Impact and correlates of sub-optimal social support among patients in HIV care.

Social support (SS) predicts health outcomes among patients living with HIV. We administered a brief, validated measure of SS, the Multifactoral Assessment of Perceived Social Support, within a patient-reported outcomes assessment of health domains in HIV care at 4 U.S. clinics in English and Spanish (n = 708). In univariate analysis, low SS was associated with poorer engagement in care, antiretroviral adherence, and health-related quality of life; current methamphetamine/crystal use, depression, anxiety, and HIV stigma (all p < 0.001); any use of either methamphetamines/crystal, illicit opioids, or cocaine/crack (p = 0.001), current marijuana use (p = 0.012), nicotine use (p = 0.005), and concern for sexually transmitted infection exposure (p = 0.001). High SS was associated with undetectable viral load (p = 0.031). Multivariate analyses found low SS independently associated with depression (risk ratio (RR) 3.72, 95% CI 2.93-4.72), lower adherence (RR 0.76, 95% CI 0.64-0.89), poor engagement in care (RR 2.05, 95% CI 1.44-2.96), and having more symptoms (RR 2.29, 95% CI 1.92-2.75). Medium SS was independently associated with depression (RR 2.59, 95% CI 2.00-3.36), poor engagement in care (RR 1.62, 95% CI 1.15-2.29) and having more symptoms (RR 1.75, 95% CI 1.44-2.13). SS assessment may help identify patients at risk for these outcomes.

[The role of the gut microbiome in idiopathic Parkinson's disease]. / Die Rolle des Darmmikrobioms beim idiopathischen Parkinson-Syndrom.

BACKGROUND: In recent years studies have provided increasing evidence suggesting an association between the (gut) microbiome and idiopathic Parkinson's disease (IPD). OBJECTIVE: The aim of this article is to summarize and evaluate existing evidence with respect to the relevance of the (gut) microbiome for IPD. MATERIAL AND METHODS: An analysis and critical review of studies in the field of IPD and (gut) microbiome were carried out. The resulting potential perspectives and therapeutic strategies are discussed. RESULTS: Despite partially divergent results between different studies (potentially due to the applied methods and variance in the composition of the investigated cohorts), there is an overlap between studies indicating an association between IPD, the microbiome and microbial metabolites. Nevertheless, the cause-effect relationship between IPD and the microbiome has still not been clarified. Taken together, existing evidence supports a potentially relevant role for the microbiome with respect to typical disease symptoms and pathogenesis of the disease. CONCLUSION: Over the past 5 years there has been an enormous increase in the evidence with respect to the relevance of the microbiome for IPD. While early work in this field was mainly descriptive, new diagnostic methods provide evidence for the underlying mechanisms and the complex interactions between man as the host, the human immune system, the enteric nervous system, gut microbiota and microbial metabolites. A relatively novel and clinically relevant field of research is how the gut microbiome can influence the success of oral pharmacotherapy and whether substitution of specific microbiome components might be used either for future therapeutic or prophylactic strategies.

Angle-dependent strong-field ionization of halomethanes.

We study, experimentally and theoretically, the ionization probability of singly halogenated methane molecules, CH3Cl and CH3Br, in intense linearly polarized 800 nm laser pulses as a function of the angle between the molecular axis and the laser polarization. Experimentally, the molecules are exposed to two laser pulses with a relative time delay. The first, weaker pulse induces a nuclear rotational wave packet within the molecules, which are then ionized by the second, stronger pulse. The angle-dependent ionization yields are extracted from fits of the measured delay-dependent ionization signal to a superposition of moments of the rotational wave packet's angular distribution. Angle-dependent strong-field ionization (SFI) yields are also calculated using time-dependent density functional theory. Good agreement between measurements and theory is obtained. Interestingly, we find a marked difference between the angle-dependence of the ionization yields for these two halomethane species despite the similar structure of their highest occupied molecular orbitals. Calculations reveal that these differences are a result of multichannel (CH3Cl) vs single-channel (CH3Br) ionization and of increased hole localization on Br vs Cl. By adding calculations for CH3F, we can discern clear trends in the ionization dynamics with increasing halogen mass. These results are illustrative, as chemical functionalization and molecular alignment are likely to be important parameters for initiating and controlling charge migration dynamics via SFI.

Probing the interplay between geometric and electronic-structure features via high-harmonic spectroscopy.

We present molecular-frame measurements of the recombination dipole matrix element (RDME) in CO2, N2O, and carbonyl sulfide (OCS) molecules using high-harmonic spectroscopy. Both the amplitudes and phases of the RDMEs exhibit clear imprints of a two-center interference minimum, which moves in energy with the molecular alignment angle relative to the laser polarization. We find that whereas the angle dependence of this minimum is consistent with the molecular geometry in CO2 and N2O, it behaves very differently in OCS; in particular, the phase shift which accompanies the two-center minimum changes sign for different alignment angles. Our results suggest that two interfering structural features contribute to the OCS RDME, namely, (i) the geometrical two-center minimum and (ii) a Cooper-like, electronic-structure minimum associated with the sulfur end of the molecule. We compare our results to ab initio calculations using time-dependent density functional theory and present an empirical model that captures both the two-center and the Cooper-like interferences. We also show that the yield from unaligned samples of two-center molecules is, in general, reduced at high photon energies compared to aligned samples, due to the destructive interference between molecules with different alignments.

Perivascular adipose tissue: epiphenomenon or local risk factor?

Obesity is associated with an increased cardiovascular risk, but the mechanisms underlying the link between increased body weight and vascular disease are incompletely understood. Over the past 15 years, perivascular adipose tissue has emerged as active component of the vessel wall involved in vascular homeostasis. However, perivascular adipose tissue can adopt detrimental properties under the influence of obesity and other factors and contribute actively to the pathophysiology of cardiovascular disease. Conversely, changes of the vessel wall may negatively affect perivascular adipose tissue qualities. In this review, we will discuss the recent literature on the possible direct and indirect connections between perivascular fat alterations and cardiovascular pathologies. In addition to clinical evidence on the association between perivascular fat mass and morphology and anthropometric measures of obesity or the reciprocal connection between perivascular fat and cardiometabolic risk factors and disease, special emphasis will be placed on results in rodent and other models and the possible direct contribution of local fat depots to vascular dysfunction, neointima formation or atherosclerosis. We will briefly highlight results from human and murine genome, miRNome and proteome-wide expression analyses of potential candidate mediators involved in its paracrine activities and present data on how the cardiovascular risk factors obesity, age or diabetes, but also the preventive measures weight loss or exercise impact on perivascular expression patterns. A better understanding of this unique adipose tissue depot, its properties and regulatory mechanisms, may create opportunities for novel diagnostic and therapeutic strategies to combat the cardiovascular consequences of increased body weight.

Twisting and Tilting l,l'-Bis(dialkylphosphino)ferrocene Bound to Low Valent Tricarbonylmaganese(I to -I). [corrected].

Recently we had reported the noninnocent behavior of 1,1'-bis(diphenylphosphino)ferrocene (dppf) in Fe(CO)3dppf [Ringenberg et al., Inorg. Chem., 2017, 56, 7501]. Moving to the left in the periodic table, HMn(CO)3(dRpf) where dRpf = dppf (1H) and 1,1'-bis(diisopropylphosphino)ferrocene (dippf) (2H) were synthesized. The hydride ligand was removed by protonation with [(Et2O)2H][B(ArF)4] ([B(ArF)4]- = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate), resulting in the rapid evolution of H2 followed by the formation of an Fe→Mn interaction. The reaction mechanism was determined by in situ IR experiments which show that directly following protonation both [1]+ and [2]+ offer an open manganese coordination site that allows for the formation of an intramolecular Fe→Mn dative bond. This process is significantly faster for [2]+ than for [1]+. The reduction chemistry as studied by cyclic voltammetry (CV) reveals that both complexes change from a distorted octahedral coordination with an Fe→Mn interaction to an open square-pyramidal configuration which is more stable for [1]0 than [2]0. Reoxidation of this square-pyramidal species proceeds more reversibly for 2 versus 1 due to the faster ferrocene ligand reorganization. The electrochemical mechanism was studied by in situ spectroscopic techniques, e.g., IR, UV-vis-NIR (near IR), and EPR spectroelectrochemistry (SEC) as well as by CV simulation. The new complexes described offer an exciting platform for the development of electrocatalysts for the reduction of CO2 to CO, or for proton reduction (2H+ + 2e- → H2).

Role of Excited States In High-order Harmonic Generation.

We investigate the role of excited states in high-order harmonic generation by studying the spectral, spatial, and temporal characteristics of the radiation produced near the ionization threshold of argon by few-cycle laser pulses. We show that the population of excited states can lead either to direct extreme ultraviolet emission through free induction decay or to the generation of high-order harmonics through ionization from these states and recombination to the ground state. By using the attosecond lighthouse technique, we demonstrate that the high-harmonic emission from excited states is temporally delayed by a few femtoseconds compared to the usual harmonics, leading to a strong nonadiabatic spectral redshift.

Increased proatherogenic monocyte-platelet cross-talk in monocyte subpopulations of patients with stable coronary artery disease.

BACKGROUND: Monocytes and platelets are important cellular mediators of atherosclerosis. Human monocytes can be divided into CD14(++) CD16(-) , CD14(++) CD16(+) and CD14(+) CD16(++) cells, which differ in their functional properties. The aim of this study was to examine monocyte subset distribution, monocyte-platelet aggregate (MPA) formation and expression of CCR5, the receptor of the platelet-derived chemokine CCL5, and to determine whether these parameters are altered in individuals with coronary atherosclerosis. METHODS: Peripheral blood cells from 64 healthy blood donors (HBDs) and 60 patients with stable coronary artery disease (CAD) were stained with antibodies against CD14, CD16, CD42b and CCR5 and analysed by flow cytometry. Circulating CCL5 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: In patients with CAD, the relative proportion of the CD14(++) CD16(-) monocyte subset was elevated (P < 0.05) and of the CD14(+) CD16(++) subset was reduced (P < 0.001) compared with the HBD group. Furthermore, MPA formation significantly increased in patients with CAD in all three monocyte subsets. In both study groups, the majority of CCR5(+) cells was detected in CD14(++) CD16(+) monocytes (P < 0.001 versus CD14(++) CD16(-) and CD14(+) CD16(++) ), although the CCR5(+) monocyte number was reduced in patients with CAD (CD14(++) CD16(-) /CD14(+) CD16(++) , P < 0.001; CD14(++) CD16(+) , P < 0.05) compared with the HBD group, particularly in those who were not taking statins. Ex vivo incubation of monocytes from HBDs with plasma from patients with CAD also decreased CCR5(+) expression (P < 0.05 versus plasma from HBDs). Serum CCL5 levels were similar in both groups. CONCLUSIONS: The increased monocyte-platelet cross-talk in patients with CAD might have contributed to atherosclerosis progression. The decreased CCR5(+) monocyte numbers in patients with CAD could have resulted from CCR5(+) cell recruitment into atherosclerotic lesions or CCR5 downregulation in response to circulating factors.

Attosecond pulse shaping around a Cooper minimum.

High harmonic generation (HHG) is used to measure the spectral phase of the recombination dipole matrix element (RDM) in argon over a broad frequency range that includes the 3p Cooper minimum (CM). The measured RDM phase agrees well with predictions based on the scattering phases and amplitudes of the interfering s- and d-channel contributions to the complementary photoionization process. The reconstructed attosecond bursts that underlie the HHG process show that the derivative of the RDM spectral phase, the group delay, does not have a straightforward interpretation as an emission time, in contrast to the usual attochirp group delay. Instead, the rapid RDM phase variation caused by the CM reshapes the attosecond bursts.

Simulation of in-vivo-equivalent epithelial barriers using a micro fluidic device.

In biomedical approaches cell culture models do often not fully represent their biological counterparts. Often the methods used do not completely mimic the in-vivo situation, either by using only single-cell-type culture approaches, or by using inadequate culture conditions. We therefore developed a variable system based on individual modules to simulate in vitro equivalent cell-barriers (e.g. for mucous layers). This system allows the growth of different communicating cell types in micro channels. Hot embossing is used to fabricate the micro structured polymer sheets. The stamp for hot embossing is fabricated by UV-lithography/electroforming or by micro milling. The system consists of a container with micro fluidic modules and a pump-system for a continuous medium-supply. An individual module is made of two micro-structured polycarbonate-sheets separated by a transmissible polycarbonate membrane. The two sheets are arranged orthogonally to induce a cross flow. The system is highly variable by channel-geometry (height and width), capacity (number of micro fluidic modules), and pore sizes of the transmissible membranes. In a first approach we simulated the intestinal mucosa. Epithelial cells and primary neurons of the enteric nervous system were cultured on both sides of the transmissible membrane within the two different compartments. So the cells could be supplied with two different media. We kept a mono-culture of primary neurons or epithelial cells for 5 days and a co-culture between these two cell-types was established for 4 days. The proposed system delivers a sophisticated model for the simulation of various epithelial layers which takes the specific biological properties into account.

BMI-independent inverse relationship of plasma leptin levels with outcome in patients with acute pulmonary embolism.

OBJECTIVE: The adipocytokine leptin is an independent cardiovascular risk factor and exerts prothrombotic effects, both in arterial and venous thrombosis. We therefore investigated the relationship between leptin levels and clinical outcome in patients with acute pulmonary embolism (PE). DESIGN: We prospectively studied consecutive patients with confirmed acute PE admitted at the University Hospital of Goettingen (Germany) between 2003 and 2009. SUBJECTS: The study subjects were a total of 264 patients with PE (median age, 68 years; interquartile range, 53-75; 60% women; body mass index (BMI) 27 kg m(-2) (24.1-31.2)). Leptin levels were determined by a commercially available enzyme-linked immunosorbent assay. Patients were followed for an adverse 30-day outcome, that is, death, circulatory collapse with need for catecholamines, intubation or resuscitation, and for long-term survival. RESULTS: The median leptin level was 10.1 ng ml(-1) (3.7-25.2). Patients (n=49; 18.6%) with a complicated 30-day course had significantly lower leptin levels (5.3 ng ml(-1) (1.8-19.7) compared with patients without complications (10.4 ng ml(-1) (4.7-25.5), P=0.02). When leptin was analyzed as a continuous variable, there was a significant 36% increase in the relative risk for early complications for every decrease in the natural logarithm of leptin by one s.d. (odds ratio (OR) 1.36 (1.06-1.76), P=0.017), independently of BMI (BMI-adjusted OR, 1.52 (1.13-2.05), P=0.006). In addition, patients within the lowest leptin tertile had a 2.8- and 2.3-fold increased risk for 30-day-complications, compared with those in the middle (P=0.011) and high tertile (P=0.030), and a worse probability of long-term survival (log-rank; P=0.018). CONCLUSION: Low plasma leptin concentration is a predictor for a complicated course and high mortality in patients with acute PE. This association is independent of known factors affecting leptin levels, including gender and obesity.

Early specification of limb muscle precursor cells by the homeobox gene Lbx1h.

During vertebrate embryogenesis, myogenic precursor cells of limb muscles delaminate from the ventro-lateral edge of the somitic dermomyotome and migrate to the limb buds, where they congregate into dorsal and ventral muscle masses. It has been proposed that the surrounding connective tissue controls muscle pattern formation in limbs. Regulatory molecules such as receptor tyrosine kinases like c-Met ( ref. 6) and those encoded by homeobox-containing genes, including c-Met (ref. 6), Tbx1 (ref. 7), Mox2 (ref. 8), Six1 and Six2 (ref. 9), Pitx2, Pax3 (refs 10,11) and Lbx1h (refs 12,13), are expressed in migrating limb precursor cells. The role of these genes in the patterning of limb muscles is unknown, although mutation of Pax3 or Met causes disruption of limb muscle development at an initial step, disturbing the epithelial-to-mesenchymal transition of the somitic epithelium. No limb muscle cells form in these mutants, and the early loss of myogenic precursor cells prevented an analysis of later functions of these genes during limb muscle development. Based on quail-chick chimaera studies, it was assumed that a cell-autonomous contribution of myogenic cells to the formation of individual limb muscles is negligible, and that an instructive role of limb mesenchyme is critical in this process. Here we show that Lbx1h determines migratory routes of muscle precursor cells in a cell-autonomous manner, thereby leading to the formation of distinct limb muscle patterns. Inactivation of Lbx1h, which is specifically expressed in migrating muscle precursor cells, led to a lack of extensor muscles in forelimbs and an absence of muscles in hindlimbs. The defect was caused by the failure of all muscle precursor cells of hindlimbs and of precursor cells of extensor muscles of forelimbs to migrate to their corresponding muscle anlagen. Our results demonstrate that Lbx1h is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles.

Gastrointestinal involvement in Parkinson's disease: pathophysiology, diagnosis, and management.

Growing evidence suggests an increasing significance for the extent of gastrointestinal tract (GIT) dysfunction in Parkinson's disease (PD). Most patients suffer from GIT symptoms, including dysphagia, sialorrhea, bloating, nausea, vomiting, gastroparesis, and constipation during the disease course. The underlying pathomechanisms of this α-synucleinopathy play an important role in disease development and progression, i.e., early accumulation of Lewy pathology in the enteric and central nervous systems is implicated in pharyngeal discoordination, esophageal and gastric motility/peristalsis impairment, chronic pain, altered intestinal permeability and autonomic dysfunction of the colon, with subsequent constipation. Severe complications, including malnutrition, dehydration, insufficient drug effects, aspiration pneumonia, intestinal obstruction, and megacolon, frequently result in hospitalization. Sophisticated diagnostic tools are now available that permit more detailed examination of specific GIT impairment patterns. Furthermore, novel treatment approaches have been evaluated, although high-level evidence trials are often missing. Finally, the burgeoning literature devoted to the GIT microbiome reveals its importance for neurologists. We review current knowledge about GIT pathoanatomy, pathophysiology, diagnosis, and treatment in PD and provide recommendations for management in daily practice.

Characterization of surgical aerosols by the compact single-particle mass spectrometer LAMPAS 3.

A new method is presented using an optical particle counter and the compact mobile laser mass spectrometer LAMPAS 3 for in situ analysis of single particles generated by electrosurgical dissection of biological tissues. The instrumental performance is demonstrated for analysing aerosol particles formed during rapid thermal evaporation of porcine liver and porcine kidney tissues. Particle number concentrations of up to 5,000 particles per cubic centimetre were detected during surgical dissection. Chemical analysis of tissue particles was performed by bipolar time-of-flight mass spectrometry. The application of an online mass spectrometric particle analysis for surgical aerosols is reported here for the first time.

Phase measurement of resonant two-photon ionization in helium.

We study resonant two-color two-photon ionization of helium via the 1s3p (1)P(1) state. The first color is the 15th harmonic of a tunable Ti:sapphire laser, while the second color is the fundamental laser radiation. Our method uses phase-locked high-order harmonics to determine the phase of the two-photon process by interferometry. The measurement of the two-photon ionization phase variation as a function of detuning from the resonance and intensity of the dressing field allows us to determine the intensity dependence of the transition energy.

Attosecond electron spectroscopy using a novel interferometric pump-probe technique.

We present an interferometric pump-probe technique for the characterization of attosecond electron wave packets (WPs) that uses a free WP as a reference to measure a bound WP. We demonstrate our method by exciting helium atoms using an attosecond pulse (AP) with a bandwidth centered near the ionization threshold, thus creating both a bound and a free WP simultaneously. After a variable delay, the bound WP is ionized by a few-cycle infrared laser precisely synchronized to the original AP. By measuring the delay-dependent photoelectron spectrum we obtain an interferogram that contains both quantum beats as well as multipath interference. Analysis of the interferogram allows us to determine the bound WP components with a spectral resolution much better than the inverse of the AP duration.

[Cystic desmoplastic small round cell tumor: tumor development from cystic-"mesothelioblastic" areas?]. / Zystischer desmoplastischer klein- und rundzelliger Tumor: Tumorentwicklung aus zystisch-"mesothelioblastischen" Arealen?

A 7-cm cystic lesion in the upper left abdomen and additional smaller solid tumor nodules were diagnosed incidentally in a 15-year-old boy without tumor symptoms. The main tumorous cystic lesion showed a flattened single-cell tumor cell component in gradual transition to stratified, papillary and truly "invasive" typical desmoplastic areas of a desmoplastic small round-cell tumor (DSRCT). The Ki-67-proliferation index gradually increased within three histologic tumor patterns up to about 70% in the typical desmoplastic (infiltrating) component. Using microdissection techniques, EWS-WT1-gene fusion transcripts were detected in the cystic (single-cell-layered), the papillary and the solid tumor proliferations (exon 7 of EWS on chromosome 22 with exon 8 of WT1 on chromosome 11). The presented case illustrates a predominant cystic growth pattern of DSRCT, in which a stepwise development in the pathogenesis of DSRCT from cystic (-"mesothelioblastic") towards a more papillary proliferation and finally typical "infiltrative" desmoplastic tumor pattern might be discussed. The cystic pattern could represent an initial stage in the development of the neoplasia. The presence of specific EWS-WT1-gene fusion transcripts in all tumor growth patterns in this respect would indicate an early event in t(11;22)(p13;q12) translocation in the pathogenesis of DSRCT.

Hydrogen-helium mixtures at megabar pressures: implications for jupiter and saturn.

Models of Jupiter and Saturn postulate a central rock core surrounded by a fluid mixture of hydrogen and helium. These models suggest that the mixture is undergoing phase separation in Saturn but not Jupiter. State-of-the-art total energy calculations of the enthalpy of mixing for ordered alloys of hydrogen and helium confirm that at least partial phase separation has occurred in Saturn and predict that this process has also begun in Jupiter.

A practice-oriented method for the analysis of coplanar tetra- to heptachlorinated terphenyls.

Polychlorinated terphenyls (PCT) were produced and used on industrial scale in the last century. Today, PCT are formed especially during combustion and some chemical conversion processes. As being persistent, low volatile chlorinated aromatics, they are continuously emitted into the environment from primary and secondary sources. Blatant knowledge gaps exist concerning environmental behavior, toxicology, and ecotoxicology of this presumably ubiquitously present substance group because of the non-availability of a generally accepted, practice-oriented, and validated analytical method for the PCT. Here, a novel and easy to conduct analytical method is presented that is applicable to environmental samples. This method is based on a thorough clean-up of the sample extracts, followed by a separation of 29 tetra- to heptachlorinated coplanar reference congeners and their quantification by means of gas chromatography coupled with mass spectrometry. For the validation of the analytical procedure, the parameters selectivity, detection limit, limit of decision, limit of quantification, measuring and method precision, linearity, specifity, and recovery rates were considered. By the method validation, it was demonstrated that this novel procedure for the analysis of PCT in environmental samples like soils/sediments, fats, and combustion residues is fit for purpose.