Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored intracellular calcium dynamics using calcium imaging techniques to measure spontaneous calcium oscillations in hPSC-CMs in the presence or absence of test compounds. For the cardiotoxicity test, hPSC-CMs were treated with various compounds, and calcium flux was measured to evaluate their effects on calcium dynamics. We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. Additionally, in the effectiveness test, hPSC-CMs were exposed to ATX-II, a sodium current inducer for mimicking long QT syndrome type 3, followed by exposure to test compounds. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics.

Arthroscopic Superior Capsular Reconstruction With Tensor Fascia Lata Allograft for Irreparable Rotator Cuff Tears: Clinical and Radiologic Outcomes for a Minimum 1-Year Follow-Up.

PURPOSE: To confirm the radiologic and clinical outcomes after performing arthroscopic superior capsular reconstruction (ASCR) using a tensor fascia lata (TFL) allograft. METHODS: Thirty-three patients with irreparable rotator cuff tears were treated with ASCR with a TFL allograft. The mean age and follow-up period were 62 years and 20.1 months, respectively. TFL allografts were used as 3, 4, and 6 layers, and the graft thickness was 3.7, 3.9, and 5.4 mm, respectively. Range of motion, visual analog scale (VAS) pain score, American Shoulder and Elbow Surgeons score, and Constant score were evaluated preoperatively and at the final follow-up. The pre-, postoperative, and final acromiohumeral distances (AHD) were compared. The graft integrity was checked through a follow-up magnetic resonance imaging at least 6 months after surgery. RESULTS: Torn grafts were identified in 6 cases (19%). AHD significantly increased from 5.0 to 8.0 mm postoperatively (P < .0001). However, there was no significant difference of 5.0 mm at the final follow-up AHD. Five cases (83%) of torn grafts were induced in the 3-layered graft sheet group, but the difference was not statistically significant (P = .067). Visual analog scale, forward elevation, internal rotation, American Shoulder and Elbow Surgeons, and Constant scores significantly improved at the last follow-up. Two cases of early infection were confirmed and the graft materials were all removed. CONCLUSIONS: Despite the possibility of early infection, ASCR using TFL allograft is a reliable procedure for the irreparable rotator cuff tear. In particular, if the number of layers of TFL allograft increases, it is judged that it could become a more effective graft. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Can convertible metal-backed glenoid components replace cemented polyethylene glenoid components in anatomical total shoulder arthroplasty?

BACKGROUND: Anatomical total shoulder arthroplasty (aTSA) has been used to manage degenerative diseases such as primary osteoarthritis. An increase in the use of this procedure has led to several developments in humeral and glenoid components to improve patient outcomes. This study aimed to compare clinical and radiological outcomes of the newly-introduced convertible metal-backed glenoid components with cemented polyethylene glenoid components in aTSA, and to determine whether the new component would be comparable to a conventional one for reducing the burden of future revision or conversion surgeries. METHODS: Medical records of fifty patients who underwent aTSA with at least two years of follow-up were retrospectively reviewed. Eighteen patients received convertible metal-backed glenoid components with vitamin E1-coated liner (MB group), while thirty-two patients received conventional cemented polyethylene glenoid components (PE group). Pre- and postoperative clinical and radiological outcomes (acromion-greater tuberosity angle [AGA] and humeral lateral offset [LO]) at final follow-up were assessed. Radiolucent lines (RLLs) and loosening around the humeral and glenoid components were also evaluated. RESULTS: Clinical outcomes improved after surgery in both groups (all p < 0.001). The arc of rotation measured by AGA improved postoperatively in both groups (all p < 0.001), and AGA and LO were not different according to the type of glenoid components (all p > 0.05). Overall complication rates including RLLs of PE and MB groups were 43.8% (14/32) and 16.7% (3/18), respectively (p = 0.031). Although the PE group had more RLLs than did the MB group (p < 0.05), related symptoms and/or glenoid implant loosening were not observed in both groups. Subscapularis failure occurred in two patients in the PE group and in one in the MB group. CONCLUSION: The convertible metal-backed glenoid implant with vitamin E1-coated liner may be a good alternative for considering the potential for an easier conversion to reverse total shoulder arthroplasty.

Biomechanical consequences of glenoid and humeral lateralization in reverse total shoulder arthroplasty.

BACKGROUND: The objective of our study was to quantify the biomechanical effectiveness of lateralization in RTSA with respect to glenoid and humeral component configurations. METHODS: Eight cadaveric shoulders were tested in a custom shoulder testing system. Three parameters, including the glenosphere thickness, humeral tray offset, and insert thickness, were assessed by implanting 8 configurations on each specimen. Humeral position, maximum internal rotation, and maximum external rotation (ER) before impingement were quantified at 0° and 30° glenohumeral abduction. The adduction angle at which the humeral component contacted the inferior scapular neck and the abduction angle where acromial notching occurred were also measured. The simulated active range of motion, including ER and abduction capability, was tested by increasing the load applied to the remaining posterior cuff and middle deltoid, respectively. Stability was evaluated by the forces that induced anterior dislocation at 30° abduction. RESULTS: The thicker glenosphere affected only lateralization, whereas the centric humeral tray and thicker insert significantly affected humeral lateralization and distalization simultaneously. Greater adduction and ER angles were found in more lateralized humerus. A significant positive correlation between humeral lateralization and ER capability was observed; however, lateralization did not significantly improve implant stability in this cadaveric testing system. CONCLUSION: Lateralization is achievable at both the glenoid and humeral sides but has different effects; therefore, lateralized implant options should be selected according to patients' needs. Lateralization is an effective strategy for reducing adduction notching while increasing ER capability. Thicker glenospheres only affected humeral lateralization. The centric humeral tray would be selected for less distalization to avoid overlengthening, whereas an eccentric humeral tray is the most effective for distalization and medialization in reducing abduction notching to the acromion and for patients with pseudoparalysis.

Clinical outcomes of reverse shoulder arthroplasty and rotator cuff repair in patients with massive rotator cuff tears without osteoarthritis: comparison using propensity score matching.

BACKGROUND: The optimal management for massive rotator cuff tears (MRCTs) without osteoarthritis (OA) remains controversial. The purpose of this study was to evaluate and compare the clinical outcomes of reverse shoulder arthroplasty (RSA) vs. rotator cuff repair (RCR) in patients with MRCTs without OA. METHODS: We conducted a retrospective data analysis of 68 patients treated for MRCTs via RSA and 215 patients treated for MRCTs via arthroscopic RCR between January 2014 and April 2019. Through propensity score matching, patients were matched for sex, age, tear size, and global fatty degeneration index. Thirty-nine patients in each group were included, and all patients had completed minimal 2-year follow-up. Postoperative radiologic evaluations of healing failure were performed. The visual analog scale score for pain, range of motion, and functional outcome measures including the American Shoulder and Elbow Surgeons score, QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score, Simple Shoulder Test score, and Constant score were assessed and compared between the 2 groups. RESULTS: Healing failure was observed in 10 patients in the RCR group (32.3%). No statistically significant differences in preoperative range of motion and functional scores were found between the RCR and RSA groups. Both groups showed significant pain relief and functional improvement at final follow-up. Patients in the RCR group showed significantly greater forward elevation (156.4° ± 23.8° vs. 139.7° ± 22.4°, P < .001) and internal rotation (thoracic vertebra, T8.2 ± 1.2 vs. T9.7 ± 2.6, P = .001). The average American Shoulder and Elbow Surgeons score was 88.3 ± 12.2 in the RCR group and 81.8 ± 16.1 in the RSA group (P = .045). The QuickDASH score was significantly higher in the RCR group (P = .019). A significantly higher Simple Shoulder Test score (9.7 ± 2.8 vs. 8.1 ± 3.0, P = .01) and a significantly higher Constant score (67.2 ± 6.5 vs. 63.2 ± 7.1, P = .011) were seen in the RCR group. CONCLUSION: Both RSA and RCR are effective and reliable treatment options for MRCTs without OA. However, the RCR group showed better shoulder function improvement than the RSA group. Considering the possible implications of RSA, RCR should be referred to as a first-line treatment option for patients with MRCTs without OA with proper indications.

Cytokine-Induced JAK2-STAT3 Activates Tissue Regeneration under Systemic or Local Inflammation.

We investigated the immune response mechanisms under systemic and local inflammation using mouse models whereby lipopolysaccharide (LPS) was administered intraperitoneally to induce systemic inflammation, and epicutaneous sensitization with ovalbumin was used to induce local inflammation. LPS increased the immune cell infiltration in the cardiac muscle near the aorta, alveoli, hepatic sinusoid, renal interstitium, and the submucosal layer of the duodenum. Similarly, ovalbumin increased the abundance of macrophages in the skin. Both LPS and ovalbumin induced NF-κB p65 and IκBα phosphorylation, as well as the expression of NF-κB target genes (TLR4, IL6, and TNFα). Additionally, both LPS and ovalbumin led to an increase in the absolute IL-1ß, IL-6, and TNFα serum levels and cytokine-related janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) phosphorylation. Moreover, the activated JAK2/STAT3 signaling increased the number of Ki67-positive cells (proliferating cells) and development pathway target gene expression (regeneration) in the inflammation models. In conclusion, LPS and ovalbumin increase immune cell infiltration in tissues, NF-κB activation, cytokine levels in serum, cytokine-stimulated JAK2/STAT3 signaling, and tissue regeneration.

The potential of locking plate with intramedullary fibular allograft to manage proximal humeral fracture with an unstable medial column.

PURPOSE: To evaluate the potential of locking compression plate with intramedullary fibular allograft in managing proximal humeral fractures with an unstable medial column. METHODS: Between March 2007 and March 2015, we retrospectively analyzed 63 patients who underwent locking plate fixation for proximal humeral fracture with an unstable medial column. All patients were assigned into group 1 (patients treated with locking plate) and group 2 (patients treated with locking plate with intramedullary fibular allograft). Groups 1 and 2 were composed of 29 and 34 patients, respectively. We analyzed bone union, the neck-shaft angle, the Constant score, the range of motion, and complications. RESULTS: The mean average bone union time of the patients was 13.9 weeks in group 1 and 11.3 weeks in group 2. The average Constant score was 67.4 in group 1 and 73.6 in group 2 (p < 0.05). The mean preoperative NSA, postoperative NSA, and NSA at the last follow-up were 104.4°, 125.8°, and 115.8°, respectively, in group 1, and 109.0°, 130.3°, and 127.1°, respectively, in group 2. The mean forward flexion, abduction, external rotation, and internal rotation were 109.0°, 48.2°, 34.0°, and L5, respectively, in group 1, and 127.5°, 118.2°, 38.7°, and L1, respectively, in group 2. In group 1, avascular necrosis occurred in one patient and screw cutout in two patients. In group 2, screw cutout occurred in one patient. CONCLUSION: In patients aged over 65 years with proximal humeral fractures, an unstable medial column was associated with poor clinical results owing to varus collapse. To prevent this, an intramedullary fibular allograft was used, and radiologic and clinical results were better with this approach than with a locking plate alone. Therefore, locking plate fixation using a fibular allograft is one of the possible treatments for patients with an unstable medial column.

Glass molding of all glass Fresnel lens with vitreous carbon micromold.

An all glass Fresnel lens (AGFL) was fabricated by glass molding with a vitreous carbon (VC) micro mold. In the glass molding process, a glass plate was heated up to its softening temperature and pressed against to the VC mold to replicate the Fresnel pattern. The VC molds having negative shape Fresnel profile were fabricated by carbonization of replicated Furan precursor using a diamond turning machined nickel master. During the carbonization process, the Furan precursor shrank due to the thermal decomposition, and this shrinkage must be compensated to obtain a precise AGFL. In this study, we examined the shrinkage ratio during the carbonization process using a preliminary experiment using the commercially available PMMA Fresnel lens as the master, and fabricated a nickel master with an enlarged Fresnel profile for shrinkage compensation. To verify the compensation method, the surface profiles of the fabricated VC mold and molded AGFL were measured and compared with the designed profile. The deviations between measured and designed profiles were less than 4 µm. In addition, the tip radii of the grooves and draft angle of the molded AGFL were within the acceptable tolerance for CPV applications.

Morphologic Factors Related to Repair Outcomes for Delaminated Rotator Cuff Tears: A Minimum 2-Year Retrospective Comparison Study.

PURPOSE: To evaluate clinical outcomes and repair integrity after en masse transosseous-equivalent suture bridge repair for delaminated rotator cuff tears and to analyze the morphologic factors related to clinical outcomes and repair integrity. METHODS: This study included 99 patients who underwent the technique of en masse transosseous-equivalent suture bridge repair for delaminated rotator cuff tears. Morphologic factors were estimated using magnetic resonance imaging, and clinical outcomes were evaluated using the University of California, Los Angeles score; American Shoulder and Elbow Surgeons score; and Constant shoulder score. The morphologic factors included the shape of delamination, retraction length of the bursal and articular layers, gap distance between the layers, and length of the intrasubstance cleavage. According to follow-up magnetic resonance imaging, cases were categorized into the intact or retear group. The morphologic factors were compared between the 2 groups, including the correlation between the morphologic factors and postoperative outcomes. RESULTS: Retears occurred in 26 of 99 cases (26%). In both the intact and retear groups, the University of California, Los Angeles, American Shoulder and Elbow Surgeons, and Constant scores improved postoperatively (P < .0001). The most common delamination shape was that of a more retracted articular layer in retears. We found no differences in retears in terms of the retraction length of the bursal layer, gap distance, and length of the intrasubstance cleavage. However, the retraction length of the articular layer differed significantly between the groups (P < .0001). No correlation between the morphologic factors and clinical outcomes was found. CONCLUSIONS: Arthroscopic en masse transosseous-equivalent suture bridge repair is a useful technique in delaminated tears to achieve optimal repair outcomes. In addition, although there was no correlation between the morphologic factors and postoperative clinical outcomes, the retraction length of the articular layer was identified as a significant factor influencing repair integrity. We recommend emphasizing the reduction of tension within the articular layer during the repair procedure. LEVEL OF EVIDENCE: Level III, retrospective comparison study.

Replication of a glass microlens array using a vitreous carbon mold.

A low-cost fabrication method for a high-surface-quality glass microlens array (MLA) was proposed using a glass molding technique with a vitreous carbon (VC) mold. A VC mold with a high-surface-quality MLA cavity was fabricated, and the glass MLA with a root mean square surface roughness of 4.59 nm was replicated using the VC mold. To obtain the glass MLA with high replication quality, the effects of molding conditions were examined. The surface quality was not degraded during the proposed VC mold fabrication method and glass molding process. The focused beam spot of the glass molded MLA was analyzed; it showed a diffraction-limited characteristic of the glass molded MLA.

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation.

Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1ß regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1ß levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.

Factors affecting rotator cuff integrity after arthroscopic repair for medium-sized or larger cuff tears: a retrospective cohort study.

BACKGROUND: We wished to identify the preoperative prognostic factors associated with structural integrity after repair of medium-sized and larger rotator cuff tears and to determine the cutoff values using receiver operating characteristic curve analysis. METHODS: The study included 180 patients with medium-sized and larger rotator cuff tears. Each had a minimum 2-year postoperative follow-up by magnetic resonance imaging. We assessed several patient-related and disease-related preoperative factors using univariate and multivariate logistic regression analysis. To determine the cutoff value for the significant variables, receiver operating characteristic curve analysis was performed. RESULTS: Retears occurred in 28 of the 180 patients (15.6%). Univariate analysis found that retear was significantly affected by the type of work and pattern of tear. The rate of retear was significantly increased in diabetes and with increasing tear size, extent of retraction, delamination, and fatty infiltration. Furthermore, reduced remnant tendon length, distance from the musculotendinous junction to the face of the glenoid, occupation ratio, and acromiohumeral interval were also significant risk factors. In the multivariate analysis, body mass index, diabetes, dyslipidemia, extent of retraction, delamination, distance from musculotendinous junction to face of glenoid, occupation ratio, fatty infiltration of infraspinatus, and acromiohumeral interval remained significant risk factors. The extent of retraction (22.2 mm) and the occupation ratio (53.5%) showed highly accurate cutoff values for predicting retear. CONCLUSION: Multiple factors influenced the healing process after rotator cuff repair. The best predictors were the extent of retraction and occupation ratio, which could help assist in determining the prognosis after rotator cuff repairs.

Human galectin-9 on the porcine cells affects the cytotoxic activity of M1-differentiated THP-1 cells through inducing a shift in M2-differentiated THP-1 cells.

BACKGROUND: In xenotransplantation, immune rejection by macrophages occurs rapidly and remains a major obstacle. Studies to control immune rejection in macrophages have been continuing to date. Recent studies have reported that human galectin-9 (hGal-9) can regulate the function of regulatory T cells (Treg), as well as cytotoxicity T cells (CTL) and natural killer cells (NK). Although the effect of hGal-9 on lymphocytes has been well studied, the relationship between hGal-9 and myeloid cells has been scarcely studied. METHODS: To confirm the decreased cytotoxic activity effect by hGal-9 in M1-differentiated THP-1 cells, we established the hGal-9 expressing transgenic porcine cell line. hGal-9 siRNA was transfected to transgenic cells and recombinant hGal-9 (rhGal-9) was treated to co-culturing condition, and then, flow cytometry assay was conducted for analyzing the cytotoxic activity of M1-differentiated THP-1 cells. Related inflammatory cytokines (IL-1ß, IL-10, TNF-α, IL-6, IL-12, IL-23, and TGF-ß) and related enzymes (iNOS and Arginase 1) were analyzed by qPCR and Western blot assay. To identify the shift in M1/M2-differentiated THP-1 cells, expression levels of CCR7, CD163, iNOS, and Arginase 1 and population of M2 marker positive cells were analyzed. RESULTS: The expression levels of pro-inflammatory cytokines in M1-differentiated THP-1 cells co-cultured with hGal-9-expressing porcine kidney epithelial cells were decreased, but not in co-cultured THP-1 cells. However, the expression levels of anti-inflammatory cytokines were also increased in co-cultured M1-differentiated THP-1 cells. The cytotoxicity effect of M1-differentiated THP-1 cells on transgenic cells was decreased while the expression levels of anti-inflammatory cytokines and M2 macrophages-related molecules were increased. M2 differentiation program was turned on while M1 program was turned down by enhancing the phosphorylation levels of Akt and PI3K and the expression level of PPAR-γ. Due to these changes, differentiation of M2 program was enhanced in cells co-cultured with hGal-9. CONCLUSIONS: These data suggested that hGal-9 has a reduction in M1-differentiated THP-1 cell cytotoxic activity-related acute immune rejection in pig-to-human xenotransplantation in addition to its role in lymphoid lineage immune cell regulation.

Characterization of a specific monoclonal antibody against immunoglobulin light kappa/L1 chain in olive flounder (Paralichthys olivaceus).

Immunoglobulins (Ig) are heterodimeric proteins that play critical roles in the adaptive immune system of vertebrates. Because of their plasticity, teleostean Igs are more diverse, and thus do not conform to mammalian classifications. Because of this, mammalian-based Ig cell markers cannot be used successfully to study immune responses in fish. There is therefore a need to produce Ig-specific cell markers for fish. Here, we attempted to identify the specific isotype detected by an Ig light chain-specific monoclonal antibody (anti-olive flounder IgL-mAb: M7C3-4) that we had previously produced [11]. Three newly identified sequences of the Ig light chain from olive flounder were classified according to their isotypes. Subsequent analyses revealed that M7C3-4 was able to specifically detect lymphocytes expressing one of the κ chains (Igκ-a) in olive flounder. Interestingly, Igκ-a+ B cells were more abundant in spleen and trunk-kidney than in peripheral blood, indicating a distribution different from that of IgM+ B cells. Our work reveals interesting aspects of B cell distribution and differentiation, and may aid in the production of suitable and effective cell markers for olive flounder.

Right hepatectomy in living donors with previous abdominal surgery.

BACKGROUND: Few studies have evaluated the impact of previous abdominal surgery (PAS) on living donor right hepatectomy (LDRH). The aim of this study was to investigate the outcomes of liver transplantation using right lobe grafts of living donors with PAS. METHODS: Data were reviewed from LDRH patients at the authors' institution between March 2008 and November 2014. LDRH patients with PAS were divided into two groups according to upper PAS (group 1) or lower PAS (group 2), and they were compared to those without PAS (group 3) who were matched 1:1 based on age, gender, and body mass index. Perioperative data, complications by the Clavien classification, and the outcomes with more than 14 months follow-up were compared. RESULTS: Twenty-three (4.9%) of a total of 471 LDRH donors had PAS. Eleven donors were assigned to group 1, 12 to group 2, and 23 to group 3. Intraperitoneal adhesions were found in 20 (87.0%) of 23 donors with PAS, of whom 5 (21.7%) had adhesiolysis-related injuries that happened more commonly in group 1 than in group 2 (P=0.025). LDRH was successfully completed under upper midline laparotomy in all donors. No donors received perioperative blood transfusion. The peak postoperative AST, ALT, INR, and total bilirubin levels made no difference between the three groups. Compared with group 3, groups 1 and 2 had a longer operative time (P=0.012) and a higher grade I complication rate (P=0.047). All donors recovered fully to their routine activities. The 23 recipients of grafts from donors with PAS showed good liver function with 1-year graft and patient survivals of 100%. CONCLUSION: A history of PAS is not a contraindication to LDRH in the current era of advanced surgical techniques.

Medialized repair for retracted rotator cuff tears.

BACKGROUND: The purpose of this study was to evaluate the functional outcomes of medialized rotator cuff repair and the continuity of repaired tendon in chronic retracted rotator cuff tears. METHODS: Thirty-five consecutive patients were selected from 153 cases that underwent arthroscopic rotator cuff repair for more than medium-sized posterosuperior rotator cuff tears between July 2009 and July 2012 performed with the medialized repair. All cases were available for at least 2 years of postoperative follow-up. The visual analog scale of pain, muscle strength, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and University of California-Los Angeles score were evaluated. RESULTS: At the final follow-up, all clinical outcomes were significantly improved. The visual analog scale score for pain improved from 6 ± 1 preoperatively to 2 ± 1 postoperatively. The range of motion increased from preoperatively to postoperatively: active forward elevation, from 134° ± 49° to 150° ± 16°; active external rotation at the side, from 47° ± 15° to 55° ± 10°; and active internal rotation, from L3 to L1. The shoulder score also improved: Constant score, from 53.5 ± 16.7 to 79 ± 10; American Shoulder and Elbow Surgeons score, from 51 ± 15 to 82 ± 8; and University of California-Los Angeles score, from 14 ± 4 to 28 ± 4. The retear cases at the final follow-up were 6 (17%). CONCLUSIONS: Medialized repair may be useful in cases in which anatomic bone-to-tendon repair would be difficult because of the excessive tension of the repaired tendon and a torn tendon that does not reach the anatomic insertion.

Characterization of monoclonal antibodies against porcine pulmonary alveolar macrophages of gnotobiotic miniature swine.

There is no sufficient porcine specific antibody available to investigate the ontogeny and development of porcine pulmonary alveolar macrophage (PAM). Therefore, several mouse anti-porcine macrophage mAbs have been produced and characterized in this study. First, the monoclonal antibody PM18-7, an IgG1, kappa isotype, bound to 91% of PAM, 6% of monocytes, and 2% of granulocytes indicating PM18-7 was found to be PAM specific. Monocyte derived macrophages could not be induced to express the PM18-7 antigen by culture. PM18-7 was immunoprecipitated with a molecule of 260 kDa under non-reducing conditions and with that of 130 kDa under reducing conditions in SDS-PAGE. Second, the monoclonal antibody PM3-15, an IgG1, kappa isotype, bound to 92% of PAM, 86% of monocytes, and 3% of granulocytes indicating PM3-15 was mononuclear phagocyte specific. PM3-15 was immunoprecipitated with a molecule of 245 kDa under non-reducing conditions and those of 150, 95 kDa under reducing conditions in SDS-PAGE. Third, the monoclonal antibody PM16-6, an IgM isotype, bound to 82% of PAM, 89% of monocytes, and 82% of granulocytes indicating PM16-6 recognizes those cells of myeloid lineage such as macrophages, monocytes and granulocyte. The antigen immunoprecipitated by PM16-6 was 120 kDa under non-reducing conditions and was 75, 25 kDa under reducing conditions. Finally, the antigen bound to PM18-7 was identified as ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, CD203a), PM3-15 was figured out as integrin alpha M beta 2 precursor (ITGaM, CD11b) and PM16-6 was identified as Thimet oligopeptidase (THOP-1) by the LC-MS/MS protein sequencing method.

Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients.

BACKGROUND: Once-daily extended-release tacrolimus (Tac-OD) has been introduced as a useful therapeutic option to increase patient adherence to immunosuppressive therapy. This study aimed to evaluate the safety, efficacy and immunosuppressant adherence of conversion from twice-daily tacrolimus (Tac-BID) to Tac-OD in stable adult living donor liver transplant (LDLT) recipients in a single institution. METHODS: Between February and May 2013, Tac-BID was converted to Tac-OD in recipients followed up for at least 12 months after transplantation and without previous rejection episodes. The switching policy was based on a dose ratio of 1:1 with dose adjustment target trough levels at 3-5 ng/mL. Tacrolimus trough levels, laboratory parameters, metabolic disorders, and adverse events were assessed. RESULTS: A total of 229 patients were enrolled in the study. The median age at conversion was 53 years (range 31-73). The median transplant duration was 35.3 months (range 12.0-95.4). During a median follow-up of 13.5 months after conversion, 9 patients returned to Tac-BID because of adverse events. No acute rejection episodes were observed. Of 214 patients still on Tac-OD at 12 months, 12 (5.6%) received a reduced dose and 95 (44.4%) required an increased dose over baseline. Overall adherence was 82.2% at the end of follow-up. CONCLUSION: The conversion from Tac-BID to Tac-OD with similar target trough levels after conversion is safe and effective for long-term stable LDLT patients.

Primary status, complementary status, and organizational survival in the U.S. venture capital industry.

We introduce a distinction between two kinds of status and examine their effects on the exit rates of organizations investing in the U.S. venture capital industry. Extending past work on status-based competition, we start with a simple baseline: we describe primary status as a network-related signal of an organization's quality in a leadership role, that is, as a function of the degree to which an organization leads others that are themselves well regarded as lead organizations in the context of investment syndicates. Combining Harary's (1959) image of the elite consultant with Goffman's (1956) concept of "capacity-esteem," we then discuss complementary status as an affiliation-based signal of an organization's quality in a supporting role. We measure complementary status as a function of the extent to which an organization is invited into syndicates by well-regarded lead organizations-that is, by those possessing high levels of primary status. Findings show that, conditioning on primary status, complementary status reduces the rate at which venture capital organizations exit the industry. Consistent with the premise that these kinds of status correspond to different roles and market identities, we also find that complementary status attenuates (and ultimately reverses) the otherwise favorable effect of primary status on an organization's life chances. Theoretically and methodologically oriented scope conditions, as well as implications for future research, are discussed.

Combination treatment against scuticociliatosis by reducing the inhibitor effect of mucus in olive flounder, Paralichthys olivaceus.

The olive flounder, Paralichthys olivaceus, is an economically important food fish in Japan and Korea. Scuticociliatosis is a major parasitic disease, and fatal infection with scuticociliates, or mixed infections with scuticociliates and other pathogenic agents (e.g., Vibrio spp.) cause severe mortalities in farmed olive flounders. To date, however, effective chemotherapeutic treatment of scuticociliatosis has only been reported at the in vitro level. In this study, we employed combination treatment, using benzalkonium chloride (to remove excess mucus from the body surface) and bronopol (to kill the parasites), to overcome the protective effect of mucus by some medicine to the scuticociliates. In the presence of the mucus mixture, the higher dose of bronopol (156 ppm) yielded morphologies and motilities similar to those of ciliates treated with the lower dose of bronopol (80 ppm) in the absence of mucus. We also investigated the in vivo effects of this treatment in field trials involving a total of 15,025 naturally infected flounders. We observed that short-term bath treatments with benzalkonium chloride (50 ppm) followed by bronopol (500 ppm) were effective, assessed by the relative percentage mortality (RPS) value. Thus, this study provides a notable therapeutic strategy by removing the mucus to treat scuticociliatosis in olive flounders at the aquaculture field level.