Effects of Buddhist walking meditation on glycemic control and vascular function in patients with type 2 diabetes.
To investigate and compare the effects of Buddhist walking meditation and traditional walking on glycemic control and vascular function in patients with type 2 diabetes mellitus. Twenty three patients with type 2 diabetes (50-75 years) were randomly allocated into traditional walking exercise (WE; n=11) or Buddhism-based walking meditation exercise (WM; n=12). Both groups performed a 12-week exercise program that consisted of walking on the treadmill at exercise intensity of 50-70% maximum heart rate for 30min/session, 3 times/week. In the WM training program, the participants performed walking on the treadmill while concentrated on foot stepping by voiced "Budd" and "Dha" with each foot step that contacted the floor to practice mindfulness while walking. After 12 weeks, maximal oxygen consumption increased and fasting blood glucose level decreased significantly in both groups (p<0.05). Significant decrease in HbA1c and both systolic and diastolic blood pressure were observed only in the WM group. Flow-mediated dilatation increased significantly (p<0.05) in both exercise groups but arterial stiffness was improved only in the WM group. Blood cortisol level was reduced (p<0.05) only in the WM group. Buddhist walking meditation exercise produced a multitude of favorable effects, often superior to traditional walking program, in patients with type 2 diabetes.


Evaluation of reverse transcription-polymerase chain reaction and simultaneous amplification and testing for quantitative detection of serum hepatitis B virus RNA.
Chronic hepatitis B virus (HBV) infection is one of the common infectious diseases in the world. HBV covalently closed circular DNA (cccDNA) is the initial template of HBV replication, which can exist in human hepatocytes for a long time and is difficult to be completely removed. It has been shown that HBV RNA can directly respond to the levels and transcriptional activity of cccDNA in hepatocytes and can be used as a surrogate marker of cccDNA transcriptional activity. At present, the detection techniques used for quantitative HBV RNA mainly include reverse transcription quantitative polymerase chain reaction (RT-qPCR) and simultaneous amplification and testing (SAT). In this study, we verified the performance of the SAT method for detecting HBV RNA and the clinical effectiveness of SAT and RT-qPCR, and compared the correlation and consistency of the two detection methods for HBV RNA detection. The results showed that the limit of detection for HBV RNA by SAT method was 50 copies/mL, with a linear range of 1 × 102-1 × 108 copies/mL. There was no difference in HBV RNA levels detected by the two methods. The correlation and consistency of the results were good, with the coefficient of determination of 0.7787 in HBeAg positive group and 0.8235 in HBeAg negative group. Therefore, this study confirmed that the SAT method and RT-qPCR for detecting HBV RNA have good agreement, which are both reliable methods to detect HBV RNA and can replace each other.


Enterovirus meningitis in Mayotte French Comoros Island, March-June 2019.
Enteroviruses (EV) are the most frequent cause of acute meningitis worldwide, and regularly responsible for outbreaks. Human parechoviruses (PeV) are associated with sepsis and meningitis in young infants. In Mayotte, a French department located in the Comoros archipelago, EVs and PeVs are not part of the routine screening of cerebrospinal fluids (CSFs) of patients with meningitis. Consequently, no data is available on EV or PeV epidemiology. Assess the need for EV and PeV diagnosis in Mayotte. CSFs collected between March and June 2019 from patients addressed to Mayotte Hospital were retrospectively screened for EV and PeV by PCR. If positive for EV, genotyping was attempted. EV and PeV RT-PCR were performed on 122/263 (46%) CSFs (45 adults, 77 children). EV meningitis was diagnosed in 16/77 children (21%) with a median age of 32 days (8-62). One 30-days-aged infant presented with a PeV infection. Fever was reported in 94% cases (16/17), followed by gastrointestinal disorders in 29% cases (5/17). EV genotyping achieved identification for 10/16 (63%) EV-positive samples. Four different EV types were identified: Echovirus 16 (E-16, n = 6), EV-B100 (n = 2), and E-14 and E-18 (n = 1, each). EV/PeV prevalence of 14% highlights the importance of implementing this diagnosis which can impact duration of hospitalization and administration of antibiotics thus reducing risk of antimicrobial resistance. Surveillance of circulating EV types is needed to understand the range of enteroviruses detected in meningitis cases in places that have been underrepresented in enterovirus surveillance studies.


Growth of pathogenic Yersinia enterocolitica strains in minced meat with and without protective gas with consideration of the competitive background flora.
The growth of two pathogenic Yersinia enterocolitica strains (O:3, O:9 at 1 degree C, 4 degrees C, 10 degrees C and 15 degrees C) in minced meat produced under sterile conditions and in minced meat with a normal background flora was investigated. In addition, the influence of treatment with a protective gas (20% CO2, 80% O2) was tested. In minced meat produced under sterile conditions and incubated under normal atmospheric conditions, Y. enterocolitica increased in numbers by only 1 log at 1 degree C and 3.5 logs at 4 degrees C within 14 days. At 10 and 15 degrees C, there was about a 5-log increase in cell numbers within 5 days. There was a marked inhibition of growth by the background flora on Y. enterocolitica. This effect was so marked that only a slight additional inhibition on the growth of Y. enterocolitica at 1, 4 and 10 degrees C was observed under the CO2:O2 modified atmosphere. This is in contrast to the situation where minced meat with a low total bacterial count was used, and the growth of Y. enterocolitica was adversely affected by the CO2:O2 environment. The significance of raw minced meat in the development of human Y. enterocolitica infections is also discussed.


The anti-fibrotic agent pirfenidone synergizes with cisplatin in killing tumor cells and cancer-associated fibroblasts.
Anti-fibrotic drugs such as pirfenidone have been developed for the treatment of idiopathic pulmonary fibrosis. Because activated fibroblasts in inflammatory conditions have similar characteristics as cancer-associated fibroblasts (CAFs) and CAFs contribute actively to the malignant phenotype, we believe that anti-fibrotic drugs have the potential to be repurposed as anti-cancer drugs. The effects of pirfenidone alone and in combination with cisplatin on human patient-derived CAF cell lines and non-small cell lung cancer (NSCLC) cell lines were examined. The impact on cell death in vitro as well as tumor growth in a mouse model was determined. Annexin V/PI staining and Western blot analysis were used to characterize cell death. Synergy was assessed with the combination index method using Calcusyn software. Pirfenidone alone induced apoptotic cell death in lung CAFs at a high concentration (1.5 mg/mL). However, co-culture in vitro experiments and co-implantation in vivo experiments showed that the combination of low doses of cisplatin (10 μM) and low doses of pirfenidone (0.5 mg/mL), in both CAFs and tumors, lead to increased cell death and decreased tumor progression, respectively. Furthermore, the combination of cisplatin and pirfenidone in NSCLC cells (A549 and H157 cells) leads to increased apoptosis and synergistic cell death. Our studies reveal for the first time that the combination of cisplatin and pirfenidone is active in preclinical models of NSCLC and therefore may be a new therapeutic approach in this disease.


Penalized-regression-based multimarker genotype analysis of Genetic Analysis Workshop 17 data.
Testing for association between multiple markers and a phenotype can not only capture untyped causal variants in weak linkage disequilibrium with nearby typed markers but also identify the effect of a combination of markers. We propose a sliding window approach that uses multimarker genotypes as variables in a penalized regression. We investigate a penalty with three separate components: (1) a group least absolute shrinkage and selection operator (LASSO) that selects multimarker genotypes in a gene to be included in or excluded from the model, (2) an allele-sharing penalty that encourages multimarker genotypes with similar alleles to have similar coefficients, and (3) a penalty that shrinks the size of coefficients while performing model selection. The penalized likelihood is minimized with a cyclic coordinate descent algorithm, allowing quick coefficient estimation for a large number of markers. We compare our method to single-marker analysis and a gene-based sparse group LASSO on the Genetic Analysis Workshop 17 data for quantitative trait Q2. We found that all of the methods were underpowered to detect the simulated rare causal variants at the low false-positive rates desired in association studies. However, the sparse group LASSO on multi-marker genotypes seems to provide some advantage over the sparse group LASSO applied to single SNPs within genes, giving further evidence that there may be an advantage to modeling combinations of rare variant alleles over modeling them individually.


New arylpiperazines with flexible versus partly constrained linker as serotonin 5-HT(1A)/5-HT(7) receptor ligands.
A series of new long-chain arylpiperazine (LCAP) derivatives with flexible and partly constrained alkyl linker were synthesized and investigated in vitro as potential serotonin 5-HT(1A) and 5-HT(7) receptor ligands. The compounds were prepared by a two-step procedure using naphthalimide and 2H-1,3-benzoxazine-2,4(3H)-dione as imides, and 1-(2-methoxyphenyl)piperazine (o-OMe-PhP) and 1,2,3,4-tetrahydroisoquinoline (THIQ) as amine pharmacophores. Modifications of the spacer structure included introduction of flexible penta- and hexamethylene chains as well as partly constrained m- and p-xylyl moieties. In general, the new compounds were more active at the 5-HT(1A) than at the 5-HT(7) receptor, and the o-OMe-PhP derivatives displayed higher affinities than their respective THIQ analogs. The spacer modifications had little effect on the observed in vitro activities. Within the o-OMe-PhP series, except for a small binding reduction for ligands containing the m-xylyl moiety, there was no substantial change in the compounds' potency at both receptors, while for the THIQ derivatives a clear structure-activity relationship was visible only for the interaction of the compounds with the 5-HT(7) receptor, which strongly favored flexible analogs.


Focal adhesion kinase: an essential kinase in the regulation of cardiovascular functions.
Recent studies using animal models have demonstrated an important role for FAK in the cardiovascular system. In particular, FAK is essential for angiogenesis in the embryo, functions in heart development and modulates the response of cardiomyocytes to pressure overload in adult mice. FAK function at the cellular level is discussed to provide insight into the mechanisms regulating these biological events and the role of FAK in controlling endothelial junctions and responses to mechanical stimulation are discussed.


Comparison of 3 optical navigation systems for computer-aided maxillofacial surgery.
To compare the accuracy of 3 computer-aided surgery systems for maxillofacial reconstruction. Evaluation of 3 computer-aided surgery systems: StealthStation, VectorVision, and Voxim. The University of California, Davis, Department of Otolaryngology computer-aided surgery laboratory. Four fresh cadaveric heads. Mean target registration error. The StealthStation was the most accurate (mean [SD] target registration error, 1.00 [0.04] mm), followed by VectorVision (1.13 [0.05] mm) and then Voxim (1.34 [0.04] mm). All values met statistical significance (P < .05). Measurable accuracy differences were found among the navigation systems evaluated. The StealthStation was the most accurate. However, the differences are small, and the clinical significance for maxillofacial reconstruction is negligible.


Apneic spells associated with timolol therapy in a neonate.
A 2-week-old premature child with congenital glaucoma secondary to anterior cleavage syndrome was treated with timolol maleate and cyclocryotherapy. The patient had apneic spells of up to 30 seconds that stopped soon after timolol maleate therapy was discontinued. No apnea was seen before timolol maleate administration, and no further spells were noted after subsequent cyclocryotherapy without timolol maleate treatment. Possible central nervous system toxicity of timol maleate or its metabolic by-products in neonates with immature blood-brain barriers was noted.


Post-thyroidectomy hypocalcemia: Is a routine preferable over a selective supplementation?
Comparative studies among protocols for the management of post-total thyroidectomy (TT) hypocalcemia are lacking. We compared the effectiveness of PTH-driven selective supplementation (PD-SS) and routine calcium and calcitriol supplementation with preoperative calcitriol administration in preventing symptomatic hypocalcemia (SH) and readmission. Three-hundred consecutive patients undergoing TT were assigned to 3 groups: the PD-SS group, the high-dose routine supplementation (HD-RS) group and the low-dose routine supplementation (LD-RS) group. Mean post-operative stay was shorter in HD-RS patients when compared to PD-SS and LD-RS (p < 0.001). Significantly more patients in the PD-SS group experienced SH (p = 0.042). The rate of post-operative hypocalcemia was not significantly different among the groups (p = 0.063). No readmission for SH or hypercalcemia occurred. HD-RS emerged as the most effective treatment to prevent SH, without increasing the risk of readmission for calcitriol-related hypercalcemia. Basing on the present results, HD-RS should be recommended as the preferable protocol.


Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.
Breast cancer radioimmunoscintigraphy targeting MUC1 expression is a growing field of work in nuclear medicine research. PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast tumors. In this study, we report production, quality control and preclinical qualifications of a copper-64 labeled PR81 for PET imaging of breast cancer. PR81 was conjugated with DOTA-NHS-ester and purified by molecular filtration followed by chelate:mAb ratio determination by spectrophotometric method. DOTA-PR81 was labeled with (64)Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the (64)Cu-DOTA-PR81 and (64)Cu-DOTA-hIgG was evaluated in BALB/c mice with breast carcinoma tumors using tissue counting and imaging. The radiochemical purity of radioimmunoconjugate was >95±1.9% (ITLC) (specific activity; 4.6 μCi/μg). The average number of chelators per antibody was 3.4±0.3:1. The (64)Cu-DOTA-PR81 showed immunoreactivity towards MUC1 antigen and MCF7 cell line with significant in vitro stability (>89% in PBS and 78±0.5% in human serum) over 48 h. Maximum internalized activity of radiolabeled PR81 in 4-8 h was 81.5%. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity compared to control probes. The results showed that (64)Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology.


Krüppel-like factor 5: a novel biomarker for lymph node metastasis and recurrence in supraglottic squamous cell laryngeal carcinoma.
Krüppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is involved in important biological processes including cell transformation, proliferation, and carcinogenesis. However, its clinical significance has remained largely unknown in laryngeal cancer. Here, specimens from 144 patients with laryngeal tumors were investigated by immunohistochemical staining for KLF5, integrin-linked kinase (ILK), and E-cadherin expressions. A clinicopathological study revealed that the KLF5 expression level in tumor cells was significantly correlated with lymph node metastasis (P < 0.05) and local recurrence (P < 0.05). In addition, KLF5, ILK, and E-cadherin (epithelial-mesenchymal transition (EMT) biomarker) expressions were correlated with each other. These findings suggest that KLF5 may be an epithelial-mesenchymal transition-associated biomarker in human laryngeal carcinomas and play important roles in the progression of laryngeal carcinomas. KLF5 immunoreactivity is therefore considered a potential lymph node metastasis and recurrence factor in human laryngeal cancers. In addition, the KLF5-mediated pathway is a potential target for elimination of laryngeal cancer in the future.


Patient-Reported Outcomes Accurately Measure the Value of an Enhanced Recovery Program in Liver Surgery.
Enhanced recovery (ER) pathways have become increasingly integrated into surgical practice. Studies that compare ER and traditional pathways often focus on outcomes confined to inpatient hospitalization and rarely assess a patient's functional recovery. The aim of this study was to compare functional outcomes for patients treated on an Enhanced Recovery in Liver Surgery (ERLS) pathway vs a traditional pathway. One hundred and eighteen hepatectomy patients rated symptom severity and life interference using the validated MD Anderson Symptom Inventory preoperatively and postoperatively at every outpatient visit until 31 days after surgery. The ERLS protocol included patient education, narcotic-sparing anesthesia and analgesia, diet advancement, restrictive fluid administration, early ambulation, and avoidance of drains and tubes. Seventy-five ERLS pathway patients were clinically comparable with 43 patients simultaneously treated on a traditional pathway. The ERLS patients reported lower immediate postoperative pain scores and experienced fewer complications and decreased length of stay. As measured by symptom burden on life interference, ERLS patients were more likely to return to baseline functional status in a shorter time interval. The only independent predictor of faster return to baseline interference levels was treatment on an ERLS pathway (p = 0.021; odds ratio = 2.62). In addition, ERLS pathway patients were more likely to return to intended oncologic therapy (95% vs 87%) at a shorter time interval compared to patients on the traditional pathway (44.7 vs 60.2 days). In oncologic liver surgery, enhanced recovery's primary mechanism of action is reduction in life interference by postoperative surgical symptoms, allowing patients to return sooner to normal function and adjuvant cancer therapies.


The effect of gestational age on the effective elastance of the respiratory system in neonates.
We measured the effective elastance of the respiratory system (E'RS) in 38 "healthy" neonates, gestational ages ranging from 28-42 weeks. E'RS was calculated by dividing the inspiratory pressure generated after nasal occlusion by the tidal volume of the breath preceding occlusion (E'RS = P/VT). E'RS decreased from 790 +/- 0.070 cm H2O/liter at 30.4 +/- 0.4 weeks of gestation to 520 +/- 0.030 at 34.5 +/- 0.3 weeks (P less than 0.01); then to 340 +/- 0.020 at 40 +/- 0.2 weeks (P less than 0.01). E'RS corrected for lung volume ("specific" E'RS) were 32 +/- 2,32 +/- 4, and 28 +/- 2 cm H2O at the above gestational ages, respectively (P greater than 0.05). We suggest: (1) the increased E'RS observed in preterm infants is lung volume dependent. Changes in lung volume may alter the geometry of the thorax, and therefore, the force/length characteristics of the respiratory muscles; (2) this increased E'RS is not of much benefit to preterm infants who have little respiratory stability when E'RS is maximum; and (3) if E'RS is an index of mechanical stability, apnea in preterm infants is independent of the mechanical properties of the respiratory system.


Relationships between surface roughness/stiffness of chitosan coatings and fabrication of corneal keratocyte spheroids: Effect of degree of deacetylation.
Fabrication of the cell spheroids from corneal keratocytes has important implications to the advance in tissue engineering while stimulation from the interface of a biopolymer coating has the ability to modulate this event. This study aims to investigate the dependence of keratocyte migration, proliferation, and differentiation on the surface roughness/stiffness of the chitosan coatings through modifications by degree of deacetylation (DD). After a series of deacetylation process, chitosan coatings with increasing DD exhibited significantly decreased surface roughness and increased surface stiffness. Relationships between the behaviors of rabbit corneal keratocytes (RCKs) and biopolymer coatings with varying DDs (between 75% and 96%) were also found during in vitro cultivation. Both the surface roughness increase and stiffness decrease could lead to enhanced cell migration, which is the main driving force for the early stage spheroid formation on chitosan substrates (e.g., within 8h). With these stimulations from the substrate interfaces, the size and morphology of RCK spheroids were greatly affected by the DD of chitosan. When fabricated on a lowered DD of chitosan material, the spheroids had a larger size with abundant extracellular matrix produced around the cells. At a later stage of spheroid cultivation (e.g., 5 days), significantly higher amount of RCKs on chitosan coatings was noted with increasing DD, indicating the substrate interface effects on cell proliferation. The keratocan expression of RCK spheroids grown on a lowered DD of chitosan was up-regulated, suggesting that both the surface roughness increase and stiffness decrease may facilitate the microenvironment for preservation of cellular phenotype. Overall, our work contributes to the scientific understanding of the keratocyte behaviors and spheroid fabrications in response to DD-mediated surface roughness/stiffness of chitosan coatings.


Comparison of Cr(VI) adsorption and photocatalytic reduction efficiency using leonardite powder.
It is very important to treat Cr(VI) from the aquatic environment due to its toxic and harmful effects. Conventional treatment methodology involving biological pathways is generally ineffective for wastewater containing Cr(VI). Therefore, it is necessary to develop environmentally friendly and economical methods to remove Cr(VI) from the aquatic environment. In this study, leonardite, which is a natural mineral that has no harmful effects on the environment, was used for Cr(VI) removal. Leonardite was used in both adsorption and photocatalytic treatment systems by only pulverizing without any chemical treatment. Characterizations of leonardite were obtained using X-ray fluorescence (XRF), fouirer transform infrared spektrofotometre (FTIR), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX) analyses methods. The effects of solution pH (2-10), particle size (45-300 μm), adsorbent dose (0.25-3 g/L), and initial concentration (10-30 mg/L) on Cr(VI) removal efficiency were investigated in both adsorption and photocatalytic experiments. In the adsorption process, a complete removal efficiency (100%) was obtained for 3 g/L of adsorbent dose with an initial Cr(VI) concentration of 10 mg/L at pH 2 for 2 h. In the photocatalytic process, 100% removal efficiency of Cr(VI) was obtained when four times less adsorbent dosage was used under the same conditions. In addition, the reuse of leonardite powder was also investigated under optimum experimental conditions. Leonardite powder preserved approximately 70% of its activity in the photocatalytic process while it lost 50% of its activity after 5 reuses in adsorption process.


Endostatin levels and the risk of subsequent preeclampsia.
To evaluate endostatin, an anti-angiogenic factor, in relation to the risk of preeclampsia (PE). In this case control study, serum samples were collected at 11-17 weeks and 18-26 weeks' gestation. Endostatin levels were expressed as adjusted multiples of the median (MoM). Logistic regression was used to calculate adjusted odds ratios (aORs) for the prediction of PE. A total of 77 women with PE and 150 controls were studied. Endostatin levels were significantly higher in women with PE compared to controls in both the first and the second trimester. At a cut-off level of 75th percentile of endostatin MoMs, the aORs for PE were 1.33 (95% confidence interval [CI], 0.68-2.58) at 11-17 weeks and 1.77 (95% CI, 0.94-3.34) at 18-26 weeks, after adjustment for ethnicity and chronic hypertension. The aORs for early-onset PE were 3.51 (95% CI, 1.18-10.43) at 11-17 weeks and 2.17 (95% CI, 0.67-7.06) at 18-26 weeks. Higher endostatin levels are associated with an increased risk of early onset PE. Endostatin alone, however, has a poor predictive value for clinical usefulness.


Integration of entomopathogenic fungi and eco-friendly insecticides for management of red palm weevil, Rhynchophorus ferrugineus (Olivier).
Red palm weevil (Rhynchophorus ferrugineus) is a voracious pest of date palm worldwide. Pakistan ranks sixth in date palm production globally. Losses to date palm plantations in Pakistan sometimes surpass 10%-20%. Most of the traditional management strategies used by farmers have been found insignificant to combat this voracious pest. The entomopathogenic fungi, Beauveria bassiana [QA-3(L) and QA-3(H)] and insecticides, Nitenpyram (Active 10% SL) [NIT (L) and NIT (H)] were applied to larval (2nd, 4th, and 6th), pupal and adult stages of R. ferrugienus. Integration or alone application of fungi with insecticides at different concentration under laboratory conditions. Combined application was depicted additive and synergistic interactions. Contrarily, highest cumulative mortality (100%) was recorded in 2nd instar larvae as compared to later instar larvae at combined application. The maximum pupal and adult mortality remained 89% and 66% respectively after treatment with [QA-3 (H) + NIT (L)]. The combination of B. bassiana at higher concentration whereas Nitenpyram at lower dose was found more lethal to larvae, pupae and adults of R. ferrugineus. This signifies the need of combining B. bassiana and bio-rational insecticides that can reduce the cost of management with least harm to environment and natural enemies.


CD20-positive primary nasal peripheral T-cell lymphoma: An analysis of one case and review of the literature.
CD20-positive T-cell lymphoma (TCL) is a very rare disease entity that is associated with the co-expressions of a range of T cell lineage makers, such as, CD2, CD3, CD5, or CD7, and CD20. The biological and clinical significance of CD20 antigen expressed in TCL has been unclear. Here, we are reporting an unusual case of CD20-positive primary nasal peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a 62-year-old female with both peripheral blood (PB) and bone marrow (BM) involvement. Flow cytometry (FC) analysis revealed CD20+ lymphoma cells in PB, BM, and lymph node (LN) and was consistent with pathological findings. FC immunophenotyping was proved of great diagnostic contribution.


The jammed Küntscher nail: a method of releasing the nail and report of a case.
A case of jamming of a Küntscher nail is presented and the technique of longitudinal splitting of the femur by which the nail was released is described. The possible causes of jamming are summarized and some precautions are suggested to avoid this dilemma. Other methods of dealing with a jammed nail are reviewed.


Polybrominated diphenyl ethers in early pregnancy and preterm birth: Findings from the NICHD Fetal Growth Studies.
Studies suggest associations between exposure to individual polybrominated diphenyl ethers (PBDEs) with preterm birth (PTB) and shorter gestational age. Little is known about exposure to PBDE mixtures and these outcomes. We evaluated associations of multiple PBDEs in early pregnancy with gestational age at delivery and PTB. Data were collected from 2046 women without obesity and 396 women with obesity from the NICHD Fetal Growth Studies, who had early pregnancy plasma PBDEs concentrations and gestational age at delivery. PTB was defined as < 37 weeks of gestation at delivery and further categorized into subtypes (late or very early/moderate; spontaneous or medically indicated). We applied (1) generalized linear models (GLM); (2) principal component analysis (PCA); and (3) Bayesian Kernel Machine Regression (BKMR) to evaluate the individual and joint associations of log-transformed PBDE concentrations with gestational age at delivery and PTB, adjusting for potential confounders and evaluating effect modifiers. In GLM analyses, a 1-standard deviation (SD) increase in log-PBDE 153 was associated with shorter gestational age at delivery [adjusted β (95% CI) = -0.19 (-0.31, -0.06) weeks] among women without obesity. In PCA analyses, 1-SD increase in the principal component summarizing most of PBDE 153 variability was associated with shorter gestational age at delivery [adjusted β (95% CI) = -0.18 (-0.30, -0.06) weeks], very early/moderate PTB [adjusted OR (95% CI) = 1.91 (1.19, 3.07)], and spontaneous PTB [adjusted OR (95% CI) = 1.34 (1.00, 1.80)] among women without obesity. Associations were stronger among non-Hispanic Black women, women with BMI ranging between 25 and 30 kg/m2, and women who were ≥35 years old among those without obesity. In BKMR analyses, a suggestive inverse association between PBDE 153 and gestational age at delivery, and an inverse U-shaped association between PBDE 154 and gestational age at delivery were observed in women without obesity. No statistically significant association of PBDEs and gestational age or PTB was observed among women with obesity. PBDEs, specifically PBDE 153, were associated with shorter gestation and higher risk of certain PTB subtypes among pregnant women without obesity.


Predictors of Multi-Vessel Identification, Outcome, and Optimal Surgical Timing for Microvascular Decompression in Hemifacial Spasm.
Hemifacial spasm (HFS) is a disabling condition that imposes significant burden upon patients. Microvascular decompression (MVD) surgery is the most effective and long-lasting treatment for HFS, but outcomes following this surgery may vary based on a variety of clinical and operative factors. A more thorough understanding of the variables that impact patient outcome after MVD surgery is needed. A systematic review and meta-analysis of Medline, Embase, and Central was conducted (n = 2108 screened; n = 86 included) with the goal of determining the impact of the following variables on outcome: duration of disease, geographic location, intraoperative use of an endoscope, and intraoperative finding of single versus multi-vessel neurovascular compression. Most cases of hemifacial spasm occur on the left side (53.9%, p < 0.001) and are more common in women than men (66.5% versus 33.5%, p < 0.0001). The offending vessel frequencies were: 40.8% anterior inferior cerebellar artery [AICA], 24.9% posterior inferior cerebellar artery [PICA], 17.2% multiple vessels, and 4.7% vertebral artery [VA]. Multiple vessel combinations involved: 26.5% PICA + AICA, 24.6% PICA + VA, 23.1% AICA + VA, and 4.7% AICA + PICA + VA. Relative to the Americas, AICA was less frequent in Europe (p = 0.005), while PICA more frequent in Europe (p = 0.009) and Asia (p < 0.0001). With endoscope assistance, frequency of multiple vessels identified was 31.7% (versus 14.7% with non-endoscopic, p = 0.005), and 27.4% for AICA (43.5% with non-endoscopic, p = 0.003). Spasm improvement was 94.1% near discharge and 96.0% at maximum follow-up. Complications occurred in 16.5% of cases, with spasm recurrence in 2.4%. Greatest frequency of spasm improvement (p < 0.0001) and lowest spasm recurrence rates (p = 0.0005) were reported in series from Asia. For every additional month of pre-operative spasm, the effect size of post-operative improvement decreased (p = 0.04). With every subsequent postoperative month, the effect size of spasm improvement increased (p = 0.0497). The frequency of spasm improvement was significantly higher in series published after 2005 (94.4% versus 97.4%, p = 0.005). Clinical outcomes following MVD for HFS have improved since 2005. Consideration should be given to earlier operation (shorter disease duration) and use of an endoscope may increase detection of multiple offending vessels. Further studies are needed to understand regional differences in culprit vessel incidence and surgical outcomes in the Americas, Europe, and Asia.


Hypertrophy cardiomyopathy: A case of infantile-onset Pompe disease in cardiac magnetic resonance findings.
There are two clinical types of Pompe disease: infantile-onset and late-onset, while the former is much more severe. We reported a typical case of Pompe disease in a 9-month infant who presenting with repeated pneumonia, growth retardation and hypomyotonia, hepatomegaly, accompany with elevated of serum creatine kinase and liver transaminase. Cardiac magnetic resonance (CMR) showed marked hypertrophy of both ventricles including the septum, and extensive myocardial late enhancement. The gene testing result was confirmed the disease finaly. Familiarity with the imaging findings can aid in making an accurate diagnosis and determining the appropriate treatment.


Crushing the circumflex stent arm in a case of proximal peristent restenosis after kissing stent for the distal left main disease.
We present a case of proximal peristent restenosis after kissing stenting in the distal left main lesion. The patient was treated by crushing the proximal portion of the circumflex stent after passing through the stent arm in the left anterior descending.


Prognostic value of myocardial hypoperfusion indexes in patients with suspected or known coronary artery disease.
We evaluated the prognostic value of exercise 201Tl indexes of myocardial hypoperfusion in patients with suspected or known coronary artery disease. Patients were divided into two groups: group I consisted of 332 patients with diagnostic electrocardiographic stress test results and group II consisted of 144 patients with nondiagnostic (inadequate or uninterpretable) stress electrocardiograms. At the 2-year follow-up, 20 hard events (16 cardiac deaths and 4 nonfatal myocardial infarctions) and 80 soft events (coronary revascularization procedures) occurred in group I. Considering total events, thallium imaging provided significant prognostic information in addition to clinical and exercise stress test data in the total study population (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, thallium imaging added incremental prognostic value only in those with positive electrocardiographic stress test results (p < 0.01). When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). In group II at the end of follow-up, 15 hard and 39 soft events had occurred. In these patients occurrence of total (p < 0.001), hard (p < 0.05), and soft (p < 0.001) events was higher in those with abnormal thallium scintigraphic results than in those without. Moreover, no clinical and exercise variable, except history of myocardial infarction, was significantly related to outcome, whereas both indexes of extent and severity of hypoperfusion were significant. The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give unique prognostic information in patients with nondiagnostic electrocardiographic stress test results. Thallium imaging provides incremental prognostic information even in patients with diagnostic electrocardiographic stress test results but not in the low-risk subset of patients without previous infarction who have negative electrocardiographic stress test results.


Generation and characterization of bovine bone marrow-derived macrophage cell line.
Macrophages, as the forefront of innate immune defense, have an important role in the host responses to mycobacterial infection. Therefore, a stable macrophage cell line is needed for future bovine immune system research on the bacterial infection. In this study, we established a bovine macrophage cell line by introducing the human telomerase reverse transcriptase (hTERT) gene into bovine bone marrow-derived macrophages (bBMMs). The TERT-bBMMs cells expressed macrophage surface antigen (CD11b, CD282) and upregulated expression of the cytokines IL-1β, IL-6, IL-10, IL-12, TNF-α in response to bacterial invasion. These results demonstrate that this cell line provide reliable cell model system for future studies on interactions between the bovine macrophages and Mycobacterium tuberculosis.


[Experimental study of mandibular periosteal distraction in rabbits].
To investigate a novel technique for new bone formation--periosteal distraction osteogenesis. A custom made periosteal distraction device was fixed to bilateral surface of the mandible in three rabbits. Periosteal distraction was performed on the left side of the mandible, the right side of the mandible served as the control. The animals were sacrificed at the end of distraction process. All the specimens were X-rayed and histologically examinated. All three animals survived with no obvious complications. Both in mass specimens and X-rays, there showed new bone formation on the distracted side of the mandible. In histological examinations, there was osteoblast-like cell infiltration and bone tissue formation in the distracted area. Periosteal distraction osteogenesis can provide a novel technique for the repair of bone defects.


HIV/AIDS: global trends, global funds and delivery bottlenecks.
Globalization affects all facets of human life, including health and well being. The HIV/AIDS epidemic has highlighted the global nature of human health and welfare and globalization has given rise to a trend toward finding common solutions to global health challenges. Numerous international funds have been set up in recent times to address global health challenges such as HIV. However, despite increasingly large amounts of funding for health initiatives being made available to poorer regions of the world, HIV infection rates and prevalence continue to increase world wide. As a result, the AIDS epidemic is expanding and intensifying globally. Worst affected are undoubtedly the poorer regions of the world as combinations of poverty, disease, famine, political and economic instability and weak health infrastructure exacerbate the severe and far-reaching impacts of the epidemic. One of the major reasons for the apparent ineffectiveness of global interventions is historical weaknesses in the health systems of underdeveloped countries, which contribute to bottlenecks in the distribution and utilisation of funds. Strengthening these health systems, although a vital component in addressing the global epidemic, must however be accompanied by mitigation of other determinants as well. These are intrinsically complex and include social and environmental factors, sexual behaviour, issues of human rights and biological factors, all of which contribute to HIV transmission, progression and mortality. An equally important factor is ensuring an equitable balance between prevention and treatment programmes in order to holistically address the challenges presented by the epidemic.


Malignant fibrous histiocytoma of the spine causing spinal neural foramen widening.
A case with a clinical picture of a chronic low back pain radiating to both lumbar regions caused by malignant fibrous histiocytoma is reported. Radiological, surgical and histopathological findings and treatment of this rare case are discussed.


Prevalence of physical activity in European adults - Compliance with the World Health Organization's physical activity guidelines.
Adults are recommended to engage in at least 150 min/week of moderate-to-vigorous physical activity (PA). This study aimed to examine the level of compliance with PA recommendations among European adults. Using data from European Social Survey round 6, PA self-report data was collected from 52,936 European adults from 29 countries in 2012. Meeting PA guidelines was assessed using World Health Organization criteria. 61.47% (60.77% male, 62.05% female) of European adults reported to be engaged in moderate to vigorous PA at least 30 min on 5 or more days per week. The likelihood of achieving the PA recommended levels was higher among respondents older than 18-24. For those aged 45-64 years the likelihood increased 65% (OR=1.65, 95% CI: 1.51-1.82, p<0.001) and 112% (OR=2.12, 95% CI: 1.94-2.32, p<0.001) for males and females, respectively. Those who were high school graduates were more likely to report achieving the recommended PA levels than those with less than high school education (males: OR=1.19, 95% CI: 1.12-1.27, p<0.001; females: OR=1.13, 95% CI: 1.06-1.20, p<0.001). Although about 60% of European adults reported achieving the recommended levels of PA, there is much room for improvement among European adults, particularly among relatively inactive subgroups.


Nickel hyperaccumulation in New Caledonian Hybanthus (Violaceae) and occurrence of nickel-rich phloem in Hybanthus austrocaledonicus.
Hybanthus austrocaledonicus (Violaceae) is a nickel (Ni) hyperaccumulator endemic to New Caledonia. One of the specimens stored at the local herbarium had a strip of bark with a remarkably green phloem tissue attached to the sheet containing over 4 wt% Ni. This study aimed to collect field samples from the original H. austrocaledonicus locality to confirm the nature of the green 'nickel-rich phloem' in this taxon and to systematically assess the occurrence of Ni hyperaccumulation in H. austrocaledonicus and Hybanthus caledonicus populations. X-ray fluorescence spectroscopy scanning of all collections of the genus Hybanthus (236 specimens) was undertaken at the Herbarium of New Caledonia to reveal incidences of Ni accumulation in populations of H. austrocaledonicus and H. caledonicus. In parallel, micro-analytical investigations were performed via synchrotron X-ray fluorescence microscopy (XFM) and scanning electron microscopy with X-ray microanalysis (SEM-EDS). The extensive scanning demonstrated that Ni hyperaccumulation is not a characteristic common to all populations in the endemic Hybanthus species. Synchrotron XFM revealed that Ni was exclusively concentrated in the epidermal cells of the leaf blade and petiole, conforming with the majority of (tropical) Ni hyperaccumulator plants studied to date. SEM-EDS of freeze-dried and frozen-hydrated samples revealed the presence of dense solid deposits in the phloem bundles that contained >8 wt% nickel. The occurrence of extremely Ni-rich green phloem tissues appears to be a characteristic feature of tropical Ni hyperaccumulator plants.


Calcium ions and the regulation of NAD+-linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues.
The effects of Ca2+ on the activity of isocitrate dehydrogenase (NAD+) in extracts of rat heart mitochondria were explored in the presence of MgCl2 by using EGTA buffers. In the absence of ADP, Ca2+ (about 30 micrometer) resulted in a slight increase in apparent Km for threo-Ds-isocitrate; in the presence of ADP, Ca2+ (about 25 micrometer) greatly lowered the apparent Km for threo-Ds-isocitrate from 227 micrometer to 53 micrometer without changing the maximum velocity. At 100 micrometer-threo-Ds-isocitrate and 1 mM-ADP, there was an 8-fold activation by Ca2+, with a Km for Ca2+ of 1.2 micrometer. This activation was also observed with Sr2+ (Km 3.1 micrometer), but not with Mn2+ (at concentrations below 2.5 micrometer). Similar effects of Ca2+ were also observed on isocitrate dehydrogenase (NAD+) activity in extracts of mitochondria from liver, kidney, brown adipose tissue and white adipose tissue of the rat. The possible regulatory role of changes in the intramitochondrial concentration of Ca2+ is discussed.


Effect size estimation: methods and examples.
While the p-value will tell the reader a study's results are statistically significant, it does not provide any information about the practical or clinical importance of the findings. Furthermore, p-values are influenced by sample size. They are more likely to be significant when sample size is large and less likely if the sample is small. Effect size estimates, on the other hand, are not sensitive to sample size and provide information about the direction and strength of the relationship between variables (e.g., a treatment and an outcome). In addition to providing valuable clinical information about study findings, effect size estimates can provide a common metric to compare results across studies. Despite their usefulness, effect size estimates are often not reported as part of the research results. Consequently, effect sizes often have to be calculated based on summary and test statistics reported in research articles. This article provides the formulas utilized to directly calculate common effective size estimates using summary statistics reported in research studies, as well as methods to more indirectly estimate these effect sizes when basis summary statistics are not reported. In addition we present formulas to compute the corresponding confidence interval for each effect size.


Auditory Brainstem Response in Patients of Tinnitus with Sensorineural Hearing Loss.
Tinnitus is defined as phantom auditory perception without corresponding acoustic or mechanical correlates in cochlea. Existing evidence on its physiological basis is wide ranging, but its origin is still under exploration. To objectify this subjective phenomenon, Auditory Brainstem response test is used. The primary purpose of our study was to ascertain any significant difference in auditory electrophysiological response parameters in sensorineural hearing loss with tinnitus group when compared to controls (normal hearing subjects). Secondary aim was to find correlation of these parameters with degree of hearing loss and severity of tinnitus. This was a case control study conducted in the department of Otorhinolaryngology in tertiary care hospital, New Delhi over a period of one and half years. The study comprised of one hundred and sixty patients out of which, fifty-five patients were sensorineural hearing loss with tinnitus and fifty-one patients were normal hearing subjects. General medical and audiological assessment was done. Significant increase in latency of wave I, III, V and increase in inter peak latency of I-III, III-V, I-V was observed in tinnitus with sensorineural hearing loss group when compared to controls. It was reported that on increasing degree of hearing loss, there was increase in latency of wave I, III, V and increase in inter peak latency of wave I-III, I-V in the former group.


MicroRNA expression profiling in peritoneal fibrosis.
Peritoneal fibrosis (PF) is an intractable complication leading to peritoneal membrane failure in peritoneal dialysis (PD). The aim of this study was to identify microRNAs (miRNAs) involved in PF. Peritoneal tissue from a PF rat model was screened for miRNA expression using microarray analysis. The expression levels of differentially expressed miRNAs were evaluated in serum and drained dialysate and associated with peritoneal membrane functions, as measured by the peritoneal equilibrium test in 33 PD patients. Furthermore, an miRNA inhibitor (anti-miRNA-21-5p locked nucleic acid (LNA): anti-miRNA-21-LNA) was intraperitoneally injected to PF model mice to investigate its effects on PF. The initial profiling study of PF rat peritoneal tissue identified 6 miRNAs (miRNA-142-3p, miRNA-21-5p, miRNA-221-3p, miRNA-223-3p, miRNA-34a-5p, and miRNA-327) whose expression was increased more than 2-fold and no miRNAs whose expression was decreased more than half. Among them, serum levels of miRNA-21-5p, miRNA-221-3p, and miRNA-327 and drained dialysate levels of miRNA-221-3p and miRNA-34a-5p were significantly correlated with peritoneal membrane functions in PD patients. Anti-miRNA-21-LNA significantly inhibited miRNA-21-5p expression in the PF mouse peritoneum, inhibited peritoneal fibrous thickening, and maintained peritoneal membrane functions. These results suggest that several miRNAs are involved in PF and that they may be useful as novel diagnostic biomarkers and therapeutic targets for PF.


Quinine- and quinidine platelet antibodies can react with GPIIb/IIIa.
Quinine- and quinidine-dependent antiplatelet antibodies are generally believed to bind to the membrane glycoprotein complex, GPIb/IX. However, we and others have found that some drug-dependent antibodies bind to platelets from patients with the Bernard-Soulier syndrome which lack these glycoproteins. We therefore studied the reactions of a group of these antibodies with normal and Bernard-Soulier platelets and their membrane proteins. As indicated by rosette formation of the sensitized platelets around protein A-Sepharose beads, two quinine- and two quinidine-dependent antibodies reacted with both normal and Bernard-Soulier syndrome platelets at a high (300 microM) concentration of drug. At a pharmacologic drug concentration (10 microM), all four antibodies reacted with normal platelets but only the two quinine-induced antibodies reacted with Bernard-Soulier platelets. Immunoprecipitation studies with solubilized, tritium-labelled normal platelets, at both high and low drug concentrations, showed that each of the four antibodies precipitated proteins corresponding to GPIb and GPIX. Fainter bands corresponding to glycoproteins IIb and IIIa, which do not label well with tritium, were also detected. With radioiodinated normal platelets, it was found that each of the four antibodies was capable of precipitating GPIIb/IIIa, but only in the presence of drug. The four antibodies also promoted drug-dependent precipitation of GPIIb and GPIIIa from lysates of radioiodinated Bernard-Soulier platelets. The two quinine-dependent antibodies precipitated these glycoproteins at both high and low drug concentrations, while the quinidine-dependent antibodies reacted much more strongly at the higher drug concentration. Precipitation of GPIb/IX was not observed with BSS platelets. Absorption of a quinine-induced antibody with Bernard-Soulier platelets in the presence of drug eliminated its ability to precipitate GPIIb and GPIIIa. However, the absorbed antibody retained the ability to precipitate GPIb from solubilized normal platelets. Thus, at least two drug-dependent antibodies were present, one specific for GPIb/IX and the other for GPIIb/IIIa. These findings indicate that glycoproteins IIb and/or IIIa, in addition to the GPIb/IX complex, can serve as targets for drug-dependent antibodies in both intact and detergent-solubilized platelet preparations.


A comparison of microtensile bond strengths of several dentin bonding systems to primary and permanent dentin.
Limited information exists with regard to the adhesive ability of glass ionomer cements (GIC) and recently developed resin-based dentin bond systems to primary dentin. The aim of this study was to compare the microtensile bond strength of a conventional GIC (Fuji IX), a resin-modified GIC (Fuji II LC), and two resin-based dentin adhesives (Prime and Bond NT with NRC and Single Bond). The bonded interfaces were also observed using field emission electron microscopy(FE-SEM). Microtensile bond test specimens were prepared on superficial dentin of primary and permanent molars. The specimens were bonded according to each manufacturer's instructions except for Prime and Bond NT/NRC which used Silux Plus resin composite instead of Dyract. Hour-glass shaped specimens were created (diameter of 1.2+/-0.02 mm) and stressed in tension at a crosshead speed of 1mm/min. Results were analyzed using two-way ANOVA and LSD test, fracture modes were analyzed using the Mann-Whitney U-test and Kruskall-Wallis test. Twelve specimens were prepared for each material on primary and permanent dentin. Samples were prepared in the same manner, then critical point dried, fractured and sputter-coated for the FE-SEM observations. Two-way ANOVA showed the overall bond strengths were greater for the permanent dentin compared with primary dentin. However, for individual material comparisons no differences among the bond strengths to primary and permanent dentin for Fuji IX (9.7, 12.2 MPa), Fuji II LC (16, 20.1 MPa), Prime & Bond NT/NRC (18.1, 21.6 MPa) and Single Bond (18.2, 21.6 MPa), were detected. However, Fuji IX bond strengths were significantly lower than the other systems tested when bonded to either primary or permanent dentin (p<0.05). Failure mode showed cohesive failure of GIC and mostly adhesive failure for the resin-based adhesives. The FE-SEM observations showed hybrid-like layer formation for the GIC materials and hybrid layer formation for the resin-based adhesives. The materials tested would be suitable for bonding to either primary or permanent dentin, but the resin-modified GIC or resin-based systems are likely to provide a stronger bond than the conventional GIC, Fuji IX.


Voice-onset time as a clue to the nature of Broca speech errors.
Blumstein, Cooper, Goodglass, Statlender, and Gottleib (Brain and Language, 9, 153-170 (1980] attempt to determine by an examination of the VOTs of aphasic speakers whether Broca's aphasics make phonemic substitutions in addition to their well-known phonetic errors. There are a number of problems with this study, mostly due to an apparent failure to fully appreciate the fact that VOT is a cover term for several acoustic features. It is suggested that VOT measurement in any given position in a word cannot solve this problem and that future studies should include glottographic observations as well as VOT measurements made in all positions in the word.


The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.
A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 μIU/mL in wk. 0, to 119 ± 19 μIU/mL (P = 0.015) and 117 ± 15 μIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect. Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.


Can patients detect peri‑implant mucosal inflammation? Results from a multicentre randomized trial.
The objective of this study was to compare patient-reported outcomes (PROs) of peri‑implant soft tissue inflammation and aesthetics around single-tooth implants in the anterior maxillary region with three different implant-abutment interface designs. Participants were randomized to one of three different types of implant-abutment interface designs [Conical (CI), flat-to-flat (FI), and Platform Switched (PS)]. Implants and provisional crowns with prefabricated titanium abutments were placed 5 months following extraction and/or ridge augmentation. Permanent ceramic crowns with zirconia abutments were placed after 12 weeks. To assess PROs, appearance and inflammation questionnaires were completed from provisional crown placement to the 3-year follow-up. Tooth appearance at the 3-year follow-up revealed a difference amongst CI, FI and PS implants (p=0.049; Kruskal-Wallis test). PS was rated better than FI (p=0.047) at 1 year for appearance of soft-tissue and satisfaction with colour. There were no differences for self-consciousness, smile and pain/discomfort while eating/hard food items. Although participants tended to rate the health of mucosa around PS implants as slighty better than the other two implant systems, the differences were minimal and inconsistent. Thus, patient satisfaction in terms self-perceived gingival health and esthetics was high for all 3 systems tested, suggesting that patients are unable to detect mucosal inflammation. Patients find it difficult to perceive mucosal inflammation; hence, it is recommended that patients attend implant follow-up visits, even if they do not perceive inflammation. The study suggests that there is a relationship between the PROs and the clinical outcomes of tested implants.


Aberrant DNA methylation in the pathogenesis of atherosclerosis.
Atherosclerosis, a multifactorial disease of large- and intermediate-sized arteries, is characterized by the accumulation of lipids and the proliferation of arterial smooth muscle cells, chronic inflammatory cells, and fibrous materials. DNA methylation involves inherent and acquired gene transcription changes, which occur independently of the DNA sequence. DNA methylation in the genome plays a major role in the development and progression of atherosclerosis. DNA methylation is a distinct and crucial mechanism that regulates genes governing cell proliferation, thereby linking environmental insults with gene regulation. DNA methyltransferases are crucial in maintaining endothelial cell integrity, promoting smooth muscle cell proliferation, and inducing the formation of arteriosclerosis in animal models. These enzymes, which influence DNA methylation in vascular cells, may be utilized to develop new diagnoses and treatments for atherosclerosis-related diseases. In this review, we focus on recent advances in the description and functional interpretation of the DNA methylome of cells and tissues involved in atherosclerosis. We also discuss the regulatory mechanism and the involvement of DNA methylation in the development and pathogenesis of atherosclerosis.


Comparison of GnRH agonists and antagonists in unselected IVF/ICSI patients treated with different controlled ovarian hyperstimulation protocols: a matched study.
To evaluate the results of the use of GnRH antagonist (GnRHant) and GnRH analog (GnRHa) in two matched groups of unselected IVF/ICSI patients in a retrospective matched pair analysis. Patients (n=52) were stimulated with human menopausal gonadotropin (hMG) and/or recombinant FSH (rFSH). In Group I (n=26) a daily dose of 0.25mg of Cetrorelix (GnRHant) was administered when follicles reached a diameter of > or = 14 mm. Patients in Group II (n=26) were first desensitized with GnRHa triptorelin long protocol, which was continued during the gonadotropins treatment until the induction of ovulation. In both groups, serum LH levels remained low during the stimulation. The mean length of stimulation, and the dose of FSH required per patient were similar in both groups. The mean E2 level on day of hCG administration was significantly higher in the patients of Group II (2076+/-1430 versus 1145+/-605 pg/ml), however, a progressive increase in serum E2 concentration during the cycle was noted in both groups. A median of 5.38 and 6.34 mature oocytes per patient was obtained, and the fertilization rate was 59.3% in Group I and 63.6% in Group II. Pregnancy rate (PR) were better in Group II (15 versus 5%), and no severe or moderate ovarian hyperstimulation syndrome (OHSS) occurred. GnRHant and GnRHa provide comparable results in unselected patients, while GnRHant allows a higher flexibility in the treatment.


Simultaneous determination of sulphamerazine, sulphamethazine and sulphadiazine in honey and chicken muscle by a new monoclonal antibody-based fluorescence polarisation immunoassay.
A new monoclonal antibody (Mab) against sulphamerazine (SMR) was produced and a fluorescence polarisation immunoassay (FPIA) based on the Mab was developed and optimized for the simultaneous qualitative screening of SMR, sulphamethazine (SMZ) and sulphadiazine (SDZ). The Mab, raised from mice immunized with SMR, was bound to bovine serum albumin (BSA) using glutaraldehyde as the coupling reagent. Fluorescein-labelled SMR and SMZ (tracer) were synthesized and purified by thin layer chromatography (TLC). Cross-reactivities below 3.6% were displayed in the optimized FPIA for another 14 sulphonamides when both tracers were employed. The limits of detection (LOD) were 0.9 ng g(-1) for SMR, 2 ng g(-1) for SMZ and 3.1 ng g(-1) for SDZ. Analysis of SMR, SMZ and SDZ fortified chicken muscle and honey samples by the FPIA showed average recoveries of 86-131% with a standard deviation (SD) of 4.6-32. Comparative analyses of a SMZ-treated chicken muscle sample by both FPIA and high performance liquid chromatograph (HPLC) showed a good correlation (r = 0.9991). The study demonstrates the practical application of FPIA in screening chicken muscle and honey samples for sulphonamides residues.


Pregnant women exercise at a higher intensity during 30 min of self-paced cycling compared with walking during late gestation: implications for 2 h postprandial glucose levels.
To compare the effect of an acute 30-min bout of self-paced stationary cycling (SC) with treadmill walking (TW) or a resting control (CON) on maternal blood glucose, insulin and metabolic responses during pregnancy. Twelve healthy women at 29.9±2.4 (mean±SD) weeks gestation consumed a 75 g carbohydrate drink as part of an oral glucose tolerance test (OGTT) following 30 min of SC, TW or CON. Blood was sampled before and after exercise, and for 2 h in response to the OGTT for the determination of glucose and insulin. Exercise intensity was monitored and enjoyment of TW and SC was assessed post-exercise. Women selectively worked harder in SC compared with TW, with a higher maternal heart rate, rating of perceived exertion, mean oxygen consumption, respiratory exchange ratio, and total energy expenditure during exercise (p<0.05). SC was also associated with significantly lower postprandial blood glucose levels at 120 min following the OGTT (6.9±0.9 mmol∙l(-1)) compared with both CON (8.1±0.7 mmol∙l(-1), p=0.001) and TW (7.8±0.9 mmol∙l(-1), p=0.004) and lower insulin at 120 min post-glucose ingestion compared with TW (p=0.021). Enjoyment was similar between exercise protocols (p=0.437). In late pregnancy, an acute 30 min bout of self-paced SC may be preferable to a matched duration of TW given the additional energy expenditure that can be achieved, which in turn appears beneficial for blunting the glycemic response to glucose ingestion.


Accuracy of a point-of-care ELISA test kit for predicting the presence of protective canine parvovirus and canine distemper virus antibody concentrations in dogs.
Canine parvovirus (CPV) and canine distemper virus (CDV) are highly infectious and often fatal diseases with worldwide distributions, and are important population management considerations in animal shelters. A point-of-care ELISA test kit is available to detect serum antibodies to CPV and CDV, and presumptively to predict protective status. The aim of this study was to determine the diagnostic accuracy of the test compared to CPV hemagglutination inhibition titers and CDV serum neutralization titers determined by a reference laboratory, using sera collected from dogs housed at animal shelters. The ELISA test was used under both field and laboratory conditions and duplicate specimens were processed using an extra wash step. The test kit yielded accurate results (CPV: sensitivity 92.3%, specificity 93.5%; CDV: sensitivity 75.7%, specificity 91.8%) under field conditions. CDV sensitivity was improved by performing the test under laboratory conditions and using an optical density (OD) meter (laboratory performed 94.0%; OD 88.1%). Point-of-care ELISA testing for serum CPV and CDV antibody titers was demonstrated to be a useful tool for determining antibody status when making decisions regarding the need for CPV and/or CDV vaccination and also in animal shelters for population management.


The application of clinical variable-based nomogram in predicting overall survival in malignant phyllodes tumors of the breast.
Background: We aimed to explore prognostic risk factors in patients with malignant phyllodes tumors (PTs) of the breast and construct a survival prediction model. Methods: The Surveillance, Epidemiology, and End Results database was used to collect information on patients with malignant breast PTs from 2004 to 2015. The patients were randomly divided into training and validation groups using R software. Univariate and multivariate Cox regression analyses were used to screen out independent risk factors. Then, a nomogram model was developed in the training group and validated in the validation group, and the prediction performance and concordance were evaluated. Results: The study included 508 patients with malignant PTs of the breast, including 356 in the training group and 152 in the validation group. Univariate and multivariate Cox proportional hazard regression analyses showed that age, tumor size, tumor stage, regional lymph node metastasis (N), distant metastasis (M) and tumor grade were independent risk factors for the 5-year survival rate of patients with breast PTs in the training group (p < 0.05). These factors were used to construct the nomogram prediction model. The results showed that the C-indices of the training and validation groups were 0.845 (95% confidence interval [CI] 0.802-0.888) and 0.784 (95% CI 0.688-0.880), respectively. The calibration curves of the two groups were close to the ideal 45° reference line and showed good performance and concordance. Receiver operating characteristic and decision curve analysis curves showed that the nomogram has better predictive accuracy than other clinical factors. Conclusion: The nomogram prediction model constructed in this study has good predictive value. It can effectively assess the survival rates of patients with malignant breast PTs, which will aid in the personalized management and treatment of clinical patients.


Comparison of uranium(VI) removal by Shewanella oneidensis MR-1 in flow and batch reactors.
To better understand the interactions among metal contaminants, nutrients, and microorganisms in subsurface fracture-flow systems, biofilms of pure culture of Shewanella oneidensis MR-1 were grown in six fracture-flow reactors (FFRs) of different geometries. The spatial and temporal distribution of uranium and bacteria were examined using a tracer dye (brilliant blue FCF) and microscopy. The results showed that plugging by bacterial cells was dependent on the geometry of the reactor and that biofilms grown in FFRs had a limited U(VI)-reduction capacity. To quantify the U(VI)-reduction capacity of biofilms, batch experiments for U(VI) reduction were performed with repetitive U(VI) additions. U(VI)-reduction rates of stationary phase cultures decreased after each U(VI) addition. After the fourth U(VI) addition, stationary phase cultures treated with U(VI) with and without spent medium yielded gray and black precipitates, respectively. These gray and black U precipitates were analyzed using high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction. Data for randomly selected areas of black precipitates showed that reduced U particles (3-6 nm) were crystalline, whereas gray precipitates were a mixture of crystalline and amorphous solids. Results obtained in this study, including a dramatic limitation of S. oneidensis MR-1 and its biofilms to reduce U(VI) and plugging of FFRs, suggest that alternative organisms should be targeted for stimulation for metal immobilization in subsurface fracture-flow systems.


Alcohol consumption and mortality from aortic disease among Japanese men: The Japan Collaborative Cohort study.
Only a few population-based prospective studies have examined the association between alcohol consumption and abdominal aortic aneurysm, and the results are inconsistent. Moreover, no evidence exists for aortic dissection. We examined the effect of alcohol consumption on risk of mortality from aortic diseases. A total of 34,720 men from the Japan Collaborative Cohort study, aged 40-79 years, without history of cardiovascular disease and cancer at baseline 1988 and 1990 were followed up until the end of 2009 for their mortality and its underlying cause. Hazard ratios of mortality from aortic diseases were estimated according to alcohol consumption categories of never-drinkers, ex-drinkers, regular drinkers of ≤30 g, and >30 g ethanol per day. During the median 17.9-year follow-up period, 45 men died of aortic dissection and 41 men died of abdominal aortic aneurysm. Light to moderate drinkers of ≤30 g ethanol per day had lower risk of mortality from total aortic disease and aortic dissection compared to never-drinkers. The respective multivariable hazard ratios (95% confidence intervals) were 0.46 (0.28-0.76) for total aortic disease and 0.16 (0.05-0.50) for aortic dissection. Heavy drinkers of >30 g ethanol per day did not have reduced risk of mortality from total aortic disease, albeit had risk variation between aortic dissection and abdominal aortic aneurysm. Light to moderate alcohol consumption was associated with reduced mortality from aortic disease among Japanese men.


Diffuse midline glioma in the spinal cord with rapid respiratory deterioration.
Neurogenic acute respiratory failure is usually caused by either infection or vascular insufficiency. We report the case of a patient who developed acute respiratory failure secondary to a spinal tumor. A 32-year-old man, presenting with numbness and muscle weakness in his legs for 2 weeks, was transferred to our hospital with worsening quadriplegia and development of respiratory symptoms. We carried out emergent spinal decompression and initiated steroid pulse therapy, with no resolution of symptoms; a tumor incision biopsy after contrast cervical magnetic resonance imaging revealed an intraspinal tumor with a pathological diagnosis of World Health Organization grade IV glioma. The patient developed bradycardia, severe sepsis, status epilepticus, and cardiopulmonary arrest due to hypoxemia and was treated with chemoradiotherapy under mechanical ventilation. He was later transferred to another hospital for subacute care. Acute respiratory failure caused by spinal tumors is uncommon. However, acute care practitioners should be mindful of neoplastic lesions as a potential cause.


Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL.
Diffuse large B-cell lymphomas (DLBCL) express CD20. CD20 expression is described as negative, weak, or normal as determined by flow cytometry (FCM) and is an important target for the treatment of DLBCL. However, the impact of CD20 levels at onset of the disease on patient prognosis has not been fully elucidated. We analyzed 174 DLBCL cases newly diagnosed between January 1998 and April 2010. The relationship of the association between CD20 levels and patients' backgrounds and prognoses was analyzed using the Kaplan-Meier method and Cox proportional hazard regression. Of the 174 patients, three cases (1.7%) were defined as CD20 negative based on immunohistochemistry (IHC). Although the other 171 cases were positive by IHC, eight cases (4.7%) were defined as negative and 33 cases (19.3%) were defined as weak when analyzed by FCM. Of the 105 patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, those who were CD20 negative (FCM) showed significantly inferior overall (hazard ratios (HR): 6.79, 95% CI: 1.32-34.96, p = 0.04) and progression-free survival (HR: 7.3, 95% CI: 1.49-35.8, p = 0.04) compared to patients who were CD20 normal. Our findings indicate that the CD20 level (FCM) at onset is an independent predictor of the prognosis of patients with DLBCL.


The role of excessive reassurance seeking: An eye tracking study of the indirect effect of social anxiety symptoms on attention bias.
High social anxiety is associated with increased attentional bias, and difficulties disengaging from relevant threat information, though social anxiety may also be associated with avoidance of threat. Few mechanisms of this relationship have been empirically evaluated, whereas theories and treatment manuals implicate avoidance and/or safety behaviors as significant agents of negative reinforcement for anxiety symptoms and search for threat. The current study sought to investigate one safety behavior, excessive reassurance seeking, as a mediator of the relationship between social anxiety and attention bias to disgust facial stimuli. Support was found for our hypotheses, such that social anxiety symptoms had an indirect effect on attention bias to disgust faces through increased reassurance seeking. These results suggest that reassurance seeking may result in disengagement of attention to threat stimuli. Specifically, social anxiety may result in a decreased threshold for negative social cues and therefore seek out reassurance feedback and avoid threatening stimuli. Future studies should test these directly and utilize a prospective design. The current study suggests that reassurance seeking may be involved in the attention bias process, providing additional data for current cognitive theories of social anxiety and additional support for reinforcement patterns of anxiety symptoms.


Risk factors and management of intra-abdominal infection after extended radical gastrectomy.
This study elucidated risk factors and management for intra-abdominal infection after extended radical gastrectomy. From 1988 to 2004, 2,076 patients with gastric cancer underwent extended radical gastrectomy at Taipei Veterans General Hospital. Risk factors for intra-abdominal infection were determined by analyzing clinicopathological factors, operative procedure, combined organ resection, operative time, blood loss, and associated disease(s). Management modalities were summarized. The overall complication rate was 18.7%. Eighty (3.9%) patients were found to have intra-abdominal infections. Age, prolonged operation time, and combined organ resection were the precipitating factors. These patients were categorized into 3 groups: intra-abdominal abscess with adequate drainage, intra-abdominal abscess without anastomotic leakage, and intra-abdominal abscess because of leakage. Adequate drainage was the primary treatment. Mortality rate was 22.5% (18), and the most common cause of mortality was intra-abdominal abscess caused by leakage. Although expert surgical skills can minimize the incidence of intra-abdominal infection, management also requires experience and training.


Altered lipoprotein subclass distribution and PAF-AH activity in subjects with generalized aggressive periodontitis.
In this study, we examined whether the documented increase of plasma triglycerides in patients with generalized aggressive periodontitis (GAgP) is associated with changes in lipoprotein subclass distribution and/or LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) activity. Lipoprotein subclasses were analyzed in whole plasma samples using nuclear magnetic resonance methods. Compared with subjects without periodontitis (NP subjects; n = 12), GAgP subjects (n = 12) had higher plasma levels of large, medium, and small VLDL (35.0 +/- 6.7 vs. 63.1 +/- 9.6 nmol/l; P = 0.025), higher levels of intermediate density lipoprotein (24.8 +/- 11.6 vs. 87.2 +/- 16.6 nmol/l; P = 0.006), lower levels of large LDL (448.3 +/- 48.5 vs. 315.8 +/- 59.4 nmol/l; P = 0.098), and higher levels of small LDL (488.2 +/- 104.2 vs. 946.7 +/- 151.6 nmol/l; P = 0.021). The average size of LDL from NP and GAgP subjects was 21.4 +/- 0.2 and 20.6 +/- 0.3 nm, respectively (P = 0.031). Compared with NP subjects, GAgP subjects had a greater number of circulating LDL particles (961.3 +/- 105.3 vs. 1,349.0 +/- 133.2 nmol/l; P = 0.032). Differences in the plasma levels of large, medium, and small HDL were not statistically significant. NP and GAgP subjects had similar plasma levels of total LDL-associated PAF-AH activity; however, LDL of GAgP subjects contained less PAF-AH activity per microgram of LDL protein (1,458.0 +/- 171.0 and 865.2 +/- 134 pmol/min/microg; P = 0.014). These results indicate that, in general, GAgP subjects have a more atherogenic lipoprotein profile and lower LDL-associated PAF-AH activity than NP subjects. These differences may help explain the increased risk of GAgP subjects for cardiovascular disease.


Spin Lattice Relaxation EPR pO2 Images May Direct the Location of Radiation Tumor Boosts to Enhance Tumor Cure.
Radiation treatment success and high tumor oxygenation and success have been known to be highly correlated. This suggests that radiation therapy guided by images of tumor regions with low oxygenation, oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. Before applying the technique to human subjects, OGRT needs to be tested in animals, most easily in rodents. Electron paramagnetic resonance imaging provides quantitative maps of tissue and tumor oxygen in rodents with 1 mm spatial resolution and 1 torr pO2 resolution at low oxygen levels. The difficulty of using mouse models is their small size and that of their tumors. To overcome this we used XRAD225Cx micro-CT/ therapy system and 3D printed conformal blocks. Radiation is delivered first to a uniform 15% tumor control dose for the whole tumor and then a boost dose to either hypoxic tumor regions or equal volumes of well oxygenated tumor. Delivery of the booster dose used a multiple beam angles to deliver radiation beams whose shape conforms to that of all hypoxic regions or fully avoids those regions. To treat/avoid all hypoxic regions we used individual radiation blocks 3D-printed from acrylonitrile butadiene styrene polymer infused with tungsten particles fabricated immediately after imaging to determine regions with pO2 less than 10 torr. Preliminary results demonstrate the efficacy of the radiation treatment with hypoxic boosts with syngeneic FSa fibrosarcoma tumors in the legs of C3H mice.


Characterisation of the tensile properties of Demineralised Cortical Bone when used as an anterior cruciate ligament allograft.
Graft choice in anterior cruciate ligament (ACL) reconstruction remains controversial and some grafts fail due to inadequate osteointegration. Demineralised cortical bone (DCB) is an osteoinductive collagen-based scaffold. The aim of this study was to measure the tensile properties of DCB from different locations and from different ages, and determine its compatibility with current ACL fixation systems. The tensile properties of DCB manufactured from femur and tibia of young (9 month) and old (2-3 years) sheep was measured to determine the most appropriate graft choice. The ultimate load and stiffness of DCB allograft using two fixation systems, interference screws and sutures tied around screw posts, was measured ex vivo in an ovine ACL reconstruction model. Comparison was made with superficial digital flexor tendon (SDFT) and ovine ACL. DCB derived from young tibia had the highest ultimate load and stiffness of 67.7 ± 10.6 N and 130.2 ± 64.3 N/mm respectively. No DCB fixation system reached the published peak in vivo force through the ovine ACL of 150 N. SDFT fixation with interference screws (308.2 ± 87.3 N) did reach the in vivo threshold but was significantly weaker than ovine ACL (871.0 ± 64.2 N). The tensile properties of DCB were influenced by the donor age and bone. Owing to inferior tensile properties and incompatibility with suspensory fixation devices, this study indicates DCB is inferior to current tendon grafts options for ACL reconstruction.


The correlation of hemoglobin and 28-day mortality in septic patients: secondary data mining using the MIMIC-IV database.
Previous studies found minimal evidence and raised controversy about the link between hemoglobin and 28-day mortality in sepsis patients. As a result, the purpose of this study was to examine the association between hemoglobin and 28-day death in sepsis patients by analyzing the Medical Intensive Care IV (MIMIC-IV) database from 2008 to 2019 at an advanced medical center in Boston, Massachusetts. We extracted 34,916 sepsis patients from the MIMIC-IV retrospective cohort database, using hemoglobin as the exposure variable and 28-day death as the outcome variable, and after adjusting for confounders (demographic indicators, Charlson co-morbidity index, SOFA score, vital signs, medication use status (glucocorticoids, vasoactive drugs, antibiotics, and immunoglobulins, etc.)), we investigated the independent effects of hemoglobin and 28-day risk of death by binary logistic regression as well as two-piecewise linear model, respectively. Hemoglobin levels and 28-day mortality were shown to be non-linearly related.The inflection points were 104 g/L and 128 g/L, respectively. When HGB levels were between 41 and 104 g/L, there was a 10% decrease in the risk of 28-day mortality (OR: 0.90; 95% CI: 0.87 to 0.94, p-value = 0.0001). However, in the range of 104-128 g/L, we did not observe a significant association between hemoglobin and 28-day mortality (OR: 1.17; 95% CI: 1.00 to 1.35, P value = 0.0586). When HGB was in the range of 128-207 g/L, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB (OR: 1.07; 95% CI: 1.01 to 1.15, P value = 0.0424). In patients with sepsis, baseline hemoglobin was related to a U-shaped risk of 28-day death. When HGB was in the range of 12.8-20.7 g/dL, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB.


[Bristow-Latarjet repairs for anterior instability of the shoulder: clinical and radiographic results at mean 8.2 years follow-up].
We reviewed, at a mean follow-up of 8.2 years, clinical and radiographic results after 93 Bristow-Latarjet procedures for anterior instability of the shoulder. There were 84 men and nine female. The average age was 23 years at the time of operative intervention. Forty-four shoulders were on the dominant side. Eighty patients practiced sports activities, with 74 patients a risk sport. Seventy-seven patients have had five or more recurrent of dislocation of the shoulder. The operations were performed by a senior surgeon. Evaluation was done by a clinician, who did not perform the operation. Clinical outcome was assessed with the Duplay score, and the satisfaction of the patients. Radiographic evaluation was done using the standard radiography of the shoulder. According to the Duplay scoring system, we have had 30.1% of excellent results, 43% of good results, 16.1% of fair results, and 10.8% of poor results. The mean Duplay score was 84.7 points with 19 points for the return in sports, 23 points for the stability, 21 points for the pain, and 22 points for the movement. The loss of rotation was less than 13 degrees (mean). Among the patients, 57.4% returned to their former sports activities at the same level, with 59.8% a risk sports. Five patients reported redislocation and eleven patients reported apprehension. The patients were painless in 75.8%. Forty-four patients were very satisfied or satisfied at follow-up. At review, there were radiological degenerative changes in nine shoulders: six in Samilson grade I, one grade II, and two grade III. There was no radiological evidence of loosing, migration or fracture of the coracoid screws, and no nonunion. We have had six cases of resorption of the coracoid tip. We are aware of the limitation of the study. It is a retrospective study and there is no control group. However, we believe that, in regard of our result, the Bristow-Latarjet procedure for anterior glenohumeral instability is safe and effective with good objective and subjective result, and a high degree of patient satisfaction. Radiological findings do not always correlate with the functional outcome and patient satisfaction. Although it is a non-anatomical repair, the Bristow-Latarjet procedure provides desirable functional results.


Intracisternal administration of interleukin-1 beta attenuates naloxone-precipitated withdrawal in morphine-dependent mice.
The effect of central administration of interleukin-1 beta on naloxone-precipitated withdrawal in morphine-dependent mice was studied. The degree of physical dependence on morphine was estimated by counting the number of jumps precipitated by naloxone, one of the typical withdrawal signs. Intracisternal (i.c.) administration of interleukin-1 beta (0.01-1 ng/5 microliters per mouse) to morphine-dependent mice 30 min prior to the injection of naloxone (10 mg/kg i.p.) decreased the number of jumps in a dose-dependent manner. The effect of interleukin-1 beta (1 ng) was significantly antagonized when it was co-administered with interleukin-1 receptor antagonist (1 microgram/mouse). These results suggest that centrally administered interleukin-1 beta could attenuate naloxone-precipitated withdrawal in morphine-dependent mice via interleukin-1 receptors in the brain. Co-administration of alpha-melanocyte-stimulating hormone (300 ng/mouse) or alpha-helical corticotropin-releasing factor (CRF)-(9-41), a CRF receptor antagonist (300 ng/mouse), with interleukin-1 beta also antagonized the inhibitory effect of interleukin-1 beta (1 ng). Moreover, i.c. administration of CRF (200 ng/mouse) significantly decreased the number of jumps.


Advances in the diagnosis and immunotherapy for ocular inflammatory disease.
Significant advances in the diagnosis and therapy for uveitis have been made to improve the quality of care for patients with ocular inflammatory diseases. While traditional ophthalmic examination techniques, fluorescein angiography, and optical coherence tomography continue to play a major role in the evaluation of patients with uveitis, the advent of spectral domain optical coherence tomography and fundus autofluorescence into clinical practice provides additional information about disease processes. Polymerase chain reaction and cytokine diagnostics have also continued to play a greater role in the evaluation of patients with inflammatory diseases. The biologic agents, a group of medications that targets cytokines and other soluble mediators of inflammation, have demonstrated promise in targeted immunotherapy for specific uveitic entities. Their ophthalmic indications have continued to expand, improving the therapeutic armentarium of uveitis specialists.


Nicotine reduces social dominance and neutralizes experience-dependent effects during social conflicts in zebrafish (Danio rerio).
Nicotine, a psychoactive pollutant, binds to nicotinic acetylcholine receptors and disrupts the cholinergic modulation and reward systems of the brain, leading to attention deficit, memory loss, and addiction. However, whether nicotine affects social behaviors remains unknown. We assessed the effects of nicotine on the fighting behavior of zebrafish. Adult zebrafish treated with 5 μM nicotine were used in dyadic fighting tests with size-matched control siblings. The results indicate that nicotine treatment not only significantly reduced the likelihood of winning but also impaired the winner-loser effects (winner and loser fish did not show higher winning and losing tendencies in the second fight, respectively, after treatment.) Nicotine led to a considerable increase in c-fos-positive signals in the interpeduncular nucleus (IPN) of the brain, indicating that nicotine induces neural activity in the habenula (Hb)-IPN circuit. We used transgenic fish in which the Hb-IPN circuit was silenced to verify whether nicotine impaired the winner-loser effect through the Hb-IPN pathway. Nicotine-treated fish in which the medial part of the dorsal Hb was silenced did not have a higher winning rate, and nicotine-treated fish in which the lateral part of the dorsal Hb was silenced did not have a higher loss rate. This finding suggests that nicotine impairs the winner-loser effect by modulating the Hb-IPN circuit. Therefore, in these zebrafish, nicotine exposure impaired social dominance and neutralized experience-dependent effects in social conflicts, and it may thereby disturb the social hierarchy and population stability of such fish.


The effect of Hubbard-like interaction on molecular magnetism of TM-coronene complex (TM = Fe and Co).
The adsorption of two transition metal adatoms, Fe and Co added to a coronene molecule were studied by means of a full potential local orbital method in the framework of relativistic density functional theory. A sequence of fixed spin moment calculations based on the Hubbard-like interaction (U) were carried out on the basis of the generalized gradient approximation (GGA) of the exchange-correlation functional. We found a transition from low-spin to high-spin state upon increasing the transition metal-coronene distance. Furthermore, the magnetism of both Fe-coronene and Co-coronene complexes revealed sensitivity to the magnitude of the U values. In our GGA+U (U = 2 eV) calculations, a low-spin ground state was found with in-plane magnetic anisotropy for both Fe-coronene and Co-coronene, whereas the GGA+U (U = 4 eV) calculations resulted in high-spin state with out-of-plane and in-plane magnetic anisotropy for Fe-coronene and Co-coronene, respectively.


Cutaneous Tuberculosis in Heart Transplant.
Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy.


Identification of a peroxisome proliferator responsive element (PPRE)-like cis-element in mouse plasminogen activator inhibitor-1 gene promoter.
PAI-1 is expressed and secreted by adipose tissue which may mediate the pathogenesis of obesity-associated cardiovascular complications. Evidence is presented in this report that PAI-1 is not expressed by preadipocyte, but significantly induced during 3T3-L1 adipocyte differentiation and the PAI-1 expression correlates with the induction of peroxisome proliferator-activated receptor gamma (PPARgamma). A peroxisome proliferator responsive element (PPRE)-like cis-element (-206TCCCCCATGCCCT-194) is identified in the mouse PAI-1 gene promoter by electrophoretic mobility shift assay (EMSA) combined with transient transfection experiments; the PPRE-like cis-element forms a specific DNA-protein complex only with adipocyte nuclear extracts, not with preadipocyte nuclear extracts; the DNA-protein complex can be totally competed away by non-labeled consensus PPRE, and can be supershifted with PPARgamma antibody. Mutation of this PPRE-like cis-element can abolish the transactivation of mouse PAI-1 promoter mediated by PPARgamma. Specific PPARgamma ligand Pioglitazone can significantly induce the PAI-1 expression, and stimulate the secretion of PAI-1 into medium.


[Musculoskeletal chronic pains and Vitamin D deficiency. Study before after in general practice].
The objective of this study was to evaluate the effect of the correction of vitamin D deficiency (defined by a rate≤50 nmol/l) on the pain, fatigue and quality of life. A pragmatic prospective study was conducted in Rhone-Alpes area, in general practices between February 1 and April 30, 2009. All patients aged 18 to 50 years consulting for diffuse musculoskeletal pain and/or chronic unexplained fatigue, with the only abnormality deficient serum vitamin D were enrolled in this study. They might agree to complete questionnaires on quality of life, pain assessment and control their vitamin D levels after treatment. Forty-nine complete records were analyzed. The deficiency was severe (mean 26 nmol/l). High doses of vitamin were necessary to correct deficiency, between 400,000 to 600,000 units. The correction of vitamin D deficiency resulted in a significant decrease in the level of pain intensity according to verbal rating scale (P=0.034) and the Digital Scale (P<0.001), consumption of analgesics (P=0.002) and discomfort in carrying out activities of daily living following: the shopping, cleaning, walking for more than a kilometer (P<0.001) and dressing (P=0.012). The correction has had a positive impact both physical, mental and social activities. Non-specific musculoskeletal pain or unexplained asthenia are common in primary care. Make a dosage of vitamin D and correct deficits is a necessity before performing complex and expensive examinations.


Cytomegalovirus disease after heart transplantation: is acyclovir prophylaxis indicated?
To determine the efficacy of acyclovir prophylaxis in preventing cytomegalovirus (CMV) disease after heart transplantation, the clinical course of 103 patients (ages, 0.1 to 62 years; mean age, 41.8 years; 87 males, 16 females) was analyzed. Active CMV infection (defined as a positive culture from any site or a fourfold increase in immunoglobulin G antibody titers) occurred in 64% (66/103) and clinical CMV disease (defined as pathologic evidence of CMV in tissue biopsy or a typical CMV syndrome with fever and two of the following: leukopenia, thrombocytopenia, atypical lymphocytes, and elevated liver function test results in a patient with CMV infection) occurred in 25% (26/103). Independent variables studied included acyclovir prophylaxis, duration of acyclovir use, duration and type of induction therapy, donor and recipient CMV status, total steroid dose at 3 and 6 months, azathioprine dose and cyclosporine level at 3 months, age, and sex. In a multivariate regression analysis, acyclovir prophylaxis was independently associated with freedom from CMV disease (p = 0.029). Positive donor CMV status (p = 0.025), higher total steroid dose at 3 months (p = 0.036), and lower azathioprine dose at 3 months (p = 0.047) were associated with higher occurrence of CMV disease. The use of antilymphocyte induction therapy was associated with an increased occurrence of active CMV infection (p = 0.022) but not CMV disease. The prophylactic administration of acyclovir reduced the occurrence of CMV disease after heart transplantation.


Inhibition of lipid peroxidation promoted by iron(III) and ascorbate.
Peroxidation of rat liver microsomes and of phospholipid isolated from them was studied using iron(III) and ascorbate initiation. One-half equivalent of citrate per iron equivalent maintained solubility of the metal ion at neutral pH. Several metal chelators, including additional citrate, blocked peroxidation, but catalase did not. These characteristics are consistent with those reported by others (D. M. Miller and S. D. Aust (1989) Arch. Biochem. Biophys. 271, 113-119). Several antioxidants, principally tocopherol analogues and nitroxides, and, as well, a nonenzymatic component of "thymol-free" catalase, potently blocked lipid peroxidation, or, equivalently, dioxygen depletion from suspensions of peroxidizing microsomes. Chromanols were the most active antioxidants. No thiol studied had significant antioxidant activity in the test system.