Glycogen, poly(3-hydroxybutyrate) and pigment accumulation in three Synechocystis strains when exposed to a stepwise increasing salt stress.

The cyanobacterial genus Synechocystis is of particular interest to science and industry because of its efficient phototrophic metabolism, its accumulation of the polymer poly(3-hydroxybutyrate) (PHB) and its ability to withstand or adapt to adverse growing conditions. One such condition is the increased salinity that can be caused by recycled or brackish water used in cultivation. While overall reduced growth is expected in response to salt stress, other metabolic responses relevant to the efficiency of phototrophic production of biomass or PHB (or both) have been experimentally observed in three Synechocystis strains at stepwise increasing salt concentrations. In response to recent reports on metabolic strategies to increase stress tolerance of heterotrophic and phototrophic bacteria, we focused particularly on the stress-induced response of Synechocystis strains in terms of PHB, glycogen and photoactive pigment dynamics. Of the three strains studied, the strain Synechocystis cf. salina CCALA192 proved to be the most tolerant to salt stress. In addition, this strain showed the highest PHB accumulation. All the three strains accumulated more PHB with increasing salinity, to the point where their photosystems were strongly inhibited and they could no longer produce enough energy to synthesize more PHB.

Negligible risk of prenatal ductus arteriosus closure or fetal renal impairment after third-trimester paracetamol use: evaluation of the German Embryotox cohort.

OBJECTIVE: Risk of fetotoxicity after paracetamol exposure in the third trimester. DESIGN: Observational cohort study and retrospective case assessment. SETTING: Germany, 2008-2017. POPULATION: Pregnant women exposed to paracetamol. METHODS: Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. MAIN OUTCOME MEASURES: The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. RESULTS: In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. CONCLUSIONS: Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. TWEETABLE ABSTRACT: Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.

Cyanobacteria Biorefinery - Production of poly(3-hydroxybutyrate) with Synechocystis salina and utilisation of residual biomass.

This study evaluates a biorefinery concept for producing poly(3-hydroxybutyrate) (PHB) with the cyanobacterial strain Synechocystis salina. Due to this reason, pigment extraction and cell disruption were investigated as pre-treatment steps for the harvested cyanobacterial biomass. The results demonstrated that at least pigment removal was necessary to obtain PHB with processable quality (weight average molecular weight: 569-988kgmol-1, melting temperature: 177-182°C), which was comparable to heterotrophically produced PHB. The removed pigments could be utilised as additional by-products (chlorophylls 0.27-1.98mgg-1 TS, carotenoids 0.21-1.51mgg-1 TS, phycocyanin 0-127mgg-1 TS), whose concentration depended on the used nutrient source. Since the residual biomass still contained proteins (242mgg-1 TS), carbohydrates (6.1mgg-1 TS) and lipids (14mgg-1 TS), it could be used as animal feed or converted to biomethane (348 mn3 t-1VS) and fertiliser. The obtained results indicate that the combination of photoautotrophic PHB production with pigment extraction and utilisation of residual biomass offer the highest potential, since it contributes to decrease the environmental footprint of the process and because biomass could be used in a cascading way and the nutrient cycle could be closed.

Processing recommendations for using low-solids digestate as nutrient solution for poly-ß-hydroxybutyrate production with Synechocystis salina.

Within the last decades, environmental pollution with persistent plastics steadily increased; therefore the production of biodegradable materials like poly-ß-hydroxybutyrate (PHB) is essential. Currently, PHB is produced with heterotrophic bacteria from crops. This leads to competition with food and feed production, which can be avoided by using photoautotrophic cyanobacteria, as Synechocystis salina, synthesizing PHB from CO2 at nutrient limitation. This study aims to increase the economic efficiency of PHB production with cyanobacteria by using nutrients from anaerobic digestate. First, growth and PHB production of S. salina in digestate fractions (supernatant and permeate, with/without precipitating agents) and dilutions thereof and then the scale-up (photobioreactor, 200 L working volume) were evaluated. With precipitated and centrifuged digestate diluted 1/3 the highest biomass (1.55gL-1) and PHB concentrations (95.4mgL-1), being 78% of those in mineral media, were achieved. In the photobioreactor-experiments biomass (1.63gL-1) and PHB concentrations (88.7mgL-1), being 79% and 72% of those in mineral medium, were reached, but in a cultivation time 10days longer than in mineral medium. The possibility to use digestate as sustainable and low cost nutrient solution for microalgae cultivation and photoautotrophic PHB production, instead of applying it on fields or processing it to achieve discharge limits, makes this application a highly valid option.

Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in women at suspected risk for thromboembolic events: a case series from the German Embryotox Pharmacovigilance Centre.

BACKGROUND: New oral anticoagulants are increasingly used in women of childbearing age, but apart from one case report there is no published experience with rivaroxaban exposure during pregnancy. METHODS: From October 2008 to December 2014, the German Embryotox Pharmacovigilance Centre identified 63 exposed pregnancies among 94 requests concerning rivaroxaban use during childbearing age. Follow-up included paediatric checks until 6 weeks after birth. RESULTS: All pregnancies with completed follow-up were exposed at least during the first trimester. Treatment indications included venous thromboembolism, knee surgery, and atrial fibrillation. 37 pregnancies were prospectively ascertained and resulted in six spontaneous abortions, eight elective terminations of pregnancy, and 23 live births. All women had discontinued rivaroxaban after recognition of pregnancy, mostly in the first trimester, but in one woman treatment continued until gestational week 26. There was one major malformation (conotruncal cardiac defect) among the 37 prospectively ascertained pregnancies in a woman with complex medication and a previous foetus with cardiac malformation without exposure to rivaroxaban. Only one case of bleeding concerning a retrospective report of surgery for missed abortion was observed in our case series. CONCLUSION: Our results might give reassurance to those women, who were inadvertently exposed to rivaroxaban in early pregnancy. However, our limited cohort size does not allow ruling out an increased malformation risk and does not support the use of rivaroxaban during pregnancy. In all cases of (inadvertent) rivaroxaban exposure during 1st trimester, anticoagulation regimen should be reconsidered and a detailed ultrasound assessment recommended to confirm normal foetal development.

Anaerobic digestion of stillage fractions - estimation of the potential for energy recovery in bioethanol plants.

Stillage processing can require more than one third of the thermal energy demand of a dry-grind bioethanol production plant. Therefore, for every stillage fraction occurring in stillage processing the potential of energy recovery by anaerobic digestion (AD) was estimated. In the case of whole stillage up to 128% of the thermal energy demand in the process can be provided, so even an energetically self-sufficient bioethanol production process is possible. For wet cake the recovery potential of thermal energy is 57%, for thin stillage 41%, for syrup 40% and for the evaporation condensate 2.5%. Specific issues for establishing AD of stillage fractions are evaluated in detail; these are high nitrogen concentrations, digestate treatment and trace element supply. If animal feed is co-produced at the bioethanol plant and digestate fractions are to be reused as process water, a sufficient quality is necessary. Most interesting stillage fractions as substrates for AD are whole stillage, thin stillage and the evaporation condensate. For these fractions process details are presented.

[Further development and validation of a clinical auditing procedure for rehabilitation facilities]. / Weiterentwicklung und Validierung eines Verfahrens zur Visitation von Rehabilitationseinrichtungen.

Visitations (audits) are considered an instrument of external quality assurance by which the structural and organizational set-up of health facilities can be assessed on site by external experts. The Deutsche Rentenversicherung Bund (including the former Bundesversicherungsanstalt für Angestellte, BfA, the statutory pension insurance agency for white collar employees) is the largest body responsible for rehabilitation in Germany, and it regularly carries out visitations in the approximately 650 rehab centres it sends its patients to. The project presented in this article aimed at developing a manual with detailed descriptions of the procedures and criteria of the assessment, as well as at checking the inter-rater-reliability of the assessment. The manual was developed in cooperation with experts of the Deutsche Rentenversicherung Bund. It contains a description of the areas to be assessed during a visitation as well as leading questions and criteria for the evaluation of single features. The manual was examined in "test visitations" in 10 centres, each of which was visited by three visitation teams (1 medical and 1 administrative expert) simultaneously. When the resulting 30 assessments were compared, the criterion "overall quality of the centre" (which was assessed on a 10-point scale) showed precise agreement in 47 %, and a deviation by 1 point in 33 % of the cases. Single features assessed on a three-point scale (no improvement needed/improvement recommended/immediate improvement obligatory) resulted in precise agreement in between 80 % ("medical and therapeutic processes") and 86 % ("structural features") of the cases. Two-point scales (condition fulfilled or not fulfilled) showed an agreement between 89 % ("internal quality management") and 97 % ("single structural features"). In order to maintain and further develop this good inter-rater-reliability, the visitors of Deutsche Rentenversicherung Bund are continually trained in applying the visitation manual. In addition to transferring knowledge, these internal training courses are aimed at exchanging views and experience in order to enhance consensus among the visitors. This approach of Deutsche Rentenversicherung Bund could be regarded as "internal quality assurance" of its visitation procedure.

[Job satisfaction in rehabilitation clinics--Development of the "MiZu-Reha" questionnaire and its use in quality assurance]. / Mitarbeiterzufriedenheit in Rehabilitationskliniken: Entwicklung des MiZu-Reha-Fragebogens und Anwendung in der Qualitätssicherung.

In this study, we report on the development and validation of a questionnaire measuring job satisfaction in rehabilitation centres. The questionnaire "Fragebogen zur Mitarbeiterzufriedenheit in Rehabilitationskliniken" ("MiZu-Reha") consists of 75 items. Three scales measure work climate, leadership and work organisation/communication. Further items assess weak points of work organisation and job satisfaction with several predefined aspects (e. g., career opportunities and salary). The scales have good internal consistency with Cronbach's alpha between 0.86 and 0.94. The dimensionality of the scales was established by confirmatory factor analyses. Correlations between the MiZu-Reha scales and independent satisfaction measures indicate the validity of the questionnaire. Correlations between the MiZu-Reha scales and indicators of patient satisfaction, process quality and outcome are in all cases positive (the higher the job satisfaction, the better the quality of rehabilitation), though weak and statistically not significant. Rehabilitation centres differ clearly from each other regarding job satisfaction of their employees. This shows the usefulness of clinic comparisons based on the MiZu-Reha. The questionnaire can be utilized in external quality assurance programmes, in the context of internal quality assurance measures (e. g. the Business Excellence Model of the European Foundation of Quality Management, EFQM) and in the use of management instruments such as the Balanced Scorecard.

[Effects of treatment in mother-child rehabilitation centres]. / Behandlungseffekte in Mutter-Kind-Einrichtungen - Ergebnisse des externen Qualitätsmanagements.

Effects of Treatment in Mother-Child Rehabilitation Centres. The study aims at an external evaluation of mother-child rehabilitation centres in Germany. The centres taking part in the project will get detailed information about their present state of quality in the dimensions of structure, process and outcome as well as patient satisfaction and job satisfaction of the employees. This article focuses on quality of outcome. Two main questions are addressed: How do women treated in mother-child rehabilitation centres assess their health problems at admission, and what are the effects after three weeks of inpatient treatment? The results show that in comparison with a German norm population, 55 % to 75 % of the women in the present study reported intense distress in all dimensions of health (somatic, functional and psychosocial). The analysis of effects after treatment confirms a distinct improvement of health status reported by patients as well as by doctors and therapists. Data of a follow-up after 6 months will show whether these positive effects can be maintained.

The effects of kanamycin injection into the fetal lamb cochlea.

Mammalian auditory hair cells have minimal capacity for repair or regeneration after a variety of insults, including acoustic trauma and aminoglycoside exposure. Although fetal tissues have a greater potential for repair and regeneration than adult tissues, there have been no reported studies on fetal hair cell response to injury in mammals. The purpose of this research was to investigate the effects of local application of kanamycin on fetal lamb cochlear hair cells. Eleven fetal lambs in the early third trimester underwent kanamycin injection through the left round-window membrane. The right ear served as a control. Click-evoked compound action potentials (CAPs) were serially recorded in 8 fetuses. CAPs were observed in all control ears. None of the 8 kanamycin-injected ears had measurable CAPs on postoperative day 1. One kanamycin-injected ear demonstrated definite CAPs, beginning on postoperative day 6. Hair cells were found to be intact in 6 of 9 kanamycin-treated ears. Hair cells were missing only in animals that went into premature labor. The presence of intact hair cells despite the loss of measurable CAPs in kanamycin-perfused lamb cochleae was striking. This finding may indicate that the fetal auditory epithelium is relatively resistant to aminoglycoside injury or may be capable of prompt repair or regeneration. Further studies on the effects of aminoglycoside injury in the fetal cochleae seem to be warranted.

[The treatment history of patients with borderline personality disorder in the Republic of Germany]. / Zur Behandlungsgeschichte und Versorgungssituation von Patientinnen mit Borderline-Persönlichkeitsstörung in der Bundesrepublik Deutschland.

The present study was undertaken to explore the treatment history of women with borderline personality disorder and to provide an estimation of the treatment costs. Using a semi-structured interview, forty-five carefully diagnosed patients were interrogated about their lifetime treatment history with respect to every inpatient and outpatient treatment received for any psychical symptoms, including physical treatment after self-injurious behaviour. Results demonstrate an extensive and protracted use of psychiatric, psychotherapeutic and physical help, and a chaotic course of treatment with discontinuance of treatments as a characteristic feature. Treatment costs were estimated at a minimum of 24,000 DM per year and patient; 22,000 DM due to hospitalisations. The unsatisfactory treatment situation for these patients in the public health system and the socioeconomic advantages of a specified treatment programme are discussed.

Fetal sheep in utero hear through bone conduction.

PURPOSE: Although the air-conduction pathway is the principal mode of sound transmission to the inner ear, this may not be true for the fetus in utero. The fetus detects and responds to sounds in the maternal environment. Exogenous sounds can reach the fetal inner ear through the ear canal and middle ear system, bone conduction, or both. This study was designed to compare the effectiveness of these two routes of sound transmission by recording cochlear microphonic potentials from the fetus in utero in response to airborne sounds. MATERIALS AND METHODS: Cochlear microphonics (CMs) recorded from one round window (RW) of fetal sheep in utero were obtained in three conditions: (1) head uncovered; (2) head covered with a neoprene hood; and (3) head covered with a neoprene hood fashioned with a hole that permitted the pinna and ear canal to be exposed. Tone bursts (0.5, 1.0, and 2.0 kHz) were delivered through a loudspeaker at high intensities (100 to 135 dB sound pressure level) to the flank of the ewe. CMs were detected with indwelling electrodes, amplified, and averaged. CM input-output functions were obtained from the fetus in each of the three conditions described above. RESULTS: CMs recorded with the head uncovered were more sensitive than were the CMs recorded with the hood in place. There was no difference in sensitivity between the condition during which the head was completely covered and the condition in which the pinna and ear canal are exposed. CONCLUSION: The principal mode of sound transmission into the fetal inner ear is through bone conduction.

Prostaglandin production in response to angiotensin-(1-7) in rabbit isolated vasa deferentia.

Angiotensin-(1-7) is a predominant metabolite of angiotensin I in brain tissue. Its neuromodulatory and prostaglandin (PG) synthesizing capabilities were investigated in the rabbit isolated vas deferens. This metabolite had no significant effect as a neuromodulator, however it increased PGE synthesis in the vasa deferentia with a potency equivalent to that of angiotensin II. The angiotensin-(1-7) has a unique spectrum of activity among the angiotensin peptides to selectively increase PG synthesis. It could be useful in defining the relevance of angiotensin-induced PG synthesis in various systems, particularly in neuronal tissue. Angiotensin-(1-7) potentially could be useful in defining angiotensin receptor subtypes, as well.