A computational simulation study to determine the biomechanical influence of posterior condylar offset and tibial slope in cruciate retaining total knee arthroplasty.

OBJECTIVES: Posterior condylar offset (PCO) and posterior tibial slope (PTS) are critical factors in total knee arthroplasty (TKA). A computational simulation was performed to evaluate the biomechanical effect of PCO and PTS on cruciate retaining TKA. METHODS: We generated a subject-specific computational model followed by the development of ± 1 mm, ± 2 mm and ± 3 mm PCO models in the posterior direction, and -3°, 0°, 3° and 6° PTS models with each of the PCO models. Using a validated finite element (FE) model, we investigated the influence of the changes in PCO and PTS on the contact stress in the patellar button and the forces on the posterior cruciate ligament (PCL), patellar tendon and quadriceps muscles under the deep knee-bend loading conditions. RESULTS: Contact stress on the patellar button increased and decreased as PCO translated to the anterior and posterior directions, respectively. In addition, contact stress on the patellar button decreased as PTS increased. These trends were consistent in the FE models with altered PCO. Higher quadriceps muscle and patellar tendon force are required as PCO translated in the anterior direction with an equivalent flexion angle. However, as PTS increased, quadriceps muscle and patellar tendon force reduced in each PCO condition. The forces exerted on the PCL increased as PCO translated to the posterior direction and decreased as PTS increased. CONCLUSION: The change in PCO alternatively provided positive and negative biomechanical effects, but it led to a reduction in a negative biomechanical effect as PTS increased.Cite this article: K-T. Kang, Y-G. Koh, J. Son, O-R. Kwon, J-S. Lee, S. K. Kwon. A computational simulation study to determine the biomechanical influence of posterior condylar offset and tibial slope in cruciate retaining total knee arthroplasty. Bone Joint Res 2018;7:69-78. DOI: 10.1302/2046-3758.71.BJR-2017-0143.R1.

Patient-specific medial unicompartmental knee arthroplasty has a greater protective effect on articular cartilage in the lateral compartment: A Finite Element Analysis.

OBJECTIVES: Patient-specific (PS) implantation surgical technology has been introduced in recent years and a gradual increase in the associated number of surgical cases has been observed. PS technology uses a patient's own geometry in designing a medical device to provide minimal bone resection with improvement in the prosthetic bone coverage. However, whether PS unicompartmental knee arthroplasty (UKA) provides a better biomechanical effect than standard off-the-shelf prostheses for UKA has not yet been determined, and still remains controversial in both biomechanical and clinical fields. Therefore, the aim of this study was to compare the biomechanical effect between PS and standard off-the-shelf prostheses for UKA. METHODS: The contact stresses on the polyethylene (PE) insert, articular cartilage and lateral meniscus were evaluated in PS and standard off-the-shelf prostheses for UKA using a validated finite element model. Gait cycle loading was applied to evaluate the biomechanical effect in the PS and standard UKAs. RESULTS: The contact stresses on the PE insert were similar for both the PS and standard UKAs. Compared with the standard UKA, the PS UKA did not show any biomechanical effect on the medial PE insert. However, the contact stresses on the articular cartilage and the meniscus in the lateral compartment following the PS UKA exhibited closer values to the healthy knee joint compared with the standard UKA. CONCLUSION: The PS UKA provided mechanics closer to those of the normal knee joint. The decreased contact stress on the opposite compartment may reduce the overall risk of progressive osteoarthritis.Cite this article: K-T. Kang, J. Son, D-S. Suh, S. K. Kwon, O-R. Kwon, Y-G. Koh. Patient-specific medial unicompartmental knee arthroplasty has a greater protective effect on articular cartilage in the lateral compartment: A Finite Element Analysis. Bone Joint Res 2018;7:20-27. DOI: 10.1302/2046-3758.71.BJR-2017-0115.R2.

Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.

Metabolic diseases affect various organs including the brain. Accumulation or depletion of substrates frequently leads to brain injury and dysfunction. Deficiency of aminopeptidase P1, a cytosolic proline-specific peptidase encoded by the Xpnpep1 gene, causes an inborn error of metabolism (IEM) characterized by peptiduria in humans. We previously reported that knockout of aminopeptidase P1 in mice causes neurodevelopmental disorders and peptiduria. However, little is known about the pathophysiological role of aminopeptidase P1 in the brain. Here, we show that loss of aminopeptidase P1 causes behavioral and neurological deficits in mice. Mice deficient in aminopeptidase P1 (Xpnpep1-/- ) display abnormally enhanced locomotor activities in both the home cage and open-field box. The aminopeptidase P1 deficiency in mice also resulted in severe impairments in novel-object recognition, the Morris water maze task, and contextual, but not cued, fear memory. These behavioral dysfunctions were accompanied by epileptiform electroencephalogram activity and neurodegeneration in the hippocampus. However, mice with a heterozygous mutation for aminopeptidase P1 (Xpnpep1+/- ) exhibited normal behaviors and brain structure. These results suggest that loss of aminopeptidase P1 leads to behavioral, cognitive and neurological deficits. This study may provide insight into new pathogenic mechanisms for brain dysfunction related to IEMs.

Preservation of kinematics with posterior cruciate-, bicruciate- and patient-specific bicruciate-retaining prostheses in total knee arthroplasty by using computational simulation with normal knee model.

OBJECTIVES: Preservation of both anterior and posterior cruciate ligaments in total knee arthroplasty (TKA) can lead to near-normal post-operative joint mechanics and improved knee function. We hypothesised that a patient-specific bicruciate-retaining prosthesis preserves near-normal kinematics better than standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining prostheses in TKA. METHODS: We developed the validated models to evaluate the post-operative kinematics in patient-specific bicruciate-retaining, standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under gait and deep knee bend loading conditions using numerical simulation. RESULTS: Tibial posterior translation and internal rotation in patient-specific bicruciate-retaining prostheses preserved near-normal kinematics better than other standard off-the-shelf prostheses under gait loading conditions. Differences from normal kinematics were minimised for femoral rollback and internal-external rotation in patient-specific bicruciate-retaining, followed by standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under deep knee bend loading conditions. Moreover, the standard off-the-shelf posterior cruciate-retaining TKA in this study showed the most abnormal performance in kinematics under gait and deep knee bend loading conditions, whereas patient-specific bicruciate-retaining TKA led to near-normal kinematics. CONCLUSION: This study showed that restoration of the normal geometry of the knee joint in patient-specific bicruciate-retaining TKA and preservation of the anterior cruciate ligament can lead to improvement in kinematics compared with the standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining TKA.Cite this article: Y-G. Koh, J. Son, S-K. Kwon, H-J. Kim, O-R. Kwon, K-T. Kang. Preservation of kinematics with posterior cruciate-, bicruciate- and patient-specific bicruciate-retaining prostheses in total knee arthroplasty by using computational simulation with normal knee model. Bone Joint Res 2017;6:557-565. DOI: 10.1302/2046-3758.69.BJR-2016-0250.R1.

Newly developed central diabetes insipidus following kidney transplantation: a case report.

Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation.

Surface parameters of ferritic iron-rich Fe-Cr alloy.

Using first-principles density functional theory in the implementation of the exact muffin-tin orbitals method and the coherent potential approximation, we studied the surface energy and the surface stress of the thermodynamically most stable surface facet (100) of the homogeneous disordered body-centred cubic iron-chromium system in the concentration interval up to 20 at.% Cr. For the low-index surface facets of Fe and Cr, the surface energy of Cr is slightly larger than that of Fe, while the surface stress of Cr is considerably smaller than that of Fe. We find that Cr addition to Fe generally increases the surface energy of the Fe-Cr alloy; however, an increase of the bulk amount of Cr also increases the surface stress. As a result of this unexpected trend, the (100) surface of Fe-Cr becomes more stable against reconstruction with increasing Cr concentration. We show that the observed trends are of magnetic origin. In addition to the homogeneous alloy case, we also investigated the impact of surface segregation on both surface parameters.

Comparison of medial and lateral meniscal transplantation with regard to extrusion of the allograft, and its correlation with clinical outcome.

We compared extrusion of the allograft after medial and lateral meniscal allograft transplantation and examined the correlation between the extent of extrusion and the clinical outcome. A total of 73 lateral and 26 medial meniscus allografts were evaluated by MRI at a mean of 32 months (24 to 59) in 99 patients (67 men, 32 women) with a mean age of 35 years (21 to 52). The absolute values and the proportional widths of extruded menisci as a percentage were measured in coronal images that showed maximum extrusion. Functional assessments were performed using Lysholm scores. The mean extrusion was 4.7 mm (1.8 to 7.7) for lateral menisci and 2.9 mm (1.2 to 6.5) for medial menisci (p < 0.001), and the mean percentage extrusions were 52.0% (23.8% to 81.8%) and 31.2% (11.6% to 63.4%), respectively (p < 0.001). Mean Lysholm scores increased significantly from 49.0 (10 to 83) pre-operatively to 86.6 (33 to 99) at final follow-up for lateral menisci (p = 0.001) and from 50.9 (15 to 88) to 88.3 (32 to 100) for medial menisci (p < 0.001). The final mean Lysholm scores were similar in the two groups (p = 0.312). Furthermore, Lysholm scores were not found to be correlated with degree of extrusion (p = 0.242). Thus, transplanted lateral menisci extrude more significantly than transplanted medial menisci. However, the clinical outcome after meniscal transplantation was not found to be adversely affected by extrusion of the allograft.

Detection of methicillin-resistant Staphylococcus aureus (MRSA) from nasal samples by multiplex real-time PCR based on dual priming AT-rich primers.

In this study, we reported on the design of a multiplex real-time PCR assay based on SYBR Green I, incorporating dual priming adenine-thymine (AT)-rich primers for direct detection of MRSA from nasal samples. The multiplex real-time polymerase chain reaction (RT-PCR) assay reported in this study is based on SYBR Green I with incorporation of six dual priming AT-rich primers designed from the SCCmec/orf junction. A string (4-6 bp) of low-melting bases, such as adenine and thymine, was incorporated into the primers, which virtually divided a single primer in two functional regions, thus decreasing non-specific PCR products. The analytical sensitivity and specificity of the RT-PCR assay was determined with genomic DNA of reference strains (MRSA, MSSA, and MRCoNS). RT-PCR assay was performed for analysis of 72 nasal swab specimens, and the results were confirmed by use of a culture method. Furthermore, the results of RT-PCR were compared with LightCycler MRSA advance test. The multiplex RT-PCR assay reproducibly detected a minimum of 1 pg genomic DNA (31.5 copy of genome) of MRSA reference strains and clinical isolates, with a specific melting peak at 83.5 ± 1.5°C, and neither fluorescence nor a melting peak was detected in non-target isolates. The concordance rate between RT-PCR assay and culture method was 87.5% with Cohen's kappa value (κ) 0.75, which showed good agreement between the two assays. The sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 93.5%, 82.9%, 80.5%, and 94.4%, respectively. In a comparative study for the detection of 72 nasal samples, the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex RT-PCR assay with respect to LightCycler MRSA advance test was 84.2%, 88.2%, 89%, and, 83.3%, respectively. The results of RT-PCR assay demonstrated high specificity (88.2%) and positive predictive value (89%) for the direct detection of MRSA from nasal samples.

Compressive surface stress in magnetic transition metals.

Because of the increased electron density within the surface layer, metal surfaces are generally expected to have tensile surface stress. Here, using first-principles density functional calculations, we demonstrate that in magnetic 3d metals surface magnetism can alter this commonly accepted picture. We find that the thermodynamically stable surfaces of chromium and manganese possess compressive surface stress. The revealed negative surface stress is shown to be ascribed to the enhanced magnetic moments within the surface layer relative to the bulk values.

Surface relaxation and stress for 5d transition metals.

Using the density functional theory, we present a systematic theoretical study of the layer relaxation and surface stress of 5d transition metals. Our calculations predict layer contractions for all surfaces, except for the (111) surface of face centered cubic Pt and Au, where slight expansions are obtained similarly to the case of the 4d series. We also find that the relaxations of the close packed surfaces decrease with increasing occupation number through the 5d series. The surface stress for the relaxed, most closely packed surfaces shows similar atomic number dependence as the surface energy. Using Cammarata's model and our calculated surface stress and surface energy values, we examine the possibility of surface reconstructions, which is in reasonable agreement with the experimental observations.

How can we make stable linear monoatomic chains? Gold-cesium binary subnanowires as an example of a charge-transfer-driven approach to alloying.

On the basis of first-principles calculations of clusters and one dimensional infinitely long subnanowires of the binary systems, we find that alkali-noble metal alloy wires show better linearity and stability than either pure alkali metal or noble metal wires. The enhanced alternating charge buildup on atoms by charge transfer helps the atoms line up straight. The cesium doped gold wires showing significant charge transfer from cesium to gold can be stabilized as linear or circular monoatomic chains.

Depressive symptoms of type 2 diabetics treated with insulin compared to diabetics taking oral anti-diabetic drugs: a Korean study.

OBJECTIVE: The purpose of this study was to examine the depressive symptoms of type 2 diabetic patients who were treated with insulin compared to those diabetics treated with oral anti-diabetic drugs in Korea. METHODS: A total 204 outpatients with type 2 diabetes were invited to complete a questionnaire using the Beck depression inventory (BDI) to measure depressive symptoms. Age, gender, body mass index, serum lipid profile, and a social history including marital status, occupation and educational background were also assessed. The presence of diabetic complications was evaluated by examining the patients' medical records. Diabetic patients who were not treated with anti-diabetic drugs were excluded. All the study subjects were classified into two groups based on their mode of therapy: the oral drug group and insulin group. The insulin group included patients treated with insulin-oral drug combinations as well as those treated solely with insulin. RESULTS: Overall, 32.4% of our diabetic subjects showed depressive symptoms with the criterion being a BDI score > or = 16. Compared to the oral drug group, the insulin group showed a significantly higher frequency of depressive symptoms (insulin group, 48.0%; oral drug group, 27.3%; p<0.01) and higher BDI scores (insulin group, 16.6+/-10.7; oral drug group, 12.6+/-8.7; p<0.01). Moreover, after an adjustment for social factors, the degree of hyperglycemia and the presence of diabetic complications, the insulin group showed a significantly higher frequency of depression (odds ratio 4.38, 95% CI 1.66-11.6, p=0.003), compared to the oral drug group. CONCLUSIONS: The data showed that insulin treatment is related to the presence of depressive symptoms, and the importance of more careful psychological support of Korean insulin-treated type 2 diabetic patients is strongly suggested.

Multicenter study on the prevalence of perennial allergic rhinitis and allergy-associated disorders.

Multicenter Study on the Prevalence of Perennial Allergic Rhinitis and Allergy-Associated Disorders This study was aimed to determine the prevalence of perennial allergic rhinitis (PAR) using the skin test, radioallergosorbent test (RAST), or multiple allergosorbent test (MAST) and to clarify the clinical aspects of the patients diagnosed as having PAR by the questionnaire survey and rhinologic examination. The 71,120 subjects who had visited the 23 otolaryngology clinics at the randomly selected tertiary referral hospitals in Korea between November 1, 1999 and April 30, 2000 were studied. PAR was diagnosed when subjects complained of two or more associated symptoms and the skin test, RAST, or MAST using perennial inhalant allergens was positive. The questionnaire survey and rhinologic examination were performed in subjects with PAR. The prevalence of PAR was 3.93%. We could find no significant difference in the prevalence of PAR between the two sexes. However, there was a significant difference in the prevalence of PAR between the child and adult groups. The chief complaints were, in order of decreasing frequency, nasal obstruction, watery rhinorrhea, and sneezing. There was a family history of PAR in 40.2% of the subjects. The 39.6% of the subjects had associated allergic diseases, being atopic dermatitis most common. In conclusion, the prevalence of PAR in tertiary referral hospitals in Korea is 3.93%. Many subjects with PAR have family history and appear to be associated with other allergic diseases.

Chemopreventive allylthiopyridazine derivatives induce apoptosis in SK-Hep-1 hepatocarcinoma cells through a caspase-3-dependent mechanism.

Dietary organosulphur compounds including diallylsulphide, a component of garlic oil, were shown to inhibit the proliferation of tumour cells. Since hepatocellular carcinoma is one of the most lethal malignancies and there is no effective preventive measure to date, we wished to pursue the chemopreventive potential of the synthetic allylthiopyridazine derivatives (K compounds) on hepatocarcinoma cells. Here, we report that the K compounds efficiently inhibited SK-Hep-1 cell proliferation through induction of apoptosis. Increased chain length at the 3-position of allylthiopyridazine ring improved the potency of growth inhibition. K compounds downregulated Bcl-2, while Bax remained unchanged, reducing the ratio of Bcl-2 to Bax. We also provide evidence that the K compound-induced apoptosis involves cytochrome c release and caspase-3 activation. These results suggest that the allythiopyridazine derivatives, especially 3-propoxy-6-allylthiopyridazine, induce apoptosis in SK-Hep-1 cells through a caspase-3-dependent mechanism, which may contribute to the chemopreventive function for hepatocellular carcinoma.

Is cholecystectomy necessary after ERCP for bile duct stones in patients with gallbladder in situ?

BACKGROUND: The requirement for subsequent cholecystectomy in patients with gallbladder in situ after endoscopic removal of stones from the common bile duct (CBD) is controversial. The aims of this study were to assess the requirement for subsequent cholecystectomy for gallbladder-related symptoms, and to identify the patients who develop symptoms after the endoscopic removal of CBD stones. METHODS: Of 241 patients with gallbladder in situ following endoscopic removal of stones from the CBD, 146 patients (78 men and 68 women; mean age 69 +/- 13 years, range 20-93) with a follow-up time of more than three months without elective cholecystectomy were enrolled in the study. Fifty-nine patients had gallbladder stones (single stones in 27 and multiple stones in 32) and 87 patients had gallbladder in situ without stones. The time from entry to the occurrences of death or cholecystectomy was evaluated retrospectively. Cox regression analysis was used to evaluate the risk factors associated with these events. RESULTS: The mean duration of follow-up was 24.1 +/- 18.0 months (range 3-70 months). During follow-up, seven patients (4.8%) underwent cholecystectomy, on average 18.4 months after CBD stone removal, as the result of acute cholecystitis in four cases, biliary pain in two cases and acute pancreatitis in one case. Laparoscopic cholecystectomy was performed in four patients and open cholecystectomy in three patients. Post-operative morbidity occurred in two patients, with improvement after conservative management. Nine patients (6.2%) died as the result of unrelated biliary disease. Age, sex, presence of gallbladder stones, multiplicity of gallbladder stones and underlying disease did not correlate with subsequent cholecystectomy by Cox regression analysis. CONCLUSION: Elective cholecystectomy is not warranted in patients with bile duct stones when the common duct can be cleared of stones by endoscopic sphincterotomy. We could not find any clinical predictors of further symptoms or complications arising from the retained gallbladder.

Synthesis of 4-phenyltetralone derivatives and reaction mechanism.

4-(p-Chlorophenyl)tetralone (6) and 7-chloro-5-(p-chlorophenyl)tetralone (9) are key intermediates for the development of benzazepinone derivative haftens. These compounds could be synthesized from 4-phenyltetralone derivatives by triflic acid catalyzed Friedel-Crafts reaction. The reaction mechanism of Friedel-Crafts alkylation/acylation with lactones in triflic acid is presented. According to our tentative research, ring opening of protonated lactone (2) occurs in alkyl cleavage and the rate of the reaction is not dependent on concentration of triflic acid. So, alkylation of lactone in Friedel-Crafts reaction is presumed to be A(AL)1. In second step, intramolecular acylation of the intermediates 4 to 6, 4 can be transformed to a triflic acid-carboxylic anhydride and then the cyclization is undergone after leaving of the triflate anion.

Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine derivatives.

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.

Some new 1,2-benzothiazine derivatives with analgesic and anti-inflammatory activities.

Twenty-three new 7-halo-4-hydroxy-2H(or alkyl)-N-(3-aralkyl-2-thio- 1-hydantoinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide derivatives were synthesized through the condensation of 7-halo-4-hydroxy-2H(or alkyl)-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxides with 1-amino-2-thio-3-aralkyl-imidazolidine-4-one. The analgesic and anti-inflammatory activities of the synthesized compounds were investigated by acetic acid-induced writhing syndrome and carrageenan rat paw edema tests. In analgesic activities most compounds exhibited higher activities than acetylsalicylic acid, but in anti-inflammatory activities most compounds except compounds 24, 36, 39 showed lower activities than indometacin.