Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma.
Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC. Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching. About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group. RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.


Exacerbation of HIV viral load simultaneous with asymptomatic reactivation of chronic Chagas' disease.
Chronic Trypanosoma cruzi infection can reactivate in patients with immunosuppression related to human immunodeficiency virus (HIV) infection, resulting in severe meningoencephalitis or myocarditis and high parasitemia. The effects of T. cruzi on HIV infection are unknown. We describe an HIV-infected patient with chronic Chagas' disease who experienced an asymptomatic T. cruzi reactivation characterized by the finding of the parasite in direct microscopic examination of blood. The patient's HIV viral load had increased simultaneously with the exacerbation of T. cruzi parasitemia and decreased to previous levels after successful antiparasitic treatment. This otherwise unexplained finding suggests that T. cruzi infection might up-regulate HIV replication, which may affect HIV disease progression. Asymptomatic reactivation of Chagas' disease has not been reported before. This could mean that the severe clinical manifestations related to the reactivation of trypanosomiasis are just the tip of the iceberg.


Biomaterial-Based bFGF Delivery for Nerve Repair.
Diseases in the nervous system are common in the human body. People have to suffer a great burden due to huge economic costs and poor prognosis of the diseases. Many treatment modalities are now available that can make recovery better. Managing nutritional factors is also helpful for such diseases. The basic fibroblast growth factor (bFGF) is one of the major nutritional factors, which plays a crucial role in organogenesis and tissue homeostasis. It plays a role in cell proliferation, migration, and differentiation, thereby regulating angiogenesis and wound healing and repair of the muscle, bone, and nerve. The study on how to improve the stability of bFGF to increase the treatment effect for different diseases has garnered tremendous attention. Biomaterials are the popular methods to improve the stability of bFGF because they are safe for the living body as they are biocompatible. Biomaterials can be loaded with bFGF and delivered locally to achieve the goal of sustained bFGF release. In the present review, we report different types of biomaterials that are used for bFGF delivery for nerve repair and briefly report how the introduced bFGF can function in the nervous system. We aim to provide summative guidance for future studies about nerve injury using bFGF.


A green sulfur bacterium from epsomitic Hot Lake, Washington, USA.
Hot Lake is a small heliothermal and hypersaline lake in far north-central Washington State (USA) and is limnologically unusual because MgSO4 rather than NaCl is the dominant salt. In late summer, the Hot Lake metalimnion becomes distinctly green from blooms of planktonic phototrophs. In a study undertaken over 60 years ago, these blooms were predicted to include green sulfur bacteria, but no cultures were obtained. We sampled Hot Lake and established enrichment cultures for phototrophic sulfur bacteria in MgSO4-rich sulfidic media. Most enrichments turned green or red within 2 weeks, and from green-colored enrichments, pure cultures of a lobed green sulfur bacterium (phylum Chlorobi) were isolated. Phylogenetic analyses showed the organism to be a species of the prosthecate green sulfur bacterium Prosthecochloris. Cultures of this Hot Lake phototroph were halophilic and tolerated high levels of sulfide and MgSO4. In addition, unlike all recognized species of Prosthecochloris, the Hot Lake isolates grew at temperatures up to 45 °C, indicating an adaptation to the warm summer temperatures of the lake. Photoautotrophy by Hot Lake green sulfur bacteria may contribute dissolved organic matter to anoxic zones of the lake, and their diazotrophic capacity may provide a key source of bioavailable nitrogen, as well.


Intestine-specific gene transcription.
The diverse cellular lineages that populate the intestinal epithelium are derived from committed stem cells located in intestinal crypts. The complex architecture of the intestinal epithelium results from well-orchestrated processes of cell-line-age allocation, proliferation of immature cells in the crypt compartment, differentiation of various cell lineages, migration of cells in defined patterns, and cell-specific programmed senescence. The patterns of intestinal gene transcription in the context of this complex architecture are regulated by the combinatorial effect of multiple positive and negative regulatory elements. Although the DNA regulatory elements required to recapitulate the pattern of endogenous gene expression appear to be spread over relatively large genomic distances, short promoters of several intestinal genes are sufficient to direct intestine-specific transcription. The sucrase-isomaltase gene promoter has multiple regulatory elements that bind tissue-restricted transcription factors. A critical factor in regulating the sucrase-isomaltase promoter is Cdx2, an intestine-specific homeobox gene related to caudal, that may also have a broader role in intestinal development and morphogenesis. As additional regulatory elements and their cognate DNA-binding proteins are identified, the challenge will be to define their integrated role in the regulation of intestine-specific genes and in the development and maintenance of the intestinal epithelium.


Force-velocity, impulse-momentum relationships: implications for efficacy of purposefully slow resistance training.
The purpose of this brief review is to explain the mechanical relationship between impulse and momentum when resistance exercise is performed in a purposefully slow manner (PS). PS is recognized by ~10s concentric and ~4-10s eccentric actions. While several papers have reviewed the effects of PS, none has yet explained such resistance training in the context of the impulse-momentum relationship. A case study of normal versus PS back squats was also performed. An 85kg man performed both normal speed (3 sec eccentric action and maximal acceleration concentric action) and PS back squats over a several loads. Normal speed back squats produced both greater peak and mean propulsive forces than PS action when measured across all loads. However, TUT was greatly increased in the PS condition, with values fourfold greater than maximal acceleration repetitions. The data and explanation herein point to superior forces produced by the neuromuscular system via traditional speed training indicating a superior modality for inducing neuromuscular adaptation. Key pointsAs velocity approaches zero, propulsive force approaches zero, therefore slow moving objects only require force approximately equal to the weight of the resistance.As mass is constant during resistance training, a greater impulse will result in a greater velocity.The inferior propulsive forces accompanying purposefully slow training suggest other methods of resistance training have a greater potential for adaptation.


Mechanism of Huoluo Xiaoling Dan in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking.
To explore the mechanism of the action of Huoluo Xiaoling Dan (HLXLD) in the treatment of psoriasis based on network pharmacology and molecular docking. The main active components and targets of HLXLD were collected from CMSP, and the targets related to psoriasis were collected from GeneCards, OMIM, TTD, DisGeNET, and DrugBank. Drug disease target genes were obtained by Venny tools, drug-component-target networks were constructed and analyzed, and pathway enrichment analysis was performed. AutoDockTools is used to connect the core components and the target, and PyMOL software is used to visualize the results. 126 active components (such as quercetin, luteolin, tanshinone IIA, dihydrotanshinlactone, and beta-sitosterol) and 238 targets of HLXLD were screened out. 1,293 targets of psoriasis were obtained, and 123 drug-disease targets were identified. Key targets included AKT1, TNF, IL6, TP53, VEGFA, JUN, CASP3, IL1B, STAT3, PTGS2, HIF1A, EGF, MYC, EGFR, MMP9, and PPARG. Enrichment analysis showed that 735 GO analysis and 85 KEGG pathways were mainly involved in biological processes such as response to the drug, inflammatory response, gene expression, and cell proliferation and apoptosis, as well as signal pathways such as cancer, TNF, HIF-1, and T cell receptor. Molecular docking showed that there was strong binding activity between the active ingredient and the target protein. HLXLD could treat psoriasis through multicomponents, multitargets, and multipathways, which provides a new theoretical basis for further basic research and clinical application.


A COVID-19 Auxiliary Diagnosis Based on Federated Learning and Blockchain.
Due to the high transmission rate and high pathogenicity of the novel coronavirus (COVID-19), there is an urgent need for the diagnosis and treatment of outbreaks around the world. In order to diagnose quickly and accurately, an auxiliary diagnosis method is proposed for COVID-19 based on federated learning and blockchain, which can quickly and effectively enable collaborative model training among multiple medical institutions. It is beneficial to address data sharing difficulties and issues of privacy and security. This research mainly includes the following sectors: in order to address insufficient medical data and the data silos, this paper applies federated learning to COVID-19's medical diagnosis to achieve the transformation and refinement of big data values. With regard to third-party dependence, blockchain technology is introduced to protect sensitive information and safeguard the data rights of medical institutions. To ensure the model's validity and applicability, this paper simulates realistic situations based on a real COVID-19 dataset and analyses problems such as model iteration delays. Experimental results demonstrate that this method achieves a multiparty participation in training and a better data protection and would help medical personnel diagnose coronavirus disease more effectively.


Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.
Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated.


Chromosome anomalies in human oocytes in relation to age.
Cytogenetic analysis of oocytes remaining unfertilized after in-vitro fertilization showed that the source of data obtained could be divided into degenerating and 'healthy' oocytes. The degenerating oocytes, which showed different degrees of chromosome breakage, accounted for a quarter of the total. They were found in older patients with a mean age of 35.0 years. The healthy oocytes without chromosome breaks were mostly haploid and fell into two main groups, those with a normal MII,23,X chromosome complement, and those abnormal in which single chromatids replaced a whole chromosome. No oocytes hyperhaploid for an extra whole chromosome were found. We hypothesize that the single chromatids at second meiotic metaphase arise by precocious division of chromosome univalents at anaphase I (predivision) and that this may be the major mechanism for trisomy formation in man, rather than the non-disjunction of whole bivalents as generally assumed.


Role of metal-catalyzed oxidation reactions in the early pathogenesis of scleroderma.
The observation that revelation of immunocryptic epitopes in self-antigens may initiate the autoimmune response has prompted the search for processes that induce novel autoantigen structure as potential initiators of autoimmunity. Recent studies have demonstrated that the autoantigens targeted in diffuse scleroderma are unified by their enrichment in nucleolini and by their susceptibility to fragmentation in a novel metal-dependent reaction that requires the generation of reactive oxygen species. Several other studies highlight the importance of reactive oxygen species as mediators of damage during ischemia-reperfusion and present evidence for increased generation of these radicals in patients with scleroderma. Together, these studies suggest a model for the pathogenesis of scleroderma in which metals and free radicals play a central, autoamplifying role.


[Prostaglandins and thromboxane in coronary arteriosclerosis].
The prostanoid status was assessed in 138 patients with coronary atherosclerosis and clinical signs of stable angina. Plasma prostaglandin F2 alpha and E1, and stable prostacyclin and thromboxane metabolites were measured radioimmunologically, using standard kits. A relationship is demonstrated between the severity of clinical manifestations, and pattern and magnitude of change in individual prostanoids.


Pharmacological and functional characterization of muscarinic receptor subtypes in developing oligodendrocytes.
This study focused on the molecular and pharmacological characterization of muscarinic acetylcholine receptors expressed by progenitors and differentiated oligodendrocytes. We also analyzed the role of muscarinic receptors in regulating downstream signal transduction pathways and the functional significance of receptor expression in oligodendrocytes. RT-PCR analysis revealed the expression of transcripts for M3, and to a lesser extent M4, followed by M1, M2 and M5 receptor subtypes in both progenitors and differentiated oligodendrocytes. Competition binding experiments using [(3)H]N-methylscopolamine and several antagonists, as well as inhibition of carbachol-mediated phosphoinositide hydrolysis, showed that M3 is the main subtype expressed in these cells. In progenitors the activation of p42/44-mitogen-activated protein kinase (MAPK) and cAMP-response element binding protein (CREB) as well as c-fos mRNA expression were blocked by the M3 relatively selective antagonist, 4-DAMP, and its irreversible analogue, 4-DAMP-mustard. Carbachol increased proliferation of progenitors, an effect prevented by atropine and 4-DAMP, as well as by the MAPK kinase inhibitor PD98059. These results indicate that carbachol modulates oligodendrocyte progenitor proliferation through M3 receptors, involving activation of a MAPK signaling pathway. Receptor density and phosphoinositide hydrolysis are down-regulated during oligodendrocyte differentiation. Functional consequences of these events are a reduction in carbachol-stimulated p42/44(MAPK) and CREB phosphorylation, as well as induction of c-fos.


Evaluation of Meibomian Gland Function after Therapy of Eyelid Tumors at Palpebral Margin with Super Pulse CO2 Laser.
To investigate the effect on meibomian gland function of super pulse carbon dioxide (CO2) laser excision in the treatment of eyelid tumors at palpebral margin. 36 patients with 36 eyelid tumor size ≤ 1 cm and within 1 mm to palpebral margin were recruited in this study. Of which, 16 cases with tumors in the upper eyelid and 20 cases in the lower eyelid were involved. The eyelid tumors of all the patients were treated by super pulse CO2 laser with its power density varied between 0.6 and 21.1 W/mm2 and in repeat mode. The laser spot size ranged from 120 to 200 μm. Ocular surface parameters including tear film break-up time (BUT) and meibograde, meibum expressibility, and meibum quality were evaluated at pretherapy, 1 week, 1 month, and 3 months posttherapy in all 36 patients. All the patients were satisfied with the therapy. No infective complications and recurrence occurred in any of the 36 patients at the following period. The eyelid wound recovered well with nearly normal appearing after 2 to 3 weeks. The morphology of limbi palpebralis, BUT, meibograde, meibum expressibility, and meibum quality of all the 36 patients showed no significant difference before and after the therapy. Super pulse CO2 laser had no effect on meibomian gland function and morphology in the excision of tumors at palpebral margins, which was an efficacy and well-tolerated therapy with lower complications and recurrence.


Speech intelligibility in aircraft noise as a function of altitude.
Few studies have addressed physiological effects of altitude and noise combined, although these two factors are inherent parts of all aviation. Altitude effects on hearing function have mainly been studied using gas mixtures with reduced oxygen content. The results have been inconclusive. The present study was designed to assess the effect of altitude on speech intelligibility in aircraft noise. The primary hypothesis was that exposure to altitude would produce a detrimental, hypoxic effect on speech intelligibility in noise. Eight male subjects with normal hearing were fitted with an aviation headset specially adapted for use with the audiometer. Pure-tone audiometry, as well as speech audiometry in noise, were performed at 0, 10,000, 13,000, and 16,000 ft simulated altitudes in a hypobaric chamber. The four test altitudes were performed double blind with respect to audiometry operator and test subject. Arterial blood gases where measured using an intra-arterial catheter. Tympanometric measurements verified full middle ear equilibration. Noise levels where monitored and logged throughout all experiments. A substantial increase in speech intelligibility in noise due to altitude was evident in our study. The physical effect of barometric pressure on noise causing an increased signal-to-noise ratio was found to greatly outweigh any possible hypoxic detrimental effect.


Enhanced acidogenic fermentation of food waste in a continuous-flow reactor.
This study was performed to improve acidogenic fermentation of food waste in a continuous-flow reactor. The fermentation of food waste is affected by the fermentation constraints such as the biodegradability of substrate, the degrading capability of microorganisms and the environmental conditions. The key factors were, therefore, examined to control the fermentation constraints, such as the effect of seed inoculation and the effect of adjusting dilution rate. Acidogenic fermentation of food waste employing rumen microorganisms resulted in the enhanced efficiency (71.2%) as compared with that (59.8%) employing mesophilic acidogens. In addition, the fermentation efficiency increased from 71.2 to 82.0% by adjusting dilution rate from 3.0 to 1.0 d(-1) depending on the state of the fermentation. The main component of the acidified product was shifted from butyric to acetic acid. This meant that the increase of the fermentation efficiency was mainly caused by the enhanced degradation of vegetables and meats. The control of the fermentation constraints was, therefore, very effective in improving the fermentation efficiency of food waste.


Integration of DNA ligation and rolling circle amplification for the homogeneous, end-point detection of single nucleotide polymorphisms.
Association studies using common sequence variants or single nucleotide polymorphisms (SNPs) may provide a powerful approach to dissect the genetic inheritance of common complex traits. Such studies necessitate the development of cost-effective, high throughput technologies for scoring SNPs. The method described in this paper for the co-detection of both alleles of a SNP in a single homogeneous reaction combines the specificity of a high fidelity DNA ligation step with the power of rolling circle amplification. The incorporation of Amplifluor energy transfer primers enables signal detection in a homogeneous format, making this approach highly amenable to automation. The adaptation of the genotyping method for high throughput screening using conventional liquid handling systems is described.


DNA-Mediated Control of Protein Function in Semi-Synthetic Systems.
The development of strategies for controlling protein function in a precise and predictable manner has the potential to revolutionize catalysis, diagnostics, and medicine. In this regard, the use of DNA has emerged as a powerful approach for modulating protein activity. The programmable nature of DNA allows for constructing sophisticated architectures wherein proteins can be placed with control over position, orientation, and stoichiometry. This ability is especially useful considering that the properties of proteins can be influenced by their local environment or their proximity to other functional molecules. Here, we chronicle the different strategies that have been developed to interface DNA with proteins in semi-synthetic systems. We further delineate the unique applications unlocked by the unprecedented level of structural control that DNA affords. We end by outlining outstanding challenges in the area and discuss future research directions towards potential solutions.


Low dose-rate fibroblast radiosensitivity and the prediction of patient response to radiotherapy.
The relationship between cellular radiosensitivity and normal-tissue response to radiotherapy in individual cancer patients has attracted increasing attention over the last few years. Recent work has suggested that a correlation exists between fibroblast sensitivity and normal-tissue reactions. We have examined the radiosensitivity of fibroblasts grown from skin biopsies of four normal individuals and three patients identified as having suffered unexpectedly severe reactions to clinical radiotherapy, called here 'over-reactor' (OR) patients. Clonogenic survival was measured after high (HDR) and low dose-rate (LDR) irradiation. By comparing the two, and LDR Recovery Factor was derived. Potentially-lethal damage repair was examined in 4 cell strains. After HDR the OR strains were indistinguishable from the normals. At LDR the range of sensitivity was expanded. The OR strains fell at the sensitive end of the range and were characterized by a lack of LDR recovery, which clearly distinguished them from the normal strains. Experimental errors were estimated by considering all the data sets together rather than viewing each experiment individually. Duplicate strains from several patients were tested, and the differences between them were found to be within the estimated experimental errors, suggesting that these differences were not biologically significant. The data are consistent with the hypothesis that normal-tissue response is linked to individual cellular radiosensitivity. Our data confirm the importance of using LDR irradiation in clinical investigations of cellular sensitivity.


[Clinical Trials for Treatment of Stroke Patients with Dysphagia by Vitalstim Electroacupuncture Combined with Swallowing Rehabilitation Training].
To observe the clinical effect of vitalstim electroacupuncture (EA) combined with swallowing rehabilitation training in the treatment of stroke patients with dysphagia. A total of 80 stroke patients with dysphagia were randomized into treatment and control groups (n=40 in each group). Patients of the control group were treated by regular medication for anti-platelet aggregation and anti-coagulation, lipid-lowering, neuroprotection, blood glucose control and blood pressure control, etc. and swallowing function rehabilitation training, and those of the treatment group treated by EA stimulation of Fengchi (GB 20), Jinjin (EX-HN 12) and Yuye (EX-HN 13) with a Vitalstim Electrostimulator and manual acupuncture stimulation of Lianquan (CV 23), Tiantu (CV 22) in combination with regular medication plus swallowing function training as those mentioned in the control group. The EA and manual acupuncture stimulation treatment was conducted once daily, 6 times a week and 4 weeks altogether. The therapeutic effect was assessed by using Kubota swallowing ability test (6 levels), dysphagia subscale (0-6 scores) of the neurological deficit degrees, videofluorography (VFG) assessment (markedly effective, effective and invalid, for evaluating the function and symmetry state of the swallowing movements), and the MOS Item Short Form Health Survey (SF-36, 8 minor items of two major aspects in physiological function, mental health, emotional function, social function and overall health) for assessing the patients' daily-life quality. After the treatment, the dysphagia score of the treatment group was signi-ficantly lower than that of the control group (P<0.05). VFG outcomes showed that, of the two 40 patients in the control and treatment groups, 16 and 23 experienced a marked improvement, 20 and 15 were effective, 4 and 2 were ineffective, with the markedly effective rate being 40.0% and 57.5%, respectively. The daily-life quality scores for physiological function, mental health, emotional function, social function and overall health were all notably increased after the treatment in both groups, particularly in the treatment group (P<0.05). The therapeutic effects of the treatment group were remarkably superior to those of the control group in improving dysphagia (showed by dysphagia score and VFG outcomes) and life quality. EA treatment combined with swallowing function rehabilitation training is effective in improving swallowing ability and daily-life quality in stroke patients with dysphagia.


[Diagnosis and surgical treatment of parathyroid neoplasms].
To explore the clinical features, diagnosis and surgical treatment of parathyroid neoplasms. From January 2003 to December 2011, a total of 51 patients were recruited. Their clinical data, presentations, examinations and surgical approaches were analyzed retrospectively. Among them, there were parathyroid adenoma (n = 32), parathyroid cysts (n = 18) and parathyroid carcinoma (n = 1). The sensitivity and positive rate of neck ultrasonography and (99)Tc(m)-methoxyisobutylisonitrile (MIBI) were 84.3% and 93.5%, 91.7% and 100.0% respectively. The high levels of serum calcium and parathyroid hormone (PTH) in 32 cases of parathyroid adenoma and 1 case of parathyroid carcinoma returned to normal after operation. The levels of serum calcium and PTH remained normal in 18 cases of parathyroid cysts. The clinical manifestations of parathyroid adenoma were complex. The serum levels of calcium and PTH and neck ultrasonography are preferred screening tools for parathyroid neoplasms.(99)Tc(m)-MIBI is suitable for tumor localization.Surgery is effective and safe for parathyroid neoplasm.Real time intraoperative monitoring of PTH is of great importance.


Dose-dependent absorption and metabolism of trans-polydatin in rats.
There is considerable evidence that stilbenes provide health benefits. trans-Polydatin is one of the major stilbenoid compounds in red wine. The purpose of this study is to investigate the dose-dependent absorption and metabolism of trans-polydatin in rats. trans-Polydatin was administered to rats by gavage at three different doses (50, 100, and 300 mg x kg(-1)). Blood samples were then collected at different time points. In situ perfusion of rat small intestine and liver was used to investigate the first-pass metabolism of trans-polydatin. trans-Polydatin and its metabolites were detected by LC-MS/MS. trans-Polydatin and its metabolites resveratrol, glucuronidated resveratrol, and glucuronidated trans-polydatin were detected in plasma within 10 min following oral administration of trans-polydatin; in situ perfusion of the rat small intestine and liver with trans-polydatin yielded the same result. The AUC(0-infinity) of trans-polydatin and its metabolites increased in a dose dependent manner following oral administration of trans-polydatin. This indicates that in the rats, trans-polydatin is absorbed in a dose-dependent manner and undergoes extensive first-pass deglycosylation and glucuronidation. Orally administered trans-polydatin, therefore, is metabolized primarily to resveratrol in the small intestine and liver, where it is further metabolized to the glucuronidated resveratrol.


Iterative Learning Model Predictive Control Based on Iterative Data-Driven Modeling.
Iterative learning model predictive control (ILMPC) has been recognized as an effective approach to realize high-precision tracking for batch processes with repetitive nature because of its excellent learning ability and closed-loop stability property. However, as a model-based strategy, ILMPC suffers from the unavailability of accurate first principal model in many complex nonlinear batch systems. On account of the abundant process data, nonlinear dynamics of batch systems can be identified precisely along the trials by neural network (NN), making it enforceable to design a data-driven ILMPC. In this article, by using a control-affine feedforward neural network (CAFNN), the features in the process data of the former batch are extracted to form a nonlinear affine model for the controller design in the current batch. Based on the CAFNN model, the ILMPC is formulated in a tube framework to attenuate the influence of modeling errors and track the reference trajectory with sustained accuracy. Due to the control-affine structure, the gradients of the objective function can be analytically computed offline, so as to improve the online computational efficiency and optimization feasibility of the tube ILMPC. The robust stability and the convergence of the data-driven ILMPC system are analyzed theoretically. The simulation on a typical batch reactor verifies the effectiveness of the proposed control method.


Haemorrhagic ileal haemolymphangioma: a case report and review of the literature.
We describe herein a 37-year-old woman with a 2-week history of melena who was eventually diagnosed with ileal haemolymphangioma, a rare benign tumour. Local mucosal congestion and swelling were found through single-balloon enteroscopy, which showed an irregular protuberance approximately 10 cm long, located 3.2 m from the Treitz ligament. We performed a laparoscopic-assisted partial resection of the small intestine combined with intestinal adhesiolysis. According to postoperative pathology, the final diagnosis was ileal haemolymphangioma with haemorrhage.


Treatment of hepatic pancreatic ductal adenocarcinoma metastases with high-dose-rate image-guided interstitial brachytherapy: a single center experience.
To evaluate the efficacy and safety of image-guided (computed tomography/magnetic resonance imaging - CT/MRI) high-dose-rate (HDR) interstitial brachytherapy (iBT) as a salvage maneuver for the treatment of hepatic metastases originating from hepatic pancreatic ductal adenocarcinoma (PDAC). PDAC metastases present a major and unresolved problem, and any surgical approach or local therapeutic intervention remains extremely controversial. A cumulative number of 45 hepatic PDAC metastases in 16 patients were treated and retrospectively analyzed. Synchronous metastatic spread was observed in five patients, metachronous in eleven. 14 patients had resection of the pancreatic primary prior to iBT: eight Whipple/PPPD and six distal pancreatectomy procedures. The hepatic metastases were progressing under chemotherapy, thus iBT was applied as a salvage maneuver with the intention of local tumor control and prolonged survival. iBT is applied interstitially, with temporarily introduced 192Ir source in a single fraction HDR irradiation regime to eradicate vital tumor cells. Response to treatment was assessed clinically with CT/MRI every three months. Local tumor control was achieved in 87% of all treated metastases. The median diameter of the irradiated lesions was 2.2 cm (range, 1-11.2 cm), the median irradiation dose was 21 Gy (range, 5-29.1 Gy). Median progression-free survival (PFS) after iBT was 3.4 months (range, 1.5-19.6 months), the median overall survival (OS) after iBT was 8.9 months (range, 3.1-29.3 months). Three major complications (CTCAE grade 3) occurred following iBT: three cases of liver abscess, which were successfully resolved with drainage and antibiotics. Overall, iBT is a safe procedure, which enables excellent rates of local tumor control and presents a viable anti-neoplastic treatment option as a salvage therapy for metastatic PDAC patients.


Superresonant Radiation Stimulated by Higher Harmonics.
Solitons propagating in media with higher-order dispersion will shed radiation known as resonant radiation, with applications in frequency broadening, deep UV sources for spectroscopy, and fundamental studies of soliton physics. Using a recently proposed equation that models the behavior of ultrashort optical pulses in nonlinear media using the analytic signal, we find that the resonant radiation associated with the third-harmonic generation term of the equation is parametrically stimulated with an unprecedented gain. Resonant radiation levels, typically only a small fraction of the soliton, are now as intense as the soliton itself. The mechanism is universal and works also in normal dispersion and with harmonics higher than the third. We report experimental hints of this superresonant radiation stimulated by the fifth harmonic in diamond.


[Some predictions of possible changes in the mortality of Bulgarian men by the year 2000].
"Dynamic sequences of general mortality rates of Bulgarian men for the period 1964-1991 are represented. Trends are evaluated by the statistical significance of linear regression coefficients of every sequence. Trends of mortality rates by [social] classes...are also represented. It is found...that the general mortality of Bulgarian men as well as their mortality from practically all leading causes had significantly increased during the period.... Based on these trends, the author foresees that today's regimen of male mortality in Bulgaria most probably will remain unchanged at least till the end of the current century...." (SUMMARY IN ENG AND RUS)


Normal distribution of regional cerebral blood flow measured by dynamic single-photon emission tomography.
Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1-10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 +/- 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = -0.33 ml/min/100 g/year; p less than 0.05).


Cloning and functional characterization of a complementary DNA encoding the murine fibroblast bombesin/gastrin-releasing peptide receptor.
The amphibian tetradecapeptide bombesin and its mammalian homolog gastrin-releasing peptide are neurotransmitters and paracrine hormones, and are mitogenic for fibroblast and small cell lung carcinoma cell lines. cDNAs encoding the bombesin/gastrin-releasing peptide receptor (BR) expressed by murine Swiss 3T3 fibroblasts were isolated using electrophysiological and luminometric Xenopus oocyte expression assays. Oocytes microinjected with BR transcripts responded to concentrations of bombesin from 1 x 10(-10) to 1 x 10(-6) M. These responses showed homologous desensitization and could be specifically blocked by bombesin antagonists. Sequence analysis showed that the BR has seven membrane-spanning domains and five potential N-linked glycosylation sites. Data base analysis showed that the BR is most homologous to the tachykinin receptors. Although tyrosine kinase activity has been associated with BR function, no tyrosine kinase homologies occur within the BR sequence.


Transcriptional hierarchy in Xenopus embryogenesis: HNF4 a maternal factor involved in the developmental activation of the gene encoding the tissue specific transcription factor HNF1 alpha (LFB1).
The tissue specific transcription factor HNF1 alpha (LFB1) expressed in liver, kidney, stomach and gut gets transcriptionally activated in Xenopus shortly after zygotic transcription starts. By microinjection into fertilized Xenopus eggs, a HNF1 alpha promoter fragment is activated in the middle part of developing larvae, reflecting the activation pattern of the endogenous HNF1 alpha gene. Mutational analysis of the HNF1 alpha promoter shows that HNF1 and HNF4 binding sites are essential for proper embryonic regulation. Since by injecting HNF4 mRNA into fertilized eggs the endogenous HNF1 alpha gene is activated ectopically and HNF4 is present as a maternal protein within an animal to vegetal gradient in the embryo, we assume that HNF4 initiates a transcriptional hierarchy involved in determination of different cell fates.


[Follow-up studies for long-term postoperative complications of Warshaw operation].
To explore the long-term postoperative complications of Warshaw operation for distal pancreatectomy with preservation of spleen. Retrospectively analyzed the clinical data of distal pancreatectomy on 84 cases between January 2006 and January 2012. Among them, 35 patients underwent Warshaw operation for distal pancreatectomy with preservation of spleen and another 23 had distal pancreatectomy with Kimura operation. All of them were followed up. All procedures were successful. There was no perioperative mortality. During the follow-up period, 2 patients undergoing Warshaw operation were lost. The median follow-up period was 2.6 years (range: 0.75-6.75). Twenty-six patients with the recent neuroimaging data showed: 5 patients were diagnosed of splenic infarction and the incidence rate was 19.2% (5/26) and 6 with gastric varices and the incidence rate was 23.1% (6/26). But none of them developed gastrointestinal hemorrhage or splenic abscess. The Warshaw operation for distal pancreatectomy with preservation of spleen may increase the risk of long-term postoperative complications so that its operative indication must be strictly mastered.


Digital phonoarthrometry of temporomandibular joint sounds: a preliminary report.
A new technique is presented for recording and evaluating the dysfunctional TMJ sounds on an objective basis. The physical implications related to TMJ phonoarthrometry (PAM) are discussed and three cases are presented. The phonoarthrography and the digital phonoarthrometry presented in this paper can be a useful harmless diagnostic tool. Differential diagnosis of TMJ pathology is possible on the basis of an acoustical analysis and it is hoped that future investigation will confirm these observations.


Bioabsorbable Steroid Eluting Stents in the Treatment of Recurrent Rathke's Cleft Cyst.
Objectives Bioabsorbable steroid eluting stents may prevent the stenosis of ostia after sinus surgery. We describe a technique utilizing this technology to prevent the reformation of Rathke's cleft cysts (RCC) after transnasal transsphenoidal surgical drainage. Design This study is based on retrospective review. Setting The research took place at Tertiary academic medical center. Participants Patients who underwent endoscopic marsupialization of RCC with stent placement were participated in this study. Main Outcome Measures Demographics, surgical history, outcomes, and complications were primary measures of this study. Results Four patients underwent drainage of a recurrent RCC with subsequent stent placement. All patients consented to off-label use of the stent. The mean age of patients was 42 years old and the number of prior drainage procedures ranged from 1 to 3. The stent was placed directly into the opening of the cyst after drainage with no other tissue placed into the cyst cavity or opening. The stents are bioabsorbable and were not removed after surgery but were evaluated endoscopically at 2 and 6 weeks after surgery. The patients have been followed for a mean of 14 months after surgery with no evidence of recurrence on endoscopic exam or imaging. No patient had cerebrospinal fluid leak during or after the operation or permanent endocrinopathy. Conclusion The use of a bioabsorbable steroid eluting stent had no unanticipated consequences and all drainage pathways of all the RCCs remain patent. The use of this technology may decrease recurrence rates in revision or complex cases where patients have extensive scarring of the operative field from prior drainage procedures. Further follow-up of the current cases and study in a larger cohort are warranted.


Hemophilus influenzae meningitis in an adult.
Hemophilus influenzae type B is no longer considered a rare cause of adult meningitis. Clinical presentation is no different from that of other types of bacterial meningitis. When H influenzae is suspected on the basis of CSF examination, the preferred treatment is chloramphenicol (Chloromycetin) with or without ampicillin until ampicillin susceptibility or beta-lactamase production is determined.


Table saw injuries: epidemiology and a proposal for preventive measures.
Table saws are ubiquitous devices in professional, home, and school woodshops that have the potential to cause severe injuries. Many of these injuries results in finger and thumb tendon, nerve, and vascular damage or amputation. Long-term outcomes of these injuries can include functional and sensory deficits. Table saw manufacturers are required to equip saws with blade guards to prevent blade contact; nevertheless, treatment of table saw injuries is a common occurrence in U.S. emergency departments. The authors performed a literature search using PubMed and the Cumulative Index to Nursing and Allied Health Literature to compile epidemiology data relevant to table saw injuries. The authors also reviewed the U.S. Consumer Product Safety Commission's briefing package on table saw blade contact injuries. Over 30,000 table saw injuries occur annually. Fingers and hands are the most frequently injured body parts, and lacerations are the most common injuries. Individuals suffering from occupational injuries tend to be younger than those injured during amateur woodworking. A small but important minority of injuries are to students participating in school shop classes. Medical costs for the treatment of table saw injuries are estimated at more than $2 billion every year. SawStop technology stops the saw blade when contact with skin is made, resulting in a small cut rather than a more complicated laceration or amputation. The application of this novel technology in saw designs can prevent serious injuries that deleteriously affect lives at the personal and societal levels.


Effect of taurine levels on liver lipid metabolism: an in vivo study in the rat.
Previous studies using guinea pigs and cats have shown that liver lipid composition is affected by intrahepatic taurine levels. The purpose of the present study was to determine whether this sulfonated amino acid could also affect lipid metabolism in the rat, an animal capable of synthesizing substantial amounts of taurine and used extensively in studies on lipid metabolism. Wide variations in the hepatic taurine content were induced by administering either 1% taurine or 1% guanidinoethane sulfonate in the drinking water for 2 weeks. These treatments increased and decreased taurine liver content, respectively, but did not affect either food or water intakes, or growth rates. The plasma concentrations of the major lipid classes in treated animals did not show any significant alteration in comparison to control animals, except for nonesterified fatty acid levels that were significantly lowered by guanidinoethane sulfonate administration. Taurine supplementation did cause a significant decrease in total hepatic lipid content that was attributable to the reduction of free and esterified cholesterol, triglyceride, and phosphatidylethanolamine hepatic concentrations. This same treatment slightly increased both bile flow and secretion of taurine-conjugated primary bile salts. In particular, the proportion of tauro-beta-muricholate significantly increased, whereas that of taurodeoxycholate greatly decreased. The administration of guanidinoethane sulfonate reduced both the bile flow and the secretion of taurine-conjugated bile salts and caused a significant alteration in the ratio between glycine- and taurine-conjugated bile salts. This did not occur after the treatment with taurine. Interestingly, we observed an inverse correlation between hepatic taurine levels and the proportion of either cholesteryl ester in hepatic lipids or taurochenodeoxycholate in biliary bile salts. These facts suggest that taurine hepatic levels influence mostly hepatic steroid metabolism, but they also affect the metabolism of other lipid classes.


Ploidy level and nucleotide variations in inflorescence dichotomous cultivars of plantain (Musa spp. AAB genome).
Inflorescence dichotomy in Musa species is a rare developmental event which leads to the production of multiple bunches on a single pseudostem at fruiting. In spite of its fascinating attraction and seductive appeal, little is known about the cytogenetic basis and molecular mechanisms that could be ascribed to this phenomenon. To bridge this gap in information, an integrative approach using cytological fingerprinting and DNA ploidy level profiling (based on chromosome counting and flow cytometry) were assayed on five inflorescence dichotomous plantain varieties and a single-bunching cultivar that served as control. This was done to assess the number and behaviour of chromosomes on the one hand and single nucleotide polymorphisms identified during analysis of nucleotide variations on the other. Chromosomes stained with aceto-orcein were very tiny, compact, metacentric and acrocentric, and differed both in number and ploidy level between the inflorescence dichotomous and single-bunching cultivars. The dichotomous plantains were mainly diploid (2n = 2x = 22) while the single-bunching 'Agbagba' cultivar was consistently a triploid (2n = 3x = 33), as revealed by histological chromosome counting and flow cytometry, implying that there was a high incidence of genomic divergence on account of ploidy variations among the different Musa cultivars. Molecular genotyping using single nucleotide polymorphisms detected on the GTPase-protein binding gene of the leaf tissue gene complex provided further evidence indicating that differences in the number of bunches among the inflorescence dichotomous cultivars could be ascribed to nucleotide diversity that was elicited by changes in amino acid sequences in the genome of the crops. Non-synonymous nucleotide substitutions resulted mainly from transversion (from purine to pyramidine and vice versa), tacitly implying that these changes were crucial and promoted a cascade of reactions in the genome that were, probably, responsible for the non-persistence of the dichotomization event(s) or the reversals in the bunch phenotype detected among the inflorescence dichotomous cultivars. This is the first report of cytogenetic fingerprints and nucleotide diversity detection among single- and multiple-bunching Musa cultivars. A clear distinction between the two groups was found that is indicative of variations both in ploidy level and nucleotide sequences. The pattern of single nucleotide polymorphisms provided profound clues suggesting that there was a high incidence of genomic divergence, due to random and unstable genetic events that were triggered by frequent spontaneous somatic mutations.


New photoluminescence acylhydrazidate-coordinated complexes.
Under the hydrothermal conditions, five new acylhydrazidate-containing compounds [Cd(EPDH)(2)(H(2)O)] 1, [Cd(MPDH)(2)] 2, [Zn(MPDH)(2)(H(2)O)(2)]·2H(2)O 3, [Pb(2)(ODPTH)(2)(phen)(2)(H(2)O)(2)] 4 and [Cd(2)(APTH)(4)(phen)(2)]·2H(2)O 5 (EPDH = 5-ethylpyridine-2,3-dicarboxylhydrazidate, MPDH = 6-methylpyridine-2,3-dicarboxylhydrazidate, ODPTH = 4,4'-oxydiphthalhydrazidate, APTH = 3-amiophthalhydrazidate, phen = 1,10-phenanthroline) were luckily obtained. Note that MPDH, EPDH and ODPTH were derived from the hydrothermal in situ acylation reactions between organic polycarboxylic acids and N(2)H(4)·H(2)O, whereas APTH originated from the hydrothermal in situ reduction reaction of NPTH (NPTH = 3-nitrophthalhydrazidate) in the presence of N(2)H(4)·H(2)O. The photoluminescence analysis indicates that all of the title compounds are fluorescent materials with maximum emissions at 530 nm for 1, 540 nm for 2, 517 nm for 3, 413 nm for 4 and 563 nm for 5, respectively. The density functional theory (DFT) calculations on the excited electronic states of compound 3 indicate that the emission is associated with the ligands, corresponding to the charge transfer from the π orbital of the acylhydrazidate ring to the π* orbital of the pyridine ring.


Effect of protein A immunoadsorption on panel lymphocyte reactivity in hyperimmunized patients awaiting a kidney graft.
Six hyperimmunized patients awaiting a kidney graft underwent immunoadsorption of separated plasma through a protein-A column to remove HLA antibodies. This procedure was partially limited by constant and rapid antibody resynthesis in spite of strong immunosuppression with cyclophosphamide and prednisolone. Only two patients could be grafted with previously positive--currently negative crossmatches. The first died of infection on day 40, having developed early chronic vascular rejection and the other returned to hemodialysis on day 285 after the development of transplant glomerulopathy. However, immunoadsorption seems to be effective in removing HLA antibodies having a titer below 1/2. Such extremely hyperimmunized patients should probably be excluded from the immunoadsorption program.


CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer.
The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.


Purified plasma factor XIIa aggregates human neutrophils and causes degranulation.
Plasma kallikrein has been shown to aggregate human neutrophils and release human neutrophil elastase. However, neutrophils resuspended in factor XII-deficient plasma released only 30% of the elastase compared with normal plasma. Isolated human neutrophils were aggregated in a concentration-dependent fashion by 0.06 to 0.6 U/mL factor XIIa (0.022 to 0.22 mumol/L). Factor XIIa (0.1 to 1.0 U/mL) also induced neutrophil degranulation as evidenced by a concentration-dependent release of the specific granule protein, lactoferrin, and azurophilic granule protease, elastase. The release of neutrophil elastase was biphasic, reaching 40% of maximum at 15 seconds with maximal release by 90 minutes. The active site of factor XIIa was required, since the synthetic inhibitor, D-Pro-Phe-Arg-CH2Cl, which reacts with an essential histidine, and the natural plasma inhibitor, Cl-inhibitor, which interacts with the critical serine, both inhibit by more than 90% the release of elastase. The heavy chain is also required, since factor XII fragments failed to aggregate neutrophils or stimulate degranulation. Factor XIIa (0.6 U/mL) can completely correct the defect in elastase release evident in factor XII-deficient plasma. These studies demonstrate that factor XIIa, at concentrations potentially obtainable in plasma in disease states, can activate neutrophils, and thus may participate in the inflammatory response.


A phase I dose-finding design with incorporation of historical information and adaptive shrinking boundaries.
Although many novel phase I designs have been developed in recent years, few studies have discussed how to incorporate external information into dose-finding designs. In this paper, we first propose a new method for developing a phase I design, Bayesian optimal interval design (BOIN)[Liu S et al. (2015), Yuan Y et al. (2016)], for formally incorporating historical information. An algorithm to automatically generate parameters for prior set-up is introduced. Second, we propose a method to relax the fixed boundaries of the BOIN design to be adaptive, such that the accumulative information can be used more appropriately. This modified design is called adaptive BOIN (aBOIN). Simulation studies to examine performances of the aBOIN design in small and large sample sizes revealed comparable performances for the aBOIN and original BOIN designs for small sample sizes. However, aBOIN outperformed BOIN in moderate sample sizes. Simulation results also showed that when historical trials are conducted in settings similar to those for the current trial, their performance can be significantly improved. This approach can be applied directly to pediatric cancer trials, since all phase I trials in children are followed by similar efficient adult trials in the current drug development paradigm. However, when information is weak, operating characteristics are compromised.


[An experimental study on the antitumor effects induced by fusions of dendritic cells with NCI-H460 lung cancer cells].
To study the antitumor effects induced by fusions of dendritic cells (DC) and NCI-H460 cells and compared with antigen pulsed DC. (1) DC were induced from human monocytes and were fused with NCI-H460 cells. Three experimental groups were set up, including group fusions cell (FC), group pulsed cell (PC) and group T cell (TC), for which T cells activated by fusions, antigen pulsed DC, and non-activated T cells were used as the effector cells respectively. The killing activity of effector cells to NCI-H460 cells were evaluated by lactate dehydrogenase method. (2) NCI-H460 cells were injected subcutaneously to BALB/c nude mice. Then 18 cancer-bearing mice were divided randomly into 3 groups, group FC, group PC and group TC. Effector cells mentioned above were inoculated subcutaneously. The tumor size and tumor weight were assessed and compared. The killing rates to NCI-H460 cells of group FC, group PC and group TC were 43.54%, 26.57% and 3.25% respectively. Comparison of the killing activity of these 3 groups showed group FC > group PC > group TC (F = 5.47, P < 0.05). The tumor size of group FC was significantly smaller than that of group PC and group TC. The tumor weights of group FC, group PC and group TC were (1,129 +/- 123) mg, (1,709 +/- 160) mg and (3,344 +/- 288) mg respectively (F = 37.05, P < 0.01). Fusions of DC and NCI-H460 cells could induce powerful antitumor immunity, which was more effective than antigen pulsed DC.


Minimal detectable change in six-minute walk test in children and adolescents with cystic fibrosis.
To provide test-retest reliability for the 6-min walk test and the physiological variables obtained during the test, and to establish the minimal detectable change for the distance walked in children and adolescents with cystic fibrosis. 40 patients performed two 6-min walk tests on the same day (separated by 30-min of rest). The perceived breathlessness and fatigue in the legs were assessed with the modified Borg scale. The peripheral muscle strength was assessed using a hand dynamometer device, the medicine ball throw test and the horizontal jump test. The test-retest reliability of the distance walked, dyspnea and fatigue in the legs were good for children (minimal detectable change90-95: 59.39-70.55 m) and for adolescents (minimal detectable change90-95: 47.81-56.8 m) with cystic fibrosis. Exercise tolerance is more related to 6-min walk work (distance walked x body weight) than to the distance walked alone and showed a positive association with peripheral muscle strength and forced vital capacity. The 6-min walk test is a reproducible and reliable tool to measure exercise tolerance for children and adolescents with cystic fibrosis. The minimal detectable changes reported for the distances achieved by these patients will be useful to identify the effectiveness of therapies aimed at alleviating or improving impaired physical capacity.IMPLICATIONS FOR REHABILITATIONThe 6-min walk test could be used to measure exercise tolerance for children and adolescents with cystic fibrosis, as it is a reliable test over time.An increase in the distance covered in the 6-min walk test that exceeds the minimum detectable change is recommended to determine improved exercise tolerance for children and adolescents with cystic fibrosis.The use of the 6-min walk work (distance walked x body weight) is recommended because it correlates better with exercise tolerance than the distance alone in children and adolescents with cystic fibrosis.


Compatibility of ZOLL Defibrillators in Simulation-Based Training.
In response to the need for high-quality cardiopulmonary resuscitation (CPR) during cardiac arrest, our institution recently purchased ZOLL R Series monitor/defibrillators. This defibrillator provides CPR quality metrics and displays a filtered rhythm through compressions. Purchase of this defibrillator resulted in a practice change and heavily impacted our simulation-based training courses by requiring providers to practice CPR and defibrillation in as close to the real environment as possible. Thus, our objective was to determine which commercial simulators would be compatible with the ZOLL R Series defibrillator system and its CPR feedback functionality in a simulation-based training setting. Our simulation center uses primarily Gaumard Scientific and Laerdal Medical simulators ranging in size from neonate to adult. Through an iterative process in the laboratory, we evaluated if, and to what level, the CPR display metrics, filtered rhythm, and idle time display could be demonstrated with CPR on the different simulators using infant, pediatric, and adult pads. Certain simulators allow demonstration and real-time practice of defibrillator functions better than others with the ZOLL R Series system when used in the context of CPR training. We have no high-fidelity infant-sized simulators that can meet the depth recommendation for chest compressions given by the American Heart Association. Ventricular fibrillation is the only rhythm that offers a filtered option. Idle time can be reliably displayed for simulators where CPR is detected. When a primary learning objective for simulation-based training involves training on the ZOLL R Series defibrillator, there are a limited number of simulators and rhythms that can accurately represent its features.


Identification of ion series using ion mobility mass spectrometry: the example of alkyl-benzothiophene and alkyl-dibenzothiophene ions in diesel fuels.
Ion mobility-mass spectrometry (IMMS) has been presented as a promising method for analysis of highly complex mixtures. This coupling adds an additional postionization separation dimension to MS. The IM separation of ions is obtained in the millisecond time scale and can be particularly helpful when chromatographic separation is not possible. For obtaining relevant information about the samples, data processing is usually the bottleneck because of the high amount of data generated with IMMS. In the current work, we present a new workflow using specific comparison software dedicated to IMMS data, which allows one to compare m/z-drift time plots to highlight differences between samples. Two diesel fuels have been compared, i.e., the feed and the product of hydrodesulfurization (HDS) process, and this approach allowed us to clearly highlight the variation of intensity of several ions distributed along the plots of both samples. Accurate mass measurements and post IM collision induced dissociation experiments allowed us to identify two series of polycyclic aromatic sulfur-containing heterocycle (PASH) compounds among the matrix ions.


Intracisternal cranial root accessory nerve schwannoma associated with recurrent laryngeal neuropathy.
Intracisternal accessory nerve schwannomas are very rare; only 18 cases have been reported in the literature. In the majority of cases, the tumor origin was the spinal root of the accessory nerve and the tumors usually presented with symptoms and signs of intracranial hypertension, cerebellar ataxia, and myelopathy. Here, we report a unique case of an intracisternal schwannoma arising from the cranial root of the accessory nerve in a 58-year-old woman. The patient presented with the atypical symptom of hoarseness associated with recurrent laryngeal neuropathy which is noted by needle electromyography, and mild hypesthesia on the left side of her body. The tumor was completely removed with sacrifice of the originating nerve rootlet, but no additional neurological deficits. In this report, we describe the anatomical basis for the patient's unusual clinical symptoms and discuss the feasibility and safety of sacrificing the cranial rootlet of the accessory nerve in an effort to achieve total tumor resection. To our knowledge, this is the first case of schwannoma originating from the cranial root of the accessory nerve that has been associated with the symptoms of recurrent laryngeal neuropathy.


Does chemical aposematic (warning) signaling occur between host plants and their potential parasitic plants?
Aposematism (warning) signaling is a common defensive mechanism toward predatory or herbivorous animals, i.e., interactions between different trophic levels. I propose that it should be considered at least as a working hypothesis that chemical aposematism operates between certain host plants and their plant predators, parasitic plants, and that although they are also plants, they belong to a higher trophic level. Specific host plant genotypes emit known repelling chemical signals toward parasitic plants, which reduce the level of, slow the directional parasite growth (attack) toward the signaling hosts, or even cause parasitic plants to grow away from them in response to these chemicals. Chemical host aposematism toward parasitic plants may be a common but overlooked defense from parasitic plants.


Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge.
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.


[Antibiotic-resistance in Italy: activity of the first year of the surveillance project AR-ISS].
The antibiotic resistance surveillance project AR-ISS, started in 2001, is based on a network of 62 sentinel microbiological laboratories throughout the country. The laboratories collect and transmit data to the Istituto Superiore di Sanità on the antibiotic susceptibility of bloodstream isolates of 7 species: Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis/faecium, Klebsiella pneumoniae/oxytoca ed Escherichia coli. They also send selected bacterial strains for further characterization. Results of the first year of surveillance are presented and are compared with data from the previous study EARSS-Italia and from other European countries. Oxacillin resistance in S. aureus appears to be stable, however, it remains one of the highest in Europe (41,5%). No strain with intermediate susceptibility or resistance to vancomycin has been isolated. In S. pneumoniae, the level of penicillin resistance is moderate (10,8%), but macrolide resistance has increased greatly (37,6% versus 28,6% of the previous study), following a tendency common to several European countries. Unexpectedly, vancomycin resistance in E. faecium was found to be 18%, the highest in Europe. Presumptive ESBL production in Gram-negative organisms can be estimated at 20% in Klebsiella and 1% in E. coli. Ampicillin and ciprofloxacin resistance in E. coli (respectively 50% and 18%) are among the highest in Europe. In conclusion, the rate of antibiotic resistance in the species studied is worrisome and requires continuing monitoring. Although some activities of AR-ISS need improvements, the surveillance has the potentiality to produce relevant and representative data about antibiotic resistance in Italy that can be used for comparison at the European level.


The Fat and Warts signaling pathways: new insights into their regulation, mechanism and conservation.
A cassette of cytoplasmic Drosophila tumor suppressors, including the kinases Hippo and Warts, has recently been linked to the transmembrane tumor suppressor Fat. These proteins act within interconnected signaling pathways, the principal functions of which are to control the growth and polarity of developing tissues. Recent studies have enhanced our understanding of the basis for signal transduction by Fat and Warts pathways, including the identification of a DNA-binding protein at the end of the pathway, have established the conservation of Fat and Warts signaling from flies to mammals, and have given us new insights into their regulation and biological functions.


Dos and don'ts for mHealth-based clinical support among clinicians in South Africa: Results from a 1-day workshop.
Digital technologies continue to penetrate the South African (SA) healthcare sector at an increasing rate. Clinician-to-clinician diagnostic and management assistance through mHealth is expanding rapidly, reducing professional isolation and unnecessary referrals, and promoting better patient outcomes and more equitable healthcare systems. However, the widespread uptake of mHealth use raises ethical concerns around patient autonomy and safety, and guidance for healthcare workers around the ethical use of mHealth is needed. This article presents the results of a multi-stakeholder workshop at which the 'dos and don'ts' pertaining to mHealth ethics in the SA context were formulated and aligned to seven basic recommendations derived from the literature and previous multi-stakeholder, multi-country meetings.


Phytotoxic chaetoglobosins are produced by the plant pathogen Calonectria morganii (anamorph Cylindrocladium scoparium).
By the application of a bioassay based on cresson seedlings, two phytotoxic compounds were isolated by thin-layer chromatography from the culture fluid of a Calonectria morganii isolate. The structure of both compounds was elucidated by ESI/MS and NMR spectroscopy. According to the Chemical Abstracts database, they were identified as chaetoglobosin A and 19-O-acetylchaetoglobosin A, mycotoxins originally described for Chaetomium globosum.


[Progress in the analysis of amino acids with special reference to the determination of the intracellular amino acid pattern].
Intracellular amino acid patterns are nowadays considered as suitable criteria to evaluate the therapeutical effects of newly developed nutritional techniques. Owing to the low sensitivity and resolution of conventional amino acid analysis (ion exchange chromatography with ninhydrin-detection), reproducible and reliable studies to assess alterations in intracellular amino acid concentrations are, however, limited. In this study, for the first time a routinely manageable HPLC method allowing fully automated determination of free amino acids by employing on-line precolumn derivatization with ortho-phthaldialdehyde is presented. The highly sensitive fluorescence detection (less than 10 pMol/amino and injection) enables the measurement of intracellular/extracellular amino acid levels in various tissues (blood, muscle, liver, kidney, leukocytes) by using minimum amounts to sample material. Furthermore, the high resolution of the HPLC method facilitates the simultaneous determination of amino acid derivatives as well as short chain peptides. The error and the reproducibility of the method (expressed as the coefficient of variation) ranged between 1.0-4.7% and 0.4-2.2%, respectively. In addition to ortho-phthaldialdehyde, alternative precolumn-derivatization reagents are described and evaluated with special regard to their applicability in the routinely manageable determination of intracellular amino acids in biological material.


Identification of patients best suited for combined liver-kidney transplantation: part II.
Liver-kidney transplantation (LKT) should be reserved for those recipients with primary disease affecting both organs. However, increasing transplant list waiting times have increased the development and duration of acute renal failure before liver transplantation. Furthermore, the need for posttransplant calcineurin inhibitors can render healing from acute renal failure difficult. Because of the increasing requests for and controversy over the topic of a kidney with a liver transplant (OLT) when complete failure of the kidney is not known, the following article will review the impact of renal failure on liver transplant outcome, treatment of peri-OLT renal failure, rejection rates after LKT, survival after LKT, and information on renal histology and progression of disease into the beginnings of an algorithm for making a decision about combined LKT.


Injury Prevention at the Bedside.
It is estimated that 1 in 4 children will have an unintentional injury that requires medical attention or intervention by the time they are 21 years of age. Emergency department staff have an opportunity to engage families in injury prevention messaging right at the bedside. Having staff who participate in an injured patient's care can better prepare a family or prevent another injury. Our emergency department staff identified these moments as prime teaching opportunities and worked with our trauma team to develop resources and education for patients and families that present to our department.


Climate causes shifts in grey seal phenology by modifying age structure.
There are numerous examples of phenological shifts that are recognized both as indicators of climate change and drivers of ecosystem change. A pressing challenge is to understand the causal mechanisms by which climate affects phenology. We combined annual population census data and individual longitudinal data (1992-2018) on grey seals, Halicheorus grypus, to quantify the relationship between pupping season phenology and sea surface temperature. A temperature increase of 2°C was associated with a pupping season advance of approximately seven days at the population level. However, we found that maternal age, rather than sea temperature, accounted for changes in pupping date by individuals. Warmer years were associated with an older average age of mothers, allowing us to explain phenological observations in terms of a changing population age structure. Finally, we developed a matrix population model to test whether our observations were consistent with changes to the stable age distribution. This could not fully account for observed phenological shift, strongly suggesting transient modification of population age structure, for example owing to immigration. We demonstrate a novel mechanism for phenological shifts under climate change in long-lived, age- or stage-structured species with broad implications for dynamics and resilience, as well as population management.


[Benign paroxysmal positional vertigo: follow-up of 165 cases treated by Semont's liberating maneuver].
The purpose of the present work has been to evaluate the effectiveness of the Semont's liberatory maneuver in treating benign paroxysmal positional vertigo (BPPV) stemming from lithiasis of the posterior semicircular canal. After taking an overview of the history, epidemiology and clinical manifestation of this pathology, the cases studied are presented: 165 cases of BPPV of the posterior semicircular canal diagnosed between September 1992 and December 1994 at the Audiology and E.N.T. Clinic of the Santo Spirito Hospital in Casale Monferrato, Italy. Diagnosis was based on careful examination of the case history and the finding of typical paroxysmal positional vertigo. Among the 1096 patients who came under observation for vertigo or instability, the incidence of BPPV was rather high: approximately 23%, predominantly females (64% of the cases). In 56% of the cases the right labyrinth was involved while the left labyrinth was involved in 39% (in 5% the form was bilateral). The average age of the patients was 60 years, with incidence being greatest in the 6th and 7th decades of life. In 10% of the cases the etiology was traumatic (cranial, cervical trauma or post otological or general surgery), in 5% it was of viral origin, in 1% of vascular origin; however, in the vast majority of cases (84%) it was idiopathic. All the patients were treated with the Semont's liberatory maneuver (repeated 1-3 times in subsequent sessions at 48 hour intervals). A full 62% of the patients treated were freed of the disorder after a single maneuver and 95.5% after 3 treatments. In 5% of the cases (3 very elderly patients), the disorder persisted even after rehabilitation with Brand Daroff's exercises. To evaluate the evolution in time, all the patients were sent a written questionnaire aimed at determining the progression of symptoms, any recurrences, the number of recurrences, and the length of time from the date of treatment. In the case of positive response, the patients were invited in for a clinical-instrumental check-up. This follow-up ranged from 6 to 30 months. At the end of May 1995 the case breakdown was as follows: 80.7% of the patients were still symptom free, most being quite satisfied with the results; 18% had had one or more recurrence of the paroxysmal positional vertigo which were successfully treated by one or more application of the Semont's maneuver.


Tumor spectrum in cancer family syndrome (hereditary nonpolyposis colorectal cancer).
The distribution of different malignant tumors was studied in 40 cancer family syndrome (CFS) families with 315 affected family members and a total of 472 separate tumors or malignant diseases. Only families with three or more first-degree family members with colorectal carcinoma were included and other CFS characteristics were required in at least two cases. Colorectal (63%), endometrial (8%), gastric (6%), biliopancreatic (4%), and uroepithelial carcinomas (2%) were the most frequent, and represent the tumors typical of CFS. Families with endometrial cancer (23, 57%) and those without endometrial cancer (17, 43%) did not differ in frequencies of other extracolonic carcinomas. Families with endometrial cancer has more affected members and especially more affected female members than those without endometrial cancer (means, 9.7 and 4.9 versus 5.5 and 1.6 per family, respectively). The authors conclude, therefore, that the occurrence of one or more types of extracolonic tumors in members of CFS families does not provide a firm basis for subdividing the CFS (or hereditary nonpolyposis colorectal carcinoma syndrome.


High rate of recombination and double crossovers in the mouse pseudoautosomal region during male meiosis.
The recombination rate in meiosis between the mouse X and Y chromosomes was analyzed. Mice heterozygous at two pseudoautosomal alleles, the steroid sulfatase gene and the Mov-15 provirus marker, were crossed. The provirus in the Mov-15 transgenic mouse strain had been previously shown to be carried in the pseudoautosomal region of the sex chromosomes. Recombination frequencies were shown to be 7-fold higher in this region in male meiosis than in female meiosis. Three-point crosses indicated the occurrence in male meiosis of double recombination events in the pseudoautosomal region, with little or no crossover interference, which is in marked contrast to observations made on the similar region of the human sex chromosomes. This result is contrary to a previous model, which predicted a single crossover event in male meiotic pairing of mammalian sex chromosomes.


Effects of the Surface Charge of Graphene Oxide Derivatives on Ocular Compatibility.
The incorporation of functional groups endows graphene oxide (GO) with different surface charges, which plays important roles in biological interactions with cells. However, the effect of surface charge of GO derivatives on ocular biocompatibility has not been fully elucidated. Previously, we found that positively, negatively and neutrally charged PEGylated GO (PEG-GO) nanosheets exerted similar effect on the viability of ocular cells. In this work, we performed in vitro and in vivo studies to comprehensively study the effect of surface charge of PEG-GO on ocular compatibility. The in vitro results showed that the cellular uptake efficacy of negatively charged PEG-GO nanosheets was significantly decreased compared with positively charged and neutrally charged analogs. However, three kinds of PEG-GO nanosheets produced similar amounts of intracellular reactive oxygen species and showed similar influence on mitochondrial membrane potential. By analysis of global gene expression profiles, we found that the correlation coefficients between three kinds of PEG-GO-treated cells were more than 0.98. Furthermore, in vivo results showed that all these PEG-GO nanosheets had no significant toxicity to ocular structure and function. Taken together, our work suggested that surface charge of PEG-GO exerted negligible effect on its ocular compatibility, except for the cellular uptake. Our work is conducive to understanding the relationship between surface charge and biocompatibility of GO derivatives.


Epidemiology of human dermatophytoses in Africa.
In this critical literature review, we summarize the epidemiological trends of dermatophytoses reported in Africa. Our findings clearly emphasize the heavy burden of dermatophytosis in Africa. Tinea capitis is the primary clinical presentation of dermatophytosis in African children throughout the entire African continent. The disease affects more than 20% of school-age children in West Africa, while the prevalence ranges from 10% to more than 70% in other regions of Africa. In African adults, the presence of tinea corporis is the most frequent indicator of dermatophytosis. However, epidemiological studies have been primarily conducted on particular patient groups that are not representative of the general population. We examined dermatophyte species distribution patterns. We observed a predominance of anthropophilic dermatophytes, mainly T. violaceum, in the North and East of Africa and both T. soudanense and M. audouinii in the Western and Central regions of the continent. Interestingly, the zoophilic species, M. canis, has recently emerged in North and East Africa. Optimization of both mycology diagnosis capacities and epidemiological methodology would provide insight into the role that climate and other global aspects of the human environment play in dermatophyte epidemiology. We advocate that using a multisectoral and collaborative strategy would strengthen such future studies.


Resequencing of Curcuma longa L. cv. Kedaram through transcriptome profiling reveals various novel transcripts.
Curcuma longa L. (Turmeric), of the family Zingiberaceae, is one of the economically as well as medicinally important plant species. It is a sterile, polyploid and vegetatively propagated spice crop cultivated usually in Southeast Asia. In the current study, we carried out re-sequencing through transcriptome profiling of Curcuma longa cv. Kedaram (Cl_Ked_6). We acquired a total of 1 GB raw data by resequencing through paired-end sequencing using Nextseq 500 platform. The raw data obtained in this study can be accessible in NCBI database with accession number of SRR3928562 with bioproject accession number PRJNA324755. Cufflinks-2.2.1 tool was used for transcriptome assembly which resulted in 39,554 numbers of transcripts. The transcript length ranged from 76 to 15,568, having N50 value of 1221 and median transcript length of 860. We annotated the transcripts using multiple databases. This data will be beneficial for studying sequence variations particularly SNPs between cultivars of turmeric towards authentic identification and discovery of novel functional transcripts in Kedaram.


RNA-based stable isotope probing and isolation of anaerobic benzene-degrading bacteria from gasoline-contaminated groundwater.
Stable isotope probing (SIP) of benzene-degrading bacteria in gasoline-contaminated groundwater was coupled to denaturing gradient gel electrophoresis (DGGE) of DNA fragments amplified by reverse transcription-PCR from community 16S rRNA molecules. Supplementation of the groundwater with [(13)C(6)]benzene together with an electron acceptor (nitrate, sulfate, or oxygen) showed that a phylotype affiliated with the genus Azoarcus specifically appeared in the (13)C-RNA fraction only when nitrate was supplemented. This phylotype was also observed as the major band in DGGE analysis of bacterial 16S rRNA gene fragments amplified by PCR from the gasoline-contaminated groundwater. In order to isolate the Azoarcus strains, the groundwater sample was streaked on agar plates containing nonselective diluted CGY medium, and the DGGE analysis was used to screen colonies formed on the plates. This procedure identified five bacterial isolates (from 60 colonies) that corresponded to the SIP-identified Azoarcus phylotype, among which two strains (designated DN11 and AN9) degraded benzene under denitrifying conditions. Incubation of these strains with [(14)C]benzene showed that the labeled carbon was mostly incorporated into (14)CO(2) within 14 days. These results indicate that the Azoarcus population was involved in benzene degradation in the gasoline-contaminated groundwater under denitrifying conditions. We suggest that RNA-based SIP identification coupled to phylogenetic screening of nonselective isolates facilitates the isolation of enrichment/isolation-resistant microorganisms with a specific function.


Increased expression of laminin-1 and collagen (IV) subunits in the aganglionic bowel of ls/ls, but not c-ret -/- mice.
Extracellular matrix molecules, including laminin, affect the development of enteric neurons and accumulate in the aganglionic colon of ls/ls mice. Quantitative Northern analysis revealed that mRNAs encoding the beta 1 and gamma 1 subunits of laminin and collagens alpha 1(IV) and alpha 2(IV) are increased in the colons of ls/ls mice. Transcripts of laminin alpha 1 were evaluated quantitatively with reverse transcription and the competitive polymerase chain reaction (RT-cPCR). The abundance of laminin alpha 1 transcripts was developmentally regulated, but greater in the ls/ls than the wild-type colon at each age examined. In situ hybridization revealed that transcripts in the colon encoding laminin alpha 1 and beta 1 and collagen alpha 2(IV) were initially expressed in the endoderm, but by E15, expression shifted to cells of the colonic mesenchyme (ls/ls > wild type) where crest-derived cells migrate. The expression of laminin alpha 1 was examined in the totally aganglionic intestine of E15 and newborn c-ret -/- mice, to determine whether an increase occurs when neurogenesis fails independently of the ls/ls defect. RT-cPCR revealed no difference from control in mRNA encoding laminin alpha 1 in the c-ret -/- colon in either E15 or newborn animals. The accumulation of immunohistochemically demonstrable laminin that is prominent in the newborn ls/ls colon could not be detected in that of c-ret -/- animals. These observations suggest that transcripts encoding laminin-1 and collagen (IV) are increased in the colon and surrounding pelvic mesenchyme of ls/ls mice because of an intrinsic lesion, rather than a secondary consequence of aganglionosis. The data are compatible with the hypothesis that the increased expression of laminin-1 contributes to the failure of crest-derived cells to complete their colonization of the ls/ls colon.


Causes and Effects Contributing to Sudden Death in Epilepsy and the Rationale for Prevention and Intervention.
Sudden unexpected death in epilepsy (SUDEP) claims the lives of one in every thousand epileptic patients each year. Autonomic, cardiac, and respiratory pieces to a mechanistic puzzle have not yet been completely assembled. We propose a single sequence of causes and effects that unifies disparate and competitive concepts into a single algorithm centered on ictal obstructive apnea. Based on detailed animal studies that are sometimes impossible in humans, and striking parallels with a growing body of clinical examples, this framework (1) accounts for the autonomic, cardiac, and respiratory data to date by showing the causal relationships between specific elements, and (2) highlights specific kinds of data that can be used to precisely classify various patient outcomes. The framework also justifies a "near miss" designation to be applied to any cases with evidence of obstructive apnea even, and perhaps especially, in individuals that do not require resuscitation. Lastly, the rationale for preventative oxygen therapy is demonstrated. With better mechanistic understanding of SUDEP, we suggest changes for detection and classification to increase survival rates and improve risk stratification.


Congenital myopathies with "diagnostic" pathological features.
This addition to the classification of myopathies is a result of the improved diagnostic techniques in muscle pathology in recent years, largely through the application of electronmicroscopy and histochemistry. After summarizing the clinical picture, the authors call for classification: (1) Congenital myopathies due to developmental arrest: myotubular myopathy, congenital fiber type disproportion. (2) Congenital myopathies due to persistent organellar regression: focal loss of cross striation, myopathy with lysis of myofibrils, nemaline body myopathy, zebra body myopathy, spheroid body myopathy, myopathy with tubular aggregates, satellite cell myopathy. (3) Congenital myopathies due to metabolic errors: mitochondrial myopathy, mitochondria-lipid-glycogen disease. (4) Congenital myopathies due to the lack of the trophic influence of innervation: central core disease, multicore, minicore disease. These congenital myopathies have been taken from the ill-defined heterogeneous conglomeration known as amyotonia congenita or floppy infant syndrome and given a place of their own.


Overexpression of the phage lambda lysozyme cloned in Escherichia coli: use of a degenerative mixture of synthetic ribosome binding sites and increase of the protein stability in vivo.
The R gene of the phage lambda coding for a lysozyme expressed at the end of an infection cycle in Escherichia coli has been cloned in a series of vector plasmids. Two methods for improving the efficiency of translation have been tested. First, the use of a bicistronic construction in which the ribosome binding site (RBS) of the first cistron is that of a highly expressed gene or the use of a degenerate mixture of synthetic oligonucleotides for the optimization of a RBS. The second strategy is more efficient: the analysis of a number of clones reveals that the LaL expression levels are increased by a factor between 3 and 6 times compared with the clone using the natural RBS. The expression levels are described by an approximately Gaussian histogram. The translation promoter that was found to afford the best expression (PL) is under the control of a thermolabile repressor. Under the expression conditions, the protein is partially proteolysed. The proteolysis is significantly decreased by adding salt to the growth medium. After optimization, an increase in expression by a factor of 40 is obtained compared with the initial conditions. An efficient purification protocol is described.


Retinal pigment epithelial tears following ranibizumab therapy for fibrovascular retinal pigment epithelial detachment due to occult age-related macular degeneration.
The aim of this paper is to report the incidence of retinal pigment epithelial (RPE) tears in patients treated with ranibizumab for subfoveal fibrovascular retinal pigment epithelial detachment (FVPED) due to occult age-related macular degeneration (AMD). Thirty patients were treated according to the following schedule: saturation phase, further treatment was based on activity of the degeneration process. Visual acuity (VA), optical coherence tomography (OCT) and fluorescein angiography (FA) parameters were evaluated and compared. Patients had a mean improvement of +4.7 ± 8.1 letters at month 12. The mean number of needed injections was 6.8 ± 1.8 (range, 3 to 9). RPE tears in fovea occurred in 8 cases (27% of all patients). Analysis of variance revealed significant upper mean values of ETDRS letters for the subgroup without RPE tears. Mean values of PED height were significant upper for RPE tears without baseline. Statistical analysis revealed that in the subgroup without RPE tears mean values of VA significantly differed in succeeding periods compare to baseline (P<0.001). Visual improvement or stabilization was observed in 90.9% of patients without RPE tears (significant improvement of 15 or more letters in 22.7% - 5/22) and in 87.5% of patients with RPE tears (significant improvement was not observed). Baseline leakage parameters, lesion and leakage parameters at month 12 were significantly higher in patients with RPE tears. The chi-square test revealed statistically significant associations between RPE tears and subretinal fluid in OCT (P<0.05) at month 12. In eyes with FVPED and RPE tears treated with ranibizumab, stabilization of visual acuity without significant improvement is predictable. One of the risk factors common to RPE tears may be baseline leakage parameters and pretreatment distorted RPE contour in OCT. During ranibizumab therapy in eyes with RPE tears, upper parameters of FVPED height may occur without significant differences in fovea and macula volume compare to eyes without RPE tears.


Long-term wavelength stabilization of a commercial pulsed dye laser.
An inexpensive device is described that stabilizes the wavelength of a commercial nanosecond-pulsed dye laser. The instrument monitors the frequency-dependent interference pattern that is generated when a portion of the dye laser output passes through an external Fabry-Perot étalon. In order to maintain a fixed wavelength, a personal computer adjusts the dye laser's grating position when the interference pattern indicates that a shift in laser wavelength has occurred. Tests indicate that this device reduces the drift of the laser's mean wavelength to < 0.0001-nm/ degrees C ambient temperature change. The feedback mechanism incorporated in this design can sustain stationary frequency stabilization for indefinite periods of time.


Improving the performance of predictive process modeling for large datasets.
Advances in Geographical Information Systems (GIS) and Global Positioning Systems (GPS) enable accurate geocoding of locations where scientific data are collected. This has encouraged collection of large spatial datasets in many fields and has generated considerable interest in statistical modeling for location-referenced spatial data. The setting where the number of locations yielding observations is too large to fit the desired hierarchical spatial random effects models using Markov chain Monte Carlo methods is considered. This problem is exacerbated in spatial-temporal and multivariate settings where many observations occur at each location. The recently proposed predictive process, motivated by kriging ideas, aims to maintain the richness of desired hierarchical spatial modeling specifications in the presence of large datasets. A shortcoming of the original formulation of the predictive process is that it induces a positive bias in the non-spatial error term of the models. A modified predictive process is proposed to address this problem. The predictive process approach is knot-based leading to questions regarding knot design. An algorithm is designed to achieve approximately optimal spatial placement of knots. Detailed illustrations of the modified predictive process using multivariate spatial regression with both a simulated and a real dataset are offered.