Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.

OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Sensory quality characteristics with different beef quality grades and surface texture features assessed by dented area and firmness, and the relation to muscle fiber and bundle characteristics.

The main objective of this study was to compare the eating quality among the groups categorized by the Korean beef quality grade and texture feature of exposed muscle surface assessed by extent of dented areas and firmness. Additionally, this study also investigated the effects of fiber and bundle characteristics on texture feature to establish the cause of differences in muscle surface texture. Significant differences were observed in the sensory quality characteristics among the quality grades mainly determined by marbling score (P < 0.05). However, the coarse texture group with a dented surface required a higher initial force to penetrate meat (P < 0.001), was more difficult to break meat into fragments (P < 0.001), and had a higher amount of perceptible residue in the mouth (P < 0.01) compared to the fine texture group. These differences in the surface texture features between the fine and coarse groups could be explained by bundle area and fiber number per each bundle.

[Operative strategy and clinical results of complex four part distal radius fractures by combined palmar and dorsal internal fixation].

Objective: To explore a standard procedure for the treatment of combined dorsal and palmar internal fixation for complex four part distal radius fractures and assess its clinical results. Methods: From May 2009 to October 2016, 38 patients(39 sides)who suffered from complex four part distal radius fractures were performed operatively with open reduction and internal fixation via combined dorsal and palmar approach in Department of Orthopaedic Trauma, Qilu Hospital of Shandong University(Qingdao). The series included 22 males(22 sides) and 16 females(17 sides). Age of the patients was 53.5 years ranging from 25 to 79 years.According to Melone classification, there were 34 sides of type of Ⅳ, 5 of type Ⅴ.According to Frykman classification, there were 15 sides of type Ⅶ, 24 sides of type Ⅷ, and all the cases were type C3 according to AO/OTA classification.Preoperatively, the key articular fragments in four part distal radius fractures were identified and the individual fracture patterns from conventional X-ray and CT-scan were analyzed. All the patients were performed combined volar and dorsal fixation.Firstly, a palmar approach which gave access to and fix the palmar-ulnar fragment and the radial styloid fragment was performed.Then a limited dorsal approach across the third extensor compartment which gave access to the dorso-ulnar fragment and a limited dorsal arthrotomy to visualize the radiocarpal joint when necessary were performed.Through dorsal approach, we can address the dorso-ulnar fragment, free intra-articular fragment and direct visualize the joint.Use of a retinacular flap was routinely advocated to help prevent against tendon irritation and rupture.The follow-up control included conventional X-ray, range of motion(ROM), grip strength, and the disabilities of the arm, shoulder and hand index(DASH), as well as the patient-rated wrist evaluation(PRWE) score for functional outcome at 6 and 12 months. Results: Thirty-three patients(34 sides) were followed up for at least 12 months.The would healed well in all cases 2 weeks postoperatively, and no soft tissue infections, necrosis or neurovascular complications occurred.All the fractures of 38 cases(39 sides)healed averaged 3.6 months(ranging from 2.5-5.7 months), and no loss of reduction occurred postoperatively.Anatomic reconstruction with a step or gap of <1 mm was achieved in 37 cases(38 sides), Whereas 5 patients were lost to follow-up at 12 months postoperatively.ROM and grip strength were all recovered to over 85% of the unaffected side(exception of the bilateral patient). Median DASH-index and PRWE were 6.5(0-17) and 9.3(0-20)respectively. Conclusion: Combined volar and dorsal approaches allow achieving anatomic reconstruction in complex four part intra-articular distal radius fractures and reveal good functional outcomes at intermediate follow-up.

Concordance of results of blood and tissue cultures from patients with pyogenic spondylitis: a retrospective cohort study.

OBJECTIVES: To investigate the concordance of results of blood and tissue cultures in patients with pyogenic spondylitis. METHODS: We searched for patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures by retrospective review of medical records in three tertiary university-affiliated hospitals between January 2005 and December 2015. The species and antimicrobial susceptibility patterns of isolates from blood and tissue cultures were compared. RESULTS: Among 141 patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures, the species of blood and tissue isolates were identical in 135 patients (95.7%, 135/141). Excluding the four anaerobic isolates, we investigated antimicrobial susceptibility patterns of 131 isolates of the same species from blood and tissue cultures. Antibiotic susceptibility patterns were identical in 128 patients (97.7%, 128/131). The most common isolates were Staphylococcus aureus (86 patients; 85 concordant and one discordant), followed by streptococcus (24 patients; 22 concordant and two discordant), and Escherichia coli (eight patients; all concordant). CONCLUSIONS: We suggest that a positive blood culture from patients with pyogenic spondylitis could preclude the need for additional tissue cultures, especially when S. aureus and streptococcus grew in blood cultures.

Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel.

Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 µg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 µm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.

Effects of eupatilin on the contractility of corpus cavernosal smooth muscle through nitric oxide-independent pathways.

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K+ -channel currents in human CCSM cells. The relaxation effect of eupatilin was evaluated by cumulative addition (10-5  m ~ 3 × 10-4  m) to CC strips precontracted with 10-5  m phenylephrine. Western blotting analysis was performed to measure myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17-kDa (CPI-17) expression and to evaluate the effect of eupatilin on the RhoA/Rho-kinase pathway. Eupatilin effectively relaxed the phenylephrine-induced tone in the rabbit CC strips in a concentration-dependent manner with an estimated EC50 value of 1.2 ± 1.6 × 10-4  m (n = 8, p < 0.05). Iberiotoxin and tetraethylammonium significantly reduced the relaxation effect (n = 8, p < 0.001 and p = 0.003, respectively). Removal of the endothelium or the presence of L-NAME or indomethacin did not affect the relaxation effect of eupatilin. In CCSM cells, the extracellular application of eupatilin 10-4  m significantly increased the outward currents, and the eupatilin-stimulated currents were significantly attenuated by treatment with 10-7  m iberiotoxin (n = 13, p < 0.05). Eupatilin reduced the phosphorylation level of MYPT1 at Thr853 of MLCP and CPI-17 at Thr38. Eupatilin-induced relaxation of the CCSM cells via NO-independent pathways. The relaxation effects of eupatilin on CCSM cells were partially due to activation of BKCa channels and inhibition of RhoA/Rho-kinase.

Direct penetration of spin-triplet superconductivity into a ferromagnet in Au/SrRuO3/Sr2RuO4 junctions.

Efforts have been ongoing to establish superconducting spintronics utilizing ferromagnet/superconductor heterostructures. Previously reported devices are based on spin-singlet superconductors (SSCs), where the spin degree of freedom is lost. Spin-polarized supercurrent induction in ferromagnetic metals (FMs) is achieved even with SSCs, but only with the aid of interfacial complex magnetic structures, which severely affect information imprinted to the electron spin. Use of spin-triplet superconductors (TSCs) with spin-polarizable Cooper pairs potentially overcomes this difficulty and further leads to novel functionalities. Here, we report spin-triplet superconductivity induction into a FM SrRuO3 from a leading TSC candidate Sr2RuO4, by fabricating microscopic devices using an epitaxial SrRuO3/Sr2RuO4 hybrid. The differential conductance, exhibiting Andreev-reflection features with multiple energy scales up to around half tesla, indicates the penetration of superconductivity over a considerable distance of 15 nm across the SrRuO3 layer without help of interfacial complex magnetism. This demonstrates potential utility of FM/TSC devices for superspintronics.

Which tissues are best for microbiological diagnosis in patients with pyogenic vertebral osteomyelitis undergoing needle biopsy?

Identification of the causative microorganism is important in the management of pyogenic vertebral osteomyelitis (PVO). The aim of this study was to investigate whether culture positive rates differ between needle biopsy sites in patients with PVO, and which tissues are best for microbiological diagnosis. Between January 2005 and December 2013, we conducted a retrospective cohort study of PVO patients who had soft-tissue abscesses (paraspinal or psoas abscesses) and who received needle biopsy for microbiological diagnosis. Needle biopsy sites were classified into two anatomical categories: vertebral bodies, or soft tissues (intervertebral discs, paraspinal abscesses, or psoas abscesses). A generalized estimating equation model was developed to identify factors associated with tissue-culture positivity. During the study period a total of 136 tissues were obtained by needle biopsy from 128 PVO patients with soft-tissue abscesses. The culture positive rates of vertebral bodies and soft tissues were 39.7% (29/73), and 63.5% (40/63), respectively (p < 0.05). In a multivariate analysis, male gender (adjusted odds ratio (aOR) 2.24, 95% CI 1.00-5.02), higher C-reactive protein (aOR 1.07, 95% CI 1.01-1.15), positive blood culture (aOR 2.57, 95% CI 1.01-6.59), and soft tissues as biopsy site compared with vertebral bodies (aOR 2.28, 95% CI 1.08-4.78) were independent factors associated with tissue culture positivity. Soft tissues were the best sites for microbiological diagnosis in PVO patients undergoing needle biopsy.

Inhibition of pulmonary cancer progression by epidermal growth factor receptor-targeted transfection with Bcl-2 and survivin siRNAs.

Clinical application of small interfering RNA (siRNA) in cancer therapy has been limited by the lack of an efficient systemic siRNA delivery system. In this report we describe an efficient siRNA delivery system directed to metastasized tumors, especially in the lungs. Anticancer siRNA was condensed in the presence of 9-arginine peptides (9Arg) and then complexed with cationic O,O'-dimyristyl-N-lysyl glutamate liposomes conjugated to antibodies against the epidermal growth factor receptor (EGFR). The ternary complex of optimized anti-EGFR-9Arg-lipoplexes exhibited efficient siRNA transfection of LS174T-Luc cancer cells grown in culture or orthotopically in mouse lungs. Anti-tumor Bcl-2/survivin siRNAs loaded in the anti-EGFR-9Arg-lipoplexes effectively suppressed transcription of their target genes, resulting in an efficient cancer cell death. Repeated intravenous administrations of the anti-EGFR-9Arg-lipoplexes effectively inhibited tumor growth in the mouse lungs and prolonged survival of the mice compared with nontargeted lipoplexes. These results suggest that the ternary complexes of anti-EGFR-9Arg-lipoplexes might have clinical applications in RNA interference cancer therapy.

Comparisons of apomorphine-induced erection and spontaneous erection in rats by telemetric assessment of intracavernosal pressure.

Although there are several methods for assessing erectile function in rats, the standard methods for telemetric monitoring have not been established. Theoretically assessment of spontaneous erection (SE) seems to be a physiologic method but it needs long measuring time and additional efforts. Apomorphine-induced erection (AIE) is one available and simple method; however, the correlation with SE has not been assessed. We compared erection profiles of AIE and SE in normal and two disease rat models using telemetric assessment of intracavernosal pressure (ICP). Seven-week-old male Sprague-Dawley rats were assigned to normal control, diabetes mellitus (DM) and hypercholesterolemia (HC) group. After 19 weeks a telemetric pressure sensor (C40; Data Sciences) was surgically implanted in the corpus cavernosum. One week later, ICP was recorded in freely moving rats after intraperitoneal apomorphine (100 µg/kg) injection (AIE) or during SE. Sexual events were visually identified and recorded. Only the pressure increases that occurred during sexual behavior were analyzed. We compared the erectile profiles such as duration, maximal ICP and the area under the curve (AUC, area under time × ICP curves). Two-way anova revealed no significant effect of the measuring methods on the mean AUC (F1,43 = 2.756, p-value = 0.104), but a significant effect of different disease models on mean AUC (two-way anova: F2,43 = 12.929, p-value < 0.001) was observed. The mean AUC of normal control rats was significantly higher than that of DM and HC rats (Bonferroni post hoc test: p < 0.001 and p = 0.001, respectively). ICP measurements using a telemetric device showed no significant difference in AUC between AIE and SE. AIE is easy and requires less time than SE measurements. Therefore, AIE could be a useful method to evaluate ICP in rats.

Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes.

In recent reports, an association between altered TRPC channel function and the development of various diabetic complications has drawn the attention of many investigators. The aim of this study was to investigate the expression of TRPC4 channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the association between erectile dysfunction (ED) and altered TRPC4 channel function. The expression of TRPC4 in the penile tissue of human, normal and diabetic rat was investigated using RT-PCR, western blotting and immunohistochemistry (IHC). In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was conducted. In vivo pelvic nerve stimulation was performed to measure erectile function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM tissues was confirmed by RT-PCR, western blot and IHC. In the diabetic rat, the expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly increased compared to control rats (p < 0.05). The change in TRPC4 expression in the diabetic rats was higher than those of the other TRPC subunits (p < 0.05). The IHC showed that only TRPC4 expression had a higher intensity in the diabetes compared to normal rats (p < 0.05). Gene transfection with TRPC4(DN) into the diabetic rats restored erectile function to levels similar to that of normal controls. Gene expression of TRPC4(DN) in CSM tissue was confirmed by RT-PCR 2 weeks after transfection. This study demonstrated that TRPC4 channel expression increased in the penile CSM cells of diabetic rats. The down-regulation of TRPC4 with DN form restored erectile function in the diabetic rats. The alteration of TRPC4 channel is one of pathophysiology of ED and could be a target for drug development for ED.

Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques.

OBJECTIVE: Few studies have investigated the relationships between visceral adipose tissue (VAT) and coronary stenosis and noncalcified plaques at the subclinical stage. The aim of this study was to investigate relationship between VAT and coronary lesions assessed by coronary computed tomography (CT) in an apparently healthy population. DESIGN: Retrospective cross-sectional study. SUBJECTS: One thousand six hundred and fifty-eight subjects free of cardiovascular disease underwent coronary CT and abdominal fat CT as part of a routine medical examination. MEASUREMENT: VAT area was measured at the level of the umbilicus using CT. Coronary stenoses and plaques were evaluated using coronary CT. RESULTS: The mean age of the study population was 55.9±8.0 years, and 1198 (72.3%) subjects were men. There were 201 subjects (12.1%) with coronary stenosis <50% and 144 (8.7%) had significant stenosis. Noncalcified plaques were observed in 108 (6.5%) subjects. Coronary stenosis <50% and noncalcified plaques increased steadily as the VAT area increased (P<0.001). The 4th quartile of VAT area was significantly associated with prevalence of coronary stenosis <50% and the presence of noncalcified plaques when compared with the first through third VAT quartiles in the cardiovascular risk factor-adjusted model (odds ratio (OR): 1.58, 95% confidence interval (CI): 1.09-2.30 and OR: 1.66; 95% CI: 1.02-2.68, respectively). CONCLUSION: Excess VAT area was associated with coronary stenosis <50% and noncalcified plaques, independent of traditional cardiovascular risk factors, in an asymptomatic population without a history of coronary artery disease.

(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease.

Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson's disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD-like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration.

A redundant epistatic interaction between IRF5 and STAT4 of the type I interferon pathway in susceptibility to lupus and rheumatoid arthritis.

OBJECTIVE: Two transcription factors in the type I interferon pathway, IRF5 and STAT4, have been genetically associated with susceptibility to both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to determine whether these two genes interact with each other to affect the disease susceptibilities. METHODS: The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software. This study analyzes the genetic data from 2558 unrelated Korean participants including 589 SLE patients, 987 RA patients, and 982 controls. RESULTS: All 12 polymorphisms were individually associated with SLE susceptibility (p = 2.49 × 10(-8) to 0.00360). Among the three SLE-associated polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3-4) indel, exhibited the lowest p value (4.60 × 10(-5)) and accounted for the observed associations of the other two single-nucleotide polymorphisms (SNPs). Among the nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49 × 10(-8)) and accounted for all the other associations. These two polymorphisms, rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE susceptibility in a redundant manner (ORinteraction = 0.77, P epistasis = 0.040). Furthermore, these two polymorphisms, which had been individually associated with RA susceptibility, also interacted for RA susceptibility in the same manner (ORinteraction = 0.75, P epistasis = 0.014). CONCLUSIONS: A redundant interaction between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling for further studies on confirmation of these findings.

Surgical treatment of enophthalmos using an endoscope and T-shaped porous polyethylene fabricated with a mirror image.

Enophthalmos is corrected mostly through reducing the enlarged orbit volume by identifying intact bone edges and spanning the defect with an implant or autogenous graft. Predicting the amount of volume which must be added to correct enophthalmos is not easy using this method, and the outcome may be unsatisfactory. In this study, the authors examined 9 patients in whom enophthalmos was caused by a defect or inadequate surgery of the orbital medial wall. The authors designed an adequately shaped implant by using the mirror image obtained before surgery, and prepared a T-shaped Medpor for each patient in order to maintain the accurate contour of the medial wall and to decrease the enlarged orbital volume. During the surgery, the T-shaped Medpor was inserted while monitoring the posterior portion of the orbital wall. Satisfactory results were obtained for all the patients. Although the new method of implant design developed by the authors in this study is limited to the reconstruction of the medial wall, it is considered useful for the surgical treatment of posttraumatic enophthalmos because it takes into account both the contour and volume of the orbital wall.

Effects of Polycan, a ß-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats.

BACKGROUND AND OBJECTIVE: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of ß-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. MATERIAL AND METHODS: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. RESULTS: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1ß, TNF-α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen-fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. CONCLUSION: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect.

Community-associated Panton-Valentine leukocidin-negative meticillin-resistant Staphylococcus aureus clone (ST72-MRSA-IV) causing healthcare-associated pneumonia and surgical site infection in Korea.

BACKGROUND: Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an important pathogen worldwide in a continent-specific manner. Clinical characteristics of infections caused by CA-MRSA other than USA300, especially in healthcare settings, have not been well established. AIM: To conduct a retrospective cohort study to determine the clinical characteristics of infections caused by Panton-Valentine leukocidin (PVL)-negative, multilocus sequence type (ST) 72 staphylococcal cassette chromosome mec (SCCmec) type IV, a major CA-MRSA clone in Korea. METHODS: ST72-IV isolates, which were susceptible to fluoroquinolones, gentamicin, rifampicin, and cotrimoxazole, were presumptively identified among 4667 MRSA isolates and then confirmed by SCCmec typing and multilocus sequence typing. A total of 124 cases of ST72-IV infections were analysed. FINDINGS: The annual incidence of infections by ST72-IV per 100,000 admissions increased from 45.5 to 66.3 cases during 2007-2009. The most frequently occurring type of infection was skin and soft tissue infection (SSTI) (46.0%), followed by pneumonia (27.4%) and bone and joint infection (9.7%). Surgical site infection accounted for 22.6% and 32.5% of community-onset (CO) healthcare-associated infection and hospital-onset (HO) infection, respectively. Pneumonia was most frequent (45.0%) among HO infection. Multivariate analysis showed that pneumonia increased the odds of all-cause mortality (odds ratio: 18.8; 95% confidence interval: 2.6-133.9) compared with other types of infection. CONCLUSIONS: Increasing trends were observed in annual incidence of CO and HO infections by ST72-IV in Korea. Pneumonia was the most frequent among HO infection and was associated with higher mortality. These findings pose important implications for successful antibiotic therapy and infection control in the era of CA-MRSA.

Family-based genome-wide association study of frontal θ oscillations identifies potassium channel gene KCNJ6.

Event-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10(-10)). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks.