Macrophage subpopulations in gingival overgrowth induced by nifedipine and immunosuppressive medication.
The immunomodulating effects of both immunosuppressive and nifedipine medication have been associated with drug-induced gingival overgrowth. The aim of the study reported here was to evaluate the presence of macrophage subpopulations in normal human gingiva and in gingival overgrowth induced by nifedipine and immunosuppressive medication. Gingival samples were taken from 11 nifedipine-medicated cardiac outpatients (nifedipine group), 11 triple-medicated organ-transplant recipients also taking nifedipine (immunosuppression plus nifedipine group), 12 triple-medicated organ-transplant recipients (immunosuppression group), and 20 generally healthy individuals (control group). Cryostat sections were stained with mAbs for inflammatory 27E10, reparative RM3/1, and resident 25F9 macrophages using an avidin-biotin enzyme complex method. Total numbers of mAb-labeled cells were determined in connective tissue beneath sulcular epithelium, connective tissue beneath oral epithelium, and middle connective tissue. Expression of 27E10 was determined in keratinocytes in the oral epithelium. Statistics analyses were undertaken using the chi-square test, the Mann-Whitney U test, the independent samples t test, analysis of variance, and analysis of covariance. Greater numbers of inflammatory 27E10-positive macrophages were found in all 3 medicated groups and counting zones than in the control group except in connective tissue beneath sulcular epithelium in the immunosuppression group. The incidence of specimens expressing 27E10 antigen throughout the oral epithelium was significantly higher in the immunosuppression group (8 of 12) than in the control group (4 of 20) and the nifedipine group (2 of 11). Numbers of reparative RM3/1-positive macrophages were significantly greater in the immunosuppression group in connective tissue beneath oral epithelium than in the control group. The effect was markedly associated with degree of inflammation. Numbers of resident 25F9-positive macrophages were lower in connective tissue beneath sulcular epithelium in the immunosuppression group, and higher in middle connective tissue in the nifedipine group than in the control group. Our results show that the nature of drug-induced gingival overgrowth differs somewhat between immunosuppressive and nifedipine medications.


Recent Advances in Novel Antiviral Therapies against Human Adenovirus.
Human adenovirus (HAdV) is a very common pathogen that typically causes minor disease in most patients. However, the virus can cause significant morbidity and mortality in certain populations, including young children, the elderly, and those with compromised immune systems. Currently, there are no approved therapeutics to treat HAdV infections, and the standard treatment relies on drugs approved to combat other viral infections. Such treatments often show inconsistent efficacy, and therefore, more effective antiviral therapies are necessary. In this review, we discuss recent developments in the search for new chemical and biological anti-HAdV therapeutics, including drugs that are currently undergoing preclinical/clinical testing, and small molecule screens for the identification of novel compounds that abrogate HAdV replication and disease.


Acute myocardial rescue with endogenous endothelial progenitor cell therapy.
Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated. Lewis rats (n=91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation. SDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12±0.02% vs. 0.06±0.01% circulating lymphocytes, p=0.005), 48hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02±1.7×10(-2)μm(3)blood/μm(3)myocardial tissue vs. 2.03±0.710(-2)μm(3)blood/μm(3)myocardial tissue, p=0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98±0.09mm vs. 0.67±0.06mm, p=0.003) and ventricular diameter (7.81±0.99mm vs. 9.41±1.1mm, p=0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4±18.1% vs. 25.3±15.6%, p=0.001; pre-load adjusted maximal power: 6.6±2.6mW/μl(2) vs. 2.7±1.4mW/μl(2), p=0.01). Neovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.


Complications of bronchoscopy for foreign body removal: experience in 1,035 cases.
Tracheobronchial foreign body aspirations, which threaten lives in childhood, also carry potential risks during and after bronchoscopy. The aim of this study is to review complications and precautions that need to be taken against possible risks. From 1987 to 2005, bronchoscopy was done in 1,035 children in our department on suspicion of foreign body aspiration. The average age of these patients, mostly male (55%), was 4.1 years. Medical history, physical examination, radiological methods and bronchoscopy were used in the diagnosis. Bronchoscopy was applied under general anaesthesia, and the respiratory and cardiac systems were closely observed for 4 hours after the process. Nine hundred eleven of 1,035 patients (88%) had a foreign body in the tracheobronchial system. In 42 of the patients, infection required aggressive medication; in 30, hypoxia and bradycardia occurred as a result of obstruction during bronchoscopy; in 37, laryngeal edema, laryngeal spasm and/or bronchospasm required ventilation support; in 6 patients, tracheobronchial system bleeding occurred; in 2 patients pneumothorax occurred, in 1 patient pneumomediastinum was observed and 6 patients needed thoracotomies because of foreign body aspiration. In this series there were 8 deaths. Bronchoscopy, performed for tracheobronchial foreign body aspiration, carries a potential life-threatening risk during and after the process. The clinician needs to be aware of these risks, take proper precautions, and perform bronchoscopy by taking the medical condition of the patient and characteristics of the inspired foreign body into consideration.


Controversies in Screening Mammography.
The utility and effectiveness of screening mammography in diagnosing breast cancer at earlier stages and reducing disease-specific mortality remain controversial especially as to when to start and stop routine mammographic screening, and whether mammograms should be performed annually or biennially in average-risk women. This manuscript will analyze the available moderate and high-quality data to analyze both the benefits (lives saved and life-years saved) and inconveniences/harms (additional views, extra biopsies/overdiagnosis, and overtreatment of ductal carcinoma in situ) of different mammography screening guidelines to assist the practitioner in counseling their patients in clinical practice.


Statistical approaches for evaluation of genetic risk factor of peripheral arterial occlusive disease.
In the paper we show results of medical study from statistical point of view. The medical study was aimed to study genetic risk factors of peripheral arterial occlusive diseases in Czech population. Two genes, CBS and MTHFR were examined, as various genotypes of these genes are thought to have impact on amino thiols, who participate in variety of reactions in vasculature. Statistical part of the study was responsible for analysis and interpretation of collected data.


Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study.
Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.


[Effect of Electroacupuncture Serum on Proliferation of Cultured Multifidus Muscle Satellite Cells and Expression of Pax-7, MyoD and p-Akt].
To observe the effect of electroacupuncture (EA) serum on proliferation of multifidus muscle sa-tellite cells (SCs) and expression of paired box transcription factor Pax-7, MyoD and protein kinase B (PKB or Akt) proteins of SCs, so as to explore its underlying mechanism in promoting repair of multifidus muscles. Thirty-two SD rats were randomly assigned to control, model, EA-Weizhong (BL 40) and EA-Shenshu (BL 23) groups. The multifidus muscle injury (MFMI) model was established by injection of 0.5% bupivacaine hydrochloride (400 μL) into the bilateral L4-L5 paravertebral muscles (4 points, 100 μL for each point). EA stimulation was separately applied to bilateral BL 40 and BL 23 for 20 min, once daily, 4 days altogether. Blood samples of the abdominal artery of rats in the above mentioned 4 groups were separately collected for extracting serum, followed by deactivation and filtration, and then were respectively applied to the Dulbecco's Modified Eagle Media (DMEM) culturing each multifidus muscle SCs of the normal serum, model serum, EA-BL 40 serum and EA-BL 40 serum+LY 294002 (an inhibitor of phosphotidylinsitol-3-kinase, PI 3 K), EA-BL 23 serum and EA-BL 23 serum+LY 294002 groups for ana-lyzing the impact of EA serum on the proliferation state of SCs by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) methods, respectively. The expression of Pax-7, MyoD and phosphorylated (p)-Akt proteins of the cultured SCs was detected for characterization of SCs by Western blot. Compared with the normal serum group, the proliferation levels (detected by both CCK-8- and EdU) and the expression levels of MyoD and p-Akt proteins of SCs in the model serum group were significantly increased (P<0.05, P<0.01), while in comparison with the model serum group, the proliferation and expression levels of MyoD and p-Akt proteins of SCs were further significantly increased in both EA-BL 23 and EA-BL 40 serum groups (P<0.01, P<0.05), but not in the EA-BL 40 serum+LY 294002 and EA-BL 23 serum+LY 294002 groups (P>0.05), suggesting an involvement of PI 3 K in the proliferation of SCs. No marked differences were found in the proliferation levels between the EA-BL 23 and EA-BL 40 serum groups and in the expression levels of Pax-7 proteins among the 6 serum groups (P>0.05). Both EA-BL 40 and EA-BL 23 serum can promote proliferation of multifidus muscle SCs, which may contribute to the effect of EA intervention in promoting repair of the injured muscle, partially by way of Akt/PI 3 K signaling.


Functional diversity of plant-pollinator interaction webs enhances the persistence of plant communities.
Pollination is exclusively or mainly animal mediated for 70% to 90% of angiosperm species. Thus, pollinators provide an essential ecosystem service to humankind. However, the impact of human-induced biodiversity loss on the functioning of plant-pollinator interactions has not been tested experimentally. To understand how plant communities respond to diversity changes in their pollinating fauna, we manipulated the functional diversity of both plants and pollinators under natural conditions. Increasing the functional diversity of both plants and pollinators led to the recruitment of more diverse plant communities. After two years the plant communities pollinated by the most functionally diverse pollinator assemblage contained about 50% more plant species than did plant communities pollinated by less-diverse pollinator assemblages. Moreover, the positive effect of functional diversity was explained by a complementarity between functional groups of pollinators and plants. Thus, the functional diversity of pollination networks may be critical to ecosystem sustainability.


The biomechanics and imaging of soccer injuries.
Soccer is one of the most popular sports worldwide and requires the player to have considerable stamina while superimposing sprinting, jumping, tackling, rapid changes of direction, and kicking. This contact sport carries a significant risk for acute and overuse injuries, with the lower limb the region most frequently injured. This article discusses the biomechanics and current role of imaging in the management of several specific soccer injuries highlighting injuries of the ankle, pelvis, and groin and specific muscle and tendon injuries commonly encountered in this athletic population.


Update in lipid alterations in subclinical hypothyroidism.
Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. Studies consistently demonstrate elevated levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, lipoprotein(a), and possibly triglycerides in individuals with overt hypothyroidism, all of which are reversible with levothyroxine therapy. Although it is estimated that 1 to 11% of all patients with dyslipidemia have subclinical hypothyroidism, the effects of subclinical hypothyroidism on serum lipid values are less clear. Apolipoprotein B levels may be increased in patients with subclinical hypothyroidism. Although some studies have demonstrated that total cholesterol and LDL-C levels are elevated in patients with subclinical hypothyroidism, others have not shown any effect of subclinical hypothyroidism on these lipid measurements. Serum triglycerides, lipid subparticle size, and LDL-C oxidizability may be altered in subclinical hypothyroidism, but these studies have also been inconsistent. The preponderance of evidence suggests that HDL-C and lipoprotein(a) levels are not altered in subclinically hypothyroid patients. Smoking and insulin resistance may modify the effects of subclinical hypothyroidism on serum lipid values. Clinical trials to date have not consistently shown a beneficial effect of levothyroxine treatment on serum lipid levels in subclinically hypothyroid patients.


Role of Aryl Hydrocarbon Receptor (AhR) in the Regulation of Immunity and Immunopathology During Trypanosoma cruzi Infection.
Resistance to Trypanosoma cruzi infection is dependent on a rapid induction of Th1-type and CD8+ T cell responses that should be promptly balanced to prevent immunopathology. T. cruzi-infected B6 mice are able to control parasite replication but show a limited expansion of Foxp3+regulatory T (Treg) cells that results in the accumulation of effector immune cells and the development of acute liver pathology. AhR is a ligand-activated transcription factor that promotes Treg cell development and suppression of pro-inflammatory cytokine production in dendritic cells, altering the course of adaptive immune response and the development of immunopathology. Here, we used different AhR-dependent activation strategies aiming to improve the Treg response, and B6 congenic mice carrying a mutant AhR variant with low affinity for its ligands (AhRd) to evaluate the role of AhR activation by natural ligands during experimental T. cruzi infection. The outcome of TCDD or 3-HK plus ITE treatments indicated that strong or weak AhR activation before or during T. cruzi infection was effective to regulate inflammation improving the Treg cell response and regularizing the ratio between CD4+ CD25- to Treg cells. However, AhR activation shifted the host-parasite balance to the parasite replication. Weak AhR activation resulted in Treg promotion while strong activation differentially modulated the susceptibility and resistance of cell death in activated T and Treg cells and the increase in TGF-β-producing Treg cells. Of note, T. cruzi-infected AhRd mice showed low levels of Treg cells associated with strong Th1-type response, low parasite burden and absence of liver pathology. These mice developed a Treg- and Tr1-independent mechanism of Th1 constriction showing increased levels of systemic IL-10 and IL-10-secreting CD4+ splenocytes. In addition, AhR activation induced by exogenous ligands had negative effects on the development of memory CD8+ T cell subsets while the lack/very weak activation in AhRd mice showed opposite results, suggesting that AhR ligation restricts the differentiation of memory CD8+T cell subsets. We propose a model in which a threshold of AhR activation exists and may explain how activation or inhibition of AhR-derived signals by infection/inflammation-induced ligands, therapeutic interventions or exposure to pollutants can modulate infections/diseases outcomes or vaccination efficacy.


Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) infection in men receiving treatment for HIV-1 infection.
To determine the prevalence of human herpesvirus 8 (HHV-8) infection in men treated for HIV-1 infection in Denver, Colorado. Cross-sectional analysis Blood samples were obtained from 216 HIV-1-infected men. Antibody to latency-associated nuclear antigen (LANA) was detected by an immunofluorescent assay and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC) was detected by polymerase chain reaction amplification. Among HIV-1-infected men who did not have Kaposi's sarcoma (KS), prevalence of HHV-8 infection was 46% (95% confidence interval [CI], 0.39-0.52). LANA seropositivity was common both among subjects with KS and subjects without KS (69% versus 42%; p = .06), but detection of HHV-8 DNA in peripheral blood was strongly associated with a diagnosis of KS (44% versus 10%; p = .001). In a univariate analysis of study subjects without KS, neither the odds of LANA seropositivity nor detection of HHV-8 DNA in PBMC was significant for CD4+ lymphocyte count, HIV-1 virus load, the use of three drug antiretroviral regimens or the prior occurrence of non-KS AIDS-related conditions. Although antibodies to HHV-8 are common among HIV-1-infected men, detection of HHV-8 DNA in PBMC is uncommon and is associated with a diagnosis of Kaposi's sarcoma.


Ischemia/Reperfusion-inducible protein modulates the function of organic cation transporter 1 and multidrug and toxin extrusion 1.
The recently identified ischemia/reperfusion-inducible protein (IRIP) has been reported to negatively modulate the activities of several transporters in cell culture systems. The goal of this study is to determine whether IRIP regulates the activities of OCT1 and MATE1, and hence the disposition in vivo of their substrate metformin, a therapeutic drug for diabetes and other obesity-related syndromes. In the uptake studies in the human embryonic kidney 293 cells overexpressing IRIP with and without OCT1 or MATE1, IRIP overexpression was found to significantly inhibit the uptake of 1-methyl-4-phenylpyridinium mediated by OCT1 or MATE1. In contrast, knockdown of IRIP by small hairpin RNA (shRNA) increased the transporter activities in vitro. IRIP overexpression decreased the membrane localization of transporter proteins without any changes in transcript levels in cells. By overexpressing IRIP in mouse liver via hydrodynamic tail vein injection, we demonstrated that increased IRIP expression could cause a significant reduction in hepatic accumulation of metformin (P < 0.01). In addition, we observed that the expression of IRIP was approximately half (P < 0.01) in ob/ob mice when compared to their lean littermates, with significant increases in hepatic Oct1 protein expression and metformin accumulation. In conclusion, IRIP negatively modulates the function of OCT1 and MATE1 in cells. Importantly, we provide in vivo evidence for such modulation that may cause an alteration in drug disposition. The regulation by IRIP on transporter activities likely occurs at a post-transcriptional level, and future studies are needed to characterize the exact mechanism.


Databases for psychiatrists.
Advances in computer technology have made databases more widespread and accessible, bringing both opportunities and benefits to psychiatrists. Their increasing usefulness has also resulted in increased expectations by others, such as accrediting agencies and payers, that psychiatrists have the capacity to manage outcome and utilization data as well as other information. This paper provides an overview of the uses of databases in psychiatry, describes basic principles and features of relational databases, and reviews some of the features of currently available database-development packages.


Functional importance of alpha adrenoceptor-mediated, D600-insensitive Ca++ entry in rabbit aorta.
Specific receptor-linked Ca++ entry (RLCa++E) was studied separately from Ca++ release and potential-dependent Ca++ entry (PDCa++E) in rabbit aorta after incubation in a Ca++-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid to bind trace levels of Ca++ and including methoxyverapamil (D600) (10(-5) M) to inhibit PDCa++E. Adding norepinephrine (NE) under these conditions resulted in a transient response which was attributed to Ca++ release from a limited cellular store. Subsequent addition of Ca++ results in a sustained contraction that was dependent upon the concentration of agonist and Ca++. This maintained response which by definition was insensitive to D600 was attributed to RLCa++E, was extensively relaxed or inhibited by nitroprusside or nitroglycerin and was partially relaxed by KCl or tetraethylammonium. Contractions due to RLCa++E alone equaled or exceeded the peak tension attained solely as a result of Ca++ release. At higher NE concentrations (greater than 10(-7) M), RLCa++E provided sufficient Ca++ to attain and sustain maximal levels of developed tension without requiring any additional Ca++ from either PDCa++E or Ca++ release. This high flux capacity of these receptor-linked Ca++ channels may partially account for the relative insensitivity of contractile responses to these higher concentrations of NE to D600. The relative contribution of PDCa++E to the elevation of myoplasmic Ca++ and concurrent sensitivity to D600 was increased at lower concentrations of NE because the degree of Ca++ release and RLCa++E were relatively small. Additionally, it appears that RLCA++E may be attenuated by concomitant membrane depolarization.


Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia.
Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.


Evaluation of an innovative radiographic technique--parallel profile radiography--to determine the dimensions of dentogingival unit.
Maintenance of gingival health is a key factor for longevity of the teeth as well as of restorations. The physiologic dentogingival unit (DGU), which is composed of the epithelial and connective tissue attachments of the gingiva, functions as a barrier against microbial entry into the periodontium. Invasion of this space triggers inflammation and causes periodontal destruction. Despite the clinical relevance of the determination of the length and width of the DGU, there is no standardized technique. The length of the DGU can be either determined by histologic preparations or by transgingival probing. Although width can also be assessed by transgingival probing or with an ultrasound device, they are either invasive or expensive This study sought to evaluate an innovative radiographic exploration technique--parallel profile radiography--for measuring the dimensions of the DGU on the labial surfaces of anterior teeth. Two radiographs were made using the long-cone parallel technique in ten individuals, one in frontal projection, while the second radiograph was a parallel profile radiograph obtained from a lateral position. The length and width of the DGU was measured using computer software. Transgingival probing (trans-sulcular) was done for these same patients and length of the DGU was measured. The values obtained by the two methods were compared. Pearson product correlation coefficient was calculated to examine the agreement between the values obtained by PPRx and transgingival probing. The mean biologic width by the parallel profile radiography (PPRx) technique was 1.72 mm (range 0.94-2.11 mm), while the mean thickness of the gingiva was 1.38 mm (range 0.92-1.77 mm). The mean biologic width by trans-gingival probing was 1.6 mm (range 0.8-2.2 mm). Pearson product correlation coefficient (r) for the above values was 0.914; thus, a high degree of agreement exists between the PPRx and TGP techniques. We conclude that the biologic width of the DGU in humans can be measured with the PPRx technique. The values obtained agree with the values obtained by transgingival probing, a technique considered standard so far. Thus, the PPRx technique offers a simple, concise, noninvasive, and reproducible method that can be used in the clinical setup to measure both the length and thickness of the DGU with accuracy.


Intein-mediated rapid purification of Cre recombinase.
Cre recombinase produced by bacteriophage P1 catalyzes site-specific recombination of DNA between loxP recognition sites in both prokaryotic and eukaryotic cells and has been widely used for genome engineering and in vitro cloning. Recombinant Cre has been overproduced in Escherichia coli and its purification involves multiple steps. In this report, we used an "intein" fusion system to express Cre as a C-terminal fusion to a modified protein splicing element, i.e., intein. The modified intein contained a Bacillus circulans chitin-binding domain which allowed binding of the fusion protein on a chitin column and could be induced to undergo in vitro peptide bond cleavage which specifically released Cre from the column. Using the intein system, we have obtained highly pure nontagged Cre after just a single chromatographic step, which corresponded to approximately 80% recovery and 27-fold purification. The activity of the purified Cre was determined in an in vitro assay system and was found to remain stable over a period of more than 6 months.


Nitrate Reductase and Soluble Cytochrome c Reductase(s) in Higher Plants.
The 4S cytochrome c (Cyt c) reductase activity of several plant species was markedly stimulated by cyanide and ferrocyanide but those of the 8S nitrate reductase component and other particulate components of the maize (Zea mays L.) scutellum by comparison, were increased only slightly. The effect of cyanide and ferrocyanide was not due to elimination of cytochrome oxidase interference but resulted from the stimulation of NADH-dependent reduction of Cyt c. A 4S Cyt c reductase component which could be isolated by ammonium sulfate fractionation and diethyl-aminoethyl-cellulose chromatography was found to be stimulated markedly by cyanide and ferrocyanide. The remaining 4S Cyt c reductase, which was insensitive to cyanide and ferrocyanide, was also fractionated with ammonium sulfate into two components. One of these, like the 8S Cyt c reductase, was sensitive to a protease from the maize roots which is relatively specific for nitrate reductase. This 4S Cyt c reductase species could be a subunit of nitrate reductase.


A study of ulnar collateral ligament of the thumb metacarpophalangeal joint.
The current study examined the biomechanical properties of intact and repaired ulnar collateral ligaments of the metacarpophalangeal joint of the thumb to determine a safe rehabilitation protocol after repair. In the first part of the study mechanical properties of the ligament were examined and the induced stress and strain were determined during simulated pinch and grip. In the second part of the study the strength and limitations of ulnar collateral ligament repair using a mini-Mitek bone suture anchor was determined. The biomechanical study was done on 16 fresh-frozen thumbs from male cadavers. Failure load, maximum stress, and Young's modulus of intact ulnar collateral ligament were 294.3 +/- 28.2 N, 11.4 +/- 1.2 MPa, and 37.3 +/- 5.1 MPa, respectively. There was no significant correlation between the low grip force and the ligament strain. There was, however, a significant correlation between the pinch force and the ligament strain. The failure load and joint rigidity of intact ulnar collateral ligaments were significantly higher (3.1 and 2.3 times, respectively) than the mini-Mitek repaired ligaments. The current study suggests that pinch activity during the rehabilitative process after repair or reattachment of the ulnar collateral ligament should be eliminated. Repaired ligaments with mini-Mitek bone suture anchors may be able to do a moderate range of motion during postoperative rehabilitation; however, additional in vivo studies are necessary before any clinical recommendation is made.


Ureteroileal anastomosis stricture after urinary diversions performed by open, laparoscopic and robotic approaches. Incidence and management in a tertiary care center.
Ureteroileal anastomosis stricture is a frequent complication after radical cystectomy and ileal conduit or orthotopic neobladder formation. We analyze their incidence based on the technique for urinary diversion and on the surgical approach (open, laparoscopic or robot-assisted). Stricture management is described, along with surgical outcomes. Descriptive retrospective study over 6 years in patients who underwent urinary diversion using ileum (ileal conduit or orthotopic neobladder). Demographic data, comorbidities, surgical approach, complications, and outcomes were collected. Minimum follow-up of 1 year. Comparison between groups using Chi-square test for dichotomous variables. Quantitative variables were compared using the Student's t-test for independent groups or Mann-Whitney test. Statistical significance if P < .05. The study included 182 patients (84% males and 16% females). Mean age 68 years. Cystectomy approach: laparoscopic (67/37%), robot-assisted (63/35%), open (43/24%). Urinary diversion: ileal conduit (138/76%) and orthotopic ileal neobladder (44/24%). Uretericre implantation technique: Bricker (108/59%) and Wallace (47/26%). Ureteroileal anastomosis strictures (50/27%): bilateral (26), left (16) and right (8). Strictures according to cystectomy approach: laparoscopic (23/46%), robot-assisted (16/32%), open (9/18%). Treatment of strictures (33/18%): ureteric reimplantation (13), indwelling nephrostomy (13), endoscopic dilatation (4), nephroureterectomy (2), endoureterotomy (1). Ureteroileal reimplantation approach: laparoscopic (5/38%), robot-assisted (6/46%), open (2/15%). Outcomes after reimplantation: restenosis (0/0%), reintervention (3/23%), contralateral ureteroileal stricture (1/8%). Surgical approach in cystectomy does not influence future development of ureteroileal strictures. Laparoscopic and robot-assisted ureteroileal reimplantation achieves high success rates.


Entropy-based texture analysis of chromatin structure in advanced prostate cancer.
A new texture operator, gray-level entropy matrix (GLEM), was developed, and nine new textural features were extracted from this matrix. These textural features were applied to light microscopy images of nuclei taken from monolayers of advanced prostate cancer cells representing two different prognostic groups: hormone-sensitive (good prognosis) and hormone-resistant (poor prognosis) tumors. A comparison between the classification results obtained from GLEM features and those obtained from standard textural estimators is also discussed. Single features that gave correct classification rates better than 65% were included in a discriminant analysis in order to find the optimal set of features to discriminate between the two prognostic groups in the training data set. The best combination of features includes three GLEM features together with ENTROPY extracted from gray-level cooccurrence matrix, and this combination gave a correct classification rate of 95% using the leaving-one-out technique. The influences of image sharpness and number of cells were also investigated. The features based on entropy or degree of scatter of minute structures can be used to discriminate between hormone-sensitive and hormone-resistant prostate carcinomas.


Charge Regulation and Electrostatic Interactions for a Spherical Particle in a Cylindrical Pore
Previous theoretical analyses of electrostatic interactions for proteins in porous media have assumed that the protein (and pore) surface maintains either constant charge or constant potential during the interaction; however, the actual surface charge is determined by the extent of the surface ionization and binding reactions, both of which are altered when the protein enters the pore due to the change in the local ionic environment caused by the distortion of the electrical potential field. Theoretical calculations for the electrostatic potential are performed for a spherical particle in a cylindrical pore, accounting for this charge regulation phenomenon using a linearized form of the charge regulation boundary condition. The equilibrium partition coefficient in the pore is then evaluated from the free energy of interaction. Specific calculations are provided for the protein bovine serum albumin, with the charge regulation parameters evaluated from a model for the detailed protein charge characteristics. Model predictions are compared with experimental data for the bovine serum albumin sieving coefficient at different pH and ionic strength. These results provide important insights into the effects of charge regulation on the magnitude of the electrostatic interactions between charged proteins and charged pores. Copyright 1997Academic Press


[Establishment of a cell suspension culture system of endangered Aquilaria sinensis (Lour.) Gilg].
Aquilaria sinensis callus induced by stem tips were used to establish the suspension cell system. The results showed that the most suitable medium for callus induction and subculture is MS + 2.0 mg x L(-1) NAA + 1.0 mg x L(-1) 6-BA. After 12 times of subculture, the energetic and loose callus, which were appropriate for cell suspension culture, were cultured and shook in liquid medium MS + 2.0 mg x L(-1) NAA + 1.0 mg x L(-1) 6-BA + 500.0 mg x L(-1) casein hydrolysate (CH) to establish the suspension cell system. The growth curve of suspension cells showed a "S" type. At the beginning of the culture, cell density increased slowly; during 4 to 6 days, suspension cells reached logarithmic growth period; during 7 to 12 days, suspension cells were in the platform period; but after 12 days, cell density and activity went down obviously. Agarwood sesquiterpenes were not detected in the suspension cells during the growth period, however, they could be detected in MeJA treated suspension cells. In this study, a stable and active growing suspension cell system was established, which was a proper system to study the mechanism of agarwood sesquiterpene formation, and additionally provided a potential way to generate agarwood sesquiterpenes through application of cell culture.


Fabrication, thermal analysis, and heavy ion irradiation resistance of epoxy matrix nanocomposites loaded with silane-functionalized ceria nanoparticles.
This paper describes a detailed understanding of how nanofillers function as radiation barriers within the polymer matrix, and how their effectiveness is impacted by factors such as composition, size, loading, surface chemistry, and dispersion. We designed a comprehensive investigation of heavy ion irradiation resistance in epoxy matrix composites loaded with surface-modified ceria nanofillers, utilizing tandem computational and experimental methods to elucidate radiolytic damage processes and relate them to chemical and structural changes observed through thermal analysis, vibrational spectroscopy, and electron microscopy. A detailed mechanistic examination supported by FTIR spectroscopy data identified the bisphenol A moiety as a primary target for degradation reactions. Results of computational modeling by the Stopping Range of Ions in Matter (SRIM) Monte Carlo simulation were in good agreement with damage analysis from surface and cross-sectional SEM imaging. All metrics indicated that ceria nanofillers reduce the damage area in polymer nanocomposites, and that nanofiller loading and homogeneity of dispersion are key to effective damage prevention. The results of this study represent a significant pathway for engineered irradiation tolerance in a diverse array of polymer nanocomposite materials. Numerous areas of materials science can benefit from utilizing this facile and effective method to extend the reliability of polymer materials.


A Novel de Novo Paracentric Inversion [inv(20)(q13.1q13.3)] Accompanied by an 11q14.3-q21 Microdeletion in a Pediatric Patient with an Intellectual Disability.
A novel de novo paracentric inversion of the long arm of chromosome 20 [inv(20)(q13.1q13.3)], detected by conventional karyotyping in a 14-year-old boy with mental retardation is described. Further investigation by array comparative genomic hybridization (aCGH) revealed that the 20q inversion was not accompanied by microdeletions/microduplications containing disease-associated genes near or at the breakpoints. Two deletions at chromosomal regions 11q14.3q21 and 20q12 of 4.5 and 1.97 Mb size, respectively, containing important online Mendelian inheritance in man (OMIM) genes, were detected. The 4.5Mb 11q14.3q21 microdeletion was contained within a region that is involved, in most of the reported cases, with the interstitial 11q deletion and may be related to the mental retardation and developmental delay present in the patient. On the other hand, the published data about the 20q12 microdeletion are very few and it is not possible to correlate this finding with our patient's phenotype. This case report contributes to the description of a new chromosomal entity, not previously reported, and is therefore important, especially in prenatal diagnosis and management of patients. Array comparative genomic hybridization has proven a useful technique for detecting submicroscopic rearrangements and should be offered prenatally, especially in cases of de novo karyotypically balanced chromosomal inversions or translocations in order to unveil other unbalanced chromosomal abnormalities such as deletions and amplifications.


An autoimmune stem-like CD8 T cell population drives type 1 diabetes.
CD8 T cell-mediated autoimmune diseases result from the breakdown of self-tolerance mechanisms in autoreactive CD8 T cells1. How autoimmune T cell populations arise and are sustained, and the molecular programmes defining the autoimmune T cell state, are unknown. In type 1 diabetes, β-cell-specific CD8 T cells destroy insulin-producing β-cells. Here we followed the fate of β-cell-specific CD8 T cells in non-obese diabetic mice throughout the course of type 1 diabetes. We identified a stem-like autoimmune progenitor population in the pancreatic draining lymph node (pLN), which self-renews and gives rise to pLN autoimmune mediators. pLN autoimmune mediators migrate to the pancreas, where they differentiate further and destroy β-cells. Whereas transplantation of as few as 20 autoimmune progenitors induced type 1 diabetes, as many as 100,000 pancreatic autoimmune mediators did not. Pancreatic autoimmune mediators are short-lived, and stem-like autoimmune progenitors must continuously seed the pancreas to sustain β-cell destruction. Single-cell RNA sequencing and clonal analysis revealed that autoimmune CD8 T cells represent unique T cell differentiation states and identified features driving the transition from autoimmune progenitor to autoimmune mediator. Strategies aimed at targeting the stem-like autoimmune progenitor pool could emerge as novel and powerful immunotherapeutic interventions for type 1 diabetes.


The stabilizing effect of silicate on biogenic and synthetic amorphous calcium carbonate.
Silicate ions increase the thermal stability of the unstable amorphous calcium carbonate (ACC). This effect was observed first by comparing ACC from two different species of cystoliths, small calcified bodies formed in the leaves of some plants. The temperature of crystallization to calcite in the silicate-rich cystoliths from M. alba is 100 °C higher than that of the silicate-poor cystoliths from F. microcarpa. The stabilizing effect is confirmed in vitro with synthetic samples differing in their silicate content. With increasing silicate concentration in ACC, the crystallization temperature to calcite also increases. A mechanism of geometric frustration is suggested, whereby the presence of the tetrahedral silicate ion in the flat carbonate lattice prevents organization into crystalline polymorphs.


Comparison of quantitative and qualitative PCR assays for cytomegalovirus DNA in plasma.
We analyzed the performance characteristics of the qualitative AMPLICOR CMV Test (Roche Molecular Systems, Pleasanton, Calif.) and quantitative COBAS AMPLICOR CMV MONITOR Test (Roche Molecular Systems) assays and compared the performance of the AMPLICOR quantitative assay with an in-house-developed cytomegalovirus (CMV) DNA PCR assay. The quantitative AMPLICOR assay was found to be more sensitive than the qualitative AMPLICOR assay. The quantitative AMPLICOR assay has a lower limit of sensitivity of 400 CMV DNA copies/ml of plasma and is linear to 50,000 CMV DNA copies/ml of plasma. Compared to the in-house PCR assay, the AMPLICOR quantitative assay gave lower viral load values at all concentrations tested, but the difference between the two assays was not consistent across the entire dynamic range of the AMPLICOR quantitative assay. At the lower end of the assay, the viral load values obtained with the in-house PCR assay were three- to fivefold (0.5 to 0.7 log units) higher than those measured with the AMPLICOR assay. At higher input concentrations, the differences between the two assays approached 10-fold. This direct comparison of the in-house assay and the quantitative AMPLICOR assay provides the ability to compare previously published in-house data with an assay widely available for future research and clinical monitoring of patients with CMV infections.


Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia.
To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.


Complete mapping of a novel HLA A*6801-restricted HIV-1 Tat epitope directly with a rapid modified enzyme-linked immunospot assay.
We identified a novel HLA A*6801-restricted HIV-1 Tat-derived cytotoxic T lymphocyte (CTL) epitope using an adapted enzyme-linked immunospot assay that allows the rapid ex vivo identification of CTL epitopes together with their associated HLA Class I restriction elements. The optimal 11 amino acid residue Tat epitope efficiently stabilized the refolding of monomeric peptide-HLA A6801 complexes in vitro and fluorochrome-labelled, tetrameric peptide-HLA A6801 complexes stained CD8 T cells specific for this epitope directly ex vivo.


Do Spiritual Health Connections Protect Adolescents When They Are Bullied: A National Study of 12,593 Young Canadians.
It has long been established that bullying has many negative impacts on the mental health of adolescents. Young people who are victimized by bullying may cope by drawing on available assets to protect themselves from harm. One such asset with ancient roots but with the potential for contemporary application is the concept of spiritual health-the idea that the connections in our lives (whether to ourselves, others, nature, or something transcendent) affect our well-being. In this study, we examined 12,593 Canadians aged 11-15 years to determine the effects of being victimized by bullying on their mental health, as measured by frequent subjective health complaints. We then explored whether strong spiritual health connections were effect modifiers that buffer such negative pathways, thereby acting as protective health assets. Data were obtained from the 2017/18 Canadian Health Behaviour in School-aged Children study. Generalized linear regression models were used to estimate associations and evaluate effect modification in different age and gender groups. Approximately 21% of participants reported being victimized by bullying. Strength of "connections to self" (i.e., a sense of meaning/purpose or joy and happiness in one's life) was found to act as an effect modifier, but in girls alone. Contrary to expectations of a buffering effect, the strongest associations between victimization and frequent health complaints were identified for girls with high connections to self. Relative risks for poor mental health among these highly self-connected girls were 1.63 [95% CI: 1.26-2.12] and 1.25 [1.06-1.47] for younger and older girls, respectively. We interpreted this unexpected finding in light of cognitive theories of trauma, which suggest that adverse events may lead to worse health outcomes among those who place particular value on their world being meaningful, controllable or benevolent. Implications for clinical intervention and health promotion are considered.


Physical activity in children and adolescents with type 1 diabetes and contem-porary methods of its assessment.
Exercise is a determinant of people's well-being, and it contributes to the prevention and treatment of numerous diseases of affluence, e.g. diabetes and obesity. The rapid pace of economic development is affecting human functioning to such a degree that the need for physical activity, which has always been recognised as a biological and natural need, has been significantly reduced. Consequently, to-day public health related problems occurring globally are connected with the increasing incidence of cardiovascular, neoplastic, and met-abolic diseases. These problems are manifested not only in adults, but they also increasingly affect children and adolescents worldwide. In the case of children with type 1 diabetes, physical activity is of particular importance because it contributes to the child's normal de-velopment and to positive effects of therapies. The paper discusses health-related benefits of physical activity in children and adolescents with type 1 diabetes, it presents recommendations related to physical activity published in Poland and abroad, and reviews contemporary methods of its assessment.


Smokers are over-represented in subjects with ahaptoglobinemia in Ghana.
Smoking has been established as a major risk factor for cardiovascular disease. It causes oxidative stress and sub-clinical inflammation, which undermine the antioxidant defense system of the body. We reasoned that natural antioxidant defense systems may be compromised in smokers. To this end, we examined whether haptoglobin (Hp), a potent antioxidant, is impacted negatively by smoking. Study participants consisted of 121 current smokers and 105 healthy non-smokers without diabetes and without blood smear-positive P. falciparum. Smokers were defined as individuals who smoke at least 1 cigarette a week and are current smokers (occasional and regular). Baseline demographics, hematological indices, lipid profiles, blood pressure, lactate dehydrogenase activity and haptoglobin phenotypes were determined. Ahaptoglobinemia was found to be highly overrepresented in smokers (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.5-6.5, p=0.002). This observation was not attributed to intravascular hemolysis. Hp2-2 phenotype was found to be under represented in smokers (OR=0.53, 95% CI=0.28-0.99, p=0.05). Smoking was confirmed to augment hypertension (diastolic blood pressure (DBP) and systolic blood pressure (SBP) in male smokers (p=0.0001). Interestingly, however, this appeared not to be related to lipid metabolism, as HDL was elevated (p=0.0007) while LDL was decreased (p=0.004) in smokers within the study population. We conclude that smoking is a risk factor for ahaptoglobinemia, which will impact negatively on anti-oxidant defenses and augment pro-oxidative stress effects.


Preemptive Intervention Beneficial for Infants with Early Signs of Autism.
According to this study: A preemptive intervention in infants showing early behavioral signs of autism spectrum disorder led to a significant reduction in the severity of these behaviors and lower odds of a diagnosis at age three.


[HIV infection in a patient with chronic cutaneous lupus].
We present a case of chronic cutaneous lupus erythematosus (CCLE) in a patient who subsequently became infected with human immunodeficiency virus, HIV-1. The symptoms attributed to CCLE had persisted for years, and curiously had disappeared by the time the patient probably became infected with HIV-1. Even if there is lack of evidence to consider HIV-1 infection as direct causative agent in the clinical remission of CCLE, this response is in accordance with previous reports from other authors, regarding the attenuating role of HIV on the clinical course of the systemic lupus erythematosus. Even if the number of reported cases is very low it is of the upmost importance to establish whether this hypothesis is correct or not, since both diseases present great difficulties regarding diagnosis, due to the important overlapping between symptoms and serological tests.


Mid-pregnancy fetal growth, uteroplacental Doppler indices and maternal demographic characteristics: role in prediction of stillbirth.
To evaluate the relative value of mid trimester fetal growth, uterine artery Doppler indices and maternal demographics in prediction of stillbirth. Retrospective cohort study; 23 894 singleton pregnancies routinely scanned between 19 and 24 weeks' gestation. Maternal characteristics included age, body mass index, ethnicity and medical history. Fetal biometry indices, birthweight and uterine artery pulsatility index values were converted to percentiles and multivariable logistic regression analysis was performed. The predictive accuracy was assessed using receiver operating characteristic curves analysis. The main outcome was prediction of preterm and term stillbirths. Non-Caucasian ethnicity, femur length centile and uterine artery pulsatility index were significantly associated with the risk of stillbirth (all p < 0.01). The detection rate of screening by maternal factors alone was 19% for all stillbirths, and 12 and 14% for term and preterm stillbirth at a 10% false positive rate, respectively. Using femur length centile alone, the detection rates were 27 and 23%, respectively. Uterine artery pulsatility index alone was able to predict 24 and 31% of term and preterm stillbirths. Screening by combining maternal factors, femur length centile and uterine artery Doppler detected 27 and 35% of term and preterm stillbirths at a 10% false positive rate. Second trimester ultrasound assessment offers an opportunity to identify pregnancies at the highest risk of stillbirth occurring as a consequence of placental dysfunction. This information may be useful to improve pregnancy outcome by identifying women who may benefit from increased ultrasound surveillance and/or timely intervention.


The role of hormone therapy and chemotherapy in oligometastatic prostate cancer.
Oligometastatic disease was proposed by Hellman and Weichselbaum in 1995 as an intermediate tumour state between localised lesions and widespread metastases, characterised by the limited number and size of metastases in specific organs such as lung, liver, bone or even brain. The oligometastatic state has increasingly been recognised as a unique clinical state during which local ablative treatment can be effective in several types of cancer, including prostate cancer. However, the role of systemic therapy, such as hormone therapy and chemotherapy, is not yet well known. Some promising data for local ablative therapy have emerged, but it remains unclear whether local therapy can eliminate the need for, androgen-deprivation therapy (ADT), or reduce the required duration. In addition, several randomised phase III trials have demonstrated survival benefits from the addition of docetaxel or abiraterone to ADT in patients with metastatic hormone-sensitive prostate cancer. These findings suggest that such aggressive treatments may improve clinical outcomes for patients with oligometastatic prostate cancer. However, the efficacy of these treatments may depend on the volume of metastases, with higher efficacy for high-volume disease. Therefore, further investigation including stratification by disease volume is warranted. This review will discuss the current evidence and controversies surrounding the role of systemic therapy in patients with oligometastatic prostate cancer.


Prognostic Nutritional Index as a Predictor of 30-Day Mortality Among Patients Admitted to Intensive Care Unit with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Single-Center Retrospective Cohort Study.
BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is significantly associated with increased mortality. The current study aimed to investigate the predictive ability of the prognostic nutritional index (PNI) in 30-day mortality among AECOPD patients admitted to the ICU. MATERIAL AND METHODS Clinical data were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into 3 groups according to the tertiles of PNI. Cox proportional hazard regressions were performed to assess the association between PNI and 30-day mortality. Subgroup analyses were performed to identify the consistency of the association. Receiver operator characteristic (ROC) curve analysis was performed to evaluate the predictive accuracy among PNI, serum albumin, neutrophil-to-lymphocyte (NLR), and platelet-to-lymphocyte ratio (PLR). RESULTS A total of 494 AECOPD patients were included in this study. The mean age was 70.8±10.4 years old. Kaplan-Meier analysis showed ongoing divergence in rates of mortality among tertiles (p<0.001). After adjusting for confounders, high PNI tertile was an independent favorable predictor of 30-day mortality (HR=0.39; 95% CI, 0.19-0.80; p=0.011) compared to low tertile reference. Subgroup analysis showed that the predictive ability of PNI was especially suitable for patients aged >70 years and with mechanical ventilation. The cut-off value of PNI was 31.8 with sensitivity 62.3% and specificity 64.1%. The area under the ROC of PNI (0.642, 95% CI, 0.560 to 0.717) was better than that of serum albumin, NLR, and PLR. CONCLUSIONS PNI could serve as a simple and reliable prognostic biomarker for AECOPD patients in the ICU.


Neisseria gonorrhoeae isolated from an unexpected site.
We describe a case of Neisseria gonorrhoeae isolated from a nipple piercing wound in a homosexual man with pharyngeal gonococcal carriage.


Return migration of New Zealanders: a profile of 1990 returnees.
"In the 1990s the population [of New Zealand] is experiencing higher levels of mobility than at any time in its history. However, with regards to European migration to New Zealand, the settler flows of the past have been overtaken in importance by reverse flows of temporary migrants. Now flows of new settlers come predominantly from Asia and the Pacific....This paper is about return migration--a process that has been largely ignored in the literature on international migration to New Zealand."


Prediction of fatigue-related driver performance from EEG data by deep Riemannian model.
Prediction of the drivers' drowsy and alert states is important for safety purposes. The prediction of drivers' drowsy and alert states from electroencephalography (EEG) using shallow and deep Riemannian methods is presented. For shallow Riemannian methods, the minimum distance to Riemannian mean (mdm) and Log-Euclidian metric are investigated, where it is shown that Log-Euclidian metric outperforms the mdm algorithm. In addition the SPDNet, a deep Riemannian model, that takes the EEG covariance matrix as the input is investigated. It is shown that SPDNet outperforms all tested shallow and deep classification methods. Performance of SPDNet is 6.02% and 2.86% higher than the best performance by the conventional Euclidian classifiers and shallow Riemannian models, respectively.


Sequential bilateral total hip replacement during the same hospitalization.
Numerous authors describe the efficacy and relative safety of simultaneous bilateral total hip replacement or bilateral surgeries separated by more than 6 weeks. We compare those reported results with our 32-year experience using a unique timing protocol: doing sequential bilateral total hip replacements during the same hospitalization separated by 5 to 7 days. From 1972 to 2004, 112 patients were selected for bilateral total hip replacement surgery during the same hospitalization. All surgeries were done using a direct lateral approach to the hip with a variety of cemented and cementless implants. Of the 112 patients, 96 charts were available for review. The average length of stay was 13.8 days. With an average of 6.3 years (range, 1-23 years) followup, Iowa hip scores improved from an average of 42 points to an average of 94 points. Implant survivorship compared favorably with other reports of similar implants, and there were no acute deep infections and two delayed infections. Sixteen patients developed medical complications, two had pulmonary emboli (one fatal) and two died (one of pulmonary embolism and one cerebral bleed not related to the surgery). Sequential bilateral total hip arthroplasty offers surgeons an alternative to simultaneous or staged surgery for the appropriately selected patient. Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.


Patulin accumulation in apples under dynamic controlled atmosphere storage.
The goal of this study was to evaluate patulin contamination in 'Galaxy' and 'Fuji Kiku' apples subjected to controlled atmosphere (CA) and dynamic controlled atmosphere (DCA) conditions. Experiments were performed and fruit were stored for nine months under refrigeration plus 7 days shelf life at 20 °C. CA and DCA were not effective in preventing patulin production in either 'Galaxy' or 'Fuji Kiku' apples. Healthy fruit were not contaminated with patulin, even when stored together with decayed apples. For 'Galaxy' apples, application of 1-methylcyclopropene increased the percentage of fruit with decay and patulin contamination. Patulin concentrations were above the maximum limit (50 μg kg-1) established in the Brazilian legislation, meaning the use of CA and DCA conditions were not advantageous in preventing patulin accumulation. In 'Fuji Kiku' apples, there was no significant difference in patulin concentration among CA, DCA-CF and DCA-RQ 1.3 treatments, and all were below the maximum.


Experimental transmission of hydropericardium syndrome and protection against it in commercial broiler chickens.
Liver collected aseptically from broiler chickens suffering from natural outbreaks of hydropericardium syndrome was homogenised in phosphate buffered saline (1:5) or normal saline (1:10). A dose of 0.25 ml of 800 g supernatant (inoculum S) in the first case or homogenate without centrifugation (inoculum T) in the second case was injected subcutaneously into 12- to 15-day-old broiler chickens. Lesions similar to natural outbreaks of the syndrome appeared in 2 to 5 days. Inoculum S inactivated with 0.1% formalin for 24 h (Vac S) or inoculum T inactivated with 0.5% formalin for 72 h (Vac T) was injected into commercial broiler chickens at 10 or 15 days of age. The birds were challenged with inoculum S or inoculum T at 20 or 25 days of age. Experimentally both vaccines gave satisfactory protection, but under field conditions, Vac T was superior.


Further studies on the phosphorylation-regulated cAMP-phosphodiesterase from the dimorphic fungus Mucor rouxii.
A partially purified preparation (200-fold) of cAMP phosphodiesterase (PDE) was obtained from Mucor rouxii grown and extracted under conditions minimizing endogenous proteolysis. Four purification steps were applied: batch DEAE-Sepharose, DEAE-Sepharose chromatography, Sephadex G-150 super-fine gel filtration and sucrose gradient centrifugation. The final PDE preparation was activatable by cAMP-dependent phosphorylation and controlled trypsin treatment. A careful correlation of protein patterns with PDE activity was done throughout the whole procedure by analyzing the active fractions of each step by mini-polyacrylamide non-denaturing gel electrophoresis. The final preparation displayed four major protein bands, none of which corresponded to PDE, although PDE activity comigrated with two of them. Some properties of this preparation were studied. Vmax increased around 10-15 fold by activation of PDE by phosphorylation or proteolysis; Km values were unaffected. PDE had Stokes radius of 3.5 nm, sedimentation coefficient of 4.3 S and molecular weight of 70,000 daltons. The treatment of sucrose gradient fractions with [gamma-32P] ATP and cAMP-dependent protein kinase catalytic subunit and further analysis through minigels showed that none of the visible bands was phosphorylated, and that among the four phosphorylated bands there was one that cosedimented and comigrated with PDE activity. Trypsin treatment of the phosphorylated samples removed the label but did not modify the staining pattern.


A Vascular Permeability Assay Using an In Vitro Human Microvessel Model Mimicking the Inflammatory Condition.
The vascular barrier is an important function of the endothelium and its dysfunction is involved in several diseases. The barrier function of the endothelial cell monolayer is governed by cell-cell, cell-extracellular matrix (cell-ECM) contacts, and inflammatory factors such as thrombin, histamine or vascular endothelial growth factor. Several in vivo and in vitro assays that measure the vascular permeability induced by these factors have been developed. However, they suffer limitations such as being challenging for assessing details of biological processes at a cellular level or lacking the architecture of a vessel, that raise the need for new methods. In vitro 3D model-based assays have thus been developed but assays for investigating compounds that protects the barrier function are lacking. Here we describe the development of an in vitro three-dimensional (3D) vascular endothelium model in which we can manipulate the endothelial barrier function and permeability to molecules, which have a molecular weight similar to human serum albumin, allowing to assess the protective effect of compounds. A microvessel was prepared by culturing human umbilical vein endothelial cells (HUVECs) within a collagen gel on a polydimethylsiloxane (PDMS) chip. Using fluorescein isothiocyanate (FITC)-conjugated dextran (70 kDa, FITC-dextran) and confocal fluorescence microscopy, we showed that the microvessel presented an effective barrier function. We were then able to induce the loss of this barrier function by treatment with the inflammatory factor thrombin. The loss of barrier function was quantified by the extravasation of FITC-dextran into collagen matrix. Furthermore, we were able to analyze the protective effect on the endothelial barrier function of the cyclic adenosine monophosphate (cAMP) analog, 8-pCPT-2'-O-Me-cAMP (also called 007). In an attempt to understand the effects of thrombin and 007 in our model, we analyzed the adherens junctions and cytoskeleton through immunostaining of the vascular endothelial cadherin and actin, respectively. Our assay method could be used to screen for compounds modulating the barrier function of endothelial cells, as well as investigating mechanistic aspects of barrier dysfunction.


Using written communication with patient groups to promote behavioral change in chronic mentally ill patients.
Patient-managed problem-solving groups have been used in inpatient settings to increase the responsible activity of patients with chronic mental illness. In a study using a repeated measures design, staff prepared written notes describing patients' adherence to programmatic expectations and submitted them to patient-managed problem-solving groups, which recommended consequences for patients' behavior. The intervention increased the frequency of targeted behavior compared with the frequency of the behavior during baseline periods. The authors suggest that this procedure may be applied to a variety of behaviors in other treatment settings.


The Peptide pools of germinating barley grains: relation to hydrolysis and transport of storage proteins.
A quantitative procedure for purifying small peptides from plant tissues, involving both ion-exchange and gel-exclusion chromatography, is described. Peptides were quantified and characterized by using the fluorescence reagents dansyl chloride and fluorescamine. Large pools of small peptides and amino acids have been identified in both the endosperm and embryo of germinating barley grains. The peptide pool of the endosperm increases during the first 3 days of germination, subsequently decreasing, an observation compatible with a role for peptides as intermediates in the breakdown of the storage proteins and their transfer to the embryo. The amino acid composition of these peptides indicates that all the major classes of storage protein contribute to the pool. The concentration of peptides produced in the endosperm during germination is sufficient for the efficient operation of the peptide transport system of the scutellar membrane characterized previously (Higgins and Payne, Planta 136: 71-76, 1977; Planta 138: 211-215 and 217-221, 1978). Data presented here indicate that peptides play at least as important a role as amino acids in the transfer of stored nitrogen from the endosperm to the embryo during germination.


Dynamics of modulated waves in a lossy modified Noguchi electrical transmission line.
We study analytically the dynamics of modulated waves in a dissipative modified Noguchi nonlinear electrical network. In the continuum limit, we use the reductive perturbation method in the semidiscrete limit to establish that the propagation of modulated waves in the network is governed by a dissipative nonlinear Schrödinger (NLS) equation. Motivated with a solitary wave type of solution to the NLS equation, we use both the direct method and the Weierstrass's elliptic function method to present classes of bright, kink, and dark solitary wavelike solutions to the dissipative NLS equation of the network. Through the exact solitary wavelike solutions to the dissipative NLS equation, we investigate the effects of the dissipative elements of the network on wave propagation. We show that the wave amplitude decreases and its width increases when the dissipative element of the network increases. It has been also found that the dissipative element of the network can be used to manipulate the motion of solitary waves through the network. This work presents a good analytical approach of investigating the propagation of solitary waves through discrete electrical transmission lines and is very important for studying modulational instability.


[Optimization of enzymatic preparation of glucose 1-phosphate by response surface methodology].
With glucose as substrate, sodium tripolyphosphate as the phosphorus acylating agent, and phosphorylase of Solanum tuberosum as the catalyst, glucose 1-phosphate was synthesized. Based on a three-level, three-variable Box-Behnken experimental design, response surface methodology was used to evaluate the effects of temperature, molar ratio of glucose to sodium tripolyphosphate and time on the production. The structure of the product was confirmed by 1H NMR spectra. The results show that the optimum conditions were as follows: temperature 35 degrees C, molar ratio of glucose to sodium tripolyphosphate 1.35:1 and time 19 h.


[Intestinal intussusception in children].
Enteric intussusception is one f the most frequent causes of acute abdomen in early childhood, with an incidence of 1.3-2/1000 children born and higher frequency from the third to the twelfth month. Primary intussusception is related to predisponsing factors such as peristalsis disorders or Peyer's patch hypertrophy induced by viral infection. Secondary intussusception is due to organic injury in the intestinal wall. The most involved sites are the terminal ileum and the ileocecum, the most frequent type is ileocolic intussusception. Many clinical forms exist, including acute enteric intussusception with its pathognomonic triad intermittent abdominal pain, emesis and rectal bleeding and the atypical form with a neurological presentation, where sopor, myosis and muscular atonicity are dominating, Intussusception can also present in a subacute or chronic form with a slow and apsecific onset. In a retrospective investigation we examined 30 cases of intussusception in children hospitalized at the Pediatric Clinic of Pisa from the 1960s up to today. Our patients (16 males and 14 females) were aged between one month and two years. Clinical presentations resulted in; typical forms (60%), atypical forms (16%), subacute forms 13%) and recurrent forms (10%). Clinical suspicion was confirmed either by the presence of blood observed during rectal exploration, which is a pathognomonic sign, or by the opaque enema which led to recovery by means of hydrostatic reduction in 40% of the cases. The remaining patients (60%) underwent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)


[Solitary rectal ulcer syndrome].
Solitary rectal ulcer syndrome (SRUS) is a chronic, benign, polymorphic disease of the rectum, the final diagnosis of which is based on histopathologic criteria. Microscopic examination shows glandular changes, oedema and obliteration of the normal architecture in the region of the lamina propria, with muslce fibre penetrating into lamina. Although SRUS pathogenesis is bound up with defecation disorder, it still remains unclear. Disease symptoms are nonspecific--in most cases defecation disorders appear (incomplete defecation, blood and mucus in stool). In some patients emotional disorders can be observed. SRUS treatment is a complex and long-lasting process. Usually it is ineffective or gives only passing effects. SRUS can often be accompanied by rectal prolapse, sometimes a hidden one. In these cases there are more therapeutic possibilities and the prognosis is slightly better. There is no method of choice for SRUS treatment and the prognosis is hard to predict. The treatment should be selected individually, depending on the symptoms intensity and the occurrence of rectal prolapse.


Histiocytic neoplasms in the era of personalized genomic medicine.
Since the discovery of B-Raf proto-oncogene (BRAF) V600E mutations in histiocytic neoplasms, diverse kinase alterations have been uncovered in BRAF V600E-wildtype histiocytoses. The purpose of this review is to outline recent molecular advances in histiocytic neoplasms and discuss their impact on the pathogenesis and treatment of these disorders. Activating kinase alterations discovered in BRAF V600E-wildtype Langerhans (LCH) and non-Langerhans cell histiocytoses (non-LCH) result in constitutive activation of the mitogen-activated protein kinase and/or phosphoinositide 3-kinases-Akt murine thymoma pathways. These kinase alterations include activating mutations in A-Raf proto-oncogene, mitogen-activated protein kinase kinase 1, neuroblastoma rat sarcoma viral oncogene homolog, Kirsten rat sarcoma viral oncogene homolog, and phosphatidylinositol-4,5-bisphosphate 3 kinase, catalytic subunit α kinases in LCH and non-LCH; BRAF, anaplastic lymphoma receptor tyrosine kinase, and neurotrophic tyrosine kinase, receptor type 1 fusions, as well as the Ets variant 3-nuclear receptor coactivator 2 fusion in non-LCH; and mutations in the mitogen-activated protein kinase kinase kinase 1 and Harvey rat sarcoma viral oncogene homolog kinases in LCH and histiocytic sarcoma, respectively. These discoveries have refined the understanding of the histiocytoses as clonal, myeloid neoplasms driven by constitutive mitogen-activated protein kinase signaling and identified molecular therapeutic targets with promising clinical responses to rapidly accelerated fibrosarcoma and mitogen-activated protein kinase kinase inhibition. Genomic analyses over the last 6 years have identified targetable kinase alterations in BRAF V600E-wildtype histiocytic neoplasms. However, despite this progress, the molecular pathogenesis and therapeutic responsiveness of non-BRAF V600E kinase alterations are still poorly defined in these disorders.


Hodgkin's lymphoma cells express alternatively spliced forms of HDM2 with multiple effects on cell cycle control.
The HDM2 oncoprotein is a cellular inhibitor of p53 and is frequently deregulated in human cancer. However, the HDM2 gene encodes alternatively spliced variants whose functional significance is poorly understood. We had previously reported the detection of alternative HDM2 forms in Hodgkin's lymphoma (HL)-derived cell lines. Here, we have cloned several of these transcripts, including the previously described HDM2-A, -B and -C (which encode the COOH terminus of HDM2), and two novel variants (HDM2-HL1 and -HL2) containing a complete p53 interaction domain. Real-time PCR assays demonstrated that HDM2-A and -B were selectively expressed by HL cell lines and primary tumors, compared with their non-neoplastic counterparts. In transient transfection experiments, alternatively spliced HDM2 isoforms were partially or totally localized within the cytoplasm. HDM2-HL2 was able to inhibit transactivation of a p53-inducible reporter construct and induced a partial relocalization of p53 to the cytoplasm. Expression of HDM2-A and -B caused the activation of p53/p21 and induced growth arrest in primary cells, but also increased the expression levels of cyclins D1 and E. Other possible genes regulated by HDM2-A and -B were identified using cDNA microarray technology. These results imply that HDM2 isoforms may have multiple effects on cell cycle control, and provide insight into the mechanisms through which these molecules contribute to tumorigenesis.


Embryo malposition as a potential mechanism for mercury-induced hatching failure in bird eggs.
We examined the prevalence of embryo malpositions and deformities in relation to total mercury (THg) and selenium (Se) concentrations in American avocet (Recurvirostra americana), black-necked stilt (Himantopus mexicanus), and Forster's tern (Sterna forsteri) eggs in San Francisco Bay (CA, USA) during 2005 to 2007. Overall, 11% of embryos were malpositioned in eggs > or =18 d of age (n = 282) and 2% of embryos were deformed in eggs > or =13 d of age (n = 470). Considering only those eggs that failed to hatch (n = 62), malpositions occurred in 24% of eggs > or =18 d of age and deformities occurred in 7% of eggs > or =13 d of age. The probability of an embryo being malpositioned increased with egg THg concentrations in Forster's terns, but not in avocets or stilts. The probability of embryo deformity was not related to egg THg concentrations in any species. Using a reduced dataset with both Se and THg concentrations measured in eggs (n = 87), we found no interaction between Se and THg on the probability of an embryo being malpositioned or deformed. Results of the present study indicate that embryo malpositions were prevalent in waterbird eggs that failed to hatch and the likelihood of an embryo being malpositioned increased with egg THg concentrations in Forster's terns. We hypothesize that malpositioning of avian embryos may be one reason for mercury-related hatching failure that occurs late in incubation, but further research is needed to elucidate this potential mechanism.


[FTIR and XRD analysis of the enzymatic degradation of crosslinked starch microspheres].
Crosslinked starch microspheres (CSM) were prepared by crosslinking of soluble starch and N, N'-methylene-bis-acrylamide in inverse suspension. In order to describe the enzymatic degradation of CSM in this experiment, soluble starch, CSM and CSM's degradation product obtained from the simulated intestinal fluid in different time were analysed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometer (XRD). The FTIR and SEM results showed that the CSM's crosslinking structure could be maintained steady in digested liquid within 3 hours. The intensity at 1,090 cm(-1) related to bending vibration bands of C--O--C, the amide band I and the amide band II became weaker in 3-12 hours along with the process of the enzymatic degradation, indicating the degradation of the molecular chain of starch and the depolymerization of the cross-linking structure. And then the disappearing of the amide band I and the amide band II indicated that the crosslinking structure was totally destructed after 12 hours and thereafter the enzymatic degradation was consistent with soluble starch. The XRD results proved that after 12 hours the CSM's degradation was similar to starch's degradation, their non-crystalline parts were decomposed, and their degree of crystallinity increased with the development of the degradation, but did not exceed the crystallinity of soluble starch.


Evolution of voltage-gated Na(+) channels.
Voltage-gated Na(+) channels play important functional roles in the generation of electrical excitability in most vertebrate and invertebrate species. These channels are members of a superfamily that includes voltage-gated K(+), voltage-gated Ca(2+) and cyclic-nucleotide-gated channels. There are nine genes encoding voltage-gated Na(+) channels in mammals, with a tenth homologous gene that has not been shown to encode a functional channel. Other vertebrate and invertebrate species have a smaller number of Na(+) channel genes. The mammalian genes can be classified into five branches in a phylogenetic tree, and they are localized on four chromosomes. Four of the branches representing the four chromosomal locations probably resulted from the chromosomal duplications that led to the four Hox gene clusters. These duplications occurred close to the emergence of the first vertebrates. The fifth branch probably evolved from a separate ancestral Na(+) channel gene. There are two branches in the invertebrate tree, although members of only one of those branches have been demonstrated to encode functional voltage-gated Na(+) channels. It is possible that the other branch may have diverged, so that its members do not represent true voltage-gated Na(+) channels. Vertebrate and invertebrate Na(+) channels appear to be derived from a single primordial channel that subsequently evolved independently in the two lineages.


Is the right amygdala involved in visuospatial memory? Evidence from MRI volumetric measures.
Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.


[Expression and significance of Toll-like receptor-4 in rats lung established by passive smoking or associated with intratracheal instillation of lipopolysaccharide].
To explore the expression and effect of Toll-like receptor 4 (TLR-4) in the lung tissue of rats established by passive smoking or intratracheal instillation of lipopolysaccharide (LPS). Eight-week-old male Sprague-Dawley rats (n = 15) were randomly divided into 3 groups, including: (1) group A: conventional breeding; (2) group B: the rats were placed into a 120-L organic glass box with twice-daily exposure to cigarette smoking plus an intratracheal instillation of water at Day 1 and 14; (3) Group C: exposure to cigarette smoking the same as group B plus intratracheal instillation of lipopolysaccharide (1 mg/kg) at Day 1 and 14. Four weeks later, general status, arterial blood gas, pulmonary function and histopathology were analyzed. The expressions of TLR-4 and nuclear factor kappa-B (NF-κB) were determined by immunohistochemistry. Western blot was used to measure the protein contents of TLR-4, NF-κB, p-Iκ-Kα/β, Iκ-Kα/β, IκB-α. And real-time polymerase chain reaction (PCR) was employed to detect the mRNA levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Rats in Groups B and C were marantic with intermittent cough and dyspnea. Peak expiratory flow (PEF) and 50% expiratory flow-volume (EP50) were much lower in Group C ((10.6 ± 1.4), (0.77 ± 0.14) ml/s) than that in Groups A ((13.5 ± 2.0), (1.01 ± 0.08) and B (12.3 ± 0.9), (0.91 ± 0.10) ml/s) (all P < 0.05). Accumulated volume (AV) and carbon dioxide pressure (PCO2) were much higher in Groups B ((4358 ± 1501) ml, (52.77 ± 1.97) mm Hg) (1 mm Hg = 0.133 kPa) and C ((10 077 ± 1866) ml, (51.03 ± 4.96) mm Hg) than that in Group A ((1735 ± 798) ml, (39.57 ± 1.43) mm Hg) (all P < 0.05). Hematoxylin and eosin stain showed chronic bronchitis and emphysema in Groups B and C. Besides, quantitative analysis demonstrated that in unit area, mean lining interval (MLI) and destruction index (DI) in Group B ((84 ± 13) µm, 0.228 ± 0.047) and Group C ((86 ± 10) µm, 0.294 ± 0.060) significantly increased versus Group A ((65 ± 6) µm, 0.036 ± 0.012) (all P < 0.05). Immunohistochemical staining indicated that the expression of TLR-4 in cytoplasm and cytomembrane and NF-κB in nucleus markedly increased in Groups B and C versus Group A. Relative expressions of TLR-4 and NF-κB assayed by Western blot increased in Group B (0.68 ± 0.03, 0.21 ± 0.08) and Group C (1.12 ± 0.11, 0.59 ± 0.06) than that in Group A (1.36 ± 0.07, 1.04 ± 0.08). Compared with Group A, the expression levels of TLR-4, NF-κB and IκB-α and the phosphorylation levels of Iκ-Kα/β in Group B and C significantly increased (all P < 0.05). The mRNA levels of TNF-α and IL-6 increased in Group B (3.95 ± 0.29, 5.04 ± 0.28) and C (5.33 ± 0.26, 7.23 ± 0.39) versus that in Group C (1.00 ± 0.37, 1.00 ± 0.25) (all P < 0.05). Both passive smoking and intratracheal instillation of LPS may cause lung injury analogous to chronic obstructive pulmonary disease via NF-κB signaling pathway. And TLR4 plays an important role in this process.


Functional improvement of patients with Parkinson syndromes using a rehabilitation training software.
Individuals with Parkinsonian disorders often face limited access to specialized physiotherapy and movement training due to staff shortages and increasing disease incidence, resulting in a rapid decline in mobility and feelings of despair. Addressing these challenges requires allocating adequate resources and implementing specialized training programs to ensure comprehensive care and support. Regarding these problems, a computer software was invented that might serve as an additional home-based extension to conventional physiotherapy. The trial took place in a rehabilitation center where every patient received equivalent treatment apart from the training program that was set up to be investigated over 3 weeks. Seventy four Patients were included and randomized between two intervention and one control group. Intervention group 1 (IG1) trained with the computer-based system two times a week while Intervention group 2 (IG2) received five training sessions a week. Using the markerless Microsoft Kinect® camera, participants controlled a digital avatar with their own body movements. UPDRS-III and Clinical measurements were performed before and after the three-week period. Patients in all groups improved in UPDRS-III pre and post intervention whereas reduction rates were higher for IG1 (-10.89%) and IG2 (-14.04%) than for CG (-7.74%). Differences between the groups were not significant (value of ps CG/IG1 0.225, CG/IG2 0.347). Growth rates for the arm abduction angle were significantly higher in IG1 (11.6%) and IG2 (9.97%) than in CG (1.87%) (value of ps CG/IG1 0.006 and CG/IG2 0.018), as was the 5-steps-distance (CG 10.86% vs. IG1 24.5% vs. UG2 26.22%, value of ps CG/IG1 0.011 and CG/IG2 0.031). The study shows the beneficial effects of computer-based training and substantiates the assumption of a similar impact in a home-based setting. The utilized software is feasible for such interventions and meets with the patient's approval. Group dynamics seem to have an additional supporting effect for the aspired objective of improving mobility and should be seen as an essential aspect of video games in therapy.


Kinetics of Strand Displacement and Hybridization on Wireframe DNA Nanostructures: Dissecting the Roles of Size, Morphology, and Rigidity.
Dynamic wireframe DNA structures have gained significant attention in recent years, with research aimed toward using these architectures for sensing and encapsulation applications. For these assemblies to reach their full potential, however, knowledge of the rates of strand displacement and hybridization on these constructs is required. Herein, we report the use of single-molecule fluorescence methodologies to observe the reversible switching between double- and single-stranded forms of triangular wireframe DNA nanotubes. Specifically, by using fluorescently labeled DNA strands, we were able to monitor changes in intensity over time as we introduced different sequences. This allowed us to extract detailed kinetic information on the strand displacement and hybridization processes. Due to the polymeric nanotube structure, the ability to individually address each of the three sides, and the inherent polydispersity of our samples as a result of the step polymerization by which they are formed, a library of compounds could be studied independently yet simultaneously. Kinetic models relying on mono-exponential decays, multi-exponential decays, or sigmoidal behavior were adjusted to the different constructs to retrieve erasing and refilling kinetics. Correlations were made between the kinetic behavior observed, the site accessibility, the nanotube length, and the structural robustness of wireframe DNA nanostructures, including fully single-stranded analogs. Overall, our results reveal how the length, morphology, and rigidity of the DNA framework modulate the kinetics of strand displacement and hybridization as well as the overall addressability and structural stability of the structures under study.


Long-term admissions to home health agencies: a life table analysis.
This article uses the first national survey of home health agencies and their patients to characterize the complete length-of-use distribution for an elderly admissions cohort. Of the 26 million older Americans admitted to home health agencies in 1992, 36% received care for at least three months, 22% for at least six months, and 15% for at least one year. Analyses suggest that one-year limits on Medicare's home health benefit would have affected a relatively small percentage of new admissions (less than 13%) but would have amounted to 300,000 or so beneficiaries in 1992. In contrast, proposals to limit Medicaid would have affected a more substantial proportion of home health agency admissions (about one fourth) but only a relatively small number of older Americans (30,000 in 1992). Such length of use limits would also disproportionately affect those at highest risk for nursing home admission: very old, unmarried, minority women with relatively unstable chronic conditions.


Area Coverage Maximization under Connectivity Constraint in Wireless Sensor Networks.
Wireless sensor networks (WSNs) have several important applications, both in research and domestic use. Generally, their main role is to collect and transmit data from an ROI (region of interest) to a base station for processing and analysis. Therefore, it is vital to ensure maximum coverage of the chosen area and communication between the nodes forming the network. A major problem in network design is the deployment of sensors with the aim to ensure both maximum coverage and connectivity between sensor node. The maximum coverage problem addressed here focuses on calculating the area covered by the deployed sensor nodes. Thus, we seek to cover any type of area (regular or irregular shape) with a predefined number of homogeneous sensors using a genetic algorithm to find the best placement to ensure maximum network coverage under the constraint of connectivity between the sensors. Therefore, this paper tackles the dual problem of maximum coverage and connectivity between sensor nodes. We define the maximum coverage and connectivity problems and then propose a mathematical model and a complex objective function. The results show that the algorithm, called GAFACM (Genetic Algorithm For Area Coverage Maximization), covers all forms of the area for a given number of sensors and finds the best positions to maximize coverage within the area of interest while guaranteeing the connectivity between the sensors.


RNA folding pathways in stop motion.
We introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are heterogeneous enough to describe metastable as well as intermediate states. These ensembles are first validated by performing a quantitative comparison against available solution nuclear magnetic resonance (NMR) data of a set of RNA tetranucleotides. Notably, the agreement is better with respect to the one obtained by comparing NMR with extensive all-atom molecular dynamics simulations. We then propose a procedure based on diffusion maps and Markov models that makes it possible to obtain reaction pathways and their relative probabilities from fragment ensembles. This approach is applied to study the helix-to-loop folding pathway of all the tetraloops from the GNRA and UNCG families. The results give detailed insights into the folding mechanism that are compatible with available experimental data and clarify the role of intermediate states observed in previous simulation studies. The method is computationally inexpensive and can be used to study arbitrary conformational transitions.


Characterizing Kaempferia parviflora extracellular vesicles, a nanomedicine candidate.
Plant-derived extracellular vesicles (EVs) are a promising candidate for nanomedicine delivery due to their bioactive cargos, high biocompatibility to human cells, biodegradability, low cytotoxicity, and potential for large-scale production. However, the research on EVs derived from medicinal plants is very limited. In this study, Kaempferia parviflora extracellular vesicles (KPEVs) were isolated by differential and sucrose density gradient centrifugation, and their size, morphology, and surface charge were characterized using transmission electron microscopy and dynamic light scattering. The biological properties of KPEVs, including their bioactive compound composition, gastric uptake, cytotoxicity, acid tolerance, and storage stability, were also examined. In addition, KPEVs had an average and uniform size of 200-300 nm and a negative surface charge of 14.7 ± 3.61 mV. Moreover, 5,7-dimethoxyflavone, the major bioactive compound of KP, was packaged into KPEVs. Meanwhile, KPEVs were resistant to gastric digestion and stably maintained at -20°C and -80°C for 8 weeks with no freeze-thaw cycle. The lipid hydrolysis during EVs storage at room temperature and 4°C were also demonstrated for the first time. Furthermore, the labeled KPEVs were internalized into adenocarcinoma gastric cells, and the cell viability was reduced in a dose-dependent manner, according to the results of the thiazolyl blue tetrazolium assay. Our study supports the potential application of KPEVs as a vehicle for anticancer or oral drugs.