HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data

Background/Aims

Quantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.

Methods

Patients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.

Results

Forty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).

Conclusions

There was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.     

Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do,Korea

Background/Aims

The prevalence of nonalcoholic fatty liver disease (NAFLD) in Korea has increased recently. The aim of the present study was to determine the regional differences in the prevalence and characteristics of NAFLD.

Methods

From January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents receiving a health examination at our institution were enrolled in this cross-sectional study. After applying exclusion criteria, the data of 141,610 subjects (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was established by ultrasound examination.

Results

The overall prevalence of NAFLD was 27.3% (38.3% in men, 12.6% in women). When standardized according to age, area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001). The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi-do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001).

Conclusions

The regional prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are needed to establish the etiology of this difference.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Favorable surgical treatment outcomes for chronic constipation with features of colonic pseudo-obstruction

AIM: To determine long-term outcomes of surgical treatments for patients with constipation and features of colonic pseudo-obstruction.METHODS: Consecutive 42 patients who underwent surgery for chronic constipation within the last 13 years were prospectively collected. We identified a subgroup with colonic pseudo-obstruction (CPO) features, with dilatation of the colon proximal to the narrowed transitional zone, in contrast to typical slow-transit constipation (STC), without any dilated colonic segments. The outcomes of surgical treatments for chronic constipation with features of CPO were analyzed and compared with outcomes for STC.RESULTS: Of the 42 patients who underwent surgery for constipation, 33 patients had CPO with dilatation of the colon proximal to the narrowed transitional zone. There were 16 males and 17 females with a mean age of 51.2 ± 16.1 years. All had symptoms of chronic intestinal obstruction, including abdominal distension, pain, nausea, or vomiting, and the mean duration of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was 1.5 ± 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total colectomy, and one patient underwent diverting transverse colostomy. There was no surgery-related mortality. Postoperative histologic examination showed hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy (n = 3). Early postoperative complications developed in six patients with CPO; wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n = 1). Defecation frequencies 3 mo after surgery improved to 4.2 ± 3.2 times/d (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32 patients; all patients had improvements in constipation symptoms, but two patients needed intermittent medication for management of diarrhea. All 32 patients had distinct improvements in constipation symptoms (with a mean bowel frequency of 3.3 ± 1.3 times/d), social activities, and body mass index (20.5 kg/m² to 22.1 kg/m²) and were satisfied with the results of their surgical treatment. In comparison with nine patients who underwent colectomy for STC without colon dilatation, those in the CPO group had a lower incidence of small bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up.CONCLUSION: Chronic constipation patients with features of CPO caused by narrowed transitional zone in the left colon had favorable outcomes after total colectomy.     

Smooth and large scale organometallic complex film by vapor-phase ligand exchange reaction

A simple and reliable method for the formation of smooth and large-scale organometallic complex thin films was developed. We applied chemical vapor deposition (CVD) for this. From the vapor-phase reaction of Mo(CO)₆ and 2,2′-bipyridine, large-scale and highly smooth Mo(CO)₄(2,2′-bipy) films were obtained. Regardless of the thickness, they show a high smoothness and stability in ambient conditions. Chemical structure and composition of the resulting film were confirmed by ¹H-NMR, Raman, FT-IR spectroscopy and elemental analyses. Smooth and uniform surface of the resulting films was characterized using AFM. We believe that our method will provide great opportunities for the fundamental studies of traditional organometallic complexes and their applications by taking advantages of thin film geometry.

Highly-smooth Mo(CO)₄(2,2′-bipy) thin film showing a color gradient depending on the thickness can be obtained by vapor-phase ligand exchange reaction.

Fabrication of organometallic complexes (OMCs) into high-quality thin films would enable observation of previously-unseen chemical reactions, and allow elucidation of properties that are difficult to detect in other phases than thin films. In addition, the thin films would have various applications in fields such as electronics, photoelectronics, optics, photonics, magnets and spintronics.^1–6 Most attempts to obtain high-quality OMC films have tried to coat pre-synthesized target complexes.⁷ However, these methods were mostly unsuccessful and if successful were not easily applied to general OMCs. Therefore, a new reliable method for the formation of high-quality OMC films is sought.Direct formation of OMC films on a target substrate is a promising method because of their good reactivity and potentially interesting electrical and optical properties. OMCs have been synthesized in solution phase, but this method is more appropriate for obtaining three-dimensional structures than for films. Also, physical vapor deposition methods to pre-synthesize OMCs are also not appropriate due to their low vapor pressure and the possibility of decomposition. Hence, development of efficient synthesis methods to obtain large-scale and uniform OMC film remains a challenge.Chemical vapor deposition (CVD) is an effective method to produce large-scale two-dimensional materials^8,9 and to form films of polymers¹⁰ and metal–organic frameworks.¹¹ Here, we report a rapid and highly efficient CVD method that uses in situ vapor-phase chemical reactions of precursors to synthesize highly-uniform thin films of OMCs. This method facilitates direct reaction of precursors without any disturbance by solvent or impurities, and therefore induces facile formation of pure, highly-uniform and smooth OMC films. It is useful for electrocatalytic CO₂ reduction¹² and ligand exchange reaction.¹³ We exploited a vapor-phase ligand exchange reaction between hexacarbonylmolybdenum(0) (Mo(CO)₆) and 2,2′-bipyridine (2,2′-bipy). The reaction was conducted in a CVD system within 5 min to yield highly-uniform, smooth, and large-scale Mo(CO)₄(2,2′-bipy) thin film for the first time. We then used the Mo(CO)₄(2,2′-bipy) film in organometallic thin-film devices and measured their electrical properties.High-quality OMC thin films were prepared using single-step CVD. The metal precursor was Mo(CO)₆ and the ligand precursor was 2,2′-bipy. The goal was to obtain Mo(CO)₄(2,2′-bipy) by a reaction that proceeds well in solution phase.^12,13 Considering the vaporization temperature of Mo(CO)₆ (94.45 °C) and 2,2′-bipy (113.75 °C) (Fig. S1^†), we chose 123 °C as a target temperature for efficient and simultaneous evaporation of precursors. In the CVD system for vapor-phase organometallic reaction (Fig. 1a), Mo(CO)₆ powder was placed 13.5 cm upstream from the center. And 2,2′-bipy powder was placed at the center. This arrangement exploits the temperature gradient in the furnace, and the higher vaporization temperature of 2,2′-bipy than of Mo(CO)₆. A SiO₂/Si target substrate was placed downstream from the center of the tube to collect product efficiently. The quartz tube was flushed using Ar, then the tube furnace was heated from room temperature to the target temperature at 10 °C min⁻¹ (Fig. 1b). After 5 min of reaction at target temperature, the power to the furnace was turned off and the sample was allowed to cool passively to room temperature.Open in a separate windowFig. 1(a) Experimental scheme of the CVD system for the synthesis of Mo(CO)₄(2,2′-bipy) thin film. (b) Molecular structure Mo(CO)₄(2,2′-bipy) obtained by vapor-phase ligand exchange reaction between Mo(CO)₆ and 2,2′-bipy.The resulting large-scale Mo(CO)₄(2,2′-bipy) film was highly uniform and had no notable physical defects or chunks (Fig. 2). We confirmed that the product did not undergo thermal decomposition at operating temperature (123 °C) (Fig. S2 and Table S1^†). The surface of the resulting film was examined using a tapping-mode atomic force microscope (AFM). To measure the thickness of the resulting film, we etched away the film except for a part that was covered using Kapton tape as a shadow mask. The film was treated using CF₄ at flow rate of 40 sccm and O₂ plasma at 5 sccm with power of 150 W power, respectively. Etching time was determined depending on film thickness, from 30 to 90 min. After the process, the measured thickness was 38.6 nm (Fig. S3a^†); the height distribution measured by AFM showed that the Mo(CO)₄(2,2′-bipy) film was highly smooth and uniform surface (root mean square roughness r_RMS = 0.267 nm, Fig. 2b), which is similar to that of a bare SiO₂/Si substrate (r_RMS = 0.249 nm, Fig. S3b^†). A scanning electron microscopy (SEM) image (Fig. S4^†) of the obtained film shows uniform and homogenous surfaces over a large area. Energy-dispersive electron energy loss spectroscopy (EELS) analysis confirmed the presence of Mo, C, N, and O (Fig. S5^†). These results demonstrate that CVD is a highly efficient approach to obtain highly-uniform OMC films.Open in a separate windowFig. 2(a) Optical microscopy image, photograph (inset), and (b) AFM image of the obtained Mo(CO)₄(2,2′-bipy) thin film. (c) Raman spectra of the Mo(CO)₄(2,2′-bipy) powder (purple), and two precursors (Mo(CO)₆ (green), 2,2′-bipy (coral blue)). (d) FT-IR spectrum of Mo(CO)₄(2,2′-bipy) thin film showing four carbonyl stretching bands.The chemical structure of the resulting film was confirmed by Raman and FT-IR analyses (Fig. 2d). For a direct comparison of the chemical structure of the resulting film with a reference, we separately synthesized Mo(CO)₄(2,2′-bipy) bulk powder by using a microwave-assisted synthesis method described elsewhere¹⁴ (ESI^†). The obtained powder was red (Fig. S6^†) and its structure as confirmed by ¹H-NMR was identical to that reported in the reference paper.¹⁴ Raman spectra (Fig. 2c) were obtained from precursors, product film, and reference powder. The carbonyl stretching band was observed at 1900–2000 cm⁻¹, and several bipyridine stretching bands were observed at 1100–1600 cm⁻¹.¹⁵ The stretching bands of the aromatic rings of 2,2′-bipy (asterisks) and the carbonyl stretching bands (triangle) were clearly resolved. The vibrational band of Mo(CO)₄(2,2′-bipy) film (red) is almost identical with the reference Mo(CO)₄(2,2′-bipy) powder (purple).To identify chemical species observed in Raman spectra, we conducted density functional theory (DFT) calculations using Dmol³ modules in Material Studio program packages (details in ESI^†). The six representative bands observed at 1170.8, 1263.5, 1322.0, 1535.5, 1563.9 and 1600.1 cm⁻¹ in the Raman spectrum of Mo(CO)₄(2,2′-bipy) film were confirmed as molybdenum-coordinated bipyridine ligand stretching bands (red), which are shifted and split from the original stretching bands of bipyridine precursor (1147.6, 1236.4, 1303.4, 1574.1, and 1590.2 cm⁻¹, blue). Also, the carbonyl stretching band shifted from 2005.9 cm⁻¹ to 1888.2 cm⁻¹ because to the new coordination bonds between molybdenum and 2,2′-bipy ligand has a weaker π-accepting ability than the previously-bonded carbonyl ligands.¹⁶ The DFT calculations generated Raman vibrational modes of precursors and film (ESI Videos^†). Also, we measured the FT-IR spectrum of Mo(CO)₄(2,2′-bipy) film by using an attenuated total reflection (ATR) mode (650–4000 cm⁻¹). The spectrum (Fig. 2d) shows carbonyl stretching bands at 2014, 1898, 1866, and 1824 cm⁻¹, which correspond respectively to A^1a₁, B₁, A^1b₁, and B₂ vibrational modes of carbonyl ligands interacting to the six-coordinated molybdenum complex; this result is a good match to reference data.¹⁷For further characterization, we measured ¹H-NMR of dissolved Mo(CO)₄(2,2′-bipy) film in CDCl₃. The NMR peaks (Fig. S7,^† triangles) match well with the reference NMR peaks of Mo(CO)₄(2,2′-bipy) powder,¹⁴ and also confirmed the presence of small amount of 2,2′-bipy precursor (squares). Grazing-incidence wide-angle X-ray scattering (GI-WAXS) measurements (Fig. S8^†) we confirmed the amorphous structure of the resulting film.One of the big advantages of CVD is that the thickness of the resulting film can be controlled easily by changing the amount of precursors. Mo(CO)₄(2,2′-bipy) films were formed on SiO₂/Si substrate by using different amounts of precursors; the films showed a continuous color gradient that depended on the thickness (Fig. 3a). The thickness can be controlled from the range of tens of nanometers to micron scale; all surfaces were highly smooth (Fig. S9^†).Open in a separate windowFig. 3(a) Photograph of Mo(CO)₄(2,2′-bipy) films showing a continuous color gradient depending on the thickness. The rightmost sample is a bare SiO₂/Si substrate. (b) I–V characteristic curve of Mo(CO)₄(2,2′-bipy) thin film; inset: photograph of the fabricated device. (c) I–V characteristics at rt ≤ T ≤ 100 °C for DC voltage −40 to 40 V.To exploit the geometrical advantage of the thin film for device fabrication, field-effect transistor (FET) electronic devices with a channel length of 20 mm (Fig. 3b, inset) were fabricated (ESI and Fig. S10^†). The I_ds–V_ds curve (Fig. 3b) of the resulting device indicated that the highest electrical conductance was 1.90 × 10⁻⁹ S, and the highest conductivity was 1.99 × 10⁻⁵ S m⁻¹. The linear characteristic of I–V curve is a sign of ohmic contact between film and electrode, as a consequence of the uniform and smooth surface of Mo(CO)₄(2,2′-bipy) film. The electrical conductance of Mo(CO)₄(2,2′-bipy) film increased as the temperature was increased from room temperature to 100 °C (Fig. 3c); this result shows the semiconducting nature of the Mo(CO)₄(2,2′-bipy) film. To compare the electrical property of film with reference powder, Mo(CO)₄(2,2′-bipy) powder was pelletized and fabricated on a SiO₂/Si substrate. The pellet was rough and thick, so we used silver paste as an adhesive electrode. The I–V characteristic curve (Fig. S11^†) of Mo(CO)₄(2,2′-bipy) pellet exhibits non-ohmic current–voltage characteristics between the pellet and the electrode, and eventually failed to measure the electrical property of the complex. These results demonstrate that the intrinsic properties of organometallic materials requires synthesis of uniform and smooth organometallic film.^18,19In summary, we synthesized large-scale, highly-uniform, smooth, and thickness-controllable Mo(CO)₄(2,2′-bipy) thin films by vapor-phase ligand exchange reaction that exploits chemical vapor deposition (CVD). Our strategy facilitates the vapor-phase reaction of precursors without any disturbance of solvent or impurities, and also yields a suitable smooth film geometry that is advantageous for various electrical and optical device applications. FET devices that use Mo(CO)₄(2,2′-bipy) thin film exhibit semiconducting behaviour. We believe that these results provide insights that will guide development of novel strategies to synthesize various OMC films for use in various electrical and optical applications.     

Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study

Summary

Although the presence of metabolic syndrome (MetS) and increasing numbers of MetS components were associated with attenuated bone loss at various skeletal sites in postmenopausal women, this beneficial effect of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects.

Introduction

Previous cross-sectional epidemiological studies reported the inconsistent results regarding the combined effects of MetS on bone mass. In our present report, we performed a large, longitudinal study to evaluate MetS in relation to annualized bone mineral density (BMD) changes in postmenopausal Korean women.

Methods

The study cohort consisted of 1,218 postmenopausal women who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. The BMD at the lumbar spine and proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and at follow-up.

Results

Following adjustment for age, baseline BMD, and lifestyle factors, the women with MetS had 21.7, 17.0, 26.7, and 31.1 % less bone loss at the total femur, femur neck, trochanter, and lumbar spine, respectively, compared with MetS-free women (P?=?0.004 to 0.041). Consistently, the rates of bone loss at all skeletal sites were linearly attenuated with increasing numbers of MetS components (P?=?0.004 to <0.001). Importantly, when weight and height were added as confounding factors, the differences and trends of annualized BMD changes according to the MetS status disappeared.

Conclusion

Our current results indicate that the beneficial effects of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. Consequently, MetS per se may not be a meaningful concept for predicting future bone loss and for explaining associations between osteoporosis and cardiovascular diseases.