The roles of nitrification and nitrate reduction pathways in nitrogen cycling of Baltic Sea

The Baltic Sea is one of the largest brackish water bodies in the world. Primary production in the Baltic Sea is limited by nitrogen (N) availability with the exception of river outlets and the northernmost phosphorus limited basin. The excess human induced N load from the drainage basin has caused severe eutrophication of the sea. The excess N loads can be mitigated by microbe mediated natural N removal processes that are found in the oxic-anoxic interfaces in sediments and water column redoxclines. Such interfaces allow the close coupling between the oxic nitrification process, and anoxic denitrification and anaerobic ammonium oxidation (anammox) processes that lead to the formation of molecular nitrogen gas. These processes are governed by various environmental parameters. The effects of these parameters on N processes were investigated in the northern Baltic Sea sediments. During summer months when the sediment organic content is at its highest, nitrification and denitrification reach their maximum rates. However, nitrification had no excess potential, which was probably because of high competition for molecular oxygen (O2) between heterotrophic and nitrification microbes. Subsequently, the limited nitrate (NO3-) availability inhibited denitrification. In fall, winter and spring, nitrification was limited by ammonium availability and denitrification limited by the availability of organic carbon and occasionally by NO3-. Anaerobic ammonium oxidation (anammox) was not an important N removal process in the northern Baltic Sea. Modeling studies suggest that when hypoxia expands in the Baltic Sea, N removal intensifies. However, the results of this study suggest the opposite because bottom water hypoxia (O2< 2 ml l-1) decreased the denitrification rates in sediments. Moreover, N was recycled by the dissimilatory nitrate reduction to ammonium (DNRA) process instead of being removed from the water ecosystem. High N removal potentials were found in the anoxic water column in the deep basins of the Baltic Proper. However, the N removal in the water column appeared to be limited by low substrate availability, because the water at the depths at which the substrate producing nitrification process occurred, rarely mix with the water at the depths at which N removal processes were found. Overall, the natural N removal capacity of the northern Baltic Sea decreased compared to values measured in mid 1990s and early 2000. The reason for this appears to be increasing hypoxia.Rehevöitynyt Itämeri- Typpiravinteiden poistokyky Suomenlahdella on heikentynyt Itämeri on yksi maailman rehevöityneimmistä meristä. Rehevöityminen ilmenee vuotuisina laajoina sinileväkukintoina ja pohjan happikatona. Yksi tärkeimmistä rehevöitymistä aiheuttavista tekijöistä on valuma-alueelta tuleva liiallinen typpiravinteiden määrä. Typpiravinteiden rehevöittävän vaikutuksen on ajateltu vähenevän luonnollisesti meren mikrobiprosesseissa. Julkaistavan väitöstutkimuksen tulokset kuitenkin osoittavat, että Suomenlahdella luonnollisen typenpoiston merkitys on vähäinen. Lisäksi tulokset vahvistavat typpikuormituksen vähentämisen tarpeellisuutta rehevöitymisen ehkäisyssä. Väitöstutkimuksessa selvitettiin typpeä poistavien mikrobiprosesseiden merkitystä ja niitä sääteleviä tekijöitä Suomenlahdella ja eteläisellä Itämerellä. Tutkimuksen tulokset osoittivat, että pohjasedimentin luonnollinen typenpoistokyky Suomenlahdella vaihtelee huomattavasti vuodenajoittain ja on pienimmillään keväällä, jolloin typpikuormitus valuma-alueelta on suurinta. Yhdeksänkymmentäluvun puolivälissä, jolloin Suomenlahden pohjan happitilanne oli nykyistä parempi, luonnollinen typenpoisto vähensi noin kolmanneksen maalta tulevasta typpikuormasta. Tällä hetkellä typpikuormasta poistuu luonnollisesti vain noin kymmenesosa. Tutkimuksessa osoitettiin rehevöitymisestä aiheutuvan pohjan happikadon pienentävän luonnollista typenpoistokykyä ja kiihdyttävän typen varastoitumista pohjasedimentteihin. Tämä johtaa rehevöitymisen noidankehään, jossa rehevöitymisestä aiheutunut hapettomuus lisää typen saatavuutta kasviplanktonille kiihdyttäen niiden kasvua. Hajotessaan lisääntynyt kasviplankton taas kuluttaa happea lisäten pohjien hapettomuutta. Vastaava mekanismi fosforiravinteen suhteen osoitettiin jo 40-luvun alkupuolella. Luonnollista typenpoistoa tutkittiin myös eteläisen Itämeren hapettomissa syvänteissä. Mittaukset osoittivat, että Itämeren syvänteiden hapettomassa vedessä on huomattava typenpoistopotentiaali, mutta potentiaali toteutuu vain kun syvänteiden hapelliset ja hapettomat vesimassat sekoittuvat keskenään. Jotta typenpoiston merkitys vedessä pystyttäisiin selvittämään tarkasti, vesimassojen sekoittumista säätelevät fysikaaliset prosessit pitäisi tuntea paremmin

Nitrification and the ammonia-oxidizing communities in the central Baltic Sea water column

The redoxclines that form between the oxic and anoxic water layers in the central Baltic Sea are sites of intensive nitrogen cycling. To gain better understanding of nitrification, we measured the biogeochemical properties along with potential nitrification rates and analyzed the assemblages of ammonia oxidizing bacteria and archaea using functional gene microarrays. To estimate nitrification in the entire water column, we constructed a regression model for the nitrification rates and applied it to the conditions prevailing in the area in 2008-2012. The highest ammonia oxidation rates were found in a thin layer at the top of the redoxcline and the rates quickly decreased below detection limit when oxygen was exhausted. This is probably because extensive suboxic layers, which are known to harbor pelagic nitrification, are formed only for short periods after inflows in the Baltic Sea. The nitrification rates were some of the highest measured in the water columns, but the thickness of the layer where conditions were favorable for nitrification, was very small and it remained fairly stable between years. However, the depth of the nitrification layer varied substantially between years, particularly in the eastern Gotland Basin (EGB) due to turbulence in the water column. The ammonia oxidizer communities clustered differently between the eastern and western Gotland Basin (WGB) and the composition of ammonia oxidizing assemblages correlated with the environmental variables. The ammonia oxidizer community composition was more even in the EGB, which may be related to physical instability of the redoxcline that does not allow predominance of a single archetype, whereas in the WGB, where the position of the redoxcline is more constant, the ammonia-oxidizing community was less even. Overall the ammonia oxidizing communities in the Baltic Sea redoxclines were very evenly distributed compared to other marine environments where microarrays have been applied previously. (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

Frequency, indications and success of out-of-hospital intubations in Finnish children

Background Earlier studies have shown variable results regarding the success of paediatric emergency endotracheal intubation between different settings and operators. We aimed to describe the paediatric population intubated by physician-staffed helicopter emergency medical service (HEMS) and evaluate the factors associated with overall and first-pass success (FPS). Methods We conducted a retrospective observational cohort study in Finland including all children less than 16 years old who required endotracheal intubation by a HEMS physician from January 2014 to August 2019. Utilising a national HEMS database, we analysed the incidence, indications, overall and first-pass success rates of endotracheal intubation. Results A total of 2731 children were encountered by HEMS, and intubation was attempted in 245 (9%); of these, 22 were younger than 1 year, 103 were aged 1-5 years and 120 were aged 6-15 years. The most common indications for airway management were cardiac arrest for the youngest age group, neurological reasons (e.g., seizures) for those aged 1-5 years and trauma for those aged 6-15. The HEMS physicians had an overall success rate of 100% (95% CI: 98-100) and an FPS rate of 86% (95% CI: 82-90). The FPS rate was lower in the youngest age group (p = .002) and for patients in cardiac arrest (p < .001). Conclusions Emergency endotracheal intubation of children is successfully performed by a physician staffed HEMS unit even though these procedures are rare. To improve the care, emphasis should be on airway management of infants and patients in cardiac arrest.Peer reviewe

Association between case volume and mortality in pre-hospital anaesthesia management: a retrospective observational cohort

Background: Pre-hospital anaesthesia is a core competency of helicopter emergency medical services (HEMS). Whether physician pre-hospital anaesthesia case volume affects outcomes is unknown in this setting. We aimed to investigate whether physician case volume was associated with differences in mortality or medical management. Methods: We conducted a registry-based cohort study of patients undergoing drug-facilitated intubation by HEMS physician from January 1, 2013 to August 31, 2019. The primary outcome was 30-day mortality, analysed using multivariate logistic regression controlling for patient-dependent variables. Case volume for each patient was determined by the number of pre-hospital anaesthetics the attending physician had managed in the previous 12 months. The explanatory variable was physician case volume grouped by low (0-12), intermediate (13-36), and high (>= 37) case volume. Secondary outcomes were characteristics of medical management, including the incidence of hypoxaemia and hypotension. Results: In 4818 patients, the physician case volume was 511, 2033, and 2274 patients in low-, intermediate-, and high-case-volume groups, respectively. Higher physician case volume was associated with lower 30-day mortality (odds ratio 0.79 per logarithmic number of cases [95% confidence interval: 0.64-0.98]). High-volume physician providers had shorter on-scene times (median 28 [25th-75th percentile: 22-38], compared with intermediate 32 [23-42] and lowest 32 [23-43] case-volume groups; P Conclusions: Mortality appears to be lower after pre-hospital anaesthesia when delivered by physician providers with higher case volumes.Peer reviewe

An analysis of prehospital critical care events and management patterns from 97 539 emergency helicopter medical service missions : A retrospective registry-based study

BACKGROUND It is largely unknown how often physicians in emergency helicopter medical services (HEMS) encounter various critical care events and if HEMS exposure is associated with particular practice patterns or outcomes. OBJECTIVES This study aimed: to describe the frequency and distribution of critical care events; to investigate whether HEMS exposure is associated with differences in practice patterns and determine if HEMS exposure factors are associated with mortality. DESIGN A retrospective registry-based study. SETTING Physician-staffed HEMS in Finland between January 2012 and August 2019. PARTICIPANTS Ninety-four physicians who worked at least 6 months in the HEMS during the study period. Physicians with undeterminable HEMS exposure were excluded from practice pattern comparisons and mortality analysis, leaving 80 physicians. MAIN OUTCOME MEASURES The primary outcome measure was a physician's average annual frequencies for operational events and clinical interventions. Our secondary outcomes were the proportion of missions cancelled or denied, time onsite (OST) and proportion of unconscious patients intubated. Our tertiary outcome was adjusted 30-day mortality of patients. RESULTS The physicians encountered 62 [33 to 98], escorted 31 [17 to 41] and transported by helicopter 2.1 [1.3 to 3.5] patients annually, given as median [interquartile range; IQR]. Rapid sequence intubation was performed 11 [6.2 to 16] times per year. Physicians were involved in out-of-hospital cardiac arrest (OHCA) 10 [5.9 to 14] and postresuscitation care 5.5 [3.1 to 8.1] times per year. Physicians with longer patient intervals had shorter times onsite. Proportionally, they cancelled more missions and intubated fewer unconscious patients. A short patient interval [odds ratio (OR); 95% confidence interval (CI)] was associated with decreased mortality (0.87; 95% CI, 0.76 to1.00), whereas no association was observed between mortality and HEMS career length. CONCLUSION Prehospital exposure is distributed unevenly, and some physicians receive limited exposure to prehospital critical care. This seems to be associated with differences in practice patterns. Rare HEMS patient contacts may be associated with increased mortality.Peer reviewe

Accuracy of prehospital clinicians' perceived prognostication of long-term survival in critically ill patients : a nationwide retrospective cohort study on helicopter emergency service patients

Objectives Prehospital critical care physicians regularly attend to patients with poor prognosis and may limit the advanced therapies. The aim of this study was to evaluate the accuracy of poor prognosis given by prehospital critical care clinicians. Design Cohort study. Setting We performed a retrospective cohort study using the national helicopter emergency medical services (HEMS) quality database. Participants Patients classified by the HEMS clinician to have survived until hospital admission solely because of prehospital interventions but evaluated as having no long-term survival by prehospital clinician, were included. Primary and secondary outcome The survival of the study patients was examined at 30 days, 1 year and 3 years. Results Of 36 715 patients encountered by the HEMS during the study period, 2053 patients were classified as having no long-term survival and included. At 30 days, 713 (35%, 95% CI 33% to 37%) were still alive and 69 were lost to follow-up. Furthermore, at 1 year 524 (26%) and at 3 years 267 (13%) of the patients were still alive. The deceased patients received more often prehospital rapid sequence intubation and vasoactives, compared with patients alive at 30 days. Patients deceased at 30 days were older and had lower initial Glasgow Coma Scores. Otherwise, no clinically relevant difference was found in the prehospital vital parameters between the survivors and non-survivors. Conclusions The prognostication of long-term survival for critically ill patients by a prehospital critical care clinician seems to fulfil only moderately. A prognosis based on clinical judgement must be handled with a great degree of caution and decision on limitation of advanced care should be made cautiously.Peer reviewe

Protein Kinase A-Mediated Effects of Protein Kinase C Partial Agonist 5-(Hydroxymethyl)Isophthalate 1a3 in Colorectal Cancer Cells

Colorectal cancer is the third most commonly occurring cancer in men and the second in women. The global burden of colorectal cancer is projected to increase to over 2 million new cases with over 1 million deaths within the next 10 years and there is a great need for new compounds with novel mechanisms of action. Our group has developed PKC modulating isophthalic acid derivatives that induce cytotoxicity towards human cervical and prostate cancer cell lines. In this study, we investigated the effects of 5-(hydroxymethyl)isophthalate 1a3 (HMI-1a3) on colorectal cancer cell lines (Caco2, Colo205 and HT29). HMI-1a3 inhibited cell proliferation, decreased cell viability and induced an apoptotic response in all studied cell lines. These effects, however, were independent of PKC. Using serine/threonine kinome profiling and pharmacological kinase inhibitors we identified activation of the cAMP/PKA pathway as a new mechanism-of-action for HMI-1a3-induced anti-cancer activity in colorectal cancer cell lines. Our current results strengthen the hypothesis for HMI-1a3 as a potential anti-cancer agent against various malignancies. Significance Statement Colorectal cancer (CRC) is a common solid organ malignancy. Here, we demonstrate that the protein kinase C (PKC) C1 domain-targeted isophthalatic acid derivative HMI-1a3 has anti-cancer activity on CRC cell lines independently of PKC. We identified protein kinase A (PKA) activation as a mechanism of HMI-1a3 induced anti-cancer effects. Our results reveal a new anti-cancer mechanism of action for the partial PKC agonist HMI-1a3 and thus provide new insights for the development of PKC and PKA modulators for cancer therapy.Peer reviewe

Validation of Score to Detect Intracranial Lesions in Unconscious Patients in Prehospital Setting

Objectives: Recognizing stroke and other intracranial pathologies in prehospital phase facilitates prompt recanalization and other specific care. Recognizing these can be difficult in patients with decreased level of consciousness. We previously derived a scoring system combining systolic blood pressure, age and heart rate to recognize patients with intracranial pathology. In this study we aimed to validate the score in a larger, separate population. Materials and methods: We conducted a register based retrospective study on patients >= 16 years old and Glasgow Coma ScorePeer reviewe