Endoscopic modified transseptal bi-nostril approach for pituitary tumors. Efficacy of complex preservation of every turbinate and olfaction: A STROBE analysis.

AIMS: Endoscopic modified transseptal bi-nostril approach minimizes turbinate and olfactory mucosal invasion and ensures preservation of the turbinates and bilateral olfaction. The main objective of this study was to investigate the pre- and postoperative variations in olfactory function in patients using this approach, and the secondary objective was to investigate the complications associated with the surgical procedure. MATERIAL AND METHODS: This study is a single-center prospective cohort study using STROBE analysis. To completely protect the bilateral turbinates and olfactory epithelium, this procedure provided access to the sphenoid sinus by a transseptal approach via the left nasal cavity and by the olfactory cleft approach via the right nasal cavity without any turbinate resection. A T&T olfactometer was used to assess the mean recognition threshold of the left, right, and bilateral nasal passages before and after surgery, and complications associated with the surgical approach were investigated. OBJECTIVES: We included 27 patients who underwent endoscopic modified transseptal pituitary surgery with an olfactory and turbinate preservation approach at our hospital between April 2018 and December 2019. RESULTS: The mean postoperative recognition threshold of the right, left, and bilateral nasal cavities did not worsen (P<0.001 for all) relative to the preoperative values, and there was no difference in values between the right and left nasal cavities (P=0.85). The nasal turbinates were preserved in all patients during the study period, and no recurrence was observed. CONCLUSION: Our modified EETSA could be implemented as an approach for turbinate and olfaction preservation.

Long-term survival of a patient with amyotrophic lateral sclerosis (ALS) who received autologous adipose-derived mesenchymal stem cells.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurodegenerative disease with a life expectancy of 3-5 years from initial symptoms. We report a case of ALS who received autologous adipose-derived mesenchymal stem cells (ADSC) and was followed up for 7 years. CASE REPORT: A 46-year-old man noticed weakness of his legs, difficulties on going down the stairs and coughing during eating in 2009. After complete workout, a diagnosis of ALS was confirmed. His ALS Functional Rating Scale-R (ALSFS-R) was 43. Symptoms rapidly progressed and he coughed and choked during eating. Starting in 2013, the patient received a total of six intravenous infusions of autologous ADSC. Changes in electromyogram, nerve conduction, and ALSFS-R were assessed. RESULTS: Soon after the administration, he noticed that he did not cough during conversation or eating food. Although he had difficulty in walking down the stairs, he remained well without coughing, dysarthria, or dysphagia. His ALSFS-R increased up to 45. Fascicular potentials were not detected in any muscles examined including trapezius muscle and rectus femoris muscles. The patient was well for 7 years after ADSC therapy by the time of this report and more than 10 years from the time of onset. CONCLUSIONS: The present case suggests that autologous ADSC can be administered safely and may be potentially useful in patients with ALS. Further investigations are warranted in order for the results to be generalized to other ALS patients.

Preemptive analgesia for endoscopic sinus surgery: a retrospective study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease, and endoscopic sinus surgery (ESS) is widely performed. However, there is no consensus regarding postoperative pain control after ESS, and postoperative opioid abuse is a problem in many countries. Acetaminophen is reportedly effective for postoperative pain control. Preemptive analgesia has received more attention lately, wherein pain is prevented before it occurs. In this study, we assessed the use of acetaminophen for preemptive analgesia during the perioperative period in ESS. METHODOLOGY: This is a retrospective study of 175 patients who underwent ESS, septoplasty, and bilateral inferior turbinate mucosal resection at our hospital from April 2016 to February 2018. In total, 82 patients received 1,000 mg of acetaminophen during surgery and 4 hours after the first dose, while 93 patients did not receive it routinely. We compared these two groups. The primary outcome was the need to use additional analgesics prescribed by the ward physician and the secondary outcomes included postoperative pain, postoperative bleeding, reoperation, blood pressure, and body temperature. RESULTS: The use of additional oral and intravenous analgesics was significantly reduced in the patients who received acetaminophen perioperatively. CONCLUSION: Preemptive analgesia during the perioperative period of ESS could lead to satisfactory postoperative pain control.

CD49d and CD49e induce cell adhesion-mediated drug resistance through the nuclear factor-κB pathway in Burkitt lymphoma.

Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin's B-cell lymphoma. Currently, multi-agent chemotherapy regimens are being used to significantly improve cure rates and achieve complete remissions in BL patients. However, drug resistance can often occur within 6 months in BL patients, contributing to poor prognosis. Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy. However, the molecular mechanism underlying CAM-DR in BL has not been identified yet. In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells. We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved. However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells. Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation. In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients.

Synchrotron-based XRD from rat bone of different age groups.

Synchrotron-based XRD spectra from rat bone of different age groups (w, 56 w and 78w), lumber vertebra at early stages of bone formation, Calcium hydroxyapatite (HAp) [Ca10(PO4)6(OH)2] bone fill with varying composition (60% and 70%) and bone cream (35-48%), has been acquired with 15keV synchrotron X-rays. Experiments were performed at Desy, Hamburg, Germany, utilizing the Resonant and Diffraction beamline (P9), with 15keV X-rays (λ=0.82666 A0). Diffraction data were quantitatively analyzed using the Rietveld refinement approach, which allowed us to characterize the structure of these samples in their early stages. Hydroxyapatite, received considerable attention in medical and materials sciences, since these materials are the hard tissues, such as bone and teeth. Higher bioactivity of these samples gained reasonable interest for biological application and for bone tissue repair in oral surgery and orthopedics. The results obtained from these samples, such as phase data, crystalline size of the phases, as well as the degree of crystallinity, confirm the apatite family crystallizing in a hexagonal system, space group P63/m with the lattice parameters of a=9.4328Å and c=6.8842Å (JCPDS card #09-0432). Synchrotron-based XRD patterns are relatively sharp and well resolved and can be attributed to the hexagonal crystal form of hydroxyapatite. All the samples were examined with scanning electron microscope at an accelerating voltage of 15kV. The presence of large globules of different sizes is observed, in small age groups of the rat bone (8w) and lumber vertebra (LV), as distinguished from, large age groups (56 and 78w) in all samples with different magnification, reflects an amorphous phase without significant traces of crystalline phases. Scanning electron microscopy (SEM) was used to characterize the morphology and crystalline properties of Hap, for all the samples, from 2 to 100µm resolution.

Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma.

Glaucoma is the second leading cause of blindness worldwide and is characterized by gradual visual impairment owing to progressive loss of retinal ganglion cells (RGCs) and their axons. Glutamate excitotoxicity has been implicated as a mechanism of RGC death in glaucoma. Consistent with this claim, we previously reported that glutamate/aspartate transporter (GLAST)-deficient mice show optic nerve degeneration that is similar to that observed in glaucoma. Therefore, drugs that upregulate GLAST may be useful for neuroprotection in glaucoma. Although many compounds are known to increase the expression of another glial glutamate transporter, EAAT2/GLT1, few compounds are shown to increase GLAST expression. Arundic acid is a glial modulating agent that ameliorates delayed ischemic brain damage by attenuating increases in extracellular glutamate. We hypothesized that arundic acid neuroprotection involves upregulation of GLAST. To test this hypothesis, we examined the effect of arundic acid on GLAST expression and glutamate uptake. We found that arundic acid induces GLAST expression in vitro and in vivo. In addition, arundic acid treatment prevented RGC death by upregulating GLAST in heterozygous (GLAST(+/-)) mice. Furthermore, arundic acid stimulates the human GLAST ortholog, EAAT1, expression in human neuroglioblastoma cells. Thus, discovering compounds that can enhance EAAT1 expression and activity may be a novel strategy for therapeutic treatment of glaucoma.

The combination of strong expression of ZNF143 and high MIB-1 labelling index independently predicts shorter disease-specific survival in lung adenocarcinoma.

BACKGROUND: The transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-related genes. The ZNF143 would show high expression of multiple solid tumours related closely to cancer cell growth, similar to the widely accepted Ki67 (MIB-1) protein, but the underlying mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143 expression with clinicopathological features and prognoses of patients with lung adenocarcinoma. METHODS: Expressions of ZNF143 and MIB-1 were immunohistochemically analysed in 183 paraffin-embedded tumour samples of patients with lung adenocarcinoma. The ZNF143 expression was considered to be strong when >30% of the cancer cells demonstrated positive staining. RESULTS: Strong ZNF143+ expression showed a significantly close relationship to pathologically moderate to poor differentiation and highly invasive characteristics. The ZNF143 positivity potentially induced cell growth of lung adenocarcinoma, correlated significantly with high MIB-1 labelling index (⩾10%). Univariate and multivariate analyses demonstrated that both strong ZNF143+ and the high MIB-1 index group have only and significantly worse survival rates. CONCLUSIONS: The combination of strong ZNF143 expression and high MIB-1 index potentially predicts high proliferating activity and poor prognosis in patients with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.

Acute hypoxia induces apoptosis of pancreatic ß-cell by activation of the unfolded protein response and upregulation of CHOP.

The success of pancreatic ß-cells transplantation to treat type 1 diabetes has been hindered by massive ß-cell dysfunction and loss of ß-cells that follows the procedure. Hypoxia-mediated cell death has been considered one of the main difficulties that must be overcome for transplantation to be regarded as a reliable therapy. Here we have investigated the mechanisms underlying ß-cell death in response to hypoxia (1% O(2)). Our studies show that mouse insulinoma cell line 6 (Min6) cells undergo apoptosis with caspase-3 activation occurring as early as 2 h following exposure to hypoxia. Hypoxia induces endoplasmic reticulum stress in Min6 cells leading to activation of the three branches of the unfolded protein response pathway. In response to hypoxia the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) is upregulated. The important role of CHOP in the apoptotic process was highlighted by the rescue of Min6 cells from hypoxia-mediated apoptosis observed in CHOP-knockdown cells. Culturing isolated pancreatic mouse islets at normoxia showed intracellular hypoxia with accumulation of hypoxia-inducible factor-1α and upregulation of CHOP, the latter one occurring as early as 4 h after isolation. Finally, we observed that pancreatic islets of type 2 db/db diabetic mice were more hypoxic than their counterpart in normoglycemic animals. This finding indicates that hypoxia-mediated apoptosis may occur in type 2 diabetes.

Comparison between chest digital tomosynthesis and CT as a screening method to detect artificial pulmonary nodules: a phantom study.

OBJECTIVES: The objective of this study was to evaluate the imaging capabilities of chest digital tomosynthesis (DT) as a screening method for the detection of artificial pulmonary nodules, and to compare its efficiency with that of CT. METHODS: DT and CT were used to detect artificial pulmonary nodules (5 mm and 8 mm in diameter, ground-glass opacities) placed in a chest phantom. Using a three-dimensional filtered back-projection algorithm at acquisition angles of 8°, 20°, 30° and 40°, DT images of the desired layer thicknesses were reconstructed from the image data acquired during a single tomographic scan. Both standard and sharp CT reconstruction kernels were used, and the detectability index (DI) valves computed for both the DT scan acquisition angles and CT reconstruction kernel types were considered. For the observer study, we examined 50 samples of artificial pulmonary nodules using both DT and CT imaging. On the basis of evaluations made by five thoracic radiologists, a jackknife free-response receiver operating characteristic (JAFROC) study was performed to compare and assess the differences in detection accuracy between CT and DT imaging. RESULTS: For each increased acquisition angle, DI obtained by DT imaging was similar to that obtained by CT imaging. The difference in the observer-averaged JAFROC figure of merit for the five readings was 0.0363 (95% confidence interval: -0.18, 0.26; F=0.101; p=0.75). CONCLUSION: With the advantages of a decreased radiation dose and the practical accessibility of examination, DT may be a useful alternative to CT for the detection of artificial pulmonary nodules.

Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours.

OBJECTIVE: The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0-1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours. METHODS: Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose-volume histograms (DVHs) were constructed to identify the incidence of RP. RESULTS: The median follow-up period was 12 months (range, 6-45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5-30 Gy (V5-30) and mean lung dose were significant factors differentiating between grade 0-1 and grade 2 RP, and V15-30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0-1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0-1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0-2 RP. CONCLUSIONS: Grade 0-2 RP was dose-volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0-2 RP. However, incidences of V15-30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.

Alendronate is more effective than elcatonin in improving pain and quality of life in postmenopausal women with osteoporosis.

UNLABELLED: A randomized controlled trial was performed to compare the short-term effects of alendronate (ALN) and ECT on pain and quality of life (QOL) in postmenopausal women with osteoporosis. Back pain and QOL [Short-Form Health Survey (SF-8)] significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group. These results suggested that ALN reduced back pain and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain. INTRODUCTION: Intramuscular ECT is known to reduce pain via the central nervous system. A multicenter randomized controlled trial was performed to compare the short-term effects of ALN and ECT on pain and QOL in postmenopausal women with osteoporosis. METHODS: One hundred and 94 postmenopausal osteoporotic women with back pain (mean age 79.8 years, range 60-96 years) were randomly divided into two groups: the ALN group (35 mg weekly) and the ECT group (intramuscular 20 units a week). The duration of the study was 6 months. The trial was completed in 97 (100%) women of the ALN group and 96 (99.0%) women of the ECT group. Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX), serum alkaline phosphatase (ALP), face scale score (FSS, back pain), and SF-8 (QOL) were monitored. RESULTS: Urinary NTX levels significantly decreased at 3 months in the ALN group, but not in the ECT group. Serum ALP levels significantly decreased at 6 months in the both groups, with a greater reduction in the ALN group. The FSS and SF-8 significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group. CONCLUSIONS: ALN suppressed bone turnover, reduced back pain, and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain.

Phase-contrast X-ray imaging of the gas diffusion layer of fuel cells.

The understanding of and in situ observation of the transport and distribution of water in carbon-paper gas diffusion layers (GDLs) using non-destructive imaging techniques is critical for achieving high performance in polymer electrolyte fuel cells (PEFCs). To investigate the behavior of water in GDLs of PEFCs, phase-contrast X-ray imaging via X-ray interferometric imaging (XII) and diffraction-enhanced imaging (DEI) were performed using 35 keV X-rays. The XII technique is useful for the radiographic imaging of GDLs and in situ observations of water evolution processes in operating PEFCs. DEI provides a way for tomographic imaging of GDLs in PEFCs. Because high-energy X-rays are applicable to the imaging of both carbon papers and heavy materials, which make up PEFCs, phase-contrast X-ray imaging techniques have proven to be valuable for investigation of GDLs.

Altered immunoglobulin A and M levels associated with changes in BAFF and APRIL after administration of intravenous immunoglobulin to treat Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of unknown etiology. Immunoregulatory abnormalities have been thought to contribute to its pathogenesis. Although treatment with intravenous immunoglobulin (IVIG) effectively prevents significant cardiac morbidity, the mechanism by which IVIG produces an effect in KD has yet to be fully elucidated. OBJECTIVE: To investigate the effects of IVIG on the immune system of patients with KD. PATIENTS AND METHODS: Eleven patients with KD (mean [SD] age, 2.2 [1.5] years) were enrolled in this prospective study and treated with high-dose IVIG therapy (2 g/kg in 1 or 2 infusions) during the acute phase of the disease. We examined immunological changes, with special reference to Ig levels and 2 previously unassessed cytokines: B cell-activating factor belonging to the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL). RESULTS: Clinical symptoms disappeared quickly in all cases, with no coronary artery abnormalities. IgA and IgM levels responded more rapidly than previously reported and reached a peak between the 3rd and 10th day after the start of IVIG treatment. The mean (SD) BAFF level was high before IVIG treatment (3234 [1904] pg/mL) and decreased significantly (1085 [257] pg/mL) after IVIG treatment, whereas the mean (SD) APRIL level before IVIG treatment (18.0 [10.0] ng/mL) rose significantly (120.6 [41.2] ng/mL). A significant inverse correlation between BAFF and APRIL was observed in patients with KD. CONCLUSIONS: These results suggest that IVIG may affect the pathogenesis of KD through alteration of BAFF/APRIL.

Preparation of gallium oxynitride powder and its nanofibers by the nitridation of a gallium oxide precursor doped with nickel or cobalt obtained via the citrate route.

Acicular crystals were grown in gallium oxynitride powder prepared by ammonia nitridation of amorphous gallium oxide precursors containing less than 5 at% of either Ni or Co, via the citrate route. The crystals were several tens of nanometres wide, several micrometres long, and grown in the temperature range 750 to 850 degrees C in a flow of ammonia of less than 200 mL min(-1). The crystal structure of the gallium oxynitride was a highly disordered 2H wurtzite-type with some 3C zinc blende-type stacking faults. The crystals grew in their basal plane changing their aspect ratio with the supplying method of small amounts of Ni or Co and an amount of residual carbon. The acicular crystals were grown by the catalytic behavior of Ni or Co to enhance one-dimensional growth in the hexagonal c-plane.

Galbeta1-6Gal, antigenic epitope which accounts for serological cross-reaction in diagnosis of Echinococcus multilocularis infection.

Parasitic helminths express various antigenic carbohydrates, which often account for serological cross-reactions. In serodiagnosis, it is essential to inspect cross-reactivity between the target parasite and other parasites in order to assess diagnostic performance. Our previous study showed that the Galbeta1-6Gal sequence was a common epitope between Echinococcus multilocularis (Em) and E. granulosus (Eg). Furthermore, compounds with this sequence from Fasciola hepatica (Fh) reportedly were recognized by sera with Eg infection. Our aim is to investigate whether this sequence is one of the widely common epitopes in many kinds of parasites. For various parasites, sera with Fh infection cross-reacted at the highest frequency (71.4%) against Em antigen. In patients with other parasitic infections, sera showed cross-reactions against Fh antigen bound to Em antigen with a high frequency (23.7%). Binding inhibition tests with commercial Galbeta1-6Gal disaccharide showed that Galbeta1-6Gal was the common epitope between not only Em, Eg and Fh, but also between various other parasites. Furthermore, the presence of the Galbeta1-6Gal epitope in Em antigen was confirmed by immunoblot testing with the specific antibody for this sequence. This study showed that the Galbeta1-6Gal sequence is one of the antigenic epitopes that accounts for serological cross-reactivity between Em and various other parasites.

Palliative effect of lafutidine on oral burning sensation.

UNLABELLED: Lafutidine is a unique histamine H(2)-receptor antagonist (H2RA) that has a sensitizing effect on capsaicin-sensitive afferent neurons (CSAN). This effect may make lafutidine useful for the treatment of burning mouth syndrome (BMS). METHODS: To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation, a randomized controlled trial was performed. Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were randomly assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine group, n = 36) or to continue to receive the previous H2RAs plus ASS gargling (control group, n = 35). The intensity of burning sensation was scored by means of a visual analog scale (VAS). RESULTS: Thirty-four patients in the lafutidine group and 30 in the control group completed the study. In the lafutidine group, the rate of improvement in the VAS score as compared with the baseline value was significant after 4, 8, and 12 weeks of treatment (P < 0.05). The improvement rate was consistently higher in the lafutidine group than in the control group; the differences between the groups were significant (P < 0.05) after 4, 8, and 12 weeks of treatment. Only two mild abdominal adverse events occurred in the lafutidine group, but neither required the termination of treatment. CONCLUSION: Oral lafutidine is very safe and effective for reducing the intensity of oral burning sensation and may therefore be a viable option for the treatment of BMS.

Direct comparison of thallium-201 and technetium-99m MIBI SPECT of a glioma by receiver operating characteristic analysis.

The diagnostic value of single photon-emission computed tomography (SPECT) has been assessed using arbitrarily determined sensitivity and specificity cut-off values. The diagnostic accuracy of thallium-201 (Tl-201) SPECT and technetium-99m methoxyisobutylisonitrile (Tc-MIBI) SPECT were compared for patients with primary glioma using receiver operating characteristic (ROC) analysis. The study population included 59 patients with gliomas. Tl and Tc-MIBI SPECT images were obtained using a multi-detector SPECT machine 15 min (early) and 3 hours (delayed) after intravenous injection of 74 MBq of Tl-chloride or 740 MBq of Tc-MIBI. The regions of interest were set on the tumor and contralateral normal white matter and tumor : normal ratios were calculated. The area z-score (A(z)) values were calculated from the areas under the ROC curves. All A(z) values were high and no statistical difference was observed between the two modalities. Both Tl and Tc-MIBI SPECT are useful imaging modalities for the evaluation of glioma malignancy.