Hydrocarbons, fatty acids, and lipids of freshwater grasses of the Potamogetonaceae family.
The composition of hydrocarbons, fatty acids, and of total, polar, and neutral lipids was studied in freshwater Potamogetonaceae grasses collected in two different regions of the Volga river. More than 40 fatty acids and hydrocarbons were separated and identified by chromato-mass spectrometry. The variability of lipid characteristics of plants of the same family is discussed.


Latent class analysis of the association between polycyclic aromatic hydrocarbon exposures and body mass index.
People experience multiple co-occurring exposures to environmental pollutants, but analyses of multiple exposures have rarely been reported. We used latent class analysis to estimate co-exposures to multiple polycyclic aromatic hydrocarbons (PAH), and tested the associations of latent classes to body mass index. We analyzed National Health and Nutrition Examination Survey (NHANES) 2013-2014 data. The sample included 2354 people aged 6-80 years. Measures included seven urinary PAH metabolites, BMI, and demographic and behavioral covariates. People were classified into mutually exclusive latent classes characterized by unique profiles of multiple PAH exposures. These classes were used as categorical independent variables in weighted multiple regression models with BMI as the dependent measure. Models were analyzed overall and by age groups (6-19, 20-59, and 60 and over.) We compared results using latent classes to results using a summed PAH exposure measure. Five latent classes were identified. Two of these classes were significantly associated with higher BMI overall (p < .0001) and for the two youngest age groups. One of these classes was characterized by high multiple exposures across all PAHs, and one by moderate exposures but relatively high naphthalene and phenanthrene. The summed PAH score was associated with higher BMI only for the youngest age group. Persons experience multiple co-exposures to PAHs that are related to BMI and obesity across age groups. Latent class analysis provides information on higher order interactions among multiple chemicals that a summed score does not. Future work may apply this approach to other outcomes or types of co-exposures.


Efficient utilization of nanospace of layered transition metal oxide HNbMoO6 as a strong, water-tolerant solid acid catalyst.
Layered HNbMoO6 was found to function as a strong solid acid catalyst, exceeding the activity of zeolites and ion-exchange resins for Friedel-Crafts alkylation. HNbMoO6 also exhibited high catalytic activity for esterification of hydrocarboxylic acid and hydration. The catalytic performance of layered HNbMoO6 is attributed to the intercalation of reactants into the interlayer and the development of strong acidity.


A new theoretical analysis of the cooperative effect in T-shaped hydrogen complexes of CnHm∙∙∙HCN∙∙∙HW with n = 2, m = 2 or 4, and W = F or CN.
In this theoretical work, a new idea about cooperativity in intermolecular clusters of CnHm∙∙∙HCN∙∙∙HW stabilized by hydrogen bonds composed by lone-electron pairs (nitrogen) and π clouds (C = C and C ≡ C) as proton acceptors is developed. The structural study and vibrational analysis have pointed out deformations in the intermolecular clusters caused by the HW terminal proton-donor, in which if W = fluorine the largest perturbation occurs. On the contrary, the HCN molecule is considered an intermolecular mediator because its structure is practically unaltered upon the formation of the trimolecular complexes. In order to understand the real contribution of the proton-donor either mediator (HCN) or terminal (HW with W = CN or F), a chemometric analysis was performed uniquely to discover which interaction plays a key role in the collapse of the cooperative effect. The formation of strongest interactions leads to more drastic variations in the energy distribution. In this way, the application of the quantum theory of atoms in molecules (QTAIM) has been extremely important because the hydrogen bond strengths followed by indiciums of covalence were predicted, and therefore the cooperative effect could be understood at last.


Increased EETs participate in peripheral endothelial dysfunction of cirrhosis.
The hyperdynamic circulation of cirrhosis participates in the pathophysiology of portal hypertension. P450-dependent epoxyeicosatrienoic acids (EET) are potent vasodilators. We evaluated plasma levels of EETs in cirrhotic patients and the effect of epoxygenase and nitric oxide synthase (NOS) inhibition on skin blood flow, measured by laser Doppler flowmetry, in normal subjects and cirrhotic patients with and without ascites. Free plasma EETs were increased in cirrhotic patients compared to normal subjects, while the ratio between 8,9-, 11,12-, and 14-15-EET was the same. In cirrhotic patients without ascites, skin blood flow was significantly increased compared to normal subjects. In patients with ascites skin blood flow was significantly reduced compared to control subjects and patients without ascites. Inhibition of epoxygenase with miconazole and of NOS with L-NG-Nitroarginine methyl ester (L-NAME) decreased basal skin flow in normal subjects and in cirrhotic patients, the effect being higher in cirrhotic patients. Miconazole caused a further decrease in flow when administered with L-NAME, both in normal subjects and in cirrhotic patients. In conclusion, EETs participate in the control of peripheral circulation of normal subjects and in the pathophysiology of peripheral vasodilatation of cirrhotic patients with ascites.


Does a temperate ungulate that breeds in summer exhibit rut-induced hypophagia? Analysis of time budgets of male takin (Budorcas taxicolor) in Sichuan, China.
Mammals maximize fitness by optimizing time and energy allocation between reproduction and survival. Describing time budgets is a way to understand a species' constraints in energy allocation. We describe a time budget for male takin (Budorcas taxicolor) in Tangjiahe Nature Reserve, China, to better understand rut-induced hypophagia, which is frequently observed in temperate ungulates that breed in autumn or in winter. Observations generally occurred at two elevations (1200-1600m and 2600-3200m), using 20-min focal animal scan sampling from 2007 to 2009. Feeding behaviors accounted for the majority in takin's time budget (61.1%) during daylight hours, relative to the other observed behaviors, such as rest (14.1%), alert behavior (10.2%) and locomotion (6.8%). We found a negative correlation between feeding behavior and rutting behavior during the rutting season. A ratio of feeding time to resting time increased from pre-rut to rut, while resting behavior did not change significantly across seasons. These results suggest the "energy saving" hypothesis could explain reduced foraging in male takin during the rut, but aspects of the species biology suggest that hypotheses for rut-induced hypophagia developed for other temperate ungulates do not apply to takin. We suggest that the unusual summer rutting season of takin releases males from the energy constraints encountered by temperate ungulates that breed in the autumn and has other benefits for offspring survival. Further research should be conducted on ungulates that exhibit rut during the summer and tropical ungulates that might not experience limited food availability following the mating season to improve our understanding on rut-induced hypophagia.


Common marmoset embryonic stem cell can differentiate into cardiomyocytes.
Common marmoset monkeys have recently attracted much attention as a primate research model, and are preferred to rhesus and cynomolgus monkeys due to their small bodies, easy handling and efficient breeding. We recently reported the establishment of common marmoset embryonic stem cell (CMESC) lines that could differentiate into three germ layers. Here, we report that our CMESC can also differentiate into cardiomyocytes and investigated their characteristics. After induction, FOG-2 was expressed, followed by GATA4 and Tbx20, then Nkx2.5 and Tbx5. Spontaneous beating could be detected at days 12-15. Immunofluorescent staining and ultrastructural analyses revealed that they possessed characteristics typical of functional cardiomyocytes. They showed sinus node-like action potentials, and the beating rate was augmented by isoproterenol stimulation. The BrdU incorporation assay revealed that CMESC-derived cardiomyocytes retained a high proliferative potential for up to 24 weeks. We believe that CMESC-derived cardiomyocytes will advance preclinical studies in cardiovascular regenerative medicine.


Use of nonabsorbable polymer ligaclip in hand-assisted laparoscopic nephrectomy for living donor.
Laparoscopic living donor nephrectomy for kidney transplantation is a technique that began in South America only recently. This procedure offers several advantages compared with open nephrectomy due to the minor pain, better cosmetic results, and shorter length of hospital stay. Herein we have described our experience with the use of nonabsorbable polymer ligaclip (NPL) to control the renal artery, vein, and ureter in hand-assisted laparoscopic donor nephrectomy (HALN). We performed a review of 85 HALNs for renal transplantation at our institution between January 2004 and August 2007. We evaluated the preoperative characteristics of the donor, surgical parameters, and complications. Fifty six percent of donors were men. Mean donor age was 34.4 years (range = 18 to 60). Left-sided nephrectomy was performed in 85%. Mean surgical time was 132 minute (range = 90 to 240) and among the last 35 nephrectomies, 120 minute (range = 90 to 180). Mean warm ischemia time was 240 seconds (range = 120 to 420). Conversion rate was 1.1%. Mortality was one case (1.1%) secondary to an episode of massive pulmonary thromboembolism. Mean length of hospital stay was 2.5 days (range 2 to 5) and mean blood loss, 125 mL. No complication related to the NPL was observed. Laparoscopy living donor nephrectomy was a safe procedure for kidney transplantation. The training and experience of the surgeon was reflected in shorter times of surgery. The NPL was safe and cost-effective, not increasing morbidity of the procedure.


The Histogenesis of the Third Pathway of Colonic Carcinogenesis in Rats.
Conventional (tubular or villous) adenomas, and the more recently described serrated adenomas, are non-invasive neoplasias that precede colon carcinomas in carcinogen-treated rats. In contrast, the histological steps antedating carcinomas in gut-associated lymphoid tissue (GALT) in rats, i.e. the third pathway of colonic carcinogenesis, remain unidentified. Aim of the study was to investigate the histological changes preceding colonic GALT carcinomas in Sprague-Dawley (SD) rats. Archived sections from previous experiments showing GALT mucosal domains in 292 rats were re-evaluated: 276 were injected with 1,2-dimethylhydrazine (DMH) suspended in ethylenedia-minetetra-acetic acid (EDTA), and 16 were controls (8 EDTA-treated, and 8 untreated). A total of 402 colonic GALT mucosal domains were found in the 292 rats: 382 in 276 DMH-treated, 10 in eight EDTA-treated, and 10 in eight-untreated rats. In DMH-treated rats, corrupted crypts (CCS; i.e. with asymmetric fission or abnormal crypt-alignment) were recorded in 50% of the GALT domains (15% had no dysplasia and 35% had epithelial dysplasia). Adenomas on top of GALT domains were found in 7%, and GALT carcinomas in 53%. Histology of the 146 colonic GALT carcinomas revealed highly differentiated carcinomas or signet-ring cell carcinomas. EDTA-treated and untreated animals showed no dysplastic CCS, or other neoplasia. This study demonstrated that GALT mucosal domains in carcinogen-treated rats often develop dysplastic CCS. Non-dysplastic CCS appear to act as scaffolds for the top-down replacement/transformation by dysplastic cells. Importantly, highly differentiated carcinomas were seen to evolve from dysplastic CCS and from adenomas, and signet-ring cell carcinomas from dysplastic goblet cells present at the base of crypts. This is the first study showing that non-invasive neoplastic lesions (dysplastic CCS and adenomas) antedate colonic GALT carcinomas in DMH-treated SD rats. The DMH-SD paradigm permits detailed study of the histological events preceding GALT carcinoma under standard laboratory conditions.


The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease.
Loss-of-function mutations in the OCRL gene, which encodes the phosphatidylinositol [PI] 4,5-bisphosphate [PI(4,5)P2] 5-phosphatase OCRL, cause defective endocytosis and proximal tubule dysfunction in Lowe syndrome and Dent disease 2. The defect is due to increased levels of PI(4,5)P2 and aberrant actin polymerization, blocking endosomal trafficking. PI 3-phosphate [PI(3)P] has been recently identified as a coactivator with PI(4,5)P2 in the actin pathway. Here, we tested the hypothesis that phosphoinositide 3-kinase (PI3K) inhibitors may rescue the endocytic defect imparted by OCRL loss, by rebalancing phosphoinositide signals to the actin machinery. The broad-range PI3K inhibitor copanlisib and class IA p110α PI3K inhibitor alpelisib reduced aberrant actin polymerization in OCRL-deficient human kidney cells in vitro. Levels of PI 3,4,5-trisphosphate, PI(4,5)P2 and PI(3)P were all reduced with alpelisib treatment, and siRNA knockdown of the PI3K catalytic subunit p110α phenocopied the actin phenotype. In a humanized OcrlY/- mouse model, alpelisib reduced endosomal actin staining while restoring stress fiber architecture and levels of megalin at the plasma membrane of proximal tubule cells, reflected by improved endocytic uptake of low molecular weight proteins in vivo. Thus, our findings support the link between phosphoinositide lipids, actin polymerization and endocytic trafficking in the proximal tubule and represent a proof-of-concept for repurposing alpelisib in Lowe syndrome/Dent disease 2.


Investigation of the incidence of heavy metals contamination in commonly used fertilizers applied to vegetables, fish ponds, and human health risk assessments.
Overuse of fertilizers on agricultural lands and fish ponds may result in serious pollution problems, such as heavy metals that can enter the food chain and pose serious health problems. Due to this, the present study investigates the incidence of heavy metals in commonly used fertilizers and its association with heavy metals in vegetables, soil, fish species, and pond water. Samples were collected from different sites (fields and ponds) in district Kohat, where the application of fertilizers was common and control groups (no fertilizers used). Heavy metal analysis was carried out through a spectrophotometer. Results showed higher Cd and Cr concentrations in triple superphosphate (TSP), Cu and Pb in nitrogen, phosphorus, and potassium (NPK), while lower concentrations were found in gypsum. In vegetables (onion, tomato, brinjal, and potato) and associated soil, most of the heavy metals concentrations were significantly higher (P < 0.05) in fertilizer-applied sites than in the control. Also, the Cd concentration in potatoes and Pb level in all vegetables obtained from sites were greater than the WHO/FAO standard limit. In the case of fish species (Hypophthalmichthys molitrix and Cyprinus carpio) muscles and their habitat (water), all the understudy heavy metals were notably higher (P < 0.05) in fertilizer-applied sites (ponds) than the control group. Collectively, in all vegetables and muscles of fish species, the bioaccumulation factor was higher in sites compared to the control. The estimated daily intake (EDI) and target hazard quotient (THQ) values were also higher in fertilizer-applied sites (fields and ponds) than control. The health index (HI) value was > 1 in vegetables (onion, tomato, and potato) and fish muscles collected from different sites compared to the control. Thus, there is the possibility of severe health risks. The use of fertilizers must be carefully monitored in order to ensure that humans and animals are safe from exposure to heavy metals.


The RNA-binding protein RNPC1 stabilizes the mRNA encoding the RNA-binding protein HuR and cooperates with HuR to suppress cell proliferation.
The RNA-binding protein HuR, a member of the embryonic lethal abnormal vision/Hu protein family, plays a critical role in many cellular processes, including cell proliferation, angiogenesis, and inflammatory response. Despite significant progresses in understanding how HuR functions, the mechanism by which HuR expression is controlled is still poorly understood. Here, we showed that RNA-binding protein RNPC1 post-transcriptionally regulates HuR expression via mRNA stability. Specifically, we showed that overexpression of RNPC1 increases, whereas knockdown or knock-out of RNPC1 decreases, the level of HuR transcript and protein. Moreover, we showed that RNPC1, but not mutant RNPC1 deficient in RNA binding, stabilizes HuR transcript via binding to its 3'-untranslated region. Furthermore, to determine the biological significance of RNPC1-enhanced HuR expression, we showed that HuR, by repressing c-Myc expression, facilitates RNPC1-mediated growth suppression. Together, we have uncovered a novel mechanism by which HuR is regulated by RNPC1 via mRNA stability and HuR is a mediator of RNPC1-induced growth suppression.


[Surgical treatment options for congenital/infantile corneal opacities and anterior segment dysgenesis].
Due to the risk of amblyopia congenital and infantile corneal opacities have a narrow therapeutic window, frequently with a complex surgical treatment. The present study gives an overview of the current treatment options for congenital and infantile corneal opacities. The results of a literature search are presented and own clinical data and examples are shown. In children ophthalmologic operations are surgically more demanding and the prognosis is generally worse. Surgical options include phototherapeutic keratectomy, crosslinking, corneal sutures, sectoral iridectomy, block excision and lamellar, penetrating, and auto-keratoplasty. An equally important part of the treatment is conservative treatment, when necessary with bandage lenses, glasses, contact lenses and occlusion. Whenever possible treatment of congenital and infantile corneal opacities should be limited to the affected layers/areas. Nevertheless, children and parents have to be prepared for many examinations, sometimes with the patient under anesthesia and should be well-informed about the prognosis and the risks.


Overall bias methods and their use in sensitivity analysis of Cochrane reviews were not consistent.
The objective of the study was to analyze methods of assessing "overall bias" in Cochrane reviews of interventions published in the Cochrane Database of Systematic Reviews and sensitivity analyses related to overall risk of bias (RoB). From Cochrane reviews published within 3 years, from July 2015 to June 2018, we extracted data regarding methods of judging overall bias for a single trial, as well as details regarding methods used in frequency of RoB in sensitivity analyses. Of the 1,452 analyzed Cochrane reviews, 409 mentioned assessment of overall RoB on a study level. In 107 reviews, authors clearly specified key domains that determined the overall RoB, whereas in the remaining reviews, assessment of overall bias was not in line with the Cochrane Handbook. Among 268 Cochrane reviews that had any RoB-related sensitivity analysis, in 56 (21%) reviews, the authors reported a significant change for at least one outcome compared with the initial analysis. Highly heterogeneous approaches to summarizing overall RoB on a study level and using RoB for sensitivity analyses may yield inconsistent and incomparable results across Cochrane reviews.


Shikonin, an inhibitor of inflammasomes, inhibits Epstein-Barr virus reactivation.
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. EBV usually establishes an asymptomatic life-long infection, but it is also associated with malignancies affecting B lymphocytes and epithelial cells mainly. The virus alternates between a latent phase and a lytic phase, both of which contribute to the initiation of the tumor process. So far, there is only a limited number of antiviral molecules against the lytic phase, most of them targeting viral replication. Recent studies provided evidence that EBV uses components of the NLRP3 inflammasome to enter the productive phase of its cycle following activation in response to various stimuli. In the present work, we demonstrate that shikonin, a natural molecule with low toxicity which is known to inhibit inflammasome, can efficiently repress EBV reactivation. Similar results were obtained with apigenin and OLT 1177, two other NLRP3 inflammasome inhibitors. It is shown herein that shikonin repressed the transcription of reactivation-induced NLRP3 thereby inhibiting inflammasome activation and EBV lytic phase induction.


Draft Genome Sequence of the Basidiomycetous Fungus Flammulina velutipes TR19.
Here, we report the draft genome sequence of Flammulina velutipes TR19, which was newly isolated from commercial strains in Japan. The genes related to fruiting body formation in the basidiomycete were identified by whole-genome analysis.


Correlations between seminal radioimmunoreactive prolactin, sperm count, and sperm motility in prevasectomy and infertility clinic patients.
Semen samples were collected from 50 prevasectomy patients and 43 infertility clinic patients. Various parameters were measured, including semen radioimmunoreactive prolactin (rPRL) levels. Linear correlations were tested between the measured parameters, and a significant correlation was found between semen rPRL concentration and sperm count for both the prevasectomy (r = 0.73, P less than 0.00002) and the clinic patients (r = 0.72, P less than 0.00002). For the clinic patients a correlation was also found between the amount of ejaculate rPRL and sperm motility (r = 0.46, P less than 0.002) and between ejaculate volume and motility (r = 0.36, P less than 0.02).


[1-stage operation in major aplasias of the ear. Value of combined plastic and functional intervention].
In spite of imperfections, combined functional and plastic surgery is of value of treating major aplasias of the ear. The two operative procedures can be performed by the same surgeon or the same team when the child has reached 5 to 6 years of age. The technique involves the use of sliding pedunculated flaps, with rotation in the auricular region, and the employ of conventional otologic microsurgical methods (homograft, moulded temporal aponeurosis). Results in 48 cases demonstrated auditory improvement of more than 20 decibels in 47-5 p. cent of cases, and 30 to 40 decibels in 20.8 p. cent.


Pneumocystis pneumonia in a patient treated with alemtuzumab for relapsing multiple sclerosis.
Pneumocystis jirovecii pneumonia (PJP) is a known risk in patients with chronic lymphocytic leukemia treated with alemtuzumab (Campath®). However, no recommendation for PJP prophylaxis for alemtuzumab use in multiple sclerosis (Lemtrada®) and no known associated PJP has been reported to date. We report a patient who developed PJP two months after receiving the first course of Lemtrada, and fully recovered after receiving cotrimoxazole treatment. We should remain vigilant of opportunistic infections in patients who develop pneumonitis and evaluate the need for PJP prophylaxis during Lemtrada treatment.


Atomic-scale imaging of individual dopant atoms and clusters in highly n-type bulk Si.
As silicon-based transistors in integrated circuits grow smaller, the concentration of charge carriers generated by the introduction of impurity dopant atoms must steadily increase. Current technology, however, is rapidly approaching the limit at which introducing additional dopant atoms ceases to generate additional charge carriers because the dopants form electrically inactive clusters. Using annular dark-field scanning transmission electron microscopy, we report the direct, atomic-resolution observation of individual antimony (Sb) dopant atoms in crystalline Si, and identify the Sb clusters responsible for the saturation of charge carriers. The size, structure, and distribution of these clusters are determined with a Sb-atom detection efficiency of almost 100%. Although single heavy atoms on surfaces or supporting films have been visualized previously, our technique permits the imaging of individual dopants and clusters as they exist within actual devices.


Stone formation in human kidney.
Microscopic crystals were found by SEM analysis in kidneys of stone forming patients as well as in kidneys of non-stone formers. In most samples calcifications were intratubular in the collecting ducts near the papillary tip. 1-2 micron sized particles lay in a gelatinous substance on the epithelium. The only difference in crystal composition is the higher phosphate content in the kidneys of the non-stone forming group. A correlation between the element concentration of the tissue and the occurrence of microliths is given by the cadmium content of the kidney samples. Both groups showed higher cadmium values in the cortex or medulla when crystals were found in the corresponding papillary samples. Urine supersaturation with respect to calcium oxalate was higher in the stone forming group caused by a higher calcium and oxalate but a lower magnesium excretion.


Chronotropic effect of D-Ala2,Leu5,Arg6-enkephalin (dalargin) is associated with activation of peripheral kappa-opioid receptors.
Intravenous infusion of D-Ala2,Leu5,Arg6-enkephalin (dalargin) caused bradycardia in narcotized rats. This effect was not observed during opioid receptor blockade with naloxone, naloxone methiodide, and norbinaltorphimine. Dalargin and (-)-U-50,488 added to Krebs-Henseleit perfusion solution for isolated rat heart decreased heart rate. Ganglionic blocker hexamethonium potentiated the negative chronotropic effect of dalargin. The negative chronotropic effect of dalargin is probably associated with activation of cardiac kappa-opioid receptors. It should be noted that dalargin caused tachycardia in some animals. This reaction was not observed after treatment with hexamethonium. The positive chronotropic effect of dalargin is probably related to modulation of the parasympathetic autonomic nervous system. Agonists and antagonists of delta-opioid receptors caused persistent bradycardia. We hypothesized that selective delta-opioid antagonists exhibit properties of partial delta-receptor agonists.


Effects of leaf nitrogen availability and leaf position on nitrogen allocation patterns in Vaccinium vitis-idaea and Vaccinium uliginosum.
Nitrogen allocation patterns from leaves of Vaccinium vitis-idaea (evergreen) and Vaccinium uliginosum (deciduous) were assessed using a foliar application of 15N labeled ammonium sulfate. These are wild perennial shrubs inhabiting arctic and subarctic regions. More label was transported from labeled leaves of Vaccinium uliginosum then Vaccinium vitis-idaea. In Vaccinium uliginosum, the amount of label transported from the labeled leaf increased as the concentration of nitrogen in the label increased. Current growth in Vaccinium uliginosum was a strong sink for nitrogen because most of the 15N transported from the labeled leaf was contained in this region. In addition, when greater quantities of nitrogen were applied, larger quantities were retained in current growth. Current growth of Vaccinium vitis-idaea, on the other hand, was not as strong a sink because regardless of the nitrogen available thru various label concentrations, the enrichment of current growth was not affected and was not significantly different from older stems or leaves. Yet, in both species, nitrogen was transported freely from leaves of all positions along the stem to all parts of the plant including roots and rhizomes. The position of the leaf along the stem had no effect on the patterns of allocation to other organs.


Is brivaracetam-induced elevation of carbamazepine-epoxide levels common and clinically relevant? - A case series.
Brivaracetam (BRV) was recently introduced for the treatment of patients with focal epilepsy. BRV undergoes relatively few interactions, but one of them leads to the elevation of carbamazepine (CBZ)-10,11-CBZ-epoxide (CBZ-E) if BRV is co-administered with CBZ. This interaction has been considered to be clinically negligible. We present a case series of nine patients. In eight of them, levetiracetam (LEV) was switched to BRV. In the remaining case, oxcarbazepine was replaced by CBZ and added to a stable BRV dose. A marked increase of CBZ-E occurred in every case and was associated with clinically relevant symptoms including blurred vision, diplopia, dizziness, or fatigue in three of them. However, in the remaining six, the elevated CBZ-E levels were not associated with any tolerability problems. The importance of CBZ-E for adverse events under CBZ may have been overemphasized in the past and is not clinically impairing in most cases treated with the combination of BRV and CBZ.


Development of the Health Incentive Program Questionnaire (HIP-Q) in a cardiac rehabilitation population.
The purpose of this study was to develop a questionnaire to facilitate the design of acceptable financial health incentive programs. A multiphase psychometric questionnaire development method was used. Theoretical and literature reviews and three focus groups generated a pool of content areas and items. New items were developed to ensure adequate content coverage. Field testing was conducted with a convenience sample of cardiac rehabilitation (CR) patients (n = 59) to establish face and construct validity (p = 0.021) and reliability (intraclass coefficients = 0.42-0.87). The final questionnaire is comprised of 23 items. This questionnaire builds on previous attempts to explore acceptability by sampling a wider range of instrumental and affective attitudes and by measuring the effect of program features on the likelihood of incentive program participation. Future research is now needed to examine whether tailoring incentives to preferences assessed by the questionnaire improves uptake and effectiveness.


Extracorporeal membrane oxygenation for acute respiratory distress syndrome in burn patients: a case series and literature update.
Acute respiratory distress syndrome (ARDS) has a reported incidence of 34-43% in ventilated burn patients and is associated with a mortality of 59% in the severe form. The use and experience with extracorporeal membrane oxygenation (ECMO) in burn patients developing ARDS are still limited. We present our results and discuss the significance of ECMO in treating burn patients. A retrospective analysis of burn patients treated with ECMO for ARDS between January 2017 and January 2019 was performed. Demographic, clinical, and outcome data were collected and analyzed. Eight burn patients were treated at our institution with ECMO in the designated time period. Of these, all but one patient had inhalation injury, burn percentage of TBSA was 37 ± 23%, ABSI score was 8.4 ± 2, and R-Baux-score was 98 ± 21. Seven patients developed severe ARDS and one patient moderate ARDS according to the Berlin classification with a PaO2/FiO2 ratio upon initiation of ECMO therapy of 62 ± 22 mmHg. ECMO duration was 388 ± 283 h. Three patients died from severe sepsis while five patients survived to hospital discharge. ECMO is a viable therapy option in burn patients developing severe ARDS and can contribute to survival rates similar to ECMO therapy in non-burn-associated severe ARDS. Consequently, patients with severe respiratory insufficiency with unsuccessful conventional treatment and suspected worsening should be transferred to burn units with the possibility of ECMO treatment to improve outcome.


Editorial Commentary: Average and Below-Average Surgeons May Struggle With the Anteromedial Portal Technique for Creating the Anterior Cruciate Ligament Femoral Socket.
Average surgeons may struggle with the anteromedial (AM) portal technique for creating the anterior cruciate ligament femoral socket. The AM portal technique is technically challenging. The AM portal technique demonstrates better surgeon-recorded stability than the transtibial technique, but no clinical differences according to a review of published, comparative research studies.


Structure/function relationships of muscarinic acetylcholine receptors.
The regions of muscarinic receptors that specify G-protein-coupling and ligand-binding have been defined in several recent studies. Overall, these studies have shown that amino acids within the third cytoplasmic loop of the receptors define their selectivity for different G-proteins, and that multiple, discontinuous epitopes contribute to their selectivities for different ligands. In fact, several competitive and allosteric antagonists can be classified into groups based on which of these epitopes contribute to their subtype selectivity. Site-directed mutagenesis, combined with covalent-labeling studies have suggested that ligands bind to a hydrophobic core of the receptors that is formed by multiple transmembrane (TM) domains. An aspartic acid located in TM3 is likely to bind to the ammonium headgroup of muscarinic ligands, and multiple hydroxyl-containing amino acids contribute to agonist but not antagonist binding. These data are discussed in the context of a computational model of a muscarinic receptor. Our model is based on a sequence alignment with bacteriorhodopsin, a seven TM protein for which a higher resolution structure is available. Most of the mutagenic data can be rationalized in the context of this model, and predict testable hypotheses concerning the mechanism by which ligands control the activity of muscarinic receptors.


Neuroprotective effects of T-817MA against noise-induced hearing loss.
Oxidative stress, including reactive oxygen species and other free radicals, is thought to play an important role in neuronal cell death, including noise-induced hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced neurotoxicity. This study examines the effects of T-817MA in noise-induced ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to noise exposure and continuing through this study. All subjects were exposed to 4-kHz octave-band noise at 120-dB SPL for 5h. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16kHz, prior to and 10 days following noise exposure. Hair cell damage was analyzed by quantitative histology. T-817MA significantly reduced threshold deficits and hair cell death. These results suggest T-817MA reduces noise-induced hearing loss and cochlear damage, suggesting functional and morphological protection.


Role of mitogen-activated protein kinases in plant immunity.
Studies of the early events that follow pathogen recognition have established the importance of mitogen-activated protein kinase (MAPK) cascades in plant defense signaling. Specific MAPK cascade components have now been identified in several species, and so it has become possible to compare defense responses to diverse pathogens and to elucidate downstream events that are initiated by these key signaling molecules. Recent work utilizing post-transcriptional gene silencing techniques and the development of stable transgenic lines for both gain- and loss-of-function analysis have further advanced our understanding of the role of MAPK cascades in plant immunity.


Outcome analysis of elderly patients undergoing laparoscopic resection rectopexy for rectal prolapse.
For treatment of rectal prolapse, abdominal approaches are generally offered to younger patients, whereas perineal, less invasive procedures are considered more beneficial in the elderly. The aim of this study was to analyze whether laparoscopic resection rectopexy (LRR) is suitable for older patients. Patients who received LRR for rectal prolapse were selected from a prospective laparoscopic colorectal surgery database. Perioperative and long-term outcome were compared between patients <75 years old (group A) and ≥75 years old (group B). Of 154 patients, 111 were in group A and 43 in group B. There was one conversion that occurred in group B. Overall mortality rate was 1.3% (n = 2). Both patients were in group B (group B, 4.7%; p = 0.079). Differences in major and minor complications between the groups were not significant. Rates of improvement for incontinence were 62.7% (group A) and 66.7% (group B; p = 0.716); for constipation, the rates were 78.9% (group A) and 73.3% (group B; p = 0.832). All recurrences occurred in group A (n = 10; overall, 10.3%; group A, 13%). After exclusion of patients who had previously received perineal prolapse surgery, recurrence rate was 3.3% overall (group A, 4.3%). This study supports the benefits of LRR for rectal prolapse in elderly patients. Age per se is not a contraindication for LRR. Elderly patients encounter complications slightly more frequently (although not statistically significant) than younger patients. Therefore, a very careful patient selection in the elderly is of paramount importance. However, the long-term outcome does not seem to differ between younger and elderly patients.


Coronary surgery in dialysis-dependent patients with end stage renal failure.
The number of patients with dialysis-dependent end stage renal failure (ESRF) and coronary heart disease (CAD) has increased in recent years. Coronary artery bypass grafting (CABG) has become the standard treatment for CAD in this patient group, but is still considered as a risk procedure due to increased mortality and morbidity. In a retrospective study we analyzed our clinical results of isolated CABG in 40 dialysis-dependent patients with ESRF (5 female and 35 male, mean age 65+/-8.4 years) and the use of extracorporeal circulation. The perioperative control group comprised 51 patients (10 female and 41 male, mean age 67+/-7.3 years) with normal renal function and isolated CABG. Demographic and preoperative data were comparable in both groups. Hospital mortality was 2.5% in patients with ESRF and 0% in patients with normal renal function. Morbidity was comparable in both groups. The mean number of grafts was 3.1+/-0.9 in the dialysis group and 2.9+/-0.8 in the control group. In the follow-up of the dialysis group (34+/-23 months) 8 patients died. CABG in patients with dialysis-dependent ESRF can be performed with good clinical results and morbidity comparable to patients with normal renal function.


Elevated adipose tissue lipoprotein lipase activity in craniopharyngioma patients.
The activity of lipoprotein lipase (LPL) was measured in adipose tissue (AT-LPL) and postheparin plasma (PH-LPL) of 13 obese patients (aged 11 to 31 years) who had surgery for craniopharyngioma 1 to 13 years earlier. AT-LPL activity (mean +/- SEM) was higher in them than in subjects matched with respect to age, sex, and relative body weight (4.6 +/- 1.1 v 2.1 +/- 0.4 mumol free fatty acids (FFA).h-1.g-1, P less than .05). The activity was also higher when expressed per fat cell.


ZAK: a MAP3Kinase that transduces Shiga toxin- and ricin-induced proinflammatory cytokine expression.
Shiga toxins (Stxs) and ricin initiate damage to host cells by cleaving a single adenine residue on the alpha-sarcin loop of the 28S ribosomal RNA. This molecular insult results in a cascade of intracellular events termed the ribotoxic stress response (RSR). Although Stxs and ricin have been shown to cause the RSR, the mitogen-activated protein kinase kinase kinase (MAP3K) that transduces the signal from intoxicated ribosomes to activate SAPKinases has remained elusive. We show in vitro that DHP-2 (7-[3-fluoro-4-aminophenyl-(4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl))]-quinoline), a zipper sterile-alpha-motif kinase (ZAK)-specific inhibitor, blocks Stx2/ricin-induced SAPKinase activation. Treatment of cells with DHP-2 also blocks Stx2/ricin-mediated upregulation of the proinflammatory cytokine interleukin-8 and results in a modest but statistically significant improvement in cell viability following Stx2/ricin treatment. Finally we show that siRNA directed against the N-terminus of ZAK diminishes Stx2/Ricin-induced SAPKinase activation. Together, these data demonstrate that a ZAK isoform(s) is the MAP3Kinase that transduces the RSR. Therefore, ZAKalpha and/or beta isoforms may act as potential therapeutic target(s) for treating Stx/ricin-associated illnesses. Furthermore, a small molecule inhibitor like DHP-2 may prove valuable in preventing the Stx/ricin-induced proinflammatory and/or apoptotic effects that are thought to contribute to pathogenesis by Stx-producing Escherichia coli and ricin.


Enhanced mechanical strength and biocompatibility of electrospun polycaprolactone-gelatin scaffold with surface deposited nano-hydroxyapatite.
In this study for the first time, we compared physico-chemical and biological properties of polycaprolactone-gelatin-hydroxyapatite scaffolds of two types: one in which the nano-hydroxyapatite (n-HA) was deposited on the surface of electrospun polycaprolactone-gelatin (PCG) fibers via alternate soaking process (PCG-HAAS) and other in which hydroxyapatite (HA) powders were blended in electrospinning solution of PCG (PCG-HAB). The microstructure of fibers was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) which showed n-HA particles on the surface of the PCG-HAAS scaffold and embedded HA particles in the interior of the PCG-HAB fibers. PCG-HAAS fibers exhibited the better Young's moduli and tensile strength as compared to PCG-HAB fibers. Biological properties such as cell proliferation, cell attachment and alkaline phosphatase activity (ALP) were determined by growing human osteosarcoma cells (MG-63) over the scaffolds. Cell proliferation and confocal results clearly indicated that the presence of hydroxyapatite on the surface of the PCG-HAAS scaffold promoted better cellular adhesion and proliferation as compared to PCG-HAB scaffold. ALP activity was also observed better in alternate soaked PCG scaffold as compared to PCG-HAB scaffold. Mechanical strength and biological properties clearly demonstrate that surface deposited HA scaffold prepared by alternate soaking method may find application in bone tissue engineering.


Features of Golenkinia sp. and microbial fuel cells used for the treatment of anaerobically digested effluent from kitchen waste at different dilutions.
The aim of this work was to study Golenkinia sp. and microbial fuel cells (MFCs) for the treatment of anaerobically digested effluent from kitchen waste (ADE-KW) with different dilution factors. A dual-chamber MFC was fabricated for treating ADE-KW in the two chambers of the MFC and harvesting Golenkinia sp. All the anodic TN was removed more than 80%. COD removal efficiency increased from 48.2% to 76% when the dilution factor increased from 1 to 4. Maximum COD and TN removal rates were 3.56 and 3.71mg·L-1·h-1 when ADE-KW was treated without dilution in the anodic chamber. All the cathodic TN and TP removal efficiencies were approximately 90%. The highest open circuit voltage (OCV) and power density were approximately 400mV and 400mW when ADE-KW was treated directly (undiluted) in the MFC, with the highest biomass and total lipid content production of Golenkinia sp. in the cathodic chamber.


Ultrasmall, water dispersible, TWEEN80 modified Yb:Er:NaGd(WO4)2 nanoparticles with record upconversion ratiometric thermal sensitivity and their internalization by mesenchymal stem cells.
This work presents the synthesis by coprecipitation of diamond shaped Yb:Er:NaGd(WO4)2 crystalline nanoparticles (NPs) with diagonal dimensions in the 5-7 nm × 10-12 nm range which have been modified with TWEEN80 for their dispersion in water, and their interaction with mesenchymal stem cells (MSCs) proposed as cellular NP vehicles. These NPs belong to a large family of tetragonal Yb:Er:NaT(XO4)2 (T = Y, La, Gd, Lu; X = Mo, W) compounds with green (2H11/2 + 4S3/2 → 4I15/2) Er-related upconversion (UC) efficiency comparable to that of Yb:Er:β-NaYF4 reference compound, but with a ratiometric thermal sensitivity (S) 2.5-3.5 times larger than that of the fluoride. At the temperature range of interest for biomedical applications (∼293-317 K/20-44 °C) S = 108-118 × 10-4 K-1 for 20 at%Yb:5 at%Er:NaGd(WO4)2 NPs, being the largest values so far reported using the 2H11/2/4S3/2 Er intensity ratiometric method. Cultured MSCs, incubated with these water NP emulsions, internalize and accumulate the NPs enclosed in endosomes/lysosomes. Incubations with up to 10 μg of NPs per ml of culture medium maintain cellular metabolism at 72 h. A thermal assisted excitation path is discussed as responsible for the UC behavior of Yb:Er:NaT(XO4)2 compounds.


[Intracellular distribution and destruction of liposomes after in vitro phagocytosis by alveolar macrophages].
Electron microscopy was used to watch and monitor free as well as phagosomically incorporated multilamellar vesicles (MLV) which were considered to be signs of rapid recycling of phagosomal membranes. Close relations were found to exist between lysosomes, on the one hand, and MLV in phagosomes, on the other. The same applied to MLV and mitochondria or nuclear membranes. Destruction of MLV was highly differentiated. Hints are given in this paper on the kinetics of such processes. These results are considered to be of some relevance to the suitability of liposomes as carriers of pharmaceutical substances.


Routine use of perfusion computed tomography for the detection of delayed cerebral ischemia in unconscious patients after aneurysmal subarachnoid hemorrhage.
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is difficult to diagnose in unconscious patients, but it is essential for the prognosis. We analyzed the diagnostic value of routinely performed perfusion computed tomography (rPCT) to detect DCI-related hypoperfusion in this subgroup of patients. Retrospective analysis of unconscious aSAH patients who underwent rPCT according to a predefined protocol. We exclusively analyzed PCT examinations in patients who were clinically and functionally asymptomatic with regard to transcranial Doppler ultrasound (TCD) and invasive neuromonitoring at the time of the PCT examination. The perfusion maps were quantitatively evaluated to detect DCI-related hypoperfusion. Possible clinical risk factors for the occurrence of DCI-related hypoperfusion in rPCT imaging were analyzed by multivariate analyses. One hundred thirty-six rPCTs were performed in 55 patients. New onset of DCI-related hypoperfusion was observed in 18% of rPCTs. The positive predictive value of rPCT to detect angiographic CVS was 0.80. Between examination days 6 and 10, the rate of DCI-related hypoperfusion was increased significantly (p < 0.05). After rPCT imaging with proof of DCI-related hypoperfusion, short-term follow-up showed secondary cerebral infarction (SCI) in 38%, compared with 5% for patients with normal perfusion on rPCT. The parameters "high risk phase (examination days 6-10)" and "new onset of DCI-related SCI" were significantly associated with the occurrence of DCI-related hypoperfusion in rPCT. In unconscious and asymptomatic aSAH patients, rPCT identifies DCI-related hypoperfusion in a relevant number of examinations. However, despite timely endovascular rescue therapy, a significant proportion of secondary infarction still occurs in this subgroup.


Animal models for studying serotonin (5-HT) receptor subtypes: relationship to 5-HT system pathologies.
Despite more than 30 years of intensive research, the specific role of serotonin (5-HT) receptor subtypes in animal models of "anxiety" still remains unclear. The present study focused on the particular role of 5-HT1A receptor subtype in aversive learning, i.e., the passive avoidance (PA) task in the rat. Taken together, the data strongly suggest that: (1) 5-HT1A receptor but not 5-HT2A receptors play a crucial role in PA; (2) the postsynaptic but not presynaptic 5-HT1A receptors are mainly involved in the regulation of PA; (3) 5-HT1A receptors appear to be directly involved both in acquisition and retrieval but not in the consolidation of PA; and (4) besides the "prototypical" 5-HT1A receptor subtype, an additional and yet-unidentified 5-HT receptor subtype seems to play an important modulatory role in PA.


Psychiatric comorbidity in women with a history of childhood sexual abuse.
Childhood sexual abuse (CSA) is associated with the development of numerous adult mental disorders. Women with a history of CSA were surveyed concerning their abuse experience and prevalence of DSM-IV mental disorders. The 63 women in the low morbidity cluster had a mean of 1.02 disorders. The 11 women in the moderate morbidity cluster had a mean of 2.36 disorders. The 16 women in the severe morbidity cluster had a mean of 4.75 disorders. Childhood family environment and CSA during preschool years were important predictors of morbidity cluster membership.


Ultrasound radiomics in the prediction of microvascular invasion in hepatocellular carcinoma: A systematic review and meta-analysis.
To systematically assess the clinical value of ultrasound radiomics in the prediction of microvascular invasion in hepatocellular carcinoma (HCC). Relevant articles were searched in PubMed, Web of Science, Cochrane Library, Embase and Medline and screened according to the eligibility criteria. The quality of the included articles was assessed based on the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. After article assessment and data extraction, the diagnostic performance of ultrasound radiomics was evaluated based on pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR), and the area under the curve (AUC) was calculated by generating the ROC curve. Meta-analysis was performed using Stata 15.1, and subgroup analysis was conducted to identify the sources of heterogeneity. A Fagan nomogram was generated to assess the clinical utility of ultrasound radiomics. Five studies involving 1260 patients were included. Meta-analysis showed that ultrasound radiomics had a pooled sensitivity of 79% (95% CI: 75-83%), specificity of 70% (95% CI: 59-79%), PLR of 2.6 (95% CI: 1.9-3.7), NLR of 0.30 (95% CI: 0.23-0.39), DOR of 9 (95% CI: 5-16), and AUC of 0.81 (95% CI: 0.78-0.85). Sensitivity analysis indicated that the results were statistically reliable and stable, and no significant difference was identified during subgroup analysis. Ultrasound radiomics has favorable predictive performance in the microvascular invasion of HCC and may serve as an auxiliary tool for guiding clinical decision-making.


Preparation and formation mechanism of BiOCl0.75I0.25 nanospheres by precipitation method in alcohol-water mixed solvents.
BiOCl0.75I0.25 crystals with irregular three-dimensional (3D) flower-like and hierarchical nanosphere-like structures were successfully synthesized in different alcohol-water mixed solvents by precipitation method. The primary formation mechanism of BiOCl0.75I0.25 nanospheres was investigated by taking water, monohydric alcohols (ethanol and isopropanol), and polyhydric alcohols (ethylene glycol, diethylene glycol, and glycerol) as solvents in the synthesis process. The obtained BiOCl0.75I0.25 samples were characterized by powder X-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy, and nitrogen adsorption. Results showed that the alcohol solvents with different physical and chemical properties used in the synthesis process performed significant functions in directing the morphology and surface pore structure of BiOCl0.75I0.25 crystals. Meanwhile, BiOCl0.75I0.25 synthesized in various solvents exhibited morphology-dependent adsorption and photocatalytic degradation abilities in removing p-hydroxyphenylacetic acid (p-HPA), which was used as a model pollutant, in aqueous solutions under simulated solar light (λ⩾290nm). In addition, the fabrication process of the crystal products was proposed through a series of time-dependent experiments.


Minimal invasive retrieval of dislodged Amplatzer occluder with subsequent impediments.
A 47-year-old female underwent interventional patent foramen ovale (PFO) closure with an Amplatzer septal occluder (AGA Medical Corporation, USA). After 48 hours of implantation, she experienced intermittent pulse synchronous retrosternal pain. Subsequently, device-associated compression of the aortic root was diagnosed. Occluder retrieval and surgical PFO-closure was accomplished successfully via minimal invasive, video-assisted anterolateral thoracotomy.


Conventional tomography in musculoskeletal trauma.
Conventional tomography utilizes controlled blurring of overlying structures, in effect, to remove these possible obscuring overlying structures and permit improved evaluation of anatomic detail within the specific layer or focal plane of interest. Although it has largely been replaced by true sectional imaging modalities such as CT and MR imaging, it remains a valuable tool in specific settings as in musculoskeletal trauma. It is particularly useful when the orientation of the pathology requires coronal or sagittal planes for optimal evaluation.


Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue in the oromaxillofacial head and neck region: A retrospective analysis of 105 patients.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the oromaxillofacial head and neck region is rare, with limited data available. This retrospective study explored the clinical features, stage, treatment, and prognosis of this disease. Overall, 105 patients with MALT lymphomas in the oromaxillofacial head and neck region were included in this retrospective analysis. SPSS 22.0 software package was used for data analysis and a two-tailed P value of ≤.05 was considered statistically significant. Primary endpoints of the study were the complete response (CR) rate, overall survival (OS), and progression-free survival (PFS). About 52% of the patients had long-term xerostomia, autoimmune diseases, or chronic parotitis and 81% had diseases involving the large salivary glands. Ann Arbor staging of the patients was as follows: stages I/II, 73 patients and stages III/IV, 32 patients. In the 97 patients followed up, CR rate after initial treatment was 80%. Tumor progression was observed in 12 patients and 14 patients died. There was a significant difference between the rate of CR in localized (87%) and disseminated (67%) lymphoma patients (P = .02). The 5- and 10-year PFS of the localized lymphoma patients were both 91%, whereas those of the disseminated lymphoma patients were 83% and 65%, respectively (P = .03). The 5-year PFS rates of the chemotherapy and non-chemotherapy groups in the disseminated lymphoma patients were 85% and 73% (P = .04). Meanwhile, the 5-year PFS rates of the rituximab and non-rituximab groups in the disseminated lymphoma patients were 100% and 70% (P = .03). In multivariate analysis, MALT Lymphoma International Prognostic Index (MALT-IPI) was an independent prognostic factor affecting OS, whereas Ann Arbor staging affected PFS. This study suggests that the outcome after initial treatment of MALT lymphomas in the oromaxillofacial head and neck region is satisfactory and that this disease progresses slowly. The CR rate and PFS of localized lymphoma patients are better than those of disseminated lymphoma patients. Systemic treatment (chemotherapy or rituximab) may improve PFS in disseminated disease patients. MALT-IPI and Ann Arbor staging are independent prognostic factors.


Microplate-bridge technique for watertight dural closures in the combined petrosal approach.
Although the combined petrosal approach has significant advantages for medium to large petroclival lesions, it carries the risk of a few major complications. The cerebrospinal fluid leak rate with this approach has been reported to be as high as 15%. To describe an innovative technique of watertight dural closure with a long microplate-bridge technique for the combined petrosal approach. We describe our method of watertight dural closures with the microplate-bridge technique for combined petrosal approaches using cadaveric heads and clinical cases. We review our postoperative outcomes in respect to cerebrospinal fluid leaks. The technique involves a fascial graft to the presigmoid-subtemporal defect, fixated with a long microtitanium plate over the cranial base side. The fascial graft is augmented by covering it with an abdominal fat graft and a vascularized pericranial flap. This technique was performed in 23 patients after surgical resection of petroclival meningiomas with only 1 postoperative cerebrospinal fluid leak (4.4%). We recommend this safe and simple closure technique during skull base surgery.


Computational modeling of a right-sided Fontan assist device: Effectiveness across patient anatomies and cannulations.
The use of mechanical circulatory support for failing Fontan patients is an area of growing interest, as the increased life expectancy of these patients continues to be accompanied by numerous end-organ complications. In vitro work has shown positive results using the CentriMag device for right-sided Fontan support, however the generalizability across various patient anatomies and cannulations is unknown. Computational simulations are first validated against in vitro modeling, then used to assess generalizability and further explore hemodynamic metrics including relative pressure changes, hepatic flow distribution, wall shear stress and power added. Computational modeling matched previous in vitro work very well, with vessel flow rates and relative average pressure change each within 1%. Positive results were seen across all patient anatomies and cannulations. On average, pressure from the vena cava to pulmonary arteries increased by 5.4 mmHg corresponding to 32 mW of power added. Hepatic flow distribution and wall shear stress were within acceptable ranges, with an average hepatic flow distribution of 47% and all patients showing ≤ 1% of the total Fontan connection surface area at a wall shear stress above 150 Pa. The positive results previously seen using CentriMag as a right-sided Fontan support device were found to be repeatable across multiple patient anatomies and cannulations. While animal models and eventual patient studies will provide further insight into the efficacy of this support strategy, our findings here suggest this method may reproduce right heart function.


Virally targeted therapies for EBV-associated malignancies.
In Epstein-Barr virus (EBV)-positive lymphomas, the presence of the EBV genome in virtually all tumor cells, but very few normal cells, suggests that novel, EBV-targeted therapies could be used to treat these malignancies. In this paper, we review a variety of different approaches currently under development that specifically target EBV-infected cells for destruction. EBV-based strategies for treating cancer include prevention of viral oncogene expression, inducing loss of the EBV episome, the purposeful induction of the lytic form of EBV infection, and enhancing the host immune response to virally encoded antigens.


Cellular and genetic studies in three UV-sensitive Chinese hamster mutants.
Three UV sensitive (UV(s)) mutants (CHO43RO, CHO423PV, CHO30PV), characterized by different levels of reduction in their ability to perform unscheduled DNA synthesis (UDS), were analysed for spontaneous and UV-induced frequency of chromosomal aberrations and for sensitivity to alkylating agents. The baseline frequency of chromosomal aberrations was in the normal range, whereas after UV irradiation a positive correlation between the degree of UV sensitivity and the rate of chromosomal breakage was observed. Survival experiments after mutagen exposure indicated that the UV(s) clones are characterized by different levels of hypersensitivity to bifunctional alkylating agents whereas the sensitivity to monofunctional alkylating agents is in the normal range. Genetic analysis performed by measuring the survival after UV in hybrids produced by fusing UV(s) cells with wild-type or UV(s) cells belonging to the six Chinese hamster complementation groups, indicated that the three clones carry recessive mutations and belong to c.g. 2. These findings suggest that defects in the same gene may result in different degrees of phenotypic alterations.


Correction to: Making urinary extracellular vesicles a clinically tractable source of biomarkers for inherited tubulopathies using a small volume precipitation method: proof of concept.
The original published article the section Acknowledgements is missing. The section is given below.


Effect of iopanoic acid on radioiodine therapy of hyperthyroidism: long-term outcome of a randomized controlled trial.
Telepaque [iopanoic acid (IA)] is believed to rapidly ameliorate hyperthyroidism; however, it may preclude subsequent 131I therapy, possibly delaying it for several months. Our objective was to see how early patients, made euthyroid with Telepaque, can be treated with 131I and to compare their short- and long-term outcome with patients treated with 131I, after making them euthyroid with carbimazole and beta-blockers. We conducted a randomized controlled trial. We studied 200 hyperthyroid patients at a tertiary care teaching institute. The IA group received Telepaque, 500 mg/d orally, for 7 d and then no medication for 1 wk followed by 131I therapy if radioiodine neck uptake had recovered. The control group received 30-40 mg oral carbimazole daily until patients became euthyroid followed by 131I. After 1 wk of Telepaque therapy and 6 wk of carbimazole, almost all patients became clinically and biochemically euthyroid, and 86 and 94% of patients were ready for 131I therapy after 1 and 2 wk off Telepaque, respectively. The cure rate, defined as euthyroid plus hypothyroid, after the first dose of 131I in controls and the IA group was 80 and 76.2%, respectively (P = 0.54). Thirty-two percent among controls and 25% in the IA group became hypothyroid within 1 yr (P = 0.33); thereafter, the annual rate of hypothyroidism was about 2% in both groups. After a mean follow-up duration of 11 yr, 58% of patients in the control group and 51% in the IA group were hypothyroid. Telepaque rapidly ameliorates hyperthyroidism without jeopardizing the subsequent radioiodine therapy, and the outcome of radioiodine therapy in this subset of patients is in no way different compared with those prepared by carbimazole.


Growing gratitude in undergraduate nursing students: Applying findings from social and psychological domains to nursing education.
Millennial students are often characterized as technology focused multitaskers, yet young nursing students are expected to focus on and thoughtfully engage with the person at the center of their caring efforts. Developing gratitude practices requires quiet contemplation and focus. Cultivating an attitude of gratitude in millennial nursing students may be one avenue to address concerns surrounding the provision of relationship based person-centered care by young nurses. In other disciplines, gratitude work has been studied extensively and is associated with several positive outcomes. Assignments included in most nursing programs can easily be modified to include a gratitude focus. Examples of gratitude assignments and the student reflection of these assignments are included here as a call for nurse educators to further study this concept.


MOC-31 Antibody Immunolabeling During Mohs Surgery.
Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS). To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs. Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4. MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly. MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.


Characterization of the adenosine receptor responsible for the inhibition of histamine and SRS-A release from human lung fragments.
The inhibitory effects of a range of natural and synthetic derivatives of adenosine on the antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung has been studied. The nucleotides ATP, ADP and AMP appear to act by being converted to adenosine. The rank order of inhibitory potency of the synthetic analogues indicates that these compounds act at an extracellular A2/Ra purinoceptor. The xanthines, 1, 3-diethyl-8-phenylxanthine, 8-phenyltheophylline and theophylline antagonized the inhibitory action of N-ethyl-carboxamideadenosine competitively. Theobromine was inactive. This supports the view that the inhibitory receptor is of the A/R type. Hexobendine and dipyridamole, reported to antagonize the uptake of adenosine, failed to modify the response of human lung fragments to adenosine. The P site agonist 2',5' dideoxyadenosine inhibited the release of histamine and SRS-A. This effect was not prevented by the inhibitors of uptake, hexobendine and dipyridamole, nor was it antagonized by 8-phenyltheophylline.


Cerebrospinal Fluid CXCL13 as Candidate Biomarker of Intrathecal Immune Activation, IgG Synthesis and Neurocognitive Impairment in People with HIV.
Plasma C-X-C-motif chemokine ligand-13 (CXCL13) has been linked to disease progression and mortality in people living with HIV (PLWH) and is a candidate target for immune-based strategies for HIV cure. Its role in central nervous system (CNS) of PLWH has not been detailed. We described CSF CXCL13 levels and its potential associations with neurological outcomes. Cross-sectional study enrolling PLWH without confounding for CXCL13 production. Subjects were divided according to CSF HIV-RNA in undetectable (< 20 cp/mL) and viremics. CSF CXCL13, and biomarkers of blood-brain barrier (BBB) impairment, intrathecal synthesis, and immune activation were measured by commercial immunoturbidimetric and ELISA assays. All subjects underwent neurocognitive assessment. Sensitivity analyses were conducted in subjects with intact BBB only. 175 participants were included. Detectable CSF CXCL13 was more common in the viremic (31.4%) compared to the undetectable group (13.5%; OR 2.9 [1.4-6.3], p = 0.006), but median levels did not change (15.8 [8.2-91.0] vs 10.0 [8.1-14.2] pg/mL). In viremics (n = 86), CXCL13 associated with higher CSF HIV-RNA, proteins, neopterin, intrathecal synthesis and BBB permeability. In undetectable participants (n = 89), CXCL13 associated with higher CD4+T-cells count, CD4/CD8 ratio, CSF proteins, neopterin, and intrathecal synthesis. The presence of CXCL13 in the CSF of undetectable participants was associated with increased odds of HIV-associated neurocognitive disorders (58.3% vs 28.6%, p = 0.041). Sensitivity analyses confirmed all these findings. CXCL13 is detectable in the CSF of PLWH that show increased intrathecal IgG synthesis and immune activation. In PLWH with CSF viral suppression, CXCL13 was also associated with neurocognitive impairment.


The effects of local insulin delivery on diabetic fracture healing.
Several studies have documented that diabetes impairs bone healing clinically and experimentally. Systemic insulin treatment has been shown to ameliorate impaired diabetic bone healing. However, these studies failed to distinguish between a direct and a systemic effect of insulin upon bone healing. A novel intramedullary insulin delivery system was used in the diabetic BB Wistar femur fracture model to investigate the potential direct effects of insulin on bone healing. Insulin delivery at the fracture site normalized the early (cellular proliferation and chondrogenesis) and late (mineralized tissue, cartilage content and mechanical strength) parameters of diabetic fracture healing without affecting the systemic parameters of blood glucose. These results suggest a critical role for insulin in directly mediating fracture healing and that decreased systemic insulin levels in the diabetic state lead to reduced localized insulin levels at fracture site with concomitant increases in diabetic fracture healing time.


Differences in crestal bone-to-implant contact following an under-drilling compared to an over-drilling protocol. A study in the rabbit tibia.
The objective of this study is to compare bone-to-implant contact (BIC) between implants inserted at high torque due to under-drilling of the crestal bone to those inserted at low torque due to over-drilling of the crestal bone. Forty implants with diameters of 3.75 mm (group A) or 3.55 mm (group B) were inserted in the proximal tibiae of NZW rabbits in two separate surgeries on day 0 or 21. Osteotomy of the crestal bone was finalized with a 3.65-mm drill. In group A, implants were inserted at torque ≥35 Ncm (under-drilling) and in group B with torque <10 Ncm (over-drilling). Implants and their surrounding bone were retrieved on day 42, thus creating 3- and 6-week observation periods, processed for non-decalcified histology and stained with toluidine blue. Crestal BIC (c-BIC) and total BIC (t-BIC) were measured. Wilcoxon test was used to evaluate differences between groups. Three weeks post-surgery, the mean c-BIC in group A was 16.3 ± 3.3 vs 31.5 ± 3.4 % in group B (P < 0.05). At 6 weeks, a similar trend was observed (group A: 28.7 ± 3.6 %; group B: 38.4 ± 4.9 %) (P > 0.05). No differences in t-BIC were noted at 3 weeks and at 6 weeks between the groups. Insertion of implants with an over-drilling protocol of the crestal aspect of the osteotomy resulted in increased short-term crestal bone-to-implant contact. Insertion of implants with a high torque following an under-drilling protocol, commonly used for immediate loading, may reduce crestal bone-to-implant contact at early healing stages.


Sequence conservation between mouse and human synphilin-1.
Synphilin-1 has been shown to interact with alpha-synuclein, which in turn is associated with Parkinson's disease. However, the function of synphilin-1 is unknown. We have cloned mouse synphilin in an attempt to describe conserved and therefore likely functional domains. The deduced amino acid sequence of the protein shows extensive homology with its human counterpart, with greatest similarities in those regions that contain ankyrin-like motifs and the coiled-coil domain. Expression of mouse synphilin-1 across tissues is similar to its human counterpart and not limited to brain. The results show that the synphilin-1 sequence and expression patterns are conserved across species.


A unique method of closure for an aortocaval fistula in association with a ruptured abdominal aortic aneurysm: report of a case.
We report herein the case of a 78-year-old man in whom an aortocaval fistula caused by spontaneous rupture of an abdominal aortic aneurysm (AAA) was successfully treated by a unique surgical technique. The aortocaval fistula had been revealed by an aortography after the patient presented with high-output heart failure. During the operation, massive bleeding from the fistula was evident. The fistula measured 2 cm in diameter, and was located between the right posterior wall of the AAA and the inferior vena cava (IVC). Direct suturing of the defect in the IVC failed to close the fistula because the tissue around it would not hold together due to degeneration. However, the bleeding was finally able to be controlled by plugging the fistula with isolated and properly trimmed omentum packed within the excluded aneurysmal sac. Unfortunately, the patient died due to respiratory failure on the 201st postoperative day. A pathological autopsy revealed that the aortocaval fistula had been closed by fibrous tissue and that the IVC was patent. Although such a drastic operative measure to repair an aortocaval fistula has never before been reported, it could be an alternative when direct closure proves unsuccessful.


Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.
Pulmonary fibrosis (PF) is a fatal and irreversible respiratory disease accompanied by excessive fibroblast activation. Previous studies have suggested that cAMP signaling pathway and cGMP-PKG signaling pathway are continuously down-regulated in lung fibrosis, whereas PDE10A has a specifically expression in fibroblasts/myofibroblasts in lung fibrosis. In this study, we demonstrated that overexpression of PDE10A induces myofibroblast differentiation, and papaverine, as a PDE10A inhibitor used for vasodilation, inhibits myofibroblast differentiation in human fibroblasts, Meanwhile, papaverine alleviated bleomycin-induced pulmonary fibrosis and amiodarone-induced oxidative stress, papaverine downregulated VASP/β-catenin pathway to reduce the myofibroblast differentiation. Our results first demonstrated that papaverine inhibits TGFβ1-induced myofibroblast differentiation and lung fibrosis by VASP/β-catenin pathway.


Surgical indications for pituitary tumors during pregnancy: a literature review.
Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks. A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy. Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit. Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.


Functional interactions of red cells sensitized by IgG1 and IgG3 human monoclonal anti-D with enzyme-modified human monocytes and FcR-bearing cell lines.
Human monoclonal IgG1 and IgG3 antibodies specific for the Rh antigen D (anti-D) were tested for their ability to promote the binding of D-positive red cells to peripheral blood monocytes and Fc receptor (FcR)-bearing cell lines (U937, K562 and Daudi). Monocyte-mediated antibody-dependent cell-mediated cytotoxicity and metabolic (chemiluminescent) responses were also determined. By comparing the activity of different cell lines in rosette assays, and by using murine myeloma IgG2a and IgG1 to block FcRI and FcRII respectively, these functional interactions of sensitized red cells (E-IgG1 and E-IgG3) with monocytes or cell lines were shown to be mediated predominantly and perhaps solely by FcRI. E-IgG3 bound to human monocytes and cell lines to a greater extent than E-IgG1. Rosette formation by E-IgG3 was relatively less susceptible to inhibition by fluid-phase murine IgG2a than was rosette formation by E-IgG1. These findings may be due to the long hinge region of IgG3 which enables it to bridge the gap between two negatively charged cells more efficiently than IgG1. Consistent with this hypothesis was the greatly increased rosette formation achieved by treating monocytes or U937 cells with neuraminidase or bromelain, procedures shown to reduce the zeta potential of these cells. The lytic and metabolic activities of untreated human monocytes were also greater towards E-IgG3 than E-IgG1, red cell binding being a prerequisite for these responses. However, after pretreatment of monocytes with neuraminidase, these responses were greater with E-IgG1 than with E-IgG3. Further, the addition of polybrene to non-specifically enhance cell to cell binding also resulted in greater lysis and chemiluminescence with E-IgG1 than with E-IgG3. These results indicate that, although E-IgG3 are more effective than E-IgG1 in promoting red cell binding to monocytes, E-IgG1 are more efficient at activating the lytic and metabolic processes providing the steric disadvantages of the shorter hinge region of cell-bound IgG1 are circumvented.


Systematic Identification, Characterization and Target Gene Analysis of microRNAs Involved in Osteoarthritis Subchondral Bone Pathogenesis.
This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone sample set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone samples. Out of eight dysregulated miRNA's, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.


Organization in vitro of ovarian cells into testicular structures.
While it has been shown previously (Zenzes et al., 1978; Ohno et al., 1978) that when dissociated testicular cells are exposed to anti H-Y antiserum in vitro they are prevented from reorganizing into testicular structures, forming ovarian follicular structures instead, the most conclusive evidence for the action of H-Y antigen would be the conversion of ovarian cells into testicular organization. Testing for H-Y antigen of the medium collected from cultivated testicular cells revealed a positive reaction. Dissociated ovarian cells of newborn rats cultivated in this medium reorganize into testicular structures. It is concluded that H-Y antigen is responsible for this histomorphologic change.


Effects of husbands' and wives' education on each other's mortality.
Education is an important predictor of one's own cardiovascular disease (CVD) and overall mortality. Little is known, however, regarding the effect of other individuals, specifically a spouse, on these risks. In the present study, we examine the contribution of a spouse's educational attainment and the effect of educational discrepancy between spouses on CVD and overall mortality. Data were taken from the Israel Longitudinal Mortality Study, which linked a 20% sample of the 1983 census to mortality records through 1992. The study cohort comprised 37,618 married couples aged 45-69 years. During the 9.5-year follow-up 6,058 men and 2,568 women died. Overall and CVD mortality hazard ratios were calculated using Cox proportional hazard regression models. We found that the educational attainment of both spouses were significant predictors of one's own overall mortality. For CVD mortality, however, a wife's educational attainment was a stronger predictor of her husband's risk of dying than his own educational level, while for women a husband's education had little affect. Educational discrepancy between partners did not affect overall mortality and had a varied effect on CVD mortality by sex. Specifically, highly educated women had an almost two-fold increased risk of CVD mortality when married to less educated husbands, while lesser-educated women were not affected by their spouses' educational attainment. Spouses' education adds valuable information when assessing mortality differentials among married persons, and socioeconomic characteristics of one's immediate family are important influences on one's health.


DNA-binding antibiotics. X-ray structure of the distamycin A analog.
The crystal structure of the antibiotic distamycin A analog containing two pyrrol carboxamide fragments has been determined. The space group of the crystals is P21/b; the unit-cell dimensions are a = 11.169, b = 21.535, c = 7.863 A, alpha = beta = 90 degrees, gamma = 122.45 degrees, Z = 4. The structure is solved by direct methods, and refined with the full-matrix least-squares procedure. The data on the structure of the pyrrol carboxamide backbone allow the following conclusions to be made about the molecular structure of the distamycin type antibiotics: (i) the amide groups have normal trans-configuration with slightly shortened C-C and C-N bonds adjacent to the pyrrol rings, (ii) the N-methyl groups of the pyrrol rings and the oxygen atoms of the amide groups have the same orientation with respect to the backbone. In the distamycin A analog molecule the pyrrol rings and amide group between them are approximately coplanar.


In vivo imaging in humanized mice.
The radiological modalities that are currently utilized as critical components in clinical medicine have also been adapted to small-animal imaging, among which are ultrasound imaging, X-ray computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Optical imaging techniques such as bioluminescence imaging (BLI) and fluorescence imaging (FLI) are approaches that are commonly used in small animals. Longitudinal surveys of living (i.e., nonsacrificed) animal models with these modalities provide some clues for the development of clinical applications. The techniques are absolutely essential for translational research. However, there are currently few tools available with sufficient spatial or temporal resolution ideal for all experimental studies. In this chapter, we provide a rationale and techniques for visualizing target cells in living small animals and an overview of the advantages and limitations of current imaging technology. Finally, we introduce a humanized mouse and a novel in vivo imaging system that we have developed. We also discuss real-time observations of reconstructs and clinical manifestations.


[MRI based volumetric assessment of knee cartilage after ACL-reconstruction, correlated with qualitative morphologic changes in the joint and with clinical outcome. Is there evidence for early posttraumatic degeneration?].
The purpose of this study was to analyze potential quantitative and qualitative changes of the knee cartilage and joint indicative of early posttraumatic OA 4 years after ACL-reconstruction and to correlate the MRI-findings with the clinical outcome (CO). 1.5 T MRI-scans were performed on 9 patients post-op and 4 years later. Using a high-resolution T 1-w-fs-FLASH-3D-sequence cartilage volume (cVol) and thickness (mTh) were quantified. Using standard PD-w fs and T 1-w sequences qualitative changes of the joint structures were analyzed based on the WORMS-score. CO was rated by an orthopaedic surgeon using Lysholm-score, OAK-score, Tegner-activity-score (TAS), and Arthrometer KT-1000 testing. Mean changes of cVol were -1.8 % (range: -5.9 %; + 0.7 %) and of mTh -0.8 % (range: -3.0 %; + 1.1 %). No significant change (95 %-CI) could be identified for any compartment. Three patients developed new peripatellar ostheophytes, acute trauma related changes mostly decreased. Mean outcome of Lysholm-score and OAK-score were 90 pts and 86 pts, mean TAS was 4.3 pts. Average maximum tibial translation reached 5.2 mm comparing to 6.7 mm on the healthy contralateral side. Despite a tendency towards decreased cVol and mTh 4 years after ACL-reconstruction qMRI revealed no significant cartilage loss. Newly developing osteophytes did not match with the observed good CO. This small pilot study motivates future quantitative and qualitative-structural MRI-based assessment of articular cartilage and other joint structures in order to improve diagnostic tools for the detection of early OA.


Carbon isotope effects associated with Fenton-like degradation of toluene: potential for differentiation of abiotic and biotic degradation.
Hydrogen peroxide (H(2)O(2))-mediated oxygenation to enhance subsurface aerobic biodegradation is a frequently employed remediation technique. However, it may be unclear whether observed organic contaminant mass loss is caused by biodegradation or chemical oxidation via hydroxyl radicals generated during catalyzed Fenton-like reactions. Compound-specific carbon isotope analysis has the potential to discriminate between these processes. Here we report laboratory experiments demonstrating no significant carbon isotope fractionation during Fenton-like hydroxyl radical oxidation of toluene. This implies that observation of significant isotopic fractionation of toluene at a site undergoing H(2)O(2)-mediated remediation would provide direct evidence of biodegradation. We applied this approach at a field site that had undergone 27 months of H(2)O(2)-mediated subsurface oxygenation. Despite substantial decreases (>68%) in groundwater toluene concentrations carbon isotope signatures of toluene (delta(13)C(tol)) showed no significant variation (mean=-27.5+/-0.3 per thousand, n=13) over a range of concentrations from 11.1 to 669.0 mg L(-1). Given that aerobic degradation by ring attack has also been shown to result in no significant isotopic fractionation during degradation, at this site we were unable to discern the mechanism of degradation. However, such differentiation is possible at sites where aerobic degradation by methyl group attack results in significant isotopic fractionation.


Significance of hepatitis B core antigen in the liver in patients with chronic hepatitis B and its relation to hepatitis B virus DNA.
Liver biopsies from 52 patients with chronic hepatitis B were investigated for the presence and distribution of HBcAg and the results were compared with the status of hepatitis B virus deoxyribonucleic acid (HBV-DNA). The patients consisted of 37 men and 15 women, aged 16-55 years (mean = 34 years). Serum alanine aminotransferase (ALT) was elevated in 50 patients (range: 18-969 U/L; mean = 290 U/L). Serological testing showed HBsAg in all, HBeAg in 45 (87%), and HBV-DNA in 28 (54%). Liver biopsies demonstrated HBcAg in 35 (67%) patients. HBcAg was not only present in 31 of 45 (69%) patients who were seropositive for HBeAg, but also in four of seven (57%) with antibody to HBeAg (anti-HBe). In 28 of 35 (80%) patients with HBcAg in the liver, serum HBV-DNA was detected. However, no serum HBV-DNA was detected in 17 patients who had no detectable HBcAg in the liver. The distribution of HBcAg in the liver was rather cytoplasmic and nuclear than nuclear alone. Among 33 patients with cytoplasmic HBcAg in the liver, 15 (45%) had an evidence of acute exacerbation of hepatitis with marked ALT elevation (range: 168-894 U/L; mean = 385 U/L) and nine patients showed severe chronic active hepatitis and confluent necrosis, histologically. These results indicate that the presence of HBcAg in the liver correlates with the amount of circulating hepatitis B virus as quantified by serum level of HBV-DNA. The predominant cytoplasmic HBcAg in the liver may suggest the possibility of multiple episodes of acute exacerbation and more severe ongoing hepatitis during the clinical course.


Visible-light-assisted peroxydisulfate activation over Ag6Si2O7/Cu(II)-modified palygorskite composite for the effective degradation of organic pollutants by radical and nonradical pathways.
Photoassisted persulfate activation (PPA) is highly efficient oxidation process, but the eligible catalysts are scarce. Herein, a visible-light-responsive Ag6Si2O7 was anchored on Cu(II)-exchanged attapulgite (Cu-Pal) via a facile precipitation-deposition method to construct a novel PDS activator. The synthesized catalyst was systemically analyzed by a series of characterization techniques. The results revealed that Ag6Si2O7 nanoparticles were evenly dispersed on Cu-Pal to form heterojunction. 16%-Ag6Si2O7/Cu-Pal, an optimal catalyst exhibited excellent catalytic performance and stability in the visible-light-assisted PDS activation for AR18 degradation. The influences of reaction parameters on this process were investigated. Under the optimal conditions ([catalyst] = 1.0 g L-1, [PDS] = 3.9 mM, pHi = 5.1), 50 mg L-1 of AR18 was completely degraded within 30 min. More importantly, quenching experiments and EPR tests revealed that besides the common SO4•- and •OH, 1O2 and O2•- were generated as main reactive oxygen species in the PPA by 16%-Ag6Si2O7/Cu-Pal. Moreover, it was found that surface hydroxyl groups of the catalyst and copper species incorporated in Pal could significantly influence PDS activation and ROS generation. Based on these results, together with PDS decomposition, fluorescent probe analysis, and XPS analysis of the used catalyst, the possible mechanisms of the PPA by 16%-Ag6Si2O7/Cu-Pal were proposed. Finally, the versatility and practicability of the established PPA process were verified by degrading other organic contaminants and testing effects of the coexisting anions and water matrices on AR18 degradation. This study may provide new insights for designing and developing the efficient heterogeneous catalysis for wastewater treatment via persulfate-based AOP.


Platelet-Rich Plasma for Skin Rejuvenation and Tissue Fill.
Platelet preparations, including platelet-rich plasma and platelet-rich fibrin matrix, have been used to improve wound healing, recovery time, and cosmetic outcomes for facial rejuvenation. Bioactive growth factors released from platelets are the putative agents in producing a reparative tissue reaction in the treated area. Different methods of processing the patients' blood will yield different types of platelet preparations with different components and properties, and it is important to understand these differences and their potential implications. More robust studies are necessary to better understand the nuances of these preparations and their optimal use.


Transient induction of c-jun during hepatic regeneration.
The cellular oncogene c-jun is transiently expressed in cultured cells stimulated to proliferate but has not been identified in normal liver. Because partial hepatectomy results in coordinated cell proliferation in the remaining liver, we investigated c-jun expression after partial hepatectomy in mice. Northern analysis of whole liver mRNA demonstrated a transient increased expression of c-jun within half an hour of the operation. The related gene junB increased only 50%, whereas c-jun expression increased 13-fold compared with sham-operated controls. To determine the cell of origin of the c-jun transcript, both in situ hybridization and Northern analysis of mRNAs from parenchymal and nonparenchymal cell fractions were performed 2 hr after partial hepatectomy. C-jun expression was found in both cell populations. To investigate the mechanism of increased c-jun expression, cycloheximide was given to some animals preoperatively. C-jun induction occurred with cycloheximide alone, but partial hepatectomy further increased c-jun expression, indicating that new protein synthesis was not required for this effect. Furthermore, run-on transcriptional assay demonstrated a twofold increase in c-jun expression. Thus c-jun expression increases after hepatectomy by transcriptional and posttranscriptional mechanisms. Because the extracellular matrix-degrading enzyme transin, which bears the recognition site for jun/AP-1, showed sustained induction after hepatectomy, we speculate that an important function of c-jun expression could be the remodeling of extracellular matrices to accommodate cell proliferation.


Impact of laparoscopic nissen fundoplication with prosthetic hiatal closure on esophageal body motility: Results of a prospective randomized trial.
Prosthetic crural closure does not adversely influence esophageal body motility. In most patients, postoperative increased dysphagia resolves spontaneously during the first months after surgery. Prospective randomized trial. We compared patients who underwent laparoscopic Nissen fundoplication with simple sutured hiatal closure and those who underwent laparoscopic Nissen fundoplication with prosthetic hiatal closure. University-affiliated community hospital. Forty consecutive patients who underwent laparoscopic Nissen fundoplication for gastroesophageal reflux disease. A 360 degrees Nissen fundoplication with simple sutured crura (n = 20; nonmesh group) vs the same procedure with posterior 1 x 3-cm polypropylene onlay mesh prosthesis (n = 20; mesh group). Recurrences; postoperative dysphagia rate; localization, length, and pressure of the lower esophageal sphincter (LES); results of 24-hour pH monitoring; esophageal body motility; peristalsis; and esophageal amplitude of contraction and interrupted waves. Preoperatively, both groups had pathological LES pressure and DeMeester scores. These values improved significantly (P < .01) after surgery and remained stable at 1 year after surgery. Patients in the nonmesh group had a significantly lower LES pressure 1 year after surgery compared with those in the mesh group. There were no significant differences in postoperative mean LES length (4.1 vs 3.8 cm), LES relaxation (93.4% vs 92.4%), and intra-abdominal LES length (2.1 vs 2.1 cm). Patients in the mesh group had fewer simultaneous waves and interrupted waves 1 year after surgery, but the difference between groups was not significant. There were no significant differences in interrupted waves and amplitude of contraction between groups 1 year after surgery. Laparoscopic Nissen fundoplication with prosthetic crural closure does not impair postoperative esophageal body motility compared with laparoscopic Nissen fundoplication with simple suture hiatal closure, although it is associated with a higher rate of short-term dysphagia.


Kinetic resolution of racemic pyrrolidine-2,5-diones using chiral oxazaborolidine catalysts.
Kinetic resolution of racemic C-3 substituted pyrrolidine-2,5-diones has been achieved for the first time using highly efficient oxazaborolidine catalysts derived from cis-1-amino-indan-2-ol.


Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects.
According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects. We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naïve SCZ subjects were compared with those of age-matched control subjects. The methylation rates were significantly lower in medicated (CpG2, P < 0.0001; CpG4, P = 0.013; CpG7, P < 0.0001; and average: 12.9 ± 1.8 vs. 14.1 ± 2.2, P = 0.005) and drug-naïve SCZ subjects (CpG1, P = 0.006; CpG2, P = 0.001; CpG3, P = 0.001; CpG5, P = 0.02; CpG6, P = 0.015; CpG7, P = 0.027; and average: 9.86 ± 0.9 vs. 11.2 ± 1.3, P = 0.002). We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naïve SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.