Complete Genome Sequence of Paraclostridium bifermentans DSM 14991.

The complete genome sequence of Paraclostridium bifermentans was obtained by assembly of Illumina and Oxford Nanopore (ONT) reads. The sequence will enable study into the organism's ability to biohydrogenate unsaturated acyl chains in the transformation of C20 polyunsaturated fatty acids (PUFAs) into the corresponding bioactive non-methylene-interrupted fatty acids (NMIFAs).

Abstracts of the 24th international isotope society (UK group) symposium: synthesis and applications of labelled compounds 2015.

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

Synaptic elimination and protection after minimal injury depend on cell type and their prelesion structural dynamics in the adult cerebral cortex.

The axonal and synaptic mechanisms underlying dysfunction and repair of the injured CNS are poorly understood. Unresolved issues include to what degree, when, and how the surviving neurons degenerate and the extent of synaptic remodeling both along the severed axon and in the nearby area. One of the main reasons is the lack of tools to study the complex asynchronous and dynamic features of individual lesioned axon responses in the intact brain. To address these issues, we combined two-photon microscopy and laser microsurgery to image the real-time reorganization of cortical circuitry at synaptic resolution for periods of up to 1 year in the brain of living mice. Injured cortical axons were eliminated proximally through a two-phase retraction process, which continued for at least 3 months postlesion and was independent of the presence of scar tissue. Remarkably, axons which later attempt to regenerate in both the mature and juvenile brain retracted less, raising the possibility that targeting retraction may improve the chances of axon regrowth after axotomy. Comparing prelesion and postlesion dynamics on the same axons over several days and weeks revealed that, although synapse formation rates were unaffected, boutons on injured axons were either rapidly and persistently lost, or extremely resistant, depending on cell-type and their prelesion structural dynamics. Our data suggest a lasting deficiency in synaptic output on surviving injured cortical axons and a surprising difference in the vulnerability of synaptic boutons after axotomy, which depend on cell-type and their recent history.

In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits.

To what extent, how and when axons respond to injury in the highly interconnected grey matter is poorly understood. Here we use two-photon imaging and focused ion beam-scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity of several neuronal populations in the intact brain. Time-lapse analysis of >100 individually ablated axons for periods of up to a year reveals a surprising inability to regenerate even in a glial scar-free environment. However, depending on cell type some axons spontaneously extend for distances unseen in the unlesioned adult cortex and at maximum speeds comparable to peripheral nerve regeneration. Regrowth follows a distinct pattern from developmental axon growth. Remarkably, although never reconnecting to the original targets, axons consistently form new boutons at comparable prelesion synaptic densities, implying the existence of intrinsic homeostatic programmes, which regulate synaptic numbers on regenerating axons. Our results may help guide future clinical investigations to promote functional axon regeneration.

Oxegen 2004: the impact of a major music festival on the workload of a local hospital.

This prospective observational study was undertaken to assess the impact of a major music festival on the workload of a local hospital. Data were collected on all attendances at Naas General Hospital from the nearby Oxegen 2004 music festival. Patient demographics, disposition and diagnoses were recorded. Emergency department activity levels were compared before, during and after the festival. Seventy-two attendees were referred to Naas emergency department over a 3-day period, representing a 45% increase in the hospital's emergency department attendance rate. Thirty-seven of these attendees (51%) required inpatient or tertiary centre services. Thirty-four attendees (47%) were noted as having consumed alcohol and/or used illicit substances. We conclude that despite the provision of on-site medical facilities, major music events are associated with a significant increase in local health care activity and expenditure.

Patient, carer and health service outcomes of nurse-led early discharge after breast cancer surgery: a randomised controlled trial.

Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed. Early discharge has been shown to improve clinical outcomes, but there has been little assessment of the psychosocial and financial impact of early discharge on patients, carers and the health service. This study aimed to evaluate the effectiveness of a nurse-led model of early discharge from hospital. Main outcome measures were quality of life and carer burden. Secondary outcomes included patient satisfaction, arm morbidity, impact on community nurses, health service costs, surgical cancellations and in-patient nursing dependency. A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were randomised to nurse-led early discharge or conventional stay. Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction, had little effect on carer burden, improved communication between primary and secondary care, reduced cancellations and was safely implemented in a mixed rural/urban setting. In total, 40% of eligible patients agreed to take part. Nonparticipants were significantly older, more likely to live alone and had lower emotional well being before surgery. This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer. However, if given the choice, most patients prefer to stay in hospital until their wound drains are removed.

The uneven landscape of newborn intensive care services: variation in the neonatology workforce.

CONTEXT: In the past 30 years, the number of neonatologists has increased while total births have remained nearly constant. It is not known how equitably this expanded workforce is distributed. OBJECTIVE: To determine the geographic distribution of neonatologists in the United States. DATA SOURCES: 1996 American Medical Association physician masterfiles; 1999 survey of all U.S. neonatal intensive care units; 1995 American Hospital Association hospital survey; and 1995 U.S. vital records. MEASURES: The number of neonatologists and neonatal mid-level providers per live birth within 246 market-based regions. RESULTS: The neonatology workforce varied substantially across neonatal intensive care regions. The number of neonatologists per 10,000 live births ranged from 1.2 to 25.6 with an interquintile range of 3.5 to 8.5. The weakly positive correlation between neonatologists and neonatal mid-level providers per live birth is not consistent with substitution of neonatal mid-level providers for neonatologists (Spearman rank-correlation coefficient, 0.17; P < 0.01). There was no difference in the percentage of neonatal fellows in the lowest and highest workforce quintile (14% vs. 16%) or in the percentage of neonatologists engaged predominantly in research, teaching, or administration (14% in lowest and highest quintiles). CONCLUSIONS: The regional supply of neonatologists varies dramatically and cannot be explained by the substitution of neonatal mid-level providers or by the presence of academic medical centers. Further research is warranted to understand whether neonatal intensive care resources are located in accordance with risk and whether more resources improve newborn outcomes.

Are neonatal intensive care resources located according to need? Regional variation in neonatologists, beds, and low birth weight newborns.

OBJECTIVE: Despite marked growth in neonatal intensive care during the past 30 years, it is not known if neonatologists and beds are preferentially located in regions with greater newborn risk. This study reports the relationship between regional measures of intensive care capacity and low birth weight infants using newly developed market-based regions of neonatal intensive care. DESIGN: Cross-sectional small-area analysis of 246 neonatal intensive care regions (NICRs). DATA SOURCES: 1996 American Medical Association and American Osteopathic Association masterfiles data of clinically active neonatologists; 1999 American Academy of Pediatrics Section on Perinatal Pediatrics survey of directors of neonatal intensive care units in the United States with 100% response rate; 1995 linked birth/death data. RESULTS: The number of total births per neonatologist across NICRs ranged from 390 to 8197 (median: 1722) and the number of total births per intensive care bed ranged from 72 to 1319 (median: 317). The associations between capacity measures and low birth weight rates across NICRs were statistically significant but negligible (R(2): 0.04 for neonatologists; 0.05 for beds). NICRs in the quintile with the greatest neonatologist capacity (average of only 863 births per neonatologist) had very low birth weight (VLBW) rates of 1.5% while those in the quintile of lowest neonatologist capacity (average of 3718 births per neonatologist) had VLBW rates of 1.3%; a similar lack of meaningful difference in VLBW rates was noted across quintiles of intensive care bed capacity. Including midlevel providers and intermediate care beds to the analyses did not alter the findings. CONCLUSIONS: Neonatal intensive care capacity is not preferentially located in regions with greater newborn need as measured by low birth weight rates. Whether greater capacity affords benefits to the newborns remains unknown.

Topology of double minutes (dmins) and homogeneously staining regions (HSRs) in nuclei of human neuroblastoma cell lines.

Amplification of the MYCN gene is a characteristic feature of many neuroblastomas and is correlated with aggressive tumor growth. Amplicons containing this gene form either double minutes (dmins) or homogeneously staining regions (HSRs). To study the nuclear topology of these tumor-specific and transcriptionally active chromatin structures in comparison to chromosome territories, we performed fluorescence in situ hybridization with a MYCN probe and various chromosome paint probes, confocal laser scanning microscopy, and quantitative three-dimensional image analysis. The dmins formed dot-like structures in interphase nuclei and were typically located at the periphery of complexly folded chromosome territories; dmins noted in the chromosome territory interior were often detected within an invagination of the territory surface. Interphase HSRs typically formed extremely expanded structures, which we have never observed for chromosome territories of normal and tumor cell nuclei. Stretches of HSR-chromatin often extended throughout a large part of the cell nucleus, but appeared well separated from neighboring chromosome territories. We hypothesize that dmins are located within the interchromosomal domain (ICD) space and that stretches of HSR-chromatin align along this space. Such a topology could facilitate access of amplified genes to transcription and splicing complexes that are assumed to localize in the ICD space.

The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity.

The three-dimensional positioning of the X-chromosomal adenine nucleotide translocase genes, ANT2 and ANT3, were compared in the active and inactive X chromosome territories (Xa and Xi) of female human amniotic fluid cell nuclei. ANT2 is located in Xq24-q25 and is transcriptionally active on Xa, but inactive on Xi. ANT3 is located in the pseudoautosomal region Xp22.3 and escapes X-inactivation. Three-color fluorescence in situ hybridization, confocal laser scanning microscopy, and three-dimensional image analysis revealed that transcriptionally active ANT2 and ANT3 genes were positioned more peripheral within their chromosome territory than the inactive ANT2 gene. The position of the latter was significantly more interior in the Xi territory. Although the volumes of both X territories were similar, 3D distances between ANT2 and ANT3 were significantly smaller in Xi compared to Xa territories reflecting different territory shapes. Our data show a correlation between 3D positioning and transcriptional activity of these X-specific genes.

Bradykinin metabolism in perfused rat kidney.

The purpose of this study was to assess the capacity of perfused rat kidney to inactivate bradykinin (BK), and to compare the BK degrading capacity of rat kidney with the BK degrading capacities of rat lung, liver, and skeletal muscle, which was approximated by perfusion of rat hind limbs. Radioactively labeled BK, with the Pro2 and Pro3 residues having been tritiated, in an asanguinous salt solution was perfused through the kidney of the rat, over a concentration range of .0028-33 microM. Rat kidney had a large capacity to degrade BK and the system did not appear to approach saturation until perfusate BK concentrations reached 24 microM. A least-squares linear regression analysis and extrapolation to zero concentration was used to obtain values for amounts of BK degraded and BK fragments formed. The amount of BK cleaved was 99.9% of the administered dose. The major tritiated BK fragments formed, and the amount of each expressed as a percentage of the amount of BK degraded during transrenal passage, were the amino acid proline derived from the Pro2 and/or Pro3 residues of BK (Pro2,3), 60%; Pro-Pro (BK 2-3), 12%; Arg-Pro-Pro-Gly-Phe (BK 1-5), 14%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro (BK 1-7), 14%. The formation of BK 2-3 is indicative of initial aminopeptidase-P cleavage of BK to yield Arg, and des-Arg1-BK. Thus in rat kidney the aminopeptidase-P pathway is the major route for BK degradation, as is the case in rat liver.

State health agencies and quality improvement in perinatal care.

The origin of the federal-state partnership in Maternal and Child Health (MCH) can be traced from the Children's Bureau grants of 1912, through the Sheppard-Towner Act, to the creation of Title V and other programs of today that mandate planning, accountability, and systems development. In the past decade with the transformation of the health care system and the emergence of managed care, there has been a resurgence of interest in public, professional, and governmental interest in quality measurement and accountability. Regional perinatal systems have been implemented in all states with varying levels of involvement by state health agencies and the public sector. This historical framework discusses two primary themes: the decades of evolution in the federal-state partnership, and the emergence in the last three decades of perinatal regional system policy, and suggests that the structure of the federal-state partnership has encouraged state variation. A survey of state MCH programs was undertaken to clarify their operational and perceived role in promoting quality improvement in perinatal care. Data and information from the survey, along with five illustrative state case studies, demonstrate great variation in how individual state agencies function. State efforts in quality improvement, a process to make things better, have four arenas of activity: policy development and implementation, definition and measurement of quality, data collection and analysis, and communication to affect change. Few state health agencies (through their MCH programs and perinatal staff) are taking action in all four arenas. This analysis concludes that there are improvements MCH programs could implement without significant expansion in their authority or resources and points out that there is an opportunity for states to be more proactive as they have the legal authority and responsibility for assuring MCH outcomes.

The New Hampshire Perinatal Program: twenty years of perinatal outreach education.

OBJECTIVE: To describe 20 years of regional outreach education by the New Hampshire Perinatal Program, its interaction with all 26 community hospitals in the state with maternity services and an additional four in adjoining Vermont. STUDY DESIGN: This paper describes educational initiatives responsive to the needs of perinatal physicians and nurses. The core of the program is the transport conference held annually at each referring hospital in which maternal-fetal and infant referrals are discussed. There are additional community hospital-based programs, programs at convenient locations in the region and medical center conferences and skills programs. RESULTS: The program annually awards 10,000 continuing medical education credits (CME) and nursing contact hours. Evaluation and feedback from all participants is encouraged. New Hampshire has one of the lowest perinatal mortality rates in the county, which reflects in part the accomplishments of the program. CONCLUSION: Perinatal outreach education is a shared responsibility of providers in both the academic center and community hospitals and is necessary to ensure optimal care for mothers and infants.

Parental dreams, dilemmas, and decision-making in cinéma vérité.

Our film Dreams and Dilemmas: Parents and the Practice of Neonatal Care is on its way to meeting its goal of furthering the "Principles for Family Centered Neonatal Care" (Harrison H. Pediatrics 1993;92:643-50) through cinéma vérité depiction of parental involvement in decision-making. Reality-based filmmaking can provide valuable and successful educational material that advances care and understanding. However, there are real practical and ethical concerns such as privacy, consent, and uncertain or unknown future impact on participants. Successful reality-based filmmaking in a complex medical environment such as a neonatal intensive care unit requires careful attention to ways of ensuring full communication between all those involved and efforts to allay participants' anxiety about being portrayed unfavorably. The most important ingredient, however, is the skill and ability of the filmmaker to engender trust.

Inappropriate use of the ambulance service.

To determine the rate of inappropriate use of the ambulance service a prospective study of patients brought to a Dublin accident and emergency (A&E) department by ambulance was performed over a 78-day period--358 cases were analysed representing 37% of the ambulance case load. The receiving A&E physician deemed 43.3% of cases to have a definite indication for calling an ambulance, 36.9% a relative indication and 19.8% to have no indication. A strong correlation was shown between a definite indication for transport by ambulance and admission to hospital. Acute medical illness was the most common presentation in the study group (45.8%). Patients themselves were predominant in calling for a 999 ambulance and 35.8% were deemed to have no indication for doing so. When a general practitioner requests the ambulance only 7.4% of cases had no indication for the action. Approximately one-third (31%) of 999 calls were made because the patient had no transport alternative. The problem of ambulance misuse is multifactorial and a variety of strategies are required to address the issue.

Alpha and beta subunits of CaM-kinase II are localized in different neurons in chick ciliary ganglion.

The ciliary ganglion of the chicken contains only two types of neurons. Using monoclonal antibodies against the alpha and the beta subunits of Ca2+/calmodulin-stimulated protein kinase II (CaMPK-II) we found that the alpha-subunit was localized to the choroid neurons while beta subunit was associated with the ciliary neurons. As both neurons receive their inputs from the oculomotor nerve, while their postganglionic axons leave via different nerves, the ciliary ganglion of the chicken is a neuronal system in which the functional differences between alpha and beta CaMPK-II homopolymers in the regulation of synaptic transmission can be investigated.