Internal limiting membrane handling in macular hole surgery: the infusion direction manipulation and infusion off techniques.

OBJECTIVE: Herein, we introduce the infusion direction manipulation technique and the infusion off technique. These relatively simple methods control intra-vitreal fluid flow direction and turbulence and release negative pressure in the microforceps to facilitate handling of the internal limiting membrane. The aim of this study is to introduce an effective and uncomplicated method to handle the internal limiting membrane (ILM) during the temporal inverted ILM flap and free ILM flap techniques in macular hole surgery by controlling the direction and status of the infusion. MATERIALS AND METHODS: The direction of the infusion flow was controlled with a free finger (usually the 4th finger) during the inverted ILM flap surgery to stabilize the flap location during the fluid-air exchange. A valved trocar was used, and the infusion was discontinued during the free ILM flap surgery. Turbulence was minimized, and negative pressure around the head-shaft junction of the microforceps was released. RESULTS: The ILM flap remained stable in all patients who underwent macular hole surgery with our technique. CONCLUSIONS: Infusion direction manipulation technique and infusion off technique are efficient and simple methods to handle the ILM during ILM surgery.

Questionable correlation of the apparent diffusion coefficient with the histological grade and microvascular invasion in small hepatocellular carcinoma.

AIM: To evaluate the correlation between the apparent diffusion coefficient (ADC) and various histopathological parameters in small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In 143 surgically resected small HCCs, the mean and minimum ADC values, tumour-to-liver ADC ratio, and normalised ADC (ADC of the HCC/ADC of the spleen) were correlated to the tumour grade, microvascular invasion (MVI), cellularity, fatty change, degree of fibrosis, and lymphocytic infiltration using linear regression analysis, the Wilcoxon rank sum test, or Spearman's rank correlation. RESULTS: No significant correlation was found between the ADC parameters and tumour grade. In the univariate analysis, the ADC ratio of the tumour was significantly correlated with MVI as well as the degree of fibrosis and lymphocyte infiltration of the HCC (p=0.017, 0.042, and 0.002, respectively). The ADC of the tumour was significantly correlated with the degree of lymphocyte infiltration of the HCC (p=0.049). In the multivariate analysis, the ADC ratio of the tumour was an independent parameter for MVI and the degree of lymphocyte infiltration of the HCC (p=0.034 and <0.001, respectively), and the ADC of the tumour was an independent parameter for the degree of lymphocyte infiltration of the HCC (p=0.009). There was no significant correlation between the other ADCs and pathological tumour parameters. CONCLUSION: The tumour grade of small HCCs was not correlated with ADC parameters. The tumour-to-liver ADC ratio was a significant independent parameter for the degree of lymphocyte infiltration and MVI of small HCCs.

Clonorchis sinensis omega-class glutathione transferases are reliable biomarkers for serodiagnosis of clonorchiasis and opisthorchiasis.

OBJECTIVES: To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. METHODS: Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87) and clonorchiasis (n = 120), as well as those in sera from patients with other helminthic infections (n = 252) and healthy controls (n = 40) were retrospectively analysed by ELISA. RESULTS: We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts (<100, n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). CONCLUSIONS: Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Clinical impact of tumor volume reduction in rectal cancer following preoperative chemoradiation.

PURPOSE: The purpose of this study was to correlate tumor volumetric analysis obtained using magnetic resonance (MR) imaging with disease-free survival in patients with advanced rectal cancer who underwent preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Institutional review board approval was obtained and patient informed consent was waived. This study included 74 patients (47 men, 27 women; mean age, 64 years±10 [SD] years) who underwent preoperative CRT and subsequent rectal surgery between January 2007 and December 2010. Two radiologists who were blinded to the clinical outcome measured tumor volume separately on two sets of MR images obtained before and after CRT. Patients were classified into two groups according to the episode of recurrence and recorded disease-free survival. To assess factors relevant to disease-free survival, univariate and multivariate Cox regression analysis were performed for tumor volume reduction ratio, circumferential resection margin, tumor regression grade, and pathologic staging. RESULTS: Tumor volume reduction ratio (P=0.009), circumferential resection margin (P=0.008) and tumor regression grade (P=0.002) were significantly associated with disease-free survival. At multivariate analysis, tumor volume reduction ratio was the single variable that was associated with disease-free survival (P=0.003). Tumor volume reduction ratio was also a reliable parameter with an excellent interobserver correlation between two readers for pre-CRT volume (ICC=0.939; 95%CI: 0.885-0.979; P<0.001) and post-CRT volume (ICC=0.889; 95%CI: 0.845-0.934; P<0.001). CONCLUSIONS: MR volumetric measurement of rectal cancer helps predict disease-free survival in patients with rectal cancer who underwent preoperative CRT.

Polymorphisms in period genes and bone response to hormone therapy in postmenopausal Korean women.

OBJECTIVE: In this study, we aimed to explore the association between polymorphisms in the period (PER) gene and bone response to hormone therapy (HT) in postmenopausal Korean women. METHODS: The PER1 c.2284C > G, c.2247C > T, PER2 c.3731G > A, PER3 c.2592G > A, c.3083T > C polymorphisms, and PER3 54bp variable number of tandem repeats (VNTR) were analyzed in 509 postmenopausal Korean women who received HT. Bone mineral density (BMD) at the lumbar spine and femoral neck before and after 1 year of HT and serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-κB ligand (sRANKL) and bone turnover markers were measured after 6 months of HT. RESULTS: The PER1 c.2884 C > G polymorphism and PER3 54bp VNTR were associated with annual percent changes in BMD of the femoral neck after 1 year of HT (p < 0.05). Changes in BMD at the femoral neck in the non-CC genotype of the PER1 c.2884C > G polymorphism and in the 4-repeat homozygote of PER3 54bp VNTR were significantly lower than those in CC genotype and non-4-repeat homozygote, respectively. The PER1 c.2884C > G polymorphism was associated with the non-response (>3% BMD loss/year after HT) of HT. The non-CC genotype of the PER1 c.2884C > G polymorphism showed a 1.92-times higher risk of non-response at the lumbar spine and/or femoral neck (p = 0.01) compared with the CC genotype. No significant changes in bone markers after 6 months of HT were noted according to the PER1 c.2884C > G polymorphism. CONCLUSIONS: The PER1 c.2884C > G polymorphism may be associated with risk of non-response to HT in postmenopausal Korean women.

Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS: Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063). CONCLUSION: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

Molecular and biochemical characterization of Paragonimus westermani tyrosinase.

Trematode tyrosinases (TYRs) play a major role in the tanning process during eggshell formation. We investigated the molecular and biochemical features of Paragonimus westermani TYR (PwTYR). The PwTYR cDNA was composed of 1568-bp encompassing a 1422-bp-long open reading frame (474-amino acid polypeptide). A strong phylogenetic relationship with Platyhelminthes and Deuterostomian orthologues was evident. The recombinant PwTYR expressed in prokaryotic cells promptly oxidized diphenol substrates, with a preferential affinity toward ortho-positioned hydroxyl groups. It demonstrated fairly weak activity for monophenol compounds. Diphenol oxidase activity was augmented with an increase of pH from 5.0 to 8.0, while monophenol oxidase activity was highest at an acidic pH and gradually decreased as pH increased. Transcription profile of PwTYR was temporally upregulated along with worm development. PwTYR was specifically localized in vitellocytes and eggs. The results suggested that conversion of tyrosine to L-dihydroxyphenylalanine by PwTYR monophenol oxidase activity might be rate-limiting step during the sclerotization process of P. westermani eggs. The pH-dependent pattern of monophenol and diphenol oxidase activity further proposes that the initial hydroxylation might slowly but steadily progress in acidic secreted vesicles of vitellocytes and the second oxidation process might be rapidly accelerated by neural or weak alkaline pH environments within the ootype.

Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.

Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-ß/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.

Three-dimensional architectural and structural analysis--a transition in concept and design from Delaire's cephalometric analysis.

The aim of this study was to present a systematic sequence for three-dimensional (3D) measurement and cephalometry, provide the norm data for computed tomography-based 3D architectural and structural cephalometric analysis, and validate the 3D data through comparison with Delaire's two-dimensional (2D) lateral cephalometric data for the same Korean adults. 2D and 3D cephalometric analyses were performed for 27 healthy subjects and the measurements of both analyses were then individually and comparatively analyzed. Essential diagnostic tools for 3D cephalometry with modified definitions of the points, planes, and measurements were set up based on a review of the conceptual differences between two and three dimensions. Some 2D and 3D analysis results were similar, though significant differences were found with regard to craniofacial angle (C1-F1), incisal axis angles, cranial base length (C2), and cranial height (C3). The discrepancy in C2 and C3 appeared to be directly related to the magnification of 2D cephalometric images. Considering measurement discrepancies between 2D and 3D Delaire's analyses due to differences in concept and design, 3D architectural and structural analysis needs to be conducted based on norms and a sound 3D basis for the sake of its accurate application and widespread adoption.

Association between polymorphisms in period genes and bone density in postmenopausal Korean women.

OBJECTIVE: In the present study, we aimed to investigate the association between genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in postmenopausal Korean women. METHODS: The PER1 c.2247C> T and c.2884C> G polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G> A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone markers including bone alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were measured, and the lumbar spine and femoral neck BMDs were also determined. RESULTS: The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD, whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with the lumbar spine BMD were observed both singly and in combination. The CC haplotype homozygotes showed significantly lower lumbar spine BMD than participants with other genotypes. Additionally, 2.01-fold higher odds for osteoporosis of the lumbar spine were found in the CC haplotype homozygotes compared to women not carrying the haplotype CC allele. No significant differences in bone markers were detected according to the PER1 haplotype genotype. CONCLUSIONS: Our results suggest that both the PER1 c.2247C> T and c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in postmenopausal Korean women.

Spin-induced band modifications of graphene through intercalation of magnetic iron atoms.

Intercalation of magnetic iron atoms through graphene formed on the SiC(0001) surface is found to induce significant changes in the electronic properties of graphene due mainly to the Fe-induced asymmetries in charge as well as spin distribution. From our synchrotron-based photoelectron spectroscopy data together with ab initio calculations, we observe that the Fe-induced charge asymmetry results in the formation of a quasi-free-standing bilayer graphene while the spin asymmetry drives multiple spin-split bands. We find that Fe adatoms are best intercalated upon annealing at 600 °C, exhibiting split linear π-bands, characteristic of a bilayer graphene, but much diffused. Subsequent changes in the C 1s, Si 2p, and Fe 3p core levels are consistently described in terms of Fe-intercalation. Our calculations together with a spin-dependent tight binding model ascribe the diffuse nature of the π-bands to the multiple spin-split bands originated from the spin-injected carbon atoms residing only in the lower graphene layer.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.

BACKGROUND: This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS: Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS: Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER: NCT01164176.

Atherogenic changes in low-density lipoprotein particle profiles were not observed in non-obese women with polycystic ovary syndrome.

STUDY QUESTION: Is a preponderance of small dense low-density lipoprotein-cholesterol (LDL-C) observed in non-obese women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Non-obese Korean women with PCOS have no quantitative or qualitative changes in LDL-C profiles. WHAT IS KNOWN ALREADY: Small dense LDL particles (sd-LDL) are more atherogenic than large buoyant ones and are strongly associated with coronary artery disease independent of other risk factors. Many investigators have found an increased proportion of atherogenic sd-LDL or a decreased mean LDL particle size in women with PCOS, but all of these studies have been based primarily on obese or overweight women with PCOS. STUDY DESIGN, SIZE, DURATION: This was a case-control study evaluating complete lipid and lipoprotein profiles in 64 PCOS patients and 64 age- and BMI-matched controls. All women with PCOS in our study population were not obese. To determine the differences in the LDL particle profiles between PCOS phenotypes, the patients with PCOS were divided into two subgroups according to the presence of clinical or biochemical hyperandrogenism. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Rotterdam criteria, we recruited 64 women (18-40 years) with PCOS who were attending a tertiary university hospital. A total of 64 premenopausal control women were matched with patients based on exact age and BMI (± 1.0 kg/m(2)). All the participants fell within the non-obese range of the BMI (<25 kg/m(2)) according to the definition of obesity for Asians. The LDL subfraction was analyzed by 3% polyacrylamide gel tube electrophoresis. Seven LDL subclasses were quantified and LDL subclasses 3-7 were small LDL subfractions. LDL subfraction scores were calculated based on the following weighted scoring system developed by the manufacturer: scores of <5.5 were categorized as phenotype A (large, buoyant LDLs), and those >5.5 were categorized as non-A phenotype (sd-LDLs). The system also determined the mean LDL particle size diameter. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the absolute level of LDL-C, mean LDL diameter or percentage of atherogenic sd-LDLs between PCOS patients and controls or between hyperandrogenic and non-hyperandrogenic PCOS subgroups. Also, none of the subjects showed a non-A LDL phenotype. The most notable finding of our study was the difference in the lipoprotein (a) levels and prevalence of its elevation in PCOS patients versus controls (P = 0.002 and P = 0.004, respectively), and between PCOS subgroups (P = 0.030 and P = 0.047, respectively). LIMITATIONS, REASONS FOR CAUTION: Inclusion of only non-obese subjects, small sample size and lack of information on other potential confounding factors, such as differences in diet and/or exercise patterns. WIDER IMPLICATIONS OF THE FINDINGS: Although our findings suggest that non-obese women with PCOS have no significant quantitative or qualitative changes in LDL-C profile, data on obese Korean women with PCOS could offer complementary findings about the possible relationship between the magnitude of obesity and LDL phenotype. Further investigations are needed to determine whether a change in lipoprotein (a) in non-obese women with PCOS is also found in other ethnic groups. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A100624). TRIAL REGISTRATION NUMBER: N/A.

The radiological parameters correlated with the alignment of the femoral component after Oxford phase 3 unicompartmental knee replacement.

The purpose of this study was to measure the radiological parameters of femoral component alignment of the Oxford Phase 3 unicompartmental knee replacement (UKR), and evaluate their effect on clinical outcome. Multiple regression analysis was used to examine the relative contributions of the radiological assessment of femoral component alignment in 189 consecutive UKRs performed by a single surgeon. The American Knee Society scores were compared between groups, defined as being within or outside recommended tolerances of the position of the femoral component. For the flexion/extension position 21 UKRs (11.1%) lay outside the recommended limits, and for posterior overhang of the femoral component nine (4.8%) lay outside the range. The pre-operative hip/knee/ankle (HKA) angle, narrowest canal distance from the distal femoral entry point of the alignment jig and coronal entry-point position had significant effects on the flexion/extension position. Pre-operative HKA angle had a significant influence on posterior overhang of the femoral component. However, there was no significant difference in American Knee Society scores relative to the position of the femoral component.

Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression.

Thyroid transcription factor 1 (TTF1), a member of the Nkx family of transcription factors required for basal forebrain morphogenesis, functions in the postnatal hypothalamus as a transcriptional regulator of genes encoding neuromodulators and hypophysiotrophic peptides. One of these peptides is gonadotrophin-releasing hormone (GnRH). In the present study, we show that Ttf1 mRNA abundance varies in a diurnal and melatonin-dependent fashion in the preoptic area of the rat, with maximal Ttf1 expression attained during the dark phase of the light/dark cycle, preceding the nocturnal peak in GnRH mRNA content. GnRH promoter activity oscillates in a circadian manner in GT1-7 cells, and this pattern is enhanced by TTF1 and blunted by small interfering RNA-mediated Ttf1 gene silencing. TTF1 transactivates GnRH transcription by binding to two sites in the GnRH promoter. Rat GnRH neurones in situ contain key proteins components of the positive (BMAL1, CLOCK) and negative (PER1) limbs of the circadian oscillator, and these proteins repress Ttf1 promoter activity in vitro. By contrast, Ttf1 transcription is activated by CRY1, a clock component required for circadian rhythmicity. In turn, TTF1 represses transcription of Rev-erbα, a heme receptor that controls circadian transcription within the positive limb of the circadian oscillator. These findings suggest that TTF1 is a component of the molecular machinery controlling circadian oscillations in GnRH gene transcription.

Association between hormone therapy and nerve conduction study parameters in postmenopausal women.

OBJECTIVE: We aimed to analyze the association between hormone therapy (HT) and nerve conduction parameters. METHODS: This retrospective study consisted of 46 postmenopausal women not receiving HT, and 18 postmenopausal women who received HT. Eligible patients were identified from the hospital's database and the nerve conduction study was performed on the upper or lower limb without pain or other symptoms. RESULTS: No significant difference was demonstrated in the unadjusted nerve conduction parameters according to HT. After adjusting for age and body mass index, the latency of the posterior tibial motor nerve in postmenopausal women receiving HT was significantly shorter than that in women not receiving HT. Moreover, the velocity of the median motor nerve tended to be faster in postmenopausal women receiving HT than those not receiving HT, although the difference was not statistically significant. CONCLUSION: These findings imply that HT may affect the nerve conduction parameters in postmenopausal women.