The incidence of dry chlorhexidine gluconate transfer from skin to surgical gloves: a simulation and in vitro study.

BACKGROUND: To prevent alcohol-based chlorhexidine from reaching the cerebrospinal fluid, it is recommended that the antiseptic solution be allowed to dry before skin palpation or puncture. However, no guidelines specify a drying time interval. Manufacturers recommend 3 min of air drying, based upon the isopropyl alcohol component. Therefore, to fill this knowledge gap, we designed a simulation study to investigate the incidence of primary chlorhexidine transfer from skin to gloves following three drying time intervals. We also investigated the incidence of secondary chlorhexidine transfer from gloves to another surface following one drying time interval. METHODS: An alcohol-based chlorhexidine antiseptic solution with dye, ChloraPrep®, was applied to the skin of the lumbar region of 20 volunteers. Cotton-tipped applicators wrapped in material from gloves were taken from the application area at 3, 4, 5, and 10 min following application. Transfer of chlorhexidine from skin to gloves, and gloves to another medium, was assessed through a chemical assay that produced a color change when chlorhexidine was present on the sample. RESULTS: The incidence of primary chlorhexidine transfer from skin to gloves at 3, 4 and 10 min following application was 99.5%, 99.4%, and 99.6%, respectively. The incidence of secondary chlorhexidine transfer from gloves to another surface was 68.9%. CONCLUSION: Gloves are routinely contaminated with chlorhexidine during central neuraxial blockade. The high incidence of secondary transfer in our simulation suggests a pathway by which chlorhexidine may gain access to the neuraxial space.

Proteome size reduction in Apicomplexans is linked with loss of DNA repair and host redundant pathways.

Apicomplexans are alveolate parasites which include Plasmodium falciparum, the main cause of malaria, one of the world's biggest killers from infectious disease. Apicomplexans are characterized by a reduction in proteome size, which appears to result from metabolic and functional simplification, commensurate with their parasitic lifestyle. However, other factors may also help to explain gene loss such as population bottlenecks experienced during transmission, and the effect of reducing the overall genomic information content. The latter constitutes an 'informational constraint', which is proposed to exert a selective pressure to evolve and maintain genes involved in informational fidelity and error correction, proportional to the quantity of information in the genome (which approximates to proteome size). The dynamics of gene loss was examined in 41 Apicomplexan genomes using orthogroup analysis. We show that loss of genes involved in amino acid metabolism and steroid biosynthesis can be explained by metabolic redundancy with the host. We also show that there is a marked tendency to lose DNA repair genes as proteome size is reduced. This may be explained by a reduction in size of the informational constraint and can help to explain elevated mutation rates in pathogens with reduced genome size. Multiple Sequentially Markovian Coalescent (MSMC) analysis indicates a recent bottleneck, consistent with predictions generated using allele-based population genetics approaches, implying that relaxed selection pressure due to reduced population size might have contributed to gene loss. However, the non-randomness of pathways that are lost challenges this scenario. Lastly, we identify unique orthogroups in malaria-causing Plasmodium species that infect humans, with a high proportion of membrane associated proteins. Thus, orthogroup analysis appears useful for identifying novel candidate pathogenic factors in parasites, when there is a wide sample of genomes available.

Synergism between the Black Queen effect and the proteomic constraint on genome size reduction in the photosynthetic picoeukaryotes.

The photosynthetic picoeukaryotes (PPEs) comprise a rare example of free-living eukaryotes that have undergone genome reduction. Here, we examine a duality in the process; the proposed driver of genome reduction (the Black Queen hypothesis, BQH), and the resultant impact of genome information loss (the Proteomic Constraint hypothesis, PCH). The BQH predicts that some metabolites may be shared in the open ocean, thus driving loss of redundant metabolic pathways in individual genomes. In contrast, the PCH predicts that as the information content of a genome is reduced, the total mutation load is also reduced, leading to loss of DNA repair genes due to the resulting reduction in selective constraint. Consistent with the BQH, we observe that biosynthetic pathways involved with soluble metabolites such as amino acids and carotenoids are preferentially lost from the PPEs, in contrast to biosynthetic pathways involved with insoluble metabolites, such as lipids, which are retained. Consistent with the PCH, a correlation between proteome size and the number of DNA repair genes, and numerous other informational categories, is observed. While elevated mutation rates resulting from the loss of DNA repair genes have been linked to reduced effective population sizes in intracellular bacteria, this remains to be established. This study shows that in microbial species with large population sizes, an underlying factor in modulating their DNA repair capacity appears to be information content.

An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design.

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

Work-leave rotation pattern and incidence of offshore workplace injury.

Background: Studies on work-leave rotation pattern and work place injuries among offshore oil and gas workers have been few and limited to a 2- or 3-week rotation schedule. Aims: To examine incidence of workplace injury in relation to the duration of time into work rotation for extended work schedules up to 24 weeks. Methods: Six-year injury data on four offshore installations were extracted. Data were analysed for incidence of injury over time and relative risk using linear trend lines and regression. Results: In total, 311 injuries for 1302 workers were analysed, 39% with rotation schedule of 4 weeks work and 4 weeks rest, 27% 8 weeks work and 4 weeks rest, 23% 16 weeks work and 4 weeks rest and 10% 24 weeks work and 4 weeks rest. Incidence of injury decreased as duration of time into the work rotation increased, corrected for exposure, and this was statistically significant for all rotations in first 4 weeks (P < 0.01). Negative correlation between time offshore and injury was observed in all schedules and consistent for age groups, categories of work, shifts and severity of injury. There was no difference in relative risk of injuries between the four schedules, when corrected for exposure and occupational risk of injury. Conclusions: These results are at variance with previous studies, although no prior study has looked beyond 3-week rotation schedule. Longer offshore schedules are safely possible and this could help decrease manpower and logistics costs for oil and gas companies coping with unprecedented low oil prices.

Effects of a head elevated ramped position during elective caesarean delivery after combined spinal-epidural anaesthesia.

BACKGROUND: Elevating the torso in a Head Elevated Ramped Position during caesarean delivery benefits the mother by improving comfort and ventilation while reducing reflux symptoms and providing a better airway position. We hypothesised that using an elevation pillow for an elective caesarean delivery under combined spinal-epidural anaesthesia would not significantly increase the time to achieve a T4 block. METHODS: Following ethical approval and informed consent, 60 women undergoing elective caesarean delivery under combined spinal-epidural anaesthesia were randomised to one of three groups: Control - horizontal with a small pillow under the head; Head Elevated Ramped Position - torso on an elevation pillow; and Head Elevated Ramped Position with initial position horizontal. Data collected were time to T4, block height at 30 and 120 min, adequate block at 12 min, need for epidural supplementation, maternal comfort and airway position assessment. RESULTS: Time to T4 among the three groups was not significantly different (P=0.14). However, there was a significant difference in achievement of block height of T4 at 12 min and greater need for epidural supplementation in the intervention groups compared to the control group (P=0.021). Non-inferiority analyses of time to T4 of both head elevated ramped positions were inconclusive about inferiority relative to the control. Head Elevated Ramped Position was significantly more comfortable than control (P=0.007). Using the level of the external auditory meatus to the sternal notch as an indicator for ease of laryngoscopy, Head Elevated Ramped Position provided a significantly better position than control (P<0.001). CONCLUSION: Elevating the parturient undergoing elective caesarean delivery into the Head Elevated Ramped Position immediately or once the block had been established did not appear to significantly alter time to an adequate block height of T4; however, the need for epidural supplementation was greater in the intervention groups. Cautious use of this novel position change can provide a more comfortable experience and provide a better airway position should conversion to general anaesthesia be required.

The distribution of recombination repair genes is linked to information content in bacteria.

The concept of a 'proteomic constraint' proposes that the information content of the proteome exerts a selective pressure to reduce mutation rates, implying that larger proteomes produce a greater selective pressure to evolve or maintain DNA repair, resulting in a decrease in mutational load. Here, the distribution of 21 recombination repair genes was characterized across 900 bacterial genomes. Consistent with prediction, the presence of 17 genes correlated with proteome size. Intracellular bacteria were marked by a pervasive absence of recombination repair genes, consistent with their small proteome sizes, but also consistent with alternative explanations that reduced effective population size or lack of recombination may decrease selection pressure. However, when only non-intracellular bacteria were examined, the relationship between proteome size and gene presence was maintained. In addition, the more widely distributed (i.e. conserved) a gene, the smaller the average size of the proteomes from which it was absent. Together, these observations are consistent with the operation of a proteomic constraint on DNA repair. Lastly, a correlation between gene absence and genome AT content was shown, indicating a link between absence of DNA repair and elevated genome AT content.

Impact of a single-day multidisciplinary clinic on the management of patients with liver tumours.

PURPOSE: Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (mdlc) affected care recommendations for patients compared with the recommendations provided before presentation to the mdlc. METHODS: We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (osp) and the mdlc. RESULTS: Most patients were white (n = 259, 76%); median age was 60 years; and 146 were women (43%). Outside providers referred 182 patients (53%); the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7-247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the osp, and a formal management plan had been formulated for about half (n = 168, 49%). Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the mdlc resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued. CONCLUSIONS: Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The mdlc is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours.

A randomized controlled trial comparing intrathecal morphine with transversus abdominis plane block for post-cesarean delivery analgesia.

BACKGROUND: Intrathecal morphine is an effective analgesic post-cesarean delivery; however, it may be contraindicated or unsuitable in some patients. We compared the efficacy and side effects of intrathecal morphine with an ultrasound-guided transversus abdominis plane (TAP) block in a randomized, controlled, double-blinded trial. The primary outcome was the morphine equivalents dose used in the first 24 h post-surgery. Secondary outcomes were pain scores and side effects, including pruritus, sedation, nausea and vomiting. METHODS: Planned recruitment was for 90 women; however, the study was terminated early. Sixty-nine women undergoing elective cesarean delivery under spinal anesthesia were enrolled. They were randomized to receive either intrathecal morphine 100 µg plus a sham TAP block or a TAP block with 0.5% ropivacaine 1.5 mg/kg, to each side to a maximum of 20 mL. Women were assessed at 2, 6, 10, 24 h and 3 months post-spinal. RESULTS: Sixty-six women completed the trial. The morphine equivalents dose used in the TAP block group was greater at 24 h compared with the intrathecal morphine group (7.5 mg (95% CI 4.8-10.2) vs. 2.7 mg (95% CI 1.0-4.3), F [1, 64]=9.62, P=0.003). There was no difference at 2, 6, or 10 h. Pain scores on rest and movement were higher in the TAP block group at all times although this only reached statistical significance at 10 h (P=0.001). Nausea and vomiting (P=0.02) and pruritus (P=0.007) were lower in the TAP block group. CONCLUSIONS: In this trial, the TAP block was associated with greater supplemental morphine requirements and higher pain scores than intrathecal morphine but fewer opioid-related side effects. The TAP block may be a reasonable alternative when intrathecal morphine is contraindicated or not appropriate.

Anterior tongue reduction surgery for paediatric macroglossia.

OBJECTIVE: Anterior tongue reduction is indicated when macroglossia causes problems with oral hygiene, airway compromise, deglutition, articulation or orthognathic complications. Causes of macroglossia include hypothyroidism, mucopolysaccharide and lipid storage disease, lymphangioma, haemangioma, neurofibroma, and muscular macroglossia. This paper presents an 11-year experience of anterior tongue reduction at Great Ormond Street Hospital. METHOD: Retrospective study of patient medical records identified from the hospital ENT database. Anterior wedge resection was the preferred technique. RESULTS: Anterior tongue reduction was performed on 18 patients, due to cystic hygroma with tongue involvement (nine patients), Beckwith-Wiedemann syndrome (eight) and Down's syndrome (one). Anterior wedge resection was preferred, using electrocautery in the majority, except for four cases involving CO2 laser. All but one patient had a good surgical outcome (i.e. tongue in mouth at rest). One patient subsequently required multiple laser procedures for recurrent macroglossia. CONCLUSION: Anterior tongue reduction can be a safe procedure, with limited post-operative morbidity, consistently resulting in good surgical outcomes and improvement in macroglossia symptoms. Speech development does not appear to be adversely affected.

Do all epistaxis patients with a nasal pack need admission? A retrospective study of 116 patients managed in accident and emergency according to a peer reviewed protocol.

INTRODUCTION: Epistaxis is the most common nasal emergency and if nasal packing is required this commonly results in admission. METHODS: A literature search could find no published (UK) protocols for the management of this common condition in accident and emergency (A&E) departments. This paper presents a retrospective review of 116 patients with epistaxis, following implementation of the new peer reviewed protocol in June 2004. RESULTS: Apart from cautery, 62 had nasal packing inserted. Only 17 required admission. Forty-six patients were discharged with nasal packing in situ and only seven (16 per cent) returned due to bleeding. The overall return rate was 11 per cent. DISCUSSION: We feel this is a safe and logical protocol. Compared to mandatory admission after nasal pack insertion, we saved 39 admissions in five months. There were also the added benefits to patients of being able to recuperate at home rather than in hospital and avoidance of the risk of hospital acquired infection.

Soiling and decay of N.M.E.P. limestone tablets.

The British National Materials Exposure Programme (N.M.E.P.) ran from 1987 to 1995 and involved exposure of a range of materials samples (including tablets of Monks Park and Portland Limestones) at over 20 sites around Britain for 1-, 2-, 4- and 8-year periods, under known climate and pollution conditions. Deterioration of the limestone tablets has previously been recorded in terms of weight change, contents of soluble salts, and visual soiling. In the present study samples from exposed and sheltered positions at Wells, Bolsover and Lough Navar have been studied using a spectrophotometer, optical microscopy and scanning electron microscopy (SEM) to investigate the distribution and nature of particulate material and its role in soiling and decay. Clearly, recognisable pollutant particles such as perforated cenospheres, are only rarely present. Organisms and organic remains, including filamentous microorganisms and pollen grains, are widely distributed. At each site, soiling has different characteristics in terms of composition and change over time related in part to differences in climate and pollution histories. There is no general link between degree of soiling and amount of decay (in terms of surface recession) as the nature of decay is a key influence on the relation between soiling and decay.

Coupling from AII amacrine cells to ON cone bipolar cells is bidirectional.

The AII amacrine cell is a critical interneuron in the rod pathway of the mammalian retina. Rod signals pass into cone pathways by means of gap junctions between AII amacrine cells and ON cone bipolar cells. Filling AII amacrine cells with Neurobiotin produces labeling of cone bipolar cells by means of these gap junctions. However, tracer injections into bipolar cells do not produce labeling of the AII network (Vaney [1997] Invest Ophthalmol Vis Sci. 38:267-273), which suggests that the AII/bipolar gap junctions allow the passage of tracer in only one direction. This mechanism stands in contrast to physiological results, which indicate that light adapted signals can pass from ON cone bipolar cells into the AII network (Xin and Bloomfield [1999] Vis Neurosci. 16:653-665). Here, we report that a variety of ON and OFF bipolar cells are sometimes anomalously coupled to the A-type horizontal cell network. These relatively rare examples do not result from dye injection errors, but seem to represent minor developmental errors. However, this provides a method to obtain Neurobiotin-filled cone bipolar cells without the necessity of impaling them with a microelectrode. Under these conditions, Neurobiotin spreads from ON cone bipolar cells into neighboring AII amacrine cells. The dye-coupled AII amacrine cells, positively identified by double labeling with an antibody against calretinin, were centered around anomalously coupled ON bipolar cells. These results indicate that AII/bipolar cell gap junctions allow tracer coupling in both directions, consistent with previous physiological results. The previous failure to detect the passage of neuronal tracer from injected bipolar cells to AII amacrine cells may reflect electrode damage or perhaps the asymmetrical voltage sensitivity of a heterotypic gap junction.

Rod pathways in the mammalian retina use connexin 36.

Many neurons in the mammalian retina are coupled by means of gap junctions. Here, we show that, in rabbit retina, an antibody to connexin 36 heavily labels processes of AII amacrine cells, a critical interneuron in the rod pathway. Image analysis indicates that Cx36 is primarily located at dendritic crossings between overlapping AII amacrine cells. This finding suggests that Cx36 participates in homotypic gap junctions between pairs of AII amacrine cells. Cx36 was also found at AII/cone bipolar contacts, previously shown to be gap junction sites. This finding suggests that Cx36 participates at gap junctions that may be heterotypic. These results place an identified neuronal connexin in the context of a well-defined retinal circuit. The absence of Cx36 in many other neurons known to be coupled suggests the presence of additional unidentified connexins in mammalian neurons. Conversely, Cx36 labeling in other regions of the retina is not associated with AII amacrine cells, indicating some other cell types use Cx36.