Genomic and Seasonal Variations among Aquatic Phages Infecting the Baltic Sea Gammaproteobacterium Rheinheimera sp. Strain BAL341.

Knowledge in aquatic virology has been greatly improved by culture-independent methods, yet there is still a critical need for isolating novel phages to identify the large proportion of "unknowns" that dominate metagenomes and for detailed analyses of phage-host interactions. Here, 54 phages infecting Rheinheimera sp. strain BAL341 (Gammaproteobacteria) were isolated from Baltic Sea seawater and characterized through genome content analysis and comparative genomics. The phages showed a myovirus-like morphology and belonged to a novel genus, for which we propose the name Barbavirus All phages had similar genome sizes and numbers of genes (80 to 84 kb; 134 to 145 genes), and based on average nucleotide identity and genome BLAST distance phylogeny, the phages were divided into five species. The phages possessed several genes involved in metabolic processes and host signaling, such as genes encoding ribonucleotide reductase and thymidylate synthase, phoH, and mazG One species had additional metabolic genes involved in pyridine nucleotide salvage, possibly providing a fitness advantage by further increasing the phages' replication efficiency. Recruitment of viral metagenomic reads (25 Baltic Sea viral metagenomes from 2012 to 2015) to the phage genomes showed pronounced seasonal variations, with increased relative abundances of barba phages in August and September synchronized with peaks in host abundances, as shown by 16S rRNA gene amplicon sequencing. Overall, this study provides detailed information regarding genetic diversity, phage-host interactions, and temporal dynamics of an ecologically important aquatic phage-host system.IMPORTANCE Phages are important in aquatic ecosystems as they influence their microbial hosts through lysis, gene transfer, transcriptional regulation, and expression of phage metabolic genes. Still, there is limited knowledge of how phages interact with their hosts, especially at fine scales. Here, a Rheinheimera phage-host system constituting highly similar phages infecting one host strain is presented. This relatively limited diversity has previously been seen only when smaller numbers of phages have been isolated and points toward ecological constraints affecting the Rheinheimera phage diversity. The variation of metabolic genes among the species points toward various fitness advantages, opening up possibilities for future hypothesis testing. Phage-host dynamics monitored over several years point toward recurring "kill-the-winner" oscillations and an ecological niche fulfilled by this system in the Baltic Sea. Identifying and quantifying ecological dynamics of such phage-host model systems in situ allow us to understand and study the influence of phages on aquatic ecosystems.

Diagnostic criteria for temporomandibular disorders: Diagnostic accuracy for general dentistry procedure without mandatory commands regarding myalgia, arthralgia and headache attributed to temporomandibular disorder.

The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen' s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.

Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study.

BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults. METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis. RESULTS: Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L-1 vs. Q1, 22-77 pmol L-1 : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L-1 (Q3-Q4, 68-432 pmol L-1 vs. Q1-Q2,4-68 pmol L-1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors. CONCLUSIONS: Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.

Reactions of Three Lactones with Cl, OD, and O3: Atmospheric Impact and Trends in Furan Reactivity.

Lactones, cyclic esters of hydroxycarboxylic acids, are interesting biofuel candidates as they can be made from cellulosic biomass and have favorable physical and chemical properties for distribution and use. The reactions of γ-valerolactone (GVL), γ-crotonolactone (2(5H)-F), and α-methyl-γ-crotonolactone (3M-2(5H)-F) with Cl, OD, and O3 were investigated in a static chamber at 700 Torr and 298 ± 2 K. The relative rate method was used to determine kGVL+Cl = (4.56 ± 0.51) × 10-11, kGVL+OD = (2.94 ± 0.41) × 10-11, k2(5H)-F+Cl = (2.94 ± 0.41) × 10-11, k2(5H)-F+OD = (4.06 ± 0.073) × 10-12, k3M-2(5H)-F+Cl = (16.1 ± 1.8) × 10-11, and k3M-2(5H)-F+OD = (12.6 ± 0.52) × 10-12, all rate coefficients in units of cm3 molecule-1 s-1. An absolute rate method was used to determine k2(5H)-F+O3 = (6.73 ± 0.18) × 10-20 and k3M-2(5H)-F+O3 = (5.42 ± 1.23) × 10-19 in units of cm3 molecule-1 s-1. Products were identified for reactions of the lactones with Cl. In the presence of O2 the products are formic acid (HCOOH), formyl chloride (CHClO), and phosgene (CCl2O), and also maleic anhydride (C2H2(CO)2O) for 2(5H)-F. In addition both reactions produced a number of unidentified products that likely belong to molecules with the ring-structure intact. A review of literature data for reactions of other furans show that the reactivity of the lactones are generally lower compared to that of corresponding compounds without the carbonyl group.

Patient-reported outcomes in the Swedish National Quality Registers.

Patient-reported outcomes (PROs) are important in the healthcare system to gain understanding of patients' views on the effects of a treatment. There is an abundance of available patient-reported outcome measures (PROMs), both disease specific and generic. In the Swedish healthcare system, the national quality registers are obliged to incorporate PROs for certification at a high level. A review of the latest annual applications for funding (n = 108) shows that at present, 93 national quality registers include some form of PROM or patient-reported experience measure (PREM). Half of the registers include some type of generic measure, more than half include disease/symptom-specific measures, and around 40% include PREMs. Several different measures and combinations of measures are used, the most common of which are the EQ-5D, followed by the SF-36/RAND-36. About one-fifth of the registers report examples of how patient-reported data are used for local quality improvement. These examples include enhancing shared decision-making in clinical encounters (most common), as a basis for care plans, clinical decision aids and treatment guidelines, to improve the precision of indications for surgery (patient and healthcare professional assessments may differ), to monitor complications after the patient has left hospital and to improve patient information. In addition, funding applications reveal that most registers plan to extend their array of PROMs and PREMs in future, and to increase their use of patient-reported data as a basis for quality improvement.

Multiple cryptic species of sympatric generalists within the avian blood parasite Haemoproteus majoris.

The avian haemosporidian parasite Haemoproteus majoris has been reported to infect a wide range of passerine birds throughout the Holarctic ecozone. Five cytochrome b (cyt b) lineages have been described as belonging to the morphological species H. majoris, and these form a tight phylogenetic cluster together with 13 undescribed lineages that differ from each other by < 1.2% in sequence divergence. Records in a database (MalAvi) that contains global findings of haemosporidian lineages generated by universal primers suggest that these lineages vary substantially in host distribution. We confirm this pattern in a data set collected at Lake Kvismaren, Sweden, where three of the generalist lineages have local transmission. However, whether these lineages represent intraspecific mitochondrial diversity or clusters of cryptic species has previously not been examined. In this study, we developed novel molecular markers to amplify the partial segments of four nuclear genes to determine the level of genetic diversity and gene phylogenies among the five morphologically described cyt b lineages of H. majoris. All five cyt b lineages were strongly associated with unique nuclear alleles at all four nuclear loci, indicating that each mitochondrial lineage represents a distinct biological species. Within lineages, there was no apparent association between nuclear alleles and host species, indicating that they form genetically unstructured populations across multiple host species.

Design and structure-activity relationships of novel inhibitors of human rhinovirus 3C protease.

Human rhinovirus (HRV) is a primary cause of common cold and is linked to exacerbation of underlying respiratory diseases such as asthma and COPD. HRV 3C protease, which is responsible for cleavage of viral polyprotein in to proteins essential for viral life-cycle, represents an important target. We have designed proline- and azetidine-based analogues of Rupintrivir that target the P2 pocket of the binding site. Potency optimization, aided with X-ray crystallography and quantum mechanical calculations, led to compounds with activity against a broad spectrum of HRV serotypes. Altogether, these compounds represent alternative starting points to identify promising leads in our continual efforts to treat HRV infections.

Impact of mechanical bowel preparation on survival after colonic cancer resection.

BACKGROUND: A randomized study in 1999-2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. METHODS: The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. RESULTS: Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17·9 per cent) of 448 patients in the MBP group and 88 (22·5 per cent) of 391 in the no-MBP group developed a cancer recurrence (P = 0·093). The 10-year cancer-specific survival rate was 84·1 per cent in the MBP group and 78·0 per cent in the no-MBP group (P = 0·019). Overall survival rates were 58·8 and 56·0 per cent respectively (P = 0·186). CONCLUSION: Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years.

A survey of spinal collateral actions of feline ventral spinocerebellar tract neurons.

The aim of this study was to identify spinal target cells of spinocerebellar neurons, in particular the ventral spinocerebellar tract (VSCT) neurons, giving off axon collaterals terminating within the lumbosacral enlargement. Axons of spinocerebellar neurons were stimulated within the cerebellum while searching for most direct synaptic actions on intracellularly recorded hindlimb motoneurons and interneurons. In motoneurons the dominating effects were inhibitory [inhibitory postsynaptic potentials (IPSPs) in 67% and excitatory postsynaptic potentials (EPSPs) in 17% of motoneurons]. Latencies of most IPSPs indicated that they were evoked disynaptically and mutual facilitation between these IPSPs and disynaptic IPSPs evoked by group Ia afferents from antagonist muscles and group Ib and II afferents from synergists indicated that they were relayed by premotor interneurons in reflex pathways from muscle afferents. Monosynaptic EPSPs from the cerebellum were accordingly found in Ia inhibitory interneurons and intermediate zone interneurons with input from group I and II afferents but only oligosynaptic EPSPs in motoneurons. Monosynaptic EPSPs following cerebellar stimulation were also found in some VSCT neurons, indicating coupling between various spinocerebellar neurons. The results are in keeping with the previously demonstrated projections of VSCT neurons to the contralateral ventral horn, showing that VSCT neurons might contribute to motor control at a spinal level. They might thus play a role in modulating spinal activity in advance of any control exerted via the cerebellar loop.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

Expertise-based randomized clinical trial of laparoscopic versus small-incision open cholecystectomy.

BACKGROUND: Several randomized clinical trials have compared laparoscopic cholecystectomy (LC) and small-incision open cholecystectomy (SIOC). Most have had wide exclusion criteria and none was expertise-based. The aim of this expertise-based randomized trial was to compare healthcare costs, quality of life (QoL), pain and clinical outcomes after LC and SIOC. METHODS: Patients scheduled for cholecystectomy were randomized to treatment by one of two teams of surgeons with a preference for either LC or SIOC. Each team performed their specific method (SIOC or LC) as a first-choice operation, but converted to open cholecystectomy and common bile duct exploration when necessary. Intraoperative cholangiography was carried out routinely. The intention was to include all patients undergoing cholecystectomy, including emergency operations and procedures involving surgical training for residents. RESULTS: Some 74·9 per cent of all patients undergoing cholecystectomy were included. Of 355 patients randomized, 333 were analysed. Self-estimated QoL scores in 258 patients, analysed by the area under the curve method, were significantly lower in the SIOC group at 1 month after surgery: median 2326 (95 per cent confidence interval 2187 to 2391) compared with 2411 (2334 to 2502) for the LC group (P = 0·030). The mean(s.d.) duration of operation was shorter for SIOC: 97(41) versus 120(48) min (P < 0·001). There were no significant differences between the groups in conversion rate, pain, complications, length of hospital stay or readmissions. CONCLUSION: SIOC had comparable surgical results but slightly worse short-term QoL compared with LC. REGISTRATION NUMBER: NCT00370344 (http://www.clinicaltrials.gov).

Evoked thalamic neuronal activity following DRG application of two nucleus pulposus derived cell populations: an experimental study in rats.

PURPOSE: To investigate the effects on evoked thalamic neuronal activity of application of notochordal cells and chondrocyte-like cells derived from nucleus pulposus (NP) onto a dorsal root ganglion (DRG) and to compare these effects with a previously reported increased thalamic activity induced by NP. METHODS: Nucleus pulposus was harvested from tail discs of adult rats and the disc cells were separated into two cell populations, notochordal cells and chondrocyte-like cells. The two cell populations were applied separately, or in combination, to the L4 DRG of anaesthetised female Sprague-Dawley rats during acute electrophysiological experiments. In control experiments, cell suspension medium was applied on the DRG. Recordings from the contralateral thalamus were sampled for 40 min while electrically stimulating the ipsilateral sciatic nerve at above Aδ-fibre thresholds. RESULTS: Application of notochordal cells resulted in a decrease in evoked thalamic activity within 10 min while chondrocyte-like cells did not induce any changes during the 40 min of recording. The difference in evoked thalamic activity 40 min after notochordal and chondrocyte-like cell application, respectively, was statistically significant. Neither an increased concentration of chondrocyte-like cells alone nor a combination of the two cell populations induced any changes in thalamic activity. CONCLUSIONS: Separate exposure of the DRG to the two NP-derived cell populations induced different effects on evoked thalamic activity, but none of the tested cell samples induced an increase in neuronal activity similar to that previously observed with NP. This indicates a high complexity of the interaction between NP and nervous tissue.

Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men.

AIMS/HYPOTHESIS: Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle. METHODS: Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR. RESULTS: HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6-8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation. CONCLUSIONS/INTERPRETATION: The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels.

Investigating primary marine aerosol properties: CCN activity of sea salt and mixed inorganic-organic particles.

Sea spray particles ejected as a result of bubbles bursting from artificial seawater containing salt and organic matter in a stainless steel tank were sampled for size distribution, morphology, and cloud condensation nucleus (CCN) activity. Bubbles were generated either by aeration through a diffuser or by water jet impingement on the seawater surface. Three objectives were addressed in this study. First, CCN activities of NaCl and two types of artificial sea salt containing only inorganic components were measured to establish a baseline for further measurements of mixed organic-inorganic particles. Second, the effect of varying bubble residence time in the bulk seawater solution on particle size and CCN activity was investigated and was found to be insignificant for the organic compounds studied. Finally, CCN activities of particles produced from jet impingement were compared with those produced from diffuser aeration. Analyses indicate a considerable amount of organic enrichment in the jet-produced particles relative to the bulk seawater composition when sodium laurate, an organic surfactant, is present in the seawater. In this case, the production of a thick foam layer during impingement may explain the difference in activation and supports hypotheses that particle production from the two methods of generating bubbles is not equal.

IgY stability in eggs stored at room temperature or at +4°C.

1. The aim of this study was to investigate the stability of immunoglobulin-Y (IgY) in stored eggs from immunised hens. 2. Eggs from individual hens were randomised and stored for up to one month at room temperature, or for up to 6 months at +4°C. IgY was extracted from the egg yolks and the antibody activities were tested by ELISA. 3. There was no significant reduction in antibody titres with egg storage under these conditions. 4. Egg yolks of immunised chickens provide an inexpensive source of large amounts of polyclonal antibodies for use in immunotherapy and immunoassays. By collecting eggs from different immunised hens and pooling their yolks, it should be possible to reduce batch-to-batch variation.

Airborne and marine microplastics from an oceanographic survey at the Baltic Sea: An emerging role of air-sea interaction?

Microplastics (MPs) pollution is one of the most important problems of the Earth. They have been found in all the natural environments, including oceans and the atmosphere. In this study, the concentrations of both atmospheric and marine MPs were measured over the Baltic along a research cruise that started in the Gdansk harbour, till the Gotland island, and the way back. A deposition box (based on a combination of active/passive sampling) was used to collect airborne MPs while, marine MPs concentrations were investigated during the cruise using a dedicated net. Ancillary data were obtained using a combination of particle counters (OPC, LAS and CPC), Aethalometer (AE33 Magee Scientific), spectrofluorometer (sea surface samples, Varian Cary Eclipse), and meteorological sensors. Results showed airborne microplastics average concentrations higher in the Gdansk harbour (161 ± 75 m-3) compared to the open Baltic Sea and to the Gotland island (24 ± 9 and 45 ± 20 m-3). These latter values are closer to the ones measured in the sea (79 ± 18 m-3). The MPs composition was investigated using µ-Raman (for the airborne ones) and FTIR (for marine ones); similar results (e.g. polyethylene, polyethylene terephthalates, polyurethane) were found in the two environmental compartments. The concentrations and similar composition in air and sea suggested a linkage between the two compartments. For this purpose, the atmospheric MPs' equivalent aerodynamic diameter was calculated (28 ± 3 µm) first showing the capability of atmospheric MPs to remain suspended in the air. At the same time, the computed turnover times (0.3-90 h; depending on MPs size) limited the transport distance range. The estimated MPs sea emission fluxes (4-18 ∗ 106 µm3 m-2 s-1 range) finally showed the contemporary presence of atmospheric transport together with a continuous emission from the sea surface enabling a grasshopper long-range transport of microplastics across the sea.

Processing information related to centrally initiated locomotor and voluntary movements by feline spinocerebellar neurones.

Feed-back information on centrally initiated movements is processed at both supraspinal and spinal levels and is forwarded by a variety of neurones. The aim of the present study was to examine how descending commands relayed by reticulospinal neurones are monitored by a population of spinocerebellar tract neurones. Our main question was whether a spinal border (SB) subpopulation of ventral spinocerebellar tract (VSCT) neurones monitor actions of reticulospinal neurones with input from the mesencephalic locomotor region (MLR) as well as from pyramidal tract (PT) neurones. In the majority of intracellularly recorded SB neurons, stimuli applied in the MLR and in the medullary pyramids evoked EPSPs in parallel with EPSPs evoked by stimulation of axons of reticulospinal neurones in the medial longitudinal fascicle (MLF). In extracellularly recorded neurones short trains of stimuli applied in the ipsilateral and contralateral pyramids potently facilitated discharges evoked from the MLF, as well as EPSPs recorded intracellularly. In both cases the facilitation involved the disynaptic but not the monosynaptic actions. These results indicate that reticulospinal neurones activating SB neurones (or more generally VSCT neurones) are co-excited by axon-collaterals of other reticulospinal neurones and by fibres stimulated within the MLR and PTs. The study leads to the conclusion that these spinocerebellar neurones monitor descending commands for centrally initiated voluntary as well as locomotor movements relayed by reticulospinal neurones. Thereby they may provide the cerebellum with feed-back information on the likely outcome of these commands and any corrections needed to avoid errors in the issuing movements.

Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?

We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones.

A trans-spinal loop between neurones in the reticular formation and in the cerebellum.

Voluntary limb movements are initiated in the brain but the neurones responsible for activating the muscles (motoneurones and interneurones) are located in the spinal cord. The spinal cord also contains neurones that provide the brain, and especially the cerebellum, with continuous information on effects of the descending commands. We show that one population of such neurones provide the cerebellum with information on how likely the brain's commands (mediated by descending reticulospinal neurones) are to be executed as planned, depending on the degree of inhibition of motoneurones. They may therefore play an important role in preventing errors in activation of motoneurones and thereby help the brain to correct its signals to the spinal cord before such errors have been committed.

Malignancies among women who gave birth after in vitro fertilization.

BACKGROUND: Relatively few studies published to date have investigated IVF and cancer risk. In this study we compared the occurrence of cancer in women who gave birth after IVF with all other women who gave birth in the study period. METHODS: All women who were treated with IVF and gave birth during the years 1982-2006 in Sweden were identified from all IVF clinics, and the occurrence of cancer in these women was identified by linkage with the nationwide Swedish cancer register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting for year of delivery and maternal age, parity and smoking. Cancer before IVF was only studied in first parity women. Specific cancer forms were also studied. RESULTS: Among 24058 women who had been treated with IVF, 1279 appeared in the cancer register. The total number of women studied in the population was 1 394 061, and 95 775 of these were registered in the cancer register. The risk for cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48] and was especially high for ovarian cancer (3.93). The risk for cancer after IVF was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than expected risk for breast and cervical cancer. The risk for ovarian cancer was increased but lower than the risk before IVF (2.13). CONCLUSIONS: Cancer or cancer treatment may increase the risk for infertility leading to IVF. After IVF, in most cases with treatment with fertility hormones, a significantly low cancer risk was found. Ovarian cancer showed an increased risk, although lower than before IVF. One possible reason is ovarian pathology causing both infertility and an increased cancer risk.