Emerging roles of mistletoes in malignancy management.
Mistletoes are a group of obligate plant semi-parasites in the order Santalales. These clumps of plants growing on a wide range of host plants have been traditionally regarded as medicinal repositories. However, current scientific discoveries have validated their health potentials like never before. Their extracts containing alkaloids, viscotoxins, lectins, and polysaccharides have been evidenced to possess a myriad biological potentials including cancer inhibition. Mistletoes have emerged as promising alternative therapy against colon, oral, lung, and pancreas cancers. The plant extracts bolster immunity, delay tumour initiation and progression, kill malignant tumours, stabilize DNA, alleviate side effects of chemotherapeutics, improve the lifespan, and coping ability of cancer patients and survivors. A range of proprietary formulations viz. Iscador, Eurixor, Helixor, Lektinol, Isorel, Iscucin, Abnoba-viscum and recombinant lectin ML-1 are already being commercialized. This review presents an informative account on the recent developments in mistletoe-mediated cancer management. The underlying mechanisms, possibilities and limitations in cancer therapeutic development are outlined for kindling both researcher and public interest.


Impulsivity predicts poorer improvement in quality of life during early treatment for people with methamphetamine dependence.
Methamphetamine dependence is associated with heightened impulsivity and diminished quality of life, but the link between impulsivity and changes in quality of life during treatment has not been examined. We aimed to investigate how different elements of impulsivity predict change in quality of life in the 6 weeks after engaging in treatment. Longitudinal, observational cohort study. Public and private detoxification and rehabilitation facilities in metropolitan Melbourne, Australia. One hundred and eight individuals with methamphetamine dependence (81 male) tested within 3 weeks of commencing treatment; 80 (74%) were followed-up at 6 weeks. The Continuous Performance Test-2 measured impulsive action (cognitive and motor impulsivity); the Delay Discounting Task measured impulsive choice. Quality of life was measured with the World Health Organization Quality of Life Scale-Brief, which includes social, psychological, physical and environment domains. Control variables included age, gender, estimated IQ, depression severity score, methamphetamine dependence severity score, cannabis dependence severity score and treatment modality. We found that all three forms of impulsivity were significant predictors of change in the social domain: motor impulsivity (β = -0.54, P = 0.013), cognitive impulsivity (β = -0.46, P = 0.029) and impulsive choice (β = -0.26, P = 0.019). Change in the psychological domain was predicted significantly by motor impulsivity (β = -0.45, P = 0.046). Control variables of age and depression were associated significantly with changes in the physical domain. In Australian methamphetamine-dependent individuals, elevated impulsivity predicts lower improvement of social and psychological quality of life in the first 6-9 weeks of treatment.


DNA triple helices: biological consequences and therapeutic potential.
DNA structure is a critical element in determining its function. The DNA molecule is capable of adopting a variety of non-canonical structures, including three-stranded (i.e. triplex) structures, which will be the focus of this review. The ability to selectively modulate the activity of genes is a long-standing goal in molecular medicine. DNA triplex structures, either intermolecular triplexes formed by binding of an exogenously applied oligonucleotide to a target duplex sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at endogenous mirror repeat sequences, present exploitable features that permit site-specific alteration of the genome. These structures can induce transcriptional repression and site-specific mutagenesis or recombination. Triplex-forming oligonucleotides (TFOs) can bind to duplex DNA in a sequence-specific fashion with high affinity, and can be used to direct DNA-modifying agents to selected sequences. H-DNA plays important roles in vivo and is inherently mutagenic and recombinogenic, such that elements of the H-DNA structure may be pharmacologically exploitable. In this review we discuss the biological consequences and therapeutic potential of triple helical DNA structures. We anticipate that the information provided will stimulate further investigations aimed toward improving DNA triplex-related gene targeting strategies for biotechnological and potential clinical applications.


E2F1 suppresses skin carcinogenesis via the ARF-p53 pathway.
The E2F1 transcription factor, which is deregulated in most human cancers by mutations in the p16-cyclin D-Rb pathway, has both oncogenic and tumor-suppressive properties. This is dramatically illustrated by the phenotype of an E2F1 transgenic mouse model that spontaneously develops tumors in the skin and other epithelial tissues but is resistant to papilloma formation when subjected to a two-stage carcinogenesis protocol. Here, this E2F1 transgenic model was used to further explore the tumor-suppressive property of E2F1. Transgenic expression of E2F1 was found to inhibit ras-driven skin carcinogenesis at the promotion stage independent of the type of promoting agent used. E2F1 transgenic epidermis displayed increased expression of p19(ARF), p53, and p21(Cip1). Inactivation of either p53 or Arf in E2F1 transgenic mice restored sensitivity to two-stage skin carcinogenesis. While Arf inactivation impaired tumor suppression and p21 induction by E2F1, it did not reduce the level of apoptosis observed in E2F1 transgenic mice. Based on these findings, we propose that E2F1 suppresses ras-driven skin carcinogenesis through a nonapoptotic mechanism involving ARF and p53.


Radiographic study of delayed tooth development in patients with dental agenesis.
The aims of this study were to compare the radiographic development of permanent teeth in a group of children affected by dental agenesis with an unaffected control group and to determine the effects of confounding factors including the severity of the dental agenesis, age, sex, ethnicity, and the number of stages used to estimate dental age. A single-center retrospective cross-sectional study of dental panoramic tomographs was undertaken between July 2007 and April 2008 in a postgraduate teaching school. A total of 139 patients (aged 9-18 years) were recruited from the orthodontic clinic on the basis of predetermined inclusion and exclusion criteria to either a dental agenesis group or a control group. Dental panoramic tomograms were assessed, and the stages of development of the permanent teeth in the left maxillary and left mandibular regions were scored by using the 12 stages of Haavikko and the 8 stages of Demirjian and Goldstein. For each tooth scored, the mean dental age and standard error were determined by using the dental age assessment method, and an estimated dental age for each subject was derived by using the weighted average method. A statistically significant delay in dental age was found in the patients with dental agenesis compared with the control group. The dental age assessment method of Haavikko showed a delay of 1.20 years (SD, 1.74), and the method of Demirjian and Goldstein showed a delay of 1.64 years (SD, 1.75). It was also observed that older patients with dental agenesis had greater delays in tooth formation (P <0.001). With the Haavikko method, for every year of chronologic age, the delay in dental age increased by 0.53 year; with the Demirjian and Goldstein method, the delay increased by 0.48 year. A significant association was seen between the severity of dental agenesis and the delay in dental age (P <0.01). With both methods, for each additional developmentally absent tooth, the dental age was delayed by 0.13 year (lower confidence interval, -0.22; upper confidence interval, 0.35). There was no evidence that sex or ethnicity has an effect on the delay in dental age in patients with dental agenesis. The development of permanent teeth in children with dental agenesis is delayed when compared with a matched control group. The severity of dental agenesis affected the magnitude of the delay (P <0.01). This delay has implications in orthodontic treatment planning and in the estimation of age for legal, immigration, archaeological, and forensic purposes.


Treatment of Diaphyseal Tibial Fractures Distal to a Total Knee Arthroplasty by Intramedullary Nailing Is Safe and Effective.
To report the clinical result of a series of patients who underwent intramedullary nailing (IMN) of tibial shaft fractures distal to a total knee arthroplasty (TKA). Retrospective case series. Level-1 trauma center. Patients who sustained a tibial shaft fracture distal to a TKA treated with an IMN. IMN of tibial shaft fractures distal to a TKA. Postoperative weight-bearing status, readmissions, and complications or failure of treatment within 90 days; Knee Injury and Osteoarthritis Outcome Scores at the final follow-up; failure of treatment; and revision surgery. Nine patients were included. The average age was 71.4 years (range 55-87 years). All TKAs were cemented. The average distance between the tibial keel and the cortical density of the tibial tubercle was 24.1 mm (range 19.5-26.7 mm). Six nails were inserted using an infrapatellar portal, 2 were inserted using a suprapatellar portal, and 1 was inserted using a lateral parapatellar approach. The median nail diameter was 10 mm (range 9-12 mm). All fractures were healed at the final follow-up. There were no infections or arthroplasty-related complications. Knee Injury and Osteoarthritis Outcome Scores ranged from 100% to 74% (median 82%). Overall, we report on the largest cohort in the literature undergoing IMN of a tibial shaft fracture distal to a TKA. We demonstrate that IMN of diaphyseal tibial fractures distal to a TKA can be performed safely. We additionally demonstrate that this treatment is highly effective in achieving fracture union with no arthroplasty-related complications. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Confirmation Bias through Selective Overweighting of Choice-Consistent Evidence.
People's assessments of the state of the world often deviate systematically from the information available to them [1]. Such biases can originate from people's own decisions: committing to a categorical proposition, or a course of action, biases subsequent judgment and decision-making. This phenomenon, called confirmation bias [2], has been explained as suppression of post-decisional dissonance [3, 4]. Here, we provide insights into the underlying mechanism. It is commonly held that decisions result from the accumulation of samples of evidence informing about the state of the world [5-8]. We hypothesized that choices bias the accumulation process by selectively altering the weighting (gain) of subsequent evidence, akin to selective attention. We developed a novel psychophysical task to test this idea. Participants viewed two successive random dot motion stimuli and made two motion-direction judgments: a categorical discrimination after the first stimulus and a continuous estimation of the overall direction across both stimuli after the second stimulus. Participants' sensitivity for the second stimulus was selectively enhanced when that stimulus was consistent with the initial choice (compared to both, first stimuli and choice-inconsistent second stimuli). A model entailing choice-dependent selective gain modulation explained this effect better than several alternative mechanisms. Choice-dependent gain modulation was also established in another task entailing averaging of numerical values instead of motion directions. We conclude that intermittent choices direct selective attention during the evaluation of subsequent evidence, possibly due to decision-related feedback in the brain [9]. Our results point to a recurrent interplay between decision-making and selective attention.


[Theoretical calculation of vibrational frequencies for clusters of (1,2-micro2-L1)(1,2-micro2-L2)-decacarbonyltriosmium [L1, L2=H, Cl, Br, I]].
Density functional theory (DFT) and ab initio method have been employed to optimize the molecular geometry of (1,2-micro2-H) (1, 2-micro2-L) Os3 (CO)10 (L: Cl, Br, I) at B3LYP/CEP-4G, B3LYP/LanL2DZ, RHF/CEP-4G and RHF/LanL2DZ levels, respectively. By using ab initio method, the authors have optimized the molecular geometry of (1,2-t12 -L)2 Os3 (CO)20 (L: H, Cl, Br, I). The calculations showed that the charge was translated from Os(CO)3 to Os(CO)4. Harmonic vibrational analysis was performed at the RHF/CEP-4G levels, and according to the frequencies and intensities of the equilibrium structure obtained by using ab initio method, the IR spectra of structure have been simulated. The calculated results were compared with each other and with available experimental data, and were discussed in detail.


[Experiences with ambulatory cytodiagnosis of the thyroid gland].
It is reported on 250 needle biopsies of the thyroid gland above all in scintigraphically cold nodes. In altogether 57% of the patients either a fully inconspicuous cell picture or degenerative findings not suspicious for malignity were present. In 28% of the cases a cyst of the thyroid gland was the result. Four tumours were cytologically established; a small carcinoma in a large nodular struma was not recognized by puncture. According to corresponding opinions the needle biopsy of the thyroid gland is a valuable supplementation of the ambulant diagnostics of the thyroid gland.


Late-onset hyperlactataemia following paediatric cardiac surgery.
To investigate the clinical significance of a late rise in blood lactate concentration, developing after PICU admission, in older children undergoing cardiac surgery. Retrospective, observational study. Single UK PICU. A total of 147 children, aged 2-16 years, in 2 cohorts: FONTAN (n = 63) Fontan operation; and MIXED (n = 84) operations of varying complexity. None. Sequential data were collected up to 12 h postoperatively: arterial blood gas, lactate, glucose concentrations; haemodynamic variables; inotropic support; urine output, core-peripheral temperature gradient. Data were collected on clinical outcomes: PICU mortality; length of ventilation, PICU stay; renal and hepatic function. Late-onset hyperlactataemia (LOH) was defined if blood lactate increased to or above 3 mmol/l. Data from the LOH group were compared to a group with a low blood lactate (<3 mmol/l) throughout (No_LOH). LOH occurred in 28 (44%) and 21 (25%) of patients in FONTAN and MIXED cohorts, respectively. A strong association was found between LOH and hyperglycaemia (P < 0.001). No significant difference was found in postoperative urine output, core-peripheral temperature gradient or inotrope requirement in the LOH versus No_LOH groups. No significant differences were found with respect to clinical outcomes in the LOH versus No_LOH groups. All LOH patients were discharged from PICU within 1 day and survived. LOH is common in older children following cardiac surgery. We found no evidence to suggest that it is associated with adverse clinical outcomes. The strong association between LOH and hyperglycaemia supports a metabolic aetiology.


CNDP1 genotype and renal survival in pediatric nephropathies.
The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying the CNDP1 Mannheim polymorphism (homozygosity for the five leucine repeat), resulting in decreased activity of the histidine-dipeptide metabolizing enzyme carnosinase. The role of CNDP1 in other nephropathies is still unknown. To evaluate the impact of the CNDP1 Mannheim allele on pediatric chronic kidney disease (CKD), we prospectively followed the long-term clinical outcome of 272 children with non-diabetic kidney disease (glomerulopathies n=32, non-glomerular kidney disease n=240). Renal failure progression was independent of CNDP1 genotype in the total cohort of CKD children. However, in patients with glomerulopathies, only 39% of patients homozygous for the CNDP1 Mannheim polymorphism attained the primary renal endpoint as compared to 77% of patients with any other CNDP1 genotype (p=0.06). Our findings in pediatric CKD patients suggest that the nephroprotective effect of the CNDP1 Mannheim variant is not restricted to patients with diabetic nephropathy.


Ultraviolet irradiation alters the density of inner mitochondrial membrane and proportion of inter-mitochondrial junctions in copepod myocytes.
The efficient production of energy via oxidative phosphorylation is essential to the growth, survival, and reproduction of eukaryotes. The behavior (position of, and communication between, mitochondria) and morphology of mitochondria play key roles in efficient energy production and are influenced by oxidative stressors such as ultraviolet (UV) radiation. We tested the hypothesis that mitochondria change their behavior and morphology to meet energetic demands of responding to changes in oxidative stress. Specifically, we predicted that UV irradiation would increase the density of inner mitochondrial membrane and proportion of inter-mitochondrial junctions to influence whole-animal metabolic rate. Using transmission electron microscopy, we found that both three and six hours of UV-A/B irradiation (0.5 W/m2) increased the proportion of inter-mitochondrial junctions (with increasing mitochondrial aspect ratio) and the density of inner mitochondrial membrane in myocytes of Tigriopus californicus copepods. Mitochondrial density increased following both irradiation treatments, but mitochondrial size decreased under the six hour treatment. Metabolic rate was maintained under three hours of irradiation but decreased following six hours of exposure. These observations demonstrate that the density of inner mitochondrial membrane and proportion of inter-mitochondrial junctions can play formative roles in maintaining whole-animal metabolic rate, and ultimately organismal performance, under exposure to an oxidative stressor.


Characterization of two new rhabdoviruses isolated from midges (Culicoides SPP) in the Brazilian Amazon: proposed members of a new genus, Bracorhabdovirus.
Itacaiunas and Curionopolis viruses were isolated from Culicoides midges in Parauapebas municipality, Pará state, Brazil, in 1984 and 1985, respectively. Itacaiunas virus infected newborn mice and mosquito cells (C6/36), but did not replicate in some mammalian cell lineages; while Curionopolis virus infected only mice. Neither virus showed a serological relationship with any of the 195 known arboviruses circulating in Brazil, nor against 38 other rhabdoviruses isolated worldwide. Both virus particles are bullet-shaped and similar in morphology to that observed for other members of the family Rhabdoviridae. Partial nucleotide sequencing of the N protein showed that those two viruses constitute a separate clade in the family Rhabdoviridae, which we propose to be a new genus, designated Bracorhabdovirus.


[Caries and malocclusions. A statistical-epidemiological study performed on 5399 children between 3 and 10 years old in the schools of Bari].
The high incidence of decay and malocclusion is an undiscussed fact now. What is the relation between this incidence and sanitary-social standards is to define still. The aim of this survey was to evaluate the incidence of decay and malocclusions in relation to different sanitary-social standards. The authors carried out an epidemiological-statistical study upon the incidence of decay and malocclusions on 5399 children whose age ranged from 3 to 10. The subjects belonged to some quarters of Bari: Palese, Santo Spirito, San Paolo e Poggiofranco. Some forms were filled in for any subject upon which data on oral health, oral hygiene and occlusal disorders were annotated. Then some groups was divided on subject's age and origin was created. The incidence of decay and malocclusions resulted extremely high in all considered groups. The examination of data showed a clanger gap about the oral hygienic standards between first three quarters, formed into A group, and Poggiofranco, in the last's favour. Students and their parents showed a serious sub-estimation of the importance of oral health. An increase of quality and number of information on oral health is indispensable for many examination children and their respective parents.


Lack of association between the CYP46 gene polymorphism and Italian late-onset sporadic Alzheimer's disease.
Recent studies have provided evidence toward the possible involvement of brain cholesterol homeostasis in late-onset Alzheimer's disease (LOAD). We analyzed an intronic T-->C substitution (rs 754203) of the cholesterol 24S-hydroxylase (CYP46) gene, encoding an enzyme acting on brain cholesterol turnover, which has been recently associated with an increased risk of AD, dependent or not on Apolipoprotein E (ApoE) genotype. No significant association was found for the CYP46 polymorphism in LOAD compared to the controls, even after stratification for the presence/absence of the ApoE*4 allele. Our data do not support a role of the CYP46 polymorphism as a possible susceptibility factor for developing AD.


Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma.
The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.


The 60-kDa precursor to the dithiothreitol-sensitive tetrameric protease of spinach thylakoids: structural similarities between the protease and polyphenol oxidase.
The 60-kDa precursor to the 39-kDa dithiothreitol-sensitive protease was purified from photosystem II membranes of spinach. When partially purified 60-kDa protein was stored at 4 degrees C, the protein was degraded to fragments of 39 and 21 kDa. The 39-kDa fragment was suggested to be identical to the 39-kDa protease from effects of dithiothreitol on these polypeptides. The N-terminal amino acid sequences of the 60-kDa protein and the 39-kDa protease were the same, APILPDVEK-, suggesting that the latter was derived from the N-terminal portion of the former. Immunostaining with polyclonal antibodies against the 60-kDa protein indicated that the 60-kDa protein represents the species that occurs in the native thylakoids. These and other structural properties suggest that the protein might be identical to polyphenol oxidase.


A Narrative Review of Common Uses of Ophthalmic Ultrasound in Emergency Medicine.
The timely evaluation of ocular conditions in the emergency department (ED) can be difficult due to a general lack of specialized equipment, trained personnel, and the time-sensitive nature of emergent ocular conditions. Recently, the use of ocular point-of-care ultrasound (POCUS) has been shown to be particularly useful in the ED. POCUS can be used to promptly diagnose various ocular pathologies, which include ocular trauma, vitreous hemorrhage, central retinal artery occlusion, and retinal detachment. This narrative review seeks to inform the reader of current literature regarding the use of POCUS for the assessment of various ocular emergencies in the ED. The goal of this review is to provide the emergency physician with succinct and up-to-date information and instruction regarding the current uses of POCUS for patients presenting with particular ocular emergencies. Ocular pathologies that are common (ocular trauma) or for which ultrasound is particularly useful (such as retinal detachment) are discussed. Other ocular pathologies are also briefly discussed, such as central retinal artery occlusion, which is a promising new application for ultrasound evaluation. There have been many studies that provide evidence for the utility of POCUS in the evaluation of trauma and other ocular pathologies, including vitreous hemorrhage, retinal detachment, and central retinal artery occlusion. Ocular POCUS is a useful modality in the evaluation of acute ocular complaints in the ED. Emergency physicians should be aware of these findings and feel confident in the utility of ocular POCUS in the ED.


Renoprotective activity of anethole- rich fraction from aromatic herbs on junk food induced diabetic nephropathy in rats.
This study was carried out to study the effect of anethole rich fraction on the Diabetic Nephropathy (DN) rats, and explore the mechanisms. Male wistar rats were grouped into 4 (n = 6 per group): Control, junk food fed DN induced rats, low dose and high dose groups. DN was induced by oral junk food feeding. They were monitored for blood glucose levels and urine protein content at regular intervals. At the end of the study, the biological and hematological parameters were measured. Pancreatic and kidney viscera were taken to observe histopathological changes. Both the doses of anethole rich fraction could drastically lower blood glucose levels, Low Density Lipoprotein (LDL), Glycated Serum Protein (GSP), Total Cholesterol (TC), Triglycerides (TG) (P < 0.01), Malondialdehyde (MDA) level (P < 0.01 or P < 0.05), increases insulin level (P < 0.01), High Density Lipoproteins (HDL), Glutathione Reductase (GSH) and Superoxide Dismutase (SOD) (P < 0.01 or P < 0.05 or P > 0.05). Both doses of anethole rich fraction also improved the pathological changes of kidney and pancreatic tissues in DN rats (P < 0.01 or P < 0.05 or P > 0.05). Hence it can be hypothesized that the high dose of anethole rich fraction (100 mg/kg) could reach the intervention effect and could ameliorate renal damage in DN rats by improving the renal functions, oxidative stress levels, glycometabolism and pathological changes of pancreas and kidney.


[67Ga]desferrioxamine--HSA: synthesis of chelon protein conjugates using carbodiimide as a coupling agent.
Desferrioxamine-human serum albumin conjugate was prepared at pH 4.7 using a water-soluble carbodiimide and at pH 7.8 using glutaraldehyde. The crude conjugate was purified by dialysis and gel filtration. The efficiency of 67Ga labeling of the purified conjugate was greater than 95%, with good in vitro stability. The specific activity ranged from 5 to 50 microCi/mg. Treatment of the conjugate with urea resulted in a 20--30-fold increase in specific activity, suggesting that a number of chelon groups are unavailable for Ga binding due to non-covalent intramolecular cross-linking.


Synthesis and study the analgesic effects of new analogues of ketamine on female wistar rats.
Ketamine (2-o-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, CI-581, Ketalar, I), a potent derivative of Phencyclidine (1-[1-phenylcyclohexyl] piperidine, CAS 956-90-1, PCP, II), and many of its analogues have shown anesthetic and analgesic effects. In this research, new derivatives of I, (2-[p-methoxybenzylamino]-2-[p-methoxyphenyl] cyclohexanone, ket-OCH3, III), (2-[p-methylbenzylamino]-2-[p-methoxyphenyl] cyclohexanone, ket-CH3, IV) and their intermediates (V-VIIII) were synthesized and the acute and chronic pains of III and IV were evaluated on rats using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests. The results werecompared with ketamine and control (saline) groups. The results indicated that in tail immersion and formalin tests, these new derivatives (III and IV) were usually effective for decreasing pain on rats.


Current endoscopic and pharmacological therapy of peptic ulcer bleeding.
Peptic ulcer bleeding is the most significant complication of ulcer disease, remaining the most important reason for upper gastrointestinal bleeding even in the era of Helicobacter eradication. Endoscopic triage and management plays a vital role in the handling of these patients, albeit in close collaboration with radiological and surgical expertise. Injection therapy, preferably with large volume epinephrine remains a core technology. Histoacryl and fibrin glue are more costly and less widely adopted alternatives. Mechanical measures are attractive and clips offer an excellent solution, particularly in soft tissues, and in combination with initial injection. Thermal methods with coagulation and coaptive axial force have similar performance characteristics. Increasingly, the combination of injection therapy with either a mechanical or thermal method appears the best option to achieve permanent haemostasis. PPIs for potent acid inhibition improves the clotting regardless of other treatment modalities. In the setting of rebleeding, patient and ulcer factors determine whether repeat endoscopy should be attempted, but the surgeon should be close at hand in this situation.


Analysis by comparative genomic hybridization of gastric cancer with peritoneal dissemination and/or positive peritoneal cytology.
Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 (P=0.033), 7q21.3 (P < 0.0001), 7q31 (P=0.013), 7q36 (P=0.033), and 22q11.2 (P=0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.


Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma.
Chitinases are enzymes that cleave chitin, a polysaccharide contained in many parasites of humans. Recent studies in mouse models of bronchial asthma have shown that acid mammalian chitinase (AMCase) is involved in the pathophysiology of asthma. It acts downstream of interleukin-13; inhibition of AMCase leads to an abrogated T-helper cell 2 inflammation, less bronchial hyperreactivity, and fewer eosinophils. The aim of this study was to identify common genetic variants in human AMCase and to use them to test for association of AMCase with pediatric asthma. By sequencing the promotor region and all 11 exons on 30 individuals, 12 high-frequency polymorphisms were identified. Genotyping of six variants in exons and one promotor polymorphism was performed on the following populations by means of restriction fragment length polymorphisms: 322 children with asthma, 270 randomly chosen adult controls, and a pediatric control population consisting of 565 children who, at age 10 yr, had never wheezed and never been diagnosed having asthma. We identified three known and two new amino acid variants. Analyses by the Armitage's trend test using both control populations showed association of the newly identified variant K17R and the nearby noncoding polymorphism rs3818822 with asthma (p = 0.0031 and p = 0.0003, respectively). In addition, haplotype analyses revealed strong association of haplotypes with the disease (asthma population vs. pediatric control subjects, p < 10(-10)). This newly described association between AMCase polymorphisms and asthma adds further evidence supporting the involvement of AMCase in the development of asthma.


Obturation of a C-shaped canal using an improved method of warm lateral condensation.
Pilot studies conducted by the authors seem to indicate that obturation of a root canal system by the lateral condensation of gutta-percha using an electrically heated spreader results in a more homogeneous mass of gutta-percha than standard lateral condensation. This article describes an improved variation which prevents inadvertent dislodgement of the mass of gutta-percha during the obturation. The authors refer to this technique as "zap and tap" and a case report describes its use to obturate a C-shaped canal system of a mandibular second molar.


How well are cardiopulmonary resuscitation and automated external defibrillator skills retained over time? Results from the Public Access Defibrillation (PAD) Trial.
The current standard for cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) retraining for laypersons is a four-hour course every two years. Others have documented substantial skill deterioration during this time period. To evaluate 1) the retention of core CPR and AED skills among volunteer laypersons and 2) the time required to retrain laypersons to proficiency as a function of time since initial training. This was an observational follow-up study evaluating CPR and AED skill retention and testing/retraining time up through 17 months after initial training. The study took place at 1,260 facilities recruited by 24 North American clinical research centers, and included 6,182 volunteer laypersons participating in the Public Access Defibrillation (PAD) Trial. Training to proficiency in either CPR only (N = 2,426) or CPR+AED (N = 3,756) was followed by testing/retraining provided three to 17 months later. Retraining was done in brief, one-on-one, individualized, interactive sessions. The outcome studied was instructors' global assessments of performance of CPR and AED skill adequacy, i.e., whether CPR actions would likely result in perfusion (yes/no) and whether AED actions would result in a shock through the heart (yes/no). For global CPR performance, 79%, 73%, and 71% of volunteers tested for the first time since initial training three to five, six to 11, and 12 to 17 months after initial training, respectively, were judged by their instructors as having adequate performance (p < 0.001, chi-square for linear trend). For global AED performance, 91%, 86%, and 84% of volunteers, respectively, were judged as having adequate performance (p < 0.001). The mean (+/- standard deviation) times required to test and retrain volunteers to proficiency were 5.7 (+/- 4.0) minutes for CPR skills and 7.7 (+/- 4.6) minutes for CPR+AED skills. Among PAD Trial volunteer laypersons participating in a simulated resuscitation, the proportions of volunteers judged by instructors to have adequate CPR and AED skills demonstrated small declines associated with longer intervals between initial training and subsequent testing. However, based on instructors' judgment, large majorities of volunteers still retained both CPR and AED core skills through 17 months after initial training. Furthermore, individual testing and retraining for CPR and AED skills were usually accomplished in less than 10 minutes per volunteer. Additional research is essential to identify training and evaluation techniques that predict adequate CPR and AED skill performance of laypersons when applied to an actual cardiac arrest.


A case of ulnar nerve section at the elbow alleviated by Martin-Gruber communicating branch. Diagnostic characterization.
Martin-Gruber communicating branch may be a confounding factor in the diagnosis of ulnar neuropathy at the elbow. It may also lead to a surprising level of motor function conservation despite evident neuropathy. We present a patient with ulnar nerve section at the elbow who underwent early treatment by nerve suture. At 7 months, function was good, despite sonographic findings of neurotmesis at the elbow. Electroneurography revealed Martin-Gruber communicating branch. This type of communicating branch can be associated with functional conservation despite ulnar nerve section. Electrophysiological and ultrasound findings can be highly contributive in defining these conditions.


Mediastinoscopy might not be necessary in patients with non-small cell lung cancer with mediastinal lymph nodes having a maximum standardized uptake value of less than 5.3.
Accurate pretreatment staging in non-small cell lung cancer remains tantamount in formulating an appropriate treatment plan. The maximum standardized uptake value obtained with integrated fluorodeoxyglucose-positron emission tomography/computed tomography has been proposed to be a predictor of malignancy in mediastinal lymph nodes. A recent study has also suggested that accuracy of integrated fluorodeoxyglucose-positron emission tomography/computed tomography might be improved by increasing the maximum standardized uptake value used for calling a lymph node positive from 2.5 to 5.3. We tested the hypotheses that the maximum standardized uptake value is a predictor of individual lymph node metastasis in non-small cell lung cancer and that pathologic staging with mediastinoscopy might not be necessary in patients with a maximum standardized uptake value of less than 5.3 in their mediastinal lymph nodes. This is a retrospective review of 765 lymph nodes sampled from 110 patients in a single institution with biopsy-proved non-small cell lung cancer. All patients underwent integrated fluorodeoxyglucose-positron emission tomography/computed tomography before biopsy or resection of their mediastinal lymph nodes. Surgical staging was the reference standard. All N2 lymph nodes were individually assessed according to station. Data were analyzed by using the Pearson chi(2) test. Twenty-one (19%) of 110 patients had N2 disease, and a total of 765 N2 lymph nodes were pathologically examined. The mean and median maximum standardized uptake values for N2 nodes with metastatic disease were 9.2 (95% confidence interval, 7.0-11.4) and 7.2 (range, 2.2-25.8), respectively. For benign N2 nodes, the mean and median maximum standardized uptake values were 1.5 (95% confidence interval, 1.4-1.6) and 1.0 (range, 1.0-9.6), respectively (P < .05). When integrated fluorodeoxyglucose-positron emission tomographic/computed tomographic scans were reinterpreted by using a maximum standardized uptake value of 5.3 as a cutoff for malignancy, sensitivity decreased from 93% to 81% (P = .15), specificity increased from 86% to 98% (P < .01), positive predictive value increased from 22% to 64% (P < .01), negative predictive value was unchanged at 99%, and overall accuracy of integrated positron emission tomography/computed tomography increased from 87% to 97% (P < .01). The maximum standardized uptake value is a predictor of individual lymph node metastasis in non-small cell lung cancer. Accuracy of integrated positron emission tomography/computed tomography is significantly improved by using a maximum standardized uptake value of 5.3 to assign malignancy, thereby dramatically decreasing the number of false-positive results. More importantly, these results suggest that some patients with non-small cell lung cancer with a maximum standardized uptake value less than 5.3 in their N2 lymph nodes might be able to forego mediastinoscopy and proceed directly to thoracotomy. This represents a significant change in the current management of standardized uptake value-positive mediastinal lymph nodes in non-small cell lung cancer.


RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3.
We previously identified proteins that bind with high affinity to a peptide corresponding to the cytoplasmic regulatory domain (KVGFFKR) of the platelet-specific integrin subunit alpha(IIb). These included a hypothetical protein termed HSPC238, recently renamed as RING finger protein, RN181. Here, we establish the presence of RN181 in human platelets by RT-PCR, Western blotting and mass spectrometry and confirm its affinity for the platelet integrin. We demonstrate that RN181 has ubiquitin E3 ligase activity and that all other components of the ubiquitination pathway are abundant in platelets, suggesting a novel link of integrin signal transduction pathways with ubiquitin-conjugation events.


Small cell carcinoma of the prostate treated with amrubicin.
We describe the use of amrubicin hydrochloride to treat small cell carcinoma of the prostate in a 23-year-old man. Initial radiological examinations of the patient revealed a pelvic tumor associated with bilateral hydronephrosis, pelvic lymph node swelling, and lumbar vertebral bone metastases. The pathological diagnosis was small cell carcinoma originating in the prostate, based on positive immunohistochemical staining for neuron-specific enolase, synaptophysin, and myoglobulin; and negative staining for CD3e, CD20, leukocyte common antigen, and CD99. The clinical stage was T4N1M1. A bilateral nephrostomy was performed to improve renal function, and an ileostomy was established to prevent ileus. The first induction chemotherapy consisted of amrubicin 35 mg/m(2) (days 1, 2, 3, monthly). The amrubicin regimen caused a dramatic reduction in tumor size, but could not be continued, because of the occurrence of grade 4 diarrhea. A different regimen was then administered, consisting of one cycle of a 50% dose and a second cycle of a 75% dose of etoposide (100 mg/m(2) days 1, 2, 3), coadministered with carboplatin (AUC 5, plasma concentration curve). Five months after the induction of chemotherapy, the patient suffered respiratory arrest and died.


The use of surface-enhanced Raman scattering (SERS) for detection of PAHs in the Gulf of Gdańsk (Baltic Sea).
A field operable surface enhanced Raman scattering (SERS) sensor system was applied for the first time under real conditions for the detection of polycyclic aromatic hydrocarbons (PAHs) as markers for petroleum hydrocarbons in the Gulf of Gdańsk (Baltic Sea). At six stations, seawater samples were taken, and the sensor system was applied in situ simultaneously. These measurements were compared to the results of conventional GC/MS laboratory analysis of the PAH concentrations in the seawater samples. For a PAH concentration above 150 ng(12PAH)l(-1), there was agreement between the SERS sensor and the GC/MS determinations. A standard addition experiment yielded a PAH concentration of 900 ng l(-1) at the Gdańsk Harbor, which was of the same order as the GC/MS determinations of 12PAHs (200 ng(12PAH)l(-1)). The high SERS detection limit for seawater samples is explained by the competition for PAHs between the sensor membrane and particulate matter surfaces. Thus, the SERS sensor can be applied, e.g., as a non-quantitative alarm sensor for relatively high PAH concentrations in heavily polluted waters. The spectral unmixing procedure applied for Gdańsk Harbor water confirmed the presence of phenanthrene at the highest concentration ([Phe]=140 ngl(-1)) and of Chr (2.7 ng l(-1)), but it did not detect the other PAHs present in the Gdańsk Harbor water, as determined by GC/MS. When compared to the past literature and databases, the SERS spectra indicated the presence of a mixture of molecules consisting of carotenoids, n-alkanes, amines or fatty acids, and benzimidazoles at the coastal station ZN2. The spectra in the offshore direction indicated carboxylic acids. Interpretation of the farthest offshore in situ SERS measurements is difficult, principally due to the limited availability of reference spectra. The detection of the lower PAH concentrations commonly found in Baltic coastal water needs further research and development to obtain better sensitivity of the SERS sensor. However, the high analytical specificity of the SERS sensor also allows the detection of other chemical species that require the development of a SERS/Raman library for specific in situ spectral interpretation.


Urolithiasis with penile erection: a rare presentation.
Urinary stones are rarely seen in the urethra and are usually encountered in men with urethral stricture or infection. We describe a unique case of giant impacted stones in a 20-year-old man with unreal penile erection.


[Prevention and treatment of hypermotive syndromes in patients needing dental care. 1. Classification, epidemiology, prevention].
In the present work the Authors analyze the frequence and the intensity of emotive reactions in patients undergoing odontoiatric treatment. They also suggest various simple systems for the dentist to prevent excessive emotive reaction of patient which include the quality of staff and equipment employed in the environment of work.


Massive Sternal Osteophyte Compressing Aortic Arch Branch Graft.
We present a dramatic computed tomography scan demonstrating compression of a brachiocephalic graft by a massive sternal osteophyte, coming to light many years after aortic arch replacement surgery.


Plasma arginine vasopressin concentrations in epileptics under monotherapy.
Plasma arginine vasopressin concentrations were determined by radio-immunoassay in 112 adult epileptics who were taking carbamazepine, phenytoin, primidone, or sodium valproate in long-term monotherapy, and in 19 controls. No significant difference was found between the groups, but some epileptics taking carbamazepine and primidone showed low values. Serum concentrations of carbamazepine did not correlate with the concentrations of plasma arginine vasopressin. In conclusion, there was no evidence of a stimulating effect of chronic carbamazepine medication or a special inhibiting effect of phenytoin on the release of vasopressin arginine from the posterior pituitary.


Study designs for identifying risk compensation behavior among users of biomedical HIV prevention technologies: balancing methodological rigor and research ethics.
The growing evidence base for biomedical HIV prevention interventions - such as oral pre-exposure prophylaxis, microbicides, male circumcision, treatment as prevention, and eventually prevention vaccines - has given rise to concerns about the ways in which users of these biomedical products may adjust their HIV risk behaviors based on the perception that they are prevented from infection. Known as risk compensation, this behavioral adjustment draws on the theory of "risk homeostasis," which has previously been applied to phenomena as diverse as Lyme disease vaccination, insurance mandates, and automobile safety. Little rigorous evidence exists to answer risk compensation concerns in the biomedical HIV prevention literature, in part because the field has not systematically evaluated the study designs available for testing these behaviors. The goals of this Commentary are to explain the origins of risk compensation behavior in risk homeostasis theory, to reframe risk compensation as a testable response to the perception of reduced risk, and to assess the methodological rigor and ethical justification of study designs aiming to isolate risk compensation responses. Although the most rigorous methodological designs for assessing risk compensation behavior may be unavailable due to ethical flaws, several strategies can help investigators identify potential risk compensation behavior during Phase II, Phase III, and Phase IV testing of new technologies. Where concerns arise regarding risk compensation behavior, empirical evidence about the incidence, types, and extent of these behavioral changes can illuminate opportunities to better support the users of new HIV prevention strategies. This Commentary concludes by suggesting a new way to conceptualize risk compensation behavior in the HIV prevention context.


The Molecule Pages database.
The UCSD-Nature Signaling Gateway Molecule Pages (http://www.signaling-gateway.org/molecule) provides essential information on more than 3800 mammalian proteins involved in cellular signaling. The Molecule Pages contain expert-authored and peer-reviewed information based on the published literature, complemented by regularly updated information derived from public data source references and sequence analysis. The expert-authored data includes both a full-text review about the molecule, with citations, and highly structured data for bioinformatics interrogation, including information on protein interactions and states, transitions between states and protein function. The expert-authored pages are anonymously peer reviewed by the Nature Publishing Group. The Molecule Pages data is present in an object-relational database format and is freely accessible to the authors, the reviewers and the public from a web browser that serves as a presentation layer. The Molecule Pages are supported by several applications that along with the database and the interfaces form a multi-tier architecture. The Molecule Pages and the Signaling Gateway are routinely accessed by a very large research community.


Control and regulation of metabolic fluxes in microbes by substrates and enzymes.
The control of enzymes and substrates on the flux through microbial metabolic pathways can be quantified in terms of flux control coefficients. In pathways involving group transfer, the summation theorem for flux control by the enzymes has to be modified: the sum of control by all enzymes is between 1 and 2. The phosphoenolpyruvate:glucose phosphotransferase system is such a pathway. Experimental determination of the control by the enzymes in this pathway is under way. The control of the enzymes on the glycolytic flux in yeast is low, with the possible exception of the uptake step. In Klebsiella pneumoniae potassium and ammonium ions can simultaneously be 'limiting', (i.e. have significant control on growth) at pH6, but not at pH8. This may be due to the fact that at pH8 the high-affinity potassium uptake system is absent.


LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1β-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p.
Long non-coding RNA 01534 (LINC01534) is highly expressed in the tissues of patients with osteoarthritis (OA). This study investigated the mechanism of LINC01534 on abnormal metabolic dysfunction in OA chondrocytes induced by interleukin-1β (IL-1β). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of LINC01534, aggrecan, collagen II, and matrix metalloproteinase (MMPs) in OA cartilage tissue or OA chondrocyte model induced by IL-1β. The expressions of aggrecan and collagen II in the chondrocyte were detected by Western blot. The levels of tumor necrosis factor-α (TNF-α), IL-8, IL-6, MMP-13, MMP-9, MMP-3, and prostaglandin E2 (PGE2) in chondrocyte were determined by enzyme-linked immunosorbernt assay. Bioinformatics, dual luciferin gene reporting, RNA pulldown, and Northern blot were used to determine the interaction between LINC01534 and miR-140-5p. The results showed that LINC01534 was upregulated in both OA cartilage tissue and OA chondrocyte model. In addition, silencing LINC01534 significantly alleviated the inhibitory effect of IL-1β on expressions of aggrecan and collagen II in chondrocytes, and significantly downregulated the expression of matrix metalloproteinases in IL-1β-induced chondrocytes. Meanwhile, silencing LINC01534 also significantly inhibited the productions of proinflammatory factors NO, PGE2, TNF-α, IL-6, and IL-8 in the IL-1β-induced chondrocytes. Furthermore, miR-140-5p was confirmed to be a direct target of LINC01534. More importantly, inhibition of miR-140-5p significantly reversed the inhibitory effect of silencing LINC01534 on abnormal matrix degradation in the IL-1β-induced chondrocyte model of OA. Therefore, LINC01534 could promote the abnormal matrix degradation and inflammatory response of OA chondrocytes through the targeted binding of miR-140-5p.


Effect of B-mode optimization techniques on fetal bowel echogenicity using computerized image analysis.
The purpose of this study was to provide and compare measurable parameters for normal fetal bowel echogenicity under predefined B-mode scanning presets. Forty healthy fetuses underwent 14- to 17-week ultrasound scans, and 40 underwent 21- to 25-week scans. Sagittal, coronal, and axial fetal abdominal images were tested using predefined B-mode presets. The presets differed from fundamental imaging by isolated activation of harmonic imaging, compound resolution imaging, speckle reduction imaging, focus and frequency composite imaging, and coded excitation imaging features. A transabdominal probe was used in all fetuses, and transvaginal images were added for the 14- to 17-week scans. The images were studied with custom-developed software, which provided a grayscale analysis of the pixels in the region of interest within the image. The mean brightness of the pixels from the fetal bowel area was calculated. The 14- to 17-week transabdominal scans showed significantly higher mean brightness on harmonic imaging compared to fundamental imaging (P < .01). Activation of coded excitation and compound resolution imaging in these scans resulted in a significant decrease in the mean brightness compared to fundamental imaging. Mean bowel brightness values on the 21- to 25-week transabdominal scans did not differ significantly with the use of the different imaging presets compared to fundamental imaging. Transabdominal harmonic imaging in the early second trimester may significantly increase the mean brightness of the fetal bowel tissue. Contrarily, compound resolution imaging and coded excitation imaging produce the opposite effect on bowel echogenicity.


Saline for peripheral intravenous locks in neonates: evaluating a change in practice.
To evaluate the efficacy of saline versus 10 units/ml heparin for peripheral i.v. flushes in neonates. A nonexperimental group design was used to compare the longevity of heparin and saline i.v. locks. A research utilization method was chosen to increase the study power while simultaneously implementing a practice change and evaluating the outcomes. Power analysis showed that a sample size of approximately 120 per group was needed to decrease the risk of beta error to 0.1. Subjects included neonates in the Special Care Nurseries at a Level III large midwestern university teaching hospital. Data were collected from a convenience sample of 123 neonates receiving 10 units/ml heparin flush into a peripheral i.v. Practice was then changed to preservative-free normal saline, and data collection continued for 117 neonates. I.v. catheter longevity. There was no significant statistical difference in i.v. catheter longevity between i.v. locks flushed with 10 units/ml heparin and those flushed with normal saline. Patient weight accounted for a significant proportion of the variance in i.v. catheter life.


African American students' reactions to Benjamin Cooke's "Nonverbal Communication Among Afro-Americans: An Initial Classification".
The nonverbal communication behavior of Black people continues to take new forms as time progresses. In Kochman's 1972 book, Rappin' and Stylin' Out: Communication in Urban Black America, Benjamin Cooke introduced an initial classification and code of nonverbal behaviors among people of African descent. In this study, students react to Cooke's study conducted in the late 1960s by commenting on Cooke's initial findings in comparison to nonverbal behaviors practiced among Black people as of late. Respondents suggest that while differences and variations exist between the expression of nonverbal behaviors exhibited by the original group studied and people recently observed, there yet remains a similarity in the cultural significance and motivation behind the displays.


Differential regulation of mTOR-dependent S6 phosphorylation by muscarinic acetylcholine receptor subtypes.
Muscarinic receptors subserve many functions in both peripheral and central nervous systems. Some of these processes depend on increases in protein synthesis, which may be achieved by activation of mammalian target of rapamycin (mTOR), a kinase that regulates protein translation capacity. Here, we examined the regulation of mTOR-dependent signaling pathways by muscarinic receptors in SK-N-SH human neuroblastoma cells, and in human embryonic kidney (HEK) cell lines transfected with individual muscarinic receptor subtypes. In SK-N-SH cells, the acetylcholine analog carbachol stimulated phosphorylation of the ribosomal S6 protein, a downstream target of mTOR. The sensitivity of the response to subtype-selective muscarinic receptor antagonists indicated that it was mediated by M3 receptors. Carbachol-evoked S6 phosphorylation was blocked by the mTOR inhibitor rapamycin, but was independent of phosphoinositide 3-kinase activation. The response was significantly reduced by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also inhibited carbachol-evoked S6 phosphorylation in HEK cells expressing M2 receptors, but was ineffective in M3 receptor-expressing HEK cells, although carbachol activated MAPK in both transfected lines. The p90 ribosomal S6 kinase has been implicated in mTOR regulation by phorbol esters, but was not activated by carbachol in any of the cell lines tested. The protein kinase C inhibitor bisindolylmaleimide I reduced carbachol-stimulated S6 phosphorylation in SK-N-SH cells, and in HEK cells expressing M3 receptors, but not in HEK cells expressing M2 receptors. The results demonstrate that multiple muscarinic receptor subtypes regulate mTOR, and that both MAPK-dependent and -independent mechanisms may mediate the response in a cell context-specific manner.


Olfactory function in patients with obstructive sleep apnea: a meta-analysis study.
This meta-analysis study was designed to analyze the olfactory function in obstructive sleep apnea patients (OSA). A comprehensive review of the English language literature regarding OSA patients and olfactory function/dysfunction was performed. The papers assessing olfactory dysfunction with Sniffin' Sticks test were taken into consideration. A total of 420 OSA patients were judged eligible for the study. The average TDI score was found to be 24.3 ± 5.6. The olfactory identification (OD), the olfactory discrimination (OD), and the olfactory threshold (OT) average values were calculated resulting 9.9 ± 2.1, 9.8 ± 1.5, and 5.3 ± 2, respectively. There were 161 healthy control subjects in this meta-analysis. The average TDI of the control group was 30.7 ± 6.0 showing a statistical difference with the group of OSA patients (p = 0.03). A linear correlation between Apnea-Hypopnea Index (AHI) increase and TDI decrease (R2 = 0.1, p = 0.05) was detected. Finally, the average values of TDI of 151 patients classified as mild-moderate OSA and 159 patients considered as severe OSA were calculated. The difference between these two groups resulted not statistically significant (p = 0.3). The comparison between OSA patients and healthy subjects using Sniffin' Sticks test showed lower values of the various olfactory parameters. Although a linear correlation between AHI increase and olfactory dysfunction was observed, no statistical difference between mild-moderate and severe OSA patients in terms of the severity of olfactory dysfunction could be proved.


Schistosoma haematobium urinary tract complications in African migrants attending primary care facilities in Paris, France: A retrospective cohort study (2004-2018).
Little is known about the burden of urogenital schistosomiasis (UGS) outside endemic areas. This study was aimed at describing urinary complications of UGS detected among African migrants in French primary care facilities. A retrospective cohort study included patients with UGS diagnosed from 2004 to 2018 in 5 primary health centers in Paris. Cases were defined by the presence of typical Schistosoma haematobium eggs at urine microscopy. Demographic, clinical, biological and imaging data were collected. Ultrasonography (U-S) findings were classified in accordance with the WHO guidelines. U-S was prescribed for all patients and performed in 100/118. Sex ratio (F/M) was 2/98, and mean age 24.4 years. Patients were from West Africa (73% from Mali) and consulted 8 months (median) after their arrival. Among the 95 patients with interpretable findings, 32 (33.7%) had abnormalities related to UGS, considered as major in 6 cases (6.3%), and mostly localized at the bladder (31/32) without detection of cancer. No sociodemographic, clinical, or biological factors were found to be associated with U-S abnormalities. All 100 patients were treated by praziquantel (PZQ). Among those with abnormalities, 20/32 received two to four doses at various time intervals. Post-cure imaging control performed in 19/32 showed persistent abnormalities in 6 patients, on average 5 months after the last PZQ uptake. Urinary tract abnormalities associated with UGS were common and predominated at the bladder. U-S should be prescribed to any patient with positive urine microscopy. Schedules for PZQ uptake and U-S monitoring for patients with complications remain to be determined.


Stabilization of the lower thoracic and lumbar spine with the internal spinal skeletal fixation system. Indications, techniques, and first results of treatment.
Since 1984, 30 patients with burst fractures of the lower thoracic and lumbar spine were treated with AO internal spinal skeletal fixation system. All patients in this series had a minimum follow-up of 12 months. This new instrumentation is a posterior intrapedicular system developed by Dick in 1982. It allows stable fixation that is limited only to adjacent spinal segments. The internal fixator permits reduction in all three planes. Independently, it is possible to add distraction or compression to the involved segments. It also is able to reduce effectively the "middle column" which is thought to be accomplished by "ligamentotaxis." In this series there were 16 neurologically intact patients and 14 with partial or complete neurologic injury. There were two minor instrumentation loosenings early in the series. Most patients in this series had a near-anatomic reduction of all three columns in the involved segment. It was also possible to re-establish the normal lordosis of the lumbar spine. The device provided sufficient rigid fixation for rapid postoperative mobilization in a light external orthosis.


Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in Baltimore, Maryland.
SARS-CoV-2 serosurveys can help characterize disparities in SARS-CoV-2 infection and identify gaps in population immunity. Data on SARS-CoV-2 seroprevalence among people who inject drugs (PWID) are limited. We conducted a cross-sectional study between December 2020 and July 2022 among 561 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study-a community-based cohort of current and former PWID in Baltimore, Maryland. Serum samples were assayed for infection-induced anti-nucleocapsid (anti-N) and infection and/or vaccination-induced anti-spike-1 (anti-S) SARS-CoV-2 IgG. We estimated adjusted prevalence ratios (aPR) via modified Poisson regression models. The median age was 59 years, 35% were female, 84% were non-Hispanic Black, and 16% reported recent injection drug use. Anti-N antibody prevalence was 26% and anti-S antibody prevalence was 63%. Anti-N and anti-S antibody prevalence increased over time. Being employed (aPR=1.53 [95%CI=1.11-2.11]) was associated with higher anti-N prevalence, while a cancer history (aPR=0.40 [95%CI=0.17-0.90]) was associated with lower anti-N prevalence. HIV infection was associated with higher anti-S prevalence (aPR=1.13 [95%CI=1.02-1.27]), while younger age and experiencing homelessness (aPR=0.78 [95%CI=0.60-0.99]) were factors associated with lower anti-S prevalence. Substance use-related behaviors were not significantly associated with anti-N or anti-S prevalence. SARS-CoV-2 seroprevalence increased over time among current and former PWID, suggesting cumulative increases in the incidence of SARS-CoV-2 infection and vaccination; however, there were disparities in infection-induced seroprevalence and infection and/or vaccine-induced seroprevalence within this study sample. Dedicated prevention and vaccination programs are needed to prevent disparities in infection and gaps in population immunity among PWID during emerging epidemics.


Ecdysone 20-monooxygenase: characterization of an insect cytochrome p-450 dependent steroid hydroxylase.
Ecdysone 20-monooxygenase, the enzyme system that hydroxylates ecdysone at C-20 of the side-chain to form ecdysterone, has been characterized in the fat body of early last instar larvae of the tobacco hornworm, Manduca sexta, using a radioenzymological assay. Ecdysterone was demonstrated to be the product of the enzyme system by high-pressure liquid chromatography, gas-liquid chromatography and mass spectrometry. Differential centrifugation, sucrose-gradient centrifugation, electron microscopy and organelle-marker enzyme analysis revealed that ecdysone 20-monooxygenase activity is associated with the mitochondria. The enzymatic properties of ecdysone 20-monooxygenase are that it is most active in a 0.05 M phosphate buffer, is inhibited by Mg2+ and exhibits pH and temperature optima at 7.5 and 30 degrees C, respectively. The enzyme complex has an apparent Km for ecdysone of 1.60 x 10(-7) M and is competitively inhibited by its product, ecdysterone, with an apparent Ki of 2.72 x 10(-5) M. The cytochrome P-450 nature of this insect steroid hydroxylase was initially suggested by its obligate requirement for NADPH and its inhibition by carbon monoxide, p-chloromercuribenzoate, metyrapone and p-aminoglutethimide but not by cyanide. Difference spectroscopy revealed the presence of cytochrome P-450 in the fat-body mitochondrial fraction. A photochemical action spectrum of ecdysone 20-monooxygenase activity confirmed the involvement of cytochrome P-450 in this monooxygenase system.


Usefulness of MEG magnetometer for spike detection in patients with mesial temporal epileptic focus.
The present study investigated the sensitivity of magnetoencephalography (MEG) for spikes depending on sensor type in patients with mesial temporal epileptic focus. We recorded MEG in 6 patients with mesial temporal epileptic focus using two sensor types (magnetometer and gradiometer) simultaneously. The number of spikes detected and the corresponding equivalent current dipole (ECD) parameters (distance from the coordinated head center (radius), and dipole moment) were evaluated with respect to sensor type. Among 426 MEG 'consensus spikes' determined by 3 reviewers, 378 spikes satisfied the predetermined criteria for source localization. Comparing ECD parameters, spikes detected by magnetometer alone displayed a smaller radius and larger dipole moment than those detected by gradiometer alone. Spikes estimated in the mesial temporal area were more frequently detected by magnetometer alone (38.5%) than by gradiometer alone (11.5%), whereas spikes in the lateral temporal area were detected less by magnetometer alone (3.7%) than by gradiometer alone (53.9%). The present results suggest that a magnetometer is advantageous for spike detection in patients with mesial temporal epileptic focus. This also implies the higher sensitivity of magnetometer for deep sources.


NHERF1 regulation of PTH-dependent bimodal Pi transport in osteoblasts.
Control of systemic inorganic phosphate (Pi) levels is crucial for osteoid mineralization. Parathyroid hormone (PTH) mediates actions on phosphate homeostasis mostly by regulating the activity of the type 2 sodium-phosphate cotransporter (Npt2), and this action requires the PDZ protein NHERF1. Osteoblasts express Npt2 and in response to PTH enhance osteogenesis by increasing mineralized matrix. The regulation of Pi transport in osteoblasts is poorly understood. To address this gap we characterized PTH-dependent Pi transport and the role of NHERF1 in primary mouse calvarial osteoblasts. Under proliferating conditions osteoblasts express Npt2a, Npt2b, PTH receptor, and NHERF1. Npt2a mRNA expression was lower in calvarial osteoblasts from NHERF1-null mice. Under basal conditions Pi uptake in osteoblasts from wild-type mice was greater than that of knockout mice. PTH inhibited Pi uptake in proliferating osteoblasts from wild-type mice, but not in cells from knockout mice. In vitro induction of mineralization enhanced osteoblast differentiation and increased osterix and osteocalcin expression. Contrary to the results with proliferating osteoblasts, PTH increased Pi uptake and ATP secretion in differentiated osteoblasts from wild-type mice. PTH had no effect on Pi uptake or ATP release in differentiated osteoblasts from knockout mice. NHERF1 regulation of PTH-sensitive Pi uptake in proliferating osteoblasts is mediated by cAMP/PKA and PLC/PKC, while modulation of Pi uptake in differentiated osteoblasts depends only on cAMP/PKA signaling. The results suggest that NHERF1 cooperates with PTH in differentiated osteoblasts to increase matrix mineralization. We conclude that NHERF1 regulates PTH that differentially affects Na-dependent Pi transport at distinct stages of osteoblast proliferation and maturation.


Recent advances in metastasis research.
Advances in the early prediction, detection, and treatment of metastatic disease has improved the outlook in cancer patients in recent decades, however, metastasis remains the major cause of death in affected individuals. Metastasis occurs in a series of discreet biological steps in which a single, frequently clinically occult micrometastatic cell travels from the primary tumor to a distant location, where it lodges, grows, and ultimately results in the patient's death. Recent work has provided many new insights in the mechanisms and biology behind metastatic spread. This short review surveys some of the most important recent developments that have helped increase our understanding of the three broad phases of metastasis - the genesis of the metastatic cell through the loss of local constraints in the primary tumor microenvironment, dissemination of the cell to a distant organ while avoiding immune surveillance, and finally lodging and growth of the overt metastasis. These studies are providing mounting evidence that the interactions between tumor and normal cells and tissues are critical for disease progression - a paradigm that will provide a fertile area for future research.


Potential role of the skin microbiota in Inflammatory skin diseases.
Inflammatory skin diseases include a variety of skin diseases, such as seborrheic dermatitis, acne, atopic dermatitis, psoriasis and so on, which are more common and tend to have a significant impact on patients' quality of life. Inflammatory skin diseases often result in physical or psychological distress; however, the pathogenesis of these diseases have not been clearly elucidated. Many factors are involved in the pathogenesis of inflammatory skin diseases, including heredity, environment, immunity, epidermal barrier, mental disorders, infection and so on. In recent years, skin microbiota has been shown to play an important role in inflammatory skin diseases. To elaborate on the specific mechanisms of inflammatory skin diseases induced by microbiota dysbiosis. We introduce the function and influence of skin microbiota in inflammatory skin diseases from the following aspects: Immunity, epigenetics, epidermal barrier and treatment. Skin microbiota can affect many aspects of the host, such as Immunity, epigenetics, epidermal barrier, and it plays an important role in the pathogenesis of inflammatory skin diseases. Skin microbiota is extremely important for maintaining the health of skin and the dysbiosis of skin microbiota is an important pathogenesis of inflammatory skin diseases.


Reproductive Factors in the Risk of Bladder Cancer and Upper Urinary Tract Cancer: The Japan Public Health Center-Based Prospective Study.
Reproductive factors are hypothesized to play a role in the incidence of bladder cancer and upper urinary tract cancer (UUTC, together, urothelial cancer). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females ages 40 to 69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 urothelial cancer cases (145 bladder cancer cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared with 49-51 years) increased bladder cancer risk in the reproductive model (HR, 2.09; 95% CI, 1.04-4.20). An association between urothelial cancer/bladder cancer and age at menopause, including both natural and surgical/induced, was significant in the reproductive model (HR, 1.74; 95% CI, 1.09-2.77; and HR, 1.94; 95% CI, 1.15-3.28, respectively). Early age at natural menopause was suggested to increase urothelial cancer risk in the reproductive model (HR, 1.78; 95% CI, 0.93-3.42). Our findings suggest a significant association between age at menopause and incidence of urothelial cancer/bladder cancer among Asian populations. This study aids understanding the role of reproductive factors in urothelial cancer/bladder cancer incidence. In Japanese populations, age at menopause is suggested to be associated with urothelial cancer/bladder cancer incidence, especially regarding early natural menopause.


Evaluating the risk to humans from mineral oils in foods: Current state of the evidence.
Key issues around the evaluation of risks to humans from mineral oils in food and feedstuffs are discussed. MOHs (MOAH and MOSH) occur in food due to intentional use, contamination from environmental sources and during transport/processing, or through migration from food contact materials. Problems in setting and enforcing human health guidelines for MOH include uncertainty around MOH toxicity and the specialist expertise needed for analysis of complex food matrices. Currently, the method of choice for measuring mineral oils is LC-GC-FID, however some complex food matrices also require additional analytical techniques to differentiate between some naturally occurring hydrocarbons and those from other sources, including of petrogenic origin. This requires the skills of an experienced analyst. Significant toxicological gaps for MOHs prevent robust human health risk assessment and the derivation of guidance values. As food-grade mineral oils are virtually MOAH-free, the key issue explored here is the relevance to humans of liver (micro)granulomas observed in F344 rats following oral intake. Available data suggest that despite the ubiquitous nature of MOH in the human diet, the prevalence of liver lipogranulomas in the population is low. These are not associated with inflammation and based on current evidence are not considered of human health significance.


Fluorescence resonance energy transfer as a probe for G-quartet formation by a telomeric repeat.
The secondary structure of guanine-rich oligodeoxynucleotides has been investigated with fluorescent probes. Intramolecular folding of a telomeric oligonucleotide into a quadruplex led to fluorescence resonance energy transfer (FRET) between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5' and 3' ends of the DNA, respectively. Depending on oligonucleotide length, quenching efficiency varied between 0.45 and 0.72 at 20 degrees C. The conjugation of the dyes to the oligonucleotide had a limited, but significant, influence on the thermodynamics of G-quartet formation. Intramolecular folding was demonstrated from the concentration independence of fluorescence resonance energy transfer over a wide concentration range. Folding of the oligonucleotide was confirmed by UV absorption, UV melting, and circular dichroism experiments. The folding of the G-quartet could be followed at concentrations as low as 100 pM. Fluorescence resonance energy transfer can thus be used to reveal the formation of multistranded DNA structures.


SARS-CoV-2 and EBV; the cost of a second mitochondrial "whammy"?
We, and others, have suggested that as the SARS-CoV-2 virus may modulate mitochondrial function, good mitochondrial reserve and health could be key in determining disease severity when exposed to this virus, as the immune system itself is dependent on this organelle's function. With the recent publication of a paper showing that long COVID could be associated with the reactivation of the Epstein Barr Virus, which is well known to manipulate mitochondria, we suggest that this could represent a second mitochondrial "whammy" that might support the mitochondrial hypothesis underlying COVID-19 severity and potentially, the occurrence of longer-term symptoms. As mitochondrial function declines with age, this could be an important factor in why older populations are more susceptible. Key factors which ensure optimal mitochondrial health are generally those that ensure healthy ageing, such as a good lifestyle with plenty of physical activity. The ability of viruses to manipulate mitochondrial function is well described, and it is now also thought that for evolutionary reasons, they also manipulate the ageing process. Given that slowing the ageing process could well be linked to better economic outcomes, the link between mitochondrial health, economics, COVID-19 and other viruses, as well as lifestyle, needs to be considered.


Selective embolization of a pulmonary artery rupture caused by a Cournand catheter.
Pulmonary artery rupture is a rare but often fatal complication of right heart catheterization. We present a case of a ruptured pulmonary artery caused by a Cournand catheter in a high-risk patient with pulmonary hypertension on oral anticoagulation with successful emergency embolization with gelatine foam.


[Valyl- and alanyl-tRNA-synthetase activity in the skeletal muscles of the rabbit in diabetes and during insulin administration].
Activities of alanyl- and valyl tRNA synthetases were considerably higher in rabbit muscle soleus than in muscle gastrocnemius. Repeated injections of insulin into normal rabbits as well as impairment of animals by experimental alloxan diabetes within two weeks did not alter significantly the activity of the synthetases in red and mixed muscles.


Treatment options for patients with stage D1 (T0-3,N1-2,M0) adenocarcinoma of prostate.
Three hundred six patients with adenocarcinoma of the prostate underwent pelvic lymphadenectomy and had Stage D1 (T0-3,N1-2,M0) disease; 171 patients underwent radical retropubic prostatectomy with or without immediate adjuvant therapy (hormonal or radiation or both) or conservative (hormonal or radiation or both) treatment alone (n = 135). Follow-up was one-half to eighteen and one-half years (mean, 5 yrs). Immediate adjuvant orchiectomy significantly (P = 0.01) improved survival (87.4% at 10 years) and nonprogression rates for patients who underwent radical prostatectomy, but not for those who had lymphadenectomy. Overall patient survival was significantly better (P = 0.005) after prostatectomy than lymphadenectomy. Residual disease (n = 43) in patients who underwent prostatectomy and received adjuvant treatment (orchiectomy or radiation or both) did not affect disease outcome. Bilateral pelvic lymphadenectomy and radical prostatectomy with immediate adjuvant orchiectomy provided survival comparable to the expected survival; conservative treatment alone was associated with rapid disease progression and poor survival and significantly (P = 0.02) higher local morbidity.


Editorial Commentary: Risk Factors of Cyclops Syndrome in Quadriceps Autograft Anterior Cruciate Ligament Reconstruction: More Helpful Data in Weighing Graft Choice.
Arthrofibrosis after anterior cruciate ligament (ACL) reconstruction can be a devastating complication with risk factors and causes not well established. Cyclops syndrome is a subtype involving localized scar anterior to the graft, which is typically treated with arthroscopic debridement. ACL quadriceps autograft is a newly popular graft option for which clinical data continue to develop. However, recent research shows possible increased risk of arthrofibrosis with quadriceps autograft. Possible causes include inability to achieve active terminal knee extension after extensor mechanism graft harvesting; patient characteristics, including female sex, and social, psychological, musculoskeletal, and hormonal differences; larger graft diameter; concomitant meniscus repair; exposed collagen fibers of the graft abrading the fat pad or tibial tunnel or intercondylar notch; smaller notch size; intra-articular cytokine; and biomechanical stiffness of the graft.


Metabolism Comparative Cytotoxicity Assay (MCCA) and Cytotoxic Metabolic Pathway Identification Assay (CMPIA) with cryopreserved human hepatocytes for the evaluation of metabolism-based cytotoxicity in vitro: proof-of-concept study with aflatoxin B1.
Recently, we have improved the cryopreservation procedures for human hepatocytes, leading to cells that can be cultured after thawing ("plateable" cryopreserved human hepatocytes). The ability to culture cryopreserved human hepatocytes allows application of the cells for prolonged incubations such as long-term (days) metabolism studies, enzyme induction studies, and cytotoxicity studies. We report here the application of the plateable cryopreserved human hepatocytes to evaluate the relationship between xenobiotic metabolism and toxicity. Two assays were developed: The Metabolism Comparative Cytotoxicity Assay (MCCA) and the Cytotoxic Metabolic Pathway Identification Assay (CMPIA). The MCCA was designed for the initial identification of the role of metabolism in cytotoxicity by comparing the cytotoxic potential of a toxicant in a metabolically competent (primary human hepatocytes) and a metabolically incompetent (Chinese hamster ovary (CHO)) cell type, as well as the evaluation of the role of P450 metabolism by comparing the cytotoxicity of the toxicant in question in human hepatocytes in the presence and absence of a nonspecific, irreversible P450 inhibitor, 1-aminobenzotriazole (ABT). The CMPIA was designed for the identification of the P450 isoforms involved in metabolic activation via the evaluation of the cytotoxicity of the toxicant in the presence and absence of isoform-selective P450 inhibitors. Results of a proof-of-concept study with the MCCA and CMPIA with a known hepatotoxicant, aflatoxin B1 (AFB1), are reported. AFB1 is known to require P450 metabolism for its toxicity. In the MCCA, AFB1 was found to have significantly higher cytotoxicity in human hepatocytes than CHO cells, therefore confirming its requirement for biotransformation to be toxic. ABT was found to effectively attenuate AFB1 cytotoxicity, confirming that P450 metabolism was involved in its metabolic activation. In the CMPIA, AFB1 cytotoxicity was found to be attenuated by ketoconazole and diethyldithiocarbamate, but not by furafylline, quinidine, and sulfaphenazole. Results with the isoform-selective inhibitors suggest that the isoforms inhibited by ketoconazole (mainly CYP3A4) and diethyldithiocarbamate (mainly CYP2A6, and CYP2E1), but not the isoforms inhibited by furafylline (mainly CYP1A2), sulfaphenazole (mainly CYP2C9) and quinidine (mainly CYP2D6) are involved in the metabolic activation of AFB1. This proof-of-concept study suggests that MCCA and CMPIA with cryopreserved human hepatocytes are potentially useful for the evaluation of the relationship between human xenobiotic metabolism and toxicity.


Reverse shoulder arthroplasty for primary glenohumeral osteoarthritis: significantly different characteristics and outcomes in shoulders with intact versus torn rotator cuff.
To compare outcomes of reverse shoulder arthroplasty (RSA) for primary osteoarthritis (OA) with and without rotator cuff (RC) tears to those with secondary OA due to RC tears. We reviewed records of all patients that received RSA for primary OA or secondary OA. All patients had preoperative radiographs, computed tomography arthrography (CTA) and/or magnetic resonance imaging (MRI) scans of their shoulders to assess their etiology, glenoid morphology, and fatty infiltration. Pre- and postoperative (at minimum follow-up of 2 years) Constant scores and range of motion were compared between patients that had RSA for primary OA with and without RC tears to those with secondary OA due to RC tears. Of the initial cohort of 605 shoulders (583 patients), 153 were lost to follow-up (25.3%), 25 required revision with implant removal (4.1%), and 13 died of causes unrelated to the surgery (2.1%), and left a final cohort of 414 patients. Of the final cohort, 97 had primary OA with intact RC, 62 had primary OA with RC tears, and 255 had secondary OA. Postoperative Constant scores were significantly higher for primary OA with intact RC (73.8±14.3), compared to both primary OA with RC tears (66.1±14.6, p<0.001) and secondary OA (64.1±14.8, p<0.001). There were no differences in pre- or postoperative scores between primary OA with RC tears and secondary OA. At 2 or more years following RSA, Constant scores were significantly higher for primary OA with intact RC, compared to either primary OA with RC tears or secondary OA, whereas there were no differences in pre- or postoperative scores of shoulders that had primary OA with RC tears versus secondary OA. The authors recommend distinguishing primary OA with intact RC from primary OA with RC tears, as the two have considerably different characteristics and prognosis following RSA.


Antioxidant polymeric nanoparticles as novel therapeutics for airway inflammatory diseases.
Successful pulmonary drug delivery requires polymeric drug delivery systems which have excellent biocompatibility and fast degradation rates, when frequent administration is necessary. Here, we report a new family of fully biodegradable hydroxybenzyl alcohol (HBA)-incorporated polyoxalate (HPOX) as a novel therapeutics of airway inflammatory diseases. HPOX was designed to incorporate antioxidant and anti-inflammatory HBA and peroxalate ester linkages capable of reacting with hydrogen peroxide (H2O2) in its backbone. HPOX nanoparticles exhibited highly potent antioxidant and anti-inflammatory effects by scavenging H2O2, reducing the generation of intracellular oxidative stress and suppressing the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin (IL)-1β in stimulated macrophages. The potential of HPOX nanoparticles as an anti-asthmatic agent was evaluated using a murine model of asthma. Intratracheal administration of HPOX nanoparticles remarkably reduced the recruitment of inflammatory cells and expression of pro-inflammatory mediators such as IL-4 and iNOS. Based on their excellent antioxidant, anti-inflammatory and anti-asthmatic activities, we believe that HPOX nanoparticles have great potential as therapeutics and drug carriers for the treatment of airway inflammatory diseases such as asthma.


Long-term follow-up of pulse width threshold of transvenous and myo-epicardial leads.
Postoperative pulse width thresholds were measured at a constant of 5 volts in 140 patients. In 41 patients, transvenous atrial and/or ventricular leads were implanted at a median age of 13 years (3-78 yrs). Myo-epicardial leads were implanted in 99 patients at a median age of 8 3/4 years (1 wk to 76 yrs). The initial rapid rise of threshold was found to persist not longer than to the third follow-up period of 11 days to 5 weeks in all atrial and transvenous ventricular leads; in myo-epicardial ventricular leads it persisted until the period of more than 5 weeks to 6 months. During initial rise, pulse width threshold m + sem did not exceed 0.45 ms. We therefore suggest that a pulse width setting of 0.5 ms at 5 V is a safe setting for this period. In only one patient did a late rise of threshold occur. The comparison of pulse width thresholds of transvenous versus myo-epicardial leads showed lower mean values for transvenous atrial leads in each follow-up period, but the difference was not statistically significant. The pulse width thresholds of transvenous ventricular leads were significantly lower than those of myo-epicardial leads in some follow-up periods. We therefore conclude that transvenous leads have a slight advantage with regard to postoperative pulse width threshold.


Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy.
Gene expression profiles in the rat hypoglossal nucleus after axotomy were demonstrated using expressed-sequence-tag (EST) approach. To demonstrate the gene-expression profiles after axotomy, nerve-transected hypoglossal nuclei were dissected and collected from about 1000 rats, with which a cDNA library was constructed. More than 750 clones were sub-cloned and sequenced from the library. The clones which hit frequently are likely to be associated with mitochondrial respiratory chain, cytoskeletal protein and protein synthesis. One hundred three clones from among the sequenced clones were further processed for histological screening using unilateral-hypoglossal nerve-transected brain sections by in situ hybridization histochemistry. In situ hybridization study revealed that 26% of clones examined showed upregulated expression of mRNA in response to axotomy. They included genes encoding proteins associated with glucose, lipid and protein metabolism, cytoskeleton, neurotransmission and immune reaction. The present EST analysis may have an advantage in targeting genes which are associated with nerve injury with a good efficacy, as compared with other methods such as differential display and subtraction.


The fluorometric assay of rat plasma corticosterone: evaluation of nonspecific fluorescence.
An analysis of 168 plasma samples from intact rats, one to 35 days of age, was performed using both brief and specific fluorometric procedures. The amount of fluorescence produced by the brief procedure which could be attributed to corticosterone ranged from a maximum of 72% to a minimum of 16% of the total fluorescence value. Corticosterone represented 50% or more of the brief assay value in only five out of 18 groups of animals assayed. Following statistical analysis of the nonspecific fluorescence, a significant variation was found due to the age of the animal. A highly significant increase in nonspecific fluorescence was found in 21-day old animals following histamine injection. It was concluded that the brief fluorometric assays for corticosterone were of little value if specificity was desired.


Creation of an Inpatient Alcohol Liver Service Improves Early Liver Disease Detection in Patients With Alcohol Use Disorder.
One of the most common and devastating complications of alcohol use disorder (AUD) is the development of alcohol-associated liver disease (ALD).1 Unfortunately, outcomes of patients with ALD are poor, in large part because patients with ALD are diagnosed at a much later stage of disease compared with patients with other causes of liver disease.2 Accordingly, earlier detection is critical in combating the high mortality associated with ALD. In this work, we sought to assess the feasibility and impact of evaluating high-risk patients with no prior documented liver disease for the presence of advanced ALD while admitted to the hospital.


Degenerative arthritis of the carpometacarpal joint of the thumb: a clinical follow-up of eleven Niebauer prostheses.
Eleven patients with disabling osteoarthritis at the base of the thumb were treated with a Dacron-reinforced trapezium replacement arthroplasty. Examination from 1 to 3 years later (average, 20 months) showed that all patients were satisfied, principally because of relief of pain. The range of motion and stability were satisfactory, although far from normal. Postoperative dislocation did not occur. This problem was eliminated by correcting hyperextension of the metacarpal phalangeal joint and by reinforcing the capsule over the trapezium with a buttress created by transferring half of the distal end of the flexor carpi radialis to the insertion of the extensor carpi radialis longus. None of the prostheses fractured and no bone erosion was seen on postoperative roentgenogram.


Merged bilateral arterial duct and circumflex retroesophageal right aortic arch in a fetus with normal intracardiac anatomy.
We report the case of a fetus with anamnios sequence and VACTERL syndrome, having a circumflex right aortic arch. Two arterial ducts join anteriorly to form a common vessel that connects to the pulmonary trunk with confluent pulmonary branches. Embryologically, the dorsal right 6th aortic arch did not disappear and the aortic arch development stopped in a symmetrical state with an exceptional "Y-shaped" merged bilateral arterial duct.


GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database.
The GTDB Toolkit (GTDB-Tk) provides objective taxonomic assignments for bacterial and archaeal genomes based on the Genome Taxonomy Database (GTDB). GTDB-Tk is computationally efficient and able to classify thousands of draft genomes in parallel. Here we demonstrate the accuracy of the GTDB-Tk taxonomic assignments by evaluating its performance on a phylogenetically diverse set of 10,156 bacterial and archaeal metagenome-assembled genomes. GTDB-Tk is implemented in Python and licensed under the GNU General Public License v3.0. Source code and documentation are available at: https://github.com/ecogenomics/gtdbtk. Supplementary data are available at Bioinformatics online.


Mediating effects of resilience on frailty and depression among older Chinese people living with HIV/AIDS: a cross-sectional study in Hunan.
Little is known about the ambiguous and complex relationship between frailty, resilience and depression in older adults living with HIV (OALHIV). Thus, the current study aimed to further clarify the relationship, as well as to investigate whether resilience plays a mediating role and to quantify the mediating effect. A cross-sectional study was conducted on patients who were aged ≥50 y with HIV/AIDS at the First Hospital of Changsha City from June to August 2019. The sociodemographic characteristics of participants, depression, resilience and frailty were evaluated by the self-developed questionnaire, the 10-item Center for Epidemiological Studies Depression Scale, the 10-item Connor-Davidson Resilience Scale and Tilburg Frailty Indicator, respectively. SPSS macro model 4 was used to analyse the mediation of resilience between frailty and depression. A total of 175 OALHIV (120 males and 55 females) were investigated in this study. The prevalence of frailty and depression was 31.4% and 30.9%, respectively. Additionally, the mediation analysis model showed that frailty could contribute to depression directly, and that it also affected depression through resilience, suggesting that resilience partially mediated the relationship between frailty and depression among OALHIV. Our findings suggest that resilience appears to be a protective factor for depression. Effective and targeted intervention on resilience is available and is crucial to improve the life quality of OALHIV.


Improving of local ozone forecasting by integrated models.
This paper discuss the problem of forecasting the maximum ozone concentrations in urban microlocations, where reliable alerting of the local population when thresholds have been surpassed is necessary. To improve the forecast, the methodology of integrated models is proposed. The model is based on multilayer perceptron neural networks that use as inputs all available information from QualeAria air-quality model, WRF numerical weather prediction model and onsite measurements of meteorology and air pollution. While air-quality and meteorological models cover large geographical 3-dimensional space, their local resolution is often not satisfactory. On the other hand, empirical methods have the advantage of good local forecasts. In this paper, integrated models are used for improved 1-day-ahead forecasting of the maximum hourly value of ozone within each day for representative locations in Slovenia. The WRF meteorological model is used for forecasting meteorological variables and the QualeAria air-quality model for gas concentrations. Their predictions, together with measurements from ground stations, are used as inputs to a neural network. The model validation results show that integrated models noticeably improve ozone forecasts and provide better alert systems.


Old and new applications of non-anticoagulant heparin.
The aim of this chapter is to provide an overview of non-anticoagulant effects of heparins and their potential use in new therapeutic applications. Heparin and heparin derivatives have been tested in inflammatory, pulmonary and reproductive diseases, in cardiovascular, nephro- and neuro-tissue protection and repair, but also as agents against angiogenesis, atheroschlerosis, metastasis, protozoa and viruses. Targeting and inhibition of specific mediators involved in the inflammatory process, promoting some of the above mentioned pathologies, are reported along with recent studies of heparin conjugates and oral delivery systems. Some reports from the institute of the authors, such as those devoted to glycol-split heparins are also included. Among the members and derivatives of this class, several are undergoing clinical trials as antimetastatic and antimalarial agents and for the treatment of labour pain and severe hereditary anaemia. Other heparins, whose therapeutic targets are non-anticoagulant such as nephropathies, retinopathies and cystic fibrosis are also under investigation.