Laser-induced dynamic alignment of the HD molecule without the Born-Oppenheimer approximation.

Laser-induced molecular alignment is well understood within the framework of the Born-Oppenheimer (BO) approximation. Without the BO approximation, however, the concept of molecular structure is lost, making it hard to precisely define alignment. In this work, we demonstrate the emergence of alignment from the first-ever non-BO quantum dynamics simulations, using the HD molecule exposed to ultrashort laser pulses as a few-body test case. We extract the degree of alignment from the non-BO wave function by means of an operator expressed in terms of pseudo-proton coordinates that mimics the BO-based definition of alignment. The only essential approximation, in addition to the semiclassical electric-dipole approximation for the matter-field interaction, is the choice of time-independent explicitly correlated Gaussian basis functions. We use a variational, electric-field-dependent basis-set construction procedure, which allows us to keep the basis-set dimension low while capturing the main effects of electric polarization on the nuclear and electronic degrees of freedom. The basis-set construction procedure is validated by comparing with virtually exact grid-based simulations for two one-dimensional model systems: laser-driven electron dynamics in a soft attractive Coulomb potential and nuclear rovibrational dynamics in a Morse potential.

Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

Percutaneous tibial nerve stimulation for idiopathic and neurogenic overactive bladder dysfunction: a four-year follow-up single-centre experience.

OBJECTIVE: Overactive bladder (OAB) affects hundreds of millions of people worldwide and has significant detrimental effects on quality-of-life. Percutaneous tibial nerve stimulation (PTNS) is endorsed in the European guidelines of Urology as second-line therapy - on par with pharmacological treatment for women with OAB. METHODS: This prospective cohort study describes our clinical experience with PTNS in a daily outpatient clinic, on a consecutive cohort. The cohort of 116 patients was mixed; including both men and women with idiopathic (iOAB) and neurogenic (nOAB) overactive bladder. Patients were treated with a 12-week course of PTNS followed by monthly maintenance treatment. Data were collected during 4 years. RESULTS: The most common indication for PTNS was OAB with urge incontinence (53%) followed by OAB-dry and nocturia (both 16%). One hundred and ten (95%) patients completed follow-up and 68 patients (62%) continued to maintenance treatment. A total of 68 patients reported an effect on PROM, BD and ICIQ-OAB, which is the same 62% that continue in maintenance PTNS. A significant decline was seen in overall ICIQ-OAB score, with a median drop from 87 to 54, a significant decline in overall frequency and nocturia on bladder diary and a shift in pad test group in 19% of the incontinence patients. CONCLUSION: PTNS shows an equally significant effect on men as well as women both in the iOAB and nOAB subgroups in a daily outpatient clinic. In our opinion, PTNS should be a standard treatment option available at urological departments, where both men and women in both sub-groups could benefit from treatment. Further randomized studies focusing on men with iOAB are needed.

Outcome following local excision of T1 anal cancers-a systematic review.

PURPOSE: In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low recurrence rates. However, chemo-radiotherapy has several side effects: dyspareunia, impotence, fecal incontinence, pain, and skin symptoms. Small/T1 tumors, without metastatic disease, can be treated with local excision alone. We aimed to systematically review the literature regarding outcome following local excision of T1 SCCA. METHODS: PubMed and Embase databases were searched for studies that investigated outcome following local excision of SCCA. RESULTS: Twenty-three studies were included. Twenty of the studies were retrospective, and three studies included more than 100 patients. Most of the studies were published before the 1980s. Overall there was great heterogeneity and missing data across the included studies when comparing patient demographics, resection margins, definitions on tumor location, and outcome. Overall 5-year survival was 69% (95% CI 66-72) following local excision. Overall 5-year recurrence was 37% (95% CI 30-45) following local excision. No complications were reported following local excision. CONCLUSION: The current literature on outcome following local excision of T1 anal cancers consists predominantly of smaller, retrospective, and heterogenous studies. Overall 5-year survival is acceptable, but worse than following chemo-radiation therapy. However, local excision seems to have no or only few minor complications. Recurrence rates are high. Therefore, a thorough follow-up program is needed when performing local excision as primary treatment for T1 SCCA. There is an evident need for further studies.

Quality of life following salvage surgery for squamous cell carcinoma of the anus.

INTRODUCTION: Squamous cell carcinoma of the anus is a rare condition. First line treatment is combined chemo-radio therapy. As many as a third of patients undergoing chemo-radiotherapy will experience recurrence. These patients often undergo salvage surgery with an extended abdominoperineal excision. The aim of this study was to examine the quality of life in disease free survivors following salvage surgery for squamous cell carcinoma of the anus. MATERIAL AND METHODS: Patients undergoing salvage surgery for SCCA at Copenhagen University Hospital Herlev between 1st of January 2011 and 31st December 2016 were identified and quality of life was assessed with EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. RESULTS: 47 patients underwent salvage surgery for relapse or residual tumor in the period. From this cohort 25 disease-free survivors were identified. Fourteen (56%) patients returned a completed questionnaire. Overall median global health status was 75(range 20-100). Functional scores were generally high. In General, symptom scores were low, however all men reported impotence with a median symptom score of 100(range 67-100) and half the women reported dyspareunia. Urinary impairment was present in half the patients. Abdominal and buttock pain scores were low. CONCLUSION: Quality of life following salvage surgery for squamous cell carcinoma of the anus is affected but at an acceptable level. However, there are considerable side-affects in the form of impotence, dyspareunia and urinary impairment.

30-day and long-term outcome following salvage surgery for squamous cell carcinoma of the anus.

INTRODUCTION: Squamous cell carcinoma of the anus (SCCA) is a rare condition. First line treatment is combined chemo-radio therapy. As many as a third of patients undergoing CRT will experience recurrence. These patients often undergo salvage surgery with an extended abdominoperineal excision. The aims of this study were 1) to assess and evaluate 30-day postoperative morbidity and mortality after salvage surgery for recurrent SCCA, and furthermore, 2) to examine secondary recurrence and long-term mortality after salvage surgery for recurrent SCCA. MATERIAL AND METHODS: Retrospective evaluation of all patients undergoing salvage surgery for SCCA at Copenhagen University Hospital Herlev between 1st of January 2011 and 31th December 2016. RESULTS: Forty-seven patients were identified. 30-day postoperative mortality was 4%. The most common postoperative complication was perineal wound defects. Within the follow-up period of median 20 (1-80) months, secondary recurrence occurred in 30% of patients. Median disease free survival was 32 months. Secondary recurrence was significantly more frequent in patients with R1 resection and pN ≥ 1. Within the follow-up period of median 25 (0-80) months, mortality was 40%. Overall median survival was 39 months. Secondary recurrence was associated with a significantly higher risk of death within the follow-up period. CONCLUSION: Salvage surgery for relapse of squamous cell carcinoma of the anus is a safe procedure with a good short-term outcome. Secondary recurrence was more frequent in patients with R1-resection and pN ≥ 1. More than one third of the patients died within the follow-up period, and mortality was significantly higher in the group of patients with secondary recurrence.

Reference values of maximum walking speed among independent community-dwelling Danish adults aged 60 to 79 years: a cross-sectional study.

OBJECTIVES: To establish reference values for maximum walking speed over 10 m for independent community-dwelling Danish adults, aged 60 to 79 years, and to evaluate the effects of gender and age. DESIGN: Cross-sectional study. SETTING: Danish companies and senior citizens clubs. PARTICIPANTS: Two hundred and fifty-two adults (167 women, 85 men) with a mean age of 70 [standard deviation (SD) 4] years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Results for the 10-m walk test (10 MWT) were used to establish reference values. RESULTS: The mean reference value for maximum walking speed over 10 m for all participants was 1.94 (SD 0.31) m/second. Reference values for women aged 60 to 69 years and 70 to 79 years were 1.96 (SD 0.26) and 1.81 (SD 0.29) m/second, respectively. Reference values for men aged 60 to 69 years and 70 to 79 years were 2.10 (SD 0.35) and 2.01 (SD 0.30) m/second, respectively. Significant differences (P<0.01) were observed in the age and gender categories. Men were found to walk faster than women, and individuals aged 60 to 69 years walked faster than individuals aged 70 to 79 years. CONCLUSIONS: This study established the reference values for maximum walking speed over 10 m among independent community-dwelling Danish adults aged 60 to 79 years. The study results showed significant differences in maximum walking speed for different ages and between men and women.

Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia.

Subchronic phencyclidine (subPCP) treatment induces schizophrenic-like behavior in rodents, including cognitive deficits and increased locomotor sensitivity towards acute administration of PCP. Evidence is accumulating that the gut microbiota (GM) influences behavior through modulation of the microbiota-gut-brain axis, and hence, part of the variation within this animal model may derive from variation in the GM. The aims of this study was to investigate first, the duration of subPCP-induced cognitive impairment in the novel object recognition test, and second, the possible effect of subchronic PCP-treatment on the GM, and the association between the GM and the behavioral parameters. The association was further investigated by antibiotic reduction of the GM. Male Lister Hooded rats were dosed twice daily i.p. with either 5mg/kg PCP or sterile isotonic saline for seven days followed by a seven-day washout period. Rats were tested in the novel object recognition and the locomotor activity assays immediately after, three weeks after, or six weeks after washout, and the fecal GM was analyzed by high throughput sequencing. Antibiotic- and control-treated rats were tested in the same manner following washout. In conclusion, subPCP-treatment impaired novel object recognition up to three weeks after washout, whereas locomotor sensitivity was increased for at least six weeks after washout. Differences in the core gut microbiome immediately after washout suggested subPCP treatment to alter the GM. GM profiles correlated to memory performance. Administration of ampicillin abolished the subPCP-induced memory deficit. It thus seems reasonable to speculate that the GM influences memory performance, contributing to variation within the model.

Genome Sequences of Two Leuconostoc pseudomesenteroides Strains Isolated from Danish Dairy Starter Cultures.

The lactic acid bacterium Leuconostoc pseudomesenteroides can be found in mesophilic cheese starters, where it produces aromatic compounds from, e.g., citrate. Here, we present the draft genome sequences of two L. pseudomesenteroides strains isolated from traditional Danish cheese starters.

Genome Sequence of Leuconostoc mesenteroides subsp. cremoris Strain T26, Isolated from Mesophilic Undefined Cheese Starter.

Leuconostoc is the main group of heterofermentative bacteria found in mesophilic dairy starters. They grow in close symbiosis with the Lactococcus population and are able to degrade citrate. Here we present a draft genome sequence of Leuconostoc mesenteroides subsp. cremoris strain T26.

Carbon nanorings: A challenge to theoretical chemistry.

High-level quantum-chemical methods show that the binding in the inclusion complex of hexamethylbenzene (HMB) in 6-cycloparaphenilacetylene (6-CPPA) cannot be explained only in terms of electrostatic interactions-caused by the polarization associated to curved pi-conjugated systems-and the inclusion of dispersion forces is definitely needed. The theoretical description of van der Waals interactions is notoriously complicated and in fact some DFT methods cannot even predict the existence of the relatively small supramolecular nanoring studied here. However, ab initio MP2 calculations agree with experimental data and show that, in the considered complex, the HMB fragment is placed at the center of the 6-CPPA ring. The binding energy, which is not available experimentally, is calculated to be around -14 kcal mol(-1) with a lower limit of -19 kcal mol(-1).

NG2 expression regulates vascular morphology and function in human brain tumours.

Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and the host tissue. The underlying mechanisms that regulate such interactions remain largely unknown. NG2 is a transmembrane proteoglycan whose presence on transformed cells has been demonstrated to increase proliferation in vitro and angiogenesis in vivo. To study the effects of NG2 during tumour growth and progression, we engineered an NG2 positive human glioma cell line (U251-NG2) from parental NG2 negative cells (U251-WT) and implanted both cell types stereotactically into immunodeficient nude rat brains. The tumours were longitudinally monitored in vivo using multispectral MRI employing two differently sized contrast agents (Gd-DTPA-BMA and Gadomer) to assess vascular leakiness, vasogenic oedema, tumour volumes and necrosis. Comparisons of Gd-DTPA-BMA and Gadomer revealed differences in their spatial distribution in the U251-NG2 and U251-WT tumours. The U251-NG2 tumours exhibited a higher leakiness of the larger molecular weight Gadomer and displayed a stronger vasogenic oedema (69.9 +/- 15.2, P = 0.018, compared to the controls (10.7 +/- 7.7). Moreover, immunohistochemistry and electron microscopy revealed that the U251-NG2 tumours had a higher microvascular density (11.81 +/- 0.54; P = 0.0010) compared to controls (5.76 +/- 0.87), with vessels that displayed larger gaps between the endothelial cells. Thus, tumour cells can regulate both the function and structure of the host-derived tumour vasculature through NG2 expression, suggesting a role for NG2 in the cross-talk between tumour-host compartments.

Association of acylated cationic decapeptides with dipalmitoylphosphatidylserine-dipalmitoylphosphatidylcholine lipid membranes.

The interaction of three acylated and cationic decapeptides with lipid membranes composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS) has been studied by means of fluorescence spectroscopy and differential scanning calorimetry (DSC). The synthetic model decapeptides that are N-terminally linked with C(2), C(8), and C(14) acyl chains contain four basic histidine residues in their identical amino acid sequence. A binding model, based on changes in the intrinsic fluorescent properties of the peptides upon association with the DPPC-DPPS membranes, is used to estimate the peptide-membrane dissociation constants. The results clearly show that all three peptides have a higher affinity to liposomes containing DPPS lipids due to non-specific electrostatic interactions between the cationic peptides and the anionic DPPS lipids. Furthermore, it is found that the acyl chain length of the peptides plays a crucial role for the binding. A preference for fluid phase membranes as compared to gel phase membranes is generally observed for all three peptides. DSC is used to characterise the influence of the three peptides on the thermodynamic phase behaviour of the binary DPPC-DPPS lipid mixture. The extent of peptide association deduced from the heat capacity measurements suggests a strong binding and membrane insertion of the C(14) acylated peptide in accordance with the fluorescence measurements.

Dynamical and structural properties of lipid membranes in relation to liposomal drug delivery systems.

The structural and dynamical properties of DPPC liposomes containing lipopolymers (PEG-lipids) and charged DPPS lipids have been studied in relation to the lipid membrane interaction of enzymes and peptides. The results suggest that both the lipid membrane structure and dynamics and in particular the appearance of small-scale lipid structures might be of importance for the activity of membrane associated and liposome degrading enzymes as well as for the membrane interaction of acylated peptides. The combined experimental and simulation results are of relevance for a rational development of peptide loaded liposomal drug delivery systems that become destabilized by membrane degrading phospholipase A(2) enzymes, which are found at elevated concentrations at diseased sites.

Association of an acylated model peptide with DPPC-DPPS lipid membranes.

The interaction between a small positively charged peptide with a N-terminally linked acyl chain and dipalmitoylphosphatidylcholine-dipalmitoylphosphatidylserine (DPPC-DPPS) lipid membranes has been studied by means of fluorescence resonance energy transfer. Two different lipid compositions were used: a neutral membrane (100 mol% DPPC), and a negatively charged membrane (30 mol% DPPS in DPPC). The fluorescence resonance energy transfer results reveal that the peptide associates with both types of membranes. Furthermore, it is found that the slope of the titration curve for the negatively charged membranes is much steeper than that for the neutral membranes. This indicates a higher binding affinity of the acylated peptide towards negatively charged lipid membranes as compared with neutral lipid membranes.

Ethnomedical information and in vitro screening for angiotensin-converting enzyme inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan and Kerala (India).

Plants utilized as traditional medicines in India have been investigated for their ability to inhibit the angiotensin converting enzyme (ACE). In total, 75 species belonging to 42 families have been investigated and new ethnomedical information has been obtained for 41 species. Four species were found to possess a high ACE inhibiting ability and were low in their tannin content.

[Survival and living conditions of surgical patients past 80 years of age]. / Overlevelse og boligforhold hos kirurgisk behandlede patienter over 80 år.

In a retrospective investigation at the department of Surgery, Frederiksberg Hospital in 1981, the frequency of operations in patients above 80 years old was 3.4% compared to 1.7% in the general population. The total number of operations in the aged group was 183. The object of this investigation was to determine the postoperative mortality and 5-year survival rate in the patients aged 80 years or more. Furthermore, the ability of the patients to stay in their homes was investigated. The patients were divided into a major surgery group and a minor surgery group depending on the extent of the operation. The postoperative mortality var 5.5%. Compared to an age and sex matched control group, only the major surgery group had a higher rate of mortality during the first six postoperative months. Among the patients who were admitted from home, 85% were discharged directly to their homes. At the end of the study period or at the time of death, the percentage of patients staying in old peoples homes was essentially the same as for the rest of the population. It is concluded that the patients aged 80 years or more tolerated surgical trauma relatively well and, that the number of geriatric operations may be anticipated to increase greatly.