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The effects of slot width for confined, laminar impinging slot jets of millimeter-scale are considered, including experimental measurements of spatially resolved distributions of local Nusselt numbers measured on a constant heat flux surface. The effects of Reynolds number, nozzle-to-plate distance, and dimensional slot width on the local Nusselt number are investigated for slot nozzle width B values of 0.5 mm, 1 .Omm, and 1.5 mm. Reynolds numbers Re range from 120 to 200, nozzle-to-plate distances HIB vary from 0.75 to 12.5, and the nozzle aspect ratio y/B is 50. Observed are different stagnation point Nusselt number Nu0 variations with Re, HIB, and B, where the onset of unsteadiness, and the intermittent flapping motion of the jet column are both associated with important varia-tions to local, stagnation region Nusselt numbers Nu0, as experimental configuration and condition change. The variations of these stagnation-point Nusselt numbers associated with these two modes of unsteadiness are characterized by correlations which provide the dependence upon Reynolds number and normalized nozzle-to-plate distance ratio, HIB, for different dimensional values of B. Also presented are stagnation region Nusselt number variations, for steady, impingement jets at values of H/B less than 4.6-7.8. These are characterized by three separate regimes of behavior, each of which shows signifi-cantly different Nu0 dependence upon Re, HIB, and B. [ABSTRACT FROM AUTHOR]

Objective: It has been expected that patient with posttraumatic recurrent anterior shoulder dislocation might have limited daily life activity because of pain and apprehension of dislocation. But there have been only a small number of investigations regarding the rotator strength in this patient. The aim of this study is to find the characteristics about rotator strength of patient with posttraumatic recurrent anterior shoulder dislocation using an isokinetic testing. Method: We enrolled thirteen patients with posttraumatic recurrent anterior shoulder dislocation and fifteen sex, age-matched healthy nonathletic subjects in this controlled study. All participants were male and there were no significant differences between the two groups in age, height, weight, BMI. Isokinetic internal rotator and external rotator strength was evaluated with a Biodex Isokinetic Testing machine (Biodex Medical Systems, Shirley, NY, USA), tests were performed at 60 deg/sec and 180 deg/sec for both sides. Peak torque normalized to body weight, external rotator to internal rotator ratio, total work and fatigue were calculated for each angular velocity. The association between internal rotator and external rotator strength and shoulder instability was analyzed by comparisons with a control group. Results: Any notable differences could not be found between the two groups given all data from no symptomatic left shoulder. There were no significant differences between the two groups statistically in internal rotation strength of right shoulder. However, there has been a tendency that at all angular velocities, external rotator peak torque to body weight, total work and external rotator to internal rotator ratio were significantly lower in the anterior instability group than the control group at all angular velocities. There was no substantial difference between those groups with respect to the fatigue of external rotator and internal rotator in our study. Conclusion: The prominent characteristics of posttraumatic recurrent anterior shoulder dislocation are external rotator weakness and loss of balance with external rotator and internal rotator. Therefore selective training using this information rotator might be helpful in conservative treatment and rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: We studied the need for distal clavicle resection by comparing rotator cuff tear patients who underwent non-surgical treatment with and without acromioclavicular joint pathology. Materials and Methods: 45 cases that had been under follow up care for at least 9 months after receiving rotator cuff repair in our hospital between Jan. 2005 and Jun. 2011 had been studied. Acromioclavicular joint pathology group and control group were classified by physical examination and MRI findings. The temporal changes in shoulder joint abduction, internal and external rotation strength, ASES and KSS score of the two groups were measured and analyzed. Results: The acromioclavicular joint pathology complicated rotator cuff injury group's strength measurements for abduction, internal rotation, external rotation were each 8.05 (±4.54), 11.33 (±6.05), 10.24 (± 5.27) preoperatively and improved to 13.26 (±5.50), 17.51 (±6.80), 15.60 (±5.37) post operatively while the KSS score and ASES score were each 49.07 (±15.28) and 48.65 (±13.27) preoperatively, improving to 84.48 (±10.96) and 84.65. (±9.86). The measurements for the group without complicating acromioclavicular pathology are as follows. The strength for abduction, internal rotation, external rotation was each 6.42 (±3.11), 7.59 (±4.81) and 7.93 (±4.49) preoperatively, improving to 15.85 (±7.35), 19.18 (± 9.14), 16.95 (±5.70) post operatively, while the KSS score and ASES score each went from 42.12 (± 6.43) and 41.37 (±7.42) to 83.44 (±6.30) and 83.17 (±7.01) respectively. The measurements for the two groups, however, did not show a statistically significant difference (p>0.05). Conclusion: Analysis of the rotator cuff injury groups with and without AC joint pathology showed that both groups had improved strength, ASES and KSS scores with no statistical difference difference among the groups. As such, it thought that conservative treatment is an acceptable alternative to distal clavicle resection. [ABSTRACT FROM AUTHOR]

Purpose: This matched case-cohort retrospective study examined the effectiveness of shed blood re-transfusion in reducing the need for allogeneic blood transfusion in computer-assisted primary cemented total knee arthroplasty (TKA). Methods: The shed blood re-transfusion system used was the cell saver system. Data from 146 cases were analyzed (73 patients with cell saver, 73 patients without cell saver). Results: The ABT rate was similar in each group. The mean allogenic blood transfusion volume was similar for each group (CS = 214 ± 453 ml, non-CS = 288 ± 447 ml). The only factors correlated with allogenic blood transfusion use were low preoperative hemoglobin and low body mass index. Two patients in cell saver group experienced shivering after re-transfusion. Conclusion: Shed blood re-transfusion provided no blood management benefits in computer-assisted primary TKA and is therefore recommended only for selected patients with low hemoglobin levels and low body mass index. [ABSTRACT FROM AUTHOR]

Purpose: High-flexion knee prosthesis designs are generally thought to be of benefit only in patients with a satisfactory preoperative flexion angle. The aim of the study was to evaluate whether high-flexion designs were indeed worthless in osteoarthritis patients with severe preoperative flexion limitation. Methods: The postoperative maximum flexion was compared in osteoarthritis patients with a preoperative maximum flexion of 100° or less, using LPS and LPS-flex implants (NexGen®; Zimmer, Warsaw, IN) in total knee arthroplasties. Data on 39 knees in the LPS group and 41 in the LPS-flex group, with a minimum of 2 years of follow-up, were reviewed retrospectively, focused on the postoperative maximum flexion. Results: Two years after operation, the LPS-flex group had a mean postoperative maximum flexion of 131 ± 10° (range, 105-140°), which was significantly higher than the 121 ± 12° (range, 95-140°) in the LPS group ( P < 0.001). In the LPS-flex group, about half of the knees ( n = 18, 44%) could achieve a maximum flexion of 140° postoperatively, but in the LPS group only five knees (13%) achieved a maximum flexion of 140°. Conclusion: Despite a different period of the operation between groups, this study suggested that osteoarthritis patients with severe preoperative flexion limitation could achieve more postoperative gain in flexion when a high-flexion prosthesis was used, compared to the flexion obtained using a standard prosthesis. [ABSTRACT FROM AUTHOR]

Purpose: Severe varus deformity may lead to premature failure of total knee arthroplasties (TKAs) because of technical difficulties associated with satisfactory alignment and good ligament balance. The aim of the study was to assess whether preoperative varus severity would affect the longevity, clinical outcomes, and complication rates of TKAs. Methods: From a prospectively collected database, we assessed outcomes in 168 knees that underwent primary TKAs using a single posterior stabilized design. These included 86 knees with mild preoperative deformity (varus mechanical tibiofemoral angle ≤5°) and 82 knees with severe preoperative deformity (varus angle ≥15°). Survivorship was analyzed by a life-table method. Clinical outcomes were also compared, including Knee Society knee and functional scores and complication rates. Results: The postoperative tibiofemoral angle of the mild varus group was 7.1° ± 2.5°, whereas that of the severe varus group was 6.4° ± 2.5° (n.s.). There were no significant differences in terms of perioperative complications. Both groups showed the same cumulative survival rate, with absence of mechanical failure, of 98% at 7 years without difference (n.s.). There were no significant between-group differences of clinical parameters throughout the each follow-up period. Conclusion: The knees with preoperative severe varus deformity were achieved the results comparable to those in knees with mild varus deformity, as determined by survival rate and clinical results. These data suggest that preoperative severe varus deformities can be successfully managed and do not have any detrimental effect on the longevity and clinical outcomes after a modern posterior stabilized TKA. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the effect of a radial tear on degenerative medial meniscus posterior horn tear extrusion and to identify predictors of medial meniscus extrusion. Methods: We reviewed the records of 102 knees with medial meniscus posterior horn tears and degeneration that underwent a partial meniscectomy. Tears were classified as root ( n = 17) and non-root ( n = 85) tears, or as radial ( n = 46) and non-radial ( n = 56) tears. Groups were compared in terms of absolute and relative meniscal extrusion, and the proportion of knees with major (>3 mm) extrusion. Multiple regression analysis was used to identify predictors of extrusion. Results: The radial group had greater mean absolute (4 ± 1 vs. 3 ± 1 mm, P = 0.001) and relative (31 ± 11 vs. 23 ± 12%, P = 0.031) extrusion than the non-radial group. The radial group also had a greater proportion of major extrusions than the non-radial group (74% vs. 26%; P = 0.016). In contrast, the root tear and non-root tear groups were similar in terms of mean absolute (3 ± 1 vs. 3 ± 1 mm, P = n.s.) and relative (30 ± 7 vs. 26 ± 13%; P = n.s.) extrusion and in terms of proportion with major extrusions (59 vs. 55%; P = n.s.). Extrusion was found to be associated with a similar strength with both the presence of a radial component and the preoperative Kellgren-Lawrence grade. Conclusion: Meniscal extrusion was greater and more severe in knees with a radial tear component than in knees without a radial component. The incidence and degree of major extrusion was similar in knees with root tears and non-root tears. A radial component and knee osteoarthritis severity were similarly predictive of absolute and relative extrusion. Meniscal extrusion in osteoarthritic knees was associated not only with degenerative meniscal tear but also with osteoarthritis severity. Therefore, arthroscopic meniscal procedures, especially meniscal repair, should be cautiously considered in patients with meniscal extrusion. [ABSTRACT FROM AUTHOR]

Patients desire less pain and faster recovery of range of knee motion after total knee arthroplasty (TKA). While minimal invasive surgery (MIS) TKA appears to meet these needs, concerns exist regarding component malpositioning. Navigation systems can reduce the incidence of component misalignment. The present prospective randomized study compared limited medial parapatellar (LMPP) and mini-midvastus (MMV) approaches in 30 patients who had bilateral simultaneous primary TKAs. Each patient underwent LMPP on one knee and MMV on the other. Both approaches were navigation-assisted. We primarily analyzed postoperative pain (using visual analog scores), range of knee motion, and hospital for special surgery (HSS) scores in the first 6 postoperative months (i.e., the early postoperative period), and secondarily analyzed perioperative parameters and radiographic outcomes. The LMPP and MMV approaches were found to be similar in terms of pain measured at postoperative 3 days, 1, 2 weeks, 1, 3, and 6 months ( P = NS). Similarly, the 2 approaches were found to be similar in terms of range of motion measured at 1, 2 weeks, 1, 3, and 6 months ( P = NS), and in terms of HSS scores measured at 1, 3, and 6 months ( P = NS). There were also no differences between groups in terms of total blood loss, approach preferred by patients, and radiographic component positioning. The present study found that navigation-assisted MMV and navigation-assisted LMPP resulted in similar outcomes in terms of pain, ROM, HSS score, and radiologic outcomes over the first six postoperative months. We recommend the LMPP approach over the MMV approach in navigation-assisted MIS TKA because it is more familiar to surgeons and is easier to convert to the conventional approach where necessary. [ABSTRACT FROM AUTHOR]

The present report describes a case of septic knee arthritis secondary to reactivated chronic osteomyelitis. The osteolytic lesion observed on the initial radiographs resulted in further imaging studies including CT and MRI, which confirmed the diagnosis. Based on the patient’s history, physical findings and imaging studies, we performed open debridement rather than arthroscopic surgery in order to treat the infected intraarticular knee joint and ream the femur intramedullary canal. Additionally, an antibiotic-impregnated cement rod was inserted into the medullary cavity to fill the dead space and eradicate the infection. A high index of suspicion combined with adequate comprehension of initial plain radiographs is essential for accurate diagnosis of septic knee arthritis with adjacent chronic osteomyelitis. [ABSTRACT FROM AUTHOR]

Equalized rectangular extension and flexion gaps are considered desirable to ensure proper kinematics in total knee arthroplasty (TKA). We compared soft tissue balancing in TKAs performed using navigation-assisted gap-balancing (60 knees) and conventional measured resection (56 knees). The outlier of soft tissue balancing was defined as a gap difference >3 mm between the medial and lateral sides in 90° flexion and extension. Medial or lateral outliers in extension or flexion were observed in 12% (7 of 60) navigation TKAs and 25% (14 of 56) conventional TKAs ( p = 0.028). There were more outliers in flexion–extension gap difference on the medial side in the conventional (23%) than in the navigation-assisted (5%) group ( p = 0.025). However, the proportion of flexion gap difference, extension gap difference, and lateral gap difference outliers did not differ significantly between the two groups ( n.s.). Additionally, clinicoradiologic outcomes were similar for the two groups except for the postoperative mechanical axis outlier ( p = 0.012). Navigation-assisted soft tissue balancing in TKA reduced not only the postoperative alignment outlier, but also the medial gap difference and achieved a more rectangular flexion and extension gap compared with conventional TKA. [ABSTRACT FROM AUTHOR]

Background: Although graft extrusion is of concern after meniscal allograft transplantation (MAT), the correlation between extrusion and clinicoradiological outcomes remains unclear. Hypothesis: Patients with graft extrusion after MAT have worse clinical outcomes and greater arthritic change than those without graft extrusion. Study Design: Cohort study; Level of evidence, 3. Methods: Forty-three patients underwent MAT between 1999 and 2004. Grafts were classified as either nonextruded (<3 mm) or extruded (≥3 mm) according to 1-year postoperative magnetic resonance imaging (MRI) findings. The mean patient age at the time of surgery was 33.5 years (range, 17-43 years), and themean follow-up period was 5.1 years (range, 3.5-8.3 years). The Lysholm score was used to evaluate knee function. In addition, preoperative and postoperative (final follow-up) measurements were taken to determine the absolute and relative (affected side/normal side) joint space width (JSW) on a standing 45° flexion posteroanterior view. Results: Magnetic resonance imaging at 1 year showed the mean graft subluxation was 3.03±0.872 mm across all patients. Twenty-six knees (60%) were classified as nonextruded and 17 (40%) as extruded. No statistical difference was found between these 2 groups regarding Lysholm score improvement after MAT. Overall, absolute and relative JSWs were slightly narrower postoperatively compared with preoperatively across all patients (mean absolute difference, 0.283 mm; mean relative difference; 4.79%; P<.001). However, extruded and nonextruded knees were similar in terms of absolute (P = .764) and relative (P = .482) JSW after MAT. The amount of extrusion did not correlate with Lysholm score or the relative difference between preoperative and postoperative JSW across all patients or in either group. Conclusion: Joint space width was slightly narrower after MAT. Extrusion had no effect on 5-year clinical or radiological outcomes. [ABSTRACT FROM AUTHOR]

Background: Erythrose reductase (ER) catalyzes the final step of erythritol production, which is reducing erythrose to erythritol using NAD(P)H as a cofactor. ER has gained interest because of its importance in the production of erythritol, which has extremely low digestibility and approved safety for diabetics. Although ERs were purified and characterized from microbial sources, the entire primary structure and the corresponding DNA for ER still remain unknown in most of erythritol-producing yeasts. Candida magnoliae JH110 isolated from honeycombs produces a significant amount of erythritol, suggesting the presence of erythrose metabolizing enzymes. Here we provide the genetic sequence and functional characteristics of a novel NADPH-dependent ER from C. magnoliae JH110. Results: The gene encoding a novel ER was isolated from an osmophilic yeast C. magnoliae JH110. The ER gene composed of 849 nucleotides encodes a polypeptide with a calculated molecular mass of 31.4 kDa. The deduced amino acid sequence of ER showed a high degree of similarity to other members of the aldo-keto reductase superfamily including three ER isozymes from Trichosporonoides megachiliensis SNG-42. The intact coding region of ER from C. magnoliae JH110 was cloned, functionally expressed in Escherichia coli using a combined approach of gene fusion and molecular chaperone co-expression, and subsequently purified to homogeneity. The enzyme displayed a temperature and pH optimum at 42°C and 5.5, respectively. Among various aldoses, the C. magnoliae JH110 ER showed high specific activity for reduction of erythrose to the corresponding alcohol, erythritol. To explore the molecular basis of the catalysis of erythrose reduction with NADPH, homology structural modeling was performed. The result suggested that NADPH binding partners are completely conserved in the C. magnoliae JH110 ER. Furthermore, NADPH interacts with the side chains Lys252, Thr255, and Arg258, which could account for the enzyme's absolute requirement of NADPH over NADH. Conclusions: A novel ER enzyme and its corresponding gene were isolated from C. magnoliae JH110. The C. magnoliae JH110 ER with high activity and catalytic efficiency would be very useful for in vitro erythritol production and could be applied for the production of erythritol in other microorganisms, which do not produce erythritol. [ABSTRACT FROM AUTHOR]

The OrthoPilot TKA navigation system (B. Braun Aesculap, Tuttlingen, Germany) offers software to optimize soft tissue balance using gap balance techniques. However, there are no studies on the reliability of the navigation-guided gap technique. The goal of this study is to establish the reliability of the navigation-guided gap technique. The investigators measured flexion and extension gap in the medial and lateral sides of the knee joint after bone resection to evaluate the reliability of navigation-guided soft tissue balancing. Gap data from 100 cases of navigation-guided total knee arthroplasty were analyzed. We defined trapezoidal gap (unsatisfactory soft tissue balance) as a gap difference > 3 mm between the medial and lateral sides in extension and a 5-mm difference in 90° of flexion. Furthermore, gap difference between flexion and extension greater than 3 mm on the medial side and 5 mm on the lateral side was also considered a trapezoidal gap. Among 100 cases, 84 showed rectangular (acceptable) gap, and 16 showed trapezoidal gap. We also evaluated the correlation between clinical results including range of motion and soft tissue balance as well as characteristics of trapezoidal gap. This study suggests that the navigation-guided gap technique is a reliable method for optimizing soft tissue balance. [ABSTRACT FROM AUTHOR]

An echiuroid species, Urechis unicinctus, was surveyed for Hox genes using polymerase chain reaction with homeobox-specific degenerate primers. We identified nine distinct homeodomain-containing gene fragments. These nine fragments were classified by comparative analysis. This analysis revealed that this echiuroid possessed at least three Hox genes from the anterior group, five from the central group, and one from the posterior group. [ABSTRACT FROM AUTHOR]

Cyclohexanone monooxygenase (CHMO) catalyzing Baeyer-Villiger oxidation converts cyclic ketones into optically pure lactones, which have been used as building blocks in organic synthesis. A recombinant Escherichia coli BL21(DE3)/pMM4 expressing CHMO originated from Acinetobacter sp. NCIB 9871 was used to produce e-caprolactone through a simultaneous biocatalyst production and Baeyer-Villiger oxidation (SPO) process. A fed-batch process was designed to obtain high cell density for improving production of e-caprolactone. The fed-batch SPO process gave the best results, 10.2 g/L of e-caprolactone and 0.34 g/(L h) of productivity, corresponding to a 10.5- and 3.4-fold enhancement compared with those of the batch SPO, respectively. [ABSTRACT FROM AUTHOR]

Investigated the effects of pH levels on aminolevulinic acid (ALA) synthase activity and ALA production in a jar-fermenter culture of recombinant Escherichia coli. Effects of certain nutritional factors on fermentative production of ALA; Stability of ALA at various pH levels; Effect of the ratio of carbon to nitrogen on the production of ALA.

The effects of nozzle diameter on heat transfer and fluid flow are investigated for a round turbulent jet impinging on a flat plate surface. The flow at the nozzle exit has a fully developed velocity profile. A uniform heat flux boundary is created at the plate surface by using gold film Intrex, and liquid crystals are used to measure the plate surface temperature. The experiments are performed for the jet Reynolds number (Re) of 23,000, with a dimensionless distance between the nozzle and plate surface (L/d) ranging from 2 to 14 and a nozzle diameter (d) ranging from 1.36 to 3.40 cm. The results show that the local Nusselt numbers increase with the increasing nozzle diameter in the stagnation point region corresponding to 0≤r/d≤0.5. This may be attributed to an increase in the jet momentum and turbulence intensity level with the larger nozzle diameter, which results in the heat transfer augmentation. In the mean time, the effect of the nozzle diameter on the local Nusselt numbers is negligibly small at the wall jet region corresponding to r/d >0.5. [ABSTRACT FROM AUTHOR]

The characteristics of flame‐kernel development in a premixed gasoline–air mixture in a cylindrical constant‐volume combustion chamber are measured. The experiments are performed with an initial temperature of 393 K, pressure of 6 bar, and equivalence ratio Φ = 0.8 with the use of various ignition systems and spark plugs. The schlieren pictures of the process are presented, and the measured results for flame velocity, heat‐release rate, and mass fraction of the burnt fuel are analyzed. [ABSTRACT FROM AUTHOR]

Abstract Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

A new bitellurophene-based π-conjugated polymer (PDPPBTe) was synthesized and its semiconducting property was utilized for detecting Br2. The PDPPBTe polymer exhibited a highly sensitive response to Br2, which was indicated by a significant variation of the drain current in thin-film transistors. [ABSTRACT FROM AUTHOR]

The use of autologous quadrupled hamstring tendon graft is a well-known technique for anterior cruciate ligament reconstruction. In cases where the diameter of the graft is inadequate, the stability of graft fixation and subsequent bone to tendon healing may be compromised. We describe a new technique to augment the autologous double looped hamstring tendon graft during anterior cruciate ligament reconstruction using cancellous bone chips. This simple technique effectively enhances graft fixation and stability. [ABSTRACT FROM AUTHOR]

Abstract Background TMC1, which encodes transmembrane channel-like protein 1, forms the mechanoelectrical transduction (MET) channel in auditory hair cells, necessary for auditory function. TMC1 variants are known to cause autosomal dominant (DFNA36) and autosomal recessive (DFNB7/11) non-syndromic hearing loss, but only a handful of TMC1 variants underlying DFNA36 have been reported, hampering analysis of genotype-phenotype correlations. Methods In this study, we retrospectively reviewed 338 probands in an in-house database of genetic hearing loss, evaluating the clinical phenotypes and genotypes of novel TMC1 variants associated with DFNA36. To analyze the structural impact of these variants, we generated two structural models of human TMC1, utilizing the Cryo-EM structure of C. elegans TMC1 as a template and AlphaFold protein structure database. Specifically, the lipid bilayer-embedded protein database was used to construct membrane-embedded models of TMC1. We then examined the effect of TMC1 variants on intramolecular interactions and predicted their potential pathogenicity. Results We identified two novel TMC1 variants related to DFNA36 (c.1256T > C:p.Phe419Ser and c.1444T > C:p.Trp482Arg). The affected subjects had bilateral, moderate, late-onset, progressive sensorineural hearing loss with a down-sloping configuration. The Phe419 residue located in the transmembrane domain 4 of TMC1 faces outward towards the channel pore and is in close proximity to the hydrophobic tail of the lipid bilayer. The non-polar-to-polar variant (p.Phe419Ser) alters the hydrophobicity in the membrane, compromising protein-lipid interactions. On the other hand, the Trp482 residue located in the extracellular linker region between transmembrane domains 5 and 6 is anchored to the membrane interfaces via its aromatic rings, mediating several molecular interactions that stabilize the structure of TMC1. This type of aromatic ring-based anchoring is also observed in homologous transmembrane proteins such as OSCA1.2. Conversely, the substitution of Trp with Arg (Trp482Arg) disrupts the cation-π interaction with phospholipids located in the outer leaflet of the phospholipid bilayer, destabilizing protein-lipid interactions. Additionally, Trp482Arg collapses the CH-π interaction between Trp482 and Pro511, possibly reducing the overall stability of the protein. In parallel with the molecular modeling, the two mutants degraded significantly faster compared to the wild-type protein, compromising protein stability. Conclusions This results expand the genetic spectrum of disease-causing TMC1 variants related to DFNA36 and provide insight into TMC1 transmembrane protein-lipid interactions.

The extragalactic background light (EBL) captures the total integrated emission from stars and galaxies throughout the cosmic history. The amplitude of the near-infrared EBL from space absolute photometry observations has been controversial and depends strongly on the modeling and subtraction of the zodiacal light (ZL) foreground. We report the first measurement of the diffuse background spectrum at 0.8–1.7 μm from the CIBER experiment. The observations were obtained with an absolute spectrometer over two flights in multiple sky fields to enable the subtraction of ZL, stars, terrestrial emission, and diffuse Galactic light. After subtracting foregrounds and accounting for systematic errors, we find the nominal EBL brightness, assuming the Kelsall ZL model, is nW m−2 sr−1 at 1.4 μm. We also analyzed the data using the Wright ZL model, which results in a worse statistical fit to the data and an unphysical EBL, falling below the known background light from galaxies at λ < 1.3 μm. Using a model-independent analysis based on the minimum EBL brightness, we find an EBL brightness of nWm−2 sr−1 at 1.4 μm. While the derived EBL amplitude strongly depends on the ZL model, we find that we cannot fit the spectral data to ZL, Galactic emission, and EBL from solely integrated galactic light from galaxy counts. The results require a new diffuse component, such as an additional foreground or an excess EBL with a redder spectrum than that of ZL. [ABSTRACT FROM AUTHOR]

Abstract Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial arch, and renal system. Sporadic cases of atypical BOR/BO syndrome have been recently reported; however, evidence on genotype–phenotype correlations and molecular mechanisms of those cases is lacking. We herein identified five SIX1 heterozygous variants (c.307dupC:p.Leu103Profs*51, c.373G>A:p.Glu125Lys, c.386_391del:p.Tyr129_Cys130del, c.397_399del:p.Glu133del, and c.501G>C:p.Gln167His), including three novel variants, through whole-exome sequencing in five unrelated Korean families. All eight affected individuals with SIX1 variants displayed non-syndromic hearing loss (DFNA23) or atypical BO syndrome. The prevalence of major and minor criteria for BOR/BO syndrome was significantly reduced among individuals with SIX1 variants, compared to 15 BOR/BO syndrome families with EYA1 variants. All SIX1 variants interacted with the EYA1 wild-type; their complexes were localized in the nucleus except for the p.Leu103Profs*51 variant. All mutants also showed obvious but varying degrees of reduction in DNA binding affinity, leading to a significant decrease in transcriptional activity. This study presents the first report of SIX1 variants in South Korea, expanding the genotypic and phenotypic spectrum of SIX1 variants, characterized by DFNA23 or atypical BO syndrome, and refines the diverse molecular aspects of SIX1 variants according to the EYA1–SIX1–DNA complex theory.

Significant improvement in targeted therapy for colorectal cancer (CRC) has occurred over the past few decades since the approval of the EGFR inhibitor cetuximab. However, cetuximab is used only for patients possessing the wild-type oncogene KRAS, NRAS, and BRAF, and even most of these eventually acquire therapeutic resistance, via activation of parallel oncogenic pathways such as RAS-MAPK or PI3K/Akt/mTOR. The two aforementioned pathways also contribute to the development of therapeutic resistance in CRC patients, due to compensatory and feedback mechanisms. Therefore, combination drug therapies (versus monotherapy) targeting these multiple pathways may be necessary for further efficacy against CRC. In this study, we identified PIK3CA mutant (PIK3CA MT) as a determinant of resistance to SMI-4a, a highly selective PIM1 kinase inhibitor, in CRC cell lines. In CRC cell lines, SMI-4a showed its effect only in PIK3CA wild type (PIK3CA WT) cell lines, while PIK3CA MT cells did not respond to SMI-4a in cell death assays. In vivo xenograft and PDX experiments confirmed that PIK3CA MT is responsible for the resistance to SMI-4a. Inhibition of PIK3CA MT by PI3K inhibitors restored SMI-4a sensitivity in PIK3CA MT CRC cell lines. Taken together, these results demonstrate that sensitivity to SMI-4a is determined by the PIK3CA genotype and that co-targeting of PI3K and PIM1 in PIK3CA MT CRC patients could be a promising and novel therapeutic approach for refractory CRC patients.

A water‐soluble polysaccharide (GFP) was isolated from Grateloupia filicina and fractionated using a DEAE Sepharose Fast Flow column to evaluate immunostimulatory activity. Carbohydrates (62.0%–68.4%) and sulfates (29.3%–34.3%) were the major components of GFP and its fractions (GFP‐1 and GFP‐2), with relatively lower levels of proteins (4.5%–15.4%) and uronic acid (1.4%–3.9%). The average molecular weight (Mw) for GFP and its fractions was calculated between 98.2%–243.7 kDa. The polysaccharides were composed of galactose (62.1%–87.2%), glucose (4.5%–33.2%), xylose (3.1%–5.3%), mannose (1.4%–2.2%), rhamnose (1.2%–2.0%), and arabinose (0.9%–1.7%) units connected through →3)‐Galp‐(1→, →4)‐Galp‐(1→, →2)‐Galp‐(1→, →6)‐Galp‐(1→, →3,4)‐Galp ‐(1→, →3,6)‐Galp‐(1→, →4,6)‐Galp‐(1→, →3,4,6)‐Galp‐(1→, →2,3)‐Galp‐(1→, →2,4)‐Galp‐(1→, →4)‐Glcp‐(1→, →6)‐Glcp‐(1→ and →4,6)‐Glcp‐(1→residues. The isolated polysaccharides effectively induced RAW264.7 murine macrophages by releasing nitric oxide (NO) and various cytokines via nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) and mitogen‐activated protein kinase (MAPK) signaling pathways. Further, the expression of toll‐like receptor‐2 (TLR‐2) and TLR‐4 in RAW264.7 cells indicated their activation through TLR‐2 and TLR‐4 binding receptors. Among the polysaccharides, GFP‐1 highly stimulated the activation of RAW264.7 cells, which was mainly constituted of (→1) terminal‐D‐galactopyranosyl, (1→3)‐linked‐ᴅ‐galactopyranosyl, (1→4)‐linked‐ᴅ‐galactopyranosyl and (1→3,4) ‐linked‐ᴅ‐galactopyranosyl residues. These findings demonstrate that GFP‐1 from G. filicina are effective at stimulating the immune system and this warrants further investigation to determine potential biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract Background Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome, WFS1 heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified two WFS1 heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of the WFS1 variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes in WFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review. Methods We performed molecular genetic test and evaluated clinical phenotypes of three WFS1-associated DFNA6/14/38 families. A putative WFS1–NCS1 interaction model was generated, and the impacts of WFS1 variants on stability were predicted by comparing intramolecular interactions. A total of 62 WFS1 variants associated with DFNA6/14/38 were included in a systematic review. Results One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7–9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val in WFS1 is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI. Conclusions We expanded the genotypic spectrum of WFS1 heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits for WFS1 heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.

Abstract Background During medial opening wedge high tibial osteotomy (MOWHTO), sometimes the plate tends to be positioned anteromedially. The plate position can affect the length of the proximal screw, which significantly affects stability after osteotomy. Therefore, research on the correlation among plate position, screw length, and clinical outcomes is needed. Methods This retrospective review examines 196 knees in 175 patients who underwent MOWHTO from May 2012 to December 2018, for symptomatic medial compartment osteoarthritis with a varus alignment of > 5°. We evaluated the anteroposterior plate position, length of proximal screw, and postoperative computed tomography (CT). We reviewed patients’ clinical outcome scores, presence of lateral hinge fracture, neurovascular complications, and infection. The correlation among proximal plate position, proximal screw length, and clinical outcomes was evaluated using Pearson’s correlation analysis. A subgroup analysis by screw angle (> 48 ° or

Objectives Aquatic therapy is a significant intervention method for both patients and healthy individuals. However, in clinical practice, quantitative measurements are rarely applied in aquatic therapy due to the disadvantages of submerging expensive instruments in water. In this study, we used readily available smartphones and armbands to measure leg segments and joint angles during aquatic gait and evaluated the reliability of these measurements. Methods Waterproof smartphones were strapped to the trunk, thighs, and shanks of 19 healthy young adults using armbands. The angles of the trunk, thigh, and shank segments were measured during aquatic gait. The measurements were repeated 1 day later. The data were analyzed to obtain the angles of the hip and knee joints. Results Measurement repeatability, calculated using the intraclass correlation coefficient (ICC), was the highest for the shank segment range of motion (ROM) (first 46.79° ± 5.50°, second 50.12° ± 9.98°, ICC = 0.78). There was high agreement in trunk segment ROM (first 6.36° ± 1.42°, second 4.29° ± 1.83°, ICC = 0.73), thigh segment ROM (first 33.49° ± 5.18°, second 37.31° ± 8.70°, ICC = 0.62), and knee joint ROM (first 52.43° ± 11.26°, second 62.19° ± 16.65°, ICC = 0.68) and fair agreement in hip joint ROM (first 34.60°±4.71°, second 37.80° ± 7.84°, ICC = 0.59). Conclusions Smartphones can be used to reliably measure leg segments and joint angles during aquatic gait, providing a simpler method for obtaining these measurements and enabling the wider use of aquatic motion analysis in clinical practice and research.

The compounds hydrangenol and hydrangenol 8-O-glucoside are abundant in Hydrangea macrophylla. This study investigated the effects of hydrangenol and hydrangenol 8-O-glucoside derived from H. macrophylla on atopic dermatitis (AD). Compared with hydrangenol 8-O-glucoside, hydrangenol resulted in more potent inhibition of interleukin 4 (IL-4) gene expression and β-hexosaminidase release, as well as more potent inhibition of the phosphorylation of signal transducer and activator of transcription 6 (STAT6). Ultra High-Performance Liquid Chromatography (UHPLC), the concentrations of hydrangenol were found to be lower than the concentration of hydrangenol 8-O-glucoside in H. macrophylla extracts. To increase the hydrangenol content of H. macrophylla extract, component conversion methods were studied. Conclusion, microwave processing was found to be the optimal method for deglycosylation. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptors (HERs) are the primary targets of many directed cancer therapies. However, the reason a specific dimer of HERs generates a stronger proliferative signal than other permutations remains unclear. Here, we used single-molecule immunoprecipitation to develop a biochemical assay for endogenously-formed, entire HER2-HER3 heterodimers. We observed unexpected, large conformational fluctuations in juxta-membrane and kinase domains of the HER2-HER3 heterodimer. Nevertheless, the individual HER2-HER3 heterodimers catalyze tyrosine phosphorylation at an unusually high rate, while simultaneously interacting with multiple copies of downstream signaling effectors. Our results suggest that the high catalytic rate and multi-tasking capability make a concerted contribution to the strong signaling potency of the HER2-HER3 heterodimers.

CFP 2 is a sulfated polysaccharide isolated from Codium fragile that shows excellent immunomodulatory activity. To reduce the side effects of 5-fluorouracil (5-FU), CFP 2 was used as a macromolecular carrier to react with carboxymethyl-5-fluorouracil (C-5-FU) to form CFP 2 -C-5-FU, which further reacted with folic acid (FA) via an ester bond to form novel conjugates (CFP 2 -C-5-FU-FA). CFP 2 -C-5-FU-FA was confirmed by nuclear magnetic resonance (NMR) analysis. In vitro drug release results showed that the cumulative release rate of C-5-FU was 49.9% in phosphate buffer (pH 7.4) after 96 h, which was much higher than that of the other groups, indicating that CFP2-C-5-FU-FA showed controlled drug release behavior. CFP 2 -C-5-FU-FA also exhibited enhanced apoptosis and cellular uptake in vitro. Further, intravenous administration of CFP 2 -C-5-FU-FA in an HCT-116 cell-bearing xenograft mouse showed that the conjugates were safe and effective drug delivery systems. These results suggest that folate-targeted conjugates can be used effectively for efficient chemotherapy of colorectal cancer. [Display omitted] • Sulfated polysaccharides (CFP2) was extracted from Codium fragile. • A novel conjugates (CFP2-C-5-FU-FA) was prepared through esterification reaction. • CFP2-C-5-FU-FA showed controlled drug release behavior in in vitro. • CFP2-C-5-FU-FA exhibited enhanced apoptosis and cellular uptake. • Anti-tumor studies performed in vivo using HCT-116 xenograft mice model. [ABSTRACT FROM AUTHOR]

Bifidobacterium bifidum, a common endosymbiotic inhabitant of the human gut, is considered a prominent probiotic microorganism that may promote health. We completely decrypted the 2.2-Mb genome sequence of B. bifidum BGN4, a strain that had been isolated from the fecal sample of a healthy breast-fed infant, and annotated 1,835 coding sequences. [ABSTRACT FROM AUTHOR]

YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells. Treatment of human gastric cancer cells with YM155 differentially induced cell death dependent on the stability of cIAP1 as well as survivin. Transfection with cIAP1 expression plasmids decreased cell sensitivity to YM155, whereas knockdown of endogenous cIAP1 using RNA interference enhanced sensitivity to YM155. In addition, double knockdown of survivin and cIAP1 significantly induced cell death in the YM155-resistant cell line, MKN45. We also showed that YM155 induced autoubiquitination and proteasome-dependent degradation of cIAP1. Surprisingly, survivin affected the stability of cIAP1 through binding, contributing to cell sensitivity to YM155. Thus, our findings reveal that YM155 sensitizes human gastric cancer cells to apoptotic cell death by degrading cIAP1, and furthermore, cIAP1 in gastric cancer cells may act as a PD marker for YM155 treatment. [ABSTRACT FROM AUTHOR]

Extragalactic background light (EBL) anisotropy traces variations in the total production of photons over cosmic history and may contain faint, extended components missed in galaxy point-source surveys. Infrared EBL fluctuations have been attributed to primordial galaxies and black holes at the epoch of reionization (EOR) or, alternately, intrahalo light (IHL) from stars tidally stripped from their parent galaxies at low redshift. We report new EBL anisotropy measurements from a specialized sounding rocket experiment at 1.1 and 1.6 micrometers. The observed fluctuations exceed the amplitude from known galaxy populations, are inconsistent with EOR galaxies and black holes, and are largely explained by IHL emission. The measured fluctuations are associated with an EBL intensity that is comparable to the background from known galaxies measured through number counts and therefore a substantial contribution to the energy contained in photons in the cosmos. [ABSTRACT FROM AUTHOR]

Sleeve fractures are generally restricted to children or adolescents, and usually occur at the lower patella pole. Here we report on a superior pole sleeve fracture in an adult that occurred following forceful passive physiotherapy after cast immobilization. To our knowledge, this is the first report of a superior pole sleeve fracture in an otherwise healthy adult. The case highlighted that a diagnosis of a superior patella pole sleeve fracture in an adult can easily be missed because it is a rare injury, and hence is unlikely to be suspected by physicians. [ABSTRACT FROM AUTHOR]

Background: Previous 3-dimensional computed tomography (3D CT) studies of knees after anterior cruciate ligament (ACL) reconstruction have compared femoral tunnel positions obtained using the transtibial and anteromedial drilling techniques. This study used postoperative in vivo 3D CT analysis to compare the locations of the femoral tunnel aperture among 3 drilling techniques used in ACL reconstruction: transtibial, anteromedial portal, and outside-in., Hypothesis: The use of the transtibial drilling technique might result in a less anatomically accurate femoral tunnel placement than the anteromedial portal and outside-in techniques., Study Design: Cohort study; Level of evidence, 3., Methods: Immediate postoperative in vivo 3D CT was used to assess the location of the femoral tunnel aperture in 153 patients who underwent single-bundle ACL reconstruction using the transtibial (n = 42), anteromedial portal (n = 73), or outside-in (n = 38) techniques. Femoral tunnel positions were measured by an anatomic coordinate axis method in the low-to-high and deep-to-shallow directions of the distal femur at 90° of knee flexion., Results: The low-to-high femoral tunnel positions were significantly higher in the transtibial group than in the anteromedial portal (P < .001) and outside-in (P < .001) groups. There were no differences among the 3 groups in the deep-to-shallow femoral tunnel positions (P = .773)., Conclusion: The transtibial technique of anatomic reconstruction resulted in more highly positioned femoral tunnels in the low-to-high direction than did the anteromedial portal and outside-in techniques. However, no significant differences in the femoral tunnel location were observed in the deep-to-shallow direction.