The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor-naïve patients with chronic HCV genotype 1b infection in a real-world cohort.

It is unclear whether multiple nonstructural (NS) 5A resistance-associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor-naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor-naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Reduced marine phytoplankton sulphur emissions in the Southern Ocean during the past seven glacials.

Marine biogenic sulphur affects Earth's radiation budget and may be an indicator of primary productivity in the Southern Ocean, which is closely related to atmospheric CO2 variability through the biological pump. Previous ice-core studies in Antarctica show little climate dependence of marine biogenic sulphur emissions and hence primary productivity, contradictory to marine sediment records. Here we present new 720,000-year ice core records from Dome Fuji in East Antarctica and show that a large portion of non-sea-salt sulphate, which was traditionally used as a proxy for marine biogenic sulphate, likely originates from terrestrial dust during glacials. By correcting for this, we make a revised calculation of biogenic sulphate and find that its flux is reduced in glacial periods. Our results suggest reduced dimethylsulphide emissions in the Antarctic Zone of the Southern Ocean during glacials and provide new evidence for the coupling between climate and the Southern Ocean sulphur cycle.

Fish intake and serum levels of organochlorines among Japanese women.

This study evaluates background serum levels of selected organochlorine compounds among Japanese women of reproductive age and investigates whether lifestyle factors, especially dietary factors, may be associated with these levels. A cross-sectional study was performed on 80 Japanese women, aged 26-43 years, who complained of infertility and were confirmed not to have endometriosis. The serum levels of total toxic equivalency (TEQ), 18 polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), 4 coplanar polychlorinated biphenyls (cPCBs), 36 ortho-substituted polychlorinated biphenyls (PCBs), and 13 chlorinated pesticides or their metabolites were measured and data were collected on the women's age, residence, occupation, body mass index (BMI), smoking and alcohol habit and 6 dietary intakes (fish, meats, rice, vegetables, fruits and dairy products). The serum median level of total TEQ was 25.1 pg TEQ/g lipid, that of PCDDs/PCDFs/cPCBs was 11.5 pmol/g lipid, that of PCBs was 0.46 nmol/g lipid, and that of total pesticides was 1.32 nmol/g lipid. The serum levels of total TEQ, PCDDs/PCDFs/cPCBs, PCBs and pesticides were positively associated with age (P for trend=0.003, 0.01, 0.005 and 0.01, respectively) and frequent fish consumption (P for trend=0.002, 0.003, 0.0003 and 0.006, respectively). Other lifestyle factors were not associated with serum organochlorine levels. The present study suggests that Japanese women who consume fish frequently in their reproductive period tend to accumulate organochlorines in their bodies.

[Clinical outcome of aortic valve replacement with 19-mm prosthetic valve in elderly patients].

From 1979 to June 2005, 90 patients aged 65 or older underwent aortic valve replacement with 19-mm prosthetic valve. They were 84 women and 6 men, with a mean age of 74. The mean body surface area was 1.35 m2. Bioprosthetic valves were implanted in 77 patients (85.6%). In-hospital mortality was 2.2% (2 of 90). There were 13 late deaths. New York Heart Association (NYHA) functional class improved to class I in most of survivors. Survival rates for 5 and 10 years were 84.9 and 71.2%, respectively. The outcome of aortic valve replacement with 19-mm prosthetic valve in elderly patients was excellent.

Development of high-order harmonic focusing system based on ellipsoidal mirror.

We have developed a focusing system for extreme ultraviolet light produced by high-order harmonic generation. An ellipsoidal mirror with a precise surface shape was fabricated and installed into the focusing system. A rigid mirror manipulator and a beam profiler were employed to perform precise and stable mirror alignment. As a demonstration of the focusing performance, high-order harmonics in the wavelength range of 13.5-19.5 nm were successfully focused into a 2.4 × 2.3 µm(2) spot.

Wavelength modulation by molecular environment in visual pigments.

The absorption and regenerability characteristics are compared for rhodopsin contained in rod outer segment membranes and purified in a series of alkyl sucrose esters. It is found that membrane-bound rhodopsin has maximum absorbance from 504 to 500 nm between 1.5 and 40 degrees C. After purification, rhodopsin absorbance can be blue-shifted by up to 6 nm, depending on the detergent species used. Only the longest chain sucrose esters give purified rhodopsin with maximum absorbance comparable to that of the native pigment. In the same manner, detergent-purified rhodopsin will be easily regenerated as long as its native spectral characteristics are maintained. Sucrose esters thus prove to be mild enough to maintain rhodopsin functionality with respect to these two properties and could probably be used successfully to maintain other membrane proteins' integrity.

Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse transcriptase messenger RNA in pancreatic juice with sample qualification.

PURPOSE: We evaluated the diagnostic efficacy of detection of human telomerase reverse transcriptase (hTERT) message, a catalytic domain of human telomerase, in endoscopic retrograde pancreatography (ERP)-derived pancreatic juice. EXPERIMENTAL DESIGN: Both hTERT and CD25 expression were detected by reverse transcription-PCR (RT-PCR) in 17 patients with pancreatic adenocarcinoma (PC), 12 patients with chronic pancreatitis (CP), and 7 patients with no ERP abnormality (N). In the same patients, beta-actin message was semiquantified by competitive RT-PCR. K-ras codon 12 mutations were concomitantly analyzed by enriched PCR-SSCP in 11 and 7 PC and CP cases, respectively. RESULTS: Expression of hTERT was detected in 88% of PC cases and 17% of CP cases but not in the normal control (N). Alterations in K-ras were detected in 73% of PC cases and 57% of CP cases, respectively. beta-Actin mRNA was expressed in >3.0 x 10(1) copies/microl in all but two PC cases in which hTERT mRNA was not detected. CD25-positive and -negative peripheral lymphocytes were isolated from a normal volunteer using a fluorescent activating cell sorter. The hTERT message was detected in CD25-positive peripheral lymphocytes and in 18, 25, and 0% of the pancreatic juice samples from PC, CP, and N cases, respectively. All CP cases expressing hTERT message were also CD25 positive. CONCLUSIONS: These results suggest that detection of hTERT mRNA in pancreatic juice is a powerful tool to discriminate PC from CP, particularly when the samples are qualified against beta-actin mRNA levels and contaminating CD25-positive lymphocytes.

Laparoscopic repair for a previously unreported form of ventral hernia on the right iliac fossa in an elderly emaciated woman.

An 81-year-old emaciated woman was admitted to our hospital with a one-year history of recurrent bilateral inguinal swellings. Palpable lumps were observed not only in bilateral groin areas, but also on the right iliac fossa (RIF) of her abdomen. During a planned transabdominal preperitoneal laparoscopic herniorrhaphy, a previously unreported form of ventral hernia was observed at a position lateral and cranial to the right internal inguinal ring, which probably corresponded to the palpable lump on the RIF. The hernia orifice was 2 cm in diameter, and a vascular structure ran through the orifice. The contents of the hernia consisted of fatty tissue arising from the retroperitoneal tissue. Routine exploration revealed orifices of the following hernias: left indirect, right direct, bilateral femoral, bilateral obturator, and right Spigelian hernia. Her postoperative course was uneventful and a mass on the right lower quadrant disappeared after operation.

Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis.

OBJECTIVE: To clarify histologic localization of estrone sulfatase in normal uterine endometrium and adenomyotic tissue and to confirm that estrone sulfatase is one of the enzymes that supplies estrogen to adenomyotic tissue. METHODS: Specimens from 21 patients who had undergone hysterectomy were obtained from uteri with histopathologically proven adenomyosis. Specimens from 28 patients who had undergone hysterectomy for a disease of the uterine cervix were used as control specimens of normal uterine endometrium. Cases of hormone-dependent disease, such as leiomyoma, adenomyosis, and endometrial neoplasm, were excluded from cases of normal endometrium. The myometrium in patients with adenomyosis was examined. These tissues were examined by immunohistochemistry using anti-estrone sulfatase monoclonal antibodies. Power analysis was performed. With alpha = 0.05, 1 - beta = 0.8, P1= 25%, and P2 = 75%, 14 specimens from each group were sufficient to detect significant differences among them. The Fisher exact test, sign test, and McNemar test were used for statistical analysis. RESULTS: In normal endometrial tissue, immunostaining for estrone sulfatase was observed only on the glandular epithelial cells of the basilar layer of the endometrium. However, all functional layers of the endometria were negative for staining for estrone sulfatase. In adenomyotic tissue, glandular epithelial cells showed immunostaining for estrone sulfatase. Rates of immunostaining in adenomyotic tissue were higher than those in the basilar layer of normal uterine endometrium (76% and 43%, respectively, P =.02). The myometrium was not stained. CONCLUSION: Estrone sulfatase may be one of the enzymes supplying estrogen for growth of adenomyosis.

American and Japanese chronic low back pain patients: cross-cultural similarities and differences.

The study compared and contrasted medical, psychological, social and general behavioral functioning of American and Japanese low back pain patients and normal controls. The Sickness Impact Profile and a standardized Medical Examination Protocol for Pain instrument were used to assess all subjects. Findings showed that the American and Japanese low back pain patients had similar and significantly higher medical-physical findings than their respective controls. Likewise, the American and Japanese low back pain patients showed significantly greater psychological, social, and general behavioral dysfunction compared to control subjects. Finally, despite similar medical and physical findings, the Japanese low back pain patients were significantly less impaired in psychological, social, vocational, and avocational functioning than the American low back pain patients. It was concluded that there were significant cross-cultural differences between the American and Japanese low back pain patients, primarily in the psychosocial and behavioral areas. However, given the small sample size, any conclusion should be considered with caution; replication is needed before more definite conclusions are possible.

Denitrification and neutralization treatment by direct feeding of an acidic wastewater containing copper ion and high-strength nitrate to a bio-electrochemical reactor process.

The feasibility of the direct denitrification treatment of copper metal pickling wastewater by using a bio-electrochemical reactor process was investigated experimentally. Carbon electrodes were installed in the reactor as the anode and cathode and denitrifying microorganisms were fixed on the surface of the cathode. The reactor was continuously operated by applying an electric current and feeding acetate. In this reactor, copper ion removal and denitrification proceeded simultaneously and the pH value of the treated water was increased almost to neutral. The electric current that passed through the cathode contributed to the removal of the copper ion and the generation of hydrogen gas. The generated hydrogen gas as well as the added acetate was effectively utilized for denitrification. A theoretical evaluation of pH in the effluent suggested that the pH increase was mainly caused by the generation of hydroxyl ion during denitrification. In addition, the inorganic carbon species generated during denitrification with acetate and by the electrochemical oxidation of anodic carbon acted as a buffer to minimize a further increase of pH at higher nitrate removal efficiencies. These results demonstrated that copper ion removal, denitrification and neutralization could be achieved simultaneously by using a single bioelectrochemical reactor.

The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis.

BACKGROUND/PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) was assessed in the diagnosis of cholestatic liver disease in infants. METHODS: ERCP was performed in 50 infants who had prolonged cholestasis. Their ages ranged from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to 6.7 kg (mean, 4.7 kg). Incomplete visualization of the biliary tree or visualization of only the pancreatic duct was followed by exploratory laparotomy. In those in whom the biliary tree was visualized completely, the caliber of the bile duct was compared with that of the pancreatic duct. RESULTS: ERCP was completed in 43 patients (success rate, 86%) without complications. In the 7 patients in whom ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory laparotomy. The other patient had congenital biliary dilatation (CBD). In 29 of the 43 patients, the biliary tree was seen partially or only the pancreatic duct was visualized. These patients had BA diagnosed by laparotomy. Complete visualization of the biliary tree was obtained in 14 patients. Of these, 9 had neonatal hepatitis (NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD. In all of the patients with NH, cholestasis improved spontaneously. The 2 patients with PIBLD had biopsy-proven disease. The caliber of the bile duct was larger than that of the pancreatic duct in NH. This relationship was not observed in PIBLD. CONCLUSIONS: ERCP is safe in infants. It is useful in the diagnosis of prolonged cholestasis.

Adenomatoid tumor of the uterus: report of a case and review of the literature.

A case of uterine adenomatoid tumor in a 47-year-old female was studied with both light and electron microscopes. The tumor was circumscribed, 2.5 cm in diameter, and located in the posterior wall of the uterus. In light microscopy, tumor cells showing "signet-ring" appearance arranged in cords or tubules. Hyaluronidase-sensitive acid mucopolysaccharide was present in the cells and luminal surfaces. Mucicarmine stain was negative and periodic acid-Schiff reaction was faintly positive. In electron microscopy, the tumor showed basal laminae, well-developed desmosomes and numerous microvilli. Intercellular spaces were present between adjacent cells. Small intercellular spaces were separated from the large lumens by desmosomes and tight junctions, while large spaces communicated with the tubular lumens. Forty-four reported cases of adenomatoid tumor in females were briefly reviewed.

Ice-based altitude distribution of natural radiation annual exposure rate in the Antarctica zone over the latitude range 69 degrees S-77 degrees S using a pair-filter thermoluminescence method.

Both ice-based altitude distributions of natural ionizing radiation exposure and the quasi-effective energy of natural radiation over Antartica over the latitude range 69 degrees S - 77 degrees S during approx. 500 days were measured using thermoluminescent dosimeters. The results shows that dependence on altitude above sea level of the exposure rate increases by almost three-fold with each increase of 2000 m of altitude, thus deviating from the general rule stating that the exposure rate should double with each 2000 m. Although the exposure rate shows a dependence on altitude, altitude dependence of the quasi-effective energy of natural radiation over Antartica is not observed. In the present study it is observed that natural radiation occurring over the ice base of Antartica consists mainly of cosmic rays.

Acid-base imbalance adapts without changes in cell polarity in cortical collecting ducts in premature rabbits.

It has been demonstrated that intercalated cells (ICs) change their cellular composition in acid stimuli in adult rabbits but not fully explained in developing rabbits. To clarify the mechanisms of adaptation in acid-base imbalance in collecting ducts in developing rabbit kidneys, we examined the cellular composition of cortical collecting ducts (CCDs) in 4-week-old rabbits. In the control group, the ratio of ICs to total CCD cells and that of peanut agglutinin (PNA) non-binding ICs to total ICs were 37.2 +/- 7.2% and 40.3 +/- 3.1%, respectively. By contrast, inconsistent with adult reports, in the acidotic group, these ratios were 38.4 +/- 5.1% and 41.9 +/- 1.7%, respectively, similar to the control group. The urinary pH in the control group was 8.20 +/- 0.14, while that in acidemia was 4.98 +/- 0.33 (p < 0.01). These data indicated that cellular remodeling of ICs in the acidotic state is less important for adaptation in the 4-week-old rabbit. Another mechanism, employing an acid-base related protein, might be playing an important role during development for acid base imbalance.

Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

OBJECTIVE: Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. METHODS: In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. RESULTS: Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). CONCLUSION: Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH.