High dose preoperative radiation and sphincter preservation in the treatment of rectal cancer.
Abdominoperineal resection and permanent colostomy have been the mainstay of treatment for rectal cancer. Automatic stapling devices have widened the scope of low anterior resection, permitting sphincter preservation for tumors originating in the upper and middle thirds of the rectum. Attempts at sphincter preservation in low rectal cancer has resulted in higher recurrence in the pelvic/perineal tissues (41%, MSKCC). In 1976, we undertook a study to expand the scope of sphincter preservation in patients with rectal cancer. Patients were selected because of the presence of unfavorable tumors or low level of rectal area (3 and 6 cm from the dentate line). Forty-three patients were treated in this program. Follow-up ranges from 24 to 96 months, with a median follow-up of 36 months. Fifteen patients were selected for unfavorable tumor types and 28 patients were selected for low level of tumor, between 3 and 6 cm. Twenty of the 28 patients with low level tumors also had unfavorable tumors. All patients received the full course of preoperative radiation (4000 to 4500 cGy in 5 weeks). Surgery was carried out 4 to 6 weeks following radiation and consisted of a sphincter saving procedure, usually by combined abdominotranssacral resection. There was no perioperative mortality. A single anastomotic breakdown required reconstruction. Thirteen patients in this group have died, 9 of these with disease and 3 without evidence of tumor. There were 6 (14%) local recurrences in the pelvic/perineal area. Survival of all patients at 4 years is 66%. This early experience indicates that the high dose preoperative radiation can minimize local recurrence in unfavorable cancers and allows sphincter saving surgery to be performed with small, safe margins in the lower rectal cancers.


Neonatal exposure to deca-brominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice.
Polybrominated diphenyl ethers (PBDEs), used as additive flame-retardants, are increasing in the environment and are present in human mother's milk, newborns and toddlers. We reported earlier that several PBDEs, highly brominated PBDEs, caused developmental neurotoxic effects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system. The present study was undertaken to explore the dose-response effects of PBDE 209 on spontaneous behaviour, habituation and its effects on the murine cholinergic system. Neonatal male NMRI mice were given 1.4, 2.3, 14 or 21micromol PBDE 209/kg body weight, when 3 days old. The agent was administered as a single oral dose via a metal gastric tube. Spontaneous behaviour and response to the cholinergic agonist nicotine were observed in adult mice at 2 and 4 months of age. Mice were also observed for anxiety-like behaviour in an elevated plus-maze. Adult mice, 2 and 4 months old, showed a dose-response related change in spontaneous behaviour, viz. were hyperactive and showed reduced or lack of habituation, effects that worsen with age. At the adult age of 4 months the susceptibility of the cholinergic system was also affected in a dose-response related manner, viz. reduced and/or hypoactive response to nicotine. This shows that PBDE 209 can be as potent as the lower brominated PBDEs in causing developmental neurotoxic defects.


Dietary patterns and breast cancer in Colombia: an ecological study.
The role that diet plays in the development of breast cancer is unclear and breast cancer continues to increase in Colombia and worldwide. The objective of this study was to assess the association between patterns of dietary consumption and the incidence of breast cancer. An ecological study was conducted in 24 geodemographic units in which 95% of the women of Colombia live. The association between breast cancer rate (dependent variable) and three dietary patterns established with factor analysis (traditional/starch, fiber/dairy and snack) was investigated using simple and multiple linear regression. The use of variables related to socioeconomic context and the duration of breastfeeding allowed for the control of possible confounding. All information was derived from concurrent national surveys or was obtained directly over a period of time close to the period during which the study was conducted. There is an inverse relationship between breast cancer rate and illiteracy rate (β=-2808.3), duration of breastfeeding (β=-3354.1), adherence to traditional/fiber dietary patterns (β=-30467) and adherence to the snack dietary pattern (β=-43612). The goodness of fit for the model was R2=84%. Increasing the duration of breastfeeding, ensuring education to promote health and following traditional food consumption patterns, regardless of what foods are consumed, can protect against the development of breast cancer.


Primary malignant carcinoid of the testis.
A primary malignant carcinoid in the testis of a 76-year-old man was studied. The clinical indication was the appearance of extensive, papular cutaneous metastases. A markedly enlarged, indurated left testis was discovered during evaluation of the skin lesions. There were no clinical features of carcinoid syndrome. Histochemically, the tumor cells were argyrophilic but nonreactive to an argentaffin stain. Electron microscopy revealed numerous round, neurosecretory-type granules that ranged from 70 to 300 nm. At the time of autopsy, metastases were found in the heart, lungs, and the opposite testis. Review of the laterature failed to uncover any previous reports of a primary malignant carcinoid in the testis.


Function of a yeast TATA element-binding protein in a mammalian transcription system.
Saccharomyces cerevisiae contains a protein which is functionally similar to the mammalian TATA element-binding transcription factor, TFIID. The yeast factor substitutes for TFIID in a mammalian RNA polymerase II in vitro transcription system, forms a stable preinitiation complex on the Adenovirus-2 major late promoter, and binds specifically to the TATA boxes of the viral promoter and the yeast CYC1 promoter. Interestingly, the yeast factor promotes initiation at a distance from the TATA element typical of a mammalian system.


A novel foam formulation of ketoconazole 2% for the treatment of seborrheic dermatitis on multiple body regions.
A novel topical foam formulation of ketoconazole has been developed for use on the scalp, body, and face. To evaluate the efficacy and safety of twice-daily treatment with ketoconazole 2% foam for seborrheic dermatitis on the scalp, body, and face. One thousand one hundred sixty-two subjects, aged 12 years or older, with mild to severe seborrheic dermatitis were randomized to receive ketoconazole foam (n=427), vehicle foam (n=420), ketoconazole cream (n=210), or vehicle cream (n=105) twice daily for 4 weeks. The primary endpoint was the proportion of subjects achieving an Investigator's Static Global Assessment score of 0 or 1 at week 4 (treatment success). A significantly greater percentage of subjects achieved treatment success using ketoconazole foam than vehicle foam (56% and 42%, respectively; P<.0001); ketoconazole foam was shown to be equivalent to ketoconazole cream. Ketoconazole foam was well-tolerated with a low incidence of treatment-related adverse events (14%; 59/427). Ketoconazole foam 2% is a safe, effective, and versatile formulation for use on the scalp, body, and face for the treatment of seborrheic dermatitis in patients aged 12 years or older.


Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma.
The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.


A case of IgD myeloma representing a missed biclonal paraproteinemia or isotype switch in a patient previously diagnosed with IgA-lambda myeloma.
Multiple myeloma is a clonal plasma cell neoplasm that is identified in the laboratory by a presence of a monoclonal immunoglobulin or increased plasma light chain levels. The most commonly identified and tested immunoglobulins are IgA, IgG and IgM. Rare cases of multiple myeloma present with monoclonal IgD and IgE paraproteins. We present a case of IgD myeloma diagnosed in a patient who had achieved partial remission from a previously diagnosed IgA myeloma, possibly representing a missed biclonal paraproteinemia or isotype switch after treatment.


Intracranial hemorrhage and hemophilia: case report and management guidelines.
Hemophiliacs, as a result of low coagulation factor levels, may suffer spontaneous intracranial hemorrhage. A case of intracranial hemorrhage in a hemophiliac patient with a history of intravenous drug abuse and HIV infection is reported. Factor replacement, airway management, and risks of HIV exposure to emergency department personnel are discussed.


Unusual Enantiodivergence in Chiral Brønsted Acid-Catalyzed Asymmetric Allylation with β-Alkenyl Allylic Boronates.
We report herein a rare example of enantiodivergent aldehyde addition with β-alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6-Di-9-anthracenyl-substituted chiral phosphoric acid-catalyzed asymmetric allylation using β-vinyl substituted allylic boronate gave alcohols with R absolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports. Moreover, in the presence of the same acid catalyst, the reactions with β-2-propenyl substituted allylic boronate generated homoallylic alcohol products with S absolute configuration. Unusual substrate-catalyst C-H⋅⋅⋅π interactions in the favoured reaction transition state were identified as the origins of observed enantiodivergence through DFT computational studies.


Cor triatriatum sinister disclosed after diagnosis of acute myocardial infarction.
We present a case of cor triatriatum sinister diagnosed occasionally after acute anterior myocardial infarction. For management of the acute myocardial infarction (AMI), urgent reperfusion therapy was successfully performed through the left anterior descending coronary artery. Thereafter, no complication associated with AMI occurred. Cor triatriatum sinister was diagnosed and assessed later by means of several modalities. Finally, medical observation was indicated for this patient. This case illustrates the importance of awareness of this congenital disease in an adult when echocardiography shows an abnormal linear echo in the mid portion of the left atrium.


[The use of transcranial magnetic stimulation in treatment of affective disorders in Parkinson's disease].
In this literature review, the authors summarize the data on affective disorders in Parkinson's disease (frequency, clinical presentations, treatment), the results on using transcranial magnetic stimulation, its safety in Parkinson's disease.


Diffuse persistent interstitial pulmonary emphysema treated by lobectomy.
Persistent interstitial pulmonary emphysema is a rare condition that occurs in preterm infants on mechanical ventilation, characterized by abnormal accumulation of air in the pulmonary interstitium, due to disruption of the basement membrane. Diffuse persistent interstitial pulmonary emphysema is observed when small cysts are noted in all lobes of the lung. The management of infants suffering from diffuse persistent interstitial pulmonary emphysema varies according to severity and stability of the patient, being either conservative treatment or aggressive surgical treatment by pneumonectomy. We report a case of an unstable patient with diffuse persistent interstitial pulmonary emphysema successfully treated by lobectomy as a form of conservative surgical approach.


Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-alpha: course and relationship with psychiatric status.
Immunotherapy with interferon-alpha (IFN-alpha) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-alpha induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT). In addition, the production of neurotoxic metabolites of KYN such as 3-hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN-alpha-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties. In a group of 24 patients treated with standard IFN-alpha for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months. No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN. The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-alpha-based immunotherapy, is neither supported nor rejected.


Effect of streptozotocin-induced diabetes on oxidative energy metabolism in rat kidney mitochondria. A comparative study of early and late effects.
The effects of streptozotocin (STZ)-induced diabetes on oxidative energy metabolism of rat kidney mitochondria were examined at the end of 1 week and 1 month of STZ treatment. At the end of 1 week of induction of diabetes, respiration rates with pyruvate + malate and succinate as the substrates increased while those with beta-hydroxybutyrate and ascorbate + TMPD decreased. Respiration with glutamate was not affected. Insulin treatment had no alleviating effect. The changes persisted through 1 month of induction of diabetes and were not corrected by insulin treatment even at this stage. beta-hydroxybutyrate dehydrogenase activity registered significant decrease while the succinate dehydrogenase activity increased in diabetic and insulin-treated diabetic animals whereas only marginal changes were evident in the composition of the cytochromes. The ATPase activity tended to be high in the diabetic groups and was restored by insulin treatment. At both the stages, i.e. early and late stages of diabetes the mitochondria were tightly coupled and the ADP/O ratios were in normal expected ranges. Taken together, the results suggest that kidney is the major target tissue to suffer impairment of mitochondrial function with the onset of the disease which persists throughout and that insulin treatment is ineffective in restoring the normal state.


Investigation of the Potential Mechanism Governing the Effect of the Shen Zhu San on COVID-19 by Network Pharmacology.
Since December 2019, coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has emerged in Wuhan and rapidly spread throughout China and even to other countries. Combined therapy with modern medicine and traditional Chinese medicine has been proposed, in which Shen Zhu San (SZS) was regarded as one of the basic prescriptions. Network pharmacological approaches along with candidate compound screening, target prediction, target tissue location, protein-protein interaction network, gene ontology (GO), KEGG enrichment analyses, and gene microarray analyses were applied. A total of 627 targets of the 116 active ingredients of SZS were identified. Targets in immune cells and tissues were much more abundant than those in other tissues. A total of 597 targets were enriched in the GO biological cellular process, while 153 signaling pathways were enriched according to the KEGG analysis. A total of 450 SARS-related targets were integrated and intersected with the targets of SZS to identify 40 common targets that were significantly enriched in five immune function aspects of the immune system process during GO analysis. Several inflammation-related pathways were found to be significantly enriched throughout the study. The therapeutic mechanisms of the effects of SZS on COVID-19 potentially involve four effects: suppressing cytokine storms, protecting the pulmonary alveolar-capillary barrier, regulating the immune response, and mediating cell death and survival.


An audit of the use of self-administered adrenaline syringes in patients with angio-oedema.
Self-administered adrenaline syringes may be prescribed for patients at risk of life-threatening episodes of angio-oedema or anaphylaxis. To determine whether patients are able to use these syringes appropriately and adequately. Twenty-nine consecutive patients who had been prescribed self-administered adrenaline syringes for severe angio-oedema were recruited. All completed a questionnaire (unsupervised), and were asked to demonstrate how to use a dummy syringe. Three of 29 (10%) patients had been prescribed syringes in the absence of severe angio-oedema or collapse. Seventeen of 29 (59%) patients had been prescribed two syringes, and 21 of 29 (72%) kept a syringe with them at all times. Twenty of 28 (71%) patients had had the use of a syringe demonstrated to them with the initial prescription, but two of 29 (7%) had never been shown how to use it. Only six of 26 (23%) patients had been told to telephone for an ambulance after using a syringe. Only seven of 29 (24%) patients would use a syringe for an episode of collapse, whereas eight of 28 (29%) would use one for an episode of lip swelling. Nine of 21 (43%) patients had not been warned about adverse effects, although 13 of 20 (65%) given adrenaline had had at least one adverse effect. Of the 25 patients asked to demonstrate their use of a syringe, only 14 (56%) were able to perform all steps correctly, and three (12%) were unable to perform any of the steps. Despite this, all 29 patients felt confident about giving themselves an injection, and most felt more secure having been prescribed syringes. As self-administered adrenaline syringes are prescribed for life-threatening events, it is vital that they are given to appropriate patients with adequate written instructions and proper demonstration at the time of the initial prescription. As a result of this study we have developed a more detailed patient information leaflet, and all patients are shown how to use a syringe for a second time when attending the clinic for follow-up.


Non-invasive method of measuring resonant frequency of a human tibia in vivo. Part 1.
We describe a method for measuring resonant frequency of a human tibia in vivo. Although the main reason for this measurement is the assessment of a fractured tibia, we emphasize the special instrumentation required; in particular the novel techniques which are used to overcome the difficulty of obtaining results through skin and soft tissue.


Endodontic treatment of trauma-induced necrotic immature teeth using a tricalcium silicate-based bioactive cement. A report of 3 cases with 24-month follow-up.
Pulp necrosis is the second most common complication after traumatic dental injuries and occurs mostly within the first 6-24 months of follow-up period, depending on the type of dental trauma. Three cases with endodontic treatment scenarios of trauma-induced necrosis in immature permanent anterior teeth. All cases were treated by full canal obturation with Biodentine (Septodont, Saint Maur des Fosses, France) and documented for a follow-up period of 24 months. Copious irrigation of the root canal, minimal mechanical preparation, use of calcium hydroxide for a short period of time and complete obturation of these immature teeth with a bioactive cement with superior mechanical properties such as Biodentine were the prominent reasons attributed to the success of these three cases.


Novel technique using cold atmospheric plasma coupled with air-polishing for the treatment of titanium discs grown with biofilm: An in-vitro study.
The aim of the present study was to assess the decontamination efficacy and titanium surface alterations of erythritol based air abrasion (AA) and cold atmospheric plasma (CAP) targeting a human complex biofilm. Saliva collected from a peri-implantitis patient was used to develop in vitro human biofilm over titanium discs with machined (group A) and moderately rough (group B) surface. The discs were treated with AA, experimental CAP or a combination of both treatments (COM). The amount of biofilm on the discs was measured by crystal violet (CV). Surface features and roughness before and after treatment were assessed by SEM and laser profilometry, respectively. The data were statistically analyzed using Kruskal Wallis followed by Dunn's multiple comparison test after being checked for normality by Shapiro-Wilk test. All the discs in group A performed better to treatments compared to group B. In both groups, CV data showed significantly lower amount of biofilm after AA treatment compared to CAP (p<0.05). Cleaning efficacy revealed relevant decontamination of both the surfaces following AA and COM treatments and almost complete biofilm removal after AA application on group A (99.92%). SEM analysis demonstrated no post-treatment alterations on the discs and laser profilometry did not show statistically significant changes in Sa and Sdr values. Decontamination with AA delivering erythritol with or without CAP is highly effective in biofilm removal from different titanium surfaces. All the tested treatments, including CAP showed no noticeable alterations of the titanium discs surface features. Further in vivo studies are necessary to understand the potential of CAP technology in implant surface decontamination.


Corticosteroids in Lupus Nephritis and Central Nervous System Lupus.
Corticosteroids are a mainstay of therapy for severe organ-threatening systemic lupus erythematosus. Lupus nephritis and central nervous system (CNS) lupus remain two of the most debilitating and potentially life-threatening manifestations of lupus. The dose and duration of corticosteroids required for control of lupus nephritis and CNS lupus have never been tested in a randomized trial design, so current recommendations are based on observation and expert opinion. As more targeted individualized therapeutic approaches are developed for lupus nephritis and CNS lupus, reliance on long-term corticosteroids will decrease, as will the long-term damage and early mortality associated with their use.


Chlamydophila pneumoniae myopericarditis in a child.
An 11-year-old boy with serologically confirmed Chlamydophila pneumoniae infection presented with clinical, laboratory, and echocardiographic changes consistent with myopericarditis. No reports on C. pneumoniae myopericarditis in children are found in the medical literature. The boy, previously healthy, presented with fever, rash, constitutional symptoms, elevated acute phase reactants, elevated cardiac enzymes, and high brain natriuretic peptide levels. Hemodynamic instabilities, including hypotension and mild hypoxia, were noted. Two-dimensional echocardiographic findings showed mildly depressed left ventricular systolic function and small pericardial effusion. Requiring inotropic support, the boy was treated with azithromycin 10 mg/kg once daily for 7 days and a single dose of intravenous immunoglobulin 2 g/kg. He recovered fully with improved left ventricular systolic function before hospital discharge. An early definitive diagnosis is essential to knowing the etiology of pediatric myocarditis. Specific therapy may play role in the management and prognosis of this disorder.


Hp0521 inhibited the virulence of H. pylori 26,695 strain via regulating CagA expression.
Hp0521 is the number of cag pathogenicity island (cagPAI) family in Helicobacter pylori (H. pylori, Hp), which encoded Cag2 protein. The aim of this study was to investigate the role of hp0521 on the H. pylori 26,695 strain. We constructed the recombinant prokaryotic expression plasmid pET-32a-hp0521 and pET-32a-hpc0521. Then, we co-cultured the H. pylori wild strain 26,695 and Δhp0521 strain with GES-1 cells to detect CagA protein transport and IL-8 secretion. We found that Δhp0521 mutation increased the expression of cagA, rpoB and promoted the transportation of CagA protein in GES-1 cells. In addition, we also observed that Δhp0521 mutation had no effect on other cagPAI protein stability and the expression of IL-8. Our findings suggested that hp0521 may down-regulated the expression of cagA, rpoB and inhibited the transportation of CagA protein in GES-1 cells and had no effect on growth.


The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics.
The laser in glaucoma and ocular hypertension (LiGHT) trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open angle glaucoma (POAG) or ocular hypertension (OHT). LiGHT is a prospective unmasked, multicentre, pragmatic, randomised controlled trial (RCT). 718 previously untreated patients with POAG or OHT were recruited at 6 UK centres between 2012 and 2014. Patients were randomised to initial SLT followed by medical therapy or medical therapy without laser. Participants will be monitored for 3 years, according to routine clinical practice. The primary outcome is EQ-5D-5L. Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index (GUI), Glaucoma Symptom Scale, Glaucoma Quality of Life (GQL), pathway effectiveness, visual function, safety and concordance. A total of 555 patients had POAG and 163 OHT; 518 patients had both eyes eligible. The mean age for patients with POAG was 64 years and for OHT 58 years. 70% of all participants were white. Median IOP for OHT eyes was 26 mm Hg and 23 mm Hg for POAG eyes. Median baseline visual field mean deviation was -0.81 dB for OHT eyes and -2.82 dB for POAG eyes. There was no difference between patients with POAG and patients with OHT on the EQ-5D-5DL; the difference between OHT and POAG on the GUI was -0.02 and 1.23 on the GQL. The LiGHT trial is the first RCT to compare the two treatment options in a real-world setting. The baseline characteristics of the LiGHT cohort compare well with other landmark glaucoma studies. ISRCTN32038223, Pre-results.


Interaction of divalent metal ions with normal and lead-inhibited human erythrocytic porphobilinogen synthase in vitro.
The effects of Zn2+, Hg2+, Cd2+, and Cu2+ on normal and lead-inhibited erythrocytic porphobilinogen synthase (PBG-S) were studied in vitro using human whole blood hemolysate. The results demonstrate that each of the divalent ions tested has a characteristic effect on the pH-activity relationship of PBG-S. The effects for a given ion are concentration- and pH-dependent. For Zn2+ these effects are also time-dependent. The results obtained provide an explanation for the contradictory reports of the action of some of the metals in vitro and indicate that future investigations of the effects of metals on an enzyme such as PBG-S are best performed over a judiciously selected pH range rather than at a single pH value. It is also shown that the metals studied will only have a significant effect on the proposed PBG-S activity ratio test for lead intoxication in instances of gross contamination of blood collection devices. The activation and/or inhibition of PBG-S and associate pH-activity profile changes resulting from interaction with the four metal ions tested were attributed to their respective affinity for the thiol and other groups at the active sites. The occurrence of a relatively specific pH optimum for PBG-S after interaction with each ion investigated remains unexplained.


Efficacy of the endoscopic management of postoperative fistulas of leakages after esophageal surgery for cancer: a retrospective series.
Anastomotic leakages are severe and often lethal adverse events of surgery for esophageal cancer. The endoscopic treatment is growing up in such indications. The aim was to evaluate the efficacy and describe the strategy of the endoscopic management of anastomotic leakages/fistulas after esophageal oncologic surgery. Single-center retrospective study on 126 patients operated for esophageal carcinomas between 2010 and 2014. Thirty-five patients with postoperative fistulas/leakages (27 %) were endoscopically managed and included. The primary endpoint was the efficacy of the endoscopic treatment. The secondary endpoints were: delays between surgery, diagnosis, endoscopy and recovery; number of procedures; material used; and adverse events rate. Uni- and multivariate analyses were carried out to determine predictive factors of success. There were mostly men, with a median age of 61.7 years ± 8.9 [43-85]. 48.6 % underwent Lewis-Santy surgery and 45.7 % Akiyama's. 71.4 % patients received neo-adjuvant chemo-radiation therapy. The primary and secondary efficacy was 48.6 and 68.6 %, respectively. The delay between surgery and endoscopy was 8.5 days [6.00-18.25]. Eighty-eight percentages of the patients were treated using double-type metallic stents, with removability and migration rates of 100 and 18 %, respectively. In the other cases, we used over-the-scope clips, naso-cystic drain or combined approach. The mean number of endoscopy was 2.6 ± 1.57 [1-10]. The mortality rate was 17 %, none being related to procedures. No predictive factor of efficacy could be identified. The endoscopic management of leakages or fistulas after esophageal surgery reached an efficacy rate of 68.8 %, mostly using stents, without significant adverse events. The mortality rate could be decreased from 40-100 to 17 %.


Endothelial cell interactions with native surfaces.
Since native vessels are presumably the ideal surface for endothelial cells, we have examined endothelial cell interactions with natural surfaces as a standard to determine the possibilities obtainable on a surface. We have examined three separate types of natural surfaces including human amnion, superficially-injured human arteries, and tanned bovine carotid arteries. When basement membrane collagen is a principal component of a surface, such as with amnion or a superficially denuded large vessel, very rapid cell attachment and spreading occurs. Intact confluent monolayers covering 100% of the amnion surface are present as early as one hour. Human arteries superficially injured to denude their endothelium also exhibit excellent affinity for EC adherence and spreading. Endothelial monolayers cover 80.8% (+/- 5.3) of this surface after one hour, with 91.4% (+/- 1.2) coverage after two hours. For tanned bovine carotid arteries, one and two hour endothelial cell incubation results in coverage of 59.2% (+/- 1.3) and 75.9% (+/- 4.1), respectively. This surface is composed of interstitial collagen of the arterial wall in medial and adventitial layers. Electron microscopy reveals excellent endothelial cell spreading with little or no exposed underlying basement membrane. This suggests that polymeric surfaces designed to mimic injured native surface could allow an endothelialized surface to develop within minutes to hours.


Antidogmatic approaches to artemisinin resistance: reappraisal as treatment failure with artemisinin combination therapy.
The definition of artemisinin resistance is becoming one of a prolonged parasite clearance phenotype, although this variable is a complex function of both host and parasite characteristics. We discuss some of the limitations of this definition of artemisinin resistance, particularly because of its potential global impact. This opinion article reviews the mechanisms underlying parasite clearance after artemisinin treatment and how these might relate to in vitro methods to assay for resistance. It revisits criteria for defining artemisinin resistance that are not currently being applied and suggests the term 'treatment failure of artemisinin combination therapy' (TFACT) as a more accurate description of most cases of 'artemisinin resistance'.


Effect of time-delay on lunar sampling tele-operations: Evidences from cardiac, ocular and behavioral measures.
The purpose of this study is to quantify performance in human-robot interaction under time-delay conditions in a lunar tele-operations sampling task, by testing the hypothesis that an increase of time-delay would lead to higher perceived workload and lower human performance in human-robotic integrated operations. Tele-operation is key in the exploration of the Moon, and allows for robotic elements to be controlled from orbital infrastructure and other planetary bodies such as the Earth. Considering that future missions aim to control rovers (amongst others for sampling tasks) from Earth (delay: 3s), the Gateway (delay: 0.5s) and the Moon (delay: 0s), control under the time-delay conditions for these locations must be studied. Time-delay can affect performance, and understanding the performance means that mission operations can be planned bottom-up, which benefits both the preparation of the crew and the design of rovers. An experiment was conducted with 18 engineers who were assigned to control a robotic arm under three time-delay conditions, representing the three control locations. Several metrics were derived from cardiac, ocular, subjective and behavioral measures. The analyses disclosed that the large time-delay condition statistically increased the perceived workload, the time to complete the mission and decreased heart rate variability compared to the other conditions. However, no effect of time-delay was found on attentional and executive abilities. The metrics proved to be effective in the study of performance quantification in human-robot interaction for tele-operations in lunar control scenarios. This approach can be implemented for a larger range of robotic activities, such as tele-operated driving.


Ethanol modulates the expression of GABA(B) receptor mRNAs in the prenatal rat brain in an age and area dependent manner.
Prenatal ethanol exposure has various deleterious effects on neuronal development. As GABA(B) receptor is known to play an important role during the development of the CNS, we now focused on its mRNA expression pattern in the rat brain during the late gestational days (GD) from 15.5 to GD 21.5. Ethanol's effect was also observed from GD 11.5 to GD 21.5. GABA(B1) receptor mRNA showed a high expression level in GD 15.5 and 19.5, while GABA(B2) receptor mRNA did in GD 15.5 and 21.5. The mRNAs levels depended on age and area during development. Ethanol exposure decreased GABA(B1) receptor from GD 11.5 to GD 19.5 with slight increases in GD 21.5. The decreasing effects were area dependent, with the highest effects in the forebrain including cortex, whereas slight effects were observed in the midbrain and hindbrain. The present results suggest an important role of GABA(B) receptor in the effects of ethanol on prenatal brain developmental processes.


Enhanced hormonal responsiveness in mammary glands from parous mice: molecular mechanisms.
Mammary glands from parous mice required lower concentrations of hormones in vitro than those from virgins to effect differentiation, as measured by lactose synthetase activity. This phenomenon could not be explained by changes in receptor levels, since both mammary gland insulin and prolactin binding, although elevated at midpregnancy, returned to baseline in tissue from parous mice. Ethidium bromide, an intercalating dye, was a potent inhibitor of lactose synthetase induction in explants from virgins but much less potent in tissue from pregnant mice; explants from parous animals displayed intermediate sensitivity, suggesting that DNA structure was permanently altered. However, casein synthesis in glands from parous mice required hormone concentrations as high as in virgins and are just as susceptible to ethidium bromide as in virgins. Similarly, the vulnerability of the casein gene to DNAase I digestion is low in mammary epithelial cells from virgins, high in cells from pregnant mice, and low again in cells from parous animals. These data suggest that during the first pregnancy of mice, there are changes in the chromatin configuration that may facilitate the transcription of milk-related mRNA. Furthermore, after mammary gland involution these changes in the casein gene undergo reversion, while those involved with lactose synthetase activity persist; this may explain the disparate hormonal responsiveness seen in these animals with respect to casein and lactose synthesis.


Detecting unapproved abbreviations in the electronic medical record.
At an emergency department (ED) in a tertiary care children's hospital with a level 1 pediatric trauma designation, unapproved abbreviations (UAAs) within electronic medical records (EMRs) were identified, and feedback was provided to providers regarding their types and use rates. Existing EMRs, including the ED physicians' patient notes were used as templates to develop a UAA list and an abbreviation detector. The detector was validated against human-screened samples of electronic ED notes from 2003 and then applied to all existing data to generate baseline rates of UAA, before intervention/implementation. Next, the validated abbreviation detector was applied prospectively in screening all EMRs monthly during a six-month period. In validation, the abbreviation detector had a sensitivity of 89%, a specificity of 99.9%, and a positive predictive value of 89%. Some 475,613 EMRs were screened, with UAAs identified at a rate of 26.4 +/- 4 per 1,000 EMRs. The most common nonmedication UAA was "qd" [11.8/1,000 EMRs], and the most common medication UAA was "PCN" [4.2/1,000 EMRs]. A total of 27,282 patient notes from 74 physicians were screened between January 1, 2007, and June 30, 2007, and 392 monthly reports were generated. Aggregate UAA use decreased by 8% (95% confidence interval [CI]: 6%-14%) per month-from 19.3 to > 12.1/100 charts, for a 37.3% decrease in UAA use in the six-month period. The estimated monthly decrease per physician was 0.9/100 (95% CI: 0.86-0.94, p < .001.) After adjusting for secular trends, the decrease was 29% in the six-month study period (95% CI: 14%-44%, p < .0001). Use of the abbreviation detector for surveillance of newly created EMRs, followed by consistent education and feedback, led to a significant decrease in UAA use in the study period.


Spin-label studies of membrane-associated denatured hemoglobin in normal and sickle cells.
A maleimide spin label (N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)-maleimide) was reacted with oxyhemoglobin-free cell stromata of normal and sickle cells. The EPR spectrum of spin-labeled red cell membranes showed that the spin labels are attached to at least two different binding sites. There was a major signal, A, which characterized a strongly immobilized environment and a minor signal, B, which characterized a weakly immobilized environment. Quantitative EPR measurements using equal amounts of Hb AA and Hb SS red blood cells demonstrated that Hb SS red cell membranes had an approximately four times higher EPR signal intensity than Hb AA red cell membranes ((7.98 +/- 1.14 . 10(5) and (2.2 +/- 1.2) . 10(5) spin labels/cell, respectively). Moreover, the ratio of signal intensities A and B are different in these cells. Comparative spectrophotometric studies of membrane-associated denatured hemoglobins of Hb AA and Hb SS red cell membranes suggested that the EPR signal A is derived from spin labels attached to membrane-associated denatured hemoglobin, while signal B is mainly from spin labels attached to membranes. The combination of EPR spectrum of Hb AA membranes pretreated with N-ethylmaleimide and that of spin-labeled precipitated hemoglobin further strengthened this conclusion.


Kinetic analysis of AUC-dependent saturable clearance of liposomes: mathematical description of AUC dependency.
The objective of this study was to examine the AUC dependency of saturable hepatic clearance (CLh) of liposomes and to postulate a mathematical model to describe the characteristics. The AUC dependency of saturable CLh was examined under intravenous rapid administration at various doses. The CLh increased with increasing blood concentration but decreased with the increase of AUC at each dose. In addition, the relationship between AUC and CLh was consistent with that observed in previously reported infusion studies. These experimental data confirm the AUC dependency of saturable CLh of liposomes. A mathematical model was developed for this AUC dependency. The decrease of CLh was described by the uptake amount (X) as follows: CLh = CLm(1-X/Xm), where CLm and Xm represent the maximum uptake clearance and the maximum uptake amount, respectively. The rate equation for uptake was analytically solved as CLh = X/AUC = Xm/AUC(1-exp(CLm/XmAUC)). Uptake clearance can be described by CLm, Xm, and AUC, and so uptake clearance is constant if AUC is constant. These experimental analyses and theoretical considerations show the validity of the AUC-dependent saturable CLh of liposomes.


Changes in male exercise performance and anthropometric variables between the ages of 19 and 30.
In order to study possible changes in Swedish men between the approximate ages of 19 and 30, 55 men from the Stockholm area were re-examined 11 years after examinations made in connection with compulsory military duty. The most pronounced finding was a 11% increase in body weight accompanied by a 19% increase in waist circumference and a 25-41% increase in skinfold thickness. A 5% increase in work output at heart rate 170 (W170) was observed but the ratio W170/weight decreased by 5%. The observed changes were even more pronounced in a subgroup who had a low exercise level in their spare time at the age of 19 as well as 30. Growth was not quite completed at the age of 19. Of the increase in height amounting to 1.3 cm, 70% was due to growth in tibial length.


Calcium ionophore-induced egg activation and apoptosis are associated with the generation of intracellular hydrogen peroxide.
The present study was designed to investigate whether calcium ionophore-induced activation and apoptosis are associated with the generation of hydrogen peroxide (H(2)O(2)) in rat eggs cultured in vitro. Culture of metaphase-II (M-II) arrested eggs in Ca(2+)/Mg(2+)-deficient medium did not induce egg activation, while a second polar body was observed in 20% of eggs when cultured in Ca(2+)/Mg(2+)-supplemented medium. In Ca(2+)/Mg(2+)-deficient medium, lower concentrations of calcium ionophore (0.2,0.4 and 0.8 microm) not only induced egg activation in a dose-dependent manner but also generation of intracellular H(2)O(2) (84.40+/-0.50 ng/egg) when compared to control eggs (80.46+/-1.34 ng/egg). The higher concentration of calcium ionophore (1.6 microm) induced apoptosis and pronounced generation of intracellular H(2)O(2) (92.43+/-0.93 ng/egg) in treated eggs. Conversely, cell-permeant antioxidant such as 2(3)-tert-butyl-4-hydroxyanisole (BHA) reduced intracellular H(2)O(2) level (81.20+/-1.42 ng/egg) and protected against calcium ionophore-induced morphological changes characteristics of egg activation and apoptosis. These results clearly suggest that calcium ionophore-induced activation and apoptosis are associated with the generation of intracellular H(2)O(2) in rat eggs.


Estimating the Impact of Daily Weather on the Temporal Pattern of COVID-19 Outbreak in India.
The COVID-19 pandemic has spread obstreperously in India. The increase in daily confirmed cases accelerated significantly from ~ 5 additional new cases (ANC)/day during early March up to ~ 249 ANC/day during early June. An abrupt change in this temporal pattern was noticed during mid-April, from which can be inferred a much reduced impact of the nationwide lockdown in India. Daily maximum (T Max), minimum (T Min), mean (T Mean) and dew point temperature (T Dew), wind speed (WS), relative humidity, and diurnal range in temperature and relative humidity during March 01 to June 04, 2020 over 9 major affected cities are analyzed to look into the impact of daily weather on COVID-19 infections on that day and 7, 10, 12, 14, 16 days before those cases were detected (i.e., on the likely transmission days). Spearman's correlation exhibits significantly lower association with WS, T Max, T Min, T Mean, T Dew, but is comparatively better with a lag of 14 days. Support Vector regression successfully estimated the count of confirmed cases (R 2 > 0.8) at a lag of 12-16 days, thus reflecting a probable incubation period of 14 ± 02 days in India. Approximately 75% of total cases were registered when T Max, T Mean, T Min, T Dew, and WS at 12-16 days previously were varying within the range of 33.6-41.3 °C, 29.8-36.5 °C, 24.8-30.4 °C, 18.7-23.6 °C, and 4.2-5.75 m/s, respectively. Thus, we conclude that coronavirus transmission is not well correlated (linearly) with any individual weather parameter; rather, transmission is susceptible to a certain weather pattern. Hence multivariate non-linear approach must be employed instead.


Quantitative trait loci mapping of polyphenol metabolites from a 'Latham' x 'Glen Moy' red raspberry (Rubus idaeus L) cross.
The objective of this study was to investigate the genetic control of polyphenol accumulation in red raspberry (Rubus idaeus L). The levels of total anthocyanins and 37 individual polyphenol metabolites were measured over three years in a raspberry biparental mapping population. Quantitative trait loci (QTLs) for these traits were mapped onto a high-density SNP linkage map. At least one QTL was detected for each trait, with good consistency among the years. On four linkage groups (LG), there were major QTLs affecting several metabolites. On LG1, a QTL had large effects on anthocyanins and flavonols containing a rutinoside or rhamnose group. On LG4, a QTL had large effects on several flavonols and on LG5 and LG6 QTLs had large effects on ellagic acid derivatives. Smaller QTLs were found on LG2 and LG3. The identification of robust QTLs for key polyphenols in raspberry provides great potential for marker-assisted breeding for improved levels of potentially health beneficial components.


Genetic control of UDPglucose:flavonol 3-O-glucosyltransferase in the endosperm of maize.
The enzyme UDPglucose:flavonol 3-O-glucosyltransferase is shown to be under the coordinate control of three genes involved in anthocyanin biosynthesis in the aleurone of maize: C, R, and BZ. Of the three, BZ appears to be the structural gene. Data presented here (dosage comparisons, induction in the mutant c-p, and effect of paramutation at R) indicate that the enzyme is inducible by substances resulting from the action of the C and R genes and that active forms of C and R are required for this induction. Mechanisms of regulation of the BZ gene by C and R are discussed.


Praxeological Enactivism vs. Radical Enactivism: Reply to Hutto.
In his recent paper "Getting Real About Pretense: A Radical Enactivist Proposal", Daniel Hutto raises several objections against our so-called praxeological enactivist account of pretense (Weichold & Rucińska 2022). He argues that one should, instead, adopt his radical enactivist explanation of pretend play. In this short reply, we defend our praxeological enactivist account against his objections, and argue that it has crucial advantages over his radical enactivist alternative.


Arachidonic acid-induced dye uncoupling in rat cortical astrocytes is mediated by arachidonic acid byproducts.
Arachidonic acid (AA) induced a concentration- and time-dependent reduction in gap junction-mediated dye coupling between cultured astrocytes. The effect was greatly diminished by inhibition of cyclooxygenases and lipoxygenases. The action of a low concentration of AA (5 microM) was also prevented by Ca2+-free extracellular solution or a high concentration of melatonin, a potent free radical scavenger, but not by Nomega-nitro-l-arginine, a nitric oxide (NO) synthase inhibitor. Thus, this effect may depend on Ca2+ influx and oxygen free radicals but not on NO generation. Cellular uncoupling induced by a high (100 microM), but not a low, AA concentration was rapidly reversed by washing with albumin containing solution. After reversal from 5 min but not 2.5 min inhibition with a high AA concentration dye coupling between astrocytes became refractory to a low concentration of AA, suggesting desensitization of the response elicited by a low concentration of the fatty acid. Dye uncoupling occurred without changes in levels and state of phosphorylation (immunoblotting and 32P-incorporation) of connexin43, the main astrocyte gap junctional protein. However, maximal cell uncoupling induced by a low (Slow action) but not by a high (Fast action) AA concentration was paralleled by a reduction in connexin43 (immunofluorescence) at cell-to-cell contacts. It is proposed that the AA-induced dye uncoupling is mediated by byproducts that induce rapid channel closure or slow removal of connexin43 gap junctions.


Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross-linking anticancer drugs by F 11782, a novel fluorinated epipodophylloid.
F 11782, or 2',3'-bis-pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D-glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2-N-methyl glucamine salt, a novel dual catalytic inhibitor of topoisomerases I and II, was identified as a potent inhibitor of nucleotide excision repair (NER) by screening procedures using the in vitro 3D (DNA damage detection) assay. F 11782 was then shown predominantly to inhibit the incision rather than the repair synthesis step, using two new methodologies derived from this 3D assay, effectively ruling out any inhibition of polymerases delta/var epsilon. Moreover, data from two other in vitro assays showed an absence of any effect of F 11782 on: (i) the DNA damage binding of the XPA-RPA complex, and (ii) on SV40 large T-antigen helicase activity. Therefore, the inhibitory activity of F 11782 on NER may involve an inhibition of the ERCC1-XPF or XPG endonuclease activity. Moreover, inhibition of DNA repair by F 11782 was confirmed in human A549 cells by monitoring unscheduled DNA synthesis following mechlorethamine treatment. Such an inhibition provides an explanation for the highly synergistic cytotoxicity observed against cultured A549 lung tumour cells, when F 11782 was combined with cross-linking agents, such as cisplatin or mitomycin C. These results emphasise the unique mode of action of this novel molecule in inhibiting NER and provide a basis for its evaluation in clinical trials in combination with DNA cross-linking agents.


Successful body flossing via indwelling nephrostomy allowing for primary realignment of bladder rupture and placement of a foley catheter into the urinary bladder.
Vesicourethral anastomosis leaks are one of the most common short-term complications following radical prostatectomy. We present a case of a 67-year-old Caucasian male who presented to our Emergency Department (ED) with abdominal pain and urinary incontinence 10 days after a robotic-assisted laparoscopic prostatectomy. Interventional radiology initially performed successful nephrostomy placement for bilateral hydronephrosis. Vesicourethral disruption was managed via a multidisciplinary approach with urology and interventional radiology in which a novel approach to realign a bladder rupture and appropriately place a foley catheter in the bladder. Vesicourethral leaks are often managed conservatively. In a few cases, such as this one, mini-invasive intervention is often required to repair the disruption.


Analysis of natural coloring matters in food. III. Application of methylation with diazomethane for the detection of lac color.
A new method has been proposed for detection of lac color in food. Lac color is a natural color additive derived from a secretion of the insect Coccus Laccae (Laccifer lacca Kerr). It is extracted from food with methanolic oxalic acid and eluted from a column of Amberlite XAD-2 with the same solvent. The fraction containing the lac color is treated with diazomethane to produce 2 reddish-orange markers. The marker species in the reaction mixture are detected by both thin-layer chromatography and reverse-phase liquid chromatography.


Determination of full-energy peak and total efficiency functions for Ge-detectors by iteration calculation using a mixed radionuclide source.
Empirical calibrations of full-energy peak and total efficiency curves for well-type and coaxial p-type germanium detectors were carried out using several combinations of practical nuclides. As a result, reliable efficiency functions of both types of detectors were successfully obtained using a home-made program coded with Visual Basic for Applications (VBA) and the "Solver" add-in in Excel™. We also examined the applicability of our advanced program to volumetric sources using squared-to-linear curve technique.


Immune defects in simian acquired immunodeficiency syndrome.
We recently reported a Simian Acquired Immunodeficiency Syndrome (SAIDS) in rhesus macaques at the California Primate Research Center. Here, we studied in vitro lymphocyte response to the mitogens Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) with and without interleukin 2 (IL-2). Immunoglobulin (IgG and IgM) and complement (C3 and C4) concentrations were determined by radial immunodiffusion. T helper and T suppressor lymphocytes were identified with the monoclonal antibodies OKT4 and OKT8. Concentrations of IgG and IgM were significantly (p less than .05) decreased. Complement component C3 did not change but C4 was increased. The absolute lymphocyte count decreased but the OKT4:OKT8 ratio was unchanged from controls. A decreased lymphocyte response to all mitogens occurred early and became more severely depressed near death. IL-2 caused a complete or partial restoration of the response to the mitogens CON A and PHA. Both the humoral and cell mediated immune responses are affected in SAIDS. The role of IL-2 in this immune defect must be studied further.


Synthesis and properties of a novel biodegradable poly(ester amine) copolymer based on poly(L-lactide) and low molecular weight polyethylenimine for gene delivery.
Gene therapy is a promising approach to the treatment of a wide range of diseases. The development of efficient and adequate gene delivery systems could be one of the most important factors. Polyethyleneimine, a cationic polymer, is one of the most successful and widely used vectors for nonviral transfection in vitro and in vivo. A novel biodegradable poly(ester amine) copolymer (PEA) was successfully prepared from low molecular weight polyethylenimine (PEI, 2000 Da) and poly(L-lactide) copolymers. According to the results of agarose gel electrophoresis, particle size and zeta potential measurement, and transfection efficiency, the PEA copolymers showed a good ability to condense plasmid DNA effectively into nanocomplexes with a small particle size (≤150 nm) and moderate zeta potential (≥10 mV) at an appropriate polymeric carrier/DNA weight ratio. Compared with high molecular weight PEI (25kDa), the PEA obtained showed relatively high gene transfection efficiency as well as low cytotoxicity in vitro. These results indicate that such PEA might have potential application as a gene delivery system.


Gender differences in physical activity and health-related behaviors among stroke survivors: data from the 5th Korea National Health and Nutrition Examination Survey.
Physical activity and health-related behaviors are important in primary prevention of stroke and are also recommended for secondary prevention. Gender differences in physical activity and health-related behaviors have been reported in various populations and diseased states but data is lacking on stroke survivors. To assess gender disparities in physical activity in stroke patients and to investigate possible reasons for such disparities. This is a cross-sectional study using nationwide data from the 5th Korean National Health and Nutrition Examination Survey (2010-2012). A total of 9539 participants (stroke (n = 170), non-stroke (n = 9369)) between the ages of 40-80, with no problems walking were included. Physical activity, smoking, and alcohol drinking of stroke survivors were assessed by gender and compared with non-stroke groups. Multiple logistic regression was used to estimate the odds ratios (ORs) for insufficient physical activity and possible explanatory variables for gender differences. Women showed higher prevalence of insufficient physical activity after adjusting for age (OR = 7.32, 95% CI: 1.89-28.32) compared to men. Medical conditions such as depression and comorbidities failed to explain the low physical activity in women with stroke but adding socioeconomic factors to the model nullified the gender difference in physical activity. In order to reduce noted gender disparities in physical activity following stroke, more focused effort to increase physical activity in women, especially with lower socioeconomic status, has to be considered.


Intolerance of uncertainty fuels preservice teachers' smartphone dependence through rumination and anxiety during the COVID-19 pandemic: A cross-sectional study.
We aimed to explore the relationship among intolerance of uncertainty (IU), rumination, anxiety, and smartphone dependence (SPD) in preservice teachers during the COVID-19 pandemic. Two cross-sectional studies were conducted with Chinese preservice teachers, using questionnaires on IU, rumination, anxiety, and SPD. Data were analyzed using AMOS 24.0 and SPSS 25.0, and the mediating mechanism was tested using the macro program Model 6. Study 1 recruited participants who were forcibly sequestered in a university due to an anti-epidemic policy during the COVID-19 crisis. Study 2 was surveyed online from different universities to replicate and enhance the reliability of Study 1 finding. Study 1 (N = 553, Mage = 20.8 ± 2.3, 30.0% female) and Study 2 (N = 1610, Mage = 21.1 ± 2.1, 51.4% female) both found that IU affected SPD through the independent mediators of rumination and anxiety, as well as the chain mediation of rumination→ anxiety. In Study 1, the indirect effect of IU on SPD was significant through rumination (β = 0.16, 95% CI [0.03, 0.06]), anxiety (β = 0.11, 95% CI [0.03, 0.06]), and the chain mediation (β = 0.02, 95% CI [0.01, 0.04]); in Study 2, the indirect effect of IU on SPD was significant through rumination (β = 0.08, 95% CI [0.05, 0.11]), anxiety (β = 0.10, 95% CI [0.08, 0.13]), and the chain mediation (β = 0.02, 95% CI [0.02, 0.03]). Two cross-sectional studies found that preservice teachers' SPD is indirectly connected to IU, mediated by rumination and anxiety, and weakly mediated by the chain mediation of rumination and anxiety. Our findings may help educators understand the impact of anti-epidemic policies on preservice teachers and possible inclusive later interventions.


A CT-based radiomics nomogram for differentiating ovarian cystadenomas and endometriotic cysts.
To construct and validate a computed tomography (CT)-based radiomics nomogram integrating radiomics signature and clinical factors to distinguish ovarian cystadenomas and endometriotic cysts. A total of 287 patients with ovarian cystadenomas (n=196) or endometriotic cysts (n=91) were divided randomly into a training cohort (n=200) and a validation cohort (n=87). Radiomics features based on the portal venous phase of CT images were extracted by PyRadiomics. The least absolute shrinkage and selection operation regression was applied to select the significant features and develop the radiomics signature. A radiomics score (rad-score) was calculated. The clinical model was built by the significant clinical factors. Multivariate logistic regression analysis was employed to construct the radiomics nomogram based on significant clinical factors and rad-score. The diagnostic performances of the radiomics nomogram, radiomics signature, and clinical model were evaluated and compared in the training and validation cohorts. Diagnostic confusion matrices of these models were calculated for the validation cohort and compared with those of the radiologists. Seventeen radiomics features from CT images were used to build the radiomics signature. The radiomics nomogram incorporating cancer antigen 125 (CA-125) level and rad-score showed the best performance in both the training and validation cohorts with AUCs of 0.925 (95% confidence interval [CI]: 0.885-0.965), and 0.942 (95% CI: 0.891-0.993), respectively. The accuracy of radiomics nomogram in the confusion matrix outperformed the radiologists. The radiomics nomogram performed well for differentiating ovarian cystadenomas and endometriotic cysts, and may help in clinical decision-making process.


Cannabinoid Oil Vaping-Associated Lung Injury and its Radiographic Appearance.
Lung injury associated with cannabinoid oil vaping is rapidly becoming a serious public health concern. We describe the clinical and radiographic presentations of 5 patients with lung injury associated with vaping cannabinoid oils seen at a single institution. Of the 5 patients with suspected vaping-associated lung injury seen at our institution, 4 required supplemental oxygen, and all these 4 were admitted to the hospital. Three patients required admission to the intensive care unit. None of the patients required mechanical ventilation. All patients demonstrated a consistent radiologic appearance of diffuse bilateral ground-glass lung opacities that spared the extreme periphery. Three patients underwent bronchoalveolar lavage, which revealed lipid-laden macrophages in 2 of them. All patients were successfully discharged from the hospital. Four received only supportive care, while the fifth required intravenous followed by oral corticosteroids. We report the clinical and radiographic presentation of 5 patients at our institution with cannabinoid oil vaping-associated lung injury. All patients displayed a consistent chest radiographic pattern of injury. Most responded to supportive care, although one required the addition of corticosteroids. Bronchoalveolar lavage results suggest that this injury may related to a toxic form of lipoid pneumonia.


In vitro evaluation of the antitumoral and antiangiogenic effects of extracts from Spondias mombin L. leaves.
The traditional ethnobotanic and pharmacologic use of Spondias mombin L. samples includes a wide range of applications. In the present study, new antiangiogenic and antitumor effects of two types of extracts from Spondias mombin L. leaves have been demonstrated by using a number of in vitro assays in both endothelial and human cancer and non cancer cells.


A novel tick antigen shows high vaccine efficacy against the dog tick, Rhipicephalus sanguineus.
Ticks are acaridae ectoparasites that, while taking a blood meal, can transmit viruses, bacteria, protozoa and filarial nematodes, which cause a variety of human and animal illnesses. The use of chemical pesticides constitutes the primary measure for control of these ectoparasites. However, the intensive use of these chemicals has drawbacks such as the contamination of food, environmental pollution and development of resistance by ectoparasites. Vaccination is considered a promising alternative for controlling infestations by ectoparasites. Although emerging tick proteins have been identified recently, and have been proposed as potential targets for generating protective molecules, only a limited number of them have been evaluated in vaccine trials. More than 80 proteins are found in eukaryotic ribosomes. The protein P0 is essential for the assembly of the 60S ribosomal subunit. We have identified an immunogenic region of the ribosomal protein P0 from Rhipicephalus sp. ticks that is not very conserved compared to host P0. The efficacy of a 20 amino acid synthetic peptide from this sequence was assayed as a vaccine antigen against Rhipicephalus sanguineus infestations in an immunization and challenge experiment on rabbits. A remarkable diminution in the viability of newly molted nymphs from larvae fed on vaccinated rabbits was observed. The number of adults and the number of eggs hatching were significantly reduced, with an overall efficacy of 90%. Our results demonstrated that immunization with an immunogenic peptide of tick protein P0 greatly reduced survival of ticks, suggesting that it has promise as an effective tick control agent.


A Simplified Thermal Proteome Profiling Approach to Screen Protein Targets of a Ligand.
Thermal proteome profiling is a powerful energetic-based chemical proteomics method to reveal the ligand-protein interaction. However, the costly multiplexed isotopic labeling reagent, mainly Multiplexed isobaric tandem mass tag (TMT), and the long mass spectrometric time limits the wide application of this method. Here a simple and cost-effective strategy by using dimethyl labeling technique instead of TMT labeling is reported to quantify proteins and by using the peptides derived from the same protein to determine significantly changed proteins in one LC-MS run. This method is validated by identifying the known targets of methotrexate and geldanamycin. In addition, several potential off-targets involved in detoxification of reactive oxygen species pathway are also discovered for geldanamycin. This method is further applied to map the interactome of adenosine triphosphate (ATP) in the 293T cell lysate by using ATP analogue, adenylyl imidodiphosphate (AMP-PNP), as the ligand. As a result, a total of 123 AMP-PNP-sensitive proteins are found, of which 59 proteins are stabilized by AMP-PNP. Approximately 53% and 20% of these stabilized candidate protein targets are known as ATP and RNA binding proteins. Overall, above results demonstrated that this approach could be a valuable platform for the unbiased target proteins identification with reduced reagent cost and mass spectrometric time.


The relationship between 17 beta hydroxysteroid dehydrogenase and breast tumour site and size.
The activity of 17 beta hydroxysteroid dehydrogenase (170HSD) was measured in adipose tissue adjacent to benign or malignant breast tumours. 170HSD activity was significantly correlated with tumour size in malignant tumours (r = 0.75) but not with benign tumours (r = 0.28). Enzyme activity was reduced in adipose tissue adjacent to tumours obtained from inferior breast quadrants.


Study of bradykinin metabolism by rat lung tissue membranes and rat kidney brush border membranes by HPLC with inductively coupled plasma-mass spectrometry and orthogonal acceleration time-of-flight mass spectrometry.
The coupling of the techniques, high-performance liquid chromatography (HPLC), orthogonal acceleration time-of-flight mass spectrometry (OATOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS) provides a very powerful method for identifying and quantifying the products of bradykinin metabolism. In this study, we were able to identify the major metabolites of bradykinin degradation reported in the literature. In addition, a new bradykinin metabolite corresponding to bradykinin 5,9 fragment (BK-(5,9)-fragment) was identified as a product of neutral endopeptidase (NEP) activity. This finding establishes that NEP cleaves bradykinin simultaneously at the positions 4-5 and 7-8. We also demonstrate the equivalent participation of NEP and angiotensin-converting enzyme (ACE) within the rat lung tissue membranes (RLTM) in bradykinin degradation, suggesting its suitability as a model for the assay of dual ACE/NEP inhibitors. On the contrary, in rat kidney brush border membranes (KBBM), ACE is not significantly involved in bradykinin metabolism, with NEP being the major enzyme.


Design and realization of a multi-coil array for B0 field control in a compact 1.5T head-only MRI scanner.
To design and implement a multi-coil (MC) array for B0 field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner. A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through. Key characteristics of the MC hardware, the B0 field generation capabilities, and thermal behavior, were optimized in simulations prior to its construction. The unit was characterized via bench testing. B0 field generation capabilities were validated on a human 4T MR scanner by analysis of experimental B0 fields and by comparing images for several MRI sequences acquired with the MC array to those acquired with the system's linear gradients. The MC system was designed to produce a multitude of linear and nonlinear magnetic fields including linear gradients of up to 10 kHz/cm (23.5 mT/m) with MC currents of 5 A per channel. With water cooling it can be driven with a duty cycle of up to 74% and ramp times of 500 μs. MR imaging experiments encoded with the developed multi-coil hardware were largely artifact-free; residual imperfections were predictable, and correctable. The presented compact multi-coil array is capable of generating image encoding fields with amplitudes and quality comparable to clinical systems at very high duty cycles, while additionally enabling high-order B0 shimming capabilities and the potential for nonlinear encoding fields.


Exploring the mechanism of solubilization and release of isoliquiritigenin in deep eutectic solvents.
Isoliquiritigenin (ISL) is a natural medicinal product with extensive pharmacological activities. However, its low solubility limits its application. Therefore, this study aimed to explore the solubilization and release mechanism of the ISL using deep eutectic solvents (DESs). The choline chloride (ChCl) and oxalic acid (OA)/malic acid (MA)/gallic acid (GA) were used to synthesize ChCl-OA/MA/GA DESs, and the solubility of ISL in these DESs was studied to explore the solubilization mechanism of ISL. The thermodynamic properties of DESs were characterized using differential scanning calorimetry (DSC). The molecular interactions in DESs were studied using spectroscopy and molecular dynamics (MD) simulations. The relative density of DESs was measured using a pycnometric method, its accuracy was validated by comparing it with the MD simulation. The release of ISL from ChCl-OA/MA/GA eutectogels was studied using Carbomer 940 as the thickener, and the release mechanism of ISL in the eutectogels was explored by the drug release kinetic model. The solubility study found that the solubility of ISL in ChCl-OA/MA/GA DESs is 30073, 5055, and 68,103 times higher than that in an aqueous solution. In addition, further studies using MD simulations revealed that enhancing the interactions between ISL and solvent molecules can improve the solubility of ISL in DESs. In vitro release studies showed that the release of ISL in ChCl-OA/MA/GA eutectogels followed a first-order release model, with correlation coefficients of 0.9812, 0.9916, and 0.9961, respectively. In conclusion, the study of the solubilization and release mechanism of ISL in DESs provides new ideas and methods for the study of poorly soluble drugs, which is expected to improve the efficacy and clinical application value of drugs.


Ion-pair solid-phase extraction and gas chromatography-mass spectrometric determination of acidic hydrolysis products of chemical warfare agents from aqueous samples.
The chemical warfare agents (CWA) degrade rapidly in aqueous samples and convert to acidic degradation products. Extraction and identification of the degradation products from complex matrices using simple sample preparation and sensitive detection and identification is the most important step in the off-site analysis of samples. In this present study, we report a simple sample preparation step based on ion-pair (IP) solid-phase extraction (SPE) for the extraction of acidic degradation products of CWA namely methyl, ethyl, propyl phosphonic acids, thiodiglycolic acid and benzilic acid. The analysis was performed on GC-MS in electron impact ionization mode. Three IP reagents triethylamine (TEA), tetrabutylammonium bromide (TBAB) and cetyltrimethyl ammonium bromide (CTAB) were used. The recoveries were estimated using the internal and external standard methods. The recovery of the compounds was almost negligible when TEA was used as IP reagent. The recoveries obtained when TBAB and CTAB were used as IP reagents were high and reproducible. The recovery of test chemicals is above 90%, except for methyl phosphonic acid and ethylphosphonic acid (20.6 +/- 3.2% and 35.8 +/- 2.5%, respectively). The minimum detection limits of the method were calculated for all chemicals in both full scan and selected ion monitoring modes. The test chemicals could be detected in microgram per litre quantities by the IP-SPE method.


Chlamydia pneumoniae, herpes simplex virus and cytomegalovirus in symptomatic and asymptomatic high-grade internal carotid artery stenosis. Does infection influence plaque stability?
Current debates are focused on inflammatory processes in atherosclerotic lesions as a possible pathomechanism for destabilization and thrombembolism. In this prospective study the role of systemic and local infection in patients with high-grade internal carotid artery stenosis (ICA) was evaluated. Serum antibody titers of 109 consecutive patients, who underwent surgery for ICA stenosis (asymptomatic n = 40, symptomatic n = 69) were prospectively measured for Chlamydia pneumoniae (Cpn) (IgA and IgG), Herpes simplex virus (HSV) (IgG, IgM) and Cytomegalovirus (CMV) (IgG, IgM) respectively. 53 carotis plaques of this group (asymptomatic n = 17, symptomatic n = 36) could be analyzed by polymerase chain reaction (PCR) for Cpn-, HSV- and CMV-DNA presence. Seropositivity was found in 61,5% for Cpn, 91,7% for HSV and 72,5% CMV respectively. No significant relation was found between symptomatic and asymptomatic patients as well as no difference was seen for presence of IgA antibodies against Cpn comparing both groups. Plaque-PCR revealed Cpn in 7 cases (13,2%), HSV in 2 cases (3,8%) and no CMV had been detected. Again, no significant relationship was found concerning symptomatic and asymptomatic patients. All 9 PCR-positive plaques displayed lesions of "complicated atherosclerosis" as central fibrous necrosis and calcification or plaque bleeding and surface thrombosis. Our results do not support the hypothesis that systemic Cpn, HSV or CMV- infection or evidence of Cpn-, HSV- or CMV-DNA in carotid plaques causes plaque destabilization and cerebral thromboembolism. Plaque infection could only be observed in cases with advanced atherosclerosis.


In vivo confocal microscopic investigation of the cornea after autologous implantation of lenticules obtained through small incision lenticule extraction for treatment of hyperopia.
To investigate re-innervation in the implanted lenticule, as well as changes to the cornea, after correcting hyperopia with an autologous implantation of a lenticule obtained through small incision lenticule extraction (SMILE). This study retrospectively analysed re-innervation in the implanted lenticule, as well as microscopic morphological changes in the corneal architecture of the recipient cornea in five patients (with myopia in one eye and hyperopia in the contralateral eye) who received SMILE in the myopic eye and femtosecond laser in situ keratomileusis (FS-LASIK) combined with lenticule implantation in the contralateral hyperopic eye. Re-innervation in the implanted lenticule, as well as microscopic morphological changes in corneal architecture, were evaluated by in vivo confocal microscopy. One patient was examined at postoperative week six, two were examined at postoperative month two, one was examined at postoperative month nine, and one was examined at postoperative month 12. Partial subbasal nerve fibre regeneration was detected in two patients (Case 4 who was examined at postoperative month nine and Case 5 who was examined at postoperative month 12). Regenerated and branched nerve fibres were detected in the implanted lenticule in Case 5 who was examined at postoperative month 12. Both the anterior and posterior interfaces showed an absence or decrease of keratocytes and the presence of small particles of various brightnesses. Keratocytes in the implanted lenticule presented abnormal morphology in size and shape after surgery in all treated eyes, but showed partial morphological recovery in two patients (Case 4 who was examined at postoperative month nine and Case 5 who was examined at postoperative month 12). These preliminary findings suggest that nerve fibres will regenerate into the implanted lenticule after autologous lenticule implantation. Keratocytes in lenticules demonstrated a gradual return to a normal morphology.


A functional comparison of tumor cell killing by activated macrophages and natural killer cells.
This report compares the sensitivity of 17 tumor cell lines to cytolysis mediated by natural killer (NK) cells or by activated, bone marrow-derived macrophages (AM) from 15 inbred mouse strains. Some tumor cell lines, notably P815, were highly sensitive to AM-mediated lysis but almost completely insensitive to NK cells, whereas other cell lines were lysed by NK cells but not AM. In a genotype survey, some low-responder strains in the NK system, such as A/Sn, were high responders in the AM system, and conversely, one intermediate to high-responder strain (C3H/HeJ) in the NK system was a low responder in AM-mediated cytolysis. In addition, macrophage cytotoxicity factor was necessary to activate macrophages, but this lymphokine did not augment NK activity. Furthermore, the NK population did not contain pre-activated macrophages since pre-activated cells were removed on glass bead columns or by iron carbonyl and a magnet; treatments which have been previously shown not to affect NK cells. These results suggest that NK cells are distinct from AM in physical characteristics, target selectivity, genotype distribution and the mechanism of cytolysis.


Effect of neomycin on post-tetanic twitch tension of the mouse diaphragm preparation.
The effect of calcium (0.5-6 mM) and neomycin (0.1-0.2 mM) on the maximum post-tetanic twitch tension (MTT) and post-tetanic depression (PTD) of the indirectly elicited twitch tension was studied on the mouse isolated phrenic nerve-diaphragm preparation. The effect of neomycin on MTT of directly stimulated twitch tension was also tested in (+)-tubocurarine pretreated preparations. Three-dimensional plots between MTT and frequency and duration of indirect tetanic stimulation revealed that the frequencies and durations inducing maximal MTT were 500 Hz for 20 s in 0.5 mM CaCl2, 100 Hz for 5 s in 2 mM CaCl2 and 100 Hz for 10 s in 6 mM CaCl2. The frequency and duration inducing maximal PTD was 100 Hz for 20 s in 0.5 mM CaCl2, but there was no PTD in 2 mM or 6 mM CaCl2. Neomycin was associated with significantly greater MTT than in control if the duration of tetanic stimulation was 1 or 2 s, while it was associated with less MTT if the duration of tetanic stimulation was 10 or 20 s. Neomycin caused PTD in 2 mM CaCl2; sometimes the depressive effect was so severe that twitch tension was abolished. The maximal depression effect was found after 100 Hz tetanic stimulation for 20 s. Increasing the extracellular calcium concentration to 6 mM antagonized the effects of neomycin on MTT and PTD, whereas neostigmine (1.6 microM) antagonized the effect partially. Neomycin had no effect on the MTT or PTD of the directly stimulated twitch tension. It is concluded that neomycin alters the conditions of tetanic stimulation inducing MTT.


Placement of a take-out container during meal influences energy intake.
A growing body of research suggests that increased portion sizes are contributing to the rising rates of obesity. However, studies that focus on environmental cues to promote portion control are relatively limited. Thus, a randomized study was conducted in a controlled laboratory setting to determine if the presence of a take-out container, given at the start of a meal, would prompt experimental group participants to decrease the portion of food consumed and reduce energy intake. Outcomes were analyzed using descriptive statistics, independent t-tests, and analysis of covariance. Results showed that placing a take-out container with the test meal led to a significant difference in energy intake (p=0.000) when compared to the control group. Participants (n=25) who were given a take-out container with their test meal consumed an average of 90 kcal less than participants (n=25) who were not given the condition. These findings suggest that a to-go container may be utilized as an effective environmental cue for guiding consumers to control serving size when faced with over-sized portions at restaurants or other food outlets.


Competitive interactions between the lake-dwelling leeches Glossiphonia complanata and Helobdella stagnalis: an experimental investigation of the significance of a food refuge.
The glossiphoniid leeches Helobdella stagnalis and Glossiphonia complanata co-exist on the stony shores of British lakes. Because both species have a similar life-style and are food limited, the question arises as to how coexistence persists. Laboratory experiments investigated if either leech has a competitive advantage on three foods, viz. oligochaete worms (Tubifex sp.), snails (Lymnaea peregra), and a worm-plus-snail mixture. A variety of densities with a range of ratios of the two leeches, and monospecific controls were used. The level of feeding ensured increasing food shortage with rising leech density. Experiments, conducted at 14° C, lasted 3 months. Regression values for growth against density in the controls indicated the occurrence of intraspecific competition in both leech species. Light mortality occurred at the highest densities. G. complanata gained significantly less weight in mixed leech cultures than in monospecific cultures at some of the highest densities when fed worms, but more weight when fed on snails. The opposite was true for H. stagnalis. When both prey types were provided, no differences at any density were observed for either leech. Differences in bodysize and feeding strategy between the leeches may be implicated in determining their feeding success on the prey types. Because the anti-predatory responses (e.g. shaking) exhibited by L. peregra are less when encountering an inactive than an active leech, the sit-and-wait strategy of G. complanata may aid snail capture. In contrast, the seek-out strategy of H. stagnalis, coupled with its relatively smaller size, may result in fewer successful captures. The active hunting strategy of H. stagnalis may be advantageous for the capture of oligochaetes which are relatively less mobile than snails. Offering both prey types simultaneously would have had an ameliorating influence on interactions between the two leeches. Findings provide support for the hypothesis that long-term co-existence between the two glossiphoniids in British lakes may depend, in part at least, on the occurrence of a snail food refuge for G. complanata.


Synergistic activation by serotonin and GTP analogue and inhibition by phorbol ester of cyclic Ca2+ rises in hamster eggs.
1. Synergistic activation of a GTP-binding protein (G protein) by external serotonin (5-hydroxytryptamine, 5-HT) and internally applied guanosine-5'-O-(3-thiotriphosphate (GTP gamma S) in hamster eggs was demonstrated by the facilitation of repetitive increases in cytoplasmic Ca2+ as measured by their associated hyperpolarizing responses (HRs) and by aequorin luminescence. 2. Rapid application of 70 nM-5-HT caused a single HR of 10-12 s duration and with a delay of 80 s. The critical concentration of 5-HT to cause an HR was 50 nM. 3. With 10 microM-5-HT four to six HRs were often elicited with a delay to the first HR of 8-30 s. HRs disappeared after prolonged or repeated application of 5-HT, indicating an apparent desensitization. 4. 5-HT-induced HRs were completely inhibited by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (TPA) (100 nM). Conversely, the PKC inhibitor sphingosine (2 microM) enhanced the series of HRs by shortening the delay to the first HR (3-9 s) and by causing more HRs. 5. Ionophoretic injection of GTP gamma S into the egg usually produced a large HR with a delay of 120-240 s followed by a series of much smaller HRs. When 5-HT was applied within 1 min of injection of GTP gamma S. 70 nM-5-HT induced a number of large HRs and even 1 nM-5-HT could induce HR(s). In contrast, when 5-HT was applied after the size of GTP gamma S-induced HRs had declined, as much as 10 microM-5-HT could only elicit a single large HR. Thus, GTP gamma S apparently caused a sensitization and then a desensitization of the action of 5-HT. 6. GTP gamma S-induced Ca2+ transients were facilitated when injected in the presence of 5-HT concentrations as low as 0.1 nM. The time delay to the first HR was 65 s in 0.1 nM-5-HT or 4 s in 100 nM-5-HT whereas it was 170 s without 5-HT (mean values). The magnitude as well as frequency of HRs succeeding the first HR was enhanced by 5-HT at concentrations above 0.01 nM. 7. TPA (100 nM) blocked the GTP gamma S-plus-5-HT-potentiated HRs after the first four to five HRs. Sphingosine (2 microM) augmented the series of HRs.(ABSTRACT TRUNCATED AT 400 WORDS)


Magnetic quantum ratchet effect in graphene.
A periodically driven system with spatial asymmetry can exhibit a directed motion facilitated by thermal or quantum fluctuations. This so-called ratchet effect has fascinating ramifications in engineering and natural sciences. Graphene is nominally a symmetric system. Driven by a periodic electric field, no directed electric current should flow. However, if the graphene has lost its spatial symmetry due to its substrate or adatoms, an electronic ratchet motion can arise. We report an experimental demonstration of such an electronic ratchet in graphene layers, proving the underlying spatial asymmetry. The orbital asymmetry of the Dirac fermions is induced by an in-plane magnetic field, whereas the periodic driving comes from terahertz radiation. The resulting magnetic quantum ratchet transforms the a.c. power into a d.c. current, extracting work from the out-of-equilibrium electrons driven by undirected periodic forces. The observation of ratchet transport in this purest possible two-dimensional system indicates that the orbital effects may appear and be substantial in other two-dimensional crystals such as boron nitride, molybdenum dichalcogenides and related heterostructures. The measurable orbital effects in the presence of an in-plane magnetic field provide strong evidence for the existence of structure inversion asymmetry in graphene.


Modification of the effects of LSD-25, d-amphetamine and tryptamine on electrically evoked responses in the visual system by methiothepin and octoclothepin.
LSD-25 (32 microgram/kg), d-amphetamine (3.2 mg/kg), and tryptamine (320 to 3200 microgram/kg) given intravenously depressed the response recorded in the visual cortex to electrical stimulation of the optic chiasm of the chloralose anesthetized cat. Relatively large doses of 1 mg/kg of the dibenzothiepin derivatives, methiothepin and octoclothepin, antagonized the depressant effects of both LSD-25 and tryptamine to a greater degree than d-amphetamine.


Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen - a suitable way to N-hydrazonation of C-H-bonds.
The sensitized photoexcitation of 2-diazocyclopentane-1,3-diones in the presence of THF leads to the insertion of the terminal N-atom of the diazo group into the α-С-Н bond of THF, producing the associated N-alkylhydrazones in yields of up to 63-71%. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products with up to 90-97% yield.


Sleeve Gastrectomy and Cholecystectomy are Safe in Obese Patients with Asymptomatic Cholelithiasis. A Multicenter Randomized Trial.
Obesity is a severe health problem. Gallstones may symptomatize after sleeve gastrectomy (SG). Concomitant laparoscopic cholecystectomy (LC) with SG is controversial. The effects of SG and LC versus delayed LC following SG in obese patients with asymptomatic gallbladder stones were evaluated. A randomized trial of 222 morbidly obese patients with gallbladder stones divided them into two equal groups: SG + LC and SG-only. This multicenter study conducted from January 2016 to January 2019. Except for operative time and postoperative hospital stay, there was no statistically significant difference between LSG + LC group and SG group (P < 0.001). In SG + LC group, LC added 40.7 min to SG, three patients (3%) required conversion, early postoperative complications occurred in 9 cases (9/111, 9%), three cases required re-intervention (3%). In SG group, the complicated cases required LC were 61 cases (61/111, 55%). Acute cholecystitis (26/61, 42.7%) was the most common gallstone symptoms. Most complicated cases occurred in the first-year follow-up (52/61, 85%). In the delayed LC group (61 patients), operative time was 50.13 ± 1.99 min, open conversion occurred in 2 cases (2/61, 3.2%), early postoperative complications occurred in four patients (4/61, 6.4%) and postoperative re-intervention were due to bile leaks and cystic artery bleeding (2/61, 3.2%). SG with LC prolongs the operative time and hospital stay, but the perioperative complications are the same as delayed LC; LC with SG minimizes the need for a second surgery. Concomitant LC with SG is safe.


Mechanisms of increased lower esophageal sphincter pressure following intraduodenal peptone infusion in dogs.
Peptone perfusion of the excluded duodenum in dogs is associated with an increase in lower esophageal sphincter pressure (LESP). This study investigates the role of cholinergic, adrenergic, and hormonal mediators in the response of the LES to intraduodenal peptone infusion. Adult dogs underwent duodenal exclusion via a Roux-en-Y pylorojejunostomy with formation of a mucocutaneous fistula. Manometric measurements of LESP and radioimmunoassay determinations of gastrin and pancreatic polypeptide (PP) blood levels were made at rest and at 15-min intervals following peptone infusion of the excluded duodenum. In control experiments, peptone infusion resulted in an increase in mean LESP at all time intervals (P less than 0.05). PP blood levels increased significantly, while gastrin levels remained unchanged. Both truncal vagotomy and pretreatment with atropine blocked the changes in LESP. PP release in response to peptone was accentuated in vagotomized dogs, while atropine suppressed the release of PP following peptone infusion. Treatment with 6-hydroxydopamine did not affect the increase in either LESP or PP blood levels observed in controls. Intravenous somatostatin suppressed the release of PP following intraduodenal peptone, but did not block the lower esophageal sphincter response. This data indicates that the increase in LESP seen following intraduodenal peptone infusion is centrally mediated and dependent on vagal innervation and cholinergic neurotransmission.


The potential of MRI-guided online adaptive re-optimisation in radiotherapy of urinary bladder cancer.
Adaptive radiotherapy (ART) using plan selection is being introduced clinically for bladder cancer, but the challenge of how to compensate for intra-fractional motion remains. The purpose of this study was to assess target coverage with respect to intra-fractional motion and the potential for normal tissue sparing in MRI-guided ART (MRIGART) using isotropic (MRIGARTiso), an-isotropic (MRIGARTanIso) and population-based margins (MRIGARTpop). Nine bladder cancer patients treated in a phase II trial of plan selection underwent 6-7 weekly repeat MRI series, each with volumetric scans acquired over a 10 min period. Adaptive re-planning on the 0 min MRI scans was performed using density override, simulating a hypo-fractionated schedule. Target coverage was evaluated on the 10 min scan to quantify the impact of intra-fractional motion. MRIGARTanIso reduced the course-averaged PTV by median 304 cc compared to plan selection. Bladder shifts affected target coverage in individual fractions for all strategies. Two patients had a v95% of the bladder below 98% for MRIGARTiso. MRIGARTiso decreased the bowel V25 with 15-46 cc compared to MRIGARTpop. Online re-optimised ART has a considerable normal tissue sparing potential. MRIGART with online corrections for target shift during a treatment fraction should be considered in ART for bladder cancer.


Pentraxin 3 as a novel early biomarker for the prediction of Henoch-Schönlein purpura nephritis in children.
We investigated the potential role of pentraxin 3 (PTX3) in Henoch-Schönlein purpura (HSP), a common multisystemic vasculitis affecting children, as a predictor of Henoch-Schönlein purpura nephritis (HSPN). A total of 108 cases consisting of 34 children with HSP, 37 children with HSPN, and 37 healthy control children were enrolled in this prospective study from March 2010 to February 2013. Blood and urine samples were collected to measure plasma PTX3, C-reactive protein (CRP), serum creatinine, blood urea nitrogen (BUN), urine microalbumin (MALB), and β2-microglobulin (β2-MG). Median plasma PTX3 concentrations were significantly higher in children with HSPN and HSP than in control subjects before treatment (6.99, 4.18-9.78 ng/ml; 3.19, 1.13-4.27 ng/ml; 1.24, 0.87-2.08 ng/ml, respectively; all p < 0.05). Median plasma PTX3 concentrations were also significantly higher in children with HSPN than in children with HSP before treatment (6.99, 4.18-9.78 vs. 3.19, 1.13-4.27 ng/ml; p < 0.05). After treatment, median plasma PTX3 concentrations significantly decreased in children with HSP (from 3.19, 1.13-4.27 to 1.08, 0.65-2.19 ng/ml; p < 0.05) and HSPN (from 6.99, 4.18-9.78 to 1.29, 1.01-2.26 ng/ml; p < 0.05). Plasma PTX3 concentration was positively correlated with CRP (rho = 0.532, p = 0.001), MALB (rho = 0.606, p < 0.001), β2-MG (rho = 0.490, p = 0.002), and 24-h urinary protein quantity (rho = 0.650, p < 0.001) in children with HSPN. Considering vasculitis, we found that PTX3 could be used as a more efficient potential predictor of HSPN than CRP as indicated by the area under the receiver operating characteristic (ROC) curve (AUCROC) of PTX3 (AUCROC = 0.837; p < 0.001) and CRP (AUCROC = 0.514; p = 0.845). The threshold PTX3 concentration with optimal sensitivity and specificity was 4.30 ng/ml (sensitivity 73.0 %, specificity 79.6 %). PTX3 seems to have an important role in multisystemic vasculitis of HSP, may be involved in the development of HSPN, and used as an early biomarker to predict HSPN.


Age and sex-related differences in risk factors for elderly suicide: Differentiating between suicide ideation and attempts.
The purpose of this study was to analyze the age and sex-related differences in socio-demographic factors that influence suicide ideation and attempts in the elderly. The total number of subjects was 93 151, of whom 8441 belonged to the high suicide-risk group (2064 male; 6377 female). Following this identification, we investigated their socio-demographic information, health status, and depressive symptoms, which might have influenced their suicide ideation and attempts. Residence in an urban area was identified as a risk factor for both male and female elderly in their 60s and 70s and female elderly in their 80s. Marital status showed a different influence on suicide ideation depending on age and sex. A negative perception of one's own health status was a significant risk factor that increased the likelihood of suicide ideation in all ages, except the female elderly in their 60s. No factor was identified that significantly influenced suicide attempts in the male elderly. However, in the female elderly, residence in an urban area and a negative perception of one's own health status were identified as significant risk factors. This study revealed that factors known to influence suicide ideation in the elderly from previous studies, such as residence area, separation from a spouse, education level, religion, and drinking, show changed influence as the elderly reach their 70s and 80s. However, a negative perception of one's own health status was a risk factor that encompassed most ages and sexes.