Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study.
Vascular endothelial growth factor (VEGF) gene therapy may be useful for the treatment of lower-limb ischemia. The objectives of this study were to evaluate safety and angiographic and hemodynamic responses of local catheter-mediated VEGF gene therapy in ischemic lower-limb arteries after percutaneous transluminal angioplasty (PTA). For this study, we recruited patients with chronic lower-limb ischemia and atherosclerotic infrainguinal occlusion or stenosis suitable for PTA. In the study, 18 patients received 2x10(10) plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 microg of VEGF plasmid, 2000 microl of DOTMA:DOPE), and 19 control patients received Ringer's lactate at the angioplasty site. Digital subtraction angiography (DSA) was used to evaluate vascularity before, immediately after, and 3 months after the PTA. Clinical follow-up data, basic laboratory tests, and ankle-brachial index (ABI) were evaluated. Primary endpoint was DSA analysis of vascularity, and secondary endpoints were restenosis rate, Rutherford class, and ABI after 3 months follow-up. No major gene transfer-related side effects or differences in laboratory tests were detected between the study groups. However, anti-adenovirus antibodies increased in 61% of the patients treated with VEGF-Ad. For the primary endpoint, follow-up DSA revealed increased vascularity in the VEGF-treated groups distally to the gene transfer site (VEGF-Ad P=0.03, VEGFP/L P=0.02) and in the VEGF-Ad group in the region of the clinically most severe ischemia (P=0.01). As for the secondary endpoints, mean Rutherford class and ABI showed statistically significant improvements in the VEGF-Ad and VEGF-P/L groups, but similar improvements were also seen in the control patients. We conclude that catheter-mediated VEGF gene therapy is safe and well tolerated. Angiography demonstrated that VEGF gene transfer increased vascularity after PTA in both VEGF-Ad- and VEGF-P/L-treated groups.


Perceptions of 'Evidence-Based Practice' among the Consumers of Adolescent Substance Use Treatment.
Several national organisations in the USA have recently developed educational materials that encourage substance use disorder treatment consumers to seek out approaches supported by scientific evidence in order to promote the use of "evidence-based practice" (EBP). This study aimed to explore how adolescents (young people age 12-17 years) with substance use disorders and their caregivers perceive, understand, and react to the concept of EBP. Qualitative focus groups and structured interviews were conducted with 29 caregivers and 24 adolescents with substance use disorders in the Northeastern USA. Discussions explored four themes: a) familiarity with EBP, b) assumptions about what EBP means, c) impressions of EBP after reading a common definition, and d) recommended terms to describe EBP in educational materials. Participants' responses were transcribed and qualitatively analysed by two independent coders. Only two of the 53 participants had ever heard the term EBP, and only one was able to define it correctly. Common assumptions about the term "evidence-based" were that it referred to treatment based on the patient's medical history, legal evidence of substance use, or the clinician's prior experience. The misperception that EBP was associated with legal evidence was common among adolescents involved in the justice system. After reading a common definition of EBP, most participants thought that the approach sounded inflexible. Alternative terms the participants recommended to educate potential treatment consumers about EBP included proven, successful, better, and therapy that works. Results suggest that future efforts to educate treatment consumers should use the phrase EBP with caution and emphasise the flexibility of the approach.


Knee mobility in femoral lengthening using Ilizarov's method.
Muscle contracture and joint stiffness are a major concern during limb lengthening using the Ilizarov method. The aim of this study was to detect factors that may influence the final loss of knee flexion. We retrospectively studied knee movement in 32 patients undergoing femoral lengthening using the Ilizarov method. The pattern of loss of knee movement showed a rapid fall in knee flexion during the latency period between operation and start of distraction, and the flexion loss continued during lengthening. There was a relationship between the worst knee range of motion achieved during lengthening and the final loss of knee flexion. Intensive physical therapy is necessary in the latency period, because there is a rapid decrease in knee flexion, as well as during the whole lengthening procedure, in which flexion loss continues. Despite the flexion loss, patients finally regain good knee function after removal of the external fixator.


Genes for the eight ribosomal proteins are clustered on the chloroplast genome of tobacco (Nicotiana tabacum): similarity to the S10 and spc operons of Escherichia coli.
The nucleotide sequence of a tobacco (Nicotiana tabacum) chloroplast gene cluster that encodes eight proteins homologous to Escherichia coli ribosomal proteins L23, L2, S19, L22, S3, L16, L14, and S8 has been determined. RNA gel blot hybridization revealed that all eight coding regions are expressed in the chloroplasts. The arrangement of the eight genes resembles that found in the E. coli S10 and spc operons. Among the eight genes, the L2 and L16 genes contain 666- and 1020-base-pair introns, respectively. These intron boundary sequences are consistent with the conserved boundary sequences of the chloroplast group III introns [Shinozaki, K., Deno, H., Sugita, M., Kuramitsu, S. & Sugiura, M. (1986) Mol. Gen. Genet. 202, 1-5].


Estimation levels of prostate-specific antigen, interleukin-8, oxidative stress and some inflammatory markers in sera of benign prostatic hyperplasia patients who have smoking habits as a risk factor.
Benign prostatic hyperplasia (BPH) is a common multifactorial inflammatory disease of older men, defined by increased growth of prostate epithelial and stromal cells. Elevation serum levels of Interleukin-8 (IL-8), oxidative stress and inflammatory markers represent predictive surrogate markers of the disease progression in smoker BPH patients. A total of 86 BPH patients and 54 control subjects were admitted to the urology unit, Rizgary Teaching Hospital in Erbil City, Iraq between January and June 2020. Sera levels of prostate-specific antigen(PSA), IL-8, malondialdehyde (MDA), high sensitive C-reactive protein (hs-CRP), testosterone and some biomarkers concentrations were measured in the patients according to instructions of manufacturers. Patients and controls were categorized into groups according to smoking status (smokers and non-smokers). The sera levels of PSA, IL-8 and inflammatory markers like oxidative stress(MDA), hs-CRP and testosterone in every smoker subgroup (BPH patients and control) increased compared to the same non-smoker subgroups and significantly increased compared with non-smoker control (p<0.05). PSA demonstrated a significant positive correlation with the following terms, IL-8, MDA, hs-CRP, testosterone and low-density lipid (LDL)(p<0.05) and, insignificant negative correlation with high-density lipoprotein(HDL), (p>0.05). The current study demonstrated mounting evidence to support the role of smoking in the pathophysiology of BPH through elevation levels of inflammatory and oxidative stress biomarkers in sera of BPH patients.


Development of molecularly imprinted electrochemical sensor with reduced graphene oxide and titanium dioxide enhanced performance for the detection of toltrazuril in chicken muscle and egg.
A molecularly imprinted electrochemical sensor for toltrazuril (TZR) detection based on molecularly imprinted polymers (MIPs) immobilized on reduced graphene oxide (rGO) and titanium dioxide (TiO2) modified platinum (Pt) electrode surface was fabricated for the first time. The synergistic fast electron transfer ability, large electroactive surface area and high catalytic activity from rGO and TiO2 contribute to amplify the electrochemical signal and consequently improve the sensitivity of the sensor. The cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) tests were used to evaluate the performance of the electrochemical sensor. The results showed that the electrochemical sensor possessed high sensitivity, good selectivity and anti-interference ability toward TZR. By using the DPV, the electrochemical sensor displayed a wide linear concentration range from 0.43 to 42.54 μg/L, with a limit of detection of 0.21 μg/L (S/N = 3). Moreover, the recoveries and relative standard deviations (RSD) were 85.0%-97.0% and 3.5%-6.4% at three concentration levels, respectively, implying that the established sensor is promising for the accurate detection of TZR at trace levels in chicken muscle and egg samples.


C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis.
Obesity induces a program of systemic inflammation that is implicated in the development of many of its clinical sequelae. Hepatic inflammation is a feature of obesity-induced liver disease, and our previous studies demonstrated reduced hepatic steatosis in obese mice deficient in the C-C chemokine receptor 2 (CCR2) that regulates myeloid cell recruitment. This suggests that a myeloid cell population is recruited to the liver in obesity and contributes to nonalcoholic fatty liver disease. We used fluorescence-activated cell sorting to measure hepatic leukocyte populations in genetic and diet forms of murine obesity. We characterized in vivo models that increase and decrease an obesity-regulated CCR2-expressing population of hepatic leukocytes. Finally, using an in vitro co-culture system, we measured the ability of these cells to modulate a hepatocyte program of lipid metabolism. We demonstrate that obesity activates hepatocyte expression of C-C chemokine ligand 2 (CCL2/MCP-1) leading to hepatic recruitment of CCR2(+) myeloid cells that promote hepatosteatosis. The quantity of these cells correlates with body mass and in obese mice represents the second largest immune cell population in the liver. Hepatic expression of CCL2 increases their recruitment and in the presence of dietary fat induces hepatosteatosis. These cells activate hepatic transcription of genes responsible for fatty acid esterification and steatosis. Obesity induces hepatic recruitment of a myeloid cell population that promotes hepatocyte lipid storage. These findings demonstrate that recruitment of myeloid cells to metabolic tissues is a common feature of obesity, not limited to adipose tissue.


Haemolymphangioma of epiglottis.
Lymphangiomas are congenital lesions of the lymphatic system which are most commonly found in the head and neck, with over 90 % of lesions manifesting in children who are less than 2 years of age. Haemolymphangiomas are rare variant of lymphangioma, with the presence of red blood cells within the lymphatic channels. Laryngeal sites are usually in continuity with foci of disease in the neck. In general, symptoms are non-specific and they vary with the site and size of the mass. Usually, they occur before 2 years of age. Isolated cases of lymphangiomas with involvement of epiglottis are rare and only a few cases have been reported so far. We are reporting the case of a six-year-old girl who presented with a mass in the epiglottis.


Symptomatic bladder endocervicosis: does it need surgery? A case report and review of the literature.
Endocervicosis of the urinary bladder is a rare benign condition exclusively seen in women, usually of reproductive age. To the best of our knowledge there are only about twenty cases reported so far. It causes non-specific symptoms and is seen as a submucosal lesion on cystoscopy. On histological examination one finds endocervical glands embedded deep within the muscle layers. It can be confused with an adenocarcinoma of the bladder. Unless the correct diagnosis is made these patients can undergo potentially debilitating surgery. As demonstrated in our patient even symptomatic endocervicosis can be managed conservatively.


Targeting the TGF-β Signaling Axis in Metastatic Colorectal Cancer: Where Do We Stand?
Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide [...].


Jasmonic acid and salicylic acid modulate systemic reactive oxygen species signaling during stress responses.
Plants can send long-distance cell-to-cell signals from a single tissue subjected to stress to the entire plant. This ability is termed "systemic signaling" and is essential for plant acclimation to stress and/or defense against pathogens. Several signaling mechanisms are associated with systemic signaling, including the reactive oxygen species (ROS) wave, calcium wave, hydraulic wave, and electric signals. The ROS wave coordinates multiple physiological, molecular, and metabolic responses among different parts of the plant and is essential for systemic acquired acclimation (SAA) to stress. In addition, it is linked with several plant hormones, including jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA). However, how these plant hormones modulate the ROS wave and whether they are required for SAA is not clear. Here we report that SA and JA play antagonistic roles in modulating the ROS wave in Arabidopsis (Arabidopsis thaliana). While SA augments the ROS wave, JA suppresses it during responses to local wounding or high light (HL) stress treatments. We further show that ethylene and ABA are essential for regulation of the ROS wave during systemic responses to local wounding treatment. Interestingly, we found that the redox-response protein NONEXPRESSOR OF PATHOGENESIS RELATED PROTEIN 1 is required for systemic ROS accumulation in response to wounding or HL stress, as well as for SAA to HL stress. Taken together, our findings suggest that interplay between JA and SA might regulate systemic signaling and SAA during responses of plants to abiotic stress or wounding.


[Improvement of hospital working conditions: ORSOSA, from research to preventive actions].
The health of hospital workers, nurses and nurse-aids constitutes a public health challenge for three reasons: maintenance of personnel at work in a context in which many express their desire to quit their jobs, protection of their health, and maintenance of quality of care. ORSOSA (ORganisation des SOins et SAnté des soignants) is a multidisciplinary interventional population health research programme designed to improve quality of life in the workplace of healthcare workers. This programme is designed to develop a tool to diagnose psychosocial and organisational work factors (POWFs) and mechanical constraints (MC), and then to implement this method in primary prevention interventions. ORSOSA consists of two steps: research (ORSOSA 1) and intervention (ORSOSA 2). In ORSOSA 1, a prospective cohort of healthcare workers was developed to construct and validate the diagnostic tool of work-related constraints at the work unit level. ORSOSA 2 consists of using the tool to implement both a collective and consensual dynamic based on collective restitution of the strengths and weaknesses of the work unit in order to propose recommendations for better quality of life at work. ORSOSA is now deployed in 4 teaching hospitals (Lille, Bordeaux, Grenoble and Strasbourg), each with 5 peripheral hospitals. Evaluation and follow-up of the programme is ongoing.


Dynamin-related protein Drp1 is required for Bax translocation to mitochondria in response to irradiation-induced apoptosis.
Translocation of the pro-apoptotic protein Bax from the cytosol to the mitochondria is a crucial step in DNA damage-mediated apoptosis, and is also found to be involved in mitochondrial fragmentation. Irradiation-induced cytochrome c release and apoptosis was associated with Bax activation, but not mitochondrial fragmentation. Both Bax and Drp1 translocated from the cytosol to the mitochondria in response to irradiation. However, Drp1 mitochondrial translocation and oligomerization did not require Bax, and failed to induce apoptosis in Bax deficient diffuse large B-cell lymphoma (DLBCL) cells. Using fluorescent microscopy and the intensity correlation analysis, we demonstrated that Bax and Drp1 were colocalized and the levels of colocalization were increased by UV irradiation. Using co-immuno-precipitation, we confirmed that Bax and Drp1 were binding partners. Irradiation induced a time-associated increase in the interaction between active Bax and Drp1. Knocking down Drp1 using siRNA blocked UV irradiation-mediated Bax mitochondrial translocation. In conclusion, our findings demonstrate for the first time, that Drp1 is required for Bax mitochondrial translocation, but Drp1-induced mitochondrial fragmentation alone is not sufficient to induce apoptosis in DLBCL cells.


Catabolite regulation of the pta gene as part of carbon flow pathways in Bacillus subtilis.
In Bacillus subtilis, the products of the pta and ackA genes, phosphotransacetylase and acetate kinase, play a crucial role in the production of acetate, one of the most abundant by-products of carbon metabolism in this gram-positive bacterium. Although these two enzymes are part of the same pathway, only mutants with inactivated ackA did not grow in the presence of glucose. Inactivation of pta had only a weak inhibitory effect on growth. In contrast to pta and ackA in Escherichia coli, the corresponding B. subtilis genes are not cotranscribed. Expression of the pta gene was increased in the presence of glucose, as has been reported for ackA. The effects of the predicted cis-acting catabolite response element (CRE) located upstream from the promoter and of the trans-acting proteins CcpA, HPr, Crh, and HPr kinase on the catabolite regulation of pta were investigated. As for ackA, glucose activation was abolished in ccpA and hprK mutants and in the ptsH1 crh double mutant. Footprinting experiments demonstrated an interaction between CcpA and the pta CRE sequence, which is almost identical to the proposed CRE consensus sequence. This interaction occurs only in the presence of Ser-46-phosphorylated HPr (HPrSer-P) or Ser-46-phosphorylated Crh (CrhSer-P) and fructose-1,6-bisphosphate (FBP). In addition to CcpA, carbon catabolite activation of the pta gene therefore requires at least two other cofactors, FBP and either HPr or Crh, phosphorylated at Ser-46 by the ATP-dependent Hpr kinase.


[An unusual mode of snake poisoning in Tunisia].
Snake poisoning constitutes a real public health problem in the North African countries. In Tunisia, snake poisonings are particularly frequent in the sub-Saharan regions (southern areas) with high mortality and possible debilitation in survivors. The most common mode of snake poisoning is biting, particularly on the extremities. The purpose of this report is to describe a case involving a patient who presented authentic systemic signs of a snake poisoning after ingesting a whole raw viper of the Cerastes cerastes species. Local signs as well as coagulation abnormalities often associated with bites by this kind of viper were not observed. The outcome was favorable after three days of hospitalization. Treatment consisted of symptomatic measures and administration of antivenom therapy.


Tunisian Native Mentha pulegium L. Extracts: Phytochemical Composition and Biological Activities.
Mint species (Lamiaceae family) have been used as traditional remedies for the treatment of several diseases. In this work, we aimed to characterize the biological activities of the total phenolic and flavonoid contents of Mentha pulegium L. extracts collected from two different regions of Tunisia. The highest amounts of total phenols (74.45 ± 0.01 mg GAE/g DW), flavonoids (28.87 ± 0.02 mg RE/g DW), and condensed tannins (4.35 ± 0.02 mg CE/g DW) were found in the Bizerte locality. Methanolic leaf extracts were subjected to HPLC-UV analysis in order to identify and quantify the phenolic composition. This technique allowed us to identify seven phenolic compounds: two phenolic acids and five flavonoid compounds, such as eriocitrin, hesperidin, narirutin, luteolin, and isorhoifolin, which were found in both extracts with significant differences between samples collected from the different regions (p < 0.05). Furthermore, our results showed that the methanolic extract from leaves collected from Bizerte had the highest antioxidant activities (DPPH IC50 value of 16.31 μg/mL and 570.08 μmol Fe2+/g, respectively). Both extracts showed high radical-scavenging activity as well as significant antimicrobial activity against eight tested bacteria. The highest antimicrobial activities were observed against Gram-positive bacteria with inhibition zone diameters and MIC values ranging between 19 and 32 mm and 40 and 160 µg/mL, respectively. Interestingly, at 10 μg/mL, the extract had a significant effect on cell proliferation of U87 human glioblastoma cells. These findings open perspectives for the use of Mentha pulegium L. extract in green pharmacy, alternative/complementary medicine, and natural preventive therapies for the development of effective antioxidant, antibacterial, and/or antitumoral drugs.


Policosanol Attenuates Cholesterol Synthesis via AMPK Activation in Hypercholesterolemic Rats.
This study was carried out to investigate the effects of policosanol on high-fat and high-cholesterol diet-induced hypercholesterolemic rats to provide strong evidence in support of its hypocholesterolemic effect. The hypercholesterolemic rats showed elevations in liver weight, total triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol in serum; however, policosanol supplementation reduced these markers significantly. In addition, we found that policosanol supplementation stimulated an increase in fecal cholesterol and bile acid contents and deactivated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase by AMP-activated protein kinase (AMPK) phosphorylation during high-fat and high-cholesterol-containing diet-induced development of hypercholesterolemia. Policosanol supplementation decreased ApoB levels and increased LDL-receptor expression, but it did not affect the hepatic ACAT2 level in livers from hypercholesterolemic rats. Moreover, supplementation with policosanol significantly decreased aortic wall thickness and levels of P-selectin and soluble vascular cell adhesion molecule (sVCAM-1) in serum. In conclusion, we suggest that policosanol supplementation induces antihypercholesterolemia by inhibiting cholesterol biosynthesis, LDL cholesterol uptake, and cholesterol excretion.


Observation of orbital angular momentum transfer from bessel-shaped acoustic vortices to diphasic liquid-microparticle mixtures.
We observe distinct regimes of orbital angular momentum (OAM) transfer from two-dimensional Bessel-shaped acoustic vortices to matter. In a homogeneous diphasic mixture of microparticles and water, slow swirling about the vortex axis is seen. This effect is driven by the absorption of OAM across the mixture, the motion following the OAM density distribution. Larger particles are formed into clusters by the acoustic radiation force, making the mixture nonhomogeneous. Here, the OAM transfer to the microparticle clusters dominates and they spin at high speeds entraining the surrounding fluid.


Quality of life related to urinary continence in adult spina bifida patients.
To analyze the correlations of bladder management technique, ambulatory status and urologic reconstruction on quality of life (QOL) as affected by urinary symptoms in adult spina bifida (SB) patients. Sixty-six adult SB patients completed the RAND 36-Item Health Survey (mSF-36) and Incontinence Quality of Life (I-QOL). Demographic information, history of urinary reconstruction, and bladder management techniques were reviewed and analyzed with respect to survey scores. Mean age of patients was 32.3 (SD ±7.2) years and 44 patients (66.7%) were female. Forty-five patients (68.2%) were mainly ambulatory, 21 (31.8%) use a wheelchair and 10 (15.2%) had urologic reconstruction, while 56 (83.3%) did not. Twelve patients (18.2%) void, 42 (63.6%) perform clean intermittent catheterization (CIC), 4 (6.1%) use an indwelling catheter, 3 (4.5%) have an ileal conduit (IC) and 5 (7.6%) mainly use diapers. Mean mSF-36 General Health score was 56.5 (SD ±22.9) and mean I-QOL Sum score was 50.9 (SD ±21.7), where lower scores reflect lower QOL. mSF-36 and I-QOL scores did not significantly correlate with bladder management technique, ambulatory status or urologic reconstruction. A correlation was noted between I-QOL scales and most mSF-36 scales (all p <0.02). In our cohort study of adult SB patients, bladder management technique and urologic reconstruction did not correlate with urinary (I-QOL) or general health (mSF-36) domains, although I-QOL and mSF-36 scores correlated closely, suggesting urinary continence is significantly related to general QOL. However, we are unable to identify a single factor that improves either urinary or general QOL.


Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.
Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.


Analysis of the most relevant anthropometric dimensions for school furniture selection based on a study with students from one Chilean region.
Most of the worldwide standards used for furniture selection suggest the use of the Stature of the school children, assuming that all the other anthropometric characteristics will also be appropriate. However, it is important to consider that students' growth differ with age. The aim of this study is to determine if Popliteal Height can be used as a better, or more adequate, measure for classroom furniture selection when comparing with Stature. This study involved a representative group of 3046 students from the Valparaíso Region, in Chile. Regarding the methodology, eight anthropometric measures were gathered, as well as six furniture dimensions from the Chilean standard. After assigning the level of school furniture using Stature and Popliteal Height to each of the students, six mismatch equations were applied. The results show that when using Popliteal Height, higher levels of match were obtained for the two more important furniture dimensions. Additionally, it also presents a better cumulative fit than Stature. In conclusion, it seems that Popliteal Height can be the most accurate anthropometric measure for classroom furniture selection purposes.


Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein).
Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme-linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone.


Renin in thymus, gut, hindlimb, and adrenal of (mRen-2)27 and normal rats: secretion and content studies.
Thymic ablation and assay of organ renin revealed that one-third of the increasing plasma level of active renin after removal of kidneys and adrenals from Ren-2 rats originates from the thymus. Splanchnic arteriovenous difference and renin content indicate that gut can account for the remainder. Secretion of active renin from these sites correlated significantly with increasing plasma potassium. Prorenin was not secreted from these sites or from hindlimb in amounts sufficient to raise the plasma level, and yet plasma prorenin remained higher than active renin throughout the 12-h protocol. The source of prorenin that accounts for the high plasma prorenin phenotype of the intact conscious Ren-2 rat was not specifically identified. When sensitive assays were used, a low level of active renin secretion from thymus and gut was also apparent 12 h after removal of kidneys and adrenals in normal Sprague-Dawley rats, and plasma prorenin was at this time higher than active renin. A likely source of this extrarenal, extra-adrenal renin is the macrophage.


[Gastric neuroendocrine tumors in a woman with systemic lupus erythematosus].
A 56-year-old woman presented with pronounced petechia. She complained about recurrent fever and night sweat for two weeks, having felt unwell during the past years. Laboratory examinations showed thrombocytopenia, leukopenia and considerably elevated liver enzymes. Antinuclear antibodies and antibodies against double-stranded DNA were positive. Sonography showed a slightly enlarged liver with multiple surrounding lymph nodes, splenomegaly and chronic-atrophic thyroiditis. Gastroscopy revealed several polypes which were immunohistochemically classified as neuroendocrine tumors (NET). Systemic lupus erythematosus (SLE) with involvement of several organs was diagnosed and high doses of steroids were given. The steroid was then gradually reduced and changed to azathioprine. The NET were removed endoscopically. Neuroendocrine tumors are rare and localised to the stomach in only 2 - 4 %. Only three cases of gastric NET in the context of SLE with autoimmune gastritis have been reported so far in the literature.


Power spectral analysis of heart rate variability: normal values of subjects over 60 years old.
Power spectral analysis of heart rate variability (HRV) provides a non-invasive method of estimating cardiac autonomic nerve activity. It has been reported that HRV decreases with age. The purpose of this study was to assess the values of and determine the reliability of HRV in healthy older people. The study found lower and highly variable values of HRV. It was concluded that the reliability of HRV in older subjects might need to be reinvestigated and only normalized values of HF and LF might be useful. Larger study groups and different recording periods of HRV are needed.


Gaze-Contingent Retinal Speckle Suppression for Perceptually-Matched Foveated Holographic Displays.
Computer-generated holographic (CGH) displays show great potential and are emerging as the next-generation displays for augmented and virtual reality, and automotive heads-up displays. One of the critical problems harming the wide adoption of such displays is the presence of speckle noise inherent to holography, that compromises its quality by introducing perceptible artifacts. Although speckle noise suppression has been an active research area, the previous works have not considered the perceptual characteristics of the Human Visual System (HVS), which receives the final displayed imagery. However, it is well studied that the sensitivity of the HVS is not uniform across the visual field, which has led to gaze-contingent rendering schemes for maximizing the perceptual quality in various computer-generated imagery. Inspired by this, we present the first method that reduces the "perceived speckle noise" by integrating foveal and peripheral vision characteristics of the HVS, along with the retinal point spread function, into the phase hologram computation. Specifically, we introduce the anatomical and statistical retinal receptor distribution into our computational hologram optimization, which places a higher priority on reducing the perceived foveal speckle noise while being adaptable to any individual's optical aberration on the retina. Our method demonstrates superior perceptual quality on our emulated holographic display. Our evaluations with objective measurements and subjective studies demonstrate a significant reduction of the human perceived noise.


Long-term follow-up of patients with liver cirrhosis after endoscopic ethanol injection sclerotherapy for esophageal varices.
Esophageal variceal hemorrhage is a severe complication of liver cirrhosis, and therapy for acute bleeding and prevention of hemorrhage are important. In this study, we evaluated the long-term cumulative survival rate of patients with esophageal varices after treatment with endoscopic ethanol injection sclerotherapy (EIS group) or pharmacological therapy (non-EIS group). All 110 patients were treated for their esophageal varices and their prognosis and complications were analyzed during the follow-up period. The cumulative survival rate in the primary preventive EIS group was superior to that in the non-EIS group. The preventive EIS group had greater long-term survival rate than those treated on an emergency group. With respect to emergency therapy, the EIS group had better survival rates than the non-EIS group during the two-year follow-up period after esophageal variceal therapy. We conclude that primary preventive EIS is an effective therapy for survival of patients with esophageal varices over a long-term period.


Suppressed expression of the cytochrome P45017 alpha protein in the testicular feminized (Tfm) mouse testes.
The testes of testicular feminized (Tfm) mice synthesize and secrete abnormally low amounts of testosterone, as a consequence of selectively decreased cytochrome P450(17 alpha) activity. To investigate the mechanism of this deficiency, three steroidogenic enzymes were immunolabeled in the testes of normal and Tfm adult (2.5-6 month old) mice. Cholesterol side-chain cleavage cytochrome P450 (P450scc) and delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were detected in the Leydig cells of both normal and Tfm mice whereas, in contrast to normal mice, only a small proportion of Leydig cells were immunostained for cytochrome P450-17 alpha-hydroxylase, C17-->20 lyase (P450(17 alpha)) in the testes of Tfm mice. The numbers of cells differed from male to male and interestingly were markedly higher in the right testis. Explants of testes from Tfm mice were kept in organ culture at 32 degrees C for 45 h, with or without dibutyryl cyclic AMP (100 or 500 mumol/l). All Leydig cells remained positive for P450scc and 3 beta-HSD, and P450(17 alpha) became detectable in the majority of Leydig cells in both left and right testes, showing that the lack of expression of P450(17 alpha) protein in Tfm mouse testes in vivo is not structural but is a regulatory phenomenon.


Major royal-jelly protein 2 and its isoform X1 are two novel safe inhibitors for hepatitis C and B viral entry and replication.
Infections with HCV and HBV are serious worldwide health problems. Here, we report the anti-HCV and -HBV proficiency of Apis mellifera major royal-jelly protein (MRJP) 2 and its isoform X1. The efficiency of these proteins was evaluated in vitro and their safety was examined in vivo in comparison with Sofosbuvir (SOF) drug. Various in-silico methodologies were achieved for better understanding the antiviral mechanism of these MRJPs. Results proved their precluding ability to the viral receptors, CD81 and scavenger receptor class B type I (SR-B1). In addition, they targeted HCV-NS3/NS4A protease, HCV-NS5B polymerase, and HBV-polymerase (DNA-dependent DNA polymerase, and reverse transcriptase). Co-treatment with these proteins exerted different efficiencies toward CD81 and SR-B1 (synergistic), HBV-enzymes (antagonistic), and HCV-enzymes (either additive or synergistic). The studied proteins maximized their antiviral effect by their safety and superior potency to SOF. Collectively, these outcomes will shed the light on MRJP2 and its isoform X1 as two promising safe-inhibitors for both HCV and HBV.


Cytological diagnosis of Xp11 translocation renal cell carcinoma: An unusual suspect in bone metastases from unknown primary malignancies.
Renal cell carcinoma (RCC) constitutes 3% of all cancers, with a higher incidence in patients with age between 60 and 70 years. RCC frequently present as a metastatic tumor at diagnosis, and bones represent one of the most frequent sites. Many cases, mainly in young patients, includes the Xp11 translocation RCC. The cytological diagnosis of Xp11 translocation RCC in adult population it is rarely performed, likely for the morphological overlap with other adult renal cell carcinoma subtypes. We retrospectively analyze a series of 92 adult patients with metastatic bone tumors, diagnosed on fine-needle aspiration cytology (FNAC) samples, focusing mainly on the cytological, immunophenotypic and molecular features of Xp11 translocation RCC. In our series 6 of 92 (6.5%) cases were metastatic RCC (mRCC), among them 2 cases were metastasis from Xp11translocation RCC. Those cases showed a bloody background, with several groups of atypical cells arranged in syncytial groups or in papillary groups composed by atypical cells with abundant cytoplasm, with scattered clear cells. TFE3 was positive on immunocytochemical analysis and specific translocation t(Xp11.23) was detected by FISH analysis. In adult patients with mRCC, it is necessary to consider also Xp11 translocation RCC among the diagnostic hypotheses. FNAC represents a valid tool to investigate bone lesions but cytological features of Xp11 translocation RCC are still poorly described and must necessarily be better defined.


Identification of a novel BRCA2 and CHEK2 A-C-G-C haplotype in Turkish patients affected with breast cancer.
Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls. We found significant associations in the analyses of CHEK2- 1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2- Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (?2=7.655; p=0.0057) in the patient group compared to controls. In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.


Management of Juvenile Polyposis Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group.
The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.


Dynamic Re-calibration of Perceived Size in Fovea and Periphery through Predictable Size Changes.
The same object produces quite distinct images in the cortical representation, depending on whether it is looked at foveally or with the periphery, yet some form of size constancy prevents us from experiencing objects inflating or deflating as we move our eyes. According to the prominent sensorimotor account of vision by O'Regan and Noë [1], we constantly learn to discount the predictable sensory effects of motor actions, such as the projection of a stimulus on a larger cortical area as it gets foveated. Although previous studies have shown that foveal and parafoveal inputs can be associated in visual memory [2, 3], trans-saccadic prediction error could in principle re-calibrate even the appearance of peripheral and foveal stimuli. Here we introduce a new paradigm that induces such changes in the relative appearance of peripheral and foveal stimuli when directly compared. Repeated exposure to a trans-saccadic change in size, though unnoticed by most observers, induced a substantial modification of perceived size that lasted at least 1 day. Prediction is not limited to the motor system but can also occur for the sensory effects of external events, such as stimulus motion. We show that perceptual re-calibration can occur in the absence of eye movements if the change in size occurs predictably while objects move across the visual field. Perceptual uniformity emerges due to the continuously updated prediction of foveal appearance based on peripheral appearance.


The effect of noise exposure during the developmental period on the function of the auditory system.
Recently, there has been growing evidence that development and maturation of the auditory system depends substantially on the afferent activity supplying inputs to the developing centers. In cases when this activity is altered during early ontogeny as a consequence of, e.g., an unnatural acoustic environment or acoustic trauma, the structure and function of the auditory system may be severely affected. Pathological alterations may be found in populations of ribbon synapses of the inner hair cells, in the structure and function of neuronal circuits, or in auditory driven behavioral and psychophysical performance. Three characteristics of the developmental impairment are of key importance: first, they often persist to adulthood, permanently influencing the quality of life of the subject; second, their manifestations are different and sometimes even contradictory to the impairments induced by noise trauma in adulthood; third, they may be 'hidden' and difficult to diagnose by standard audiometric procedures used in clinical practice. This paper reviews the effects of early interventions to the auditory system, in particular, of sound exposure during ontogeny. We summarize the results of recent morphological, electrophysiological, and behavioral experiments, discuss the putative mechanisms and hypotheses, and draw possible consequences for human neonatal medicine and noise health.


Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol.
Rats, trained to discriminate between delta 9-THC (5 mg/kg) and a control solution, using a T-maze, were submitted to generalization tests wih delta 9-THC (2.5 and 1.25 mg/kg), CBD (40 mg/kg) and the mixtures of delta 9-THC (5 and 1.25 mg/kg) with CBD (40 mg/kg). Doses of delta 9-THC smaller than the training dose, produced a progressive reduction in the number of correct responses together with a decrease in the running time. The choice made by the animals under the effect of CBD (40 mg/kg) did not differ from that of the animals given the control solution but their running time was significantly longer. The mixtures of CBD (40 mg/kg) with delta 9-THC (5 and 1.25 mg/kg) produced approximately 50% response to both sides of the maze, and with run times greater than those observed with delta 9-THC (5 mg/kg). The results suggest that the simultaneous administration of the two cannabinoids might produce a qualitative stimulus different from that produced by delta 9-THC alone.


[Carcinoma in situ of the testis: predisposition, evolution and early detection].
Carcinoma in situ (CIS), also known as intratubular germ cell neoplasia unclassified, is the common obligate precursor lesion of malignant testicular seminomatous and non-seminomatous germ cell tumors (GCT), which show a steadily increasing incidence in Europe. Although GCT is a potentially curable cancer with excellent prognosis even in patients with organ metastasis, many patients suffer from chemotherapy-associated effects and some develop a secondary (non-germ cell) malignancy. Recently, genome-wide association studies revealed genetic predispositions linked to six genes (KITL, SPRY4, BAK1, TERT, ATF7IP, DMRT1). Exposure to environmental factors was also linked to increased prevalence of testicular dysgenesis and CIS/GCT by the action of hormone disruptors on embryonal gonadal tissue during pregnancy. By unknown mechanisms these genetic and environmental factors might create a disturbed microenvironment in the fetal testis leading to survival of embryonic germ cells and subsequent malignant transformation might result in CIS. Molecular pathways involved in this process include activated cKIT pathway and LIN28 associated deregulation of miRNA targets. The challenge for the future is to identify high risk patients prior to invasive GCT, to develop non-invasive tests for detection of CIS on seminal material and elucidate the precise role of the microenvironment in CIS initiation.


The durability of ceramic coated dental instruments.
This study investigates the hardness, structure, composition, and thickness of coatings on two dental instruments and the changes which occurred when the instruments were subjected to conditions that closely match their clinical use. One group of instruments had a titanium nitride coating that was approximately 8 micrometers thick and had a hardness of 19.5 GN/m2. The coating on the other instrument was alumina (aluminium oxide) and contained some microcracks even when new; this coating was thicker (approximately 30 micrometers) and had a hardness less than the titanium nitride coating (15.8 GN/m2). The results showed that the titanium nitride coating was structurally superior compared with the aluminium oxide coating. Laboratory wear tests against composite resin showed that the wear resistance of titanium nitride was superior to that of stainless steel whether assessed in terms of weight or volume loss.


Retinal Cholesterol Content Is Reduced in Simvastatin-Treated Mice Due to Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol.
Statins, a class of cholesterol-lowering drugs, are currently being investigated for treatment of age-related macular degeneration, a retinal disease. Herein, retinal and serum concentrations of four statins (atorvastatin, simvastatin, pravastatin, and rosuvastatin) were evaluated after mice were given a single drug dose of 60 mg/kg body weight. All statins, except rosuvastatin, were detected in the retina: atorvastatin and pravastatin at 1.6 pmol and simvastatin at 4.1 pmol. Serum statin concentrations (pmol/ml) were 223 (simvastatin), 1401 (atorvastatin), 2792 (pravastatin), and 9050 (rosuvastatin). Simvastatin was then administered to mice daily for 6 weeks at 60 mg/kg body weight. Simvastatin treatment reduced serum cholesterol levels by 18% and retinal content of cholesterol and lathosterol (but not desmosterol) by 24% and 21%, respectively. The relative contributions of retinal cholesterol biosynthesis and retinal uptake of serum cholesterol to total retinal cholesterol input were changed as well. These contributions were 79% and 21%, respectively, in vehicle-treated mice and 69% and 31%, respectively, in simvastatin-treated mice. Thus, simvastatin treatment lowered retinal cholesterol because a compensatory upregulation of retinal uptake of serum cholesterol was not sufficient to overcome the effect of inhibited retinal biosynthesis. Simultaneously, simvastatin-treated mice had a 2.9-fold increase in retinal expression of Cd36, the major receptor clearing oxidized low-density lipoproteins from Bruch's membrane. Notably, simvastatin treatment essentially did not affect brain cholesterol homeostasis. Our results reveal the statin effect on the retinal and brain cholesterol input and are of value for future clinical investigations of statins as potential therapeutics for age-related macular degeneration.


MRI brain changes in subjects with Down syndrome with and without dementia.
Individuals with Down syndrome (DS), a disorder of known genetic etiology (trisomy of chromosome 21), exhibit several types of structural brain abnormalities that are detectable pathologically and by MRI. In addition, in middle age, individuals with DS develop histological and, in some cases, clinical features of Alzheimer's disease (AD). Abnormalities in MRI scans of 50 adults with DS, 11 of whom had clinical dementia, are described and compared with those of 23 cognitively normal, healthy subjects who were matched for age, sex, and race. Qualitative visual analogue scale (VAS) ratings on MRI hard copies for all subjects and computer-aided volume measures for a subsample of subjects were carried out. On VAS, subjects with DS had larger lateral ventricles, a higher frequency of posterior fossa arachnoid cysts/megacisterna magna and fewer scans rated as normal compared with controls. Quantitatively, total brain and gray-matter volumes were reduced in DS, as were the volumes of the left hippocampus and amygdala; ventricle volumes were larger. Post hoc comparisons of subjects with DS with and without dementia revealed that on VAS the former had more generalized atrophy for age, mesial temporal shrinkage, and third ventricular enlargement. Similarly, total brain, left hippocampus, and left amygdala volumes were reduced quantitatively in subjects with DS with dementia, while ventricular volumes were increased.


Biodynamic ontology: applying BFO in the biomedical domain.
We propose a modular formal ontology of the biomedical domain with two components, one for biological objects, corresponding broadly to anatomy, and one for biological processes, corresponding broadly to physiology. The result constitutes what might be described as a joint venture between two perspectives--of so-called three-dimensionalism and four-dimensionalism--which are normally regarded as incompatible. We outline an approach which allows them to be combined together, and provide examples of its application in biomedicine.


[Knowledge and attitudes of health professionals towards advance directives].
To evaluate the degree of knowledge and attitudes of medical and nursing professionals in two health departments to advance directives, as well as to examine their association with the sociodemographic and occupational variables of the professionals. A cross-sectional survey on 329 health professionals was carried out through the internet and a standardised procedure. The knowledge and attitudes of the professionals about advance directives were examined using two validated questionnaires of 17 and 12 items, respectively. Sociodemographic and professional data were also collected from the participants. 45% of the professionals were physicians, with X¯=13,1 (SD: 8.3) years of professional experience. Sixty-seven point five percent were women and the mean age was 38.9 (SD: 9.2) years. Professionals had very positive attitudes towards the advance directives document (X¯=75.37;SD: 11.97;R=0-90), although their level of knowledge about them was medium-low (X¯=9.31;SD: 2.73;R=0-18). Both the level of knowledge and self-perception were associated with previous training in palliative care, experience with document management, reading, or the demand for information. Completing the document related to self-perception of knowledge. Attitudes towards the document related to experience in its use and a positive attitude toward training. The professionals showed positive attitudes towards the advance directive document although low knowledge about it. Experience with the document was the only variable associated with both the knowledge and the attitudes of the professionals.


Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris.
An excess of androgen is believed to contribute to development of acne in some patients. Because oral contraceptives (OCs) may reduce the active androgen level, hormonal therapy with OCs has been used successfully to treat patients with acne, although this treatment has previously not been studied in placebo-controlled trials. Our purpose was to evaluate the efficacy of a triphasic, combination OC (ORTHO TRI-CYCLEN [Ortho-McNeil Pharmaceutical, Raritan, N.J.], norgestimate/ethinyl estradiol) compared with placebo in the treatment of moderate acne vulgaris. Two hundred fifty-seven healthy female subjects, 15 to 49 years of age with moderate acne vulgaris, were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial. Each month for 6 months, subjects received either 3 consecutive weeks of the OC (i.e., tablets containing a fixed dose of ethinyl estradiol [0.035 mg] and increasing doses of norgestimate [0.180 mg, 0.215 mg, 0.250 mg]) followed by 7 days of inactive drug or placebo (color-matched tablets). Efficacy was assessed by facial acne lesion counts, an investigator's global assessment, a subject's self-assessment, and an analysis of within-cycle variation (cycle 6) in lesion counts. Of the 160 subjects in whom efficacy could be evaluated, the OC group showed a statistically significantly greater improvement than the placebo group for all primary efficacy measures. The mean decrease in inflammatory lesion count from baseline to cycle 6 was 11.8 (62.0%) versus 7.6 (38.6%) (p = 0.0001), and the mean decrease in total lesion count was 29.1 (53.1%) versus 14.1 (26.8%) (p = 0.0001) in the OC and placebo groups, respectively. In the investigator's global assessment, 93.7% of the active treatment group versus 65.4% of the placebo group were rated as improved at the end of the study (p < 0.001). Six of the seven secondary efficacy measures (total comedones, open comedones, closed comedones, papules, pustules, and the subject's self-assessment of study treatment) were also significantly more favorable in the OC group compared with the placebo group. An OC containing 0.035 mg of ethinyl estradiol combined with the triphasic regimen of norgestimate is a safe and effective treatment of moderate acne vulgaris in women with no known contraindication to OC therapy.


Spontaneous mediastinal hemorrhage secondary to oral anticoagulation.
We report a rare case of spontaneous mediastinal hemorrhage secondary to appropriate oral anticoagulation in an otherwise healthy 35-year-old woman. This case was unique in view of the patient's age and the fact that she had no underlying pathologic condition. Although the literature describes only two other cases of spontaneous mediastinal hemorrhage secondary to oral anticoagulant therapy alone, such bleeding has also been observed in patients on combined oral anticoagulant and fibrinolytic therapy and on heparin therapy. Therefore, this kind of hemorrhage should be included in the differential diagnosis of chest pain in such patients. The diagnosis is confirmed by chest X-ray films, computer tomographic scanning, and digital angiography. Supportive treatment is usually sufficient, since tamponade tends to intervene before cardiac compromise can occur.


1064 nm Q-switched Nd:YAG laser for the treatment of Argyria: a systematic review.
Argyria is a benign skin disease characterized by blue to slate-grey discoloration that is caused by deposition of silver granules in the skin and/or mucus membranes as a result of long-term ingestion of ionized silver solutions or exposure to airborne silver particles. The skin discoloration can be generalized or localized and is exacerbated by sunlight. The skin discoloration is usually permanent, and until recently, there has been no effective treatment for argyria. Over the past 6 years, a number of case reports and one case series have described cases of argyria that were successfully treated with a 1064 nm Q-switched (QS) neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; however, a review of these studies has never been reported in the dermatologic literature. To review the use of the 1064 nm QS Nd:YAG laser for the treatment of argyria. A search of the National Library of Medicine's PubMed Database and the SCOPUS Database was performed to find articles that detailed the treatment of argyria with 1064 nm QS Nd:YAG laser. Six articles were selected for inclusion in this review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd:YAG laser offers a novel and effective treatment for argyria. A systematic review of the dermatologic literature revealed a limited number of case reports and case series using this treatment. However, the results gleaned by the authors from the literature review provide important information to the clinician. For patients with argyria, a single pass of the 1064 nm QS Nd:YAG laser offers immediate, effective and sustained pigment clearing without any long-term adverse effects.


[Combined effect of an Ehrlich ascites tumor growth-inhibiting extract and adrenaline on cell division by that tumor in vitro].
It has been shown that both Ehrlich's ascites carcinoma (EAC) growth inhibition extract and adrenaline exert a pronounced inhibitory effect on cell division of this carcinoma in vitro. As a result of administering the extract in doses of 0.5 and 1 ml/per sample this effect lasted one and two hours, respectively, while with adrenaline (2.5 micrograms/ml) this effect lasted three hours with subsequent normalization of the mitotic index. Addition of adrenaline to the samples containing the extract was followed by the enhancement and prolongation of the inhibitory effect: at doses of the extract 0.5 and 1 ml the inhibition persisted 2 and 4 hours, respectively. The action of the extract with adrenaline was reversible. The data obtained indicate that despite the fact that mitosis-inhibiting activity of the EAC cell extract may be manifest in the absence of adrenaline, the latter affects the pattern of the extract action.


African fermented dairy products - Overview of predominant technologically important microorganisms focusing on African Streptococcus infantarius variants and potential future applications for enhanced food safety and security.
Milk is a major source of nutrients, but can also be a vehicle for zoonotic foodborne diseases, especially when raw milk is consumed. In Africa, poor processing and storage conditions contribute to contamination, outgrowth and transmission of pathogens, which lead to spoilage, reduced food safety and security. Fermentation helps mitigate the impact of poor handling and storage conditions by enhancing shelf life and food safety. Traditionally-fermented sour milk products are culturally accepted and widely distributed in Africa, and rely on product-specific microbiota responsible for aroma, flavor and texture. Knowledge of microbiota and predominant, technologically important microorganisms is critical in developing products with enhanced quality and safety, as well as sustainable interventions for these products, including Africa-specific starter culture development. This narrative review summarizes current knowledge of technologically-important microorganisms of African fermented dairy products (FDP) and raw milk, taking into consideration novel findings and taxonomy when re-analyzing data of 29 publications covering 25 products from 17 African countries. Technologically-important lactic acid bacteria such as Lactococcus lactis and Streptococcus infantarius subsp. infantarius (Sii), Lactobacillus spp. and yeasts predominated in raw milk and FDP across Africa. Re-analysis of data also suggests a much wider distribution of Sii and thus a potentially longer history of use than previously expected. Therefore, evaluating the role and safety of African Sii lineages is important when developing interventions and starter cultures for FDP in Africa to enhance food safety and food security. In-depth functional genomics, epidemiologic investigations and latest identification approaches coupled with stakeholder involvement will be required to evaluate the possibility of African Sii lineages as novel food-grade Streptococcus lineage.


[The effects of early escharectomy on resting energy expenditure in the severely burned patients].
To investigate the effect of early escharectomy on resting energy expenditure (REE) in severely burned patients dynamically with the metabolic monitoring and diagnostic system. Fifty-six adult male patients with severe burns were divided into early escharectomy (group A, n = 39, escharectomy within 5 PBDs) and non-early escharectomy (group B, n = 17, escharectomy after 5 PBDs) groups. The wounds of full thickness and deep partial thickness burn in the two groups were all excised and covered with allogeneic skin and autologous micro-skin in the first operation. The changes in REE were observed dynamically at the bedside of the patients with the metabolic monitoring and diagnostic system. The plasma contents of IL-6, IL-8, TNF-alpha and LPS from 9 patients in group A and 7 in group B were also determined dynamically. All patients survived. The REE in both groups was elevated markedly, but REE in group A was lower compared with group B before and after escharectomy within 14 days. (P < 0.05). The plasma level of IL-6, IL-8, TNF-alpha and LPS in group A were obviously lower than those in group B (P < 0.05). The hypermetabolic response of burn patients with severe burns could be lowered by early escharectomy, and it seemed to be related to the decrease of the release of proinflammatory mediators.


Towards quantitative perfusion MRI of the lung in COPD: The problem of short-term repeatability.
4D perfusion magnetic resonance imaging (MRI) with intravenous injection of contrast agent allows for a radiation-free assessment of regional lung function. It is therefore a valuable method to monitor response to treatment in patients with chronic obstructive pulmonary disease (COPD). This study was designed to evaluate its potential for monitoring short-term response to hyperoxia in COPD patients. 19 prospectively enrolled COPD patients (median age 66y) underwent paired dynamic contrast-enhanced 4D perfusion MRI within 35min, first breathing 100% oxygen (injection 1, O2) and then room air (injection 2, RA), which was repeated on two consecutive days (day 1 and 2). Post-processing software was employed to calculate mean transit time (MTT), pulmonary blood volume (PBV) and pulmonary blood flow (PBF), based on the indicator dilution theory, for the automatically segmented whole lung and 12 regions of equal volume. Comparing O2 with RA conditions, PBF and PBV were found to be significantly lower at O2, consistently on both days (p<10-8). Comparing day 2 to day 1, MTT was shorter by 0.59±0.63 s (p<10-8), PBF was higher by 22±80 ml/min/100ml (p<3·10-4), and PBV tended to be lower by 0.2±7.2 ml/100ml (p = 0.159) at both, RA and O2, conditions. The second injection (RA) yielded higher PBF and PBV, which apparently contradicts the established hypothesis that hyperoxia increases lung perfusion. Quantification of 4D perfusion MRI by current software approaches may thus be limited by residual circulating contrast agent in the short-term and even the next day.


SIK3-HDAC4 signaling regulates Drosophila circadian male sex drive rhythm via modulating the DN1 clock neurons.
The physiology and behavior of many organisms are subject to daily cycles. In Drosophila melanogaster the daily locomotion patterns of single flies are characterized by bursts of activity at dawn and dusk. Two distinct clusters of clock neurons-morning oscillators (M cells) and evening oscillators (E cells)-are largely responsible for these activity bursts. In contrast, male-female pairs of flies follow a distinct pattern, most notably characterized by an activity trough at dusk followed by a high level of male courtship during the night. This male sex drive rhythm (MSDR) is mediated by the M cells along with DN1 neurons, a cluster of clock neurons located in the dorsal posterior region of the brain. Here we report that males lacking Salt-inducible kinase 3 (SIK3) expression in M cells exhibit a short period of MSDR but a long period of single-fly locomotor rhythm (SLR). Moreover, lack of Sik3 in M cells decreases the amplitude of PERIOD (PER) cycling in DN1 neurons, suggesting that SIK3 non-cell-autonomously regulates DN1 neurons' molecular clock. We also show that Sik3 reduction interferes with circadian nucleocytoplasmic shuttling of Histone deacetylase 4 (HDAC4), a SIK3 phosphorylation target, in clock neurons and that constitutive HDAC4 localization in the nucleus shortens the period of MSDR. Taking these findings together, we conclude that SIK3-HDAC4 signaling in M cells regulates MSDR by regulating the molecular oscillation in DN1 neurons.


How does the trabecular meshwork regulate outflow? Clues from the vascular endothelium.
Although it is well known that the trabecular meshwork plays a central role in regulating the outflow of aqueous humor from the eye, the cellular mechanisms and events responsible for this function are poorly understood. In contrast, the mechanisms by which vascular endothelial cells modulate the permeability of blood vessels have been more thoroughly investigated. It is hypothesized that the cells of the TM employ mechanisms similar to those observed in the vascular endothelium to modulate aqueous humor permeability. Specifically, it is hypothesized that the cells of the TM employ Na-K-Cl cotransport to modulate their intracellular volume and thus the volume of the paracellular pathways through which aqueous humor may travel. The current knowledge about the role of Na-K-Cl cotransport and volume regulation in the regulation of vascular permeability, and evidence that similar physiologic events occur in the TM are reviewed. In addition, the implications for further study of aqueous humor outflow physiology are discussed.


Health literacy as a social vaccine in the COVID-19 pandemic.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus in the coronavirus family, causing the coronavirus disease (COVID-19). Biomedical vaccines are key but alongside biomedical vaccines, a social vaccine can be similarly useful to prevent infection from SARS-CoV-2, if applied as a health promotion strategy. In order to slow down and control the spread of SARS-CoV-2, applying the social vaccine concept should be considered in parallel. From a health promotion perspective, a social vaccine is a process of social and political mobilization driven by governmental and non-governmental organizations aiming at populations by applying interventions such as health communication, education and mass media campaigns as well as determinant-based programs to address environmental factors influencing personal behavior and community capacities to cope with and overcome the societal burdens of COVID-19. In this context, health literacy is significant, as seen in the role it plays in empowering citizens during the COVID-19 pandemic and enabling them to deal with health information considering COVID-19. As a public health strategy, health literacy as a social vaccine will enable individuals and communities to mitigate the spread of the virus by understanding and applying information as provided through governments and health authorities. The aim of this article is to explore health literacy as a promising social vaccine and opportunity to utilize social vaccination and thus be considered as a key public health approach-both bottom-up and top-down-to support the combat of COVID-19 and future states of emergency.


Association of surfactant protein A2 with acute respiratory failure in children.
Interactions among single nucleotide polymorphisms (SNPs) of surfactant protein (SP) are associated with acute respiratory failure (ARF) and its short-term outcome, pulmonary dysfunction at discharge (PDAD) in children. However, genetic association studies using individual SNPs have not been conducted before. We hypothesize that SP genetic variants are associated with pediatric ARF and its short-term complications by themselves. We used available genotype and clinical data in the Floros biobank consisting of 248 children aged ≤24 months with ARF; 86 developed PDAD. A logistic regression analysis was performed for each of the 14 selected SNPs, SP-A1 and SP-A2 genotypes. A p-value less than the Bonferroni correction threshold was considered significant. A likelihood ratio test was done to compare two models (one with demographic data and another with genetic variants). Before Bonferroni correction, female sex is associated with a decreased risk of ARF. Black race and the rs721917 of the SFTPD are associated with increased risk of ARF. After Bonferroni correction, the 1A0 1A1 genotype of SFTPA2 was associated with decreased risk of ARF. The likelihood ratio test showed that the model of the genotype information with demographic data was a better fit to predict ARF risk. None of the SP SNPs and SP-A1, SP-A2 genotypes were associated with PDAD. Our results indicate that SNPs and genotypes of SPs involved in innate immunity and host defense play an important role in ARF and, in the future, may be used as biomarkers.


[Actinomycin DO inhibition of RNA biosynthesis and its interaction with DNA preparations].
Actinomycin D0 differing from actinomycin D in replacement of I residue of sarcosine by glycine in one of the peptide chains was found to have a lower inhibitory effect on RNA synthesis in various biological systems. On interaction of E. coli with DNA actinomycin D0 formed a complex with DNA having the binding constant K=1.6 with 10-5 which was 100 times lower than the binding constant of actinomycin D. Therefore, actinomycin D0 formed a complex with DNA which was 100 times less stable than actinomycin D. Actinomycins D0, D and II having different conformations in buffer on interaction with DNA formed complexes having similar conformations. The conformational change from free actinomycin to bound actinomycin was found difficult in case of actinomycin D0 because of its slow rate of complex formation with DNA as compared to that of other actinomycins complex formation with DNA.


Influence of a collapsed coastal landfill on metal levels in sediments and biota--a portent for the future?
In May 2008 a coastal landslide deposited landfill debris onto the shore near Lyme Regis, UK. Six months later, intertidal sediments and biota from the area were sampled to determine whether the landslip had affected distribution and bioavailability of metals in the area and if there were any biological effects. Highest sediment concentrations for the majority of metals occurred near the landslip zone and in several cases exceeded Threshold Effects or Probable Effects Levels (As, Cu, Hg, Ni, Pb, Zn). The 1 M HCl-extractable fraction of Cd, Pb and Zn in sediments also increased near the landslip. Metal bioaccumulation by intertidal biota showed variability between different species and metals, but there were several instances of increased accumulation near the landslip through increased availability from seawater, sediment and dietary sources. In most cases, metal concentrations in molluscs exceeded Oslo and Paris Commission (OSPAR) background concentrations (BCs) together with background assessment concentrations (BACs) at some sites. Kidney tissues in winkles (Littorina littorea) were measured for evidence of oxidative stress using the Total Oxyradical Scavenging Capacity (TOSC) assay. Responses to peroxynitrite, peroxyl and hydroxyl radicals suggested raised levels of TOSC in animals from the sites close to or east of the landfill waste. There have been very few studies of direct impact of landfills on the marine environment and this study could serve as a practical model for similar events driven by sea level rise.


A self-quenched galactosamine-serum albumin-rhodamineX conjugate: a "smart" fluorescent molecular imaging probe synthesized with clinically applicable material for detecting peritoneal ovarian cancer metastases.
Fluorophore activation after cellular internalization of a targeted fluorescently labeled conjugate is an effective molecular imaging strategy to increase target-to-background ratios. The D-galactose receptor on ovarian cancer cells has been used to target self-quenched avidin-rhodamineX conjugates in which the avidin component binds to D-galactose receptor and the rhodamines are optically activated by dequenching only after cellular internalization. As a nonimmunogenic alternative of avidin, galactosamine-conjugated serum albumin (GmSA) targets the D-galactose receptor with higher binding affinity and has more conjugation sites available for rhodamineX than avidin. GmSA was conjugated with 20 rhodamineX molecules (GmSA-20ROX) to create a self-quenching complex, which was compared with a conjugate consisting of GmSA and a single rhodamineX (GmSA-1ROX) in ex vivo chemical activation characteristics, intracellular activation, and in vivo molecular imaging for detecting peritoneal micrometastases of SHIN3 ovarian cancer. GmSA-20ROX was five times brighter than GmSA-1ROX when incubated with SHIN3 ovarian cancer cells for 3 h. Submillimeter SHIN3 ovarian cancer implants in the peritoneal cavity were clearly visualized in vivo with spectral fluorescence imaging due to the high tumor-to-background ratio. The sensitivity and specificity of GmSA-20ROX for implant detection were determined by colocalization of the rhodamineX emission with red fluorescent protein expressed constitutively in the SHIN3 tumor implants. Among 336 lesions, sensitivity and specificity were 99%/99%, respectively, for GmSA-20ROX, whereas the results for GmSA-1ROX were only 24%/100% (n = 388), respectively, for lesions approximately 0.8 mm or greater in diameter. Self-quenched GmSA-20ROX is more efficient than previous d-galactose-targeted fluorescent conjugates.


Technical aspects of inductively coupled plasma bioanalysis techniques.
This White Paper is focused on the technical aspects regarding quantifying pharmaceutically derived inorganic elements in biomatrices in support of GLP nonclinical and clinical studies using inductively coupled plasma (ICP) techniques. For decades ICP has been used in support of Environmental Protection Agency analyses and has more recently been applied for use in the pharmaceutical industry. Current bioanalytical method validation and sample analysis regulatory guidance applies to chromatographic platforms used for analysis of large- and small-molecule PK and TK assessments; however, it is not directly applicable to all aspects of various ICP techniques. Increasingly, quadrupole and high-resolution ICP-MS methods of analysis are being used to quantify inorganic elements contained in pharmaceutical compounds and biomatrices. Many elements occur endogenously in biomatrices, affecting quantification of blanks, standard curve samples, QC samples, and the selection of appropriate levels for the LLOQ.


Prognostic factors for hepatocellular carcinoma recurrence.
The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.


Comparison of sucralfate and ranitidine twice daily in duodenal ulcer treatment: a multicenter randomized double-blind study.
Sucralfate and ranitidine were compared in the treatment of duodenal ulcer in this multicenter, randomized, double-blind study. A total of 165 patients with endoscopically proven duodenal ulceration were included in the trial and randomized to treatment with sucralfate, 2 g b.i.d. (morning and evening with an empty stomach), or ranitidine, 150 mg twice daily. All patients were endoscopically examined after 4 and, if unhealed, 8 weeks. Of the patients considered suitable for analysis at 4 weeks, 73.5% (61 of 83) of the sucralfate group demonstrated healing of the ulcer in comparison with 63.3% (50 of 79) of the ranitidine group. At 8 weeks cumulative healing rates were 89% (74 of 83) and 84.8% (67 of 79), respectively. When smokers were considered separately, healing rates at 4 weeks were 69.2% (36 of 52) for sucralfate and 53.3% (24 of 45) for ranitidine. At 8 weeks cumulative healing rates were 92.3% (48 of 52) and 77.7% (35 of 45), respectively (p less than 0.05). Overall, there was no difference in the two groups regarding symptom relief and side effects. These results suggest that these drugs are equally effective in the short-term treatment of duodenal ulcer, although in smokers sucralfate appears to be more effective than ranitidine.


Patterns of cranial shape diversification during the phylogenetic branching process of New World monkeys (Primates: Platyrrhini).
One of the central topics in evolutionary biology is understanding the processes responsible for phenotypic diversification related to ecological factors. New World monkeys are an excellent reference system to investigate processes of diversification at macroevolutionary scales. Here, we investigate the cranial shape diversification related to body size and ecology during the phylogenetic branching process of platyrrhines. To investigate this diversification, we used geometric morphometric techniques, a molecular phylogenetic tree, ecological data and phylogenetic comparative methods. Our statistical analyses demonstrated that the phylogenetic branching process is the most important dimension to understand cranial shape variation among extant platyrrhines and suggested that the main shape divergence among the four principal platyrrhine clades probably occurred during the initial branching process. The phylogenetic conservatism, which is the retention of ancestral traits over time within the four principal platyrrhine clades, could be the most important characteristic of platyrrhine cranial shape diversification. Different factors might have driven early shape divergence and posterior relative conservatism, including genetic drift, stabilizing selection, genetic constraints owing to pleiotropy, developmental or functional constraint, lack of genetic variation, among others. Understanding the processes driving the diversification among platyrrhines will probably require further palaeontological, phylogenetic and comparative studies.


[Conjunctival replacement--comparative animal experiment study].
In a rabbit study a new material for conjunctival reconstruction was compared to lyophilized, amniotic membranes, which have been used for a long time. Standardized conjunctival defects were covered with thin, heterologous, glutaraldehyde-treated pericardium in one group, while in the other group lyophilized amnion grafts were used. In addition, conventional running suture fixation of the patches was compared to a fibrin sealing technique. The macroscopic findings during the follow-up period and the histological results are reported.


Thalamic contributions to Basal Ganglia-related behavioral switching and reinforcement.
Although the existence of prominent connections between the intralaminar thalamic nuclei and the basal ganglia has long been established, the limited knowledge of the functional relevance of this network has considerably hampered progress in our understanding of the neural mechanisms by which the thalamostriatal system integrates and regulates the basal ganglia circuitry. In this brief commentary, we will address this gap of knowledge through a discussion of the key points of a symposium entitled "Thalamic Contributions to Basal Ganglia-Related Behavioral Switching and Reinforcement" that will be presented at the 2011 Society for Neuroscience meeting. Recent anatomical and physiological data that support the role of the thalamostriatal system in action selection, attentional shifting, and reinforcement will be discussed. We will also address the possibility that degeneration of the thalamostriatal system could underlie some of the deficits in redirection of attention in response to salient stimuli seen in Parkinson's disease.


Synthesis of ZnWO4/Ag3PO4 p-n heterojunction photocatalyst and enhanced visible-light photocatalytic applications.
The ZnWO4/Ag3PO4 nanocomposites synthesized by simple precipitation processes were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and UV-vis diffuse reflectance spectra. The results indicated that the ZnWO4 nanorods dispersed well on the surface of Ag3PO4 particles and ball-and-rod structure p-n heterojunctions were successfully fabricated. In subsequent degradation experiments of methyl orange (MO), ZnWO4/Ag3PO4 composites showed the highest photocatalytic activity compared to pure Ag3PO4 and ZnWO4, due to the presence of ZnWO4/Ag3PO4 heterojunctions, which could separate and transfer the electron-hole pairs generated by visible light and enhance the photocatalytic performance of the catalysts. The band gap structure and degradation mechanism of the enhanced photocatalytic materials are also discussed in this article. In conclusion, the ZnWO4/Ag3PO4 composite is a promising and excellent photocatalyst for the degradation of dye wastewater under visible light irradiation.


Soil chemical and physical properties at the Bear Brook Watershed in Maine, USA.
Acidic deposition leads to the acidification of waters and accelerated leaching and depletion of soil base cations. The Bear Brook Watershed in Maine has used whole-watershed chemical manipulations to study the effects of elevated N and S on forest ecosystem function on a decadal time scale. The objectives of this study were to define the chemical and physical characteristics of soils in both the reference and treated watersheds after 17 years of treatment and assess evidence of change in soil chemistry by comparing soil studies in 1998 and 2006. Results from 1998 confirmed depletion of soil base cation pools and decreased pH due to elevated N and S within the treated watershed. However, between 1998 and 2006, during a period of declining SO4(2-) deposition and continued whole-watershed experimental acidification on the treated watershed, there was little evidence of continued soil exchangeable base cation concentration depletion or recovery. The addition of a pulse of litterfall and accelerating mineralization from a severe ice storm in 1998 may have had significant effects on forest floor nutrient pools and cycling between 1998 and 2006. Our findings suggest that mineralization of additional litter inputs from the ice storm may have obscured temporal trends in soil chemistry. The physical data presented also demonstrate the importance of coarse fragments in the architecture of these soils. This study underscores the importance of long-term, quantitative soil monitoring in determining the trajectories of change in forest soils and ecosystem processes over time.


MicroRNA-30a-5p Promotes Chronic Heart Failure in Rats by Targeting Sirtuin-1 to Activate the Nuclear Factor-κB/NOD-Like Receptor 3 Signaling Pathway.
MicroRNA-30a-5p (miR-30a-5p) has been identified as a marker of heart failure; however, its functional mechanisms in chronic heart failure (CHF) remain unknown. We aim to investigate the role of miR-30a-5p targeting sirtuin-1 (SIRT1) in myocardial remodeling in CHF via the nuclear factor-κB/NOD-like receptor 3 (NF-κB/NLRP3) signaling pathway. CHF rat models were established using aortic coarctation. The expression of miR-30a-5p, SIRT1, and the NF-κB/NLRP3 signaling pathway-related factors in CHF rats was determined. The CHF rats were then respectively treated with altered miR-30a-5p or SIRT1 to explore their roles in cardiac function, myocardial function, inflammatory response, pathological changes, and cardiomyocyte apoptosis. The binding relation between miR-30a-5p and SIRT1 was confirmed. MiR-30a-5p was upregulated whereas SIRT1 was downregulated in myocardial tissues of CHF rats. MiR-30a-5p inhibition or SIRT1 overexpression improved cardiac and myocardial function, and suppressed the inflammatory response, alleviated pathological changes and inhibited cardiomyocyte apoptosis in CHF rats. MiR-30a-5p targeted SIRT1 to regulate the NF-κB/NLRP3 signaling pathway. In CHF rats, downregulated miR-30a-5p and silenced SIRT1 could reverse the beneficial effects of downregulated miR-30a-5p. Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway.


Efficacy of 'Gamadent' toothpaste on the healing of gingival tissues: a preliminary report.
The aim of this randomised, parallel, double-blind study, in which 28 adult patients diagnosed with chronic gingivitis or early stages of chronic periodontitis were recruited, was to evaluate the efficacy of 'Gamadent' toothpaste compared to a placebo toothpaste. 'Gamadent' toothpaste has all the basic constituents of a toothpaste with the addition of a sea cucumber extract (SCE) of the species Stichopus sp. 1 to improve the healing potential of tissues. The placebo has the same basic constituents minus the extract. Out of the 28 patients, 14 were placed in the test group who used the 'Gamadent' toothpaste, and 14 patients were placed in the control group (2 control subjects defaulted and were excluded), who brushed using the placebo toothpaste. The longitudinal study was carried out over a period of 3 months with assessments made at baseline, 1 month, 2 months and 3 months after conventional therapy at the baseline visit. The clinical parameters used during the trial were Plaque Index (PI), Gingival Index (GI), Papilla Bleeding Index (PBI) and Probing Pocket Depth (PPD). A predetermined number of sites on a molar, premolar, canine and an incisor were examined and evaluated in each quadrant. After the baseline assessment, the patients had full mouth scaling and debridement as well as oral hygiene instructions. Patients were instructed to brush their teeth twice a day with the toothbrush provided (Oral-B plus, size 35) and toothpaste (test or control), using the Bass technique. At the 1-month assessment, there were significant mean reductions to baseline mean values in PI (P < 0.005) and GI (P < 0.001) in the test group as compared to the control group. At the end of the 2-month interval, significant reductions were observed in PI, PBI and PPD (P < 0.001). By the end of 3 months, there were significant differences in the mean reduction of all the parameters i.e. PI, PBI, GI and PPD (P < 0.001), between the test and control sites. In conclusion, 'Gamadent' toothpaste provided noteworthy benefits, producing statistically significant improvement in all clinical parameters compared to the placebo during the healing phase after conventional initial therapy.


Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study.
Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. Full-thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage-like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies.


CORRELATION OF CD4+Т LYMPHOCYTES ACTIVATION WITH INTERLEUKIN IL-9, IL-17, IL- 22 PROFILES IN THE PERIPHERAL BLOOD OF PATIENTS WITH PLAQUE PSORIASIS.
Psoriasis is a T cell mediated chronic inflammatory skin disease affecting about 2% of the population worldwide. Recently has established the central role of IL-23/Th17 immune axis in the pathogenesis of psoriasis and different subclasses of T cells including Th1 and Th17 cells are involved in initiation and amplification of the skin inflammation process, in addition, in cases of recurrent psoriasis, Th22 cells play the role of memory cells with the help of Th9 cells, which are also important in this process. The main goal was to evaluate the ratio of T cell profile and IL23/Th17 axis by evaluating IL17A, IL22, IL9 in peripheral blood of persons with moderate to severe plaque psoriasis. We have estimated the activation of IL-23/Th17 axis by evaluating the level of IL-17A, IL-22 and IL-9 in peripheral blood of patients with plaque psoriasis (n=18) with different severity of the disease (PASI from 10 to 40) comparing the results with data obtained from healthy persons (n=15). The expression of CD69 activation marker on T helper cells has been evaluated as well. The results were analyzed using FACScan flow cytometer (Becton Dickinson). The percentage of CD3 + T lymphocytes in the peripheral blood of patients with psoriasis was not significantly different compared to normal healthy volunteers, however, the level of expression of CD4 + T cells was reduced. We observed a dramatic increase in IL22 along with a decrease in the level of expression of IL-9 and IL-17, the expression of Th activation marker (CD69) was also decreased in comparison with the control group. The T cell profile and the IL-23/Th17 axis functional activity levels were significantly different from the literature data obtained about the inflammatory region (psoriatic lesions on the skin). IL-9 and IL-17 expression levels are decreased in peripheral blood Th cells, which may be explained by mobilization of the corresponding Th9 and Th17 cells into the inflammatory site.


Highly Transparent, Yet Photoluminescent: 2D CdSe/CdS Nanoplatelet-Zeolitic Imidazolate Framework Composites Sensitive to Gas Adsorption.
In this work, thin composite films of zeolitic imidazolate frameworks (ZIFs) and colloidal two-dimensional (2D) core-crown CdSe/CdS nanoplatelet (NPL) emitters with minimal scattering are formed by a cycled growth method and yield highly transparent coatings with strong and narrow photoluminescence of the NPLs at 546 nm (FWHM: 25 nm) in a solid-state composite structure. The porous ZIF matrix acts as functional encapsulation for the emitters and enables the adsorption of the guest molecules water and ethanol. The adsorption and desorption of the guest molecules is then characterized by a reversable photoluminescence change of the embedded NPLs. The transmittance of the composite films exceeds the values of uncoated glass at visible wavelengths where the NPL emitters show no absorption (>540 nm) and renders them anti-reflective coatings. At NPL absorption wavelengths (440-540 nm), the transmittance of the thin composite film-coated glass lies close to the transmittance of uncoated glass. The fast formation of innovative, smooth NPL/ZIF composite films without pre-polymerizing the colloidal 2D nanostructures first provides a powerful tool toward application-oriented photoluminescence-based gas sensing.