Principal neuronal organization in the frog optic tectum revealed by a current source density analysis.
In the frog optic tectum, the spatiotemporal pattern of neuronal activity evoked by electrical stimulation of the optic tract was examined by means of a current source density (CSD) analysis. The CSD depth profile was highly reproducible in different experiments. In all seven CSD profiles, three current sinks A, B, and D were observed in the retinorecipient layers. Four out of the seven profiles show additional two sinks C and E below the retinorecipient layers. Very small and short lasting sinks related to afferent fiber activities precede sinks A and B by about 1 ms, which could be accounted for by monosynaptic delay, in the corresponding depth region. The earliest prominent sink A at the bottom of the retinorecipient layers reflects only excitatory monosynaptic activities derived from R3 and/or R4 retinal ganglion cells. The second prominent sink B in the superficial retinorecipient layer is composed partly of excitatory monosynaptic activity from medium-sized myelinated optic fibers. It may involve excitatory monosynaptic activity from unmyelinated optic fibers and further polysynaptic activity. The fourth prominent sink D in the intermediate retinorecipient layer partially reflects excitatory monosynaptic activity derived from unmyelinated optic fibers. It may also involve further polysynaptic activity. In contrast with these three sinks, the third prominent sink C and fifth sink E exclusively reflect intratectal polysynaptic activity that has not been reported in any previous CSD studies in the frog optic tectum. These sinks almost overlap spatially in the tectal layer. We also measured the intratectal resistance changes and computed inhomogeneous CSD depth profiles to show that the results from homogeneous CSD computation assuming constant conductivity are valid for our present study. Finally, we compared the present results with previously reported CSD studies on the frog optic tectum and discuss consistencies and discrepancies among these experiments.


A GABA/benzodiazepine receptor complex from bovine brain: purification, reconstitution and immunological characterization.
A GABA/benzodiazepine receptor complex was purified from bovine cerebral cortex. The receptor fraction displayed binding sites for benzodiazepines as well as high and low affinity binding sites for GABA which are characteristics of the membrane-bound receptor. Two monoclonal antibodies of which one was directed against the 50 kd and the other against the 55 kd subunit were used for immunoprecipitation studies. Both of them were shown to quantitatively precipitate the entire receptor population. These results indicate that the binding sites for benzodiazepines and GABA (high and low affinity sites) reside on the same receptor complex containing a mixture of 50 kd and 55 kd subunits. Reconstitution of the receptor in phospholipid vesicles was achieved.


Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials.
Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds.


[Technical advances in the surgical management of thoracoabdominal aortic aneurysms].
Thoracoabdominal aortic aneurysmectomy ranks among the major cardiovascular surgical procedures. During the last two decades perioperative results have improved to the point that surgery should be discussed in the vast majority of patients seen with a thoracoabdominal aortic aneurysm. This progress is largely attributable to a variety of technical improvements including: aortic reconstruction using the graft inclusion technique, usually with direct reattachment of aortic branches to the prosthetic graft; distal aortic perfusion; selective use of deep hypothermic circulatory arrest in anatomically complex situations; preoperative visualization of arterial blood supply to the spinal cord using selective arteriography of intercostal and lumbar arteries. Current perioperative mortality is around 10% whereas the spinal cord complication rate is between 5% and 20% according to clinical and anatomical conditions. Future efforts should concentrate on the prevention of spinal cord complications.


Semi-integrative Voltammetry as an Efficient Tool To Study Simple Electrochemical Systems in Deep Eutectic Solvents.
The utilization of deep eutectic solvents (DESs) in electrochemical studies has grown in recent years due to their low cost and environmental friendliness compared to traditional ionic liquids. However, the determination of diffusion coefficient (D) and heterogeneous constant rate (k0) using the traditional electrochemical approach may mask some concerns because of the high viscosity and limited conductivity in these media. In this work, it is shown that the determinations of D and k0 in glyceline DES by voltammetric studies using the Nicholson approach is problematic. Furthermore, the semi-integrative approach is evaluated which reveals that it is an efficient tool to determine such parameters that have a significant influence of the electrolyte viscosity and conductivity. The D values are 2.8 × 10-8 and 4.2 × 10-8 cm2 s-1 for Nicholson and semi-integrative approaches, respectively, using 0.05 M FeCl3 in glyceline at 30 °C, which indicates an underestimation of D by employing the Nicholson equations. Also, k0 is obtained using Saveant's methodology which cannot be obtained by the typical evaluation of ΔEp (Nicholson's approach) when ΔEp > 200 mV as it occurs in the case of concentrations ≥ 0.25 M FeCl3, depending on the potential scan rate.


Prognostic value of circulating tumor cells in esophageal cancer.
To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.


Brain protection therapy in acute cerebral infarction.
Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core.


Preoperative treatment of benign insulinoma: diazoxide or somatostatin analogues?
Surgery is the ideal treatment of insulinoma. However, systemic therapy may be required to prevent severe preoperative hypoglycaemia, when surgery is contraindicated, delayed or refused and in case of unresectable metastatic disease. Diazoxide is commonly used but is not always effective and can cause serious side effects. Somatostatin analogues (octreotide and lanreotide) may be an alternative option. We report the case of a 27-year-old patient with insulinoma in whom diazoxide was compared with lanreotide before operation. A diagnosis of insulinoma was made on the basis of a fasting test and a 2 cm tumour confirmed in the body of the pancreas, with a high uptake of 111-In-pentreotide. Diazoxide was initiated and increased to a maximal tolerated dose of 450 mg/day. Because of dyspnoea and persisting hypoglycaemia, diazoxide was shifted to lanreotide 120 mg. All symptoms resolved without hypoglycaemia. According to the EORTC quality score of life, the score without treatment, under diazoxide, under lanreotide and after surgery were respectively 84.7, 73.3, 90.9 and 99.1. Thus, providing a positive Octreoscan, somatostatin analogues may be a safe, effective and well-tolerated option in patients with insulinoma refractory and/or intolerant to diazoxide or with a high risk of fluid retention.


Orthopaedic manifestations of arthrogryposis-renal dysfunction-cholestasis syndrome.
Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome (MIM♯208085) is a rare multisystem disorder, which involves the kidney, liver, skin, and central nervous and musculoskeletal systems. It is inherited as an autosomal-recessive trait, associated with germ-line mutations in the VPS33B gene. In this study, the authors reviewed the orthopaedic manifestations of ARC syndrome. Ten patients diagnosed as having ARC syndrome were the subjects of this study. ARC syndrome was confirmed by mutation analysis in 8 of the 10 patients. Medical records and radiographs were retrospectively reviewed with a focus on musculoskeletal manifestations. Seven patients either expired at 4 to 19 months of age or were presumed to have expired. The remaining 3 patients remained alive at the time of writing this manuscript and were aged from 7 to 23 months. All patients showed musculoskeletal symptoms and/or signs, which included vertical talus (7 feet, 4 patients), pes calcaneovalgus (4 feet, 3 patients), hip dislocation (6 hips, 3 patients), pathologic fractures (5 fractures in 5 patients), and rigid kyphosis (2 patients). No surgical intervention was performed. Orthopaedic treatments, other than fracture management, were abandoned soon after diagnoses were made. ARC syndrome should be included in the differential diagnosis of arthrogryposis. As there is no specific effective treatment for renal dysfunction and cholestasis, orthopaedic intervention should be postponed until long-term survival is expected, though this is unlikely. Level IV, diagnostic studies, case series.


Superconductivity above 100 K in single-layer FeSe films on doped SrTiO3.
Recent experiments on FeSe films grown on SrTiO3 (STO) suggest that interface effects can be used as a means to reach superconducting critical temperatures (Tc) of up to 80 K (ref. ). This is nearly ten times the Tc of bulk FeSe and higher than the record value of 56 K for known bulk Fe-based superconductors. Together with recent studies of superconductivity at oxide heterostructure interfaces, these results rekindle the long-standing idea that electron pairing at interfaces between two different materials can be tailored to achieve high-temperature superconductivity. Subsequent angle-resolved photoemission spectroscopy measurements of the FeSe/STO system revealed an electronic structure distinct from bulk FeSe (refs , ), with an energy gap vanishing at around 65 K. However, ex situ electrical transport measurements have so far detected zero resistance-the key experimental signature of superconductivity-only below 30 K. Here, we report the observation of superconductivity with Tc above 100 K in the FeSe/STO system by means of in situ four-point probe electrical transport measurements. This finding confirms FeSe/STO as an ideal material for studying high-Tc superconductivity.


Different cytokine profiles in patients with chronic and acute reactive arthritis.
Analysis of cytokine production in patients with acute and chronic reactive arthritis (AcReA/ChrReA) in order to search for new treatment possibilities. Cytokine production by peripheral blood and synovial fluid mononuclear cells (PBMCs/SFMCs) of 28 patients with AcReA, 27 patients with ChrReA, 26 patients with rheumatoid arthritis (RA) and 31 healthy controls was analysed by enzyme-linked immunosorbent assay (ELISA) and flow-cytometry. Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-10 was measured by ELISA, while the percentages of TNF-alpha-, IFN-gamma- and IL-4-positive CD3+ cells were determined in the same groups of patients and healthy subjects using flow cytometry. Spontaneous TNF-alpha production observed in PBMCs of ChrReA, but not of AcReA, patients was significantly higher (P<0.001) than in healthy controls. The percentages of TNF-alpha-positive CD3+ blood cells in ChrReA exceeded that of RA patients and healthy controls (P<0.05 and P<0.001, respectively). Also, the percentages of IFN-gamma-positive CD3+ cells were significantly higher in peripheral blood and synovial fluid of ChrReA patients (P<0.05 and P<0.05, respectively) as compared with AcReA. In ChrReA spontaneous IL-10 production in PBMCs was similar to that observed in healthy controls, while in RA and AcReA the production of IL-10 was significantly increased (P<0.05 and P<0.05, respectively). IL-4 production was low in all study groups with no significant differences detected. High production of TNF-alpha and IFN-gamma detected in ChrReA supports the possible use of anti-TNF-alpha treatment in ChrReA.


Contextual variation in the acoustic and perceptual similarity of North German and American English vowels.
Strange et al. [J. Acoust. Soc. Am. 115, 1791-1807 (2004)] reported that North German (NG) front-rounded vowels in hVp syllables were acoustically intermediate between front and back American English (AE) vowels. However, AE listeners perceptually assimilated them as poor exemplars of back AE vowels. In this study, speaker- and context-independent cross-language discriminant analyses of NG and AE vowels produced in CVC syllables (C=labial, alveolar, velar stops) in sentences showed that NG front-rounded vowels fell within AE back-vowel distributions, due to the "fronting" of AE back vowels in alveolar/velar contexts. NG [I, e, epsilon, inverted c] were located relatively "higher" in acoustic vowel space than their AE counterparts and varied in cross-language similarity across consonantal contexts. In a perceptual assimilation task, naive listeners classified NG vowels in terms of native AE categories and rated their goodness on a 7-point scale (very foreign to very English sounding). Both front- and back-rounded NG vowels were perceptually assimilated overwhelmingly to back AE categories and judged equally good exemplars. Perceptual assimilation patterns did not vary with context, and were not always predictable from acoustic similarity. These findings suggest that listeners adopt a context-independent strategy when judging the cross-language similarity of vowels produced and presented in continuous speech contexts.


MicroRNA profiling analysis throughout tomato fruit development and ripening reveals potential regulatory role of RIN on microRNAs accumulation.
The development and ripening of tomato fruit are complex processes involving many gene regulatory pathways at the transcriptional and post-transcriptional level. Ripening inhibitor (RIN) is a vital transcription factor, which targets numerous ripening-related genes at the transcriptional level during tomato fruit ripening. MicroRNAs (miRNAs) are a class of short noncoding RNAs that play important roles in post-transcriptional gene regulation. To elucidate the potential regulatory relationship between rin and miRNAs during fruit development and ripening, we identified known miRNAs and profiled their expression in wild-type tomato and rin mutant using a deep sequencing approach combined with quantitative RT-PCR. A total of 33 known miRNA families were identified, of which 14 miRNA families were differently accumulated. Subsequent promoter analysis showed that possible RIN-binding motifs (CArG-box) tended to occur frequently in the promoter regions of partial differently expressed miRNAs. In addition, ethylene may participate in the regulation of miRNAs accumulation during tomato fruit ripening. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay confirmed the direct binding of RIN to the promoter of MIR172a. Collectively, these results showed a close correlation between miRNA expression and RIN as well as ethylene, which further elucidated the regulatory roles of miRNAs during fruit development and ripening and enriched the regulatory network of RIN in tomato fruit.


Review of the bamboo-feeding genus Agrica Strand (Hemiptera: Cicadellidae: Deltocephalinae), with description of two new species from China.
The bamboo-feeding leafhopper genus Agrica Strand (Cicadellidae: Deltocephalinae) is reviewed. Two new species, A. bisubula sp. nov. and A. longispina sp. nov. from China (Guizhou), are described and illustrated. The male genitalia of A. arisana (Matsumura, 1914) are described for the first time. A key is provided to distinguish known species of the genus.


Sources of anomalous diffusion on cell membranes: a Monte Carlo study.
A stochastic random walk model of protein molecule diffusion on a cell membrane was used to investigate the fundamental causes of anomalous diffusion in two-dimensional biological media. Three different interactions were considered: collisions with fixed obstacles, picket fence posts, and capture by, or exclusion from, lipid rafts. If motion is impeded by randomly placed, fixed obstacles, we find that diffusion can be highly anomalous, in agreement with previous studies. In contrast, collision with picket fence posts has a negligible effect on the anomalous exponent at realistic picket fence parameters. The effects of lipid rafts are more complex. If proteins partition into lipid rafts there is a small to moderate effect on the anomalous exponent, whereas if proteins are excluded from rafts there is a large effect on the anomalous exponent. In combination, these mechanisms can explain the level of anomaly in experimentally observed membrane diffusion, suggesting that anomalous diffusion is caused by multiple mechanisms whose effects are approximately additive. Finally, we show that the long-range diffusion rate, D(macro), estimated from fluorescence recovery after photobleaching studies, can be much smaller than D(micro), the small-scale diffusion rate, and is highly sensitive to obstacle densities and other impeding structures.


Aberrant RNA Splicing Is a Primary Link between Genetic Variation and Pancreatic Cancer Risk.
Understanding the genetic variation underlying transcript splicing is essential for fully dissecting the molecular mechanisms of common diseases. The available evidence from splicing quantitative trait locus (sQTL) studies using pancreatic ductal adenocarcinoma (PDAC) tissues have been limited to small sample sizes. Here we present a genome-wide sQTL analysis to identify SNP that control mRNA splicing in 176 PDAC samples from TCGA. From this analysis, 16,175 sQTLs were found to be significantly enriched in RNA-binding protein (RBP) binding sites and chromatin regulatory elements and overlapped with known loci from PDAC genome-wide association studies (GWAS). sQTLs and expression quantitative trait loci (eQTL) showed mostly nonoverlapping patterns, suggesting sQTLs provide additional insights into the etiology of disease. Target genes affected by sQTLs were closely related to cancer signaling pathways, high mutational burden, immune infiltration, and pharmaceutical targets, which will be helpful for clinical applications. Integration of a large-scale population consisting of 2,782 patients with PDAC and 7,983 healthy controls identified an sQTL variant rs1785932-T allele that promotes alternative splicing of ELP2 exon 6 and leads to a lower level of the ELP2 full-length isoform (ELP2_V1) and a higher level of a truncated ELP2 isoform (ELP2_V2), resulting in decreased risk of PDAC [OR = 0.83; 95% confidence interval (CI), 0.77-0.89; P = 1.16 × 10-6]. The ELP2_V2 isoform functioned as a potential tumor suppressor gene, inhibiting PDAC cell proliferation by exhibiting stronger binding affinity to JAK1/STAT3 than ELP2_V1 and subsequently blocking the pathologic activation of the phosphorylated STAT3 (pSTAT3) pathway. Collectively, these findings provide an informative sQTL resource and insights into the regulatory mechanisms linking splicing variants to PDAC risk. In pancreatic cancer, splicing quantitative trait loci analysis identifies a rs1785932 variant that contributes to decreased risk of disease by influencing ELP2 mRNA splicing and blocking the STAT3 oncogenic pathway.


Ehrlichia chaffeensis proliferation begins with NtrY/NtrX and PutA/GlnA upregulation and CtrA degradation induced by proline and glutamine uptake.
How the obligatory intracellular bacterium Ehrlichia chaffeensis begins to replicate upon entry into human monocytes is poorly understood. Here, we examined the potential role of amino acids in initiating intracellular replication. PutA converts proline to glutamate, and GlnA converts glutamate to glutamine. E. chaffeensis PutA and GlnA complemented Escherichia coli putA and glnA mutants. Methionine sulfoximine, a glutamine synthetase inhibitor, inhibited E. chaffeensis GlnA activity and E. chaffeensis infection of human cells. Incubation of E. chaffeensis with human cells rapidly induced putA and glnA expression that peaked at 24 h postincubation. E. chaffeensis took up proline and glutamine but not glutamate. Pretreatment of E. chaffeensis with a proline transporter inhibitor (protamine), a glutamine transporter inhibitor (histidine), or proline analogs inhibited E. chaffeensis infection, whereas pretreatment with proline or glutamine enhanced infection and upregulated putA and glnA faster than no treatment or glutamate pretreatment. The temporal response of putA and glnA expression was similar to that of NtrY and NtrX, a two-component system, and electrophoretic mobility shift assays showed specific binding of recombinant E. chaffeensis NtrX (rNtrX) to the promoter regions of E. chaffeensis putA and glnA. Furthermore, rNtrX transactivated E. chaffeensis putA and glnA promoter-lacZ fusions in E. coli. Growth-promoting activities of proline and glutamine were also accompanied by rapid degradation of the DNA-binding protein CtrA. Our results suggest that proline and glutamine uptake regulates putA and glnA expression through NtrY/NtrX and facilitates degradation of CtrA to initiate a new cycle of E. chaffeensis growth. Human monocytic ehrlichiosis (HME) is one of the most prevalent, life-threatening emerging infectious zoonoses in the United States. HME is caused by infection with E. chaffeensis, an obligatory intracellular bacterium in the order Rickettsiales, which includes several category B/C pathogens, such as those causing Rocky Mountain spotted fever and epidemic typhus. The limited understanding of the mechanisms that control bacterial growth within eukaryotic cells continues to impede the identification of new therapeutic targets against rickettsial diseases. Extracellular rickettsia cannot replicate, but rickettsial replication ensues upon entry into eukaryotic host cells. Our findings will provide insights into a novel mechanism of the two-component system that regulates E. chaffeensis growth initiation in human monocytes. The result is also important because little is known about the NtrY/NtrX two-component system in any bacteria, let alone obligatory intracellular bacteria. Our findings will advance the field's current conceptual paradigm on regulation of obligatory intracellular nutrition, metabolism, and growth.


[Cholestasis in adults. 2. Clinical signs and symptomatic treatment].
Cholestasis, a frequent occurrence in clinical practice, can be suspected when confronted to clinical signs (pruritus and jaundice) and/or increased blood level of alkaline phosphatases, gammaglutamyl transpeptidase and/or conjugated bilirubin. This short review will deal with the management of clinical manifestations and extrahepatic complications, whatever the cause of cholestasis. The management according to etiology will be dealt with in a separated chapter.


Cystic diseases of the kidney: molecular biology and genetics.
Cystic diseases of the kidney are a very heterogeneous group of renal inherited conditions, with more than 33 genes involved and encompassing X-linked, autosomal dominant, and autosomal recessive inheritance. Although mostly monogenic with mendelian inheritance, there are clearly examples of oligogenic inheritance, such as 3 mutations in 2 genes, while the existence of genetic modifiers is perhaps the norm, based on the extent of variable expressivity and the broad spectrum of symptoms. To present in the form of a mini review the major known cystic diseases of the kidney for which genes have been mapped or cloned and characterized, with some information on their cellular and molecular biology and genetics, and to pay special attention to commenting on the issues of molecular diagnostics, in view of the genetic and allelic heterogeneity. Data Sources.-We used major reviews that make excellent detailed presentation of the various diseases, as well as original publications. There is already extensive genetic heterogeneity in the group of cystic diseases of the kidney; however, there are still many more genes awaiting to be discovered that are implicated or mutated in these diseases. In addition, the synergism and interaction among this repertoire of gene products is largely unknown, while a common unifying aspect is the expression of nearly all of them at the primary cilium or the basal body. A major interplay of functions is anticipated, while mutations in all converge in the unifying phenotype of cyst formation.


Protective role of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in human lymphocytes in vitro.
Antioxidants and plant products are reported to reduce the genotoxic damage of steroids. In our present study we have tested different dosages of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in the presence of S9 mix. Treatments with nordihydroguaiaretic acid (NDGA) results in the reduction of the genotoxic damage. A significant decrease was observed at all the tested doses of NDGA in sister chromatic exchanges of number of abnormal cells. The results suggest a protective role of NDGA against the genotoxic damage.


Association of microRNA biogenesis pathway gene variants and alcohol dependence risk.
Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 (χ(2) = 9.066, p = 0.003; odds ratio [OR] = 0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 (χ(2) = 4.111, p = 0.043; OR = 0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 (χ(2) = 5.291, p = 0.021; OR = 1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 (χ(2) = 11.139, p = 0.001) and DGCR8 rs1640299 (χ(2) = 13.001, p = 0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future.


A randomised trial to compare 200 mg micronised progesterone effervescent vaginal tablet daily with 250 mg intramuscular 17 alpha hydroxy progesterone caproate weekly for prevention of recurrent preterm birth.
For prevention of a recurrent preterm birth (PTB), intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC) weekly is recommended. Vaginal progesterone is preferred for women at risk for PTB due to a short cervical length, but may be useful in women with a prior PTB. However, there is no consensus about the optimal vaginal formulation or its efficacy as compared to 17 OHPC to prevent recurrent PTB. We randomised 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous PTB, of a singleton (>16 to <37 weeks of gestation) to receive the 200 mg vaginal progesterone effervescent tablet daily (Group A) or IM 17-OHPC, 250 mg weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate of <37 weeks was similar (20% in Group A and 20.8% in Group B, p = .918). The PTB rate of <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar in the two groups. Two neonates in Group A and four neonates in Group B required NICU admission, one of whom (Group B) died due to prematurity. Twenty percent of women in Group A and 29.2% in Group B reported adverse effects from their respective study medications (p = .408, NS). Thus, there did not appear to be a difference between vaginal progesterone and 17-OHPC when used for the prevention of a recurrent PTB. Impact statement What is already known on this subject? Progesterone administration is useful for prevention of a recurrent preterm birth (PTB) and these women are prescribed the intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC), 250 mg, weekly. Some studies found that vaginal progesterone (once daily) is also beneficial in these women, but there is no consensus regarding its efficacy when compared to 17 OHPC, or its optimal formulation and dose. What do the results of this study add? In the present study, 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous singleton PTB or mid-trimester abortion were randomised to receive 200 mg of vaginal progesterone effervescent tablet daily (Group A) or 250 mg IM 17-OHPC weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate <37 weeks was similar in the two groups (20% in Group A and 20.8% in Group B, p = .918). The PTB rate <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar. Twenty percent of women in Group A and 29.2% of women in Group B reported adverse effects from their respective study medications (p = .408, NS). Thus, there did not appear to be a difference between the vaginal progesterone effervescent tablet and 17-OHPC when used for the prevention of a recurrent PTB. What are the implications of these findings for clinical practice and/or further research? The vaginal progesterone effervescent tablet may be a suitable alternative to IM 17 OHPC to prevent recurrent PTB. Future studies should identify the most appropriate route (IM or vaginal) and vaginal progesterone formulation for PTB prevention in women at risk for a recurrent PTB and in women with a short cervical length.


Diastereoselective aminooxygenation and diamination of alkenes with amidines by hypervalent iodine(III) reagents.
Diastereoselective anti-aminooxygenation and anti-diamination of alkenes with amidines were enabled by hypervalent iodine(III) reagents such as PhI(OCOR)2 and PhI(NMs2)2, respectively. The present transformation offers diastereochemically pure dihydroimidazoles divergently from E- and Z-alkenes.


Electronic structure of the sulfonyl and phosphonyl groups: a computational and crystallographic study.
A computational and X-ray crystallographic investigation of the electronic and geometric structures of a range of sulfonyl (-SO(2)-) and phosphonyl (-PO(2)--) containing species was undertaken to investigate the nature of valency and bonding in these functional groups. The traditional representation of sulfonyl and phosphonyl species is with octet-violating Lewis structures, which require d-orbital participation at the central atom. However, computational studies cast serious doubt upon this bonding model. In this work, we have employed NBO/NRT analysis to investigate hybridization, atomic formal charges, donor-acceptor interactions, and resonance structure contributions. Our results predict that within sulfonyl and phosphonyl systems, bonding interactions are highly polarized, of the form X+-Y- (X = P, S), and possess additional contributions from reciprocal n --> sigma* interactions where substituents off sulfur or phosphorus simultaneously act as donors and acceptors. Experimental evidence for the proposed bonding arrangement is provided for the sulfonyl functional group through a series of low-temperature X-ray structure correlations for sulfate monoesters, sulfamates, and methanesulfonates. Examination of changes to bond lengths and geometries upon substituent variation support the computational results. Together, our studies lend support for a bonding network in sulfonyl and phosphonyl groups composed of polar interactions augmented with reciprocal hyperconjugative bonding, which does not necessitate significant d-orbital participation nor formal octet violation at the central sulfur or phosphorus.


Mouth width prediction in craniofacial identification: cadaver tests of four recent methods, including two techniques for edentulous skulls.
An understanding of the structural relationships between the soft tissue anatomy of the face and the hard tissue anatomy of the skull is significant for craniofacial identification methods employed in forensic anthropology and forensic dentistry. Typically, mouth characteristics have been predicted from the teeth but this proves problematic in edentulous skulls. Some clue may, however, be provided by non-dental features. This study investigates the usefulness of the infraorbital and the mental foramen position for determining mouth width and additionally reports on accuracy tests using two other recently proposed methods that depend on the teeth: i) Krogman and İşcan's radiating mouth width prediction guideline; and ii) Stephan and Henneberg's 75% rule. Dissections of nine human cadavers indicate that the most accurate mouth width prediction method is the 75% rule (mean error of -2.4 mm) followed by the distance between the infraorbital foramen (mean error of -3.3 mm). Krogman and İşcan's radiating method, as interpreted by Wilkinson, underestimated mouth width by 7.3mm on average, while the distance between the mental foramen underestimated mouth width by 12.9 mm. These results suggest that the infraorbital foramen can be used as a relatively good predictor of mouth width in edentulous skulls, however, the 75% rule should be given precedence if the dentition is present.


[Study of Determination of Oil Mixture Components Content Based on Quasi-Monte Carlo Method].
Gasoline, kerosene, diesel is processed by crude oil with different distillation range. The boiling range of gasoline is 35 ~205 °C. The boiling range of kerosene is 140~250 °C. And the boiling range of diesel is 180~370 °C. At the same time, the carbon chain length of differentmineral oil is different. The carbon chain-length of gasoline is within the scope of C7 to C11. The carbon chain length of kerosene is within the scope of C12 to C15. And the carbon chain length of diesel is within the scope of C15 to C18. The recognition and quantitative measurement of three kinds of mineral oil is based on different fluorescence spectrum formed in their different carbon number distribution characteristics. Mineral oil pollution occurs frequently, so monitoring mineral oil content in the ocean is very important. A new method of components content determination of spectra overlapping mineral oil mixture is proposed, with calculation of characteristic peak power integrationof three-dimensional fluorescence spectrum by using Quasi-Monte Carlo Method, combined with optimal algorithm solving optimum number of characteristic peak and range of integral region, solving nonlinear equations by using BFGS(a rank to two update method named after its inventor surname first letter, Boyden, Fletcher, Goldfarb and Shanno) method. Peak power accumulation of determined points in selected area is sensitive to small changes of fluorescence spectral line, so the measurement of small changes of component content is sensitive. At the same time, compared with the single point measurement, measurement sensitivity is improved by the decrease influence of random error due to the selection of points. Three-dimensional fluorescence spectra and fluorescence contour spectra of single mineral oil and the mixture are measured by taking kerosene, diesel and gasoline as research objects, with a single mineral oil regarded whole, not considered each mineral oil components. Six characteristic peaks are selected for characteristic peak power integration to determine components content of mineral oil mixture of gasoline, kerosene and diesel by optimal algorithm. Compared with single point measurement of peak method and mean method, measurement sensitivity is improved about 50 times. The implementation of high precision measurement of mixture components content of gasoline, kerosene and diesel provides a practical algorithm for components content direct determination of spectra overlapping mixture without chemical separation.


Centre of mass movement and mechanical energy fluctuation during gallop locomotion in the Thoroughbred racehorse.
During locomotion cyclical interchange between different forms of mechanical energy enhances economy; however, 100% efficiency cannot be achieved and ultimately some mechanical work must be performed de novo. There is a metabolic cost associated with fluctuations in mechanical energy, even in the most efficient animals. In this study we investigate the exchanges between different forms of mechanical energy involved in high-speed gallop locomotion in Thoroughbred race horses during over-ground locomotion using innovative, mobile data collection techniques. We use hoof-mounted accelerometers to capture foot contact times, a GPS data logger to monitor speed and an inertial sensor mounted over the dorsal spinous processes of the fourth to sixth thoracic vertebrae (the withers) of the horse to capture trunk movement with six degrees of freedom. Trunk movement data were used to estimate the movement of the centre of mass (CoM). Linear (craniocaudal, mediolateral and dorsoventral) and rotational (roll, pitch and heading) kinematic parameters (displacement, velocity and acceleration) were calculated for seven horses at gallop speeds ranging from 7 to 17 m s(-1) during their regular training sessions. These were used to estimate external mechanical energy (potential energy and linear kinetic energy of the CoM) as well as selected components of internal energy (angular kinetic energy). Elastic energy storage in the limbs was estimated from duty factor, sine wave assumptions and published leg stiffness values. External mechanical energy changes were dominated by changes in craniocaudal velocity. Potential energy change, which was in phase with craniocaudal energy during the front limb stances, was small. Elastic energy storage in the limbs was small compared to the overall amplitude of fluctuation of external mechanical energy. Galloping at high speeds does not therefore fit classical spring mass mechanics.


Decentralized clinical trial design using blood microsampling technology for serum bioanalysis.
Background: Alternatives to phlebotomy in clinical trials increase options for patients and clinicians by simplifying and increasing accessibility to clinical trials. The authors investigated the technical and logistical considerations of one technology compared with phlebotomy. Methodology: Paired samples were collected from 16 donors via a second-generation serum gel microsampling device and conventional phlebotomy. Microsamples were subject to alternative sample handling conditions and were evaluated for quality, clinical testing and proteome profiling. Results: Timely centrifugation of blood serum microsamples largely preserved analyte stability. Conclusion: Centrifugation timing of serum microsamples impacts the quality of specific clinical chemistry and protein biomarkers. Microsampling devices with remote centrifugation and refrigerated shipping can decrease patient burden, expand clinical trial populations and aid clinical decisions.


Nocardia asteroides as a cause of pneumonia in a buffalo calf.
Pulmonary nocardiosis has been described in a four-month-old male buffalo calf (Bubalus bubalis) with a history of respiratory distress lasting ten days. Microscopic examination of tissue imprints from the infected lungs revealed numerous Gram-positive, acid-fast, fine, branched, filamentous organisms which were morphologically identical with those of Nocardia spp. Cultures of pneumonic lung specimens on plain Sabouraud medium yielded pure growth of Nocardia asteroides at 37 degrees C. Lungs from ten healthy buffalo gave negative results for bacteria, suggesting that N. asteroides does not occur as a commensal in the pulmonary tissues. Epidemiological investigation established the source of infection in the immediate environment of the animal. It is emphasised that N. asteroides may be considered to be a respiratory pathogen and should be included in differential diagnosis of pulmonary diseases.


Effect of the SinR protein on the expression of the Bacillus subtilis 168 lytABC operon.
Transcription of the lytABC operon was determined by extension of primers on RNAs isolated from strains bearing a deficient sinR gene. A SinR null mutant, in which part of the sinR gene was deleted, exhibits a pattern identical to that characteristic of FlaB (SigD) deficient mutants, i.e., loss of the signal corresponding to the SigD-dependent promoter, but not of that recognized by the SigA form of the RNA polymerase. However, strains bearing either flaD1 or flaD2, two different point mutations of gene sinR, were characterized by a complete loss of signals corresponding to both promoters. Thus, modified FlaD1 and FlaD2 proteins behave like a repressor affecting the expression of lytABC more severely than does the absence of SinR, The most obvious interpretation of this observation is a direct interaction between the SinR protein and the promoters recognized by the SigD form of the RNA polymerase.


Thirty Years of Experience at the First Tunisian Kidney Transplant Center.
The aim of this study was to report the results of 30 years of experience at the first kidney transplant center in Tunisia. All kidney transplants performed at the center between June 1986 and June 2016 were included. The study period was divided into 3 decades. Recipient and donor data and follow-up information were obtained from a local database and patient medical records. Comparative analyses were performed using the t test for continuous variables and the Χ² test for qualitative variables. Patient and graft survival rates were calculated according to the actuarial method, and comparison of survival curves was performed according to the logrank test. The mean age of recipients was 32.7 ± 11.5 years (range, 6-65 y) with a gender ratio of 2.2. Duration of prekidney transplant dialysis varied from 2 months to 20 years (median, 27.5 mo); 1.7% of patients underwent transplant preemptively. Kidneys were recovered from deceased donors in 21.2% of cases and from living donors in 78.8%. The proportion of deceased donors dropped from 27.4% during the period 2006-2010 to 12.9% during the period 2011-2015 (P < .04). Patient survival rates at 1, 5, 10, 15, and 20 years were 96%, 89.3%, 79.5%, 71.1%, and 65.4%. Graft survival rates were 95%, 86.5%, 76.2%, 66.3%, and 57.2%. The annual graft loss was 2.9%, with a mortality rate of 2.4% and without significant differences between patients receiving deceased-donor and living-donor organs. Kidney transplant activity remains suboptimal in our country. The reduction in deceased-donor organs could be related to the political transformations facing our country with their resulting social and economic consequences. Efforts should be made to increase governmental resources and to improve both public awareness of organ donation and the motivation of transplant teams.


Cerebral hyperperfusion syndrome after revascularization surgery in patients with moyamoya disease.
Moyamoya disease (MMD) is a progressive occlusive disease of the distal internal carotid artery that is primarily treated by superficial temporal artery-middle cerebral artery (STA-MCA) bypass. Despite its effectiveness, several postoperative complications have been reported with STA-MCA bypass. Cerebral hyperperfusion syndrome (CHS) after STA-MCA has attracted considerable attention as a hemodynamics-related complication because more cases of CHS after STA-MCA bypass are reported in MMD than in non-MMD patients. The mechanisms underlying CHS after revascularization in MMD patients are poorly understood. This report presents a comprehensive review of the literature on CHS after revascularization in MMD patients, focusing on the pathogenesis, clinical features, imaging techniques, treatment, and prognosis of CHS. Impaired cerebrovascular autoregulation has been implicated in the pathogenesis of CHS, which is characterized by unilateral headache, face and eye pain, seizures, and focal neurological deficits secondary to cerebral edema, and intracranial hemorrhage. Imaging techniques, such as single photon emission computed tomography (SPECT), 3-T magnetic resonance imaging/angiography, and selective arterial spin-labeling magnetic resonance imaging, are valuable for identifying patients at risk for CHS. Treatment strategies include strict blood pressure control, intracranial hemorrhage prevention, and free oxygen radical scavenger administration. Most patients can achieve a satisfying prognosis after effective treatment.


Extrinsic whitening effects of sodium hexametaphosphate--a review including a dentifrice with stabilized stannous fluoride.
The number of tooth whitening products available to patients has grown dramatically during recent years. While peroxide is the primary agent found in products that bleach and remove intrinsic sources of discoloration, various ingredients are incorporated in formulations to remove and inhibit extrinsic sources of tooth discoloration, ie, tooth stain. Recently, an advanced antitartar ingredient with extrinsic-stain-inhibiting benefits was introduced: sodium hexametaphosphate. This long-chain condensed phosphate, also known as polypyrophosphate, chemically removes existing stains and provides long-lasting inhibition of new-stain chromogen adsorption. Sodium hexametaphosphate was originally introduced in a sodium fluoride dentifrice formulation and was later marketed in a chewing gum delivery system. Recently, sodium hexametaphosphate was launched in another dentifrice formulation containing stabilized stannous fluoride (Crest Pro-Health). This article reviews published clinical and laboratory data demonstrating sodium hexametaphosphate's extrinsic whitening benefits in all three formulations.


Influence of surgery on survival in 145 patients with left main coronary artery disease.
A total of 145 patients with greater than 50% obstruction of the left main coronary artery (LMC) were studied by coronary arteriography. Of the 140 who survived cardiac catheterization, 121 were considered operable by coronary arteriography, and 19 were inoperable. Of the 121 operable patients, 32 were treated medically, and 89 had aortocoronary bypass surgery. Surgical mortality was 11%. The follow-up was from 1 to 72 months with a mean follow-up of 15 months. A survival table was plotted over a 24-month period. At 90 days survival in surgical patients was 85%, medical patients 72%, and inoperable patients 64%. At one year 82% of surgical patients were alive compared with 61% of medically treated operable patients (P less than 0.05). Thereafter, the survival rate remained stable up to 23 months. Survival in inoperable patients was 38% at one year. Improved surgical survival was associated with the presence of preoperative collateral vessels and a left ventricular stroke index greater than 18 g-m/m2. The study demonstrates that survival is improved significantly by surgery in LMC patients. Since mortality occurs early after coronary arteriography, surgery should be offered early to operable patients.


Neuroendocrine regulation of skin dendritic cells.
It has long been postulated that stress can affect certain skin conditions, and there is increasing experimental evidence that the neuroendocrine system can directly participate in cutaneous inflammation. Neurohormones, such as glucocorticoids and catecholamines, can reach the skin through the bloodstream after activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, respectively. Multiple neuropeptides, among them calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, pituitary adenylate cyclase-activating peptide, substance P, vasoactive intestinal peptide, and norepinephrine, may be released by cutaneous nerves or resident and infiltrating cells within the skin. Systemic neuromediators and cutaneous nerves can influence a number of target cells within the skin, among them Langerhans cells. Most of the experimental evidence to date indicates a suppressive effect of the neurohormones and neuropeptides on Langerhans cell function and cutaneous inflammation, but it has become evident lately that the timing of exposure to a stimulus is critical to the outcome of the immune response. Thus, administration of a stress hormone or exposure to a stressor before the dendritic cell (DC) encounters an antigen (Ag) may diminish the immune response toward that Ag, while a stressor may enhance immune function when acting on a maturing DC or before reexposure to the Ag. The neuroendocrine regulation of skin DCs is a complex system allowing for a quick adaptation to various stressors. Such a system, originally evolved to defend the organism against invading pathogens and maintain homeostasis, may under certain conditions become unbalanced and ultimately exacerbate cutaneous inflammation.


[Biomedical science in the era of complete sequence of human genome].
Human Genome Project has already produced a draft sequence of the human genome. The article discusses scientific and some social aspects of the Human Genome Project, especially its influence on practice and the future of molecular medicine.


Microenvironment-controlled encapsulation (MiCE) process: effects of PLGA concentration, flow rate, and collection method on microcapsule size and morphology.
To evaluate the real-time effects of formulation and instrumental variables on microcapsule formation via natural jet segmentation, a new microencapsulation system termed the microenvironment-controlled encapsulation (MiCE) process was developed. A modified flow cytometer nozzle hydrodynamically focuses an inner drug and outer polymer solution emanating from a coaxial needle assembly into a two-layer compound jet. Poly(lactic-co-glycolic acid) (PLGA) dissolved in a water-miscible organic solvent resulted in formation of reservoir-type microcapsules by interfacial phase separation induced at the boundary between the PLGA solution and aqueous sheath. The MiCE process produced microcapsules with mean diameters ranging from 15-25 microm. The resultant microcapsule size distribution and number of drug cores existing within each microcapsule was largely influenced by the PLGA concentration and microcapsule collection method. Higher PLGA concentrations yielded higher mean diameters of single-core microcapsules. Higher drug solution flow rates increased the core size, while higher PLGA solution flow rates increased the PLGA film thickness. The MiCE microencapsulation process allows effective monitoring and control of the instrumental parameters affecting microcapsule production. However, the microcapsule collection method in this process needs to be further optimized to obtain microcapsules with desired morphologies, precise membrane thicknesses, high encapsulation efficiencies, and tight size distributions.


Cell surface hydrophobicity and mycolic acid composition of Rhodococcus strains isolated from activated sludge foam.
The bacteria causing foaming in activated sludge plants are considered to be hydrophobic, and their hydrophobicity is assumed to be a crucial factor in their foam-forming ability. This study showed no consistent relationship between cell surface hydrophobicity (CSH), as determined by microbial adherence to hydrocarbons, of three Rhodococcus spp. isolated from activated sludge foam and their ability to produce a stable foam. There also appeared to be no correlation between the mycolic acid composition of these strains, in terms of chain length or degree of unsaturation, and either CSH or foaming ability. Zeolite and bentonite successfully prevented foaming by a Rhodococcus sp. in pure culture, which suggests that cell surface charge may also play a role in foam stabilisation.


Organ donation, patients' rights, and medical responsibilities at the end of life.
The 2006 revision of the Uniform Anatomical Gift Act (UAGA) attempts to enhance the availability of organs in part by granting new authority to organ procurement organizations over patients who are near death and may be candidates for donation after death while limiting patients' end of life (EOL) decisional authority through advance directives or surrogates. To examine the revised UAGA that may alter the ethics and law of EOL medical care in the United States. To analyze the revised UAGA in light of established legal and ethical standards. We evaluated the 2006 UAGA and accompanying commentary. Case law and ethics literature regarding informed consent and EOL care, state laws and regulations concerning advance directives and medical licensure, and literature concerning the fiduciary obligations of physicians were reviewed and compared with the 2006 UAGA and its 2007 amendment. We examined the legal and medical ethics literature to evaluate the 2006 UAGA and its 2007 amendment. The 2006 UAGA reflects the important public policy goal of making more organs available for transplantation. However, it transfers authority over EOL decisions from patients or surrogates to organ procurement organizations, which is inconsistent with EOL U.S. common law and the ethical and legal standards that govern medicine. The extent of informed consent transferred to organ procurement organizations at the time of signing a donor registry card is legally and ethically uncertain under the UAGA. As states consider enacting the 2006 UAGA, further revisions should be considered to balance the public policy goals of increasing the availability of donated organs with truly informed and voluntary EOL decisions for patients. Further revision of the 2006 UAGA is necessary to respect patients' civil liberties and the professional integrity of physicians who have legally and ethically recognized fiduciary duties to their dying patients.


The role of Langerhans cells in the sexual transmission of HIV.
Sexual transmission of HIV is the most common mode of infection in the global HIV epidemic. In the absence of an effective vaccine, there is an urgent need for additional strategies to prevent new HIV infections. An emerging body of evidence now indicates that Langerhans cells (LC) are initial cellular targets in the sexual transmission of HIV, and CD4- and CCR5-mediated infection of LC plays a crucial role in virus dissemination. However, interactions between HIV and LC are complex. For example, it is evident that HIV can interact concomitantly with non-LC dendritic cells in two separate and distinct ways: a CD4- and CCR5-dependent infection pathway and a CD4- and CCR5-independent capture pathway mediated by DC-SIGN, a C-type lectin molecule. Thus, there may be multiple ways by which HIV interacts with target cells in the genital mucosa. This review focuses on the recent advances regarding the cellular events that may occur during heterosexual transmission of HIV.


Scheduled dosage regimen by irreversible electroporation of loaded erythrocytes for cancer treatment.
Precise control of cargo release is essential but still a great challenge for any drug delivery system. Irreversible electroporation (IRE), utilizing short high-voltage pulsed electric fields to destabilize the biological membrane, has been recently approved as a non-thermal technique for tumor ablation without destroying the integrity of adjacent collagenous structures. Due to the electro-permeating membrane ability, IRE might also have great potential to realize the controlled drug release in response to various input IRE parameters, which were tested in a red blood cell (RBC) model in this work. According to the mathematical simulation model of a round biconcave disc-like cell based on RBC shape and dielectric characteristics, the permeability and the pore density of the RBC membrane were found to quantitatively depend on the pulse parameters. To further provide solid experimental evidence, indocyanine green (ICG) and doxorubicin (DOX) were both loaded inside RBCs (RBC@DOX&ICG) and the drug release rates were found to be tailorable by microsecond pulsed electric field (μsPEF). In addition, μsPEF could effectively modulate the tumor stroma to augment therapy efficacy by increasing micro-vessel density and permeability, softening extracellular matrix, and alleviating tumor hypoxia. Benefiting from these advantages, this IRE-responsive RBC@DOX&ICG achieved a remarkably synergistic anti-cancer effect by the combination of μsPEF and chemotherapy in the tumor-bearing mice model, with the survival time increasing above 90 days without tumor burden. Given that IRE is easily adaptable to different plasma membrane-based vehicles for delivering diverse drugs, this approach could offer a general applicability for cancer treatment.


Maryland dentists' knowledge of oral cancer prevention and early detection.
To reduce the morbidity and mortality associated with oral cancers, dentists must have accurate knowledge and skills to detect and diagnose oral cancers at early stages. The authors' study found gaps in dentists' knowledge of risk factors and procedures for diagnosing oral cancers. Increasing health literacy for oral cancers among dental professionals may lead to increased health literacy for oral cancers among the public because dental professionals are a key source of oral health information for the public.


Zero-dipole molecular organic cations in mixed organic-inorganic halide perovskites: possible chemical solution for the reported anomalous hysteresis in the current-voltage curve measurements.
Starting from a brief description of the main architectures characterizing the novel solar technology of perovskite-based solar cells, we focus our attention on the anomalous hysteresis experimentally found to affect the measurement of the current-voltage curve of such devices. This detrimental effect, associated with slow dynamic reorganization processes, depends on several parameters; among them, the scan rate of the measurements, the architecture of the cell, and the perovskite deposition rate are crucial. Even if a conclusive explanation of the origin of the hysteresis has not been provided so far, several experimental findings ascribe its origin to ionic migration at an applied bias and dielectric polarization that occurs in the perovskite layer. Consistently, a dipole-moment-reduced cation such as formamidinium ion is experimentally reported to quantitatively reduce the hysteresis from perovskite-based devices. By means of a density-functional theory-based set of calculations, we have predicted and characterized guanidinium ion (GA = (+)[C(NH2)3], a zero-dipole moment cation by symmetry)-based organic-inorganic halide perovskite's structural and electronic properties, speculating that such a cation and the alloys it may form with other organic cations can represent a possible chemical solution for the puzzling issue of the hysteresis.


Significance of genetic polymorphism of CYP2D6 in the pathogenesis of systemic sclerosis.
Systemic sclerosis (SSc) belongs to the group of systemic diseases of the connective tissue, which are characterized by a chronic autoimmune inflammatory process. The studies on etiopathogenesis of autoimmune diseases focus on the impact the genetically conditioned impairment of xenobiotic metabolism may exert. The genetically polymorphic CYP2D6 is one of the most important phase I drug metabolizing enzymes. The knowledge of oxidation polymorphism in the course of SSc may be helpful in choosing more efficient and safer therapy, particularly in the case of a disease involving various organs and treated with drugs belonging to diverse therapeutic groups. The aim of the study was to evaluate the CYP2D6 polymorphism in the SSc patients and to investigate a possible correlation with disease susceptibility. The study was carried out in 77 patients with SSc and 129 healthy volunteers. The CYP2D6 genotypes were analyzed by polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. Risk of SSc development for particular genotype carriers expressed by the odds ratio (OR) was statistically significantly higher for subjects with CYP2D6*1/CYP2D6*4 (OR = 3.2; p = 0.001). A statistically significant correlation between the CYP2D6*4 allele prevalence and the risk for developing SSc was found (OR = 1.6; p = 0.029). The obtained results may suggest the influence of CYP2D6*4 gene mutated alleles on increased incidence of systemic sclerosis.


Deceptive vibratory communication: pupae of a beetle exploit the freeze response of larvae to protect themselves.
It is argued that animal signals may have evolved so as to manipulate the response of receivers in a way that increases the fitness of the signallers. In deceptive communication, receivers incur costs by responding to false signals. Recently, we reported that pupae of the soil-inhabiting Japanese rhinoceros beetle Trypoxylus dichotoma produce vibratory signals to deter burrowing larvae, thereby protecting themselves. In the present study, monitoring of vibrations associated with larval movement revealed that T. dichotoma larvae remained motionless for ca 10 min when pupal vibratory signals were played back transiently (freeze response). Furthermore, pupal signals of T. dichotoma elicited a freeze response in three other scarabaeid species, whose pupae do not produce vibratory signals. This indicates that the freeze response to certain types of vibration evolved before the divergence of these species and has been evolutionarily conserved, presumably because of the fitness advantage in avoiding predators. Pupae of T. dichotoma have probably exploited pre-existing anti-predator responses of conspecific larvae to protect themselves by emitting deceptive vibratory signals.


Multimodal cerebral monitoring and decompressive surgery for the treatment of severe bacterial meningitis with increased intracranial pressure.
Bacterial meningitis is still associated with a high mortality, mainly because of cerebral herniation as a result of increased intracranial pressure. Published data stress the necessity of an early diagnosis and immediate start of antibiotic therapy. Nevertheless, there are only few reports in which therapeutic strategy was based on the monitoring and the reduction of intracranial pressure (ICP). We report one case of bacterial meningitis caused by Neisseria meningitidis with an initial ICP value of 60 mmHg, which was treated by large hemicraniectomy and ventriculostomy, leading to a favorable neurological long-term result. The surgical decision was accelerated by an accurate ICP evaluation based on cerebral monitoring [transcranial Doppler ultrasonography (TCD) and intracranial ICP-device]. In selected patients with bacterial meningitis and clinical and radiological evidence of elevated ICP, cerebral monitoring and aggressive reduction of ICP may be crucial to improve survival and neurological outcome. When maximal medical ICP treatment fails to reduce severe intracranial hypertension, decompressive craniectomy should be rapidly proposed.


The Polyvalent Role of CD30 for Cancer Diagnosis and Treatment.
CD30, also known as TNFRSF8 (tumor necrosis factor receptor superfamily member 8), is a protein receptor that is heavily glycosylated inside the Golgi apparatus, as well as a tumor marker that is found on the surface of specific cells in the body, including certain immune cells and cancer ones. This review aims to shed light on the critical importance of CD30, from its emergence in the cell to its position in diagnosing various diseases, including Hodgkin lymphoma, where it is expressed on Hodgkin and Reed-Sternberg cells, as well as embryonal carcinoma, anaplastic large cell lymphoma (ALCL), and cutaneous T-cell lymphoma (CTCL). In addition to its role in positive diagnosis, targeting CD30 has been a promising approach treating CD30-positive lymphomas, and there is ongoing research into the potential use of CD30-targeted therapies for autoimmune disorders. We aim to elaborate on CD30's roles as a tumor marker, supporting thus the hypothesis that this receptor might be the aim of cytostatic treatment.


[Effect of different crystalloids on internal environment in patients with septic shock receiving early fluid resuscitation: a prospective randomized controlled trial].
To compare the effect of 0.9% NaCl solution, Ringer solution, and acetate sodium potassium magnesium calcium glucose solution (ASPMCG solution) on internal environment in patients with septic shock receiving early fluid resuscitation. A prospective randomized controlled trial was conducted. From June 2016 to January 2018, a total of 280 patients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital were enrolled. All eligible patients were randomly divided into 0.9% NaCl solution group (group N), Ringer solution group (group L) and ASPMCG solution group (group P) with random number table. In all patients, catheters were placed in the right internal jugular vein or subclavian vein and were infused with 30 mL/kg of corresponding crystalloid within 3 hours after admission. According to fluid responsiveness, the rehydration rate and fluid volume were determined by the researcher within 6 hours. Other treatments were based on the 2012 Surviving Sepsis Campaign (SSC) guidelines during the study. In this study, 6-hour or 24-hour fluid volume and 7-day exogenous insulin use were recorded. The changes in arterial blood pH, base excess (BE), blood glucose (Glu), lactic acid (Lac), and serum Na+, K+, Cl-, Ca2+ were observed at 0, 3, 6, 24 hours, and 3 days and 7 days of resuscitation. In this study, a total of 1 082 patients were admitted to the ICU, and patients who did not meet the diagnostic criteria for septic shock, death or discharge within 24 hours of ICU admission were excluded. Finally, 280 patients with septic shock were enrolled in the analysis, with 94 patients in group N, 94 patients in group L and 92 patients in group P. There was no significant difference in the amount of crystalloid, colloidal fluid, total fluid within 6 hours or 24 hours or exogenous insulin dose within 7 days among the three groups. After fluid resuscitation, blood Cl- concentration in the three groups was increased in different degrees, peaked at 24 hours, but it in group N was significantly higher than that in group L and group P (mmol/L: 107.5±5.6 vs. 106.1±4.8, 105.1±4.2, both P < 0.05). Moreover, blood Ca2+ concentration also showed an increased tendency, it was significantly lower at 3 hours and 6 hours in group N than that in group L and group P (mmol/L: 1.10±0.08 vs. 1.15±0.09, 1.12±0.10 at 3 hours, 1.12±0.10 vs. 1.16±0.08, 1.15±0.09 at 6 hours, all P < 0.05). There was no significant difference in blood Cl- or Ca2+ between groups L and P (both P > 0.05). Arterial blood pH, BE, Glu, Lac, Na+, or K+ at each time point during fluid resuscitation also showed no difference among the three groups. Among patients with septic shock receiving early fluid resuscitation, compared with Ringer solution and ASPMCG solution, 0.9% NaCl solution may cause hyperchloremia and hypocalcemia, but has no significant effect on acid-base balance. Chinese Clinical Trial Registry, ChiCTR-IOR-16009176.


Mechanics-based design of lithium-ion batteries: a perspective.
From the overall framework of battery development, the battery structures have not received enough attention compared to the chemical components in batteries. The mechanical-electrochemical coupling behavior is a starting point for investigation on battery structures and the subsequent battery design. This perspective systematically reviews the efforts on the mechanics-based design for lithium-ion batteries (LIBs). Two typical types of mechanics-based LIB designs, namely the design at the preparation stage and that at the cycling stage, have been discussed, respectively. The former systemizes the structure design of multiscale battery components from the particle level to the cell level. The latter focuses on the external mechanics-related control, including external pressures and charge-discharge protocols, of in-service LIBs. Moreover, the general problems currently being faced in the mechanics-based LIB design are summarized, followed by the outlook of possible solutions.


A qualitative synthesis of drawing-based research on the illness-related experiences of children living with physical health problems.
The strengths of drawing-based approaches for encouraging children's participation in health research and facilitating communication with them have been increasingly acknowledged in the medical literature. However, there is a lack of methodological discussion on drawing-based approaches suitable for researching children living with physical health problems. The present study systematically reviewed qualitative research using drawing-based approaches on the experiences of children living with physical health problems and summarised how the approaches were used as well. We identified 54 studies from five databases. The characteristics of qualitative methods and drawing-based approaches were analysed. To obtain an overall understanding of the illness-related experiences of these children, qualitative data generated from the included studies were synthesised using the thematic synthesis approach. This systematic review highlights the appropriateness and accuracy of the use of drawings-based approaches in health research with children on their illness-related experiences, fostering inclusive participation and engagement of young generations.


A review on dural tail sign.
"Dural tail sign" (DTS) which is a thickening of the dura adjacent to an intracranial pathology on contrast-enhanced T1 MR Images, was first thought to be pathognomonic of meningioma, however, many subsequent studies demonstrated this sign adjacent to various intra- and extra-cranial pathologies and in spinal lesions. In this paper we outline the history, accompanying pathologies and the differentiation and probable pathophysiology of DTS. We also discuss whether we can predict tumoral involvement of the dural tail before surgery and whether the dural tail adjacent to a tumor should be resected.


The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1.
To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.


Cardioprotective effect of bepridil on ischemic myocardial damages in dogs.
The cardioprotective effect of bepridil was investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline was administered and 25 min later the left anterior descending coronary artery (LAD) was occluded for 2 hr; in the bepridil group, bepridil (1 mg/kg) was administered 25 min before 2 hr LAD occlusion and followed by a constant infusion (1 mg/kg/hr). Blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after occlusion, mitochondria were prepared from both nonischemic and ischemic areas in each group, and their function was measured polarographically. Fractionation of myocardial tissue from both nonischemic and ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. In the bepridil group, decrease in heart rate was observed without significant changes in blood pressure. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 hr occlusion were observed. Administration of bepridil significantly maintained the mitochondrial function and significantly prevented the leakage of lysosomal enzymes. These results indicate that bepridil might have a cardioprotective effect on ischemic myocardium.


[Effects of antibiotic and anti-inflammatory treatment on serum PSA and free PSA levels in patients with chronic prostatitis IIIA].
To investigate the effect of antibiotics and a nonsteroidal anti-inflammatory agent on the level of total prostate specific antigen (PSA) and free PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA. A total of 228 outpatients diagnosed as with chronic prostatitis III A received 4-week antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were determined before and after the treatment, and the changes analyzed. Significant variations were observed in the median PSA concentrations (3.51 microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F-PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes obtained 4 weeks after the treatment showed no statistical difference from those observed 8 weeks after the treatment. Chronic prostatitis IIIA appears to contribute to increased serum PSA levels in some men. Antibiotic and anti-inflammatory treatment could significantly reduce the PSA level and increase F-PSAR.


Mapping of linear epitopes of human papillomavirus type 16: the L1 and L2 open reading frames.
Certain types of human papillomavirus (HPV), notably HPV type 16, are associated with flat or inverted proliferative lesions of the cervix uteri that can progress to malignancy. As a first step towards the serological study of the epidemiology of HPV, we have synthesized the entire amino acid sequences of the 2 major viral capsid proteins of HPV type 16, L1 and L2, as a set of 66 synthetic 20-residue peptides with an overlap of 5 amino acids. The peptides were tested for reactivity with IgA, IgG and IgM antibodies in the sera of 30 patients with HPV-16-carrying cervical neoplasms. Both IgG and IgM antibody responses were detected, but most of the reactivity found was of the IgA class. The most immunoreactive peptides were further analyzed for reactivity with sera from 22 patients with parotid gland tumors and with sera from 38 healthy individuals. The L2-encoded protein contained only one major linear epitope, which was not specific for HPV-16-carrying neoplasms. In contrast, the L1-encoded protein contained several epitopes that were regularly immunoreactive with antibodies present in the sera of patients with HPV-16-carrying cervical neoplasms, but only rarely so in the sera of patients with other tumors or of healthy individuals.


The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases.
With over 4 decades of seminal contributions to the development and application of BMT, Dr. Thomas stresses the importance of collaboration between rheumatologists and transplant clinicians in developing this evolving area of treatment. While the debate concerning the value of TBI in the conditioning regimen and the use of autologous or allogeneic stem cells will continue, he states there is simply no other way to answer these questions than to begin well designed clinical studies. As pointed out by Dr. Hahn, unexpected post-transplant complications may arise in patients with SSc and SLE and possibly require modifications to the transplant procedure similar to the experience in patients with other specific diseases. Other difficulties may be encountered, including restricted funding of the transplant procedure by insurance carriers. The emergence of managed care contracts and payer limitations in the United States described by Dr. Appelbaum could hinder the development of innovative, curative therapies. As initial clinical data are being collected, it is vital to actively support patient referral and participation in clinical studies that will ultimately establish the indications, risks, costs, and benefits of hematopoietic stem cell transplantation for autoimmune disease.


Robustness of metacommunities with omnivory to habitat destruction: disentangling patch fragmentation from patch loss.
Habitat destruction, characterized by patch loss and fragmentation, is a major driving force of species extinction, and understanding its mechanisms has become a central issue in biodiversity conservation. Numerous studies have explored the effect of patch loss on food web dynamics, but ignored the critical role of patch fragmentation. Here we develop an extended patch-dynamic model for a tri-trophic omnivory system with trophic-dependent dispersal in fragmented landscapes. We found that species display different vulnerabilities to both patch loss and fragmentation, depending on their dispersal range and trophic position. The resulting trophic structure varies depending on the degree of habitat loss and fragmentation, due to a tradeoff between bottom-up control on omnivores (dominated by patch loss) and dispersal limitation on intermediate consumers (dominated by patch fragmentation). Overall, we find that omnivory increases system robustness to habitat destruction relative to a simple food chain.


Mucoepidermoid carcinoma of the thyroid gland.
An extremely rare case of mucoepidermoid carcinoma of the thyroid in a 56-year-old woman is presented. The patient clinically having Hashimoto's thyroiditis was noted a nodule in her neck. The tumor was sited in the midportion of the left lobe of the thyroid, and histologically it showed both squamous features and mucin production. The squamous cells were arranged in solid sheets with horny pearls and the mucous cells tended to line dilated duct-like elements. Ultrastructurally, the epidermoid cells had aggregates of tonofilaments and well-developed desmosomal attachments, and the mucous cells contained numerous mucin granules in their cytoplasm. Immunohistochemical studies revealed that cytokeratin antibodies showed positivity for both the lining cells and squamous cells, whereas carcinoembryonic antigen positivity was found in the lining cells and intraluminal material. The tumor cells were negative for thyroglobulin, calcitonin, vimentin, chromogranin, and neuron-specific enolase. These unusual histologic and immunohistochemical features are suggestive of a tumor related to the so-called "solid cell nest" of the thyroid.


Determination of the isoelectric points of low and high molecular mass ampholytes by capillary electrophoresis.
A methodology for a reliable and absolute determination of isoelectric points of amphoteric species by capillary zone electrophoresis is proposed. The principle of this absolute method consists in the application of an additional electroosmotic and/or hydrodynamic flow of a background electrolyte. This allows the measurement of electrophoretic mobilities of substances close to their isoelectric points where the net electric charge is very low and electrophoretic mobility tends to zero. The mobilities are measured at various pH values of the electrolyte so as to find the pH at which the substance moves through the separation column at zero mobility under the action of the additional flow only. The number of required measurements is lowered to the minimum with the help of the iterative procedure based on the Regula Falsi algorithm. The precision of the proposed method is predicted theoretically. The feasibility is demonstrated on real samples. The isoelectric points of histidine, myoglobine and ribonuclease are found from their titration curves.


Telehealth to support practice in remote regions: a survey among medical residents.
Medical workforce distribution represents a particular challenge in Quebec, Canada. Telehealth is considered a promising tool to provide access to health care, but also to increase professional support in remote regions. This survey was aimed at exploring medical residents' perceptions toward telehealth and its potential impact on their intention to practice in remote regions. A questionnaire was distributed to a convenient sample of medical residents. A total of 67 questionnaires were analyzed. Analyses were performed to explore relationships between factors related to residents' intention to practice in remote regions and factors associated with their intention to use telehealth. Residents perceived telehealth positively and thought that it could influence favorably medical practice in remote regions. Furthermore, telehealth was associated with better continuing medical education and this factor is a strong predictor of medical residents' intention to practice in remote regions. Telehealth constitutes a precious tool to support the delivery of health services in remote regions and to facilitate the work of physicians. Nonetheless, telehealth alone would not solve medical resource shortages in remote regions.


[A case of centroblastic lymphoma of the thyroid gland].
A case of a 49-year male patient with centroblastic lymphoma of the thyroid gland is presented. Centroblastic lymphoma was diagnosed with cytological and immunocytochemical examination of the biopsy specimen, and verified with histological examination of tumor section collector intraoperationally. Diagnosed tumor was classified as II AE degree. No signs of lymphocytic thyroiditis co-existing with centroblastic lymphoma were noted. The patient was treated chemically with CBVPM/AVBP regimens for 8 months. Complete remission still lasting, i.e. 96 months after completion of chemotherapy, was achieved.


Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome.
To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in severe acute respiratory syndrome (SARS) patients. Sixty-one cases of SARS with positive antibodies to SARS coronavirus (SARS-CoV) were classified into the following categories: initial stage (3 - 7 days), peak stage (8 - 14 days), and remission and recovery stage (15 - 27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-alpha and TGF-beta 1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases. The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages (P < 0.01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage (P < 0.05). And it was more significantly higher in remission and recovery stage than in peak stage (P < 0.01). The mean concentrations of IL-16 and TNF-alpha in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage (P < 0.01). SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage (P < 0.01), but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses (P < 0.05). The mean concentration of serum TGF-beta1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-beta1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group (P < 0.01). Most proinflammatory cytokines and TGF-beta 1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.


Effect of fluoride on growth and acid production by Streptococcus mutans in dental plaque.
The aim of this study was to measure the effect of fluoride on the production of organic acids by Streptococcus mutans in dental plaque. The effect was studied in a simplified model of dental plaque with gnotobiotic rats monoinfected with S. mutans Ny341. Adaptation of S. mutans to fluoride was induced by feeding one group of the rats on fluoride-containing diet and drinking water. No difference was found in the accumulation of S. mutans on the teeth between the fluoride-adapted and the control groups. However, there was a significant difference in the amount of lactic acid in metabolically resting plaque between the groups, lactic acid being lower in the fluoride-adapted plaque. At 5 min after a rinse containing 10% sucrose, a high level of lactic acid was found in plaque from animals not exposed to fluoride. Rinses containing 4 or 20 mM fluoride before the sucrose rinse significantly inhibited the lactic acid production in the control group. In the plaque from rats on fluoridated diet and drinking water the sucrose-induced production of lactic acid was not inhibited by a 4 mM fluoride rinse. Moreover, the production of lactic acid in the fluoride-adapted plaque was prolonged. The results indicate that due to fluoride adaptation the inhibition of acid production is unlikely to be important for the caries-preventive action of fluoride.


Brain tumor inhibition in experimental model by restorative immunotherapy with a corpuscular antigen.
In view of the advances in our understanding of anti-tumor immune response, it is now tempting to contemplate the development of immunotherapies for malignant brain tumors, for which no effective treatment exists. Immunotherapy, with agents known as biological response modifiers (BRMs) are thus gaining increasing interest as the fourth modality of treatment. A non-specific BRM, sheep erythrocytes (SRBC) when administered (ip, 7% PCV/V, 0.5 ml) in a group of animals at the end of seventh month of ethylnitrosourea administration, resulted in significant increase in the mean survival time (> 350 days). Studies conducted for growth kinetics pattern with proliferation index and fluorochrome (HO-33342) uptake techniques at the tissue culture level exhibited a regulatory inhibition of the cells isolated from tissue excised from the tumor susceptible area of brain of SRBC treated animals. Moreover, histological examination of brain from animals showed immunomodulatory role of SRBC in experimentally induced brain tumor. Further probe into the mechanisms involving immunological investigations at the cellular level in these animals indicated an augmented and potentiated cell mediated immune response (CMI) as evidenced by enhanced spontaneous rosette forming capacity and cytotoxic activity of lymphocytes and neutrophil (PMN) mediated phagocytosis respectively. The observations suggest that SRBC down regulate malignant growth pattern of experimental brain tumors either by an immunologically enhanced killing of tumor cells and/or by directly inhibiting the tumor growth possibly via a stimulated cytokine network. Thus, a corpuscular antigen, can potentiate CMI response in experimentally induced brain tumor animal model, in which response induced in the periphery are able to mediate anti-tumor effects in the brain.


Psychological stress among undergraduate medical students.
The aim of this study was to determine the prevalence of psychological stress among medical students and to identify its symptoms and association with depression. A cross-sectional study design was used. Three-hundred and ninety-six medical students at a university in Malaysia were included in the study. Tools similar to the General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI) were used to screen for psychological stress and depression, respectively. 41.9% of the medical students were found to have psychological stress, which was significantly associated with depression (chi2=4.636, df=1, p<0.05). Psychological stress is common among medical students and is associated with depression.


[Corneal penetration of PAMAM dendrimers-coated puerarin liposomes].
To study the corneal penetration of PAMAM dendrimers-coated puerarin liposomes in rabbits. Evaluated PAMAM (G2, G3) dendrimers-coated puerarin liposomes were prepared and the in vitro transcorneal penetration were compared to puerarin drop solution and uncoated liposomes. The effect of different proportion of PAMAM to phospholipids in formulation on corneal penetration and the penetration parameters were investigated. The steady state fluxes and permeability coefficients of puerarin by PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated puerarin liposomes were greater than that by puerarin drop solution and uncoated liposomess (P < 0.01), meanwhile the PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated liposomes were better than other ratios of coated liposomes for improvement of corneal penetration (P < 0.01). The PAMAM coated liposomes is able to enhance the corneal penetration of puerarin and promising as an ocular drug carriers.


Potential value of liposomes containing muramyl dipeptide for augmenting the tumoricidal activity of human alveolar macrophages.
Potentiation of the tumoricidal activity of human alveolar macrophages (AM) by muramyl dipeptide (MDP) and MDP in liposomes (liposome-MDP) was examined. Significant increase in AM-mediated cytotoxicity against allogeneic melanoma cells required the interaction of AM with liposome-MDP for a minimum of 4 h. The uptake by human AM of liposomes containing fluorescent quinacrine was examined. A linear correlation was found between the amount of liposomes added to AM monolayers and their phagocytosis of liposome-entrapped quinacrine. Addition of phosphatidylserine to liposomes composed of phosphatidylcholine enhanced both the phagocytosis of liposomes and the ability of liposome-MDP to potentiate the tumoricidal activity of human AM. In experiments on the dose response of liposomes containing 10 micrograms/ml MDP, 50 nmol of liposomes/10(5) AM caused maximal activation of human AM, and greater than 100 nmol of liposomes was less effective. These results show that multilamellar vesicle liposomes containing MDP are more effective than free MDP in potentiating the tumoricidal activity of human AM during culture for 4 h.


Robotic Heller's cardiomyotomy for achalasia: early outcomes for a high-volume UK centre.
Heller's cardiomyotomy (HCM) is the gold standard treatment for achalasia. Laparoscopic HCM has been shown to be effective with low rates of symptom recurrence, though oesophageal mucosal perforation rates remain high. The aim of this prospective case series is to assess the short-term complication rates and perioperative outcomes for the first cohort of patients undergoing robotic-assisted HCM for achalasia in a single high-volume UK centre. Data were collected from a prospective cohort of patients who underwent robotic HCM at a single high-volume UK centre. Outcomes were assessed using the Eckhard score, which was calculated after their routine postoperative clinic appointments. Thirteen patients underwent robotic HCM during the study period; this is the second largest reported case series in the European literature. There were no intraoperative oesophageal perforations. Six patients were discharged as day cases, six patients were discharged on the first postoperative day and one patient's hospital stay was two nights. There was a single perioperative complication of urinary retention. All patients reported improvement of symptoms following their operation, and all had a postoperative Eckhard score of less than 3, indicating their achalasia was in remission. This cohort has demonstrated that robotic HCM has an exceptional safety profile and results in high levels of symptom resolution, even early in the learning curve. The robotic approach may be superior to laparoscopy as it allows more precise identification and dissection of the oesophageal muscle fibres, which likely reduces the risk of inadvertent mucosal damage or incomplete myotomy.