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APOE-ɛ4 is a genetic risk factor for Alzheimer's disease (AD). AD is associated with reduced cerebral blood flow (CBF) and with microvascular changes that limit the transport of oxygen from blood into brain tissue: reduced microvascular cerebral blood volume and high relative transit time heterogeneity (RTH). Healthy APOE-ɛ4 carriers reveal brain regions with elevated CBF compared with carriers of the common ɛ3 allele. Such asymptomatic hyperemia may reflect microvascular dysfunction : a vascular disease entity characterized by suboptimal tissue oxygen uptake, rather than limited blood flow per se. Here, we used perfusion MRI to show that elevated regional CBF is accompanied by reduced capillary blood volume in healthy APOE-ɛ4 carriers (carriers) aged 30-70 years compared with similarly aged APOE-ɛ3 carriers (noncarriers). Younger carriers have elevated hippocampal RTH and more extreme RTH values throughout both white matter (WM) and cortical gray matter (GM) compared with noncarriers. Older carriers have reduced WM CBF and more extreme GM RTH values than noncarriers. Across all groups, lower WM and hippocampal RTH correlate with higher educational attainment, which is associated with lower AD risk. Three days of dietary nitrate supplementation increased carriers' WM CBF but caused older carriers to score worse on two of six aggregate neuropsychological scores. The intervention improved late recall in younger carriers and in noncarriers. The APOE-ɛ4 gene is associated with microvascular changes that may impair tissue oxygen extraction. We speculate that vascular risk factor control is particularly important for APOE-ɛ4 carriers' healthy aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Anaerobic digestion of organic waste into methane and carbon dioxide (biogas) is carried out by complex microbial communities. Here, we use full-length 16S rRNA gene sequencing of 285 full-scale anaerobic digesters (ADs) to expand our knowledge about diversity and function of the bacteria and archaea in ADs worldwide. The sequences are processed into full-length 16S rRNA amplicon sequence variants (FL-ASVs) and are used to expand the MiDAS 4 database for bacteria and archaea in wastewater treatment systems, creating MiDAS 5. The expansion of the MiDAS database increases the coverage for bacteria and archaea in ADs worldwide, leading to improved genus- and species-level classification. Using MiDAS 5, we carry out an amplicon-based, global-scale microbial community profiling of the sampled ADs using three common sets of primers targeting different regions of the 16S rRNA gene in bacteria and/or archaea. We reveal how environmental conditions and biogeography shape the AD microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 692 genera and 1013 species. These represent 84-99% and 18-61% of the accumulated read abundance, respectively, across samples depending on the amplicon primers used. Finally, we examine the global diversity of functional groups with known importance for the anaerobic digestion process., (© 2024. The Author(s).)

Microbial communities are responsible for biological wastewater treatment, but our knowledge of their diversity and function is still poor. Here, we sequence more than 5 million high-quality, full-length 16S rRNA gene sequences from 740 wastewater treatment plants (WWTPs) across the world and use the sequences to construct the 'MiDAS 4' database. MiDAS 4 is an amplicon sequence variant resolved, full-length 16S rRNA gene reference database with a comprehensive taxonomy from domain to species level for all sequences. We use an independent dataset (269 WWTPs) to show that MiDAS 4, compared to commonly used universal reference databases, provides a better coverage for WWTP bacteria and an improved rate of genus and species level classification. Taking advantage of MiDAS 4, we carry out an amplicon-based, global-scale microbial community profiling of activated sludge plants using two common sets of primers targeting regions of the 16S rRNA gene, revealing how environmental conditions and biogeography shape the activated sludge microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 966 genera and 1530 species that represent approximately 80% and 50% of the accumulated read abundance, respectively. Finally, we show that for well-studied functional guilds, such as nitrifiers or polyphosphate-accumulating organisms, the same genera are prevalent worldwide, with only a few abundant species in each genus., (© 2022. The Author(s).)

Microbial communities in activated sludge (AS) are the core of sanitation in wastewater treatment plants (WWTPs). Microbial communities in AS have shown seasonal changes, however, long-term experiments (>2 years) are rarely conducted, limiting our understanding of the true seasonal dynamics in WWTPs. In this study, we resolved the microbial seasonal dynamics at the species level in four municipal full-scale WWTPs, sampled every 7-10 days, during 3-5 consecutive years. By applying a new time-series analysis approach, we revealed that the seasonal pattern was species-specific, where species belonging to the same functional guild or genus may show different seasonal dynamics. Species could be grouped into cohorts according to their seasonal patterns, where seasonal cohorts showed repeatable annual dynamics across years and plants. Species were also grouped according to their net growth rate in the AS (i.e., growing species and disappearing species). Growing species were more prevailing in spring and autumn cohorts, while disappearing species, which were only present due to the continuous immigration from influent wastewater, were mostly associated with winter and spring cohorts. Most known process-critical species, such as nitrifiers, polyphosphate accumulating organisms and filamentous organisms, showed distinct species-specific patterns. Overall, our study showed that overarching seasonal patterns affected microbial species in full-scale AS plants, with similar seasonal patterns across plants for many dominant species. These recurrent seasonal variations should be taken into account in the operation, understanding and management of the WWTPs., (© 2022. The Author(s).)

Human skin has been classified as a non-volatile memristor and it is shown that information can be stored within for at least three minutes. Here we investigate whether it is possible to store information up to 20 minutes. Furthermore, we investigate whether the information can be based on four different states, not just two (binary). We stored the information into the skin of the forehead of the test subjects under three different electrodes, which allows in principle for 64 different combinations (3 electrodes, 4 states) and one can think of numbers on the base of four. For this experiment, we decided on the numbers 123 4 and 302 4 (that correspond to numbers 27 and 50 in the decimal system). Writing of the different states was done by the application of DC voltage pulses that cause electro-osmosis in the sweat ducts (nonlinear electrical measurements). Based on our results, we were not able to distinguish between four different states. However, we can show that binary information storage in human skin is possible for up to 20 minutes., Competing Interests: Conflict of interest Authors state no conflict of interest., (© 2021 Oliver Pabst, Øystein Magnus Sørebø, Karoline Sjøen Andersen, Erlend Lemva Ousdal, Sean William Bråthen, Badi Ur Rehman, Haiatullah Gholami, Zhijian Zhou, Koki Takahashi, Diriba Tasfaye Dumesso, Mellie Merete Livingston, Wesley Julian Lodewijk, Stian Sæther, Alireza Eskandari Turk, Peter Louis Uller, published by Sciendo.)

The assembly of bacterial communities in wastewater treatment plants (WWTPs) is affected by immigration via wastewater streams, but the impact and extent of bacterial immigrants are still unknown. Here, we quantify the effect of immigration at the species level in 11 Danish full-scale activated sludge (AS) plants. All plants have different source communities but have very similar process design, defining the same overall environmental growth conditions. The AS community composition in each plant was strongly reflected by the corresponding influent wastewater (IWW) microbial composition. Most species in AS across the plants were detected and quantified in the corresponding IWW, allowing us to identify their fate in the AS: growing, disappearing, or surviving. Most of the abundant species in IWW disappeared in AS, so their presence in the AS biomass was only due to continuous mass-immigration. In AS, most of the abundant growing species were present in the IWW at very low abundances. We predicted the AS species abundances from their abundance in IWW by using a partial least square regression model. Some species in AS were predicted by their own abundance in IWW, while others by multiple species abundances. Detailed analyses of functional guilds revealed different prediction patterns for different species. We show, in contrast to the present understanding, that the AS microbial communities were strongly controlled by the IWW source community and could be quantitatively predicted by taking into account immigration. This highlights a need to revise the way we understand, design, and manage the microbial communities in WWTPs., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Ischemic heart disease is one of the leading causes of deaths worldwide. A major hindrance to resolving this challenge lies in the mammalian hearts inability to regenerate after injury. In contrast, zebrafish retain a regenerative capacity of the heart throughout their lifetimes. Apex resection (AR) is a popular zebrafish model for studying heart regeneration, and entails resecting 10-20% of the heart in the apex region, whereafter the regeneration process is monitored until the heart is fully regenerated within 60 days. Despite this popularity, video tutorials describing this technique in detail are lacking. In this paper we visualize and describe the entire AR procedure including anaesthesia, surgery, and recovery. In addition, we show that the concentration and duration of anaesthesia are important parameters to consider, to balance sufficient levels of sedation and minimizing mortality. Moreover, we provide examples of how zebrafish heart regeneration can be assessed both in 2D (immunohistochemistry of heart sections) and 3D (analyses of whole, tissue cleared hearts using multiphoton imaging). In summary, this paper aims to aid beginners in establishing and conducting the AR model in their laboratory, but also to spur further interest in improving the model and its evaluation.

Background: Patients with atrial fibrillation and atrial flutter scheduled to undergo open heart surgery can receive ablation treatment of arrhythmogenic foci during the same intervention. Sinus rhythm is restored in the majority in the short term, but the long-term results are more uncertain. This study, which is part of the international CURE-AF trial, evaluates results after Cox-Maze IV surgery for atrial fibrillation in Norway at six-year follow-up., Material and Method: Nineteen patients were included in this prospective cohort study. Atrial fibrillation had persisted for 40 months in the group with long-standing persistent atrial fibrillation (n = 12) and 6 months in the group with persistent atrial fibrillation (n = 7). Surgery for atrial fibrillation was performed according to the Cox-Maze IV procedure in the CURE-AF protocol. Follow-up in the first 12 months was strictly according to the CURE-AF protocol, thereafter conducted by the primary health service., Results: Sinus rhythm was restored in 11 patients at the time of discharge and in 14 patients six months postoperatively. After 5-6 years of follow-up, all patients with long-standing persistent atrial fibrillation had experienced recurrence. Two achieved sinus rhythm after electroconversion. Six of the seven in the group with persistent atrial fibrillation had sinus rhythm after 5-6 years., Interpretation: The results were good initially, with restoration of sinus rhythm in more than two thirds of the patients after 6-9 months. Five years later, a high recurrence rate was found in patients with long-standing persistent atrial fibrillation. Several recurrences had not been detected by the public health service or treatment had not been attempted.

High-throughput 16S rRNA gene amplicon sequencing is an essential method for studying the diversity and dynamics of microbial communities. However, this method is presently hampered by the lack of high-identity reference sequences for many environmental microbes in the public 16S rRNA gene reference databases and by the absence of a systematic and comprehensive taxonomy for the uncultured majority. Here, we demonstrate how high-throughput synthetic long-read sequencing can be applied to create ecosystem-specific full-length 16S rRNA gene amplicon sequence variant (FL-ASV) resolved reference databases that include high-identity references (>98.7% identity) for nearly all abundant bacteria (>0.01% relative abundance) using Danish wastewater treatment systems and anaerobic digesters as an example. In addition, we introduce a novel sequence identity-based approach for automated taxonomy assignment (AutoTax) that provides a complete seven-rank taxonomy for all reference sequences, using the SILVA taxonomy as a backbone, with stable placeholder names for unclassified taxa. The FL-ASVs are perfectly suited for the evaluation of taxonomic resolution and bias associated with primers commonly used for amplicon sequencing, allowing researchers to choose those that are ideal for their ecosystem. Reference databases processed with AutoTax greatly improves the classification of short-read 16S rRNA ASVs at the genus- and species-level, compared with the commonly used universal reference databases. Importantly, the placeholder names provide a way to explore the unclassified environmental taxa at different taxonomic ranks, which in combination with in situ analyses can be used to uncover their ecological roles., (Copyright © 2020 Dueholm et al.)

Background: To reduce the incidence of hypoxic brain injuries among newborns a national cardiotocography (CTG) education program was implemented in Denmark. A multiple-choice question test was integrated as part of the program. The aim of this article was to describe and discuss the test development process and to introduce a feasible method for written test development in general., Methods: The test development was based on the unitary approach to validity. The process involved national consensus on learning objectives, standardized item writing, pilot testing, sensitivity analyses, standard setting and evaluation of psychometric properties using Item Response Theory models. Test responses and feedback from midwives, specialists and residents in obstetrics and gynecology, and medical and midwifery students were used in the process (proofreaders n = 6, pilot test participants n = 118, CTG course participants n = 1679)., Results: The final test included 30 items and the passing score was established at 25 correct answers. All items fitted a loglinear Rasch model and the test was able to discriminate levels of competence. Seven items revealed differential item functioning in relation to profession and geographical regions, which means the test is not suitable for measuring differences between midwives and physicians or differences across regions. In the setting of pilot testing Cronbach's alpha equaled 0.79, whereas Cronbach's alpha equaled 0.63 in the setting of the CTG education program. This indicates a need for more items and items with a higher degree of difficulty in the test, and illuminates the importance of context when discussing validity., Conclusions: Test development is a complex and time-consuming process. The unitary approach to validity was a useful and applicable tool for development of a CTG written assessment. The process and findings supported our proposed interpretation of the assessment as measuring CTG knowledge and interpretive skills. However, for the test to function as a high-stake assessment a higher reliability is required.

Background: The main treatment of lung cancer (stage 1 and 2) is lung resection surgery. The risk of postoperative pulmonary complications is high and therefore standard postoperative care involves respiratory physiotherapy. The purpose of this systematic review is to create an overview of the evidence on respiratory physiotherapy after lung resection surgery on mortality rate (within 30 days) and postoperative pulmonary complications., Methods and Analysis: The review will include randomized or quasi-randomized controlled studies investigating the effect of all types of respiratory physiotherapy on mortality and postoperative pulmonary complications after lung resection surgery. Furthermore, the effect of respiratory physiotherapy is evaluated on secondary outcomes such as length of hospital stay, lung volumes and function, and adverse events. The method of the planned review is described in this paper. The literature search will include the databases PubMed, Cochrane (Central), Embase, Cinahl and PEDro. The literature search is being performed in 2017. If meta-analyses are not undertaken, a narrative synthesis of the available data will be provided. The protocol was registered in PROSPERO on the 10th of October 2016 (registration number CRD42016048956)., Ethics and Dissemination: Conclusion of this systematic review is expected available in the second half of 2017., (© 2017 The Authors.)

Background: Accidental hypothermia with arrested circulation remains a condition associated with high mortality. In our institution, extracorporeal circulation (ECC) rewarming has been the cornerstone in treating such patients since 1987. We here explore characteristics and outcomes of this treatment, to identify significant merits and challenges from 3 decades of experience in ECC rewarming., Methods: Sixty-nine patients rewarmed by ECC during the period from December 1987 to December 2015 were analyzed. One patient was excluded from the analyses because of combined traumatic cerebral injury. The analysis was focused on patient characteristics, treatment procedures, and outcomes were focused. Survivors were evaluated according to the cerebral performance categories scale. Simple statistics with nonparametric tests and χ 2 tests were used. Median value and range are reported., Results: Median age was 30 years (minimum 1.5, maximum 76), and the cause of accidental hypothermia was cold exposure (27.9%), avalanche (5.9%), and immersion/submersion accidents (66.2%). Eighteen patients survived (26.5%). The survival rate did not improve during the years. Survivors had lower serum potassium (p = 0.002), higher pH (p = 0.03), lower core temperature (p = 0.02), and shorter cardiopulmonary resuscitation time (p = 0.001), but ranges were wide. Although suspected primary hypoxia and hypothermia were associated with lower survival, we observed a 10.5% survival of these victims. Sixteen survivors had good outcome (cerebral performance category 1 or 2), whereas 2 patients with suspected primary hypoxia survived with severe cerebral disability (cerebral performance category 3)., Conclusions: Despite extended experience with ECC rewarming, improved handling strategies, and intensive care, no overall improvement in survival was observed. Good outcome was observed even among patients with a dismal prognosis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

How differentiation between cell types evolved is a fundamental question in biology, but few studies have explored single-gene phenotypes that mediate first steps towards division of labour with selective advantage for groups of cells. Here, we show that differential expression of the FLO11 gene produces stable fractions of Flo11 + and Flo11 - cells in clonal Saccharomyces cerevisiae biofilm colonies on medium with intermediate viscosity. Differentiated Flo11 +/- colonies, consisting of adhesive and non-adhesive cells, obtain a fourfold growth advantage over undifferentiated colonies by overgrowing glucose resources before depleting them, rather than depleting them while they grow as undifferentiated Flo11 - colonies do. Flo11 +/- colonies maintain their structure and differentiated state by switching non-adhesive cells to adhesive cells with predictable probability. Mixtures of Flo11 + and Flo11 - cells from mutant strains that are unable to use this epigenetic switch mechanism produced neither integrated colonies nor growth advantages, so the condition-dependent selective advantages of differentiated FLO11 expression can only be reaped by clone-mate cells. Our results show that selection for cell differentiation in clonal eukaryotes can evolve before the establishment of obligate undifferentiated multicellularity, and without necessarily leading to more advanced organizational complexity., (© 2016 The Author(s).)

Background: Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture., Methods: Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes., Results: Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4° (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months., Conclusion: Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture., Trial Registration: This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ).

Background: Recent studies have focused on the use of fixed-rate intraaortic balloon pumping (IABP) during cardiopulmonary bypass (CPB) to achieve pulsatile flow. Because application of an IABP catheter may represent a functional obstruction within the descending aorta, we explored the effect of IABP-pulsed CPB-perfusion with special attention to perfusion above and below the IABP balloon., Methods: Sixteen animals received an IABP catheter that remained turned off position (NP group, n = 8) or was switched to an automatic mode of 80 beats/min during CPB (PP group, n = 8). Flow-data and pressure-data were obtained above and below the IABP balloon. Tissue perfusion was evaluated by microspheres., Results: IABP-pulsed CPB-perfusion, as assessed at 30 minutes on CPB, increased proximal mean aortic pressure (p < 0.05) and carotid artery blood flow (p < 0.001), but decreased distal mean aortic pressure (p < 0.001). The decrease of distal mean aortic pressure in the PP group was associated with a 75 % decrease (p < 0.001) of renal tissue perfusion. During nonpulsed perfusion the respective variables remained essentially unchanged compared with pre-CPB levels., Conclusions: Using IABP as a surrogate to achieve pulsatile perfusion during CPB contributes significantly to lowered aortic pressure in the distal portion of aorta and impaired tissue perfusion of the kidneys. The results are focusing on effects that may contribute to organ dysfunction and acute kidney injury. Consequently, assessment of perfusion pressure distal to the balloon should be addressed whenever IABP is used during CPB., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Increased navicular drop is associated with increased risk of lower extremity overuse injuries and foot orthoses are often prescribed to reduce navicular drop. For laboratory studies, transparent shoes may be used to monitor the effect of orthoses but no clinically feasible methods exist. We have developed a stretch-sensor that allows for in-shoe measurement of navicular drop but the reliability and validity is unknown. The purpose of this study was to investigate: 1) the reliability of the stretch-sensor for measuring navicular drop, and 2) the concurrent validity of the stretch-sensor compared to the static navicular drop test., Methods: Intra- and inter-rater reliability was tested on 27 participants walking on a treadmill on two separate days. The stretch-sensor was positioned 20 mm posterior to the tip of the medial malleolus and 20 mm posterior to the navicular tuberosity. The participants walked six minutes on the treadmill before navicular drop was measured. Reliability was quantified by the Intraclass Correlation Coefficient (ICC 2.1) and agreement was quantified by Limits of Agreement (LOA). To assess concurrent validity, static navicular drop was measured with the stretch-sensor and compared with static navicular drop measured with a ruler on 27 new participants. Linear regression was used to measure concurrent validity., Results: The reliability of the stretch-sensor was acceptable for barefoot measurement (intra- and inter-rater ICC: 0.76-0.84) but lower for in-shoe measurement (ICC: 0.65). There was a significant association between static navicular drop measured with the stretch-sensor compared with a ruler (r = 0.745, p < 0.001)., Conclusion: This study suggests that the stretch-sensor has acceptable reliability for dynamic barefoot measurement of navicular drop. Furthermore, the stretch-sensor shows concurrent validity compared with the static navicular drop test as performed by Brody. This new simple method may hold promise for both clinical assessment and research but more work is needed before the method can be recommended.

Background: Acute dysfunction of mechanical aortic valve prostheses is a life-threatening adverse event. Pannus overgrowth, which is fibroelastic hyperplasia originating from the periannular area, is one cause of dysfunction. The aim of this study was to determine the annual incidence of readmittance resulting from acute obstruction caused by pannus during 30 years of observation in patients with Medtronic-Hall aortic valve prostheses and to analyze the risk factors associated with pannus development., Methods: From 1982 to 2004, 1,187 patients in our department underwent aortic valve replacement with Medtronic-Hall mechanical monoleaflet valve prostheses. As of December 31, 2012, 27 of these patients (2.3%) had presented with acute valve dysfunction caused by pannus obstruction., Results: The annual incidence of pannus was 0.7 per 1,000. The median time from the primary operation to prosthetic dysfunction was 11.1 years (range, 1.2 to 26.8 years). Of the 20 patients who underwent reoperation, 2 died. Seven patients died before reoperation. Women had a higher risk for the development of obstructing pannus, and patients with pannus obstruction were younger. Valve size was not an independent risk factor., Conclusions: Women and younger patients are at higher risk for pannus development. When acute dysfunction by pannus is suspected in a mechanical aortic valve, an immediate echocardiogram and an emergency aortic valve replacement should be carried out because of the potential of a fatal outcome., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate how pulsed versus nonpulsed cardiopulmonary bypass influences microvascular fluid exchange in an experimental setup combining a nonpulsatile perfusion pump and an intra-aortic balloon pump., Methods: A total of 16 pigs were randomized to pulsatile cardiopulmonary bypass perfusion with an intra-aortic balloon pump switched to an automatic 80 beats/min mode after the start of cardiopulmonary bypass (pulsatile perfusion [PP] group, n = 8) or to nonpulsatile cardiopulmonary bypass with the pump switched to the off position (nonpulsatile [NP] group, n = 8). Normothermic cardiopulmonary bypass was initiated after 60 minutes of stabilization and continued for 3 hours. The fluid needs, plasma volume, colloid osmotic pressure in plasma, colloid osmotic pressure in interstitial fluid, hematocrit, and total tissue water content were recorded, and the protein masses and fluid extravasation rates were calculated., Results: After cardiopulmonary bypass was started, the mean arterial pressure increased in the PP group and decreased in the NP group. At 180 minutes, the mean arterial pressure of the PP and NP groups was 70.9 ± 2.7 mm Hg and 55.9 ± 2.7 mm Hg, respectively (P = .004). The central venous pressure (right atrium) had decreased in the NP group (P = .002). A decreasing trend was seen in the PP group. No between-group differences were present. The hematocrit and colloid osmotic pressure in plasma and interstitial fluid had decreased similarly in both study groups during cardiopulmonary bypass. The plasma volume of the PP group had decreased initially but then returned gradually to precardiopulmonary bypass levels. In the NP group, the plasma volume remained contracted (P = .02). No significant differences in the fluid extravasation rate were obtained. The fluid extravasation rate of the PP group tended to stay slightly higher than the fluid extravasation rate of the NP group at all measurement intervals. The total tissue water content increased significantly in a number of organs compared with that in the control animals. However, differences in the total tissue water content between pulsed and nonpulsed perfusion were absent., Conclusions: No significant differences in the fluid extravasation rates were present between pulsed and nonpulsed cardiopulmonary bypass perfusion in the present experimental setup., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Microbial populations adapt to environmental fluctuations through random switching of fitness-related traits in individual cells. This increases the likelihood that a subpopulation will be adaptive in a future milieu. However, populations are particularly challenged when several environment factors change simultaneously. We suggest that a population can rapidly adapt to multiple environmental changes if individual members stochastically flip a hub-switch that controls a set of adaptive phenotypes in a single event. This mechanism of coupling phenotypic outcomes via a hub-switch can protect a population against large fluctuations in size. Here we report that the general amino acid transporter Gap1 is a potential hub-switch. The GAP1 gene is flanked by two direct repeats that can lead to GAP1 deletions (∆gap1) and a self-replicating GAP1 circle. Thus, an isogenic GAP1 population can differentiate into two variant, reversible genotypes, ∆gap1 or GAP1 (circle). These subpopulations have different phenotypic advantages. A ∆gap1 population has a selective advantage on allantoin or ammonium as a nitrogen source and high stress tolerance. Advantages of the GAP1 population include amino acid uptake, fast energy recruitment by trehalose mobilization, and in some cases, adherent biofilm growth. Our proposed model of a hub-switch locus enhances the bet-hedging model of population dynamics.

Measurements on microbubbles clearly indicate a relation between the ambient pressure and the acoustic behavior of the bubble. The purpose of this study was to optimize the sensitivity of ambient pressure measurements, using the subharmonic component, through microbubble response simulations. The behavior of two microbubbles corresponding to two different contrast agents was investigated as a function of driving pulse and ambient overpressure p(ov). Simulations of Levovist using a rectangular driving pulse show an almost linear reduction in the subharmonic component as p(ov) is increased. For a 20 cycle driving pulse, a reduction of 4.6 dB is observed when changing p(ov) from 0 to 25 kPa. Increasing the pulse duration makes the reduction even clearer. For a pulse with 64 cycles, the reduction is 9.9 dB. This simulation is in good correspondence with measurement results presented in the literature. Further simulations of Levovist show that also the shape and the acoustic pressure of the driving pulse are very important factors. The best pressure sensitivity of Levovist was found to be 0.88 dB/kPa. For Sonazoid, a sensitivity of 1.14 dB/kPa has been found, although the reduction is not completely linear as a function of the ambient pressure.

Objective: Twenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results., Patients and Methods: The treatment of six female and 20 male patients (median age: 26.7 years; range 1.9--76.3 years) rewarmed in the period 1987--2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (n=17), avalanche (n=1) or prolonged exposure to cold surroundings (n=8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (n=22), whereas in those with respiration/circulation (n=4) only oxygen therapy via a face mask was given., Results: Nineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1--2 days due to severe hypoxic brain injury (n=5), cerebral bleeding (n=1) or irreversible cardiopulmonary insufficiency (n=4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (n=15) (submersions (n=14); avalanche accident (n=1)) and the non-asphyxia group (n=11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the non-asphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group., Conclusion: Patients with non-asphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion.

Background: Different techniques have been used for treatment of victims with accidental hypothermia. We have used cardiopulmonary bypass (CPB) for rewarming hypothermic patients with circulatory failure or cardiac arrest. This report summarises our experiences with this patient group., Material and Methods: 23 patients, submersions (n = 15), avalanche (n = 1) and primary hypothermia (immersion/air cooling) (n = 7), were rewarmed using extracorporeal circulation with standard equipment for open-heart surgery., Results: On a clinical basis, two patient populations could be identified; one group for whom asphyxia was probably present prior to and during cooling, and another group for whom asphyxia was unlikely. In the first group, one of 13 patients survived compared to the latter group where six out of ten survived. A search for laboratory and other variables that with certainty could contribute to the prediction of prognosis was unsuccessful., Interpretation: Due to lack of safe prognostic predictors, all accidental hypothermic victims with circulatory failure should be rewarmed by cardiopulmonary bypass before further therapeutic decisions are made.

Since 1991, leaders in health policy from the legislative and executive branches of state government have come together, with financial support and staff collaboration from the Milbank Memorial Fund, to share their experiences and to work on practical solutions to pressing health care problems. What began with a handful of states at the forefront of health reform is now the Reforming States Group (RSG), a bipartisan, voluntary association that includes leaders from over 40 states. This article describes the origins, history, and future prospects of the RSG.

Objective: Evaluation of wedge resection of the lung without pleurodesis or pleurectomy as a method of surgical treatment for spontaneous pneumothorax in terms of complications, recurrence rate and postoperative complaints., Methods: Retrospective study of 132 operations for spontaneous pneumothorax in 120 patients (84 men and 36 women: mean age 34 years, range 14-77) performed between 1974 and 1993. The mean observation time was 84 months (range 6-229) and a 100% follow-up rate of all survivors (97%) was achieved., Results: The indications for surgery were recurrent pneumothorax (52%), persisting air leak during first episode (45%), or hemothorax (3%). Perioperative findings were single bullous disease (86%), 2-3 bullae (6%), diffuse bullous disease (5%) and no bullous disease in 3% of the cases. The overall complication rate was 16% (30-day mortality 1%, reoperation for postoperative bleeding 2%, bronchopneumonia 8%, new pneumothorax during hospital stay 5%). The late recurrence rate (operated lung) was 5%. All recurrences were successfully treated by drainage (n = 3), exsufflation (n = 1) or observation only (n = 3). Reoperation was not necessary. Thirty-seven percent of the patients had postoperative complaints which they associated with the operation., Conclusion: Lung resection without pleurodesis or pleurectomy is a simple, safe and effective method of the surgical treatment of spontaneous pneumothorax in terms of complications and recurrence rate in patients with limited bullous disease.

On the basis of 21 cases of congenital pseudarthrosis of the tibia, which were radiologically typed and later personally examined, it was found that all cases of the dysplastic type also showed evidence of neurofibromatosis. No evidence of neurofibromatosis was found among the cystic and the clubfoot type of pseudarthroses.

The photo-oxidation of cytochrome f (cytochrome c(554)) in bundle sheath cells isolated from leaves of maize (Zea mays var. DS 606A) has been compared with that in intact maize leaf and in isolated pea leaf cells (Pisum sativum L.). In all cases, illumination with red light caused a negative absorbance change at 554 nm which was attributed to the oxidation of cytochrome f. The extent of this change was greater using monochromatic red light at wavelengths above 700 nm compared with wavelengths below 700 nm. 3-(3,4-Dichlorophenyl)-1, 1-dimethylurea abolished this difference in bundle sheath cells. After illumination for 1 minute or longer in bundle sheath cells, reduction of cytochrome f in the dark was rapid only if the wavelength of the illuminating light was below 700 nm. In the presence of 3-(3,4-dichlorophenyl)-1, 1-dimethlyurea, reduction was slow after illumination at all wavelengths.Cytochrome f photo-oxidation was also followed in cells of a mutant of Chlamydomonas reinhardi, ac-21, which has isolated chloroplasts that exhibit photochemical reactions similar to those shown by isolated bundle sheath chloroplasts. No evidence was obtained for photoreduction of cytochrome f in the mutant.It was concluded that in the chloroplast of the intact bundle sheath cell of maize there is electron flow between photosystem II and cytochrome f resulting in photoreduction of the cytochrome.

The photochemical activities of chloroplasts isolated from bundle sheath and mesophyll cells of maize (Zea mays var. DS606A) have been measured. Bundle sheath chloroplasts are almost devoid of grana, except in very young leaves, while mesophyll chloroplasts contain grana at all stages of leaf development.Chloroplast fragments isolated from bundle sheath cells showed a light-dependent reduction of potassium ferricyanide, 2, 6-dichlorophenolindophenol, mammalian cytochrome c, plastocyanin, and Euglena cytochrome c(552). These activities were inhibited by 3-(3, 4-dichlorophenyl)-1, 1-dimethylurea at 1.25 micromolar. However, the photoreduction of NADP from water was extremely low or absent, except in chloroplasts from very young leaves, and the capacity for NADP reduction appeared to be related to the degree of grana formation.Photosystem I activity was present in bundle sheath chloroplast preparations at all stages of leaf growth and senescence examined. However, the activity was lower than in isolated mesophyll chloroplasts. NADPH diaphorase activity was comparable in both types of chloroplast.Chloroplasts isolated from bundle sheath cells of plants grown under a variety of conditions, including continuous and intermittent light, high and low light intensities, and high temperature, exhibited photosystem II activity.

The pH dependence of the photoreduction of ferricyanide and the photoreduction of NADP from water and photosystem I activity have been compared in isolated chloroplasts from mesophyll and bundle sheath cells of Zea mays. The maximum activity of photoreduction of ferricyanide occurs at pH 8.5 in isolated mesophyll chloroplasts. The addition of methylamine does not cause a marked shift in the pH maximum, but brief sonication lowers the pH maximum to 7.0. In contrast, isolated bundle sheath chloroplasts have a pH maximum at 7.0 and the shape of the pH versus activity curve is similar to that of sonicated mesophyll chloroplasts. When photoreduction of ferricyanide by the isolated chloroplasts is measured at their pH maxima, the values for bundle sheath chloroplasts are about half those of methylamine-treated mesophyll chloroplasts on a chlorophyll basis.The pH maxima for the photoreduction of NADP from water and photosystem I activity are similar in both mesophyll and bundle sheath chloroplasts with maximum activity occurring at pH 7.0 in both cases. In the presence of added plastocyanin and ferredoxin NADP-reductase, the photosystem I activities of both sonicated mesophyll and sonicated bundle sheath chloroplasts are significantly higher than those of the unsonicated preparations. On a chlorophyll basis, photosystem I activity of bundle sheath chloroplasts is at least twice that of mesophyll chloroplasts.

Photoreduction of NADP from water in agranal chloroplasts isolated from the leaf bundle sheath cells of Zea mays (var. DS 606A) or Sorghum bicolor (var. Texas 610) was dependent upon addition of plastocyanin as well as ferredoxin. Activity was further increased by the addition of ferredoxin NADP-reductase. Saturation for plastocyanin was reached at about 6 micromolar. In contrast, grana-containing chloroplasts isolated from leaf mesophyll cells of these plants or from pea (Pisum sativum L.) leaves did not require either plastocyanin or ferredoxin NADP-reductase for NADP photoreduction from water, although with some preparations plastocyanin stimulated the activity.Photosystem I activity, which was low in washed preparations of bundle sheath chloroplasts, was also stimulated by plastocyanin. The effect of plastocyanin on photosystem I activity in the grana-containing chloroplasts was similar to that on NADP photoreduction from water.In the presence of plastocyanin, the rates of NADP photoreduction from water were about the same in the agranal and granal chloroplasts, but photosystem I activity was considerably higher in bundle sheath chloroplasts. In these chloroplasts photosystem II appeared to limit the rate of NADP photoreduction.The results indicated that the agranal bundle sheath chloroplasts reduced plastocyanin via photosystem II and oxidized it via photosystem I. Both types of maize chloroplast photoreduced oxidized plastocyanin, but in the presence of methyl viologen, reduced plastocyanin was photo-oxidized only by the bundle sheath chloroplasts.