Impact of different dietary sodium reduction strategies on blood pressure: a systematic review.
High sodium intake was found to be associated with increased blood pressure. Decreasing dietary sodium intake can effectively reduce blood pressure, especially among hypertensive individuals, but the extent of reduction remains debatable. The effectiveness of different sodium reduction strategies on blood pressure reduction was identified in the current review. Randomized controlled trials and clinical trials on dietary sodium intake and blood pressure published from 23 March 2008 to 23 March 2021 were collected from the PubMed database. Twenty-six studies were included and divided into four subgroups based on the types of interventions identified. Subgroups included a low-sodium diet (1) in a group with or without added sodium, (2) through food substitutes, (3) through health education and behavior change, and (4) through salt substitutes. Reduction of dietary sodium intake resulted in a mean difference of 4.51 mmHg (95% CI: 3.35-5.67) in systolic blood pressure and 2.42 mmHg (95% CI: 1.61-3.23) in diastolic blood pressure. The effectiveness of these strategies was approximated from the difference in 24-h urinary sodium excretion between the intervention and control groups, which was 53.74 mmol/day (95% CI: 31.95-75.53). When analyzed, the low-sodium diet without added sodium showed the greatest significant differences in blood pressure (7.58/4.01 mmHg) and 24-h urinary sodium excretion (101.49 mmol/day), whereas the low-sodium diet through food substitutes yielded the lowest significant differences in blood pressure (2.26/0.81 mmHg) and 24-h urinary sodium excretion (25.78 mmol/day). Thus, reducing sodium intake can be an effective strategy for the prevention and treatment of hypertension.


Investigation of silk as a phantom material for ultrasound and photoacoustic imaging.
Comprehensive characterization of biomedical imaging systems require phantoms that are easy to fabricate and can mimic human tissue. Additionally, with the arrival of engineered tissues, it is key to develop phantoms that can mimic bioengineered samples. In ultrasound and photoacoustic imaging, water-soluble phantom materials such as gelatin undergo rapid degradation while polymer-based materials such as polyvinyl alcohol are not conducive for generating bioengineered tissues that can incorporate cells. Here we propose silk protein-based hydrogels as an ultrasound and photoacoustic phantom material that has potential to provide a 3D environment for long-term sustainable cell growth. Common acoustic, optical, and biomechanical properties such as ultrasound attenuation, reduced scattering coefficient, and Young's modulus were measured. The results indicate that silk acoustically mimics many tissue types while exhibiting similar reduced optical scattering in the wavelength range of 400-1200 nm. Furthermore, silk-based materials can be stored long-term with no change in acoustic and optical properties, and hence can be utilized to assess the performance of ultrasound and photoacoustic systems.


alpha Chain and gamma chain abnormal hemoglobins in newborn babies: structural and genetic aspects.
Structural studies and quantitative analyses were conducted on the hemoglobin of 55 newborn babies. Seven alpha chain variants (G-Philadelphia, Montgomery, Inkster, I-Philadelphia, Matsue-Oki, Winnipeg, and O-Indonesia) were present in 26 heterozygous newborns (17 black, eight Caucasian, and one Indonesian). The relative amount of the alpha X containing abnormal Hb F of the Hb G-Philadelphia and Hb Winnipeg babies was less than observed in heterozygous adults, which may indicate a decreased rate of assembly of the alpha X-gamma dimer over that of the alpha X-beta dimer. Of the 29 newborns with gamma chain variants, 16 were Caucasian babies; of these 15 had a Hb A gamma F-Hull heterozygosity and one a Hb G gamma F-Marietta heterozygosity. Six black babies were heterozygous for Hb A gamma F-Texas-I and six for Hb G gamma F-Port Royal. One Japanese baby had a heterozygosity for A gamma F-Iwata and a second was heterozygous for A gamma TF-Yamaguchi. Quantitative analyses of the isolated normal Hb Fo as well as an evaluation of the relative amounts of the Hb Fx in the red cell lysates gave data useful for a speculation of the genetic condition in each of these babies. It was concluded that the babies with the Hbs F-Texas-I, F-Iwata, F-Hull, and F-Marietta were simple heterozygotes with either the G gamma x A gamma/G gamma x A gamma X or the G gamma x A gamma/G gamma X x A gamma genic arrangement. The babies with Hb F-Port Royal had a G gamma x G gamma X/G gamma x A gamma arrangement, which may result from a (to be determined) gene conversion. The newborn baby with Hb F-Yamaguchi has the G gamma x A gamma x/A gamma T-X.-. genic arrangement, suggesting the presence of three distinctly different gamma chain genes of which one, the A gamma T-X gene, produces an A gamma chain (with threonyl at position gamma 75 and an Asn at position gamma 80) at a level usually seen for G gamma rather than A gamma chains. These studies were greatly facilitated by the use of high pressure liquid chromatographic methods.


Optimization of a lattice structure inspired by glass sponge.
The biomimetic design of engineering structures is based on biological structures with excellent mechanical properties, which are the result of billions of years of evolution. However, current biomimetic structures, such as ordered lattice materials, are still inferior to many biomaterials in terms of structural complexity and mechanical properties. For example, the structure ofEuplectella aspergillum, a type of deep-sea glass sponge, is an eye-catching source of inspiration for biomimetic design, many researches have introduced similar architecture in cellular solids. However, guided by scientific theory, how to surpass the mechanical properties ofE. aspergillumremains an unsolved problem. We proposed the lattice structure which firstly surpass theE. aspergillummechanically. The lattice structure of the skeleton ofE. aspergillumconsists of vertically, horizontally, and diagonally oriented struts, which provide superior strength and flexural resistance compared with the conventional square lattice structure. Herein, the structure ofE. aspergillumwas investigated in detail, and by using the theory of elasticity, a lattice structure inspired by the biomimetic structure was proposed. The mechanical properties of the sponge-inspired lattice structure surpassed the sponge structure under a variety of loading conditions, and the excellent performance of this configuration was verified experimentally. The proposed lattice structure can greatly improve the mechanical properties of engineering structures, and it improves strength without much redundancy of material. This study achieved the first surpassing of the mechanical properties of an existing sponge-mimicking design. This design can be applied to lattice structures, truss systems, and metamaterial cells.


The SCF/KIT axis in human mast cells: Capicua acts as potent KIT repressor and ERK predominates PI3K.
The SCF/KIT axis regulates nearly all aspects of mast cell (MC) biology. A comprehensive view of SCF-triggered phosphorylation dynamics is lacking. The relationship between signaling modules and SCF-supported functions likewise remains ill-defined. Mast cells were isolated from human skin; upon stimulation by SCF, global phosphoproteomic changes were analyzed by LC-MS/MS and selectively validated by immunoblotting. MC survival was inspected by YoPro; BrdU incorporation served to monitor proliferation. Gene expression was quantified by RT-qPCR and cytokines by ELISA. Pharmacological inhibitors were supplemented by ERK1 and/or ERK2 knockdown. CIC translocation and degradation were studied in nuclear and cytoplasmic fractions. CIC's impact on KIT signaling and function was assessed following RNA interference. ≈5400 out of ≈10,500 phosphosites experienced regulation by SCF. The MEK/ERK cascade was strongly induced surpassing STAT5 > PI3K/Akt > p38 > JNK. Comparison between MEK/ERK's and PI3K's support of basic programs (apoptosis, proliferation) revealed equipotency between modules. In functional outputs (gene expression, cytokines), ERK was the most influential kinase. OSM and LIF production was identified in skin MCs. Strikingly, SCF triggered massive phosphorylation of a protein not associated with KIT previously: CIC. Phosphorylation was followed by CIC's cytoplasmic appearance and degradation, the latter sensitive to protease but not preoteasome inhibition. Both shuttling and degradation were ERK-dependent. Conversely, CIC-siRNA facilitated KIT signaling, functional outputs, and survival. The SCF/KIT axis shows notable strength in MCs, and MEK/ERK as most prominent module. An inhibitory circuit exists between KIT and CIC. CIC stabilization in MCs may turn out as a therapeutic option to interfere with allergic and MC-driven diseases.


Development of an implantable infusion pump for sustained anti-HIV drug administration.
Factors such as insufficient drug potency, non-compliance and restricted tissue penetration contribute to incomplete suppression of Human Immunodeficiency Virus (HIV) and the difficulty to control this infection. Infusion via standard catheters can be a source of infection, which is potentially life threatening in these patients. We developed an implantable infusion pump, allowing to accommodate large volumes (16-50mL) of high viscous solutions (up to 23.96mPas at 39 degrees C) of anti-HIV agents and providing sustained release of medication: a standard Codman 3000 pump, which was initially developed to release aqueous solutions ( approximately 0.7mPas) into the spinal cord such as for pain medication, was transformed for release of viscous solutions up to 40mPas by adapting the diameter of the capillary flow restrictor, the capillary length and way of catheterisation--by placing the indwelling catheter in the vena cava. A pilot study of the pump implanted in 2 dogs showed continuous steady-state release of the protease inhibitor darunavir (25mg/dog/day administered for 25 days), thereby achieving plasma concentration levels of approximately 40ng/mL. Steady-state plasma levels were reproducible after monthly refill of the pumps. In conclusion, the implantable adapted Codman 3000 constant-flow infusion pump customized to anti-HIV therapy allows sustained release of anti-HIV medication and may represent an opportunity to reduce the pill burden and complexity of dosing schemes associated with common anti-HIV therapy.


Phenylbutyric acid induces the cellular senescence through an Akt/p21(WAF1) signaling pathway.
It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21(WAF1) induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21(WAF1) pathway by PERK inhibition.


Effect of perezone, aminoperezone and their corresponding isomers isoperezone and isoaminoperezone upon in vitro platelet aggregation.
The effect on platelet aggregation of perezone, isoperezone, aminoperezone and isoaminoperezone has been determined in human platelets, using adenosinediphosphate (ADP), epinephrine and collagen as inducers. Perezone inhibited ADP- epinephrine- and collagen-induced platelet aggregation; isoperezone, aminoperezone and isoaminoperezone did not. The difference in biological responses could be the result of their structures. While isoperezone, aminoperezone and isoaminoperezone have carbonyl groups in the vicinity of other functional groups, this is not the case for perezone, in which one of the carbonyl groups has an adjacent free position.


Degradation of phenol by ball-milled activated carbon (ACBM) activated dual oxidant (persulfate/calcium peroxide) system: Effect of preadsorption and sequential injection.
This study explored pre-adsorption and sequential injection of dual oxidant (DuOx) of persulfate (PS) and calcium peroxide (CP) for phenol degradation in an aqueous solution. Ball-milled activated carbon (ACBM) was used as the catalyst in the following systems: pre-adsorption and sequential injection of PS and CP (ACBM + PS + CP), pre-adsorption and simultaneous injection of PS and CP (ACBM + PS/CP), simultaneous injection of ACBM, PS, and CP (ACBM/PS/CP), simultaneous injection of ACBM and PS (ACBM/PS), and simultaneous injection of ACBM and CP (ACBM/CP). The ACBM had a larger specific surface area, more graphitic structures, and more defects. Moreover, it showed better phenol removal when introduced simultaneously with PS and CP. The phenol removal was most the efficient in ACBM + PS + CP (98.8%) with a near-neutral final pH, followed by ACBM + PS/CP, ACBM/PS, ACBM/PS/CP, and ACBM/CP. This indicates that pre-adsorption and separate injection of PS and CP were the key strategy for improved performance and maintained favorable pH for the activation of PS and CP. The dual oxidant system (PS/CP) is superior to single oxidant systems (PS or CP). Scavenger experiments and the electron spin resonance spectra (ESR) demonstrated that non-radical species (1O2) were dominantly involved in ACBM + PS + CP, but radical species (HO•, SO4•-) also contributed. HCO3- and HPO42- inhibited phenol degradation in ACBM + PS + CP, whereas Cl- and HA had negligible effects. The ACBM + PS + CP showed high total organic carbon removal and ACBM was recyclable with a slight decrease in activity. This work is important as it provides a detailed insight into the strategy of pre-adsorption and sequential injection of dual oxidants for a practical and cost-effective method of groundwater remediation.


Relationship between muscle volume and muscle torque of the hamstrings after anterior cruciate ligament lesion.
This study was conducted to identify factors other than morphological muscle strength factors that affect injured and uninjured sides of knee flexors with anterior cruciate ligament (ACL) lesions. The study population consisted of 22 patients with ACL lesions. Their hamstring muscle volume was measured on MRI, and muscle torque per muscle volume was calculated as the peak torque of knee flexion divided by hamstring muscle volume. The mean muscle torque per unit volume of hamstrings in patients with ACL rupture was 0.09 ± 0.02 Nm/cm(3) at 60°/s and 0.08 ± 0.01 Nm/cm(3) at 180°/s on the injured side, and 0.11 ± 0.02 Nm/cm(3) at 60°/s and 0.08 ± 0.01 Nm/cm(3) at 180°/s on the uninjured side. The mean muscle torque per unit volume of hamstrings in control subjects was 0.11 ± 0.02 Nm/cm(3) at 60°/s and 0.08 ± 0.03 Nm/cm(3) at 180°/s. One-factor ANOVA analysis found no significant differences between the three groups at either flexion velocity. Neurological dysfunction does not appear to exist in knee flexor muscles after ACL injury, unlike the quadriceps. Since the mechanism of muscle weakness will differ depending on the muscle, it is important for clinicians to take this discrepancy into consideration. II.


Changes in tight junctions of rat intestinal crypt cells associated with changes in their mitotic activity.
The freeze-fracture appearance of tight junctions between rat duodenal crypt cells was studied in normal, mitotically suppressed, and mitotically enhanced animals. In normal animals crypt cell tight junctions present a pleomorphic appearance. The population includes junctions resembling postmitotic junctions of the intestinal villus, junctions composed largely or completely of particle chains, and regions at the cell apex in which junctions are absent for 3-4 micron distances laterally. Mitotic suppression by inhibition of DNA synthesis with cytosine arabinoside results in the disappearance of pleomorphism and crypt tight junctions progressively come to resemble those of the intestinal villus. With recovery from the drug and further synchronization with Colcemid, the crypt cells undergo a mitotic burst, and all varieties of unusual junctional configurations are observed with increased frequency.


Identification of HTLV-I sequence in cord blood mononuclear cells of neonates born to HTLV-I antigen/antibody-positive mothers by polymerase chain reaction.
We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV-I) provirus in cord blood mononuclear cells of neonates born to HTLV-I carrier mothers. Out of 40, three subjects were found to contain the HTLV-I provirus genome. These three subjects remained HTLV-I sequence-positive in follow-up study. On the other hand, when examined by a conventional technique for detection of HTLV-I-associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV-I-associated antigen-negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV-I infection in neonates born to HTLV-I carriers.


Cyclooxygenase-2 is over-expressed in Chinese esophageal squamous cell carcinoma, and correlated with NF-kappaB: an immunohistochemical study.
Cyclooxygenase-2 (COX-2), the inducible isoform of the key enzyme in the synthesis of prostaglandins, has been found to be over-expressed in several human cancers. The aim of the present study was to investigate immunohistochemical expression of COX-2 in esophageal squamous cell carcinoma (SCC) and relationship with clinicopathological parameters and NF-kappaB. Expression of COX-2 and NF-kappaB was investigated in 69 cases of esophageal SCC by immunohistochemistry and the correlation of COX-2 expression with clinicopathological features and NF-kappaB staining was examined. Thirty-one esophageal SCC (31/69, 44.9%) had positive expression of COX-2. COX-2 was expressed significantly higher in well-differentiated tumors (16/23, 69.6%) than that in moderate (13/34, 38.2%) and poor (2/12, 16.7%) differentiation (P = 0.034). COX-2 expression was increasingly progressive with the advance of the clinical stages significantly (P = 0.045). The correlation between COX-2 (47/99, 47.5%) and NF-kappaB/p50 (54/99, 54.5%) immunostaining was statistically significant (P = 0.030). COX-2 is over-expressed in esophageal SCC, especially in a well differentiation, correlated with tumor progression, and possibly regulated by NF-kappaB.


Prenatal diagnosis and natural history of the fetus with a congenital diaphragmatic hernia: initial clinical experience.
To study the accuracy of prenatal diagnosis and define the natural history of fetal congenital diaphragmatic hernia (CDH), we reviewed experience with CDH at The University of California, San Francisco (UCSF) over the last three years. All nine babies born in our institution (inborns) and six of 11 babies referred from other hospitals after birth (outborns) died, an overall mortality of 75%. All had pulmonary hypoplasia. Forty percent had associated malformations or chromosomal abnormalities, a higher incidence than generally reported. Prenatal sonograms were available in all nine inborn cases. CDH was correctly diagnosed prospectively in only five, but could be recognized retrospectively in all nine cases using the sonographic criteria developed from the study. Polyhydramnios was present in all nine cases; in seven cases sonography was performed because the woman was large-for-dates clinically. There were no false positive interpretations, and when necessary the diagnosis was confirmed by amniography. All nine cases of CDH detected in utero died. Seven deteriorated so rapidly that surgical repair could not even be attempted. Two who had optimal care (maternal transport, immediate resuscitation and operation) died after repair despite maximal intensive care including vasodilator therapy. Despite the theoretical advantages of maternal transport to pediatric surgical specialty centers, a majority of fetuses with a prenatal diagnosis of CDH will die because their lungs are inadequate to support extra-uterine life even at term.


Dermoscopy for challenging melanoma; how to raise the 'red flag' when melanoma clinically looks benign.
Melanoma may mimic clinically a number of benign skin tumours by exhibiting overlapping features that do not allow accurate differentiation. Dermoscopy is a noninvasive diagnostic tool allowing the evaluation of specific subsurface morphological structures that are useful in most cases to distinguish melanoma from other melanocytic and nonmelanocytic skin tumours. In order to minimize the risk of missing melanoma, the diagnosis should be based on a good correspondence between the clinical and the dermoscopic findings. The case presented here refers to a melanoma clinically simulating dermatofibroma that was biopsied because dermoscopic examination revealed unusual features that did not confirm the clinical diagnosis.


Characterisation of the porcine eyeball as an in-vitro model for dry eye.
To characterise the anatomical parameters of the porcine eye for potentially using it as a laboratory model of dry eye. Anterior chamber depth and angle, corneal curvature, shortest and longest diameter, endothelial cell density, and pachymetry were measured in sixty freshly enucleated porcine eyeballs. Corneal steepest meridian was 7.85±0.32mm, corneal flattest meridian was 8.28±0.32mm, shortest corneal diameter was 12.69±0.58mm, longest corneal diameter was 14.88±0.66mm and central corneal ultrasonic pachymetry was 1009±1μm. Anterior chamber angle was 28.83±4.16°, anterior chamber depth was 1.77±0.27mm, and central corneal thickness measured using OCT was 1248±144μm. Corneal endothelial cell density was 3250±172 cells/mm2. Combining different clinical techniques produced a pool of reproducible data on the porcine eye anatomy, which can be used by researchers to assess the viability of using the porcine eye as an in-vitro/ex-vivo model for dry eye. Due to the similar morphology with the human eye, porcine eyeballs may represent a useful and cost effective model to individually study important key factors in the development of dry eye, such as environmental and mechanical stresses.


DNA-protection and antioxidant properties of fermentates from Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933.
DNA protective and antioxidant activity of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933 were evaluated by Escherichia coli-based Lux biosensors. Two biosensor strains of E. coli, MG1655 (pColD-lux) and MG1655 (pSoxS-lux), which react on DNA damage and superoxide-anion radical activity, were used. SOS-response and Sox-response were stimulated by addition of dioxidine (2,3-Quinoxalinedimethanol,1,4-dioxide) and paraquat (N,N'-dimethyl-4,4'-bipyridinium dichloride) respectively. Preparations of both Bacillus fermentates demonstrated DNA protective and antioxidant (superoxide scavenging) activity (up to 60·19%). The strain К1933 is, in general, characterized by higher DNA protective activity (28·85%), with parameters of antioxidant activity of both bacilli strains being statistically not significantly different. Sporogenous potential probiotic micro-organisms with antioxidant and DNA protective activities can become an effective tool for compensation of various negative oxidative stress processes in humans. In humans, oxidative stress is a cause or an important component of many serious diseases, as well as being one of the age influencing factors. Environmental stresses lead to the increase in levels of reactive oxygen species (ROS). Oxidative DNA damage is a side effect of nonspecific inflammation. These human health challenging factors trigger the search for health-promoting bacteria capable of production of antioxidants and DNA-protectors. In this study, two Bacillus strains of interest were shown to produce noticeable DNA protective and antioxidant activities.


Reasoning in Life: Values and Normativity in Georges Canguilhem.
This paper aims at giving an account of the philosophy of norms of Georges Canguilhem in the framework of his philosophical vitalism. According to Canguilhem, vitalism is not a metaphysical or ontological theory, but rather a general attitude or a perspective about life and living beings, both understood employing the axiological concept of 'normativity'. This notion allows Canguilhem to enlarge the concept of life beyond the field of biological phenomena, encompassing also phenomena of the social world, included technique and scientific knowledge and rationality. Canguilhem's perspective relocates human activities within a vitalistic conception of life, which redefines the meaning of human reason by putting it in relation to values and norms.


Nomenclature for synthetic peptides representative of immunoglobulin chain sequences. WHO-IUIS Nomenclature Sub-Committee.
The source (species of origin), type, and subgroup (where applicable) of the immunoglobulin chain are indicated prior to the numbers of the first and last amino acid residues comprising the synthesized sequence (stated in parentheses), e.g., human gamma 1 (289-298) or rat epsilon (143-147). Square brackets indicate that the peptide is an analogue; substituted amino acids are identified by the three-letter code; superscripted numbers indicating the residue at which the substitution, removal or addition occurs. Further substitutions are specified within round brackets. For example, human gamma 1 (289-298) [D-Thr298] and human gamma 1 (289-298) [Asn (CHO)297].


Offering Psychological Support to University Students in Poland During the COVID-19 Pandemic: Lessons Learned From an Initial Evaluation.
This perspective article aims to present insights into an initiative to provide free psychological support to students at the University of Gdańsk (UG) - one of the first universities in Poland to offer such help - during the first major COVID-19 pandemic lockdown in March 2020. We begin by introducing key psychological consequences of the pandemic, with particular emphasis on university students, according to Pandemic Management Theory (PMT). Next, we highlight the most significant challenges reported to us by the students in response to the support initiative and applied psychological interventions (including psychoeducation, relaxation, arranging day plans, taking care of relationships, and "just" talking). We conclude by reflecting on the challenges for mental health posed by the COVID-19 pandemic as well as the outcome of our initiative - the creation of the Academic Psychological Support Centre at the University of Gdańsk. These insights and lessons learned from developing our practice can help enhance the effectiveness of future psychological support programs through the pandemic and beyond.


Fractional calculus in mathematical oncology.
Even though, nowadays, cancer is one of the leading causes of death, too little is known about the behavior of this disease due to its unpredictability from one patient to another. Classical mathematical models of tumor growth have shaped our understanding of cancer and have broad practical implications for treatment scheduling and dosage. However, improvements are still necessary on these models. The primary objective of the present research is to prove the efficiency of fractional order calculus in mathematical oncology, more specifically in tumor growth modeling. For this, a generalization of the four most used differential equation models in tumor volume measurements fitting is realized, using the corresponding fractional order equivalent. Are established the fractional order Exponential, Logistic, Gompertz, General Bertalanffy-Pütter and Classical Bertalanffy-Pütter models for a treated and untreated dataset. The obtained results are compared by Mean Squared Error (MSE) with the integer order correspondent of each model. The results prove the superiority of the fractional order models. The MSE of fractional order models are reduced at least at half in comparison with the MSE of the integer order equivalent. It is demonstrated in this way that fractional order deterministic models can offer a good starting point in finding a proper mathematical model for tumor evolution prediction. Fractional calculus is a suitable method in this case due to its memory property, aspect that particularly characterizes biological processes.


Recovery and systems transformation for schizophrenia.
The Recovery Movement, initiated in the 1990s by mental health consumer groups and leaders, has emerged as a major force in the mental health field. This movement has been gaining strength and promises to impact mental health service delivery through innovations in care that other models of care have not offered. Recent efforts to conceptualize and study recovery empirically have bolstered the movement from a scientific standpoint. This article reviews the growing literature regarding recovery, offers a conceptual framework for understanding recovery, and discusses a specific manner in which systems transformation has begun to occur.


Oral candidiasis treatment with Brazilian ethanol propolis extract.
The Brazilian commercial ethanol propolis extract, also formulated to ensure physical and chemical stability, was found to inhibit oral candidiasis in 12 denture-bearing patients with prosthesis stomatitis candidiasis association.


Isotype restriction of murine antibodies towards the loop region of hen's egg white lysozyme.
Monoclonal antibodies specific for the loop determinant (residues 64-80) of hen's egg white lysozyme demonstrated an immunoglobulin class restriction. Only IgM response against the loop could be evoked in mice, irrespective of whether the immunogen was the intact native lysozyme as such, or the loop peptide covalently conjugated to a synthetic carrier, poly-DL-alanyl-poly-L-lysine (A-L). Despite the fact that in polyclonal antisera from mice immunized with lysozyme, the ELISA-titre of anti-loop reactivity was very low, 26% of the total anti-lysozyme response could be accounted for by the loop when expressed as the percentage of anti-lysozyme hybridoma colonies producing monoclonal antibodies reactive with the loop. The results can be interpreted either as determinant controlled isotype restriction, or alternatively, as an affinity restriction leading to the phenomenon that antibodies of isotypes other than IgM are formed, but are of too low avidity to be detected by the ELISA method.


Bedside diagnosis of spontaneous bacterial peritonitis using reagent strips.
To determine the efficacy of reagent strip for bedside diagnosis of spontaneous bacterial peritonitis (SBP). Cross-sectional analytical study. Shaikh Zayed Postgraduate Medical Institute from November 2003 to August 2004. Patients with cirrhosis and ascites underwent diagnostic paracentesis. Fluid was checked for leukocyte esterase released by PMN by using Combur 10 urine strip and graded for color change from 0-3. Fluid was also analyzed by cytology for PMN count. Results of both methods were compared to determine sensitivity, specificity and accuracy of strip for diagnosis of SBP. Of 214 paracentesis performed, SBP was diagnosed in 38 patients whereas 176 were negative for infection. Strip test was 97.7% sensitive and 89.4% specific with positive predictive value of 90%, negative predictive value of 97.7% and accuracy of 96.2%, when reagent strip grade 3 was considered as positive for diagnosis. Reagent strip is a quick bedside test, highly sensitive and specific for the diagnosis of SBP, based on polymorphonuclear count in ascitic fluid, to initiate early treatment, thus improving patient's outcome.


[Aspartate aminotransferase and glutamate dehydrogenase activity in the rat brain during infrared laser exposure].
In experiments in vivo it was shown that upon low-intensity infrared irradiation changes in the activity of main enzymes of glutamic acid metabolism are a function of time of exposure and flux density.


Differential display screening for specific gene expression induced by dietary nonsteroidal estrogen.
The dietary phytoestrogen, daidzein, produced a biphasic response in cell proliferation of cultured, estrogen-responsive human breast carcinoma MCF-7 cells. Cell growth was stimulated at a daidzein concentration of 0.25 microg/ml whereas the addition of daidzein at concentrations >25 microg/ml significantly inhibited cell growth in a dose-dependent fashion, resulting in an IC50 value of 50 microg/ml. Upon exposure to 50 microg/ml of daidzein, cell morphology was severely altered, cell volume decreased, and condensation of the chromosomes was clearly noticeable. To identify genes whose expression were inhibited by daidzein, a differential display reverse transcriptase polymerase chain reaction assay (DD-RT-PCR) was performed and the cDNA fragments of several daidzein-regulated genes were visualized. The sequence of one of the cloned cDNA fragments that showed differential mRNA expression level in response to daidzein at a concentration of 50 microg/ml had a high homology with a cDNA expressed in fetal human brain, EST 06411.


Intracochlear drug delivery in combination with cochlear implants : Current aspects.
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., for delivery of glucocorticosteroids, antiapoptotic substances, or neurotrophins to the inner ear. The performance of cochlear implants may thus be improved by protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can also be achieved by use of a biocompatible, resorbable controlled-release drug-delivery system. Two case reports for intracochlear controlled release drug delivery in combination with cochlear implants are presented. In order to treat progressive reduction in speech discrimination and increased impedance, two cochlear implant patients successfully underwent intracochlear placement of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using a computer model. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies.


The effect of TGF-beta on the induction CD8 and NK1.1 expression in CTLL-2 cell line.
The presence of CD8+ T-cells expressing NK cell associated markers (TNK cells) has been observed in several experimental models, which suggests that NK cells may belong to the T-cell lineage. We used the CTLL-2 cell line, which is NK1.1+ CD3- TCR+ CD4- CD8- cells in the presence of IL-2, to investigate whether these cells can be switched to CD8+ or CD4+ cells, like TNK cells, by the TGF-beta. CTLL-2 cells were cultured with TGF-beta or other cytokines and activators in the presence of IL-2. In order to see the surface and intracytoplasmic antigen expression in a single-cell level, simultaneous surface CD4, CD8, TCR with NK1.1, and intracytoplasmic NK1.1 staining was performed and three-color flow cytometric analysis was performed. During routine passage, less than 5% of cells were CD8a+, although 20-40% of cells expressed CD8a when treated with IL-2 + TGF-beta, whereas TPA + Calcium ionophore, IFN-gamma, and TNF-alpha cause no significant changes in the proportion of CD8+ cells. Twenty percent of CTLL-2 cells expressed NK1.1 with IL-2 treatment, and this expression was also increased up to 65%-70% with IL-2 + TNF-beta. Furthermore, most of the CD8 positive cells showed intracytoplasmic NK1.1. Our results indicated that these would be useful models to investigate CD8 precursor potentials in populations of CD4-CD8- (double negative) cells and the relationship of NK1.1. These results also support a role for TGF-beta in T-cell differentiation and the hypothesis that T-cells and NK cells may have the same ontogeny.


Laparoscopy-assisted pancreaticoduodenectomy as minimally invasive surgery for periampullary tumors: a comparison of short-term clinical outcomes of laparoscopy-assisted pancreaticoduodenectomy and open pancreaticoduodenectomy.
Few reports have described laparoscopy-assisted pancreaticoduodenectomy (LAPD) as an alternative to the conventional open approach for periampullary tumors. The safety and feasibility of this procedure remain to be determined. In this study, we compared the short-term clinical outcomes of LAPD with those of open pancreaticoduodenectomy (OPD). A retrospective review of patients who had undergone pancreaticoduodenectomy for periampullary tumors between June and December 2014 was conducted. Patient demographic data and their pathological and short-term clinical parameters were compared between the LAPD and OPD groups. Fifty-two patients were included in the study: 18 had undergone LAPD and 34 had undergone OPD. The mean operation time was longer for LAPD than for OPD (531.1 vs. 383.2 min, P < 0.001). The estimated blood loss, rate of blood transfusion, surgical resection margin status, and number of lymph nodes retrieved were similar in both groups. Overall morbidity and the incidence of pancreatic fistula did not differ significantly between the two groups. However, the mean length of hospital stay was significantly shorter in the LAPD group (12.6 vs. 18.6 days, P = 0.001). LAPD is a technically safe and feasible alternative treatment for periampullary tumors, with short-term clinical outcomes equivalent to those of OPD, with a shorter hospital stay.


Evidence-based and unlicensed indications for proton pump inhibitors and patients' preferences for discontinuation: a pilot study in a sample of Italian community pharmacies.
Despite the widespread use of proton pump inhibitors (PPIs), little is known about the appropriateness of treatment according to the indications reported by patients and their involvement in the process of treatment discontinuation. In patients who are unlikely to benefit, the medication should be stopped and dose tapering is recommended to reduce the risk of rebound symptoms. The aims of this pilot study were to evaluate the appropriateness of treatment according to the reported indications by PPI users, patients' preferences for drug withdrawal, and the modalities of previous attempts to discontinue the medications. This observational study was conducted in nine community pharmacies. Each pharmacist was asked to interview a sample of patients with prescriptions for PPIs and to collect a minimum set of information about socio-demographic characteristics, drug indication, duration of drug treatment, number of drugs used for acid-related disorders, preference about drug withdrawal, previous attempts at drug discontinuation and the method of drug tapering when this was performed. The study included 260 patients, 126 (48·5%) females; 81 patients received more than one drug for acid-related problems and the second medication was more frequently prescribed by a general practitioner, community pharmacist or specialist. Unlicensed indication was reported by 125 patients, and 77 patients did not receive any information about the duration of treatment. Fifty-one patients were in favour of drug discontinuation. PPI withdrawal was attempted but was unsuccessful in 12 cases. Nine patients discussed the method of drug withdrawal with their physician, and abrupt discontinuation was the most frequent suggestion. Many patients were treated with PPIs for unlicensed indications such as gastroprotection because of the number of concomitant drugs used or unspecified gastroprotection. Recommendations about the main indications and the duration of treatment are essential to avoid unnecessary prescriptions and undefined prolongation of drug use. Correct information about the method of drug discontinuation is essential for success. Many patients using PPIs are treated for unlicensed indications such as non-specific gastroprotection. The use of more than one drug for acid-related disorders is frequent among PPI users although this is not supported by evidence. Patients should be given clear and appropriate information about the duration of treatment and method of drug discontinuation.


Cytokine responses in immunized and non-immunized calves after Ostertagia ostertagi infection.
The objective of this study was to evaluate abomasal cytokine responses in helminth-naive calves and calves vaccinated with protective antigen fractions from Ostertagia ostertagi after an experimental challenge infection with infective third stage (L3) larvae. Abomasal lymph nodes and/or abomasal mucosa were collected and messenger RNA for the Th1 cytokines (IFN-gamma, IL-2, IL-12 p40 subunit), the Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IL-15) and the Th3/Tr cytokine TGF-beta was quantified by real-time RT-PCR. Vaccination had no effect on cytokine profiles in either the abomasal lymph nodes or the abomasal mucosa. However, following infection all calves showed a significant decrease in the Th1 cytokines, IFN-gamma and IL-12 p40, and a significant increase in the Th2 cytokines, IL-4, IL-5, IL-10 and IL-13 in the lymph nodes, compared to non-infected calves. No correlation between the Th2 response and protection induced by vaccination could be demonstrated. In contrast, a Th2 pattern was not observed in the mucosa of the infected calves, which exhibited an increase in IFN-gamma as well as in the Th2 cytokines IL-4, IL-5 and IL-10 mRNA. No significant association was observed in the abomasal mucosa between any examined cytokine mRNA level and immune effector responses such as parasite-specific antibodies or the number of mucosal mast cells or eosinophils.


Evidence for the separate molecular expression of four distinct polymorphic Ia epitopes on cells of DR4 homozygous individuals.
The monoclonal antibodies 109d6 and IVD12 reacted with separate polymorphic Ia epitopes in immunofluorescent studies. Using a panel of lymphoblastoid B cell lines, antibody 109d6 reacted with all HLA-DR4 or DR7 positive lines in a pattern resembling the MT3 specificity recognized by human alloantisera. The antibody IVD12 reacted with all HLA-DR4 and two of three DR5 positive B cell lines suggesting that it recognized a specificity similar to MB3. The intensity of fluorescence was greater on DR5(+) cell lines than on DR4(+) cell lines relative to the amount of a nonpolymorphic Ia determinant. Among 45 unrelated control individuals reactivity with antibody 109d6 was correlated most closely with (r = 0.724) but not identical in occurrence to the MT3 specificity. Cocapping experiments demonstrated that the 109d6 epitope and the IVD12 epitope were present on independently redistributed cell surface molecules of DR4 homozygous lymphoblastoid cell lines. Furthermore, the DR4 alloantigens detected by an absorbed polyclonal human alloserum were similarly identified on molecules that were independent from those bearing either the 109d6 epitope or the IVD12 epitope. Taken together, these data indicate the existence of at least four distinct, serologically defined Ia molecular species.


LHRH-immunoreactive structures in the sheep brain.
Neural structures containing luteinizing hormone-releasing hormone (LHRH) are characterized in adult ewe and female lamb brains. Three anti-LHRH antisera are used in an immunofluorescent or immunoperoxidase method. On our preparations, all three gave the same results, expressed as number of labelled cells (about 2500 in a whole brain). It was found that 95% of the LHRH-immunoreactive cells are located in the preoptico-hypothalamic area, where cell bodies are localized mainly (50%) in the area surrounding the organum vasculosum of the lamina terminalis (OVLT); they are also found in a more anterior section of the medial part of the olfactory tubercle and the medial septum (14%), in a more posterior situation in the anterior and lateral hypothalamus (16%), and in the mediobasal hypothalamus (15%). Fibres originating in various part of the whole preoptico-hypothalamic group reach the OVLT and the median eminence. The remaining cells (5%) and fibres are found in various tel-, di-, and mesencephalic areas.


The Complete Genome Sequence of Bacillus thuringiensis Strain ATCC 13367 Features a cry-Containing Chromosome.
We report the high-quality closed genome sequence of Bacillus thuringiensis ATCC 13367, which is used as a bioinsecticide. The genome features a 328-kbp plasmid and a 5.8-Mbp chromosome. The genome is atypical for the species since it lacks a plasmid pesticidal crystal protein (cry) gene and instead features a chromosomal cry gene like that of B. thuringiensis HER1410.


Relationship between the number of remaining teeth and physical activity in community-dwelling elderly.
The relationship between oral health and general health in the elderly has been much studied. However, further studies focussing on the influence of oral health on the quality of life (QOL) among the elderly are required. The goal of this study was to evaluate the relationship between oral health and physical or cultural activities. Subjects were 101 community-dwelling elderly persons who were functionally independent (mean age 70.3). Oral health status was evaluated according to the number of remaining teeth and the number of functional teeth. Physical and cultural activities were evaluated from self-reported information. The relationship between oral health and physical or cultural activities was examined by logistic regression analysis. About 60% of subjects took part in cultural activities, and less than half actively exercised (leisure sports, 33.6%; travel, 42.6%). Persons with 20 or more remaining teeth were more active in leisure sports (Odds ratio (OR)=4.86, 95% confidence interval (CI)=1.34, 17.38) and travel (OR=5.42, 95% CI=1.63, 18.08) than those with fewer than 20 remaining teeth. These results suggest that the number of remaining teeth is associated with physical activity in elderly persons.


Prevalence of right ventricular involvement in inferior wall infarction assessed with myocardial imaging with thallium-201 and technetium-99m pyrophosphate.
To assess the prevalence and clinical relevance of right ventricular involvement in acute inferior wall infarction, 78 consecutive patients with the latter condition were studied with thallium-201 and technethium-99m pyrophosphate myocardial imaging. Right ventricular involvement was determined from superimposition of the 45 degree left anterior oblique thallium-201 and technetium-99m pyrophosphate images. All 78 patients shoed thallium-201 defects. Sixty-four patients had positive pyrophosphate scans, and 24 of these (37.5 percent) showed right ventricular involvement. None of the patients with right ventricular involvement in this consecutive series showed the classic signs of severe right ventricular failure, although subclinicalright ventricular dysfunction may have been present. There was no significant difference in the incidence of cardiogenic shock between the groups with and without right ventricular involvement. It is concluded that right ventricular involvement in acute inferior wall infarction is relatively frequent but not necessarily associated with severe right-sided pump failure. In patients with acute inferior wall infarction and severe pump failure, dual imaging provides a simple nonivasive method of identifying the subgroup of patients with right ventricular involvement who may benefit from volume loading.


Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomised phase II study. The EORTC Lung Cancer Cooperative group.
The EORTC Lung Cancer Cooperative group performed a randomised phase II study in patients with small cell lung cancer comparing the standard cyclophosphamide/doxorubicin/etoposide (CDE) regimen with two regimens containing the new and active cisplatin derivative, carboplatin, 400 mg/m2 in combination with ifosfamide, a drug without important myelotoxicity, at a dose of 5 g/m2 (IMP) or the non-myelotoxic drug vincristine twice 2 mg (VP). Of 178 evaluable patients, 63 received CDE [30 limited disease (LD), 33 extensive disease (ED)], 55 received IMP (22 LD, 33 ED) and 60 (26 LD, 34 ED) were treated with VP. The response duration was not statistically different: CDE 31 weeks, IMP 29 weeks and VP 21 weeks. The time to progression after CEE was 28 weeks, IMP 24 weeks and VP 17 weeks. This was significantly shorter after VP than after CDE (P = 0.017). The 60% response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable, and dose reduction for myelosuppression was necessary in only a minority of the patients. We conclude from this study that the combination of carboplatin, at the maximally tolerated dose of 400 mg/m2, in combination with ifosfamide 5 g/m2, is an active regimen with efficacy comparable with the standard CDE regimen.


Intestinal lymphangiectasia markedly improved with antiplasmin therapy.
A 35-yr-old woman with intestinal lymphangiectasia was treated with trans-4-aminomethyl cyclohexane carboxylic acid. After 6 wk of antiplasmin therapy, her serum total protein increased to normal levels and 131I-polyvinyl pyrrolidone excretion was also normalized. With a daily administration of trans-4-aminomethyl cyclohexane carboxylic acid, the patient has manifested no symptoms for 8 yr up to the present. Throughout the clinical course, the values for euglobulin lysis time showed a close relationship to changes in serum total protein. It was then suggested that increased plasma fibrinolysis may enhance lymphatic permeability to plasma proteins. During this treatment, a decreased percentage of T lymphocytes became normalized together with serum immunoglobulin values. In addition, the therapy has resulted in the disappearance of duodenal lesions observed endoscopically.


Overexpression in E. coli and purification of the L. pneumophila Lpp2981 protein.
The Lpp2981 gene from Legionella pneumophila, the causative agent of Legionnaire's disease, was cloned into the pMWT7 plasmid. The construct was used to express this gene in Escherichia coli. Five different bacterial strains were tested to overexpress the gene but without success. Sequence analysis revealed a cluster of four rare codons near the 5'-end of the gene. These codons were replaced with those commonly used in E. coli. The mutated Lpp2981 gene was successfully expressed in all the E. coli strains tested. The expressed protein (with an apparent molecular mass of 30 kDa) was collected in the insoluble fraction of the cell lysate, purified as inclusion bodies and functionally reconstituted into liposomes. The highest level of overexpression was obtained in E. coli C0214 after 6 h of induction with isopropyl-β-D-thiogalactopyranoside at 37 °C, yielding 74 mg of purified protein per liter of culture. We conclude that the clustering of rare codons at the 5'-end of the open-reading frame is a critical factor for the heterologous expression of Lpp2981 in E. coli.


Impaired responsiveness of paraventricular neurosecretory neurons to osmotic stimulation in rats after local anesthesia of the subfornical organ.
Extracellular recordings were obtained from 32 phasically active neurosecretory cells in the hypothalamic paraventricular nucleus (PVN) of urethane-anesthetized male rats. None of the PVN cells changed their activity to intracarotid infusions of isotonic saline (0.15 M NaCl solution, 0.05 ml). Of these PVN neurons, 26 displayed an increase in neuronal activity following intracarotid infusions of hypertonic saline (0.2 M NaCl solution, 0.05 ml), while the remainder were unresponsive. Microinjection of the local anesthetic lidocaine into the subfornical organ (SFO) reversibly diminished the excitatory response to the infusions of hypertonic saline in 10 out of 15 PVN neurons tested, whereas the injection of lidocaine into the vicinity of the SFO (n = 4) or the third ventricle (n = 4) did not cause a marked change. These results show an involvement of the SFO in the mechanism of osmotic activation of putative vasopressin (AVP)-secreting neurons in the PVN.


Urodynamic evaluation of patients after the Camey operation.
Ten patients were evaluated urodynamically 3 to 18 months after they underwent the Camey operation. Of these patients 2 had total diurnal and nocturnal continence, 1 was totally incontinent and 6 were incontinent to various degrees that necessitated the use of 1 to 3 pads or diapers per day. All but 2 of the Camey neobladders had cystoplasty contractions at a capacity of 50 to 200 ml. The 2 totally continent patients had no cystoplasty contractions. The bladder in the totally incontinent patient had good capacity, good compliance and low pressure contractions up to a volume of 400 ml. The condition in this patient may be attributed to sphincteric incontinence. Urinary flow is achieved by abdominal straining and is interrupted. Vesicoureteral reflux occurred in 3 of 20 renal units.


Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition.
The integrin α9β1 binds a number of extracellular matrix components to mediate cell adhesion, migration and tissue invasion. Although expressed in a variety of normal human cells including endothelium, it is also expressed in cancer cells. We have previously shown that α9β1 binds VEGF-A to facilitate angiogenesis, an important component of the tumor microenvironment. As α9β1 induces accelerated cancer cell migration, we wished to determine what role it played in cancer growth and metastasis. In this study, we show that α9β1 expression induces molecular changes consistent with epithelial-mesenchymal transition. In addition, we found that α9β1 forms a tri-partite protein complex with β-catenin and E-cadherin, which dissociates following integrin activation and subsequent src and β-catenin phosphorylation. These findings were consistent in cells in which: α9β1 was exogenously over-expressed, or when its expression was suppressed in cancer cells endogenously expressing α9β1. These in vitro results are biologically significant as α9β1-expressing cancer cells induce greater tumor growth and metastases in mice as compared to the cells without α9β1 expression or when integrin expression is suppressed. Furthermore, integrin α9β1 is expressed in primary human small cell lung cancer and patients having a high expression of α9β1 demonstrated significantly worse long-term survival compared with patients with low α9β1 expression. These findings highlight a novel mechanism of integrin α9β1 function in human cancer.


A study on the IgE levels of military recruits and association with HLA antigens.
To identify antigen marker(s) on lymphocytes for the immunoregulation of IgE immunoglobulin. For this purpose, IgE determinations were performed on 58 recruits who were arbitrarily selected for HLA typing. Thirty-three recruits with IgE values ranging from 24 to 142 U/ml (71 U/ml (71 U/ml average) showed a slight increase in incidence for HLA-A23, -A33 and BW-15 when compared to a group of 25 recruits whose IgE values ranged from 153 to 2128 U/ml (615 U/ml average). Examination for C-loci specificity indicated that CW-1, CW-3 and CW-4 similar for both groups; however, the "low" IgE group had a frequency of 55.5% of recruits possessing CW-2 antigen compared with only 15% for the "high" group. The value for the "high" IgE appears to be similar to that of the normal population (10% incidence) and only slightly elevated when compared to 7% (2/29) found when the identical CW-2 antisera were tested with laboratory personnel. Thus the associations of HLA-CW2 with the recruits within the "low" IgE group suggests that this HLA marker may be an expression for a suppressed response for IgE immunoglobulin. Viral and bacterial infections, found frequently in these recruits, are discussed as a possible cause of this suppression.


[Determination of several environmental contaminants in human body].
To detect common environmental pollutants in human body. Urine samples were collected from 80 healthy subjects. Chromatography mass spectrometry (GC-MS), HPLC and ELISA were applied to detect several common environmental pollutants in urine samples. DBP and methylbenzene were present in 75.3% and 41.2% of urine samples. The methanal and AFM1 were found in most of urine samples (approximately 91≊97%). By contrast, PCBs, CPZ, 4, 5-DCC were found in less than 5 samples, but there was no TMT detected. Some of the environmental pollutants including carcinogens are detected in urine samples in this study.


Effects of morphine on electrical activity of the rectum in man.
1. The effects of morphine on the electrical activity of the human rectum were investigated. 2. In healthy volunteers, morphine (0.04-0.16 mg/kg, i.v.) induced spike activity that could become cyclical. 3. All the effects of morphine were antagonized by naloxone (0.03-0.2 mg/kg, i.v.), but not blocked by atropine (0.007-0.014 mg/kg, i.v.). 4. In patients with spinal cord injury, morphine was observed to have similar excitatory effects. Spinal cord transection was complete in all patients, so that participation of supraspinal nervous structures in these effects could be ruled out. The sacral parasympathetic nervous centres could not have been involved in two patients in whom the medullary cone was also destroyed. The thoracolumbar sympathetic nervous centres were not completely destroyed in any of the patients, however, so that the possibility that these centres may have been involved cannot be entirely ruled out. 5. Morphine failed to activate an aganglionic rectum in a patient with Hirschsprung's disease, indicating that it had no direct effect on smooth muscle cells. It is therefore probable that morphine may have an effect on the intrinsic innervation.


Multimodal management of urolithiasis in renal transplantation.
To report the largest single series of renal transplant patients (adults and children) with urolithiasis, assess the risk factors associated with urolithiasis in renal transplant recipients, and report the outcome of the multimodal management by endourological and open procedures. The records of all patients undergoing renal transplantation between 1977 and 2003 were reviewed. In all, 2085 patients had a renal transplant at our centre and 21 (17 adults and four children) developed urinary tract calculi. Their mode of presentation, investigations, treatments, complications and outcomes were recorded. Investigations included one or more of the following; ultrasonography (US), plain abdominal X-ray, intravenous urography, nephrostogram and computed tomography. Management of these calculi involved extracorporeal shock wave lithotripsy (ESWL), flexible ureteroscopy and in situ lithotripsy, percutaneous nephrolithotomy (PCNL), open pyelolithotomy and open cystolitholapaxy. Thirteen patients had renal calculi, seven had ureteric calculi and one had bladder calculi. The incidence of urolithiasis was 21/2085 (1.01%) in the series. Urolithiasis was incidentally discovered on routine US in six patients, six presented with oliguria or anuria, including one with acute renal failure, four with a painful graft, three with haematuria, one with sepsis secondary to obstruction and infection and in one, urolithiasis was found after failure to remove a stent. Ten patients (63%) had an identifiable metabolic cause for urolithiasis, two by obstruction, two stent-related, one secondary to infection and in six no cause was identifiable. Thirteen required more than one treatment method; 13 (69%) were treated by ESWL, eight of whom required multiple sessions; eight required ureteric stent insertion before a second procedure and four required a nephrostomy tube to relieve obstruction. Two patients had flexible ureteroscopy and stone extraction, three had a PCNL and one had open cystolithotomy. PCNL failed in one patient who subsequently had successful open pyelolithotomy. All patients were rendered stone-free when different treatments were combined. The incidence of urolithiasis in renal transplant patients is low. There is a high incidence of metabolic causes and therefore renal transplant patients with urolithiasis should undergo comprehensive metabolic screening. Management of these patients requires a multidisciplinary approach by renal physicians, transplant surgeons and urologists.


Arterial switch for transposition with left outflow tract obstruction: outcomes and risk analysis.
The long-term results and indications of the arterial switch operation (ASO) for transposition of the great arteries (TGA) and anatomic left ventricular outflow tract obstruction (LVOTO) remain undetermined. The aims of this study were to determine long-term outcomes and prognostic factors in this specific population. Between 1986 and 2011, 55 patients with TGA and anatomic LVOTO underwent ASO. Anatomic LVOTO was defined as an echocardiographic peak LVOT gradient exceeding 20 mm Hg associated with an anatomic narrowing. Forty-three patients had a ventricular septal defect. Median follow-up was 7.9 ± 6.5 years (maximum, 25 years). Univariate and multivariate risk analyses for late LVOTO, aortic regurgitation, LVOT reintervention, and death were performed. The early mortality rate was 11% (n = 6); 2 deaths were LVOTO-related. At the latest follow-up, 3 patients (5%) had a LVOTO, 7 (13%) had moderate aortic regurgitation, and 4 (7%) had LVOT reoperation. Actuarial freedom from LVOT reoperation was 90% ± 5% at 10 and 15 years. The mean LVOT peak gradient was 3 ± 9 mm Hg at the latest follow-up. A preoperative pulmonary valve z-score of less than -1.7 (odds ratio, 19; p = 0.02) and an atrioventricular valve-related LVOTO (odds ratio, 15; p = 0.02) are independent predictors of recurrent LVOTO. A preoperative pulmonary valve z-score of less than -1.8 is an independent predictor of LVOT reoperation (odds ratio, 17; p = 0.03). The LVOT gradient per se and the presence of ventricular septal defect or a bicuspid valve do not influence outcomes. Long-term outcomes of ASO for patients with TGA and anatomic LVOTO are satisfactory in selected patients. A lower preoperative pulmonary valve z-score and complex multilevel atrioventricular valve-related LVOTO are independent predictors of recurrent LVOTO and LVOT reoperation. TGA/LVOTO patients with pulmonary valve z-score exceeding -1.8 and resectable valvular or subvalvular LVOTO, or both, should be candidates for ASO, regardless of the severity of the LVOT peak gradient.


Survivin expression in intracranial ependymomas and its correlation with tumor cell proliferation and patient outcome.
Survivin expression has been described as prognostic factor in various tumor types and has been shown to correlate with cytologic anaplasia in ependymoma. We immunohistochemically studied survivin expression and its association with Ki-67 and topoisomerase IIalpha (TIIalpha) expression and outcome in 63 patients with intracranial ependymoma. Survivin is expressed in a fraction of nuclei of tumor and endothelial cells including mitotic figures. Survivin indices range from 0.6% to 43.2% and correlate with Ki-67 and TIIalpha indices. On average, 62.86% of Ki-67-expressing tumor cell nuclei coexpress survivin, whereas 92.2% of survivin-expressing nuclei coexpress Ki-67. High survivin, Ki-67, and TIIalpha indices univariately correlated with an unfavorable outcome. In multivariate analysis, only the Ki-67 index remained an independent prognostic factor. In ependymoma, survivin is expressed in a subset of proliferating cells. High survivin expression is associated with poor patient outcome. However, the Ki-67 index is a more accurate prognostic marker than the survivin or TIIalpha index.


Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California.
We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk.


Octreotide for treatment of chylothorax after repair of congenital diaphragmatic hernia.
Chylothorax is a recognized cause of morbidity after repair of congenital diaphragmatic hernia (CDH). Management may include prolonged hospitalization with cessation of enteral feedings, repeated aspiration, chest tube drainage, total parenteral nutrition, and introduction of a medium chain triglyceride (MCT) diet as the effusion resolves. The authors report that the successful deployment of octreotide, a somatostatin analogue, hastened resolution of a postoperative chylothorax in a newborn infant with CDH.


Diagnostic impact of 18F-FDG PET-CT evaluating solid pancreatic lesions versus endosonography, endoscopic retrograde cholangio-pancreatography with intraductal ultrasonography and abdominal ultrasound.
This prospective single-centre phase II trial assessed the diagnostic impact of (18)F-FDG PET-CT in the evaluation of solid pancreatic lesions (phi >or= 10 mm) compared to endosonography (EUS), endoscopic retrograde cholangio-pancreatography (ERCP) with intraductal ultrasound (IDUS), abdominal ultrasound (US) and histopathological reference. Forty-six patients (32 men/14 women, phi 61.7 years) with suspected pancreatic neoplasms underwent PET-CT with contrast-enhanced biphasic multi-detector CT of the upper abdomen followed by a diagnostic work-up with EUS, ERCP with IDUS and US within 3 weeks. PET-CT data sets were analysed by two expert readers in a consensus reading. Histology from surgery, biopsy/fine-needle aspiration and/or clinical follow-up >or=12 months served as standard of reference. Twenty-seven pancreatic malignancies were histopathologically proven; 19 patients had benign diseases: 36/46 lesions (78%) were detected in the head of the pancreas, 7/46 and 3/46 in the body and tail region, respectively. Sensitivity and specificity of PET-CT were 89% and 74%, respectively; positive predictive value (PPV) and negative predictive value (NPV) were 83% and 82%, respectively. Sensitivity (81-89%), specificity (74-88%), PPV (83-90%) and NPV (77-82%) achieved by EUS, ERCP and US were not significantly different. PET analysis revealed significantly higher maximum mean standardised uptake values (SUV(max) 6.5+/-4.6) in patients with pancreatic malignancy (benign lesions: SUV(max) 4.2+/-1.5; p<0.05). PET-CT revealed cervical lymphonodal metastasis from occult bronchogenic carcinoma and a tubular colon adenoma with intermediate dysplasia on polypectomy, respectively. (18)F-FDG PET-CT achieves a comparably high diagnostic impact evaluating small solid pancreatic lesions versus conventional reference imaging modalities. Additional clinical diagnoses are derived from concomitant whole-body PET-CT imaging.


The role of Chlamydia trachomatis in Bartholin's gland abscess.
Chlamydia trachomatis is becoming increasingly known for its ability to cause severe injury to the female genital tract. Little investigation has been done in its role in diseases of Bartholin's glands. We present what we believe to be the first case report of an abscess of a Bartholin's gland in which Chlamydia trachomatis was a major pathogen. This communication also review the literature concerning the microbiology of Bartholin's gland abscess.


Blindly using Wald's test can miss rare disease-causal variants in case-control association studies.
There are four tests--the likelihood ratio (LR) test, Wald's test, the score test and the exact test--commonly employed in genetic association studies. On comparison of the four tests, we found that Wald's test, popular in genome-wide screens due to its low computational demands, exhibited a paradoxical behaviour in that the test statistic decreased as the effect size of the variant increased, resulting in a loss of power. The LR test always achieved the most significant P-values, followed by the exact test. We further examined the results in a real data set composed of high- and low-cholesterol subjects from the Dallas Heart Study (DHS). We also compared the single-variant LR test with two multi-variant analysis approaches--the burden test and the C-alpha test--in analysing the sequencing data by simulation. Our results call for caution in using Wald's test in genome-wide case-control association studies and suggest that the LR test is a better alternative in spite of its computational demands.


Population pharmacokinetic and pharmacodynamic modeling of epinephrine administered using a mobile inhaler.
Inhaled epinephrine is a potential alternative to self-administered intramuscular epinephrine in imminent anaphylactic reactions. The objective was to develop a pharmacokinetic-pharmacodynamic model describing exposure and effects on heart rate of inhaled epinephrine. Data from a 4-phase cross-over clinical trial in 9 healthy volunteers including 0.3 mg intramuscular epinephrine, two doses of inhaled epinephrine (4 mg/mL solution administered during [mean] 18 and 25 min, respectively) using a mobile pocket inhaler, and an inhaled placebo were analyzed using mixed-effects modeling. Inhaled epinephrine was available almost immediately and more rapidly than via the intramuscular route (absorption half-live 29 min). Epinephrine plasma concentrations declined rapidly after terminating inhalation (elimination half-life 4.1 min) offering the option to stop exposure in case of adverse events. While the expected maximum concentration was higher for inhaled epinephrine, this was not associated with safety concerns due to only moderate additional hemodynamic effects compared to intramuscular administration. Bioavailability after inhalation (4.7%) was subject to high interindividual and interoccasional variability highlighting that training of inhalation would be essential for patients. The proposed model suggests that the use of a highly concentrated epinephrine solution via inhalation may offer an effective treatment option in anaphylaxis, while efficacy in patients remains to be shown.


Effect analysis of repeat sternotomy in pediatric cardiac operations.
Reoperation for congenital heart disease may be associated with cardiac or vascular injuries during repeat sternotomy, resulting in increased mortality and/or morbidity rates. The aim of this study was to determine the frequency of these cardiac injuries and the associated outcome. Between January 2012 and December 2013, 4256 sternotomy procedures were performed at the Pediatric Cardiac Center in Fuwai Hospital, including 195 repeat sternotomy procedures (RS). We retrospectively studied the clinical data of 195 RS patients and 250 randomly selected primary sternotomy (PS) patients. Demographic and operative details, major injures (MI), and clinical outcomes were compared between the two groups. We also assessed the risk factors for major injury and in-hospital mortality and morbidity. Significant differences were observed between the RS and PS groups in terms of skin incision to cardiopulmonary bypass(CPB) time, overall CPB time, cross-clamp time and blood requirement, and ventilation time (p < 0.001). MI during RS occurred in 7 of the 195 patients (3.6 %), while operative mortality was 1.0 % (2/195). However, in the RS patients, mortality and morbidity rates were not significantly different between the MI subgroup and the non-MI subgroup (p = 1.000 and 0.556, respectively). Additionally, no significant difference was found between the RS and PS groups in terms of mortality (p = 1.000) and morbidity (p = 0.125). Both RS and MI are not associated with increased risk of operative mortality and morbidity. Outcomes for reoperative pediatric operations in contemporary practice are similar with those for primary operations.


[Rare lesion of the median nerve caused by elbow dislocation with avulsion of the epicondylus humeri medialis in childhood].
A case of posterior dislocation of the elbow complicated by intraarticular entrapment of the median nerve is reported. Sixteen cases have previously been described in the literature. The mechanism of the injury is discussed. Early exploration of the nerve is advised when signs of median nerve deficit persist following reduction of the dislocated elbow.


Interventional cardiology in adults with congenital heart disease.
Interventional cardiac catheterization has become an integral component of the management of adults with congenital heart disease. The origins of this approach come from the paediatric interventional experience, although techniques and indications for interventional cardiac catheterization in adults are now being developed for use in the burgeoning field of adult congenital heart disease. Progress in the application and acceptance of interventional cardiac catheterization in this setting has been swift, and the pace is quickening. This Review provides a broad overview of some of the most common procedures used in the treatment of adults with congenital heart lesions, with an emphasis on new tools that have revolutionized the field. Specifically, we discuss interventions that can be broadly classified into the following groups: techniques for closing shunt lesions, valvular interventions, methods for achieving patency of vascular obstructions, and selected additional interventions applicable to some complex lesions. We emphasize the need for a thorough understanding of the anatomy of the lesion, its natural or unnatural history, and indications for intervention before the procedure takes place. Such procedures must be performed in centres where the operators are knowledgeable of the lesions being addressed, with full surgical, anaesthetic, nursing and imaging support.


Zidovudine phosphorylation after short-term and long-term therapy with zidovudine in patients infected with the human immunodeficiency virus.
Resistance of human immunodeficiency virus (HIV) to zidovudine (AZT) has been associated with mutations in the viral reverse transcriptase gene. However, recent studies suggest that host cellular factors such as a decreased thymidine kinase activity or an increased cellular P-glycoprotein expression may be important. This study compared concentrations of zidovudine monophosphate, zidovudine diphosphate, and zidovudine triphosphate with P-glycoprotein expression in peripheral blood mononuclear cells from patients receiving long-term (> 18 months) and short-term (< 2 months) zidovudine treatment. Ten subjects in the short-term group and 11 subjects in the long-term group with CD4 counts between 300 and 500 received a single oral dose of zidovudine (200 mg) after a 24-hour washout period. Blood samples were collected at 0, 1, 2, 4, and 6 hours. Intracellular nucleotide concentrations were measured by a combined HPLC-radioimmunoassay method, and P-glycoprotein expression was determined by fluorescence activated cell sorting (FACS) analysis with use of the monoclonal mouse antibody MRK-16. Zidovudine monophosphate was the predominant compound, accounting for 73.4% +/- 7.1% (SD) of the total phosphates in the long-term treatment group and 74.2% +/- 15.0% (SD) in the short-term group. Zidovudine diphosphate accounted for 13.3% +/- 3.3% (SD) in the long-term group and 12.5% +/- 6.6% (SD) in the short-term group. Zidovudine triphosphate accounted for 13.4% +/- 4.1% (SD) in the long-term group and 13.5% +/- 8.3% (SD) in the short-term group. Mean peak concentrations for the active zidovudine triphosphate were 0.04 +/- 0.02 (SD) pmol/10(6) cells in both groups. Comparison of the individual zidovudine phosphate concentrations and P-glycoprotein expression revealed no significant difference in the two patient populations. These data suggest that intracellular phosphorylation does not change over time and that zidovudine does not select for P-glycoprotein expressing cells.


Sequence analysis of bovine lens aldose reductase.
The covalent structure of bovine lens aldose reductase (alditol-NADP+ oxidoreductase, EC 184.108.40.206) was determined by sequence analysis of peptides generated by specific and chemical cleavage of the homogeneous apoenzyme. Peptides, purified by reverse-phase high performance liquid chromatography were subjected to compositional analysis and sequencing by gas-phase automated Edman degradation. Aldose reductase was found to contain 315 amino acid residues. The enzyme is blocked at the amino terminus, and mass spectrometry was employed to identify the blocking acetyl group and to sequence the amino-terminal tryptic peptide. The aldose reductase was shown to contain no carbohydrate despite the fact that the enzyme contains the consensus sequence -Asn-Lys-Thr- for N-linked glycosylation. Comparative sequence analysis and application of algorithms for prediction of secondary structure and nucleotide binding domains are consistent with the view that aldose reductase is a double-domain protein with a beta-alpha-beta secondary structural organization. The NADPH binding site appears to be associated with the amino-terminal half of the enzyme. Modeling studies based on the tertiary structures of dihydrofolate and glutathione reductases indicate that the NADPH binding site begins at Lys-11 and continues with a beta-alpha-beta fold characteristic of nucleotide binding proteins.


Lysine demethylase KDM3A regulates nanophotonic hyperthermia resistance generated by 2D silicene in breast cancer.
Breast cancer (BC) is the most common malignant disease affecting women's health worldwide. The benefits from conventional therapeutic modalities are severely limited. An increasing number of promising photothermal materials have been recently developed and introduced into the therapeutic regimens of BC, but the underlying biological mechanism remains unclear. Silicon-based materials have enjoyed many popularities in the biomedical field owing to their desirable biocompatibility, biodegradability and versatility. Herein, we introduced two dimensional (2D) silicene nanosheets (SNSs) into the BC treatment and achieved profound photothermal-ablation efficacy. Importantly, this work reveals the underlying biological mechanism and regulation factors of photonic hyperthermia in BC. The RNA sequencing and immunoblot demonstrated that photothermia enhanced apoptosis in BC by activating caspase 3 and caspase 7. Importantly, knockdown of lysine demethylase KDM3A sensitized BC to photothermia epigenetically. It has been revealed that KDM3A could erase p53K372me1 and suppress the anti-cancer functions of p53, leading to the downregulation of pro-apoptotic proteins-PUMA and NOXA verified by Co-IP and ChIP-qPCR assays. Therefore, our results not only import near infrared light (NIR) induced photothermal ablation generated by SNSs-BSA into the BC treatment, but also clarify the underlying mechanism and regulation factors for further photothermal performance optimization and clinical translation.


Predictors of long-term success and failure in primary and revision endoscopic dacryocystorhinostomy.
Although endoscopic dacryocystorhinostomy (endo-DCR) is a common treatment of nasolacrimal duct obstruction, little is known about the determinants of surgical success and failure. The purpose of this study was to identify patient- and technique-specific factors that may influence surgical outcomes of primary and revision endo-DCR. A retrospective review was conducted of 596 patients who underwent endo-DCR over a 30-year period (1989-2018). Patients' demographics and surgical techniques were assessed. Among the cohort of patients (n = 478) who underwent primary endo-DCR, 10% (n = 48) required revision surgery. Patients who failed primary DCR tended to be younger (p = 0.015) and were less likely to have chronic sinonasal inflammation on histopathology (p = 0.047) than the successful surgery group. After adjusting for patient demographics and comorbidities, the occurrence of a postoperative complication was significantly associated with primary DCR failure (odds ratio [OR], 2.2; p = 0.032). Among the cohort of patients (n = 118) who underwent revision endo-DCR, 8.5% (n = 10) required additional revision surgery. Patients who failed revision DCR tended to be younger (p = 0.022), more likely to have had intraoperative laser usage (p = 0.031), and more likely to have had an intraoperative complication (p = 0.013) than the successful revision surgery group. Endo-DCR failure was not associated with smoking status, middle turbinate resection, or intraoperative visualization of the internal common punctum (p > 0.05). An understanding of factors associated with primary and revision endo-DCR failure can help to inform preoperative counseling, intraoperative surgical technique, and postoperative care in the treatment of patients with nasolacrimal duct obstruction.


Nutritional status of Kadazan children in a rural district in Sabah, Malaysia.
The nutritional status of 896 Kadazan children below 6 years of age from 23 villages of Tambunan District were studied. When stunting and wasting were defined as those who were below two standard deviations of height-for-age and weight-for-height (Waterlow et al, 1977) and based on the National Center for Health Statistics reference population, 67.6% of boys and 66.8% of girls were stunted while 12.3% of boys and 8.3% of girls were wasted. Weaning foods and toddler feeding practices were unsatisfactory. The role of health education on child care and feeding practices is emphasized.


[The influence of experimental traffic noise on autonomous functions of normotensives and hypertensives after stress (author's transl)].
In a series of experiments on 12 normotensives and 12 essential hypertensives the influence of traffic noise (81 dB) on autonomous functions after stress exposure was examined. The process of the stress reaction was started by visually presented arithmetic tasks under affecting noise. With normotensives and hypertensives this combination of stressors led to a significant increase of the systolic and diastolic blood pressure, heart rate, and muscle tone. The influence of traffic noise directly following the combination of stressors was examined in an intraindividual comparison with a resting-time period. During the period of noise, significantly higher values with blood pressure data only were found with normotensives and hypertensives as well. The comparison between the normotensive and the hypertensive group during the combination of stressors and during the following resting period showed no significant differences in reaction whereas during the second stressor hypertensives compared to normotensives showed strong, partly significant adaptation reactions of blood pressure with regard to the preceding experimental phase.


Cyclic GMP and cyclic AMP levels in median eminence, hypothalamus and pituitary gland of the rat after decapitation or microwave irradiation.
Cyclic AMP and cyclic GMP content of the median eminence (ME), medial basal hypothalamus (MBH), posterior pituitary (PP) and anterior pituitary (AP) of inact male rats was measured by radioimmunoassay following decapitation or exposure to microwave irradiation (MW). Levels of both nucleotides in MW irradiated animals were higher in all three nervous tissues studied than in the AP. Following decapitation cyclic AMP levels increased strikingly in the MBH and ME, slightly in the AP, but remained unchanged in the PP. Cyclic GMP levels increased more markedly in the ME than in the MBH, slightly in the PP and did not change in the AP. The distinct synthesizing capability of the cyclic AMP and cyclic GMP generating systems in the ME, a region rich in neurohormones known to control anterior pituitary function, raises the possibility that these nucleotides are involved in the process of neurohormone secretion by the ME.


Atomic-level structural responsiveness to environmental conditions from 3D electron diffraction.
Electron microscopy has been widely used in the structural analysis of proteins, pharmaceutical products, and various functional materials in the past decades. However, one fact is often overlooked that the crystal structure might be sensitive to external environments and response manners, which will bring uncertainty to the structure determination and structure-property correlation. Here, we report the atomic-level ab initio structure determinations of microcrystals by combining 3D electron diffraction (3D ED) and environmental transmission electron microscope (TEM). Environmental conditions, including cryo, heating, gas and liquid, have been successfully achieved using in situ holders to reveal the simuli-responsive structures of crystals. Remarkable structural changes have been directly resolved by 3D ED in one flexible metal-organic framework, MIL-53, owing to the response of framework to pressures, temperatures, guest molecules, etc.


Impact of ambulatory physiotherapy on motor abilities of elderly subjects with Alzheimer's disease.
We investigated the impact of ambulatory physiotherapy (AP) on motor abilities in elderly subjects with Alzheimer's disease (AD). Subjects with mild to moderate AD were included and divided into "physiotherapy group" (PG) and "no physiotherapy group" (NPG) according to whether or not they received AP between inclusion (T0) and the second time of assessment, between 15 and 36 months after inclusion (T1). The follow-up duration, Mini-Mental State Examination, Tinetti and mini motor test (MMT) scores, Timed Up & Go test (TUG), gait speed (GS), one-leg balance (OLB), history of falls within the last 6 months (HF), ability to rise from the floor (RFF) and the use of a walking aid (UWA) were recorded at T0, and after at least 15 months of follow up (T1). A total of 50 subjects were included in the NPG and 20 in the PG. At baseline, these groups were not significantly different for all the parameters recorded. The anova showed a progression of cognitive disorders in the two groups between T0 and T1 (P < 0.001), which was similar in the two groups (P = 0.83). For each postural and motor quantitative test (Tinetti, MMT, TUG, GS) the anova showed a main effect of time of assessment (All P < 0.05) associated with a group × time of assessment interaction (All P < 0.05). The comparison between the two groups with regard to the evolution of qualitative parameters showed a significant difference for the OLB test only. No significant difference was found for RFF, HF and UWA. There was a significant improvement or stability of motor abilities in the PG; while these abilities decreased in the NPG.


Fusion of enveloped virus nanoparticles with polyelectrolyte-supported lipid membranes for the design of bio/nonbio interfaces.
Fusion of lipid-enveloped viruses with endosomal membranes triggered by low pH in the endosome is a key step in the course of viral infection. This ubiquitous mechanism can be used to integrate functional nanoparticles of viral origin into composite materials consisting of a polyelectrolyte multilayer with an adsorbed lipid membrane in a natural and biomimetic way. Polyelectrolyte multilayers as the support for the lipid membrane are a versatile means to combine the biological functions of the viral surface with the multiplicity of polyelectrolyte borne functions into a novel bio/nonbio composite material.


Sinus of Valsalva dilates disproportionately in aortic root aneurysm with moderate to severe aortic regurgitation: quantitative assessment by transesophageal echocardiography.
Geometric change of the aortic valve and root in patients with aortic root aneurysm has not been well investigated. The aim of this study was to quantitatively assess the characteristics of aortic valve and root morphology in patients with aortic root aneurysm. Ten aortic root aneurysm patients (eight males, group A) with moderate to severe aortic regurgitation and ten controls with normal aortic valves (seven males, group N) were examined by transesophageal echocardiography. We measured the diameter of the aortic annulus, sinus of Valsalva, sinotubular junction (STJ) and ascending aorta, and the length of the valve coaptation and annulus to the leaflet tip. We also measured the cusp projection area, STJ arc length, leaflet tip-Valsalva wall diameter and inter-commissural diameter in each Valsalva sinus/cusp [left coronary cusp (LCC), right coronary cusp (RCC), non-coronary cusp (NCC)]. The diameters of the sinus of Valsalva (P = 0.003), STJ (P = 0.005) and ascending aorta (P = 0.008) were more significantly enlarged in group A than in group N, and the valve coaptation length was significantly shorter in group A than in group N (3.1 ± 1.1 vs. 4.9 ± 1.1 mm/m(2), P = 0.007). Moreover, the annulus to leaflet tip length was significantly longer in group A than in group N (P = 0.049). There was no significant difference in the size of the LCC, RCC and NCC in group N, although there was disproportion in the size of those cusps in group A, with the largest being in RCCs. In patients with aortic root aneurysm, Valsalva sinuses disproportionately dilate with different size, causing the loss of coaptation.


In vitro evaluation of neuraminidase inhibitors using the neuraminidase-dependent release assay of hemagglutinin-pseudotyped viruses.
For the treatment of influenza virus infections, neuraminidase inhibitors (NAIs) that prevent the release of virus particles have been effective against most influenza strains. Several neuraminidase (NA) assays are available for the evaluation of NAIs. To understand the NAI functions under physiological conditions, assays mimicking viral particle release should be useful. We have constructed retrovirus-based reporter viruses that are pseudotyped with hemagglutinin (HA) glycoprotein by transfection of producer cells using plasmids expressing retroviral gag-pol, influenza HA, NA, and firefly luciferase genes. Similarly to the life cycle of influenza viruses, the release of pseudotype viruses also requires neuraminidase functions. This requirement was used to develop an assay to evaluate NAI activities by measuring inhibition of pseudotype virus production at different NAI concentrations. The pseudotype virus release assay was used to determine the IC(50) values of Oseltamivir carboxylate, Zanamivir, and the novel phosphonate congeners of Oseltamivir against N1 group neuraminidases and their H274Y Oseltamivir carboxylate-resistant mutants. The deduced IC(50) values obtained using the release assay correlated with those determined using the fluorogenic substrate 2'-(4-methylumbelliferyl)-alpha-d-N-acetylneuraminic acid (MUNANA) and also correlated with the infectivity results.


Multichannel recording of median nerve somatosensory evoked potentials.
Clinical applications of multichannel (>or=64 electrodes) electroencephalography (EEG) have been limited so far. Amplitude variability of evoked potentials in healthy subjects is large, which limits their diagnostic applicability. This amplitude variability may be partially due to spatial undersampling of anatomical variations in cortical generators. In the present study, we therefore investigated whether 128-channel recordings of somatosensory evoked potentials (SEPs) can reduce this amplitude variability in healthy subjects. Additionally, we explored the relation between amplitude and age. We recorded median nerve SEPs using a 128-channel EEG system in 50 healthy subjects (20-70 years) and compared N20, P27, and P45 amplitude as obtained with a 128-channel analysis method - based on butterfly plots and spatial topographies - and as obtained using a conventional one-cortical-channel configuration and analysis. Scalp and earlobe references were compared. Although amplitude variability itself was not reduced, a reduced coefficient of variation was obtained with the 128-channel method due to higher SEP amplitudes, compared to the conventional one-channel method, independent of reference. These results suggest that at the cost of some additional preparation time, the 128-channel method can measure SEP amplitude more accurately and might therefore be more sensitive to physiological and pathological changes. For optimal amplitude estimation, we recommend to increase the number of centroparietal electrodes or, preferably, to perform at least a 64-channel recording.


Peak of neuromuscular activation and angle where it occurs during bench press exercise performed with different repetition number and duration in resistance trained individuals.
The present study compared neuromuscular activation, measured by surface electromyography (EMG) amplitude [measure by EMG peak (EMGPEAK)] and range of motion (ROM) where EMGPEAK occurred between two training protocols, matched by time under tension, but with a different number and duration of repetitions. Sixteen recreationally trained males performed 2 training protocols with 3 sets, 180 s of rest with 60% of one-repetition maximum(1RM) on the bench press performed in a Smith machine. Protocol A consisted of 6 repetitions with a repetition duration of 6 s and protocol B consisted of 12 repetitions with a repetition duration of 3 s. EMG activity of anterior deltoid, pectoralis major and triceps brachii muscles were recorded. The results showed a general higher EMG amplitude (regardless of the muscle) in protocol B (p = 0.010), and pectoral and triceps brachii consistently presented higher neuromuscular activation than anterior deltoid at both protocols (p = 0.007). Additionally, the ROM where EMGPEAK occurred in triceps brachii was in the middle of the concentric action (~50% of ROM), this occurred in the first half of the same action (~24% of ROM) in the other muscles. In conclusion, protocol B demonstrated an increased EMG amplitude over protocol A, although both protocols responded similarly by achieving the highest EMG amplitude at same ROM among the muscles analysed.


Fast-spiking interneurons and gamma oscillations may be involved in the antidepressant effects of ketamine.
Accumulating lines of evidence have indicated that a non-selective N-methyl-d-aspartate (NMDA) receptor antagonist ketamine exerts fast and robust antidepressant effects via stimulating glutamate transmission and activating the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Moreover, NMDA receptor antagonist has the ability to reduce the activity of fast-spiking (FS) interneurons which results in the disinhibition of pyramidal neurons and increases the glutamate transmission. We therefore hypothesize that FS interneurons may play an important role in the antidepressant effects of ketamine. Quantification of FS interneurons function via analyzing gamma oscillations may guide the antidepressant therapy of ketamine in clinical practice.


α-Cyperone, isolated from the rhizomes of Cyperus rotundus, inhibits LPS-induced COX-2 expression and PGE2 production through the negative regulation of NFκB signalling in RAW 264.7 cells.
The rhizomes of Cyperus rotundus (Cyperaceae) have been used in Asian traditional medicine for the treatment of several inflammatory diseases. However, the anti-inflammatory effects of α-cyperone, a major active compound of Cyperus rotundus, are poorly understood. PGE2 and cytokines released from cells were measured using an EIA assay kit. The expression of iNOS, COX-2, TNF-α, and IL-6 was measured by real-time RT-PCR and/or Western blot analysis. A luciferase assay was performed to measure the effect of α-cyperone on NFκB activity. The n-hexane fraction of the 80% EtOH extract from the rhizomes of Cyperus rotundus was found to inhibit both NO and PGE2 production in RAW 264.7 cells. α-Cyperone isolated from the n-hexane fraction significantly inhibited PGE2 production by suppressing the LPS-induced expression of inducible COX-2 at both the mRNA and the protein levels. In contrast, α-cyperone had little effect on NO production and iNOS expression. Additionally, α-cyperone downregulated the production and mRNA expression of the inflammatory cytokine IL-6. Moreover, treatment with α-cyperone suppressed the transcriptional activity of NFκB and the nuclear translocation of the p65 NFκB subunit in LPS-induced RAW 264.7 cells. The anti-inflammatory activity of α-cyperone is associated with the down-regulation of COX-2 and IL-6 via the negative regulation of the NFκB pathway in LPS-stimulated RAW 264.7 cells.