Evaluation of drought stress level in Sargent's cherry (Prunus sargentii Rehder) using photosynthesis and chlorophyll fluorescence parameters and proline content analysis.
Sargent's cherry trees (Prunus sargentiiRehder) are widely planted as an ornamental, climate change-sensing species. This study investigated changes in the soil moisture content, fresh weight, photosynthesis and chlorophyll fluorescence properties, and the chlorophyll and proline content of four-year-old P. sargentii seedlings after 30 days of drought stress. In the trees subjected to drought stress treatment, soil moisture content decreased, and the fresh weight of the aboveground part of the plant decreased. However, there was no significant difference in the root growth of the dried plants. Among the photosynthesis parameters, Pn MAX, E and gs showed a significant (p < 0.001) decrease after 15 days in dry-stressed seedlings, but there was no difference between treatments in WUE until 20 days, and there was a significant (p < 0.001) difference after 24 days. Chlorophyll fluorescence parameters, Fv/Fm, ΦPSII, Rfd, NPQ, and Pn MAX, also increased after 10 days in dry-stressed seedlings, but these changes did not reach statistical significance compared to the control treatment. These results may suggest that drought stress highly correlates with photosynthesis and chlorophyll fluorescence parameters. Chlorophyll content also significantly decreased in the seedlings under drought stress compared with the control treatment. The proline content decreased until the 10th day of drought stress treatment and increased after the 15th day, showing an increase of 10.9% on the 15th day and 57.1% on the 30th day, compared to the control treatment. These results suggest that photosynthesis, chlorophyll fluorescence parameters, and proline content can be used to evaluate drought stress in trees. The results of this study can contribute to the management of forests, such as the irrigation of trees when pore control ability and photosynthesis ability decrease.


A Case of Toxic Epidermal Necrolysis Caused by Lamotrigine Combined With Valproic Acid and Literature Review.
After suffering from frequent symptomatic seizures secondary to cerebral hemorrhage, a 58-year-old male patient was prescribed a one-time 50 mg dose of lamotrigine, which he took for a week. However, the patient's seizure symptoms were not controlled until a dosage of 500 mg of sodium valproate tablets was taken twice daily, which ultimately resolved his seizures. Unfortunately, about two weeks after the combination, the patient developed a rash. Nine days later, the patient developed new blisters, necrotizing epidermal desquamation, and lesions over 80% of their body surface area. This was diagnosed as toxic epidermal necrolysis (TEN) resulting from the combination of lamotrigine and sodium valproate. The sodium valproate and lamotrigine were discontinued and treated symptomatically for about one month. The patient's condition improved as the fatal rash gradually subsided. However, after the onset of TEN, unexpected psychiatric symptoms such as poor sleep, less than four hours of sleep, irritability, paranoia, crying, fear of rash recurrence, and suspicious hallucinations and delusions emerged in the patient. Surprisingly, after discontinuation of lamotrigine and sodium valproate due to the rash, the patient did not experience any further seizures.


Congenital microtia patients: the genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration.
Mesenchymal stem cells (MSCs) exosomes were previously shown to be effective in articular cartilage repairing. However, whether MSCs exosomes promote mature cartilage formation of microtia chondrocytes and the underlying mechanism of action remains unknown. Additionally, some hurdles, such as the low yield and unsatisfactory therapeutic effects of natural exosomes have emerged when considering the translation of exosomes-therapeutics to clinical practices or industrial production. Herein, we investigated the roles of human adipose-derived stem cells (ADSCs) exosomes in modulating microtia chondrocytes and the underlying mechanism of action. Special attention was also paid to the mass production and functional modification of ADSCs exosomes. We firstly used porous gelatin methacryloyl (Porous Gelma) hydrogel with pores size of 100 to 200 μm for 3D culture of passage 2, 4 and 6 ADSCs (P2, P4 and P6 ADSCs, respectively), and obtained their corresponding exosomes (Exo 2, Exo 4 and Exo 6, respectively). In vitro results showed Exo 2 outperformed both Exo 4 and Exo 6 in enhancing cell proliferation and attenuating apoptosis. However, both Exo 4 and Exo 6 promoted chondrogenesis more than Exo 2 did. Small RNA sequencing results indicated Exo 4 was similar to Exo 6 in small RNA profiles and consistently upregulated PI3K/AKT/mTOR signaling pathway. Notably, we found hsa-miR-23a-3p was highly expressed in Exo 4 and Exo 6 compared to Exo 2, and they modulated microtia chondrocytes by transferring hsa-miR-23a-3p to suppress PTEN expression, and consequently to activate PI3K/AKT/mTOR signaling pathway. Then, we designed genetically engineered exosomes by directly transfecting agomir-23a-3p into parent P4 ADSCs and isolated hsa-miR-23a-3p-rich exosomes for optimizing favorable effects on cell viability and new cartilage formation. Subsequently, we applied the engineered exosomes to in vitro and in vivo tissue-engineered cartilage culture and consistently found that the engineered exosomes could enhance cell proliferation, attenuate apoptosis and promote cartilage regeneration. Taken together, the porous Gelma hydrogel could be applied to exosomes mass production, and functional modification could be achieved by selecting P4 ADSCs as parent cells and genetically modifying ADSCs. Our engineered exosomes are a promising candidate for tissue-engineered ear cartilage regeneration.


Hierarchical predictive coding in distributed pain circuits.
Predictive coding is a computational theory on describing how the brain perceives and acts, which has been widely adopted in sensory processing and motor control. Nociceptive and pain processing involves a large and distributed network of circuits. However, it is still unknown whether this distributed network is completely decentralized or requires networkwide coordination. Multiple lines of evidence from human and animal studies have suggested that the cingulate cortex and insula cortex (cingulate-insula network) are two major hubs in mediating information from sensory afferents and spinothalamic inputs, whereas subregions of cingulate and insula cortices have distinct projections and functional roles. In this mini-review, we propose an updated hierarchical predictive coding framework for pain perception and discuss its related computational, algorithmic, and implementation issues. We suggest active inference as a generalized predictive coding algorithm, and hierarchically organized traveling waves of independent neural oscillations as a plausible brain mechanism to integrate bottom-up and top-down information across distributed pain circuits.


The transient receptor potential channels in rheumatoid arthritis: Need to pay more attention.
Rheumatoid arthritis (RA) is characterized by the augment of vascular permeability, increased inflammatory cells infiltration, dysregulated immune cells activation, pannus formation and unbearable pain hyperalgesia. Ca2+ affect almost every aspect of cellular functions, involving cell migration, signal transduction, proliferation, and apoptosis. Transient receptor potential channels (TRPs) as a type of non-selective permeable cation channels, can regulate Ca2+ entry and intracellular Ca2+ signal in cells including immune cells and neurons. Researches have demonstrated that TRPs in the mechanisms of inflammatory diseases have achieved rapid progress, while the roles of TRPs in RA pathogenesis and pain hyperalgesia are still not well understood. To solve this problem, this review presents the evidence of TRPs on vascular endothelial cells in joint swelling, neutrophils activation and their trans-endothelial migration, as well as their bridging role in the reactive oxygen species/TRPs/Ca2+/peptidyl arginine deiminases networks in accelerating citrullinated proteins formation. It also points out the distinct functions of TRPs subfamilies expressed in the nervous systems of joints in cold hyperalgesia and neuro-inflammation mutually influenced inflammatory pain in RA. Thus, more attention could be paid on the impact of TRPs in RA and TRPs are useful in researches on the molecular mechanisms of anti-inflammation and analgesic therapeutic strategies.


Dramatic Changes in Health Care Professions in the Past 40 Years.
During the forty-year life of the Journal of Ambulatory Care Management, revolutionary transformations have occurred in the roles of existing health professions, as has the emergence of new categories of health professionals. This paper specifies the reasons for these dramatic changes, the new types of health care professions that have emerged, changes in existing professions, and suggestions of future directions. Many of these changes will be impacted by what occurs in Washington, DC in the debate over the Accountable Care Act.


Reflectivity and anisotropic optical functions of quaterthiophene single crystals.
Polarized reflectance spectra of quaterthiophene single crystals are reported with different angles and planes of incidence. The strong dependence of the spectral features on the experimental configuration is described by an orthorhombic model and the components of the complex diagonal dielectric tensor are given.


Aging by Near-Extinctions in Many-Variable Interacting Populations.
Models of many-species ecosystems, such as the Lotka-Volterra and replicator equations, suggest that these systems generically exhibit near-extinction processes, where population sizes go very close to zero for some time before rebounding, accompanied by a slowdown of the dynamics (aging). Here, we investigate the connection between near-extinction and aging by introducing an exactly solvable many-variable model, where the time derivative of each population size vanishes at both zero and some finite maximal size. We show that aging emerges generically when random interactions are taken between populations. Population sizes remain exponentially close (in time) to the absorbing values for extended periods of time, with rapid transitions between these two values. The mechanism for aging is different from the one at play in usual glassy systems: At long times, the system evolves in the vicinity of unstable fixed points rather than marginal ones.


Norepinephrine secretion and production in diabetic autonomic neuropathy.
Orthostatic hypotension (OH) in patients with diabetic autonomic neuropathy may result from sympathetic neuronal dysfunction and inadequate norepinephrine (NE) release as patients shift from the supine to an upright posture. The biochemical basis for this physiological abnormality is not understood. We measured basal supine NE secretion and production in 10 diabetic patients with OH, 9 diabetic patients without OH, and in 13 age-matched normal subjects. Apparent NE secretion, the rate at which NE enters the bloodstream, was 1.22 +/- 0.24 (SEM) nmol/m2 X min in the diabetic patients with OH, significantly lower than in the diabetic patients without OH and normal subjects in whom apparent NE secretion rates were 2.27 +/- 0.48 and 1.86 +/- 0.12 nmol/m2 X min, respectively. NE production, estimated from integrated NE metabolite excretion, was 10.2 +/- 0.85 nmol/mg creatinine in the diabetic patients with OH, which was significantly lower (P less than 0.01) than that in the diabetic patients without OH and normal subjects in whom NE production was 14.8 +/- 1.8 and 16.9 +/- 1.2 nmol/mg creatinine, respectively. These data demonstrate that supine basal apparent NE secretion and NE production are decreased in patients with OH secondary to diabetic autonomic neuropathy.


Identification of lncRNA-miRNA-mRNA ceRNA network as biomarkers for acute kidney injury.
Acute kidney injury (AKI) is a global problem due to its high morbidity and mortality. The aim of this study was to identify the key RNAs involved in the ischemia/reperfusion (I/R) or cisplatin (CIS) induced AKI. Gene Expression Omnibus database was used to download the microarray dataset GSE106993, GSE130814 and GSE98622. Differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs were identified in I/R and CIS induced AKI. The target miRNAs of DE lncRNAs were predicted from miRDB, and the miRNA of lncRNA target mRNAs were predicted form StarBase dataset. The ceRNA regulatory networks, GO and KEGG enrichment analysis, and protein-protein interaction (PPI) of I/R and CIS induced AKI specific genes were constructed. The CIBESORT was applied to infer the proportion of 22 immune infiltration cells based on gene expression profiles of I/R and CIS induced AKI. Totally, 2 DE-lncRNAs and 375 DE-mRNAs were identified in I/R and CIS induced AKI. The common ceRNA network was constructed between CIS group and I/R induced AKI group, which contained 2 lncRNAs (Platr7 and Gm15611), 65 mmu-miRNAs and 167 mRNAs. The 167 common mRNAs were enriched in the biological process of transcription regulation, metabolic process, cell proliferation, the cellular component (CC) of extracellular region and space, the molecular function of DNA binding, and transcription regulator activity in CIS and IRI induced AKI. The common 167 mRNAs involved in the MAPK signaling pathway and JAK-STAT signaling pathway were identified. Protein-Protein Interaction (PPI) Network of ceRNAs network expressed gene was constructed, including 81 nodes, which contained 3 upregulated genes and 78 downregulated genes. Among them, mitochondrial apoptosis-related genes Pmaip1 and Nptx1 showed significantly high expression in the GSE98622 and GSE106993 data sets. The investigation to the connection between the gene expression profiles and immune cell infiltration showed considerable differences in immune cell percentage between AKI group and normal group. Novel lncRNAs and mRNAs were identified, which may serve as potential biomarkers to predict the diagnostic and therapeutic targets for AKI patients based on a large-scale sample. More importantly, the ceRNA network of I/R or CIS induced AKI was constructed, which provides valuable information to further explore the molecular mechanism underlying onset and progression of AKI.


Abstinence, anticipation, reduction, and treatment (AART): a stepwise approach to the management of atypical antipsychotic side effects.
Antipsychotic medications, specifically the atypical agents, serve as first-line treatment options for patients with psychotic disorders, including individuals with schizophrenia or schizoaffective disorder. Atypical antipsychotics are also often prescribed off-label as either the primary treatment or as an adjunctive treatment for individuals with other disorders, including mood disorders without psychosis, behavioral disorders, and insomnia. Despite the generally superior side-effect profiles of atypical antipsychotics compared with typical antipsychotic agents, the atypicals have been associated with a number of serious side effects, including metabolic disorders, cardiovascular disorders, seizures, hyperprolactinemia, and movement disorders. This article offers a stepwise approach to the management of antipsychotic side effects: Abstinence, Anticipation, Reduction, and Treatment (AART). The steps in AART are hierarchical, but often overlap in the areas of risk prevention and minimization. The authors discuss issues relevant to each level of intervention and provide suggestions for integrating the AART approach into a comprehensive treatment plan. By incorporating this stepwise approach into their clinical decision-making process, prescribers may be able to optimize the risk:benefit ratio associated with the prescription of atypical antipsychotics.


Sequential sampling in clinical cytogenetics: a quality control viewpoint.
We have observed that there is some resemblance between the problems of sampling in industrial quality control and the process of diagnosis of mixed cell populations in cytogenetics. This resemblance enabled us to draw from the methodology of the former science to solve some diagnostic problems in the latter. We considered which of the several sampling procedures available for quality control would be more efficient and more suitable in clinical cytogenetics, concluding that 'sequential sampling' combines both features. We also studied the effect that some abnormalities due to technical factors had on sample size required to reach a diagnosis with a given level of confidence. We give a set of tables for sequential sampling in diagnostic laboratories, illustrating their use in discriminating between mosaicism and pseudomosaicism in prenatal diagnosis and in the diagnosis of the fragile X syndrome. Finally, we discuss the merits of sequential sampling as shown here, comparing it with the current method used in cytogenetics to exclude chromosomal mosaicism.


Biofilm removal from implants supported restoration using different instruments: a 6-month comparative multicenter clinical study.
The aim of this study was to compare the efficacy of different instruments on biofilm removal from implant supported restorations. The study was designed as comparative multicenter clinical study including patients proceeding from the Milan, Naples, and Buenos Aires, with a peri-implant mucositis. Implants enrolled for the study were allocated in 4 groups and treated with ultrasonic scalers with plastic tips, with titanium curettes, with airflow with glycine powder, and with rubber cup and polishing paste, respectively. mPI was assessed at baseline, immediately after therapy, at 1, 3, and 6 months. mBI, PD, and REC were assessed at baseline, 1, 3, and 6 months. All parameters were recorded on six sites per implant. Kruskal-Wallis and Mann-Whitney tests were used to compare groups and centers. A generalized linear model for repeated measures was chosen for inter-group comparison. An intra-group comparison was performed with repeated measure ANOVA test to assess differences between baseline and recalls. A total of 89 patients (39 males, 50 females) were enrolled in the study, and 141 implants were available for the analysis. 55 implants were enrolled in University of Buenos Aires, 32 in University of Milan, and 54 in University of Naples. There were no significant differences between the four groups in inflammatory status reduction of peri-implant mucosa. Non-surgical therapy is effective in reducing peri-implant mucositis. Sonic scaler with plastic tip and rubber cup with polishing paste showed higher efficacy when compared with titanium curettes or airflow with glycine powder.


Tramadol infusion for the pain management in sickle cell disease: a case report.
We present the analgesic management of a 4-year-old child who suffered from severe abdominal and leg pain during his first vaso-occlusive crisis with sickle cell disease, diagnosed as beta/S disease when he was 1 year old. His mother and father were carriers of beta-thalassemia and hemoglobin S, respectively. He had an upper respiratory tract infection in which a vaso-occlusive crisis was precipitated. On admission to hospital, fever, severe abdominal and leg pain were noted. Hemoglobin was 4 g x dl(-1) with accompanying prominent reticulocytosis and acute spleen enlargement. These findings indicated a sequestration crisis as well as vaso-occlusive disease. He was transfused with packed red cells. Paracetamol (40-60 mg x kg(-1) x day(-1)) and ibuprofen (20 mg x kg(-1) x day(-1)) were administered to relieve pain. The child experienced moderate to severe pain (Oucher score 60-80) despite nonopioid analgesics, so a tramadol infusion (0.25 mg x kg(-1) x h(-1)) was started. During the tramadol infusion no morphine was required, the intensity of pain gradually decreased (Oucher score 20) and the child was able to move his legs. At the end of 3 days splenomegaly regressed, no fever and pain were observed and the infusion was stopped. In conclusion, tramadol infusion i.v. (0.25 mg x kg(-1) x h(-1)) combined with nonopioids was effective to relieve moderate to severe pain due to vaso-occlusive crisis and can be recommended before using morphine in a pediatric sickle cell crisis.


[Functional activity of the alpha1-proteinase inhibitor in serum and bronchoalveolar lavage fluid in congenital lung emphysema].
Pulmonary emphysema is thought to be due to an elastase-antielastase imbalance which leads to the destruction of alveolar walls. It is generally agreed that cigarette smoking is the major cause of acquired emphysema although many smokers fail to develop overt disease. Cigarette smoke inactivates alpha 1-proteinase inhibitor (alpha 1PI) which is believed to be the major antielastase in the lower respiratory tract. There is, however, controversy regarding the activity of alpha 1PI in smokers compared with nonsmokers. We, therefore, investigated the trypsin inhibitory capacity (TIC), the pancreatic elastase inhibitory capacity (PEIC), and the amount of immunoreactive alpha 1PI in serum and bronchoalveolar lavage fluid (BALF) of 24 individuals (15 smokers, 5 former smokers, 4 non-smokers) with clinical signs of emphysema and 32 persons (15 smokers, 6 former smokers, 11 non-smokers) without emphysema. Pancreatic elastase is known to be inhibited only by non-oxidised alpha 1PI whereas trypsin is inhibited by both native and oxidised alpha 1PI. Serum values of TIC/alpha 1PI and PEIC/alpha 1PI did not differ between the groups of subjects with emphysema (TIC/alpha 1PI: 0.71 +/- 0.12; PEIC/alpha 1PI: 0.44 +/- 0.06) and without emphysema (TIC/alpha 1PI: 0.68 +/- 0.13; PEIC/alpha 1PI: 0.41 +/- 0.07). Both serum-inhibitory capacities were found to be smaller than unit (= 1) indicating inactivation of alpha 1PI. BALF values of TIC/alpha 1PI showed a wide variation. TIC/alpha 1PI was greater than unity in 84% of subjects with emphysema (2.06 +/- 1.28) compared to 61% without emphysema (1.14 +/- 1.07) providing evidence for the presence of additional inhibitor(s) in those lavage fluids.(ABSTRACT TRUNCATED AT 250 WORDS)


The French registry of Acute ST elevation or non-ST-elevation Myocardial Infarction (FAST-MI): study design and baseline characteristics.
The FAST MI registry was designed to evaluate the 'real world' management of patients with acute myocardial infarction (MI), and to assess their in-hospital, medium- and long-term outcomes. Patients were recruited consecutively from intensive care units over a period of one month (from October 2005), with an additional one-month recruitment period for diabetic patients. The study included 3059 MI patients in phase 1 and an additional 611 diabetic patients in phase 2. Altogether, 53% of the patients had a final diagnosis of Q wave MI and 47% had non Q wave MI. Patients with Q wave MI were more likely to be men, younger, more frequently with a family history or a history of smoking. Patients with non Q wave MI had worst baseline demographic and clinical characteristics mainly explained by their older age. Time from symptom onset to hospital admission was less than three hours for 22% of the patients with Q wave MI and for 14% of the non Q wave MI patients. Among patients with Q wave MI, 64% received reperfusion therapy, 35% with primary percutaneous coronary interventions, 19% with pre-hospital thrombolysis and 10% with in-hospital thrombolysis. Over 70% of patients received statin therapy during the hospital stay and over 90% anti platelet agents. In-hospital mortality was 5.8% in patients with Q wave MI and 4.9% in patients with non Q Wave MI. At discharge beta-adrenergic blockers and statins and, to a lesser extent, medications of the renin angiotensin system were commonly prescribed. Over 90% received antiplatelet agents.


Metabolic and hormonal responses to a single session of kumite (free non-contact fight) and kata (highly ritualized fight) in karate athletes.
BACKGROUND: Several studies report martial arts as a good model for investigating neuroendocrine responses to competitive fighting. However, little is known on the metabolic responses elicited by elite athletes during fighting. In particular, the metabolic picture in elite athletes of martial arts is little known. AIM: In the present study, our aim was to investigate the acute effects of a session of karate practice on the glucose-insulin system. SUBJECTS AND METHODS: Ten healthy individuals (6M/4F; BMI: 22.1 ± 0.7 kg/m(2); 21.9 ± 1.1 years, mean ± SE) who practice karate in national or international competitions were enrolled. All participants completed two experimental trials in a randomised-crossover fashion. A basal blood sample was collected from each athlete to assess plasma glucose, insulin, cortisol, testosterone and catecholamines, before karate training session. In two separate days, another blood sample was collected from each participants after 3 min of real fighting (kumite) and 3 min of ritualized simulation of combat (kata). RESULTS: In both trials, plasma glucose resulted to be higher at the end the of performance compared to the basal (p < 0.001 after kumite and p < 0.02 after kata). In contrast, insulin was similar in the basal and after physical activity in the two trials. Catecholamines were higher after kata and kumite sessions with respect to the basal values (p < 0.04) and, in particular, epinephrine post-kumite values were much greater than those measured after kata. CONCLUSIONS: Our results indicate that unlike performances of karate (kumite and kata) elicit different plasma glucose increases. In particular, we found that glucose and epinephrine concentrations increased more after kumite than after kata.


Substances affecting the infection and replication of human immunodeficiency virus (HIV).
The effects of various compounds were studied quantitatively on the growth of human immunodeficiency virus (HIV). For this we used a human T-cell leukemia virus type I carrying cell line, MT-4 which is most permissive for HIV infection. The results are summarized as follows: 1) Prostaglandin E2 and 12-0-tetradecanoylphorbol-13-acetate enhanced the production of HIV significantly in MT-4 cells as well as a continuous HIV producer Molt-4/HTLV-III cells. 2) Interferon gamma, retinoic acid and 3'-azido-3'-deoxythymidine inhibited the replication of HIV at the concentrations which were not cytotoxic. Mechanism of action of these compounds and its clinical implications are discussed.


Effect of antihistamine-containing syrup on salivary metabolites: an in vitro and in vivo study.
This study tested the null hypothesis that antihistamine-containing syrup does not change salivary metabolites in vitro and in vivo. For the in vitro experiments, saliva from 10 volunteers was mixed with a syrup or pill suspension of loratadine (1 mg/ml Claritin®, Schering-Plough, Rio de Janeiro, Brazil). For the in vivo experiment, 10 volunteers performed a mouth rinse with 10 mL of antihistamine syrup (Claritin®; Schering-Plough, Rio de Janeiro, Brazil) for 20 seconds and then discarded the rinse water. After 20 seconds, 5 mL of unstimulated whole saliva was spit into a plastic tube kept on ice. The protein profile of in vitro and in vivo experiments was analyzed using 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The samples were also analyzed by nuclear magnetic resonance (NMR) spectroscopy, followed by Principal Component Analysis and Wilcoxon test (p < 0.05). There were differences in salivary metabolites after syrup interaction. The salivary concentrations of acetate, n-caproate, arginine, glutamate, and lysine among other metabolites were reduced with the syrup in both in vivo and in vitro experiments (p < 0.05), but no differences were observed when the pill suspension was used (p > 0.05). Similar changes in metabolite profiles were observed in both in vitro and in vivo experiments. Electrophoresis revealed no difference in the salivary protein pattern. The null hypothesis was rejected because the intake of syrup medicine changes the salivary composition and influences oral homeostasis and susceptibility to oral diseases.


The reversion of anti-cancer drug antagonism of tamoxifen and docetaxel by the hyaluronic acid-decorated polymeric nanoparticles.
Docetaxel (DTX) and tamoxifen (TMX) are first-line drugs used to treat breast cancer. However when used in combination, they produce antagonism because of their differential metabolic pathways. In order to prevent this antagonism, an amphiphilic copolymer, cholesterol modified hyaruronic acid (HA-CHOL), was synthesized for investigating the co-delivery of TMX and DTX. In vitro drug release experiment of the Co-encapsulated (encapsulated DTX+TMX) nanoparticles (Co-NPs) revealed that NPs with unique release mechanism can markedly reduce the release of these drugs in the circulatory system. However, when reaching in cell, TMX can release rapidly to prevent DTX from coming into contact with metabolizing enzymes. In vitro cytotoxicity experiment revealed that the Co-NPs exhibited a significant synergistic effect for inhibiting the proliferation of the cancer cell lines A549, MCF7 and S180. NPs carrying Coumarin-6(Cou6) exhibited increased cellular uptake compared with Cou6 solution at similar drug concentrations. As an in vivo treatment of xenograft tumors involving 180 cells, the Co-NPs displayed a clear tumor-inhibiting effect. This led us to conclude that the reversion of drug antagonism by NPs was attributed to the increased stability of the nanoparticles in the blood circulation, the efficient cellular uptake, the hierarchical drug metabolism in the tumor and the good and orderly delivery of the drugs to the tumor tissue.


Hyaluronic acid concentration in postmenopausal facial skin after topical estradiol and genistein treatment: a double-blind, randomized clinical trial of efficacy.
The aim of this work was to compare the effects of estradiol and genistein treatment on hyaluronic acid (HA) concentration in postmenopausal facial skin. In this study, 30 postmenopausal women were evaluated in a prospective, randomized, double-blind trial. The volunteers were postmenopausal women treated in the Gynecology Department of the Federal University of São Paulo. The participants were divided into two groups: group E, treated with 0.01% 17β-estradiol gel (n = 15), and group G, treated with 4% genistein gel (isoflavones, n = 15). The treatment lasted for 24 consecutive weeks. Preauricular skin biopsies were performed for each participant at baseline (E1 and G1) and after treatment (E2 and G2) to evaluate HA concentration in tissue. The materials were processed using immunohistochemical and biochemical methods. After 24 weeks of treatment, HA concentration increased in both groups, but the effect was greater for estradiol treatment than for genistein treatment. Our data suggest that both treatments may enhance HA concentration in postmenopausal skin but that estrogen produces results that are greater than those produced by isoflavones.


Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland.
The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.


Minimally invasive surgery versus sternotomy in native mitral valve endocarditis: a matched comparison.
The present study compared the clinical outcomes between minimally invasive surgery (MIS) and median sternotomy (MS) in patients with native mitral valve infective endocarditis. From 2009 to 2019, a total of 154 patients with acute (n = 131, 85%) or subacute (n = 23, 15%) native mitral valve infective endocarditis were included in the study. One-to-one nearest neighbour propensity score matching considering endocarditis severity using the dedicated De Feo score and 19 other clinically relevant baseline variables resulted in a population of 39 matched pairs. The matched cohort was investigated regarding operative and postoperative outcomes. Both groups showed similar results regarding cardiopulmonary bypass time [MIS: 96 min (77-138), MS: 99 min (88-127); P = 0.780] and aortic cross-clamp time [MIS: 64 min (54-90), MS: 65 min (59-83); P = 0.563], whereas overall operative time was shorter through minimally invasive access [MIS: 138 min (112-196), MS: 187 min (175-230); P = 0.005]. Although the rate of revision for bleeding was similar in both groups [MIS: 12.8% (n = 5), MS: 10.3% (n = 4); P = 1.000], MIS was associated with fewer red blood cell unit transfusions [MIS: 1 unit (0-4), MS: 4 units (2-10); P = 0.001] and fewer fresh frozen plasma unit transfusions [MIS: 0 units (0-0), MS: 1 unit (0-5); P = 0.002]. MIS was associated with a shorter ventilation time [MIS: 708 min (429-1236), MS: 1440 min (659-4411); P = 0.024] and a lower rate of reintubation after extubation [MIS: 5.1% (n = 2), MS: 25.6% (n = 10); P = 0.021]. In patients suffering from native mitral valve infective endocarditis, MIS provides significant clinical benefits over sternotomy in selected patients. 117, 121.


Keratocystic odontogenic tumor invading the maxillary sinus: a case report of collaborative surgery between an oral surgeon and an otorhinolaryngologist.
We report a case of keratocystic odontogenic tumor (KCOT) in a 21-year-old female patient. The patient was referred to our clinic from a dental clinic for the radical treatment of recurrent KCOT in the maxilla. She had undergone conservative drainage surgery twice at that clinic.The tumor was cystic and covered with a bony capsule, which extended high into the maxillary sinus. A pinhole fistula, which was created during a previous surgery, was identified in the gingivobuccal sulcus. The whole tumor was successfully removed using a bidirectional approach from the fistula and from the antrostomy in the middle meatus. This report shows that the intimate collaboration between an otorhinolaryngologist and an oral surgeon could provide a minimally invasive, and at the same time, radical surgical treatment for certain kinds of tumor in the head and neck region. We also recommend the introduction of endoscopic surgeries by the oral surgeon.


Past and recent physical activity and risk of hip fracture.
A population-based case-control study was conducted to examine the effects of past and recent physical activity on the risk of hip fracture in women. Cases included females aged 55-84 years with a first diagnosis of hip fracture in 1989 in metropolitan Toronto, Canada. Controls were a population-based random sample frequency matched by 5-year age groups. Data were collected on 381 cases and 1,138 controls by self-administered mailed questionnaires or telephone interviews. Past activity was calculated as a compilation of activity scores at ages 16, 30, and 50 years. Recent activity was defined as activity in the past year for controls and activity in the year before fracture for cases. Multiple logistic regression was used to control for age, previous fracture, obesity, smoking, osteoporosis, epilepsy, stroke or Parkinson's disease, daily intake of dietary calcium, and duration of use of supplemental calcium, fluoride, and estrogen. After recent activity was adjusted for, statistically significant effects were found for women who in the past had been active (odds ratio estimate (OR) = 0.66, 95% confidence interval (CI) 0.45-0.96) or very active (OR = 0.54, 95% CI 0.33-0.88). After past activity was adjusted for, a similar protective effect was found for women who were moderately active recently (OR = 0.61, 95% CI 0.41-0.90), but women who were very active recently were not protected from hip fracture (OR = 1.15, 95% CI 0.72-1.83). This study showed evidence of independent protective effects of past physical activity and of moderate levels of recent physical activity on the risk of hip fracture in postmenopausal women.


Swallowing of central bearing plate.
While he was being fitted for complete dentures, the patient swallowed the central bearing plate that had become detached. The plate was lodged in the hypopharyngeal region of the pharynx and, with the patient under intravenous sedation, laryngoscope and biopsy forceps were used to retrieve it. Precautions that must be taken to prevent such occurrences include the proper attachment of the device components and testing for security, as well as upright positioning of the patient. The components should be explained to patients and they should be given instructions to eject immediately any part of the device that becomes dislodged.


How to control cyclic nucleotide signaling by light.
Optogenetics allows to non-invasively manipulate cellular functions with spatio-temporal precision by combining genetic engineering with the control of protein function by light. Since the discovery of channelrhodopsin has pioneered the field, the optogenetic toolkit has been ever expanding and allows now not only to control neuronal activity by light, but rather a multitude of other cellular functions. One important application that has been established in recent years is the light-dependent control of second messenger signaling. The optogenetic toolkit now allows to control cyclic nucleotide-dependent signaling by light in vitro and in vivo.


Intrinsic determinants of temperament.
Infant twins have been recruited to participate in a longitudinal assessment of temperament, beginning at three months of age. The twins are brought into a structured laboratory setting and are videotaped as they interact with the mother, with staff personnel, and with each other. The infant's temperament is rated from the videotapes, and additional data are obtained by having the parents fill out the Infant/Toddler Temperament Questionnaire at each visit. A neonatal assessment has also been done for most twins to obtain initial measures of irritability, reactivity and soothability. Monozygotic twins showed high concordance for irritability as neonates, and for ratings of emotional tone at 12 months. Monozygotic twins also tended to show synchronized patterns of change between ages. The questionnaire ratings correlated significantly with the laboratory ratings at six and 12 months, and this convergent linkage between two sources argues for a core temperament profile that manifests itself with some consistency.


Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products: A Scientific Statement From the American Heart Association.
Vaping and electronic cigarette (e-cigarette) use have grown exponentially in the past decade, particularly among youth and young adults. Cigarette smoking is a risk factor for both cardiovascular and pulmonary disease. Because of their more limited ingredients and the absence of combustion, e-cigarettes and vaping products are often touted as safer alternative and potential tobacco-cessation products. The outbreak of e-cigarette or vaping product use-associated lung injury in the United States in 2019, which led to >2800 hospitalizations, highlighted the risks of e-cigarettes and vaping products. Currently, all e-cigarettes are regulated as tobacco products and thus do not undergo the premarket animal and human safety studies required of a drug product or medical device. Because youth prevalence of e-cigarette and vaping product use was as high as 27.5% in high school students in 2019 in the United States, it is critical to assess the short-term and long-term health effects of these products, as well as the development of interventional and public health efforts to reduce youth use. The objectives of this scientific statement are (1) to describe and discuss e-cigarettes and vaping products use patterns among youth and adults; (2) to identify harmful and potentially harmful constituents in vaping aerosols; (3) to critically assess the molecular, animal, and clinical evidence on the acute and chronic cardiovascular and pulmonary risks of e-cigarette and vaping products use; (4) to describe the current evidence of e-cigarettes and vaping products as potential tobacco-cessation products; and (5) to summarize current public health and regulatory efforts of e-cigarettes and vaping products. It is timely, therefore, to review the short-term and especially the long-term implications of e-cigarettes and vaping products on cardiopulmonary health. Early molecular and clinical evidence suggests various acute physiological effects from electronic nicotine delivery systems, particularly those containing nicotine. Additional clinical and animal-exposure model research is critically needed as the use of these products continues to grow.


Superhydrophobicity and superhydrophilicity of regular nanopatterns.
The hydrophilicity, hydrophobicity, and sliding behavior of water droplets on nanoasperities of controlled dimensions were investigated experimentally. We show that the "hemi-wicking" theory for hydrophilic SiO(2) samples successfully predicts the experimental advancing angles and that the same patterns, after silanization, become superhydrophobic in agreement with the Cassie-Baxter and Wenzel theories. Our model topographies have the same dimensional scale of some naturally occurring structures that exhibit similar wetting properties. Our results confirm that a forest of hydrophilic/hydrophobic slender pillars is the most effective superwettable/water-repellent configuration. It is shown that the shape and curvature of the edges of the asperities play an important role in determining the advancing angles.


Inhibition of hydrogenase synthesis by DNA gyrase inhibitors in Bradyrhizobium japonicum.
Derepression of an uptake hydrogenase in Bradyrhizobium japonicum is dependent on a microaerophilic environment. Addition of DNA gyrase inhibitors during depression of hydrogenase specifically prevented expression of the hydrogenase enzyme. Antibodies to individual hydrogenase subunits failed to detect the protein after derepression in the presence of inhibitors, although there was no general inhibition of protein synthesis. The general pattern of proteins synthesized from 14C-labeled amino acids during derepression was not significantly different whether proteins were labeled in the presence or in the absence of gyrase inhibitors. In contrast, if transcription or translation was inhibited by addition of inhibitors of those functions, virtually no proteins were labeled during derepression. This indicated that most of the 14C-labeled proteins were synthesized de novo during derepression, synthesis of most proteins was unaffected by gyrase inhibitors, and the dependence of hydrogenase synthesis on gyrase activity was a specific one.


Cardiac Myxoma as a Rare Cause of Pediatric Arterial Ischemic Stroke: Case Report and Literature Review.
Cardiac disorders are the second leading cause of pediatric arterial ischemic stroke (AIS). Limited literature is available on pediatric AIS caused by cardiac myxoma, a rare tumor in childhood. We describe a new case of pediatric AIS due to a previously unknown atrial myxoma and we conduct a literature review on children with AIS due to cardiac myxoma. We identified 41 published pediatric cases of AIS and cardiac myxoma, including ours (56% males, median age at AIS was 11 years [range: 3-18]). AIS presentation was most frequently with hemiparesis/hemiplegia (89%). Multiple brain ischemic lesions were detected in 69% of patients, and arteriopathy in 91%. Seven patients underwent mechanical thrombectomy. At AIS presentation, 73% of children had one or more of the following clinical symptoms/signs suggesting a possible underlying cardiac myxoma: Carney's complex, cardiac auscultation abnormalities, extraneurological symptoms/signs, such as skin signs (12, 38, and 65%, respectively). Cardiac myxoma was diagnosed within 72 hours in 68% of cases. Death occurred in 11%, and 40% had persistent neurological deficits. Neurological presentation of AIS due to cardiac myxoma is similar to that of AIS with other etiologies, although clues suggesting a possible underlying cardiac myxoma can be detected in most cases. A timely diagnosis of cardiac myxoma in patients with AIS may favor prompt identification of candidates for endovascular therapy. Therefore, we suggest that in otherwise-healthy children presenting with AIS, transthoracic echocardiography should be performed early after stroke presentation.


[Anterior sacral meningocele. Apropos of 11 cases].
The authors report 11 cases of anterior sacral meningocele, cystic mass connected with lumbar sac through a sacral bony defect: 2 children and 9 adults. Clinic presentations are analysed. Examination including, X ray, ultrasonography, scanner is discussed. The authors believe that these lesions must be treated surgically because a risk of rupture in the rectum with important meningitis exists. There is also a septic risk if an error of diagnosis ends at a puncture. The transacral approach is easy and it gives the best results.


CD13 and CD10 expression of granulocytes as markers for the functioning of the immune system: quantification of the expression of membrane molecules using 1:1 labeled monoclonal antibodies and flow cytometry.
HLA-DR expression on monocytes as a marker for the functioning of the immune system is known to be severely depressed in immunodeficiency. Up to now, other markers for the function of the immune system are scarce. In the peripheral blood of patients with open heart surgery the expression of the membrane peptidases neprilysin/CD10 and aminopeptidase N/CD13, was determined on granulocytes in comparison to the monocytic HLA-DR expression. We used the QuantiBRITE flow cytometry system, which yields an absolute antigen expression value (antibodies bound per cell) and may be useful in standardizing surface antigen expression analysis. This system makes use of a highly purified phycoerythrin-labeled antibody with a 1:1 fluorochrome-to-protein ratio, and multilevel calibrated beads with known absolute phycoerythrin fluorescence. Our results show that both membrane peptidases on granulocytes show a similar time-course of expression after heart surgery as do HLA-DR molecules on monocytes, with a decrease from days one to three and a subsequent recovery to normal values. In future analyses a possible relationship between the immunodeficiency of patients and a diminished expression of both membrane peptidases on granulocytes has to be investigated.


cDNA cloning, heterogeneous expression and biochemical characterization of a novel trypsin-like protease from Nilaparvata lugens.
A reverse transcription-polymerase chain reaction (RT-PCR) strategy was used to clone diverse trypsin-like protease gene transcripts from midguts of the brown planthopper Nilaparvata lugens Stål (Homoptera: Delphacidae). Six individual trypsin-like protease transcripts were identified. On the basis of one nucleotide sequence of the six clones, a full-length cDNA sequence (1902 bp) was obtained by rapid amplification of cDNA ends (RACE). The cDNA contained an 1128-bp open reading frame encoding a putative protein of 375 amino acids with typical features of the trypsin-like protease. Heterogeneous expression of the coding sequence for the mature peptide in Escherichia coli cells showed that the expressed protease with a molecular weight of 27.0 is active, for its BApNAse activity assayed by using BApNA (N-benzoyl-D,L-arginine-p-nitroanilide) as substrate. The protease had its maximum activity at pH 8.0 and 35 degrees C. A much better stability was observed at pH values above 4.0 and temperatures below 40 degrees C. The enzyme was strongly inhibited by serine protease inhibitor. The trypsin-like protease is therefore likely one of the major digestive proteases responsible for protein hydrolysis in N. lugens gut, and multiple gene families encoding digestive proteases may help in adaptation of this sap-sucker to different rice varieties.


Relationships Between Dissolved Organic Matter Composition and Photochemistry in Lakes of Diverse Trophic Status.
The North Temperate Lakes Long-Term Ecological Research site includes seven lakes in northern Wisconsin that vary in hydrology, trophic status, and landscape position. We examine the molecular composition of dissolved organic matter (DOM) within these lakes using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) and quantify DOM photochemical activity using probe compounds. Correlations between the relative intensity of individual molecular formulas and reactive species production demonstrate the influence of DOM composition on photochemistry. For example, highly aromatic, tannin-like formulas correlate positively with triplet formation rates, but negatively with triplet quantum yields, as waters enriched in highly aromatic formulas exhibit much higher rates of light absorption, but only slightly higher rates of triplet production. While commonly utilized optical properties also correlate with DOM composition, the ability of FT-ICR MS to characterize DOM subpopulations provides unique insight into the mechanisms through which DOM source and environmental processing determine composition and photochemical activity.


[Epileptic syndromes in childhood associated with secondary generalized tonic-clonic seizures].
To study a group of patients with secondary generalized tonic-clonic seizures (SGTCS) in view of nosology, medical history, clinical, electroencephalographic and neuroimaging features. The study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. SGTCS were observed in many epileptic syndromes. The most frequent were symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less frequent. The onset of epilepsy ranged over a wide age range from the first month of life to 18 years. The average age of onset was 5.7±4.96 years. SGTCS as the only type of paroxysms were observed in 28.3% of cases. Two or more types of seizures were observed in 71.7% of patients, three or more types in 39.3%. Epileptiform activity on EEG during long VEM was detected in 91.3% of patients with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency of seizures by 50% or more was found in 33.6% of patients treated with AEP. No effect was observed in 9.3% of patients. Significant differences in the prognosis and therapeutic approaches to specific epileptic syndromes associated with SGTCS necessitate the use of the entire spectrum of diagnostic measures, which should include careful history taking, clinical examination, video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain, genetic testing.


Why We Still Need Reliable Animal Models.
Animal models are still an essential tool for identifying key molecular mechanisms and pathophysiological manifestations of different diseases, as well as for the analysis of the most effective intervention for the treatment and reduction of the consequences of pathophysiological conditions [...].


Influencing factors of nurses' short-term bereavement reactions after patient death.
An online cross-sectional survey was performed among 181 nurses in mainland China who experienced their most recent patient death within the last month. Multivariate linear regressions were used following bivariate analysis to identify influencing factors for their short-term professional bereavement reactions. More intensive reactions were associated with the nurse's fewer experiences of patient death; the nurse's employment in the intensive care unit rather than the emergency, oncology, geriatrics, or internal medicine departments; and the patient experiencing more pain in the last few days. Higher reaction scores were also reported by nurses who lost the patient more than 1 week prior.


Federal government forgets nurse role in the bush.
In summary the current Federal Budget has failed nurses. There is no recognition in the budget of significant issues facing nursing in Australia especially in the bush. The Budget obviously was designed to appease the medical lobby groups. It is clear that nurses and their organisations will need to work hard to restore the equilibrium so that when we look at a health budget we look at health care not just medical care.


Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells.
Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified. We hypothesized that caffeine evokes effects on GAS by activation of oral and gastric TAS2Rs and demonstrate that caffeine, when administered encapsulated, stimulates GAS, whereas oral administration of a caffeine solution delays GAS in healthy human subjects. Correlation analysis of data obtained from ingestion of the caffeine solution revealed an association between the magnitude of the GAS response and the perceived bitterness, suggesting a functional role of oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine, was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1 cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeine's bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bitter-masking compounds could be potentially useful therapeutics to regulate gastric pH.


2-Azabicyclo (2.2.2)octane analogues of the prodine analgetics.
The synthesis and analgetic activity of analogues of prodine-type analgetics in which the conformation of the piperidine ring is restricted in the boat form using the 2-azabicyclo (2.2.2)octane nucleus are reported. One of these analogues, 2-methyl-6-trans-phenyl-6-cis-propionoxy-2-azabicyclo (2.2.2)octane (3), showed significant analgetic activity (ED50 equals 3.1 mg/kg).


Neuroprotective Effects of n-3 Polyunsaturated Fatty Acid-Enriched Phosphatidylserine Against Oxidative Damage in PC12 Cells.
Neurodegenerative diseases are defined by progressive loss of specific neuronal cell populations and are associated with protein aggregates. Oxidative stress has been implicated in their pathological processes. Previous studies revealed that docosahexaenoic acid (DHA) is beneficial in neurodegenerative diseases. Phospholipids (PLs) derived from marine products are rich in DHA and eicosapentaenoic acid (EPA). In the present study, we investigated the neuroprotective effects of DHA-enriched and unenriched phosphatidylcholine (PC) and phosphatidylserine (PS) on oxidative stress induced by hydrogen peroxide (H2O2) and tert-butylhydroperoxide in PC12 cells. Cell viability and leakage of lactate dehydrogenase results showed that the neuroprotective effect of PS was superior to that of PC. DHA- and EPA-enriched PC and PS were superior to that without DHA or EPA; in addition, the improvement with n-3 polyunsaturated fatty acid-enriched PS (n-3 PS) was dose dependent. Acridine orange/ethidium bromide staining showed that DHA- and EPA-enriched PS (DHA/EPA-PS) could significantly inhibit apoptosis. Mechanistic studies revealed that EPA-PS and DHA-PS were effective to increase superoxide dismutase (SOD) levels by 48.4 and 58.2 % and total antioxidant capacity (T-AOC) level by 51 and 94 %, respectively, in the H2O2 model. Similar results for SOD and T-AOC levels were shown in the t-BHP model. EPA/DHA-PS could downregulate the messenger RNA level of Caspase-3, Caspase-9, and Bax, upregulate Bcl-2, inhibit Bax, and increase Bcl-2 at protein level. In conclusion, EPA/DHA-PS could protect PC12 cells from oxidative stress and prevent mitochondrial-mediated apoptosis. Our findings indicate that the neuroprotective effects of DHA/EPA-PLs depend on the molecular form. Further studies are necessary to reveal detailed mechanisms and structure-effect relationships.


The use of GIS to support sustainable management of vineyards in Plovdiv, Bulgaria.
Vine is a traditional branch of plant growing in Bulgaria. The exact location of the vine culture is a specific complex of environmental factors influencing its development, such as climate, soil, landscape and traditions of the region. GIS is a platform to better manage, evaluate and present spatial data in a useful visual form. It's improves the decision-making by combining data with accurate location and management the vineyards. In the present survey were studied and analyzed the factors in choosing an appropriate location for the cultivation of vine varieties in selected regions of Plovdiv. Climatic and soil characteristics, topography and environmental factors as well as presence of virus vector nematodes from family Longidoridae in creating the vines through GIS spatial analysis are taken into account.


Etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) as outpatient salvage therapy for refractory multiple myeloma.
Fifty-six patients with refractory multiple myeloma were treated with intermittent courses of etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) every 4th week. The overall response rate was 30%. Durable remissions exceeding 1 year were obtained in 12 of the 17 responding patients. A significant prolongation of the survival time was found for responding patients (median 13 months) compared to those patients who did not respond (median 9 months) to EACB therapy (p = 0.01). A low frequency of neutropenic fever episodes was noted compared to other salvage treatment regimens. The EACB regimen was usually well tolerated and could be administered safely on an out-patient basis. This regimen might be an alternative especially for elderly patients unresponsive to initial therapy.


Age-related differences in MAP kinase activity in VSMC in response to glucose or TNF-alpha.
Aortic vascular smooth muscle cells (VSMC) were used to study the effect of age on responses to high glucose concentrations or the cytokine, tumor necrosis factor-alpha (TNF-alpha). Activator protein-1 (AP-1) binding to DNA increased more in VSMC from old versus young rats (P < 0.02) and was related to increased expression of its components, c-Fos, Fra-1, and JunD. The relationship to upstream signals, i.e., activities of mitogen-activated protein kinases (MAPK), was studied using antibodies to total and phosphorylated forms of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. High glucose and TNF-alpha increased ERK phosphorylation more in old (P < 0.05); whereas only TNF-alpha induced JNK activation in young (P < 0.04). PD98059, a MEK inhibitor, attenuated AP-1 activation, lowered c-Fos and Fra-1 protein levels and reduced cell number and cells positive for proliferating cell nuclear antigen in old. We concluded that age differentially influenced activation of signaling pathways in VSMC exposed to high glucose or TNF-alpha. This may contribute to the increased risk for vascular disease associated with aging and diabetes mellitus (DM).


Diagnostic problems in breast pathology: the benefit of ultrastructural and immunocytochemical analysis.
This report deals with the diagnostic importance of intracytoplasmic lumina. The separation between tubular carcinoma and sclerosing adenosis, and the ultrastructural features of variants of lobular carcinoma are discussed. The role of electron dense granules as well as other markers for neuroendocrine cells are evaluated, and finally, the difficult separation of both small-cell and spindle cell tumors is considered.


A strategy for designing multi-taxa specific reference gene systems. example of application--ppi phosphofructokinase (ppi-PPF) used for the detection and quantification of three taxa: maize (Zea mays), cotton (Gossypium hirsutum) and rice (Oryza sativa).
In the first part of the paper, we report the description of a new strategy for the development of a plant reference gene system that can be used for genetically modified organism (GMO) analysis. On the basis of in silico research for candidate genes, the design of degenerate primers allowed the obtention of genomic sequences of the selected gene ppi-phosphofructokinase ( ppi-PPF) for nine taxa in which GMOs have been developed. The comparison and the analysis of inter- and intraspecies sequence variability were performed using a large number of species and cultivars. As an example of application following the detection of single nucleotide polymorphism, we designed specific conventional and real-time polymerase chain reaction tests for the detection and quantification of three taxa, namely, maize, cotton, and rice. This system was highly specific and sensitive. The gene copy number conservation among different cultivars was analyzed and confirmed with a sequencing step. This reference gene system is adequate for use in routine assays for the quantification of GMOs. We then explain briefly the constraints faced and propose recommendations when designing a reference gene system depending on the species to be targeted.


Detection of Helicobacter Pylori infection by invasive and non-invasive techniques in patients with gastrointestinal diseases from Iraq: A validation study.
There is still no agreement on the gold standard technique for diagnosing of H. Pylori in Iraq, as well as a paucity of data on the validity of different diagnostic techniques. This study aimed to investigate the prevalence of this bacterium with different methods and compare them to the quantitative polymerase chain reaction (qPCR) as a golden standard technique among Iraqi patients. In total, 115 Iraqi patients strongly suspected of H. pylori infection were enrolled in the current study. Invasive techniques including rapid urease testing (RUT) and gastric tissue culture in addition to non-invasive techniques including 14C-Urea breath test (14C-UBT), stool antigen test (SAT), CagA-IgG serology, and qPCR were performed to confirm the H. pylori infection. The qPCR was used as the gold standard to estimate the sensitivity, specificity, positive and negative predictive values for the studied diagnostic tests. Overall, the prevalence rate of H. pylori in Iraqi patients was ranged from 47.8 to 70.4% using different methods. The positive results for each test were as follows: qPCR 81, (70.4%) UBT 79 (68.7%), SAT 77 (67%), RUT 76 (66.1%), Cag-IgG 61 (53%), and culture 55 (47.8%). The 14C-UBT showed the highest overall performance with 97.5% sensitivity, 97% specificity, and total accuracy of 97.3% followed by SAT, RUT, Cag-IgG, and culture method. Based on the accuracy of the studied methods for H. pylori detection, they can be arranged in order as follows: qPCR > UBT > SAT > RUT> CagA IgG > culture. Since a universal gold standard assay for the diagnosis of H. pylori has not yet been established in Iraq, the UBT may be recommended as first choice due to its higher performance compared to other methods.


Sigmoido-vesical fistula secondary to sigmoid colon cancer presenting as urinary tract infection with Lactococcus lactis: A case report.
A colovesical fistula is a pathological communication between the colon and bladder. The symptoms include pneumaturia, fecaluria, and a lower urinary tract infection. The diagnosis is based on clinical symptoms, but the symptoms are not specific. Therefore, confirming the diagnosis is challenging. Urine cultures performed in patients with colovesical fistulas usually show growth of Escherichia coli or mixed growth of bowel organisms. Urinary tract infections caused by Lactococcus lactis are very rare, as it is rarely considered pathogenic in humans. We report the case of a 70-year-old woman who presented with symptoms of a recurrent urinary tract infection. Urine cultures were positive for L. lactis. Abdominopelvic computed tomography (CT) revealed focal thickening of the bladder wall and gas in the bladder. Cystoscopic examination and colonoscopy revealed sigmoid colon cancer and a sigmoido-vesical fistula. Laparoscopic surgical treatment was done. The patient recovered and was discharged 3 weeks later without chemoradiotherapy. On follow-up after 6 months, the patient was asymptomatic and stable. To our knowledge, this is the second reported case of L. lactis infection of the urinary tract and the first reported case in adults. L. lactis infection usually indicates the presence of serious underlying diseases such as malignancies, uncontrolled diabetes, and organ failure.


F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses.
A useful approach for exploring gene function involves generating mutant mice from genetically modified embryonic stem (ES) cells. Recent advances in genetic engineering of ES cells have shifted the bottleneck in this process to the generation of mice. Conventional injections of ES cells into blastocyst hosts produce F0 generation chimeras that are only partially derived from ES cells, requiring additional breeding to obtain mutant mice that can be phenotyped. The tetraploid complementation approach directly yields mice that are almost entirely derived from ES cells, but it is inefficient, works only with certain hybrid ES cell lines and suffers from nonspecific lethality and abnormalities, complicating phenotypic analyses. Here we show that laser-assisted injection of either inbred or hybrid ES cells into eight cell-stage embryos efficiently yields F0 generation mice that are fully ES cell-derived and healthy, exhibit 100% germline transmission and allow immediate phenotypic analysis, greatly accelerating gene function assignment.


Betterland: an interactive cd-rom guide for children with cystic fibrosis.
Effective management of cystic fibrosis (CF) depends on adherence to a daily multi-component regimen. Segregation policies have been reported to lead to a dramatic fall in the incidence of cross infection rates in specialist CF centres. Previously, peers provided a valuable source of information and support; segregation means that there is virtually no contact with other people with CF. In this context the Betterland CD-ROM was developed with the aim of improving knowledge and understanding and helping children and young people cope with time-consuming CF treatments (inhalation therapies and physiotherapy) and painful procedures by using filmed-model approaches. Betterland is an interactive computer game, designed in the style of a theme park. Patient and carer feedback has been positive and the CD-ROM has been incorporated into a nurse-led Moving to High School (MotHS) programme, as well as the patient education work of the CF multidisciplinary team, particularly clinical nurse specialists.


Surfactant Proteins in Smoking-Related Lung Disease.
Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted in the alveoli by type II epithelial cells and is found in the fluid lining the alveolar surface. The protein part of surfactant constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and SP-C), which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Several studies have shown that cigarette smoke seems to affect, in several ways, both surfactant homeostasis and function. The alterations in surfactants' biophysical properties caused by cigarette smoking, contribute to the development of several smoking related lung diseases. In this review we provide information on biochemical and physiological aspects of the pulmonary surfactant and on its possible association with the development of two major chronic diseases of the lung known to be related to smoking, i.e. chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Additional information on the possible role of surfactant protein alterations and/or dysfunction in the combination of these two conditions, recently described as combined pulmonary fibrosis and emphysema (CPFE) are also provided.


Translocation of Mg2+-dependent phosphatidate phosphohydrolase between cytosol and endoplasmic reticulum in a permanent cell line from human lung.
Incubation of A549 cells with digitonin for 4 min resulted in the release of over 90% of the lactate dehydrogenase activity into the medium. Approximately 80% of the Mg2+-dependent but only 7% of the Mg2+-independent phosphatidate phosphohydrolase activity was released in the presence of digitonin. Pretreatment of the cells with oleate reduced the efflux of the Mg2+-dependent phosphatidate phosphohydrolase activity to approximately 5% of total. Oleate did not affect the release of lactate dehydrogenase or the release of the Mg2+-independent phosphohydrolase activity. Incubation of A549 cells with [3H]oleate for 60 min led to incorporation of the label into phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, diacylglycerol, monoacylglycerol, and triacylglycerol, in ascending order. When the level of exogenous oleate was increased to over 2.0 mM, there was a marked increase in the incorporation into monoacylglycerol and diacylglycerol. Only small amounts of radioactivity were associated with phosphatidic acid. Time course studies revealed that the amount of radioactive phosphatidate remained low throughout the incubation period. These investigations were interpreted to indicate that free fatty acids can promote the translocation of the Mg2+-dependent phosphatidate phosphohydrolase activity from cytosol to membrane fractions. This translocation could, at least theoretically, function to facilitate the metabolism of increased amounts of phosphatidate.


Association of the thyroglobulin gene polymorphism with autoimmune thyroid disease in Chinese population.
This study was performed to identify the presence of previously reported thyroglobulin (Tg) gene single nucleotide polymorphisms (SNPs) in Han Chinese Asians, and to investigate their potential relation to autoimmune thyroid disease (AITD). Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) in 228 Chinese patients with AITD (146 with Graves' disease and 82 with Hashimoto's thyroiditis) and 131 healthy Chinese controls. (1) The occurrence of four common Tg gene SNPs (E10SNP24 T/G and E10SNP158 T/C in exon 10, E12SNP A/G in exon 12, and E33SNP C/T in exon 33) was confirmed in this Chinese population. No differences in allele and genotype frequencies were found between AITD patients and control subjects, or between male and female individuals in any group. Neither were differences in allele frequencies observed when Graves' disease (GD) or Hashimoto's thyroiditis (HT) patients were analyzed separately. (2) Haplotype analysis of these four SNPs revealed that the G-C-A-C haplotype was significantly associated with HT (P < 0.01, OR = 3.06, OR 95% CI [1.326-7.089]) and with serum anti-Tg antibody (Tg-Ab) positive AITD patients (P = 0.028, OR = 3.34). Our study confirms the existence of four SNPs among Han Chinese. In addition, the association of one SNP haplotype with HT suggests that Tg may be an AITD susceptibility gene.


Proper processing of a G protein gamma subunit depends on complex formation with a beta subunit.
G protein beta and gamma subunits function as a tightly associated complex. We show that complex formation with the beta subunit is a critical step for post-translational processing of a gamma subunit. When expressed alone in a cell line, the gamma 3 subunit type is isoprenylated but degraded; co-expression with the beta 1 subunit type stabilizes the gamma 3 protein. Furthermore, our experiments with partial cell fractionation indicate that the gamma 3 protein is localized differently in the cell depending on whether or not it is bound to the beta subunit. Binding of the gamma subunit to the beta subunit is thus one of the prerequisites for the appropriate intracellular localization of the beta gamma complex and potentially, for normal G-protein function.


[Interference research of umbilical cord mesenchymal stem cells on the pulmonary fibrosis in silicosis rats].
Objective: To explore the effect of the umbilical cord mesenchymal stem cells(UC-MSCs) on the pulmonary fibrosis in silicosis rats. Methods: SPF male Sprague Dawley rats were randomly divided into control group, silica model group and UC-MSCs treatment group with 12 rats each group. SiO(2) intra-tracheal injection(0.5 ml of 50 mg/ml/rat) were applied to silica model group and UC-MSCs treatment groups. After that UC-MSCs treatment group received 1 ml UC-MSCs suspension (3×10(6) cells/ml) by tail vein injection on the 29th, 36th, 43th and 50th day after exposure to the first silica suspension. On the 60th and 75th day after exposure to silica suspension, all animals were examed for pulmonary CT. Then the rats were euthanized on 75th day after the first exposure to silica.Lung's histopathological examination of the rats from all the groups were carried out. The content of hydroxyproline in lungs, TGF-β1 and IL-6 in serum were examined. Results: The lung's histopathological examination showed no obvious inflammatory cell and no fibrosis in the lung tissue of the control group, there were a lot of inflammatory cell aggregation and collagen fiber deposition in silica model group, while in the UC-MSCs intervention group and treatment group, there were less inflammatory cells and collagen fiber. The rats from silica model groups had higher HYP, TGF-β1 and IL-6 than the rats from UC-MSCs treatment group and control group. Lung fields of rats in the control group were clear and no obvious high-density shadow. Different-sized granular high-density shadows or reticular fibrous shadows were found diffusely distributed in the lungs of the rats in silica model group. Lung field of rats in UC-MSCs intervention group and treatment group were less high density shadows, and more clear. Conclusion: UC-MSCs can alleviate the pulmonary fibrosis in silica model rats through regulating the secretion of some fibrosis related cytokines.


Real-World Early Treatment with Room Temperature-Stable Recombinant Factor VIIa in Hemophilia A/B and Inhibitors: SMART-7™ Post Hoc Analyses.
Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature-stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven ® ), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature-stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.


[The regulative effects of Aspergillus fumigatus on expression of glucocorticoid receptor in asthmatic rats].
Objective: To study the regulative effects of Aspergillus fumigatus (A.fumigatus) on expression of glucocorticoid receptor (GCR) in asthmatic rats. Methods: Wistar rats were randomly divided into 4 groups: a normal control group (UC), a normal control with A. fumigatus group (UC+ AF), an OVA group (OVA), and an OVA with A. fumigatus group (OVA+ AF). OVA and OVA+ AF groups were sensitized and challenged with OVA to establish asthmatic models. UC and UC+ AF groups were given normal saline as controls. After the last challenge, OVA+ AF and UC+ AF groups were given A. fumigatus spores intranasally. Airway hyper-responsiveness, eosinophil percentage (Eos%) and serum IgE level were measured to confirm the establishment of asthmatic models. Sections of pulmonary tissue were stained with hematoxylin-eosin (HE) and the expression of GCR mRNA and protein in lung tissues were measured by qRT-PCR and Western blot. Lung tissues and blood were plated on the potato dextrose agar(PDA)medium and cultured for 24 h to measure the number of colony. Results: The Penh value, Eos% in BALF and serum IgE level in UC+ AF group were slightly higher than those in the UC group (all the P>0.05). The Penh value, Eos% in BALF and serum IgE level in OVA group were significantly higher than those in the UC group (all the P<0.05). The Penh value in OVA+ AF group was significantly increased compared with the OVA group at the concentration of 25 g/L and 50 g/L of methacholine (all the P>0.05). Pulmonary histology revealed that both OVA group and OVA+ AF group showed high levels of inflammatory cell infiltration of bronchus and lung vessels, interstitial edema and smooth muscle thickening, while the UC and UC + AF groups were normal. Compared with the UC group, the expressions of GCR mRNA and protein in UC+ AF group and OVA group were decreased significantly (GCR mRNA in UC, UC+ AF and OVA group were 0.93±0.15, 0.65±0.10, 0.72±0.22, respectively, F=10.744, P<0.01; GCR protein in UC, UC+ AF and OVA group were 100±0, 89±8, 82±15, respectively, F=18.939, P<0.01). The expressions of GCR mRNA and protein in OVA+ AF group were further decreased than those in OVA group (GCR mRNA: OVA group: 0.72±0.22 vs OVA+ AF group: 0.52±0.08, t=2.462, P<0.05; GCR protein: OVA group: 81.88±15.41 vs OVA+ AF group: 59.09±7.60, t=2.997, P<0.05). The ratio of A. fumigatus colonization in lung tissues in OVA+ AF group (4/8) was higher than the UC+ AF group (0/8). Conclusion:A. fumigatus exposure can down-regulate the expression of GCR in the lung, which maybe an important mechanism of steroid-resistant asthma.


Pandemic Exposure, Post-traumatic Stress Disorder, Conflict Behaviors, and Online Aggressive Behaviors Among College Students During the COVID-19 Pandemic: Examining the Moderating Role of Gender.
The COVID-19 pandemic impacts people's mental health and behaviors, but the influence mechanism between pandemic exposure, conflict behaviors, and online aggressive behaviors during the COVID-19 outbreak remains unclear. This study will address this gap. Data were collected from 1,153 college students in an online survey that included an pandemic experiences scale, a post-traumatic stress disorder (PTSD) scale, a conflict behaviors scale, and an online aggressive behaviors scale. Structural equation modeling and multi-group comparisons were used to analyze the data. Pandemic exposure positively predicted conflict and online aggressive behaviors through hyperarousal symptoms, and negatively predicted these behaviors through intrusive symptoms. The mediating roles of avoidance and negative alterations in cognition and mood symptoms in the relations between pandemic exposure and conflict behaviors and online aggressive behaviors were non-significant. Among male students, pandemic exposure directly predicted conflict and online aggressive behaviors, but for female students, pandemic exposure indirectly influenced these behaviors through intrusive and hyperarousal symptoms. The intrusive and hyperarousal symptoms play mediating roles in the relations between pandemic exposure and conflict behaviors and online aggressive behaviors. Gender plays a moderating role in the above mediating mechanism.


Photochemistry of formaldehyde under tropospheric conditions.
We report new results on the absorption cross sections and photochemical quantum yields for radical (H + HCO) production from formaldehyde in the wavelength interval from 308-320 nm, obtained at resolutions of better than 0.1 nm. The absorption cross sections, measured at resolutions close to the limit for Doppler broadening of HCHO, show rotationally resolved fine structure, with maximum values higher than those obtained in previous, lower resolution, studies. In this wavelength region, absorption cross sections peak at 2.3 x 10(-19) cm2 molecule(-1), but band-integrated values are in excellent accord with previous measurements. HCO absorption coefficients, measured by cavity ring-down spectroscopy following UV photolysis of HCHO at wavelengths across the 2(0)(1)5(0)(1), 2(0)(2)4(0)(3) and 2(0)(3)4(0)(1) bands of the A1A2-X1A1 transition, generally mimic the parent absorption band profiles. Division of these absorption coefficients by the high resolution parent absorption cross sections gives relative quantum yields for the H + HCO radical product channel that can be put on an absolute scale using single-wavelength literature values. These quantum yields are observed to show some variation with parent excitation wavelength (and thus with excited vibronic level). Addition of 200 Torr of N2 increases the HCO quantum yields.


Self-cleaning Metal Organic Framework (MOF) based ultra filtration membranes--a solution to bio-fouling in membrane separation processes.
Bio-fouling is a serious problem in many membrane-based separation processes for water and wastewater treatment. Current state of the art methods to overcome this are to modify the membranes with either hydrophilic additives or with an antibacterial compound. In this study, we propose and practise a novel concept to prevent bio-fouling by developing a killing and self-cleaning membrane surface incorporating antibacterial silver nanoparticles and highly hydrophilic negatively charged carboxylic and amine functional groups. The innovative surface chemistry helps to reduce the contact angle of the novel membrane by at least a 48% and increase the pure water flux by 39.4% compared to the control membrane. The flux drop for the novel membrane is also lower (16.3% of the initial flux) than the control membrane (55.3% of the initial flux) during the long term experiments with protein solution. Moreover, the novel membrane continues to exhibit inhibition to microbes even after 1320 min of protein filtration. Synthesis of self-cleaning ultrafiltration membrane with long lasting properties opens up a viable solution for bio-fouling in ultrafiltration application for wastewater purification.


Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease.
A double-blind study comparing the effects of carbidopa and levodopa combined in a single tablet with levodopa alone was undertaken in 50 patients with Parkinson's disease. After 6 months, there was a statistically significant improvement over baseline in total score, rigidity, and tremor only in the patients randomized to carbidopa/levodopa. In addition, 40 percent of the patients treated with carbidopa/levodopa showed obvious clinical improvement (a greater than 50 percent reduction in their total score) over treatment with levodopa alone. However, after 2 years, only 20 percent continued to show this improvement. Nausea, vomiting, and anorexia developed in 56 percent of patients on levodopa but in only 27 percent of patients on carbidopa/levodopa. However, abnormal involuntary movements, observed in 48 percent of patients on levodopa, were present in 77 percent of patients on carbidopa/levodopa. Despite the increase in abnormal involuntary movements, carbidopa/levodopa is more effective than levodopa.


Cell-free nucleic acids in prenatal diagnosis and pregnancy-associated diseases.
There is a great effort to find out the biological role of cell-free nucleic acids (cfNAs). They are considered very promising targets in the diagnosis of genetic diseases. Non-invasive sampling (liquid biopsy) has recently become a very popular method, and new molecular biological techniques have been developed for these types of samples. Application of next-generation sequencing (NGS) and massively parallel sequencing (MPS) is spreading fast. These are the part of the arsenal of the modern prenatal genetic diagnostic laboratories by now. Cell-free DNA based noninvasive prenatal testing accounts for more than half of the prenatal genetic tests performed, it is gradually replacing the invasive amniocentesis or chorionic villus sample-based diagnostics. Besides that, new non-coding RNAs are taking more attention: microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) are in the focus of the clinical research to detect the most common pregnancy-associated diseases, like preeclampsia, fetal growth restriction, congenital heart diseases and gestational diabetes. The research is at advanced stage on the use of microRNAs, while lncRNAs and circRNAs are still promising targets. In this review, comprehensive information is given about the recent developments on this field.


Clinical and parasitological evaluation of dogs naturally infected by Leishmania (Leishmania) chagasi submitted to treatment with meglumine antimoniate.
Aiming to evaluate the efficacy of the treatment of canine visceral leishmaniasis, to verify the occurrence of a possible disease relapse, and to search for the presence of the parasites after the end of the treatment, seven dogs naturally infected by Leishmania (Leishmania) chagasi were used. The dogs were subjected to a treatment with 75 mg/kg meglumine antimoniate subcutaneously every 12 h for 21 days, and followed-up for a period of 6 months. During the whole experimental period the animals wore deltamethrin collars and were kept in a screened kennel to avoid reinfection. Lymph node and bone marrow aspiration biopsy was carried out to search for the parasite at seven moments: before the treatment, 30, 60, 90, 120, 150 and 180 days after the start of the treatment. After the end of the experiment all dogs were humanely euthanized. Then, spleen and liver "imprints" and in vitro cultures were carried out to search for amastigote forms of the parasite. During the treatment all animals presented remission of symptoms. However, two dogs were observed to present new symptoms in the course of the experiment. At the end of the experiment, the presence of amastigote forms of the parasite was evidenced in five of the seven dogs. This enabled us to conclude that the treatment promoted clinical cure but did not eliminate the parasites completely.


Effect of CYP3A5*3 polymorphism on pharmacokinetic drug interaction between tacrolimus and amlodipine.
The objective of this study was to evaluate the effect of the CYP3A5*3 allele on the pharmacokinetics of tacrolimus and amlodipine, and drug-drug interactions between them in healthy subjects. Pharmacokinetic drug interactions between tacrolimus and amlodipine were evaluated in a randomized, 3-period, 6-sequence crossover study in healthy Chinese volunteers according to CYP3A5 genotype. A single-dose and multiple-dose study were designed. A 96-h pharmacokinetic study followed either tacrolimus or amlodipine dose, and the washout periods between the study phases were 14 days. In the single-dose study, apparent oral clearance (CL/F) of tacrolimus (5 mg) in CYP3A5 expressers was 3.8-fold (p = 0.008) higher than that in CYP3A5 non-expressers. Amlodipine decreased mean tacrolimus CL/F in CYP3A5 expressers by 2.2-fold (p = 0.005), while it had no effect on that in CYP3A5 non-expressers. The CL/F of amlodipine in CYP3A5 non-expressers was 2.0-fold (p = 0.001) higher than that in CYP3A5 expressers. Tacrolimus increased mean amlodipine CL/F in CYP3A5 expressers by 1.4-fold (p = 0.016) while it had no effect on that in CYP3A5 non-expressers. Tacrolimus slightly reduced the AUC₀-∞ of amlodipine in both CYP3A5 expressers and non-expressers. Dose adjustment of tacrolimus should be considered according to CYP3A5*3 genetic polymorphism when tacrolimus is coadministered with amlodipine.


Effects of food-simulating liquids on surface properties of giomer restoratives.
This study examined the effects of food-simulating liquid (FSL) on the hardness and roughness of giomer restoratives based on pre-reacted glass ionomer (PRG) technology. The materials investigated included a regular (Beautifil II [BT]) and a recently introduced injectable (Beautifil Flow Plus F00 [BF]) hybrid PRG composite. A direct hybrid composite (Filtek Z250 [ZT]) and an indirect hybrid composite (Ceramage [CM]) were used for comparison. The materials were placed into customized square molds (5 mm × 5 mm × 2.5 mm), covered with Mylar strips, and cured according to manufacturers' instructions. The materials were then conditioned in air (control), distilled water, 50% ethanol solution, and 0.02 N citric acid at 37°C for seven days. Specimens (n=6) were then subjected to hardness testing (Knoop) and surface profilometry. Data were analyzed using one-way analysis of variance and post hoc Scheffe test (p<0.05). Mean Knoop hardness values for the control group (air) ranged from 53.4 ± 3.4 (BF) to 89.5 ± 5.2 (ZT), while mean surface roughness values values ranged from 0.014 ± 0.002 (ZT) to 0.032 ± 0.001 (BT). All materials were significantly softened by FSL. The degree of softening by the different FSLs was material dependent. The hardness of giomers was most affected by citric acid and ethanol. The smoothest surface was generally observed with the control group. Giomer restoratives were significantly roughened by citric acid.


[AP4-assocated hereditary spastic paraplegias].
In the course of studies of spastic paraplegias in Russian patients to detect AP4-associated forms, estimate their proportion in the total SPG group and analyze clinical and molecular characteristics. Five families of Russian ethnicity: four with SPG47, one with SPG51 (4 girls and a boy aged 2.5-9 years) were studied. Clinical and genealogical methods, whole-exome sequencing (WES) and verification by familial Sanger sequencing were used. In our total group, including 118 families with 21 different forms, SPG AP4-associated forms accounted for 4.2% owing mainly to SPG47 (3.4%, 5th place in SPG structure; 20% and 2nd place in AE subgroup.) In non-consanguineous, unrelated SPG47 families three patients had identical genotypes: homozygosity for an earlier reported mutation c.1160_1161 delCA (p.Thr387ArgfsTer30) in AP4B1 exon 6; the 4th patient was compound-heterozygous for the same mutation and novel c.1240C>T (p.Gln414Ter) in exon 7. Frequency of c.1160_1161 delCA may be caused by founder effect in Slavic populations though the idea needs additional studies. The SPG51 patient was compound heterozygous for novel AP4E1 mutations c.2604delA (p.Ser868fs) and c.3346A>G (p.Arg1116Gly). Parent's heterozygosity in all cases was confirmed by Sanger sequencing. Phenotypes were typical: early development delay, muscle hypotony transforming into sever spasticity, mental deficiency, microceplaly (in all SPG47 cases), epilepsy (in 3 SPG47 and SPG51 cases), MRI changes, mainly hydrocephalus and/or hypoplasia of corpus callosum (in 3 SPG47 cases) and few extraneural signs. AP4-associated SPG should be taken into consideration in patients with early-onset severe nervous diseases mimicking non-genetic organic CNS disorders and massive exome sequencing (WES or other variants) should be performed.


Stress: a self-management approach and nursing care plan for nurses.
Stress is unavoidable but can be controlled to provide the energy for health, growth, and the development of human potential. This article provides a self-management approach and a nursing care plan for nurses.


Study of the possible enteropancreatic circulation of pancreatic amylase in the dog.
The possible existence of an enteropancreatic circulation of amylase was investigated in the dog. Endogenous amylase concentration in pancreatic venous blood was consistently greater than that in arterial blood, indicating a net flux of amylase from the pancreas to blood. Less than 0.02% of the metabolic clearance of 125I-amylase was accounted for by 125I-amylase in pancreatic secretions, indicating a minimal flux of amylase from the blood to pancreatic secretions. The venous-arterial amylase concentration across gut segments containing large quantities of amylase was not significantly different from 1.00, indicating absorption of less than 0.2% of the luminal amylase per hour. No 125I-amylase was detectable in serum after endoscopic instillation of labeled enzyme into the duodenum. These studies demonstrate negligible intestinal absorption of amylase and negligible pancreatic extraction of amylase, indicating negligible enteropancreatic circulation of pancreatic amylase in the dog.


Primary aldosteronism caused by unilateral adrenal hyperplasia.
In the hypertensive population, primary aldosteronism has been reported to have a prevalence of 0.1% to 2%, with the main causes being aldosterone-producing adenomas and bilateral hyperplasia. However, there is a third rare entity, called unilateral adrenal hyperplasia, that contributes to primary aldosteronism. Unilateral hyperplasia and primary aldosteronism are the subjects of this case review.


Immunotherapy alone or chemo-immunotherapy as front-line treatment for advanced non-small cell lung cancer.
Immunotherapy, either as monotherapy or in combination with chemotherapy, has demonstrated superior efficacy to chemotherapy alone in the frontline setting. To date, there has been no randomized study comparing immunotherapy alone with chemo-immunotherapy. This paper reviews the immunobiological rationale for combining chemotherapy with checkpoint inhibitors as well as the data from recent phase-3 studies to understand the risks and benefits associated with either therapeutic approach for diverse patient populations. Frontline pembrolizumab monotherapy remains the treatment of choice for patients with high PD-L1 expression. For those with low PD-L1 expression, pembrolizumab in combination with chemotherapy can be considered.


Press releases: translating research into news.
While medical journals strive to ensure accuracy and the acknowledgment of limitations in articles, press releases may not reflect these efforts. Telephone interviews conducted in January 2001 with press officers at 9 prominent medical journals and analysis of press releases (n = 127) about research articles for the 6 issues of each journal preceding the interviews. Seven of the 9 journals routinely issue releases; in each case, the editor with the press office selects articles based on perceived newsworthiness and releases are written by press officers trained in communications. Journals have general guidelines (eg, length) but no standards for acknowledging limitations or for data presentation. Editorial input varies from none to intense. Of the 127 releases analyzed, 29 (23%) noted study limitations and 83 (65%) reported main effects using numbers; 58 reported differences between study groups and of these, 26 (55%) provided the corresponding base rate, the format least prone to exaggeration. Industry funding was noted in only 22% of 23 studies receiving such funding. Press releases do not routinely highlight study limitations or the role of industry funding. Data are often presented using formats that may exaggerate the perceived importance of findings.