Loneliness during the Covid-19 pandemic in Germany: Impact of social factors and polygenic risk scores on interpersonal differences in loneliness and mental health.

OBJECTIVES: The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. METHODS: From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. RESULTS: Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. CONCLUSION: As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures.

[Operational availability of ground-based emergency medical services in Rheinland-Palatinate: state-wide web-based system for collation, display and analysis]. / Verfügbarkeit bodengebundener Notarztstandorte in Rheinland-Pfalz : Landesweites webbasiertes Erfassungs-, Anzeige- und Auswerteinstrument.

BACKGROUND: A growing number of reports have been published in Germany related to problems with the operational readiness of mobile emergency physician services, although no systematic analyses have yet been presented. However, such investigations form the prerequisite for the deployment of countermeasures. METHODS: Rhineland-Palatinate (4,060,000 inhabitants, 7,753 mi(2)) is a typical territorial state in the southwest of Germany with extensive wooded areas covering 42% of the state and only few metropolitan areas. These basic conditions represent a challenge to the provision of state-wide emergency medical services (EMS). On behalf of the Ministry of the Interior a web-based platform for the collation, display and analysis of the operational readiness of all 68 ground-based physician-staffed emergency units within the state was developed. Of these units 61 are affiliated to hospitals and 7 units to medical practices and 89,000 emergency missions are carried out annually. RESULTS: Within the study period (April 2009-March 2010) 56 of the 68 units (82.4%) reported 1 or more periods of unavailability of operational readiness. In total 2,613 periods of temporary unavailability were documented with a mean duration of 8.9 h. The mean unavailability of operational readiness was 3.9% for the whole state, 6.2% for the northern and 1.6% for the southern EMS districts. In 7 of the units (10.3%) the degree of unavailability exceeded 5% and in 8 units (11.7%) it exceeded 10%. Two thirds of all suspended services were the result of shortages of emergency physicians, with considerably higher deficits at bases affiliated with hospitals of lower levels of care or in rural regions. CONCLUSIONS: This tool enables the large-scale collation and analysis of the operational readiness of physician-based ambulance services. Currently the state does not suffer from a general lack of emergency physicians. However, rural areas as well as bases affiliated with small hospitals show a considerable deficit in operational readiness caused by a shortage of staff. These deficits may be partially compensated by optimized planning and disposition within rescue coordination centers. Moreover, they call for corrective actions in the light of health care politics. In addition, analyses of other elements of EMS (i.e. rescue helicopters) should be undertaken.

Preliminary Findings Associate Hippocampal 1H-MR Spectroscopic Metabolite Concentrations with Psychotic and Manic Symptoms in Patients with Schizophrenia.

BACKGROUND AND PURPOSE: Previous hippocampal proton MR spectroscopic imaging distinguished patients with schizophrenia from controls by elevated Cr levels and significantly more variable NAA and Cho concentrations. This goal of this study was to ascertain whether this metabolic variability is associated with clinical features of the syndrome, possibly reflecting heterogeneous hippocampal pathologies and perhaps variability in its "positive" (psychotic) and "negative" (social and emotional deficits) symptoms. MATERIALS AND METHODS: In a sample of 15 patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, we examined the association of NAA and Cho levels with research diagnostic interviews and clinical symptom ratings of the patients. Metabolite concentrations were previously obtained with 3D proton MR spectroscopic imaging at 3T, a technique that facilitates complete coverage of this small, irregularly shaped, bilateral, temporal lobe structure. RESULTS: The patient cohort comprised 8 men and 7 women (mean age, 39.1 [SD, 10.8] years, with a mean disease duration of 17.2 [SD, 10.8] years. Despite the relatively modest cohort size, we found the following: 1) Elevated Cho levels predict the positive (psychotic, r = 0.590, P = .021) and manic (r = 0.686, P = .005) symptom severity; and 2) lower NAA levels trend toward negative symptoms (r = 0.484, P = .08). No clinical symptoms were associated with Cr level or hippocampal volume (all, P ≥ .055). CONCLUSIONS: These preliminary findings suggest that NAA and Cho variations reflect different pathophysiologic processes, consistent with microgliosis/astrogliosis and/or lower vitality (reduced NAA) and demyelination (elevated Cho). In particular, the active state-related symptoms, including psychosis and mania, were associated with demyelination. Consequently, their deviations from the means of healthy controls may be a marker that may benefit precision medicine in selection and monitoring of schizophrenia treatment.

On the mechanism of membrane damage by Staphylococcus aureus alpha-toxin.

Rabbit or human erythrocytes lysed with Staphylococcus aureus alpha-toxin were solubilized with Triton X-100, and the toxin was subsequently isolated by gel chromatography, sucrose density gradient centrifugation, and reincorporation into liposomes. In the presence of Triton X-100, the toxin exhibited a sedimentation coefficient of 11S and eluted at a position between those of IgG and alpha 2-macroglobulin in gel chromatography. A single polypeptide subunit of 34,000 mol wt was found in SDS PAGE. In the electron microscope, ring-shaped or cylindrical structures were observed, 8.5-10 nm in diameter, harboring central pits or channels 2-3 nm in diameter. An amphiphilic nature of these structures was evident from their capacity to bind lipid and detergent, aggregation in the absence of detergents, and low elutability from biological and artificial membranes through ionic manipulations. In contrast to the membrane-derived form of alpha-toxin, native toxin was a water-soluble, 34,000 mol wt, 3S molecule, devoid of an annular structure. Because studies on the release of radioactive markers from resealed erythrocyte ghosts indicated the presence of circumscribed lesions of approximately 3-nm effective diameter in toxin-treated membranes, the possibility is raised that native alpha-toxin oligomerizes on and in the membrane to form an amphiphilic annular complex that, through its partial embedment within the lipid bilayer, generates a discrete transmembrane channel.

Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study.

PURPOSE: To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. PATIENTS AND METHODS: Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0-1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. RESULTS: A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). CONCLUSIONS: The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.

Induction of pathogen resistance in barley by abiotic stress.

Enhanced resistance of barley (Hordeum vulgare L. cv. Ingrid) against barley powdery mildew (Blumeria graminis f. sp. hordei race A6) was induced by abiotic stress in a concentration-dependent manner. The papilla-mediated resistance was not only induced by osmotic stress, but also by proton stress. Resistance was directly correlated with increasing concentrations of various salts in the nutrient solution. Resistance induced by proton stress also depended on the stress intensity. Resistance induction occurred even at low stress intensities. Any specific ion toxicity affecting the fungal growth directly, and therefore leading to enhanced pathogen resistance, can be excluded because of the independence of resistance induction of the ion used and of the time course of sodium accumulation in the leaves. BCI-4, a marker for benzo[1,2,3]thiadiazolecarbothioic acid S-methyl ester (BTH)-induced resistance was not induced by these abiotic stresses. However, resistance was induced in the same concentration-dependent manner by the application of the stress hormone ABA to the root medium. During the relief of water stress, resistance did not decrease constantly. On the contrary, after a phase of decreasing resistance for 24 h the pathogen resistance increased again for 48 h before decreasing finally to control levels.

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours.

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).

Electrodecantation of serum proteins.

The sedimentation of albumin under the action of the electric and gravitational fields was determined as a function of time in discontinuous experiments in a rectangular cell, using serum with the albumin fraction stained blue. It was shown that even under the influence of strong electric fields, the upper boundary of the albumin layer fell no further than the mid-point of the cell. In continuous single-stage separation of gamma-globulin from other serum proteins, only about half the gamma-globulins can be obtained from the solution because it remains homogeneously distributed throughout the solution and is only free from albumin and other proteins in the upper half of the cell. In experiments with continuously operated triangular cells, the process was optimized to give gamma-globulin of 97.5% purity in a yield of 80%, at serum flow-through rates of up to 0.5 l/h in a block composed of 40 cells.

Improved methodology for the quantitative analysis of mixtures by band centrifugation: reversible equilibration in immunoglobulin preparations.

Double-sector aluminium centerpieces are modified for use in analytical high-speed band centrifugation up to 60,000 rpm. A method has been developed for testing IG preparations according to administrative regulations with special regard to precision and reproducibility. The proposed band-forming centrifugation method with scanner registration in UV absorption optics and special evaluation of the curves gives values in comparison to well-known procedures by Svedberg and Pedersen. Subjective and systematic errors are especially estimated with this method and the sensitivity is best suited to automatic computerization and results are therefore readily available at the end of the centrifuge run within a few minutes. Investigations have been undertaken to analyze reversible equilibration in immunoglobulin preparations; the results are discussed.

Gel chromatography for control purposes of human albumin preparations.

Information on molecular composition of human albumin preparations is important for characterization of these protein mixtures. Permeation chromatography in gel columns is best suited for separative analysis with respect to time consumption and experimental and instrumental expenditure. Standardization, precision and reproducibility of this quality control method have been especially considered in our investigations and the best conditions for practical performance and evaluation have been established. Results will be discussed in comparison to those of sedimentation analysis in the ultracentrifuge.

Gel chromatography applied to quantitation of components of IgG preparations.

Investigations were undertaken to standardize gel chromatography for quality control of IgG preparations. Great importance was attached to convenience of procedure. With application of the optimal type ofgel, Ultrogel AcA 34, the influence on quality of separation of various experimental parameters such as pH and ionic strength of the eluant, volume and concentration of the sample, flow rate and direction, and temperature were tested. Various methods of evaluation were applied. According to the demands, quantitation of components may be performed by collection of fractions and determination of peak volumes and protein concentrations, by determination of peak areas on absorbance recordings, or automatically by use of an integrator or a computer. The results obtained by gel chromatography are discussed and compared with the results of analytical ultracentrifugation.

Purification of oligomeric staphylococcal alpha-toxin by affinity chromatography on digitonin-sepharose.

An effective concentration of alpha-toxin from Staphylococcus aureus Wood 46, directly from the culture supernatant, could be achieved by adsorption on digitonin-sepharose and elution with 3 mol/l sodium thiocyanate (NaSCN). The toxin was further purified by gelchromatography. The purified product yielded 1 single protein band upon SDS-polyacrylamide electrophoresis. It was nonhemolytic, but reacted with anti-alpha-toxin under complement fixation. Dialysis against 0.14 mol/l NaCl with hydrophobic amino acids partially reactivated the alpha-hemolytic activity of the toxin. Ultracentrifugal analysis yielded sedimentation coefficients for the purified toxin of approximately 3,7 S when dissolved in 3 mol/l NaSCN and of about 12 S after dialysis against 0.14 mol/l NaCl (Table 1). The spontaneous oligomerization of the alpha-toxin during dialysis against 0.14 mol/l NaCl possibly resulted from a change in configuration induced by its adsorption to digitonin-sepharose.

Studies of the ligand binding to cholera toxin, I. The lipophilic moiety of sialoglycolipids.

The fixation of cholera toxin by ganglioside GGtet1 is dependent on the nature of the carbohydrate as well as the lipid moiety of the glycolipid. The role of the lipid in binding to the toxin investigated with synthetic ganglioside analogues (gangliosidoides). The interaction between glycolipid and toxin was followed by precipitate formation, by inhibition of toxicity and in polyacrylamide gel electrophoresis. For specific precipitation, an aliphatic hydrocarbon chain at least 14 C-atoms in length is required. Some of the gangliosidoides form high molecular weight complexes with cholera toxin at lower molar ratios of ligand to protein than the natural compound. None of the synthetic gangliosidoides equalled natural ganglioside in its ability to inhibit the effects of the toxin in vivo, but some did show considerable inhibitory activity ih monosialo-gangliotetraose or corresponding sialo-glycolipids prevents the easy degradation of the B-protein of cholera toxin into protein subunits by sodium dodecylsulfate.