc., Naples, USA). It was inserted in the nonunion site through an arthroscopic volar approach. Bone union was obtained at 3 months with lasting correction of the scaphoid humpback deformity and DISI. The functional result at 6 months was excellent. There were no complications. Scaphoid nonunion with humpback deformity and DISI may be treated arthroscopically with a corticocancellous bone graft.

Distal radius fracture fixation with a volar locking plate and endoscopic carpal tunnel release using a single 15mm approach: Feasibility study.

Distal radius fractures (DRF) may trigger, reveal or decompensate acute carpal tunnel syndrome (CTS) in 0.5-21% of cases. Internal fixation and median nerve release must then be carried out urgently. Less invasive approaches have been described for both the median nerve release using an endoscopic device and for the DRF fixation using a volar locking plate. We assessed the feasibility of DRF fixation and median nerve release through a single, minimally-invasive 15mm approach on a series of 10 cases. We reviewed retrospectively 10 consecutive cases of DRF associated with symptomatic CTS in 8 women and 2 men, aged 57 years on average. CTS was diagnosed clinically. All patients were treated during outpatient surgery with a volar locking plate and endoscopic carpal tunnel release using a single 15mm minimally-invasive approach. In one case, arthroscopic scapholunate repair was also required. Six months after the procedure, all patients were reviewed with a clinical examination and a radiological evaluation. The average values for the clinical and radiological outcomes were as follows: pain on VAS 1.5/10; QuickDASH 14.3/100; flexion 90%; extension 90.6%; pronation 95.6%; supination 87.9%; grip strength 90.1%; 2PD test 5.2mm (4-8mm). Five complications occurred: two cases of temporary dysesthesia in the territory of the median nerve and one case of temporary hypoesthesia of the palmar branch of the median nerve, which had all completely recovered; two cases of complex regional pain syndrome type I, which were still active at 6 months. Despite its methodological weaknesses, our study is the only one to describe the technical feasibility of a single 15mm minimally-invasive approach for both internal fixation using a volar locking plate and endoscopic nerve release, with no serious complications. This technique should be added to the surgical toolbox of minimally-invasive procedures for the hand and wrist.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Proximodistal interphalangeal arthrodesis of the little finger: A series of 7 cases.

As an alternative to amputation of the little finger, we report here seven cases of shortening arthrodesis carried out by resecting the middle phalanx and proximodistal interphalangeal (PDIP) arthrodesis. Our cohort consisted of 6 males and 1 female (58years average age), with a stiff little finger secondary to Dupuytren's disease or trauma. All fingers were approached dorsally; after resection of the middle phalanx and decortication of the subchondral bone, fusion of the remaining phalanges was performed using an intramedullary self-breaking screw-pin. At a mean follow-up of 34.9months, pain decreased significantly (1.4/10 versus 5.4/100 preoperatively), the QuickDASH score improved significantly (33/100 versus 51/100 preoperatively) and all the joints had fused. One patient suffered from cold intolerance. PDIP arthrodesis is an alternative salvage procedure to amputation for multioperated stiff little fingers that does not burn any bridges if it fails.

Thorough debridement and immediate primary wound closure for animal bite injuries of the upper limbs.

PURPOSE: Animal bite injuries are often encountered in daily practice. In particular, these injuries of the upper limbs can result in severe functional impairment. We have performed early debridement of contaminated tissue and primary closure for these injuries. METHODS: The subjects consisted of 15 patients (6 males and 9 females) aged 1-91 years (mean 53.6 years) who visited our hospital due to animal bite injuries (dog in 9 patients, cat in 6). The bite site was the forearm in 5 patients and the hand in 10. In the operating room, contaminated tissue was removed, and primary wound closure was performed after irrigation. RESULTS: The bite penetrated to the muscle layer in 6 patients, tendon sheath in 5, joint in 1, bone in 1, and involved only the subcutaneous tissue in 3 patients. The mean period until the completion of wound treatment was 19.8 ± 8.4 days. As complications, numbness of finger, metaphalangeal joint contracture and superficial radial nerve injury were observed in each one case. In a patient with bite injury of the palmar and dorsal sides of the thumb reaching the bone, additional debridement was necessary. At the final observation, the visual analog scale was 1.2 ± 1.4, and the Quick Disabilities of the Arm, Shoulder, and Hand score was 9.7 ± 12.2. CONCLUSIONS: Debridement to achieve wound closure is indispensable in patients with animal bite injuries of the upper limbs. The results of our study suggest that thorough debridement allows primary closure, even for animal bite injuries.

Distal radius fixation through a mini-invasive approach of 15 mm. Part 1: feasibility study.

The aim of this study was to determine the feasibility of a mini-approach for distal radius volar plating. A 15-mm incision was made in 11 cadaver wrists. A 41 mm length and 24 mm width plate was placed deep to the pronator quadratus then fixed using 2 K-wires. The 2 central epiphyseal screws were placed before pin removal, the lateral screws followed and finally the proximal ones. The number of control views needed was on average 1.9 mm, and the position of the plate was good in 10 cases and average in 1 case. The size of the incision after the operation was on average 16.3 mm. No complications were found. Our results show that volar plate fixation of distal radius fracture is feasible through a 15 mm approach. This approach is esthetic, respects noble structures and facilitates reduction due to ligamentotaxis.

Graner's procedure in Kienböck disease: a series of four cases with 25years of follow-up.

UNLABELLED: Advanced stages of Kienböck's disease are treated by several techniques, one of which is Graner's procedure, nearly abandoned nowadays. The results of long-term follow-up of a series of four cases Graner's procedure are presented. Four patients were reviewed with a follow-up of 25years. There were two women and two men mean aged 37years at the time of surgery. Two of them were manual workers. Graner's procedure was the first surgery in three cases and secondary to failure of radius shortening in one case of Stage IIIa. Three patients underwent bone healing and the fourth benefited secondarily from radiocarpal arthrodesis. At maximal follow-up, the mean DASH score was 36.6 and pain assessed by visual analogic scale was 3.25 out of 10; the range of movement was half of the opposite side; the wrist strength was 80.9% of the opposite side. In the three consolidated cases, a spontaneous remodeling of the radiocarpal articular surfaces was noted. Graner's procedure is logical as it aims at creating a new radiocarpal articulation, either by the fusion of the lunate with the capitate (Graner I) or by replacing the lunate with the head of the capitate (Graner II and III). However, this old procedure should no longer be one of the surgical procedures for Kienböck disease due to its drawbacks: necrosis or non-union of the head of the capitate, necessity to perform a wrist fusion in the long-term and side effects of bone graft harvesting. LEVEL OF EVIDENCE: II. Retrospective study.

Ulnar nerve transposition using a mini-invasive approach: case series of 30 patients.

The treatment of ulnar nerve compression at the elbow remains controversial. No single technique has yet proven its superiority. We describe a technique combining the advantages of the mini-invasive approach with those of transposition. We present the results of 30 patients, of mean age 52 years, who underwent anterior subcutaneous transposition of the ulnar nerve using a mini-invasive approach with a follow-up of more than six months. The incision measures 3 cm. The results were evaluated by measuring pain intensity, quick disabilities of the arm shoulder and hand (DASH), grip strength and pinch, and McGowan score, pre- and post-operatively. All parameters were improved post-operative. The mean pain score went from 5.5 to 4, the quick DASH from 48 to 38, mean grip strength from 28 to 31 kg, and mean pinch strength from 4.7 to 6.4 kg. The McGowan score was also improved; pre-operatively, there were 16 patients at stage III, seven patients stage II, seven patients stage I, and post-operatively there was one patient stage III, three patients stage II, 16 patients stage I, and 10 patients stage 0. Analysis of our series shows that a 3 cm incision without endoscopy allows subcutanous transposition, with results at least as good as those with other techniques. The advantages of our technique are that it is easy, has a limited approach, preserves blood supply, allows placement of the nerve in a favourable environment, and decreases nerve stretching during elbow flexion.

Should we stop oral anticoagulants in the surgical treatment of carpal tunnel syndrome?

INTRODUCTION: It is usual to stop the intake of oral anticoagulants (anti-vitamin K) before surgery. Some authors have shown that during minimal surgery, the relay with low molecular weight heparin (LMWH) may lead to more thromboembolic complications. We present a prospective comparative study while evaluating the results of stopping or continuing anticoagulants in the surgery for carpal tunnel syndrome. MATERIAL AND METHODS: Our series included 21 patients (24 hands) taking anticoagulants on a long-term basis. For the first nine patients (group I), treatment with anticoagulants was stopped before the surgery. For the following 12 patients (group II), treatment with anticoagulants was not interrupted. The evaluation was based on the measurement of pain (VAS), functional score of the Quick D.A.S.H. and grip strength (Jamar®) and search for a haematoma or thromboembolism). RESULTS: The pain decreased by 3.5 points in both groups. The Quick D.A.S.H. decreased by 19.9 and 27.7 points in groups I and II, respectively. The average grip strength decreased by 2.5 kg in group I and increased by 3.8 kg in group II. A subcutaneous haematoma that got healed by itself was observed in group II. We did not observe any thromboembolic complications. DISCUSSION: In conclusion, it seems pointless to stop anticoagulants before surgical treatment of carpal tunnel. The first reason is that continuing anticoagulants does not result in a bleeding risk. The second reason is that this approach removes the theoretical risk of thromboembolic complications during a poorly monitored relay.

[A trick to improve the technique of the IntraVascular Stent (IVaS): "Clip Stent"]. / Une astuce pour améliorer la technique du stent intravasculaire (IVaS) : le "Clip Stent".

The infra-millimetre vessels are difficult to suture, because the placement of forceps in the lumen is delicate and threads often cross the walls. The technique of the IntraVascular Stent (IVaS), developed to remedy it, did not make the proof of its superiority. The purpose of this study was to analyze the results of a variant, the Clip Stent. Our series included two groups of 10 rats. In group I, the artery of the tail was anastomosed by threads of nylon 10/0. In group II, the artery was anastomosed according to the technique of Clip Stent including three stages: introduction of a monothread of polypropylene 6/0, anastomosis by threads of nylon 10/0, ablation of the Clip Stent and the closure of possible leaks. The assessment consisted in measuring the time of anastomosis, in counting the number of separate threads and leaks, and in testing the permeability. The time of anastomosis was longer 12 minutes in the group II. The number of points by anastomosis was 6.5 in the group I and of 5.5 in the group II. The permeability was 90% in two groups. The Clip Stent is faster than the IVaS. It is useless to realize vascular threads of the lumen before the introduction of the stent. Once the stent in position, it cannot traumatize the intima and its migration is impossible. Contrary to the IVaS, the Clip Stent allows to realize the last threads stent in position, by releasing the tourniquet. The ablation is safe. Its superiority to the conventional methods remains to demonstrate by improving its introduction in the lumen.

Development of a pattern to measure multiscale deformation and strain distribution via in situ FE-SEM observations.

We investigated a method for measuring deformation and strain distribution in a multiscale range from nanometers to millimeters via in situ FE-SEM observations. A multiscale pattern composed of a grid as well as random and nanocluster patterns was developed to measure the localized deformation at the specimen surface. Our in situ observations of a carbon fiber-reinforced polymer matrix composite with a hierarchical microstructure subjected to loading were conducted to identify local deformation behaviors at various boundaries. We measured and analyzed the multiscale deformation and strain localizations during various stages of loading.

Significant relationship between local angle at fused segments and C2-7 angle: Average duration of longer than 20 years after anterior cervical discectomy and fusion.

BACKGROUND: The authors have focused their attention to the radiological durability of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF) using autologous bone grafting. MATERIALS AND METHODS: Among the patients who underwent ACDF with trans-unco-discal (TUD) approach between 1976 and 1997, 22 patients (16 males and 6 females) made return visits for a clinical evaluation. Patients with trauma or previously treated by anterior cervical fusion or by posterior decompression were excluded from the present study. Clinical evaluation included adjacent segment degeneration (ASD), osseous fusion, local angle at the fused segments and C2-7 angle of cervical spine. RESULTS: The duration after ACDF ranged from 13 to 34 years with an average of 21.3 ± 7.0 years. A single level fusion was done on 8 patients, 2 levels on 11 patients, 3 levels on 2 patients, and 4 levels on 1 patient. Imaging studies indicated that 12 of the 22 patients (54.5%) were graded as having symptomatic ASD. Osseous bony fusion at ACDF was recognized in all cases. None of the patients demonstrated kyphotic malalignment of the cervical spine. Average degrees of local angle at the fused segments and the C2-7 angle were 7.06 and 17.6, respectively. Statistical analysis indicated a significant relationship between the local at the fused segments and C2-7 angles. CONCLUSIONS: Sagittal alignment of the cervical spine was durable long after ACDF when the local angle at the fused segments was well stabilized.

[Combined aortic root replacement and pectus excavatum correction in Marfan's syndrome].

A 53-year-old man with Marfan's syndrome was admitted for repair of annulo-aortic ectasia (58 mm). He had also severe pectus excavatum. The skin was incised along the sternal midline. The pectoral muscles were detached laterally. After the perichondrium and costal cartilages were resected bilaterally. the left-sided intercostal muscles and perichondrial sheaths were divided 3 cm lateral to the sternum. To place the retractor in parasternal position, excellent exposure of the heart and aortic root was enabled. The aortic root was replaced with a Carboseal graft. Chest wall reconstructions was completed by modified Ravitch procedure with Gore-tex sheet The patient was discharged after an uneventful recovery on postoperative day 14.

Multidimensional standard curve for the development process of human fetuses.

The present paper considers a multidimensional view of the standard for the development process of human fetuses. An efficient method by which to find a multidimensional standard curve for the development process of human fetuses is proposed in which a logistic function with three parameters is utilized as an underlying model and a nonlinear regression method is applied. The proposed method also identifies an approximate prediction region, which can be efficiently applied to diagnose fetal malformation.

Surgical repair of pelvic-floor prolapse: lessons learned from longitudinal follow-up of quality-of-life survey.

BACKGROUND: Scant evidence has been reported on the evaluation of quality-of-life (QOL) in patients who had undergone surgical treatment due to pelvic floor prolapse including cystocele. The aim of this study is to evaluate the impact of surgical intervention on patients' QOL before and after surgery. METHODS: Between 1997 and 2007, 135 patients (median age: 66.6 years) with pelvic floor prolapse including cystocele underwent bladder neck suspension with anterior/posterior colporrhaphy. The follow-up period was 39.6 months. Seventy-two patients (53 %) had urinary incontinence. The cystocele was graded as mild (grade 2), moderate (grade 3), and severe (grade 4) in 35, 60, and 40, respectively, according to the Baden-Walker classification. A urodynamic study was performed in 69 patients (51 %) who had obstructive symptoms with 100 ml or more of postvoid residual urine. Postoperative QOL was longitudinally assessed in 114 patients by scoring three disease-specific items (sensation of vaginal bulging, obstructive symptoms, urinary incontinence), and one overall health-related QOL (HR-QOL), and compared with corresponding baseline scores. RESULTS: A longitudinal study demonstrated that a significant improvement in these symptoms was sustained at a median follow-up of 62.2 months. HR-QOL was significantly associated with vitality assessed by SF 36 (p = 0.036). Multivariate analysis revealed that update urinary incontinence, pre-operative HR-QOL was independent prognostic factors for predicting postoperative patient's satisfaction. CONCLUSIONS: Although surgical repair of pelvic floor prolapse can achieve acceptable results with intermediate-term durability as well as improving the QOL, preoperative patients' HR-QOL may be considered in the decision making process for treatment.

Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma.

BACKGROUND: Ras association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC. PATIENTS AND METHODS: The study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5' CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing. RESULTS: High levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053). CONCLUSION: These results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.

Relationship between body mass index and periodontitis in young Japanese adults.

BACKGROUND AND OBJECTIVE: Obesity has been implicated as a risk factor for several chronic health conditions. Recent studies have reported a relationship between obesity and periodontitis, but few studies have investigated this relationship in adolescents. The purpose of the present study was to investigate the relationship between body composition (i.e. body mass index and body fat) and periodontitis in university students in Japan. MATERIAL AND METHODS: Medical and oral health data were collected in a cross-sectional examination conducted by the Health and Environment Center of Okayama University. Students aged 18-24 years (n = 618), who were interested in receiving an oral health examination, were included in the analysis. The community periodontal index was used to assess periodontal status. Subjects with a community periodontal index score of 0-2 were considered as controls and those with a community periodontal index score of > 2 were considered to have periodontitis. Logistic regression analysis was used to estimate the association between body mass index and periodontitis. RESULTS: The body mass index of all subjects was < 30 kg/m2. Age and body mass index were significantly associated with the community periodontal index. Logistic regression analysis revealed a 16% increased risk for periodontitis per 1-kg/m2 increase in body mass index (adjusted odds ratio, 1.16; 95% confidence interval, 1.03-1.31; p < 0.05). CONCLUSION: Body mass index could be a potential risk factor for periodontitis among healthy young individuals (i.e. those with a body mass index of < 30 kg/m2). It may be useful to include an evaluation of body mass index on a regular basis in university general and oral health examinations.

[Histoculture drug response assay guided concurrent chemoradiotherapy for non-small cell lung cancer].

Retrospective analysis was done to evaluate concurrent chemoradiotherapy (CCRT) using chemotherapeutic agents judged to be sensitive by histoculture drug response assay (HDRA) for non-small cell lung cancer (NSCLC). We treated 21 NSCLC patients with CCRT using senstivie agents judged by HDRA from 1999 to 2004. Objective response was evaluated in 20 patients. They were consisted of 1 complete response (CR) case, 18 partial response (PR) cases, and 1 stable disease (SD) case. The response rate was 95%. Ten cancer related deaths were observed during 816 +/- 861 (60-2,780) days follow-up. Median survival time was 604 days. One- and 5-year survival rates were 73.9% and 40.3%, respectively. In conclusion, HDRA may improve efficacy of CCRT for NSCLC.