Comparison of propafenone and disopyramide for treatment of chronic ventricular arrhythmias: placebo-controlled, double-blind, randomized crossover study.
In a double blind, placebo-controlled study, the efficacy of propafenone, a new antiarrhythmic drug was compared to that of disopyramide. Sixteen patients with frequent and complex premature ventricular contractions (PVCs) were studied by serial 24-hour ambulatory monitoring, while they were receiving propafenone, 300 mg, and disopyramide, 200 mg, both every 8 hours. A reduction in the mean frequency of PVCs per hour, in comparison to the placebo period, from 574 +/- 535 to 100 +/- 130, was observed after propafenone (p less than 0.005) and from 629 +/- 455 to 231 +/- 280 after disopyramide (p less than 0.008). A greater than 70% reduction in PVCs in comparison to placebo was observed in 11 of 14 after propafenone and 9 of 15 after disopyramide (NS). A greater than or equal to 90% reduction in PVCs was observed in 9 of 16 with propafenone and in 4 of 15 with disopyramide (p less than 0.05). The suppression of complex PVCs (repetitive, polymorphic, or more than 5/min with bigeminism) was observed in 11 of 14 after propafenone and in 9 of 14 after disopyramide. The abolition of nonsustained ventricular tachycardia was observed in 6 of 6 and 3 of 5, respectively, after propafenone and disopyramide (p less than 0.05). A lower incidence of side effects, 4 of 16 vs 8 of 16, was observed during propafenone than during disopyramide treatment. We conclude that propafenone, in a dose of 900 mg daily, is more effective than disopyramide, in a dose of 600 mg daily, in the treatment of frequent and complex PVCs and nonsustained ventricular tachycardias. Propafenone also showed a lower incidence of side effects.


Atypical demyelinating lesions in patients with multiple sclerosis.
We describe an atypical MRI appearance of multiple sclerosis (MS). Lesions characterized on T2-weighted images by a well-defined rim of increased signal intensity and a concentric region of higher signal intensity were seen in 6 of 132 patients with MS. On T1-weighted images these lesions were evident as regions of low signal intensity, often with a rim of contrast enhancement or increased signal intensity. These appearances tended to be shown by new, evolving lesions.


Long-term follow-up of paediatric anorectal anomalies and the role and efficacy of parent support groups for such conditions.
There are a multitude of parent support groups for most life situations and medical conditions. The aim of this study was to discover defining characteristics and to evaluate the structure and effectiveness of parent support groups in paediatric anorectal anomalies. Over 200 non-profit organisations and parent support groups were sent questionnaires to determine their effectiveness. Many of these were excluded as they were deemed not relevant to the final study. A final 20 groups were included for review, questions were based around origins, activities, education and evaluation, organisational structure and their affiliations with the health care team. Most groups had similar origins, usually an educated parent who had a child born with the condition and a zest for further knowledge and understanding and a desire to share this with others in a similar situation. Only 20% received government funding; few had paid staff and half had good relations with the local medical and paramedical fraternity. The majority had a team of long-term enthusiastic volunteers who remained with the group to support others long after their own child was no longer a concern. Some support groups offer a valuable service to families alongside the medical and paramedical fraternity. These groups provide families with the day-to-day lived experiences through social media, networking and meetings. Some provide more formal educational conferences designed to bring families, the medical and paramedical fraternity together to learn valuable lessons from each other.


Assessment of tumor promoting effects of amniotic and umbilical cord mesenchymal stem cells in vitro and in vivo.
Human mesenchymal stem cells (hMSCs) have been applied in a variety of therapies recently. However, the role of MSCs in tumor progression remains largely elusive. Some studies demonstrated that MSCs can promote tumor growth, while others had opposite results. Therefore, the lack of evidence about the effect of MSCs on tumor cells impedes its further use. In the current study, hMSCs from amniotic membrane (hAMSCs) and umbilical cord (hUCMSCs) were used to evaluate the effects of MSCs on tumor development in vitro and in vivo. Two different animal models based on subcutaneous xenograft bearing nude mice and a murine experimental metastatic model were established for in vivo study. Moreover, cytokines regulated by MSCs co-cultured with cancer cells SPC-A-1 were also analyzed by cytokine array. Our results indicated that hUCMSCs not only did not promote proliferation in cancer cells, but also inhibited migration. In addition, they inhibited tube formation in human umbilical vein endothelial cells (HUVECs). Although hAMSCs also showed inhibitory effects on cancer cell motility, the proliferation of cancer cells was indeed enhanced. The in vivo data revealed that hUCMSCs did not promote tumor progression in lung adenocarcinoma and gastric carcinoma xenografts. Nevertheless, hAMSCs could do. The results from murine experimental metastatic model also demonstrated that neither hUCMSCs nor hAMSCs significantly enhanced the lung metastasis. The data from cytokine array showed that 11 inflammatory factors, 8 growth factors and 11 chemokines were remarkably secreted and changed. In view of the data from in vitro and in vivo studies, the exploitation of hUCMSCs in new therapeutic strategies should be safe compared to hAMSCs under malignant conditions. Moreover, this is the first report to systematically elucidate the possible molecular mechanisms involved in UCMSC- and AMSC-affected tumor growth and metastasis.


Synthesis of (±)-γ-rubromycin via a new hypoiodite-catalytic oxidative cycloetherification.
A new synthesis of γ-rubromycin is presented through a new oxidative, bisbenzannulated spiroketalization as a key step which is catalyzed by an in situ generated hypoiodite species, developed previously by our group. This key transformation has high efficiency and convenient conditions. This is a new and efficient catalytic application for organohypoiodine reagents.


Residual Mammographic Microcalcifications and Enhancing Lesions on MRI After Neoadjuvant Systemic Chemotherapy for Locally Advanced Breast Cancer: Correlation with Histopathologic Residual Tumor Size.
To evaluate the accuracy of residual microcalcifications on mammogram (MG) in predicting the extent of the residual tumor after neoadjuvant systemic treatment (NST) in patients with locally advanced breast cancer and to evaluate factors affecting the accuracy of MG microcalcifications using magnetic resonance imaging (MRI) as a reference. The patients who underwent NST and showed suspicious microcalcifications on MG comprised our study population. Clinicopathologic and imaging (MG, MRI) findings were investigated. Agreement between image findings and pathology was assessed and factors affecting the discrepancy were analyzed. Among 207 patients, 196 had residual invasive ductal carcinoma or ductal carcinoma-in-situ (mean size, 3.78 cm). The overall agreement of residual microcalcifications on MG predicting residual tumor extents was lower than MRI in all tumor subtypes (intraclass correlation coefficient [ICC] = 0.368 and 0.723, p < 0.0001). The agreement of residual MG microcalcifications and pathology was highest in HR(+)/HER2(+) tumors and lowest in the triple-negative tumors (ICC = 0.417 and 0.205, respectively). Multivariate linear regression analysis revealed that a size discrepancy between microcalcifications and histopathology was correlated with molecular subtype (p = 0.005). In HR(+)/HER2(-) and triple-negative subtypes, the mean extents of residual microcalcification were smaller than residual cancer, and overestimation of tumor extent was more frequent in HR(+)/HER2(+) and HR(-)/HER2(+) tumors. The extent of microcalcifications on MG after NST showed an overall lower correlation with the extent of the pathologic residual tumor than enhancing lesions on MRI. The accuracy of residual tumor evaluation after NST with MG and MRI is affected by their molecular subtype.


Topical photodynamic therapy for patients with therapy-resistant lesions of cutaneous T-cell lymphoma.
Photodynamic therapy after topical application of 5-aminolevulinic acid is an effective therapy for nonmelanoma epithelial skin cancers. It has also been used for some cases of cutaneous T-cell lymphoma. We treated 4 patients with different cutaneous T-cell lymphomas with photodynamic therapy. Those patients had previously reached a partial remission with more conventional therapies, but single lesions had remained. In all of these cases a complete remission of these lesions was achieved. We, therefore, suggest that photodynamic therapy can be a useful additional treatment modality for patients with therapy-resistant lesions of cutaneous T-cell lymphoma.


Secretagogue-produced duodenal ulcers in the rat.
Duodenal ulcers were produced in rats by the subcutaneous infusion for 6-48 hours of two gastric secretagogues in combination: pentagastrin (2 or 4 microgram kg-1 min-1) and carbachol (0-4 or 0-8 microgram kg-1 min-1). With increasing duration of infusion and higher doses there were increases in the incidence, severity, number and perforation rate of duodenal ulcers, their caudad distribution and mortality from peritonitis. This method of producing duodenal ulcers may sufficiently resemble the clinical situation to provide a model for the study of anti-ulcer drugs and the natural history of duodenal ulcers.


Antagonism of the interleukin-1 receptor following traumatic brain injury in the mouse reduces the number of nitric oxide synthase-2-positive cells and improves anatomical and functional outcomes.
Interleukin (IL)-1beta plays an important role in the inflammatory response that results from traumatic brain injury and antagonism of the actions of this cytokine can affect outcome. We subjected male mice to aseptic cryogenic injury and assessed recovery through anatomical, histological and functional measures following treatment with recombinant mouse IL-1 receptor antagonist (IL-1ra). A single dose (1 microg, i.c.v.) at the time of injury reduced lesion volume 3 days later, as assessed by Nissl staining, and also the number (30%) of FluoroJade-positive degenerating neurones. Mice treated with IL-1ra performed better on the beam balance and in the grid test as compared with vehicle-treated animals. Furthermore, IL-1ra-treated animals showed fewer (40%) nitric oxide synthase-2-positive cells in and around the lesion. These data suggest that activation of the IL-1 receptor following trauma contributes to the pathology and that antagonism can reduce both anatomical and functional consequences of neuroinflammation.


Andreas Vesalius' 500th Anniversary: First Description of the Mammary Suspensory Ligaments.
Sir Astley Paston Cooper has, to date, been acknowledged to be the first to describe the suspensory ligaments of the breast, or Cooper's ligaments, in 1840. We found these ligaments to be recorded in the first edition of 'De Humani Corporis Fabrica Libri Septem' by Andreas Vesalius, published in 1543. To commemorate Vesalius' 500th birthday, we quote and discuss this earlier record. Vesalius' record of the nature and function of the fleshy membrane between mammary gland and pectoral muscle, the hard fat intervening the mammary glands, and the fibers running from the fleshy membrane to the skin are a clear representation of posterior layer of the superficial fascial system, the fibro-adipose stroma surrounding and linking the mammary glandular elements, and the suspensory ligaments as we know them. Vesalius recorded the anatomy and function of the latter structures nearly 300 years before Sir Astley Paston Cooper did.


Regulation of cAMP-dependent protein kinase subunit levels in Friend erythroleukemic cells. Effects of differentiation and treatment with 8-Br-cAMP and methylisobutyl xanthine.
Friend erythroleukemic cells contain both type I and type II cAMP-dependent protein kinases. The amounts of type I and type II regulatory subunits (R I and R II) were established by a combination of the equilibrium binding of cyclic [3H]AMP and specific immunoprecipitation. In control cells the total specific cAMP-binding activity was 9.8 pmol/mg of cytosolic protein and the ratio of R II to R I was 1.2. After the induction of differentiation by growth in 2% dimethyl sulfoxide, the total cAMP-binding capacity doubled, but larger and opposing changes in R II and R I levels were observed. The concentration of R II tripled (to 16.6 pmol/mg) while R I content (1.5 pmol/mg) declined to one-third of the control cell level, resulting in an R II:R I value of 11.1. Treatment of Friend cells with 0.5 mM 8-bromoadenosine 3':5'-monophosphate (8-Br-cAMP) and 0.2 mM methylisobutyl xanthine for 2 days did not stimulate cell differentiation. however, the cAMP-binding capacity nearly doubled and the cells accumulated a high level of R II while R I declined. This resulted in a distribution of R subunits closely resembling that of differentiated cells. Cyclic AMP-stimulated histone kinase activity increased in proportion to cAMP-binding activity during differentiation; no such increase was seen following 8-Br-cAMP treatment. Fractionation of cytosolic extracts by DEAE-cellulose chromatography revealed that both R I and R II were fully associated with the catalytic subunit (C) of protein kinase before and after differentiation. In extracts of 8-Br-cAMP-treated cells all of R I and 40 to 60% of R II were not associated with C. Free R II isolated from these cells was indistinguishable from RII present in holoenzyme. Thus, erythroid differentiation of Friend cells results in a coordinate accumulation of R II and C subunits as well as a decline in R I content. In contrast, chronic exposure to 8-Br-cAMP elicits similar changes in R subunit levels but disrupts the coordinate regulation of R and C content.


Impact of residual renal function and HCV seropositivity on plasma CD40/CD40L system and oxidative status in haemodialysis patients.
We evaluated the impact of residual renal function (RRF) on oxidative stress (SOX) and CD40/CD40L system in haemodialysis (HD) patients. We determined sCD40, sCD40L and SOX marker-Cu/Zn superoxide dismutase (Cu/Zn SOD) levels in HD patients with RRF, with anuria (A) and in healthy controls. sCD40 and Cu/Zn SOD plasma levels were higher in both groups of dialyzed patients compared to controls (all p<0.001), and they were higher in A than in RRF patients (all p<0.01). In RRF group, sCD40/sCD40L and Cu/Zn SOD were significantly higher in anti-HCV-seropositive (anti-HCV[+]) patients than in their anti-HCV[-] counterparts. This phenomenon was not observed in A group. Multiple regression analysis showed that Cu/Zn SOD, kt/V and low fibrinogen were the independent factors affecting sCD40 levels in the whole HD group. The loss of RRF and HCV seropositivity increased plasma levels of sCD40/sCD40L and oxidative status in HD patients.


Metal-organic frameworks (MOFs) composite of polyaniline-CNT@aluminum succinate for non-enzymatic nitrite sensor.
Nitrite has been linked to a variety of health issues, as well as cancer and oxygen deficiency when its allowable limit is exceeded. Nitrite monitoring and detection are required due to the negative effects on public health. Metal-organic frameworks (MOFs)-based nanomaterials/composites have recently been shown to have the potential for various biological and medical applications like sensing, imaging, and drug delivery. As a result, this research creates an efficient electrochemical sensor by incorporating MOFs into polyaniline (PANI)/carbon nanotube (CNT) cast on the GCE. In situ oxidative polymerization was used to construct an aluminum succinate MOF (Al-Succin)-incorporated CNT/PANI nanocomposite (PANI/CNT@Al-Succin) and well characterized by various characterization techniques, namely, field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric-differential thermal analysis (TGA-DTA), cyclic voltammetry (CV), and four probes to measure DC electrical conductivity. Cyclic voltammetry and linear sweep voltammetry techniques were employed to detect nitrite on the surface of PANI/CNT@Al-Succin-modified glassy carbon electrode (GCE). PANI/CNT@Al-Succin-modified GCE demonstrated good current response and electrocatalytic property towards nitrite compared to bare GCE. The newly synthesized electrode exhibited a high electrocatalytic activity towards nitrite oxidation and showed a linear response ranging from 5.7 to 74.1 μM for CV and 8.55-92.62 μM for LSV. The obtained LOD values for CV (1.16 μM) and LSV (0.08 μM) were significantly below the WHO-defined acceptable nitrite limit in drinking water. Results of recovery studies for real samples of apple juice, orange juice, and bottled water were 98.92%, 99.38%, and 99.90%, respectively. These values show practical usability of PANI/CNT@Al-Succin in real samples.


Mechanics of slope walking in the cat: quantification of muscle load, length change, and ankle extensor EMG patterns.
Unexpected changes in flexor-extensor muscle activation synergies during slope walking in the cat have been explained previously by 1) a reorganization of circuitry in the central pattern generator or 2) altered muscle and cutaneous afferent inputs to motoneurons that modulate their activity. The aim of this study was to quantify muscle length changes, muscle loads, and ground reaction forces during downslope, level, and upslope walking in the cat. These mechanical variables are related to feedback from muscle length and force, and paw pad cutaneous afferents, and differences in these variables between the slope walking conditions could provide additional insight into possible mechanisms of the muscle control. Kinematics, ground reaction forces, and EMG were recorded while cats walked on a walkway in three conditions: downslope (-26.6 deg), level (0 deg), and upslope (26.6 deg). The resultant joint moments were calculated using inverse dynamics analysis; length and velocity of major hindlimb muscle-tendon units (MTUs) were calculated using a geometric model and calculated joint angles. It was found that during stance in downslope walking, the MTU stretch of ankle and knee extensors and MTU peak stretch velocities of ankle extensors were significantly greater than those in level or upslope conditions, whereas forces applied to the paw pad and peaks of ankle and hip extensor moments were significantly smaller. The opposite was true for upslope walking. It was suggested that these differences between upslope and downslope walking might affect motion-dependent feedback, resulting in muscle activity changes recorded here or reported in the literature.


Prognostic values of KAI1 and survivin expression in an infiltrating ductal carcinoma of the breast.
To investigate KAI1 and survivin expression in infiltrating ductal carcinomas, and to evaluate the relationship between clinicopathological factors and KAI1 and survivin expression levels in breast cancers. KAI and survivin expression levels were measured in 62 patients, using immunohistochemical staining. Western blot analysis was performed on eight frozen cases. DNA ploidy was determined by flow cytometry. The results of the KAI1 expression analyses were as follows: in 14 cases (22.6%) levels were preserved (++), in 30 cases (48.4%) levels were reduced (+), in 18 cases (29.0%) no KAI1 expression was detected, so these were designated 'lost' (-). Results of assessments of survivin expression were as follows: six cases (9.7%) were strong positive (++), 28 cases (45.15%) were positive (+), and 28 cases (45.15%) were negative. Survivin (p=0.0009) and KAI1 (p=0.0091) expression levels were directly correlated with survival rate. However, no significant difference was determined to exist between survivin and KAI1 expression levels and the clinicopathological factors. DNA ploidy did not correlate with survivin and KAI1 expression levels and survival rate. Four different groups, according to their survivin and KAI1 expression levels, correlated with the clinical stage and survival rate. KAI1 and survivin expression levels might be prognostic factors in breast cancers.


Evidence-based review of oral traditional Chinese medicine compound recipe administration for treating weight drop-induced experimental traumatic brain injury.
Recently, a number of studies conducted and published in China have suggested that traditional Chinese medicine compound recipe (TCMCR) may be beneficial in the treatment of experimental traumatic brain injury (TBI). In this study, we conducted a systematic review and meta-analysis of the efficacy of TCMCR in TBI model with weight drop method to provide robust evidence on the effects of TCMCR and to determine whether TCMCR can be recommended for routine treatment or considered as a standard treatment for TBI. We identified eligible studies by searching five electronic databases on April 1, 2014, and pooled the data using the random-effects model. Results were reported in terms of standardized mean difference (SMD). We also calculated statistical heterogeneity, evaluated the studies' methodological quality and investigated the presence of publication bias. Totally, 187 relevant publications were searched from databases, 25 of which met our inclusion criteria. The overall methodological quality of the most studies was poor, and there was evidence of statistical heterogeneity among studies along with small-study effects. Meta-analysis showed statistically significant effects indicating that TCMCR has a beneficial effect on TBI. Despite the limitations, we concluded that TCMCR may reduce brain water content, improve BBB permeability, and decrease TNF-α/NO expression after experimental TBI in terms of overall efficacy. However, our review also indicates that more well-designed and well-reported animal studies are needed.


Genetic variants in PSEN2 and correlation to CSF β-amyloid42 levels in AD.
Beta-amyloid 42 (Aβ42) concentrations in cerebrospinal fluid (CSF) are significantly decreased in Alzheimer's disease (AD). The aim of this study was to correlate genetic variability in presenilin 2 (PSEN2) in relation to Aβ42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF Aβ42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and Aβ42 levels. One distinct haploblock in PSEN2 was detected and the frequent haplotypes were analyzed using 4 tagging single nucleotide polymorphisms (SNPs). We found an association between haplotype 2 and higher CSF Aβ42 concentrations (p = 0.021) and lower Aβ42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower Aβ42 levels (p = 0.009). Additive regression analysis showed an association of Aβ42 level with APOE genotype (p = 0.024), haplotype 4 (p = 0.064), and haplotype 5 (p = 0.04), whereas gender, age at onset and Mini Mental State Examination (MMSE) remained insignificant. Using CSF Aβ42 as a biomarker we replicated genetic influences in APOE and observed a significant influence of a new haplotype in PSEN2. A better understanding of genetic influences on biomarkers like CSF Aβ42 might help to stratify patients and develop specific treatment strategies.


Strategic filtering of high-energy visible light expands neural correlates of functional vision particularly in older participants.
In this study we assessed the neural correlates of functional vision while varying patterns of light filtration. Four filter conditions used relatively flat filtering across the visible spectrum while one filter was a step filter that selectively absorbed violet light (wavelengths below about 415 nm). Neural effects were quantified by measuring the BOLD response ((T2*-based fMRI) while subjects performed a challenging visual task (judging gap direction in Landolt Cs that randomly varied in size). In general (based on p < 0.01 directional criterion not corrected for aggregated error), as filtering increased (less interference by bright light), brain activity associated with the task also increased. This effect, even using the most conservative statistics, was most evident when using the violet filter (especially for the older subjects) despite only reducing the very highest energy portion of the visible spectrum. This finding suggests that filtering can increase neural activity associated with functional vision; such effects might be achievable through filtering just the highest visible energy (violet).


Importance of in vivo dosimetry as part of a quality assurance program in tangential breast treatments.
The investigation of the accuracy and reproducibility in the daily dose delivered in tangential breast treatments with in vivo dose measurements. In vivo dose measurements performed on the tangential treatment fields of 35 breast cancer patients are analysed for three units: a 6 MV linear accelerator, an old Cobalt unit and a new Cobalt unit. The results are plotted in frequency distributions. Deviations on the mean are often the expression of a systematic error in one of the core procedures of a department. A large spread of the results around the mean indicates a high burden of random set-up errors and/or systematic errors in individual patients. The reproducibility in dose delivery is studied by comparing repetitive checks to their respective mean for investigation of random day-to-day variation. A small systematic error on the entrance dose (+ 1.4%) is detected on the old Cobalt unit due to a discrepancy between measured and published percentage depth dose values. An unexpected systematic overdosage (+ 6%) is detected after implementation of a new software for dose calculation, proving that treatment quality is a process needing continuous monitoring. The transmission measurements demonstrate a systematic error in dose delivery of 1.5 to 3% due to the assumption that the breast is water equivalent when calculating the dose. The large spread of the transmission measurements (sa = 7.7%) shows that the weakest point in the treatment preparation chain is inaccurate acquisition of external body contours, leading to systematic errors in dose delivery for specific patients. The standard deviation for the reproducibility is 3.1% for the old Cobalt unit, vs. 1.6% on the other units, demonstrating the influence of staffing and mechanical characteristics of the units on daily precision in dose delivery. In vivo dosimetry is an important tool in a departmental quality assurance program to detect systematic errors in dose delivery, to identify inadequate treatment situations, to investigate weak points in the chain of treatment preparation and to ensure accurate dose delivery for individual patients. The predictive value of a single check for the accuracy in dose delivery during the whole treatment series is high for reproducible treatment methodologies.


The effects of simultaneous antegrade/retrograde cardioplegia on cellular volumes and energy metabolism.
Simultaneous antegrade/retrograde cardioplegia (SARC) has been employed frequently during cardiac surgery to preserve the jeopardized myocardium. However, retrograde perfusion of SARC may interfere with myocardial drainage and disrupt myocardial fluid homeostasis, which may affect the myocardial energy metabolism and contractile function. The study was, therefore, designed to assess the effects of SARC on myocardial fluid homeostasis, cellular volumes, and energy metabolism. Eight isolated pig hearts were subjected to a protocol consisting of a 20-minute control perfusion, 120-minute SARC, and 20-minute reperfusion. The myocardial water content was monitored using near-infrared spectroscopy. Phosphorus-31 magnetic resonance ((31)P MR) spectroscopy was used to monitor the volumes of both intracellular and extracellular compartments and assess myocardial energy metabolism. The near-infrared spectra showed that the 120-min SARC resulted in a 60 +/- 12% increase in the myocardial water content. (31)P MR spectra showed a 36 +/- 4% increase in the intracellular compartment and a 54 +/- 8% increase in the extracellular compartment during SARC relative to their initial volumes measured during control perfusion (100%). However, the myocardial energy metabolites (adenosine triphosphate [ATP] and phosphocreatine [PCr]) remained unchanged during the 120-minute SARC. Moreover, during reperfusion, the hearts showed an almost complete recovery in the left ventricular-developed pressure. A prolonged SARC resulted in water accumulation in both extracellular and intracellular compartments in the normal myocardium. Although its detrimental effect on tissue fluid homeostasis did not jeopardize the myocardial energy metabolism, a prolonged use of SARC should be avoided, particularly in the diseased hearts.


Time-dependent alteration of insulin-like growth factor gene expression during nerve regeneration in regions of muscle enriched with neuromuscular junctions.
Insulin-like growth factors (IGFs) increase the rate of motor axon elongation, prevent motoneuron death, and may support the reestablishment of synapses following nerve injury. In situ hybridization was used in the present study to examine the temporal and spatial distribution of IGF gene expression in soleus muscle following sciatic nerve crush in rats. In intact muscle, IGF-II gene expression was generally low, and localized to interstitial cells, possibly fibroblast and Schwann cells. These cells were found in the middle of muscle which is enriched in neuromuscular junctions. IGF-II gene expression, 4-6 days postcrush, was increased in interstitial cells. Thereafter, IGF-II gene expression was also increased in muscle cells or cells closely associated with muscle fibers, such as satellite cells. IGF-II gene expression was increased to a much greater extent in the midregion of muscle enriched in end-plates than in the two ends of muscle, but returned towards normal following the reestablishment of functional synapses. On the other hand, IGF-I gene expression was only slightly increased following nerve crush, and this increase was associated with interstitial, but not muscle cells. These results show that the IGF-I and IGF-II genes are regulated by independent signals and may play separate roles during nerve regeneration. For example, a regional increase in IGF-II gene expression may support preferential nerve terminal sprouting in the middle of muscle enriched in neuromuscular junctions, thereby increasing the probability for the reestablishment of synapses.


Intrathecal normal saline without preservative does not have a local anesthetic effect.
The effects of intrathecally administered normal saline (preservative-free) were studied in patients undergoing differential spinal block anesthesia for evaluation of chronic pain below the waist. The injection of 5 ml saline did not significantly change the sensitivity to pinprick measured in the lower back and both lower extremities. Temperature measurement in both the lower extremities and psychogalvanic skin reflex did not show evidence of sympathetic block; the psychogalvanic skin reflex was abandoned because of inconsistent results. These findings refute the earlier conclusion of Urban and McKain who found that normal saline acts as a weak local anesthetic when injected intrathecally. We recommend use of normal saline (preservative-free) in 5 ml doses as a placebo for differential spinal block anesthesia.


The effects of hypoxemia on myocardial blood flow during exercise.
We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Intrapancreatic common hepatic artery arising from the superior mesenteric artery, a challenging anatomic variation in a multiorgan harvesting.
Understanding abdominal vascular anatomy is crucial for multiorgan recovery. In this case report, we have described a common hepatic artery that arises from the superior mesenteric artery but follows an intrapancreatic course. The donor was ideal for multiorgan recovery and the recipient was a 29-year-old woman awaiting a second transplant owing to primary nonfunction of her first engrafted organ. The indication for transplantation was secondary biliary cirrhosis. A type I diabetic recipient on dialysis therapy was awaiting the kidney and pancreas. The urgent condition of our liver recipient combined with the anatomical finding prioritized liver procurement, therefore the pancreas was discarded. The recognition of all anatomic variations will allow us to improve the use of the scarce resource of deceased donor organs.


5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione derivatives of brefeldin A: Design, synthesis and cytotoxicity in MDA-MB-231 human breast cancer cells.
27 novel 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione derivatives of brefeldin A were designed and synthesized to make them more conducive to the cancer treatment. The antiproliferative activity of all the target compounds was tested against six human cancer cell lines and one human normal cell line. Compound 10d exhibited nearly the most potent cytotoxicity with IC50 values of 0.58, 0.69, 1.82, 0.85, 0.75, 0.33 and 1.75 μM against A549, DU-145, A375, HeLa, HepG2, MDA-MB-231 and L-02 cell lines. Moreover, 10d inhibited metastasis and induced apoptosis of MDA-MB-231 cells in a dose-dependent manner. The potent anticancer effects of 10d were prompted based on the aforementioned results, the therapeutic potential of 10d for breast cancer was worth further exploration.


Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E2 (COX-2) production of flavonoids from seeds of Prunus tomentosa Thunberg.
Chemical investigation of the 80% Me(2)CO extract from the seeds of Prunus tomentosa led to the isolation and identification of six flavonoids: kaempferol (1), kaempferol 3-O-alpha-L-rhamnopyranoside (2; afzelin), kaempferol 3-O-beta-D-(6-acetyl)-glucopyranosyl(1-->4)-alpha-L-rhamnopyranoside (3; multiflorin A), kaempferol 3-O-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranoside (4; multiflorin B), quercetin 3-O-alpha-L-rhamnopyranoside (5; quercitrin), and quercetin 3-O-beta-D-glucopyranosyl (1-->4)-alpha-L-rhamnopyranoside (6; multinoside A). Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E(2) production in interferon-gamma (INF-gamma) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro (COX-2) of the isolated compounds were evaluated. Compounds 1, 5, and 6 exhibited potent anti-oxidative activity in the DPPH radical scavenging assay with IC(50) values of 57.2, 59.4, and 54.3 microg/mL respectively. The positive control, ascorbic acid, had an IC(50) of 55.5 mug/mL. Compounds 1, 5, and 6 also reduced COX-2 levels in a dose dependent manner with IC(50) values of 10.2, 8.7, and 9.6 microg/mL respectively, with the positive control, indomethacin, having an IC(50) of 5.1 microg/mL. All six compounds inhibited NO production in a dose dependent manner with IC(50) values of 35.1, 42.8, 40.0, 44.8, 43.7, and 43.9 microg/mL respectively, while the positive control, L-NMMA, had an IC(50) of 42.1 microg/mL.


The recruitment times and firing patterns of the medullary respiratory neurones of the cat.
The brainstem of anaesthetized cats was explored for respiratory neurones with microelectrodes in the regions of the nucleus retroambigualis (ventrolateral region) and the nucleus tractus solitarius (dorsomedial region). These neurones were analysed with respect to their firing patterns and recruitment times, as referenced to the respiratory cycle. All of the respiratory neurones showed a stable and ordered pattern of firing. Four groups of neurones with similar characteristics within each group, but differing from each other, were statistically examined; the inspiratory neurones of the dorsomedial region, the 'late' inspiratory neurones of the ventrolateral region, the 'early' inspiratory neurones of the ventrolateral region and the expiratory neurones of the ventrolateral region.


Tigecycline susceptibility in Klebsiella pneumoniae and Escherichia coli causing neonatal septicaemia (2007-10) and role of an efflux pump in tigecycline non-susceptibility.
To investigate the trend of tigecycline susceptibility and mechanisms behind tigecycline non-susceptibility in Klebsiella pneumoniae and Escherichia coli isolates causing neonatal septicaemia (2007-10). MICs of tigecycline for the isolates were determined. The isolates were evaluated for β-lactamases and carbapenemases. Molecular typing of the tigecycline-resistant isolates was performed. Expression of efflux pump genes (acrA, acrB and tolC) and regulators (soxS and ramA) was examined by real-time RT-PCR and western blotting. Sequencing of the ramA and ramR genes was carried out to identify mutations within these genes. Tigecycline susceptibility was evaluated in all K. pneumoniae (n = 57) and E. coli (n = 19) blood isolates. The prevalence of extended-spectrum β-lactamase (ESBL)-producing organisms was high, but tigecycline non-susceptibility remained low in these isolates. Though MIC values of tigecycline remained in the susceptible range, there was a 2-fold increase in the value of MIC90 from 2007 to 2010. Over the 4 year period K. pneumoniae showed higher MIC values of tigecycline in comparison with E. coli. Tigecycline non-susceptibility was not observed among carbapenem-resistant isolates. Only two ESBL-producing clonally distinct K. pneumoniae isolates showed tigecycline resistance with overexpression of ramA and the AcrAB-TolC pump. No mutations were present within the ramA and ramR genes that might enhance the expression of the pump. The study showed for the first time the trend of tigecycline susceptibility in E. coli and K. pneumoniae causing neonatal septicaemia. Tigecycline still has potent antimicrobial effects against most ESBL- or carbapenemase-producing K. pneumoniae and E. coli, but the increasing MIC values make it essential to be vigilant.


Designer self-assembling peptide nanofiber scaffolds for 3D tissue cell cultures.
Biomedical researchers have become increasingly aware of the limitations of time-honored conventional 2D tissue cell cultures where most tissue cell studies have been carried out. They are now searching for 3D cell culture systems, something between a petri dish and a mouse. It has become apparent that 3D cell culture offers a more realistic micro- and local-environment where the functional properties of cells can be observed and manipulated that is not possible in animals. A newly designer self-assembling peptide scaffolds may provide an ideally alternative system. The important implications of 3D tissue cell cultures for basic cell biology, tumor biology, high-content drug screening, and regenerative medicine and beyond could be profound.


Establishment and manipulation of monkey and human embryonic stem cell lines for biomedical research.
We have established several embryonic stem (ES) cell lines of the cynomolgus monkey. They maintain the normal karyotype and pluripotency in culture for long periods. We obtained government approval and grants to produce human ES cell lines from frozen surplus embryos in April 2002. We have established and characterized three human ES cell lines (KhES-1, KhES-2, KhES-3). We started distribution of human ES cells to other research groups in March 2004. It would be important to produce genetically modified monkey and human ES cells for various purposes. After improvement of the transfection and selection methods, we have produced monkey ES cells with integrated transgenes at efficient and reliable rates. We are also investigating reprogramming of somatic cells into pluripotent stem cells by cell fusion with ES cells. Such reprogramming could be used to produce pluripotent stem cells for each patient without therapeutic cloning, which would raise ethical concerns.


Design and synthesis of new classes of heterocyclic C-glycoconjugates and carbon-linked sugar and heterocyclic amino acids by asymmetric multicomponent reactions (AMCRs).
While chemical efficiency relies on several factors, the multicomponent reaction (MCR) approach was considered as a powerful synthetic tool for preparing target molecules of biological relevance in an efficient manner. Four classes of new bioactive molecules were designed and synthesized by asymmetric MCRs, in some cases with the cooperation of polymer-assisted solution-phase (PASP) technique. These include (a) C-glycosyl dihydropyrimidines and dihydropyridines via Biginelli and Hantzsch cyclocondensations, (b) C-glycosyl beta-amino acids via Mannich- and Reformatsky-type reactions, (c) C-glycosyl beta-lactams via Staudinger reaction, and (d) heterocyclic alpha-amino acids (glycine and alanine) via the Biginelli and Hantzsch reactions.


Prevalence of conduction abnormalities in a systolic heart failure population by race, ethnicity, and gender.
There is paucity of data regarding conduction abnormalities in the Hispanic population with systolic heart failure (HF). We aimed to evaluate the prevalence of electrocardiogram (ECG) abnormalities in a systolic HF population, with attention to the Hispanic population. A cross sectional study of 926 patients enrolled in a systolic HF disease management program. ECGS were obtained in patients with an ejection fraction (EF) ≤ 40% by echocardiography at enrollment. Univariate and multivariate analysis adjusted by ethnicities was performed. White patients exhibited higher prevalence of atrial fibrillation (14.7%) than black patients (8.0%, P = 0.01) whereas Hispanics presented higher prevalence of paced rhythm (14.3% in Hispanics vs. 6.5% in whites and 5.2% in blacks, P<0.01 for both comparisons), higher prevalence of left bundle branch block (LBBB, 14.5% in Hispanics vs. 8.8% in whites and 5.8% in blacks, P = 0.002) and increased frequency of abnormal QT intervals (76.7% in Hispanics) than whites (59.6%) and blacks (69%) patients (P< 0.01 for both comparisons). A QRS interval greater than 120 ms was less prevalent among blacks (15.8% vs. 26.0% in whites and 25.3% in Hispanics, P = 0.01 for both comparisons). Univariate and multivariate analysis disclosed no influence of other characteristics (age, sex, coronary artery disease, hypertension, ejection fraction, medications) in the ECG findings. Hispanics with Systolic HF presented with increased prevalence of paced rhythm, LBBB, and abnormal QT intervals. Attention should be addressed to these ECG variations to recommend additional guidance for therapeutic interventions and provide important prognostic information.


Traumatic lung cysts after penetrating chest injury. Report of three cases.
Three cases of traumatic lung cysts after penetrating chest injury are described and distinguished from pulmonary haematomas. The literature on pulmonary haematomas and traumatic lung cysts is briefly reviewed.


Mitigation of Fumonisin Biomarkers by Green Tea Polyphenols in a High-Risk Population of Hepatocellular Carcinoma.
Green tea polyphenols (GTP) are highly effective in inhibiting a variety of tumorigenic effects induced by carcinogens. In this study we assessed GTP mitigation on biomarkers of fumonisin B1 (FB1), a class 2B carcinogen, in blood and urine samples collected from an intervention trial. A total of 124 exposed people were recruited and randomly assigned to low-dose (GTP 500 mg, n = 42), high-dose (GTP 1,000 mg, n = 41) or placebo (n = 41) for 3 months. After one-month of intervention, urinary FB1 was significantly decreased in high-dose group compared to that of placebo group (p = 0.045), with reduction rates of 18.95% in the low-dose group and 33.62% in the high-dose group. After three-month intervention, urinary FB1 showed significant decrease in both low-dose (p = 0.016) and the high-dose (p = 0.0005) groups compared to that of both placebo group and baseline levels, with reduction rates of 40.18% in the low-dose group and 52.6% in the high-dose group. GTP treatment also significantly reduced urinary excretion of sphinganine (Sa), sphingosine (So), and Sa/So ratio, but had no effect on serum Sa, So, and Sa/So ratio. Analysis with mixed-effect model revealed significant interactions between time and treatment effects of GTP on both urinary free FB1 levels and Sa/So ratios.


Differential influence of ampullary and isthmic derived epithelial cells on zona pellucida hardening and in vitro fertilization in ovine.
The central role of the oviduct, as the site of zona pellucida (ZP) maturation, fertilization and early embryogenesis, has been recognized. The objective of this study was to investigate whether ampullary and isthmic derived epithelial cells have different effects on in vitro ZP hardening, in vitro fertilization (IVF) and in vitro culture (IVC) of the resulting embryos. Cumulus oocyte complexes (COCs) were matured in a coculture system with ampullary/isthmic epithelial cells, TCM199 supplemented with insulin-like growth factor I (IGF-I) and epithelial derived growth factor (EGF) (GF treated group), conditioned media produced using ampullary (ACM), isthmic (ICM), COCs+ampullary, and COCs+isthmic epithelial cells, contactless culture system, oviductal fluid, GF+ACM/ICM, and drops of TCM199 (control), for 24h. The matured oocytes were randomly divided into two groups: Group I was subjected to ZP digestion; Group II underwent IVF. The duration of the ZP digestion, in a coculture system with ampullary epithelial cells (AE) was significantly increased (p<0.05), compared with other groups. Penetrated oocytes and monospermic fertilization were significantly increased (p<0.05) in the AE group. The mean number of spermatozoa per penetrated oocyte was reduced dramatically for the AE group (p<0.05). A significant increase (p<0.05) in the embryo development was observed in all treated groups, compared to the control. Results revealed that epithelial cells harvested from the ampullary segment of the oviduct had in vitro specialized role in ZP hardening and have subsequent IVF and IVC outcomes.


SNF2H interacts with XRCC1 and is involved in repair of H2O2-induced DNA damage.
The protein XRCC1 has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors. Repair foci clearly represent the recruitment and accumulation of DNA repair factors at sites of damage; however, uncertainties remain regarding their organization in the context of nuclear architecture and their biological significance. Here we identified the chromatin remodeling factor SNF2H/SMARCA5 as a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1. The proficiency of repairing H2O2-induced damage was strongly impaired by SNF2H knock-down, and similar impairment was observed with knock-down of both XRCC1 and SNF2H simultaneously, suggesting their role in a common repair pathway. Most SNF2H exists in the nuclear matrix fraction, forming salt extraction-resistant foci-like structures in unchallenged nuclei. Remarkably, damage-induced formation of both PAR and XRCC1 foci depended on SNF2H, and the PAR and XRCC1 foci co-localized with the SNF2H foci. We propose a model in which a base excision repair complex containing damaged chromatin is recruited to specific locations in the nuclear matrix for repair, with this recruitment mediated by XRCC1-SNF2H interaction.


Silencing of circUSPL1 represses breast cancer progression by targeting miR-1296-5p/MTA1 axis.
The effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague. The expression level of circUSPL1, miR-1296-5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5-ethynyl-2'-deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl-2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR-1296-5p and circUSPL1 or MTA1 was affirmed using dual-luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo. CircUSPL1 and MTA1 expression level was increased, but miR-1296-5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR-1296-5p, and downregulation of miR-1296-5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR-1296-5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR-1296-5p and regulating MTA1. CircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR-1296-5p, which might provide a theoretical basis for BC treatment.


Unique cell membrane expression of topoisomerase-II alpha as a useful diagnostic marker of liposarcoma.
Topoisomerase-II alpha (Topo-II alpha) is known as a cell cycle-related intranuclear marker. To the best of our knowledge, the expression of Topo-II alpha on extranuclear sites has not been reported. The aim of the present study was to determine the usefulness of Topo-II alpha immunostaining for detecting the lipoblasts that are essential to diagnosing liposarcoma. Surgical specimens, including benign lipomatous tumors (four cases), well-differentiated liposarcomas (three cases), myxoid liposarcomas (six cases), pleomorphic liposarcomas (two cases), dedifferentiated liposarcomas (two cases), myxoid malignant fibrous histiocytomas (six cases), and one case of mesenteric panniculitis, were studied. Samples were immunostained using antibodies for Topo-II alpha, S-100 protein and Ki-67. In addition, we used the western blot method to investigate immunohistochemical-affinity in adipocytes. Mature adipocytes and lipoblasts in all of the benign and malignant lipomatous tumors intensively expressed cell contours positivity for Topo-II alpha. Cytoplasm of the lipoblasts occasionally reacted to the antibody and highlighted intracytoplasmic small unilocular, multivacuolated, or bubble-like patterns. Western blot analysis confirmed a 70 kDa product reactive to Topo-II alpha in the cell membrane fragment of mature adipocytes. S-100 protein expressed adipocytes and lipoblasts, but the detection of lipoblasts was not as easy as in Topo-II alpha immunostaining. Immunoreactivity of Ki-67 was limited to the nuclei, and the nuclear labeling index of Ki-67 correlated with that of Topo-II alpha. The immunoreactivity of Topo-II alpha for lipoblasts was more sensitive and obvious than those of S-100 protein. Immunostaining using the antibody for Topo-II alpha seems to be useful in recognizing lipoblasts that have been overlooked in hematoxylin-eosin-stained preparations, and is a useful marker for diagnosing liposarcoma.


Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.
This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.


KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner.
Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.


Studies On The Parasitic Helminths Of Korea: II. Parasites Of The Rat, Rattus Norvegicus Erxl. In Seoul, With The Description Of Capillaria Hepatica(Bancroft, 1893) Travassos, (1915).
An investigation of the helminth parasites of house rat R. norvegicus Erxl. in Seoul has been carried on four years. A total of 325 rat was examined. Ten species of helminths were considered, of which 4 species were recored for the first time from Korea. The adult worm of Capillaria hepatica, the most common parasite of house rats in Seoul, was observed experimentally, and provided a more complete description of this worm.


Identification of DNAH6 mutations in infertile men with multiple morphological abnormalities of the sperm flagella.
Male infertility due to spermatogenesis defects affects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. Here we describe three men with primary infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) from two unrelated Han Chinese families. We performed whole-exome sequencing (WES) and Sanger sequencing on the proband of family 1, and found that he carried novel compound heterozygous missense mutations in dynein axonemal heavy chain 6 (DNAH6) that resulted in the substitution of a conserved amino acid residue and co-segregated with the MMAF phenotype in this family. Papanicolaou staining and transmission electron microscopy analysis revealed morphological and ultrastructural abnormalities in the sperm flagella in carriers of these genetic variants. Immunostaining experiments showed that DNAH6 was localized in the sperm tail. This is the first report identifying novel recessive mutations in DNAH6 as a cause of MMAF. These findings expand the spectrum of known MMAF mutations and phenotypes and provide information that can be useful for genetic and reproductive counseling of MMAF patients.


mRNA from mutant Y1 adrenal cells directs the synthesis of altered regulatory subunits of type 1 cAMP-dependent protein kinase.
The molecular basis for altered cyclic AMP-dependent protein kinase activity was examined in three different mutant clones (Kin-1, Kin-7, and Kin-8) derived from the Y1 mouse adrenocortical cell line. Parental Y1 cells and the Kin mutants were labeled with L-[35S] methionine and the regulatory subunit of the type 1 cAMP-dependent protein kinase isozyme (RI) was immunoprecipitated from each clone with a specific guinea pig antiserum. When analyzed by electrophoresis on isoelectric focusing gels, the immunoprecipitates from mutant clones exhibited parental forms of RI plus an additional acidic variant form which likely accounted for altered cAMP-dependent protein kinase activity. Poly(A+) RNA was isolated from Y1 and Kin mutant cells and was translated in a cell-free, reticulocyte lysate system in the presence of L-[35S]methionine. The RI synthesized from poly(A+) RNA was immunoprecipitated from the translation mixture and analyzed on isoelectric focusing gels. The poly(A+) RNA from the Kin mutant clones directed the synthesis of parental and acidic variant forms of RI. These results suggest that the altered electrophoretic forms of RI arise from mutations in one of two RI genes rather than from post-translational modifications of the protein. The coexistence of parental and variant forms of RI in the Kin mutants indicate that the mutations are codominant.


Insights from Expanded Adverse Childhood Experiences Screening in a Hospital-Based Outpatient Psychiatry Service.
Adverse childhood experiences (ACEs) are associated with poor mental health in adulthood. Comprehensive prevalence data encompassing all 10 ACE questionnaire items has not previously been described in a hospital-based outpatient psychiatric clinic. This study assessed the prevalence of 10 ACEs in such a clinic and correlated ACEs with indicators of case severity. For 252 patients newly evaluated in an urban clinic, a retrospective chart review was completed and data was collected on ACE questionnaire responses, psychiatric, substance-related, and medical diagnoses, psychiatric hospitalizations, suicide attempts, and suicide and violence risk. Patients in the clinic had an average of 3.4 ACEs, higher than national community sample averages of 1.6. The percentages of patients with at least one, two, and four ACEs were 82% (n = 207), 68% (n = 172), and 42% (n = 106) respectively (compared with 61%, 38%, and 15% nationally). ACEs had statistically significant correlations with an increased number of psychiatric diagnoses, substance use disorders, medical illnesses, suicide attempts, and suicide risk level. This study demonstrated that patients seeking psychiatric care from a hospital-based outpatient clinic are likely to be traumatized to a degree far exceeding what is typical in the general population. While a high prevalence of ACEs in a psychiatric population is an expected finding given the literature to date, this is the first study presenting data on the prevalence of ACEs in such a hospital-based community clinic. Additionally this study reinforces prior research correlating childhood adversity and case severity.


Sex differences in piercing-sucking sites on leaves of Ligustrum lucidum (Oleaceae) infested by the Chinese white wax scale insect, Ericerus pela (Chavannes) (Hemiptera: Coccidae).
The type of host tissues and cells ingested by piercing and sucking insects greatly affects their nutrient intake, which may subsequently affect insect fitness. This study describes the sex differences in feeding site selection between male and female nymphs of the Chinese white wax scale insect (CWWS), Ericerus pela (Chavannes), feeding on leaves of the Chinese privet, Ligustrum lucidum. Our data showed that the stylet tips of female nymphs terminated in the phloem sieve elements of main or lateral veins, while those of male nymphs terminated in the palisade parenchyma. We concluded that female nymphs fed from sieve elements and males fed from parenchyma cells. The potential impact of these feeding patterns was discussed in relation to the selection of a site for attachment, nutrient acquisition, and mouthpart stretching mechanism. Among these factors, selection of a site for attachment and mouthpart stretching mechanism may be the main cause of sex differences in feeding sites between female and male nymphs of CWWS.


In vitro effects of lidocaine on contractility of circular and longitudinal equine intestinal smooth muscle.
The purpose of the study was to compare the contractility-enhancing effects of lidocaine in equine jejunal circular (CSM) and longitudinal smooth muscle (LSM) in vitro. In previous studies, more pronounced effects of lidocaine were observed in ischaemia-reperfusion (IR) injured smooth muscle. Therefore in this study, effects were examined in both non-injured control tissues and tissues challenged by a defined, artificial IR injury. Isometric contractile performance of CSM and LSM, assessed by frequency (F), amplitude (A) and mean active force (MAF) of contractions, was defined as contractility. LSM featured lower basic contractility compared to CSM. Lidocaine provoked contractility-enhancing effects in both smooth muscle layers, but except for F at high lidocaine concentrations, contractility of LSM remained lower throughout the trial. Additionally, higher lidocaine concentrations were required to cause significant effects in LSM. No differences were observed in contractility of control and IR injured smooth muscle, but higher lidocaine concentrations were needed to provoke effects in IR injured smooth muscle. In contrast to CSM, contractility of LSM did not decrease at comparably high lidocaine concentrations. Differences in basic contractility of CSM and LSM might be explained by physiologically lower activity of LSM per se or by a thinner LSM layer with fewer smooth muscle cells taking part in contractions. The smaller thickness of the LSM layer may also contribute to persisting discrepancies in contractility following lidocaine application. Additionally, variations in lidocaine concentrations necessary for inducing significant effects could result from differences in the molecular structure of CSM and LSM cells.


Work stress and emotional exhaustion in nurses: the mediating role of internal locus of control.
Burnout is a major problem for nursing. There is a strong relationship between work stress and emotional exhaustion. Although studies report a negative correlation between the internal locus of control and emotional exhaustion and work stress, the number of studies available on the subject is limited. This study intends to examine the extent to which the relationship between work stress and emotional exhaustion is mediated by nurses' internal locus of control. The study adopted a cross-sectional survey design. The data were analyzed using structural equation modeling techniques. The study sample consisted of 347 nurses who worked in a university hospital in Izmir, Turkey and who agreed to participate in the study. The Work-Related Strain Inventory was used to evaluate the nurses' work stress level, Maslach Burnout Inventory was used to evaluate their emotional exhaustion levels, and the Locus of Control Scale was used to evaluate the internal locus of control. The variables of the study were based on the Neuman Systems Model. Work stress was positively related to internal locus of control (β3 = .21, p < .001), which was, in turn, negatively associated with emotional exhaustion (β = -.03, p > 0.1). Internal locus of control was negatively related to emotional exhaustion (β = -.14, p < .001). Work stress is directly (β = .87, p < .001) and indirectly related to emotional exhaustion (mediated by internal locus of control β = .84, p < .001). Work stress is directly (β = .87, p < .001) and indirectly related to emotional exhaustion (mediated by internal locus of control, β = .84, p < .001). Although the relationship between emotional exhaustion and work stress was mediated, the impact of internal locus of control was limited. It is recommended that different variables be included in future studies so that they can mediate the relationship between work stress and emotional exhaustion.


Tupaia MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB.
Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.


A Hansel & Gretel breadcrumb-style dynamically deployed communication network paradigm using mesh topology for planetary subsurface exploration.
We introduce a dynamically deployed communication network (DDCN) paradigm using mesh topology in support of a distributed robotic multi-agent approach for the autonomous exploration of subsurface environments, i.e., caves, lava tube caves, lakes, and oceans, etc. The DDCN, comprising wireless communication beacons autonomously deployed via a rover or submersible in a Hansel & Gretel-inspired breadcrumb style, allows for the longest and most robust communication link between subterranean robotic agent(s) within, e.g., a lave tube cave or a subsurface ocean, and associated surface-borne robotic agent(s). Moreover, we briefly touch on the development of a robotic testbed and wired/wireless communication beacons in support of such astrobiological surface/subsurface exploration scenarios. Candidate lava tube caves have been identified on the Moon and Mars, raising possibilities for planetary exploration, astrobiology, habitat construction for future astronauts, and potential mining operations. Subterranean caverns, and in particular relatively deep lava tube caves, provide a possible refuge for life under otherwise challenging planetary surface conditions, and, as such, are of prime astrobiological relevance. Lava tube caves or other subsurface environments may also be suitable habitats for astronauts and subsequent human settlement but are yet to be explored in part due to difficulties ensuring continued communication with a robotic probe inside these environments. Moreover, the existence of subsurface oceans on ocean worlds, such as Europa, Enceladus, and Titan, has been backed by varying levels of evidence since the 1980s, though there has been no confirmation, i.e., direct observation, thus far. Such environments are also shielded from radiation, and, in combination with the hypothesized presence of water, are additional candidate environments for finding extant or fossilized life. The DDCN paradigm introduced herein directly addresses NASA's Space Technology Grand Challenges - "All Access Mobility" by enabling the most unconstrained exploration of subsurface environments through a dynamic communication network which ensures transmission of data from and possibly commands to the subsurface robotic probe. 2023 COSPAR. Published by Elsevier B.V. All rights reserved.


Relationship between perinatal and neonatal indices and intelligence quotient in very low birth weight infants at the age of 6 or 8 years.
The majority of children born with very low birth weight (VLBW; < 1500g) enter mainstream schools. They experience significant neurodevelopmental disabilities during childhood. The specific aims of our study were to evaluate the neonatal outcomes of VLBW infants and whether they would influence intelligence quotient (IQ), cognitive function and learning disabilities at the age of 6 or 8 years. We enrolled VLBW neonates who weighed less than 1500g and who were delivered at Shin-Kong Wu Ho-Su Memorial Hospital in 1996 and 1999. The psychological assessments were applied with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) for age 6 and Wechsler Intelligence Scale for Children-Third Edition (WISC-III) for age 8. We recorded their demographic data, ventilation duration by days, length of stay, use of surfactant, respiratory distress syndrome (RDS), and other complications. According to whether the full scale intelligence quotient (FSIQ) was above or below the average score (FSIQ = 90), we divided VLBW children into two groups (< 90, n = 17; > or = 90, n = 21). The children with lower gestational age had lower FSIQ (p = 0.013). The higher FSIQ group (> or = 90) showed more prenatal steroid use (5/17, 29.4% vs. 14/21, 66.7%; p = 0.049). There were more boys in the lower FSIQ group (< 90, 13/17, 76.5% vs. > or = 90, 7/21, 33.3%; p = 0.011). The average IQ scores were 78.11 +/- 9.05 and 102.57 +/- 8.89 in the FSIQ < 90 and FSIQ > or = 90 groups, respectively. The groups were similar in ventilation duration by days, use of surfactant, frequency of sepsis, RDS, bronchopulmonary dysplasia, patent ductus arteriosus, intraventricular hemorrhage and retinopathy of prematurity. In our study, the children with lower gestational age had lower FSIQ. There was no significant association between small for gestational age and IQ performance. The neonatal outcomes of VLBW infants did have less impact on IQ performance later in life.


Autosomal dominant familial Mediterranean fever-like syndrome with amyloidosis.
We report a pedigree in which a syndrome that resembled familial Mediterranean fever occurred in four family members over three successive generations. All four patients had systemic amyloidosis. Typically, patients with familial Mediterranean fever show an autosomal recessive inheritance pattern. The disorder commonly afflicts Sephardic Jews, Arabs, and persons of Turkish descent. Colchicine therapy dramatically reduces the attack rate of serositis. The family described herein is unique because of their European ethnicity and the autosomal dominant inheritance pattern. Unlike typical familial Mediterranean fever, colchicine had no influence on the attacks and did not prevent amyloidosis in the three patients who received this treatment.


The Causes and Laryngeal Electromyography Characteristics of Unilateral Vocal Fold Paralysis.
To investigate the causes and laryngeal electromyography (LEMG) characteristics of unilateral vocal fold paralysis (UVFP). We retrospectively analyzed the history and LEMG of 337 patients with unilateral vocal fold immobility. The etiology was reviewed and the characteristics of LEMG (including spontaneous potential, recruitment potential, evoked potential, synkinesia, and et al.) were analyzed. The causes included injury (177 cases, 52.5%), idiopathic causes (72 cases, 21.4%), infection (61 cases, 18.1%), tumor and compressive factors (27 cases, 8.0%). Among the injury group, 161 cases were caused by surgery (111 cases of thyroid surgery), and 16 cases were caused by trauma. LEMG showed that complete nerve injury was present in 72.9% of the injury group, 66.7% of the tumors or compressive factors group, 49.2% of the infection group, and 44.4% of the idiopathic group. Of the 337 patients, 136 patients (40.4%) had synkinesia in the posterior cricoarytenoid muscles, and only two of these patients also had synkinesia in the thyroarytenoid muscles. The proportion of complete recurrent laryngeal nerve (RLN) injury in patients with synkinesia was higher than that of patients without synkinesia. The main cause of vocal fold paralysis is neck surgery, most commonly thyroid surgery. Patients with different causes of paralysis had different severities of RLN injury. LEMG showed that surgery or trauma accounted for the highest proportion of complete nerve injury. Patients with severe RLN injury were more prone to synkinesia, and the posterior cricoarytenoid muscles were more likely to have synkinesia than the thyroarytenoid muscles.


Bullard laryngoscopy by naïve operators in the cervical spine immobilized patient.
To determine ease of Bullard laryngoscopy by naïve operators during cervical spine immobilization, 21 residents, naïve to the Bullard laryngoscope, were assigned to perform Bullard laryngoscopy and standard direct laryngoscopy on the Laerdal SimMan Universal Patient Simulator while the rigid cervical spine function was engaged. Sequences were repeated. Success of laryngeal intubation, time to intubation, ease of intubation, and grade of laryngoscopic view were recorded and compared. Pairwise comparisons of consecutive times between standard and Bullard devices showed significant difference in mean times at first attempt, 28.8 (95% confidence interval [CI] 18.1-39.5) seconds in favor of Macintosh laryngoscopy, but no statistical differences between devices at second and third attempts, with differences in mean times of 4.5 (95% CI 2.5-6.5) and 3.8 (95% CI, 0.1-7.7) seconds, respectively. Similarly, ease of use was statistically unchanged over time for Macintosh laryngoscopy, but there was statistically significant improvement in ease of use for the Bullard. The Bullard laryngoscope is an easily mastered airway management device for intubation of the cervical spine immobilized patient.


What is effective in malignant middle cerebral artery infarction: reperfusion, craniectomy, or both? An experimental study in rats.
We sought to evaluate the effects of reperfusion and craniectomy treatment at different time points after middle cerebral artery (MCA) occlusion on infarct volume and neurological outcome in MCA infarction in rats. We used an endovascular technique to obtain MCA occlusion in 182 rats. Thirteen groups with 14 animals each were investigated: control group 1 with no treatment; groups 2 to 7 with only reperfusion or craniectomy at 1, 4, or 12 hours, respectively; and groups 8 to 13 with reperfusion at 1 or 4 hours combined with craniectomy at 1, 4, or 12 hours, respectively. We used infarct volume and neurological performance as study end points in all animals at day 7. Neurological score and infarct volume in animals undergoing early reperfusion at 1 hour were significantly smaller (1.8/79+/-59 mm3) than those in control animals (3.8/225+/-26 mm3) (P<0.01). Reperfusion at 4 hours (2.8/182+/-62 mm3) and 12 hours (3.7/231+/-69 mm3) did not result in significant improvement. Animals undergoing craniectomy at 1, 4, and 12 hours demonstrated significantly better outcome and significantly reduced infarct volume (1.6/96+/-30 mm3, 1.9/109+/-39 mm3, and 2.6/150+/-34 mm3, respectively) (P<0.05). Compared with 1 treatment at a time, combined reperfusion and craniectomy did not result in a significant additional benefit. Early reperfusion and craniectomy at 1 hour are both effective in large MCA infarction. While reperfusion later than 1 hour was not beneficial, late craniectomy at 4 and 12 hours still resulted in significant improvement of neurological score and reduction of infarction size. Combined treatment at different time points yields no significant additional benefit compared with 1 treatment at a time.


Origins of the specificity in the intercalation of ethidium into nucleic acids. A theoretical analysis.
The sequence preferences observed in the intercalative binding of ethidium to dinucleoside phosphates have been theoretically examined. This specificity is for pyrimidine (3'--5') purine sequences as compared to their purine (3'--5') pyrimidine sequence isomers. It is shown that the stacking energies between the ethidium cation and the base pairs are fairly constant for all combinations of bases at the intercalation site. In contrast, the energy of unwinding the double helix to assume the geometry of the intercalation complex shows substantial sequence differences. Thus, the specificity observed is more readily explained in terms of these conformation energy changes than by preferential stacking interactions. These results imply that there may be a large class of intercalating molecules which exhibit similar pyrimidine (3'--5') purine sequence specificity.


Visual symptoms in the presentation of Creutzfeldt-Jakob disease.
We describe a 68-year-old man with a previous history of neurosurgical repair of a skull fracture, who presented to the ophthalmology clinic with progressive visual decline. His initial visual acuity was 6/30 in the right eye and 6/48 in the left, and over 2 weeks this progressed to hand movements in both eyes. No ocular abnormalities were identified. He was noted to be increasingly confused and a subsequent MRI showed extensive bilateral posterior cortical changes consistent with cytotoxic oedema. An electroencephalogram was suggestive of encephalopathy, particularly involving the occipital lobe. He was diagnosed with the Heidenhain variant of Creutzfeldt-Jakob disease (CJD), confirmed by a positive cerebrospinal fluid 14-3-3 protein. Classically, patients with CJD present with rapidly progressive cognitive decline, ataxia and myoclonus. However, visual symptoms are a common and perhaps underrecognised manifestation of CJD. Patients can present with isolated visual symptoms which precede cognitive decline by weeks due to predominantly occipital lobe disease. This presentation is classified as the Heidenhain variant of CJD.


CPGs may not be best for older patients.
Researchers evaluate CPGs for nine of 15 most common chronic diseases. Non-pharmacological guidelines, as well as meds, may contradict each other. In hypothetical patient, recommended medications would cost more than dollar 400 per month.


The influence of epidural analgesia on cesarean delivery rates: a randomized, prospective clinical trial.
The effects of epidural analgesia on the progress of labor are controversial. The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients randomly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief. From January 1995 to May 1996, 318 spontaneously laboring, term, nulliparous patients were randomly assigned to receive either intravenous opioids or epidural analgesia for pain relief. Labor was managed according to the principles of active management of labor. Cesarean delivery was performed for obstetric indications. Data analysis was conducted on an intent-to-treat basis. A subanalysis was subsequently performed on patients who were compliant with the allocated form of treatment. One hundred sixty-two patients were randomly assigned to receive intravenous meperidine and 156 were randomly assigned to receive epidural analgesia. Maternal age, gravidity, race, gestational age, and cervical dilatation at admission and at first analgesic dose did not differ between the groups. Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups, being 13.6% in the opioid group and 9.6% in the epidural group (relative risk 0.70, 95% confidence interval 0.38-1.31, P >.05). Cesarean delivery rates for the indication of dystocia also did not differ, being 10.5% in the opioid group and 5.8% in the epidural group (relative risk 0.56, 95% confidence interval 0.26-1.21, P >.05). Subanalysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group (n = 147) were 3 times more likely to have an active phase duration >/=8 hours and were 10 times more likely to require >/=2 hours in the second stage of labor than were those in the opioid group (n = 78). There were no significant differences in cesarean delivery rates in this subanalysis, being 7.7% in the opioid group and 8.8% in the epidural group (relative risk 1.15, 95% confidence interval 0.45-2.91, P >. 05). The cesarean delivery rates for dystocia were also similar in the subanalysis, being 3.8% in the opioid group and 5.5% in the epidural group (relative risk 1.42, 95% confidence interval 0.39-5. 22, P >.05). Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome.


A rapid gas-liquid chromatographic estimation of nicotine in biological fluids.
A rapid gas-liquid chromatographic method for the estimation of nicotine in plasma is described. Nicotine is extracted from alkalinized plasma into diethyl ether. This is then concentrated by evaporation and, after an acid back extraction is re-extracted into n-heptane (nitrogen detector) or dichloromethane (flame ionization detector) before injection onto the gas chromatography. Thirty samples a day can be analysed by this method which enables concentrations of 0.1 ng ml- minus 1 nicotine to be measured. It is thus possible to measure nicotine in plasma and urine samples from non-smokers.


Explorating the mechanism of Huangqin Tang against skin lipid accumulation through network pharmacology and experimental validation.
Huangqin Tang (HQT), a famous prescription with the effect of clearing pathogenic heat and detoxifying, was first recorded in "Treatise on Typhoid and Miscellaneous Diseases". It has proved that HQT has good anti-inflammatory and antioxidant effects and can improve acne symptoms clinically. However, the study on the regulation of HQT on sebum secretion which is one of the inducements of acne is not enough. This paper aimed to investigate the mechanisms of HQT in the treatment of skin lipid accumulation by network pharmacology and validating the results via in vitro experiments. Network pharmacology was employed to predict the potential targets of HQT against sebum accumulation. Then, the palmitic acid (PA)-induced SZ95 cell model was established to evaluate the effect of HQT on lipid accumulation and anti-inflammation, and the core pathways predicted by network pharmacology were verified in cell studies. 336 chemical compounds and 368 targets in HQT were obtained by network pharmacology, of which 65 targets were related to sebum synthesis. 12 core genes were revealed by protein-protein interaction (PPI) network analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results suggested that AMP-activated protein kinase (AMPK) signaling pathway might play a crucial role in regulating lipogenesis. In vitro experiments, HQT suppressed lipid accumulation, downregulated the expressions of sterol-regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS), and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor reversed HQT-mediated sebosuppressive effect. The results disclosed that HQT ameliorates lipogenesis in PA-induced SZ95 sebocytes partially through the AMPK signaling pathway.


Bacterial lysates as a potentially effective approach in preventing acute exacerbation of COPD.
The use of bacterial lysates to reduce acute exacerbations of COPD (AECOPDs) is an intriguing concept. Bacterial lysates are powerful inducers of a specific immune response against bacterial infections, but their mechanism of action is not fully understood. Apparently, they lower bacterial carriage levels in the respiratory tract, decrease the incidence and severity of exacerbations, decrease hospitalizations owing to exacerbations, and reduce the need for antibiotics. Unfortunately, almost all trials conducted to date are small and methodologically flawed. Further studies are needed to produce a greater level of evidence that can support the recommendation for a more widely use of bacterial lysates as a prophylactic treatment of AECOPDs.


Compositional statistics: an improvement of evolutionary parsimony and its application to deep branches in the tree of life.
We present compositional statistics, a new method of phylogenetic inference, which is an extension of evolutionary parsimony. Compositional statistics takes account of the base composition of the compared sequences by using nucleotide positions that evolutionary parsimony ignores. It shares with evolutionary parsimony the features of rate invariance and the fundamental distinction between transitions and transversions. Of the presently available methods of phylogenetic inference, compositional statistics is based on the fewest and mildest assumptions about the mode of DNA sequence evolution. It is therefore applicable to phylogenetic studies of the most distantly related organisms or molecules. This was illustrated by analyzing conservative positions in the DNA sequences of the large subunit of RNA polymerase from three archaebacterial groups, a eubacterium, a chloroplast, and the three eukaryotic polymerases. Internally consistent results, which are in accord with our knowledge of organelle origin and archaebacterial physiology, were achieved.


Functional genomics and target validation approaches using antisense oligonucleotide technology.
The recent increase in the amount and rate of accumulation of genomic information has created new challenges for the pharmaceutical industry. These include how best to rapidly and efficiently identify key genes responsible for complex disease phenotypes and how to use this information to develop new and specific classes of drugs. Antisense technology offers a powerful approach to identify novel cellular networks and signaling "cassettes" and provides a method to validate genes in vivo as attractive drug targets.


Prospective cohort of parameters of glycemic and lipid metabolism after abdominoplasty in normal weight and formerly obese patiens.
Obesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. In order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. No statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p <0.001) between the groups. Abdominoplasty was not able of changing tests that assess glycemic and lipid metabolism three months after the operation. Our attention was drawn to the fact that patients who had massive weight loss had better control of LDL cholesterol (p = 0.033) and non-HDL cholesterol (p = 0.020), despite having higher weight and body mass index (p <0.001).


Orientation-specific attachment of polymeric microtubes on cell surfaces.
Tubular particles presenting heterogeneous regions of chemistry on the tube-ends versus the side are fabricated and are shown to control the particle orientation on the surface of live lymphocytes. Controlling the orientation of anisotropic microparticles on cell surfaces is of interest for biomedical applications and drug delivery in particular, since it can be used to promote or resist particle internalization.


Evaluation Effects of Laser Therapy and Extracorporeal Shock Wave Therapy with Clinical Parameters and Magnetic Resonance Imaging for Treatment of Plantar Fasciitis in Patients with Spondyloarthritis: A Randomized Controlled Trial.
Low-level laser therapy (LLLT) and extracorporeal shock wave therapy (ESWT) is applied in the conservative treatment of inflammatory plantar fasciitis, which is also a characteristic feature of spondyloarthritis (SpA) (Gill, 1997 and Roxas, 2005). We determined and compared the effectiveness of LLLT and ESWT using magnetic resonance imaging (MRI). This study is a prospective, randomized, comparative, single-blind clinical study. Voluntarily followed 40 patients with the diagnosis of SpA and having pain at the heels at least for 6 months. Patients were divided randomly into two treatment groups. One group undertook 14 sessions of infrared Ga-Al-As LLLT, and the other group undertook 3 sessions ESWT. Feet functions of the patients were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) and Roles and Maudsley Scoring; VAS was evaluated for foot pain and function. In clinical assessment, disease activity was carried out by applying the BASDAI, the functional assessment was evaluated through the BASFI, and the patient quality of life was evaluated through the ASQoL; enthesitis was scored according to MASES assessment, performed before and at 1 month after treatment. The thickness of the plantar fascia was measured with MRI before and 1 month after treatment. Compared with the pretherapy, progress in the feet function by AOFAS and Roles-Maudsley scoring and decrease in VAS levels were statistically significant in both groups (p < 0.001). Only the VAS exercise score was superior to LLLT (p < 0.05). The thickness of the plantar fascia had decreased significantly on MRI in all two groups. The treatment of plantar fasciitis with LLLT and ESWT was more successful in pain improvement and functional outcomes with the dose, frequency, and duration used in our study.


General and paediatric dentists' knowledge, attitude and practises regarding the use of Silver Diammine Fluoride for the management of dental caries: a national survey in the Netherlands.
Silver Diammine Fluoride (SDF) is a topical medication used to arrest cavitated carious lesions non-invasively. The primary aim was to investigate, and analyse the relationships between; knowledge, attitudes and practises (including barriers and facilitators) for SDF use in the management of dental caries by general dental practitioners (GDPs) and paediatric dentists (PDs) in the Netherlands. A secondary aim was to explore any differences in these, between these groups. A randomly selected sample of 600 Dutch GDPs (out of 9,502 respectively) and all 57 registered Dutch PDs were invited to participate in this cross-sectional survey, consisting of four sections: (1) participant characteristics, (2) knowledge (through responses to summative questions), (3) attitudes (through statement agreement using 5-point Likert scale), and (4) practises, use, barriers and facilitators (through multiple choice questions). The response rates were: GDPs 23% (n = 140) and PDs 47% (n = 27). Knowledge: out of 15 questions to test understanding of SDF, the mean number of correct answers were GDPs 6.7; standard deviation (SD) 2.6 and PDs 7.4, SD 2.2 with no significant difference. The mean overall attitude score showed positive attitudes towards SDF use for both groups. Compared to GDPs, PDs were more likely to use SDF (p < 0.001) and expected to increase their use (p = 0.037). The main barrier for users was parental acceptance (47%) and for non-users it was lack of knowledge (60%). The main facilitator for both users and non-users was gaining knowledge through courses and workshops, followed by written information leaflets about SDF for parents. Less than half of the knowledge questions about SDF were answered correctly. Despite low knowledge, attitude towards SDF use was positive. Practitioners believed that its use would be facilitated by professionals having more accessible information and training and by the availability of parent information leaflets. Furthermore, SDF is used more frequently by PDs than GDPs.


A sensitive latex agglutination method for the detection of soluble fibrin in plasma.
A sensitive method is described for the rapid detection of soluble fibrin in human plasma. It is based on the agglutination of Latex particles suspended in a solution of purified fibrin monomers and Blue Dextran 2000. Photometric registration of the decrease in optical density (OD) during agglutination allows the results to be quantitated. The deltaOD depends on the ratio of fibrin monomers to fibrinogen in the tested plasma rather than on the absolute amount of fibrin monomers present.


[Tuberculosis of the larynx in patients treated in laryngological clinic No. 2 in Zabrze].
3 cases of tuberculosis of the larynx were presented in this paper. Provisional diagnosis was tumor of the larynx. Further specialistic investigations e.g. MDL and biopsy were done and revealed proper diagnosis tuberculosis of the larynx.


Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope.
A unique, protective cell envelope contributes to the broad drug resistance of the nosocomial pathogen Acinetobacter baumannii. Here we use transposon insertion sequencing to identify A. baumannii mutants displaying altered susceptibility to a panel of diverse antibiotics. By examining mutants with antibiotic susceptibility profiles that parallel mutations in characterized genes, we infer the function of multiple uncharacterized envelope proteins, some of which have roles in cell division or cell elongation. Remarkably, mutations affecting a predicted cell wall hydrolase lead to alterations in lipooligosaccharide synthesis. In addition, the analysis of altered susceptibility signatures and antibiotic-induced morphology patterns allows us to predict drug synergies; for example, certain beta-lactams appear to work cooperatively due to their preferential targeting of specific cell wall assembly machineries. Our results indicate that the pathogen may be effectively inhibited by the combined targeting of multiple pathways critical for envelope growth.


Knock-sideways by inducible ER retrieval enables a unique approach for studying Plasmodium-secreted proteins.
Malaria parasites uniquely depend on protein secretion for their obligate intracellular lifestyle but approaches for dissecting Plasmodium-secreted protein functions are limited. We report knockER, a unique DiCre-mediated knock-sideways approach to sequester secreted proteins in the ER by inducible fusion with a KDEL ER-retrieval sequence. We show conditional ER sequestration of diverse proteins is not generally toxic, enabling loss-of-function studies. We employed knockER in multiple Plasmodium species to interrogate the trafficking, topology, and function of an assortment of proteins that traverse the secretory pathway to diverse compartments including the apicoplast (ClpB1), rhoptries (RON6), dense granules, and parasitophorous vacuole (EXP2, PTEX150, HSP101). Taking advantage of the unique ability to redistribute secreted proteins from their terminal destination to the ER, we reveal that vacuolar levels of the PTEX translocon component HSP101 but not PTEX150 are maintained in excess of what is required to sustain effector protein export into the erythrocyte. Intriguingly, vacuole depletion of HSP101 hypersensitized parasites to a destabilization tag that inhibits HSP101-PTEX complex formation but not to translational knockdown of the entire HSP101 pool, illustrating how redistribution of a target protein by knockER can be used to query function in a compartment-specific manner. Collectively, our results establish knockER as a unique tool for dissecting secreted protein function with subcompartmental resolution that should be widely amenable to genetically tractable eukaryotes.