[Reasons for Emergency Department Visits: Results of a Patient Survey]. / Beweggründe für die Inanspruchnahme von Notaufnahmen ­ Ergebnisse einer Patientenbefragung.

OBJECTIVES: The number of patients visiting emergency departments (ED) is steadily increasing. The cause for this rise in Germany is unclear and less examined. This study aimed to assess the reasons of walk-in patients to visit EDs by using a direct survey. METHODS: During a period of 4 weeks, 2 010 walk-in patients were anonymously surveyed in 2 major Berlin hospitals using a standardized questionnaire. Descriptive statistics were used for data analysis. RESULTS: More than 90% of patients assessed themselves as an emergency and three-quarters of patients reported pain. The majority of patients (57%) tried to contact statutory health insurance (SHI) office-based physicians in advance and 59% of patients said they would make use of ambulatory emergency facilities if they were available and well established. However, 55% of patients were unaware of the emergency service of the association of SHI physicians. CONCLUSION: The results indicate that centralized ambulatory emergency facilities should be available 24/7 at hospitals with EDs. Therefore, future planning of emergency services should integrate providers of ambulatory and inpatient sector. International experience suggests that different instruments aiming at better coordination of care, such as integrated call centers, extended ambulatory services and facilities for less urgent cases located in or nearby hospitals with EDs should also be implemented in Germany.

[Patients with Acute, Non-Traumatic Abdominal Pain in German Emergency Departments: A Prospective Monocentric Observation Study]. / Patienten mit akutem, nicht traumatischem Abdominalschmerz in der zentralen Notaufnahme ­ eine prospektive, monozentrische Beobachtungsstudie.

Background: Up to 11 % of patients in an Emergency Department (ED) present with non-traumatic acute abdominal pain. Based on this presenting symptom, this study aimed to analyse how residents (surgery, internal medicine, anaesthesiology and other fields) working in an ED during their second and third year of education treat these patients. Material and Methods: We performed a prospective, monocentric observation study in an ED in accordance with the STROBE recommendations, following the recommendations from the Ethics Committee of the University of Ulm (application no. 335/12) and the Declaration of Helsinki. The hospital's data protection officer approved the study. During a 12-month period (Dec. 2012 to Dec. 2013), a random sample of patients with non-traumatic abdominal pain was obtained in the ED of a major German acute care hospital by an independent observer, who was not part of the ED team. In addition to demographic data, the study focused on analysing processes and patient care (including medical history taking and physical examinations). In addition, subgroups were defined (clinical background of the treating physician, severity pursuant to the Manchester Triage Score [MTS]). Results: 143 patients met the inclusion criteria. The clinical background of the physician had no influence on the reviewed processes such as medical history taking, initial examinations, the request of consultative examinations or diagnostic procedures. Patients triaged as "urgent" were treated significantly earlier than patients triaged as "non-urgent" (time to first physician contact 26 ± 24 vs. 46 ± 34 min, p < 0.001). However, the overall time spent in the ED was equal (210 ± 79 vs. 220 ± 114 min, p = 0.555). Yet the initially estimated urgency was correlated with the need for hospitalisation (share: 57 %). Conclusion: The overall compliance with standards of care was high. The clinical background (surgery, internal medicine, anaesthesiology, other fields) of the physician in charge of initial treatment had no influence on the reviewed processes.

Hepatitis C virus infection and kidney transplantation in 2014: what's new?

Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.

Rapid point-of-care detection of SARS-CoV-2 infection in exhaled breath using ion mobility spectrometry: a pilot study.

BACKGROUND: An effective testing strategy is essential for pandemic control of the novel Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Breath gas analysis can expand the available toolbox for diagnostic tests by using a rapid, cost-beneficial, high-throughput point-of-care test. We conducted a bi-center clinical pilot study in Germany to evaluate breath gas analysis using multi-capillary column ion mobility spectrometry (MCC-IMS) to detect SARS-CoV-2 infection. METHODS: Between September 23, 2020, and June 11, 2021, breath gas measurements were performed on 380 patients (SARS-CoV-2 real-time polymerase chain reaction (PCR) positive: 186; PCR negative: 194) presenting to the emergency department (ED) with respiratory symptoms. RESULTS: Breath gas analysis using MCC-IMS identified 110 peaks; 54 showed statistically significant differences in peak intensity between the SARS-CoV-2 PCR-negative and PCR-positive groups. A decision tree analysis classification resulted in a sensitivity of 83% and specificity of 86%, but limited robustness to dataset changes. Modest values for the sensitivity (74%) and specificity (52%) were obtained using linear discriminant analysis. A systematic search for peaks led to a sensitivity of 77% and specificity of 67%; however, validation by transferability to other data is questionable. CONCLUSIONS: Despite identifying several peaks by MCC-IMS with significant differences in peak intensity between PCR-negative and PCR-positive samples, finding a classification system that allows reliable differentiation between the two groups proved to be difficult. However, with some modifications to the setup, breath gas analysis using MCC-IMS may be a useful diagnostic toolbox for SARS-CoV-2 infection. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on September 21, 2020 (NCT04556318; Study-ID: HC-N-H-2004).

Role of mannose-binding lectin-2 polymorphism in the development of acute cellular rejection after transplantation for hepatitis C virus-induced liver disease.

UNLABELLED: The development of liver and graft disease is suspected to be affected by genetic diversity. Mannose-binding lectin-2 (MBL-2) is an important immunomodulatory factor that is involved in complement activation. The aim of our study was to elucidate the role of MBL-2 genotypes after liver transplantation (LT) for hepatitis C virus (HCV)-induced liver disease regarding the incidence of acute cellular rejection (ACR), graft inflammation, fibrosis development, and antiviral treatment response. METHODS: A group of 149 patients who underwent LT for HCV-induced liver disease were genotyped for MBL-2 (rs7096206; G/C) by TaqMan genotyping assay. We evaluated 518 post-LT protocol biopsies and at least 98 urgent liver biopsies regarding graft fibrosis stages, inflammation grades, and evidence for rejection within MBL-2 genotype groups. RESULT: No association of MBL-2 polymorphisms was observed regarding inflammation, fibrosis, and antiviral treatment outcome. However, the C allele of the MBL-2 gene (P = 0.001) and gender compatibility (P = 0.012) were factors significantly associated with the incidence of ACR. CONCLUSION: MBL-2 polymorphisms and gender are involved in the development of ACR after LT. CC genotype and gender match may be regarded as risk factors for ACR in HCV-positive graft recipients. Further studies are needed to confirm and verify this observation in non-HCV groups as well.

Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: a case report and review of the literature.

OBJECTIVE: To report a case of an uncommon and up to date unpublished peracute and overwhelming muscle pain following administration of ciprofloxacin. CASE SUMMARY: A 58-year-old male developed fulminating musculoskeletal pain associated with third-time exposure to ciprofloxacin administered for treatment of chronic otitis media. Symptoms resolved slowly after intense combined analgetic therapy and cessation of ciprofloxacin therapy. 24 h after ciprofloxacin discontinuation the symptoms had completely disappeared and no more analgetic treatment was needed. Laboratory values, especially muscle enzymes, did not reveal any pathological pattern. The patient's past medical history highlighted reproducible side effects with both systemic and local administration of ciprofloxacin including milder symptoms of the musculoskeletal system. DISCUSSION: Common side effects of fluoroquinolones include gastrointestinal, central nervous and allergic reactions, but also more uncommon reactions such as tendonitis and rhabdomyolysis. In our case, there had been no signs of rhabdomyolysis. Besides an elevated IgE level no clinical signs of a true anaphylactic reaction associated with release of mast cell mediators had been observed. A pharmacokinetic interaction between ciprofloxacin and the patient's comedication carbamazepine is unlikely to be the responsible mechanism, since fluoroquinolones inhibit cytochrome P450 isoenzyme CYP1A2 but not CYP3A4 which metabolizes carbamazepine. CONCLUSION: To our knowledge, this is the first report describing fulminating musculoskeletal pain following administration of ciprofloxacin without any signs of rhabdomyolysis. Physicians should notice that there is a variety of adverse reactions of this usually well-tolerated agent and they should be aware of unusual complaints of their patients who receive fluoroquinolone treatment.

Relative efficacy of water use in five varieties of Abelmoschus esculentus (L.) Moench. under water-limited conditions.

In the present investigation, five varieties of okra (Abelmoschus esculentus (L.) Moench.) were screened for their water use efficiency under two water regimes, viz., 60% and 100% filed capacity. Drought stress was imposed at 60% field capacity from 30 to 70 days after sowing, while the control pots were maintained at 100% field capacity throughout the period of entire growth. Biomass and yield, leaf area duration, cumulative water transpired water use efficiency, net assimilation rate, mean transpiration rate and harvest index under water deficit level were measured. Water use efficiency significantly increases in all the okra varieties under water-limited environment. Drought stress decreased the biomass and yield, leaf area duration, cumulative water transpired, net assimilation rate, mean transpiration rate and harvest index in the okra varieties studied. But among the varieties, variety JK Haritha showed better results. None of the varieties studied had showed increased drought tolerance than the control.

Protection of Vigna unguiculata (L.) Walp. plants from salt stress by paclobutrazol.

A pot culture experiment was conducted to estimate the stress ameliorating ability of paclobutrazol, a triazole fungicide in Vigna unguiculata (L.) Walp. plants. Treatments were given as 80 mM NaCl, 80 mM NaCl+15 mg l(-1) paclobutrazol and 15 mg l(-1) paclobutrazol alone. The samples were collected on 60 and 80 days after sowing (DAS). NaCl stress inhibited the root and stem length, total leaf area, fresh weight (FW), dry weight (DW) and activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX). Plants treated with NaCl with paclobutrazol increased these parameters to a larger extent when compared to NaCl stressed plants. The results showed that the paclobutrazol significantly ameliorated the adverse effects of NaCl stress in V. unguiculata plants.

Mineral uptake and biochemical changes in Helianthus annuus under treatment with different sodium salts.

Experiments were conducted to study the effects of different sodium salts viz., sodium chloride (NaCl), sodium sulphate (Na(2)SO(4)) and sodium carbonate (Na(2)CO(3)) on growth, dry matter production, mineral contents, biochemical constituent and enzyme activities of sunflower (Helianthus annuus L.). The germinating sunflower seeds were treated with 10, 20 and 50mM NaCl and Na(2)SO(4) and 5, 10 and 15 mM Na(2)CO(3). The seedling growth, minerals, chlorophyll content and biochemicals like protein and free amino acid contents with enzyme activities like ATPase and protease were analysed on 8 DAS. The seedlings were separated into root, stem, leaf and cotyledon on 8 DAS. All the treatments decreased the germination percentage; shoot length, root length, leaf area and dry weight, chlorophyll and protein contents significantly. Potassium, sodium and free amino acid contents; activities of ATPase and protease were increased when compared to control. This effect was very high in the Na(2)CO(3) treated seedlings this was followed by Na(2)SO(4) and NaCl treated seedlings. From the results of this investigation, it is clear that, the sunflower seedlings were affected significantly in the Na(2)CO(3) treatments, and followed by Na(2)SO(4) and NaCl treatments.

A slow-cycling subpopulation of melanoma cells with highly invasive properties.

Melanoma is a heterogeneous tumor with different subpopulations showing different proliferation rates. Slow-cycling cells were previously identified in melanoma, but not fully biologically characterized. Using the label-retention method, we identified a subpopulation of slow-cycling cells, defined as label-retaining cells (LRC), with strong invasive properties. We demonstrate through live imaging that LRC are leaving the primary tumor mass at a very early stage and disseminate to peripheral organs. Through global proteome analyses, we identified the secreted protein SerpinE2/protease nexin-1 as causative for the highly invasive potential of LRC in melanomas.

Carbohydrate metabolism in Dioscorea esculenta (Lour.) Burk. tubers and Curcuma longa L. rhizomes during two phases of dormancy.

We have examined the changes in carbohydrate metabolism in food yam (Dioscorea esculenta (Lour.) Burk.) tubers and in an economically important spice cum medicinal plant turmeric (Curcuma longa L.) rhizomes under storage. Both specimens showed varied levels of dormancy and sprouting appeared at the end of dormant period. Harvested, fully matured tubers of yam and rhizomes of turmeric were stored in wooden boxes under the conditions of 28+/-2 degrees C temperature and 65-75% relative humidity (RH) in dark. The starch, sugars, enzymes of starch degradation, respiration, glycolysis, tricarboxylic acid (TCA) cycle and oxidative pentose phosphate pathway (PPP) were studied during 1-70 days after harvest (DAH). This investigation revealed that, the starch degradation and the enzymes involved, viz. alpha-amylases and starch phosphorylase showed a lower level of activity during early period of dormancy, while sugar content and enzymes of carbohydrate metabolism increased rapidly during sprouting. The isoenzymic profiles of alpha-amylases showed marked variations in these two phases. The key enzymes of glycolysis, TCA cycle and PPP, viz. aldolase, succinic dehydrogenase, malic dehydrogenase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were increased even before the visible appearance of sprouting and their activities were at their maximum during sprouting. Based of the observations the dormancy period may be distinctly divided into peak period of rest and presprouting period.

Growth, biochemical modifications and proline metabolism in Helianthus annuus L. as induced by drought stress.

In the present investigation, two watering treatments, viz., 100% and 60% field capacity (FC) were used to understand the effects of water deficit on early growth, biomass allocation, pigment and biochemical constituents and proline metabolism of five varieties of Sunflower (Helianthus annuus L.) plants. We found that there was a significant difference in early growth, dry matter accumulation, pigment, biochemical constituents and proline metabolism among the five varieties. The root length, shoot length, total leaf area, fresh and dry weight, chlorophyll a, b, total chlorophyll and carotenoid were significantly reduced under water stress treatments. Water stress increased the proline, free amino acid and glycinebetaine contents along with increased activity of gamma-glutamyl kinase but the activity of proline oxidase reduced as a consequence of water stress.

Alterations in osmoregulation, antioxidant enzymes and indole alkaloid levels in Catharanthus roseus exposed to water deficit.

Catharanthus roseus (L.) G. Don plants were grown in different water regimes in order to study the drought induced osmotic stress and proline (PRO) metabolism, antioxidative enzyme activities and indole alkaloid accumulation. The plants under pot culture were subjected to 10, 15 and 20 days interval drought (DID) stress from 30 days after sowing (DAS) and regular irrigation was kept as control. The plants were uprooted on 41DAS (10DID), 46DAS (15DID) and 51DAS (20DID). The drought stressed plants showed increased aminoacid (AA), glycine betaine (GB) and PRO contents and decreased proline oxidase (PROX) and increased gamma-glutamyl kinase (gamma-GK) activities when compared to control. The antioxidative enzymes like peroxidase (POX) and polyphenol oxidase (PPO) increased to a significant level in drought stressed plants when compared to control. The drought stressed C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to well-watered control plants. Our results suggest that the cultivation of medicinal plants like C. roseus in water deficit areas would increase its PRO metabolism, osmoregulation, defense system and the level of active principles.

Water deficit stress mitigation by calcium chloride in Catharanthus roseus: effects on oxidative stress, proline metabolism and indole alkaloid accumulation.

The present investigation was conducted to determine whether CaCl(2) increases Catharanthus roseus drought tolerance and if such tolerance is correlated with changes in oxidative stress, osmoregulation and indole alkaloid accumulation. C. roseus plants were grown under water deficit environments with or without CaCl(2). Drought induced oxidative stress was measured in terms of lipid peroxidation (LPO) and H(2)O(2) contents, osmolyte concentration, proline (PRO) metabolizing enzymes and indole alkaloid accumulation. The plants under pot culture were subjected to 10, 15 and 20 days interval drought (DID) stress and drought stress with 5mM CaCl(2) and 5mM CaCl(2) alone from 30 days after planting (DAP) and regular irrigation was kept as control. The plants were uprooted on 41 DAS (10 DID), 46 DAS (15 DID) and 51 DAS (20 DID). Drought stressed plants showed increased LPO, H(2)O(2), glycine betaine (GB) and PRO contents and decreased proline oxidase (PROX) activity and increased gamma-glutamyl kinase (gamma-GK) activity when compared to control. Addition of CaCl(2) to drought stressed plants lowered the PRO concentration by increasing the level of PROX and decreasing the gamma-GK activities. Calcium ions increased the GB contents. CaCl(2) appears to confer greater osmoprotection by the additive role with drought in GB accumulation. The drought with CaCl(2)-treated C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to drought stressed and well-watered plants.

Induction of drought stress tolerance by ketoconazole in Catharanthus roseus is mediated by enhanced antioxidant potentials and secondary metabolite accumulation.

A pot culture experiment was conducted to estimate the drought stress mitigating effect of ketoconazole (KCZ), a fungicide cum plant growth regulator, in Catharanthus roseus plants. The plants under pot culture were subjected to drought stress and drought stress with KCZ from 30 days after sowing (DAS) and regular irrigation was kept as control. Antioxidant contents and activities of antioxidant enzymes were estimated from root, stem and leaf of both control and treated plants. The alkaloid ajmalicine was extracted and estimated from the roots of control, drought stressed and KCZ treated plants. Individual and combined drought stress and KCZ treatments increased ascorbic acid, alpha-tocopherol contents, superoxide dismutase, ascorbate peroxidase, catalase and polyphenol oxidase activities when compared to control. There was a significant enhancement in ajmalicine production under KCZ treated plants under drought stress when compared to well watered control as well as drought stressed plants. The KCZ treatment resulted in partial mitigation of drought stress by increasing the antioxidant potentials in C. roseus plants.

Pseudomonas fluorescens enhances biomass yield and ajmalicine production in Catharanthus roseus under water deficit stress.

The effect of plant growth promoting rhizobacteria (PGPR) like Pseudomonas fluorescens on growth parameters and the production of ajmalicine were investigated in Catharanthus roseus under drought stress. The plants under pot culture were subjected to 10, 15 and 20 days interval drought (DID) stress and drought stress with Pseudomonas fluorescens at 1mgl(-1) and 1mgl(-1)Pseudomonas fluorescens alone from 30 days after planting (DAP) and regular irrigation was kept as control. The plants were uprooted on 41 DAS (10 DID), 46 DAS (15 DID) and 51 DAS (20 DID). Drought stress decreased the growth parameters and increased the ajmalicine content. But the treatment with Pseudomonas fluorescens enhanced the growth parameters under drought stress and partially ameliorated the drought induced growth inhibition by increasing the fresh and dry weights significantly. The ajmalicine content was again increased due to Pseudomonas fluorescens treatment to the drought stressed plants. From the results of this investigation, it can be concluded that, the seedling treatments of native PGPRs can be used as a good tool in the enhancement of biomass yield and alkaloid contents in medicinal plants, as it provides an eco-friendly approach and can be used as an agent in water deficit stress amelioration.

Changes in antioxidant metabolism of Vigna unguiculata (L.) Walp. by propiconazole under water deficit stress.

In the present study, a pot culture experiment was conducted to estimate the ameliorating effect of propiconazole (PCZ) on drought stress in cowpea (Vigna unguiculata (L.) Walp.) plants. From 30 days after sowing (DAS), the plants were subjected to 3, 6 and 9 days interval drought (DID) stress and drought stress with PCZ at 15 and 15 mg l(-1) PCZ alone and 1 day interval irrigation was kept as control. The plant samples were collected on 34 DAS (3 DID), 37 DAS (6 DID) and 40 DAS (9 DID). The plants were separated into root, stem and leaf for estimating the antioxidant contents and activities of antioxidant enzymes. Individual and combined drought stress and PCZ treatments increased ascorbic acid (AA), alpha-tocopherol (alpha-toc) contents, superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and polyphenol oxidase (PPO) activities when compared to control. The PCZ treatment mitigated the adverse effects of drought stress by increasing the antioxidant potentials and thereby paved the way for overcoming drought stress in V. unguiculata plants.

Effect of paclobutrazol on water stress amelioration through antioxidants and free radical scavenging enzymes in Arachis hypogaea L.

An investigation was carried out to find out the extent of changes occurred in groundnut (Arachis hypogaea L.) cultivars in response to paclobutrazol (PBZ) treatment under water deficit stress. Two groundnut cultivars namely ICG 221 and ICG 476 were used for the study. Individual treatment with PBZ and drought stress showed an increase in ascorbic acid, alpha-tocopherol and reduced glutathione, superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) activities. PBZ with drought stressed plants maintained higher levels of antioxidant and scavenging enzymes. Significant differences were observed between cultivars and treatments. These results suggests that the adverse effects of water stress can be minimized by the application of PBZ by increasing the antioxidant levels and activities of scavenging enzymes such as SOD, APX and CAT. The Cv. ICG 221 appears to be more tolerant to water stress than the ICG 476.

A stress-induced early innate response causes multidrug tolerance in melanoma.

Acquired drug resistance constitutes a major challenge for effective cancer therapies with melanoma being no exception. The dynamics leading to permanent resistance are poorly understood but are important to design better treatments. Here we show that drug exposure, hypoxia or nutrient starvation leads to an early innate cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells (IDTCs). Transition into the IDTC state seems to be an inherent stress reaction for survival toward unfavorable environmental conditions or drug exposure. The response comprises chromatin remodeling, activation of signaling cascades and markers implicated in cancer stemness with higher angiogenic potential and tumorigenicity. These changes are characterized by a common increase in CD271 expression concomitantly with loss of differentiation markers such as melan-A and tyrosinase, enhanced aldehyde dehydrogenase (ALDH) activity and upregulation of histone demethylases. Accordingly, IDTCs show a loss of H3K4me3, H3K27me3 and gain of H3K9me3 suggesting activation and repression of differential genes. Drug holidays at the IDTC state allow for reversion into parental cells re-sensitizing them to the drug they were primarily exposed to. However, upon continuous drug exposure IDTCs eventually transform into permanent and irreversible drug-resistant cells. Knockdown of CD271 or KDM5B decreases transition into the IDTC state substantially but does not prevent it. Targeting IDTCs would be crucial for sustainable disease management and prevention of acquired drug resistance.