Quantifying the reduction of airborne infectious viral load using a ventilated patient hood.

BACKGROUND: Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking. AIM: We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments. METHODS: We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer. FINDINGS: The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate. CONCLUSION: A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.

Hazara Nairovirus Requires COPI Components in both Arf1-Dependent and Arf1-Independent Stages of Its Replication Cycle.

Hazara nairovirus (HAZV) is an enveloped trisegmented negative-strand RNA virus classified within the Nairoviridae family of the Bunyavirales order and a member of the same subtype as Crimean-Congo hemorrhagic fever virus, responsible for fatal human disease. Nairoviral subversion of cellular trafficking pathways to permit viral entry, gene expression, assembly, and egress is poorly understood. Here, we generated a recombinant HAZV expressing enhanced green fluorescent protein and used live-cell fluorescent imaging to screen an siRNA library targeting genes involved in cellular trafficking networks, the first such screen for a nairovirus. The screen revealed prominent roles for subunits of the coat protein 1 (COPI)-vesicle coatomer, which regulates retrograde trafficking of cargo between the Golgi apparatus and the endoplasmic reticulum, as well as intra-Golgi transport. We show the requirement of COPI-coatomer subunits impacted at least two stages of the HAZV replication cycle: an early stage prior to and including gene expression and also a later stage during assembly and egress of infectious virus, with COPI-knockdown reducing titers by approximately 1,000-fold. Treatment of HAZV-infected cells with brefeldin A (BFA), an inhibitor of Arf1 activation required for COPI coatomer formation, revealed that this late COPI-dependent stage was Arf1 dependent, consistent with the established role of Arf1 in COPI vesicle formation. In contrast, the early COPI-dependent stage was Arf1 independent, with neither BFA treatment nor siRNA-mediated ARF1 knockdown affecting HAZV gene expression. HAZV exploitation of COPI components in a noncanonical Arf1-independent process suggests that COPI coatomer components may perform roles unrelated to vesicle formation, adding further complexity to our understanding of cargo-mediated transport.IMPORTANCE Nairoviruses are tick-borne enveloped RNA viruses that include several pathogens responsible for fatal disease in humans and animals. Here, we analyzed host genes involved in trafficking networks to examine their involvement in nairovirus replication. We revealed important roles for genes that express multiple components of the COPI complex, which regulates transport of Golgi apparatus-resident cargos. COPI components influenced at least two stages of the nairovirus replication cycle: an early stage prior to and including gene expression and also a later stage during assembly of infectious virus, with COPI knockdown reducing titers by approximately 1,000-fold. Importantly, while the late stage was Arf1 dependent, as expected for canonical COPI vesicle formation, the early stage was found to be Arf1 independent, suggestive of a previously unreported function of COPI unrelated to vesicle formation. Collectively, these data improve our understanding of nairovirus host-pathogen interactions and suggest a new Arf1-independent role for components of the COPI coatomer complex.

Pharmacokinetics/pharmacodynamics of antipseudomonal bacteriophage therapy in rats: a proof-of-concept study.

OBJECTIVES: Pan-drug-resistant (PDR) Pseudomonas aeruginosa is one of the three top-priority pathogens identified by the WHO, and bacteriophages have been investigated as an alternative therapy. However, knowledge on the pharmacokinetics/pharmacodynamics (PK/PD) of phage therapy is sparse, limiting its clinical applications. This study aimed to evaluate the PK/PD of the antipseudomonal phage øPEV20 in vivo following intravenous administration. METHODS: Healthy Sprague-Dawley rats were given øPEV20 as a single intravenous bolus of ~6, 9 and 11-log10PFU/rat. Arterial blood was sampled over 72 h. At 72 h, the animals were killed and multiple tissues were harvested for biodistribution studies. A PK model was developed using the importance sampling algorithm and deterministic simulations with a PD model were performed. RESULTS: A three-compartment model with non-linear clearance described the exposure of øPEV20 in blood. Model evaluation indicated that the model was robust and parameter estimates were accurate. The median (standard error) values of model-predicted PK parameters for VC, VP1, VP2, Q1, Q2, Vm and Km were 111 mL/rat (8.5%), 128 mL/rat (4.97%), 180 mL/rat (4.59%), 30.4 mL/h/rat (19.2%), 538 mL/h/rat (4.97%), 4.39 × 1010 PFU/h/rat (10.2%) and 1.64 × 107 PFU/mL/rat (3.6%), respectively. The distribution of øPEV20 was not homogeneous; there was preferential accumulation in the liver and spleen. Deterministic simulations with a PD model confirmed the importance of the host immune system in facilitating phage-mediated bacterial elimination. CONCLUSIONS: We developed a robust PK model to describe the disposition of phages in healthy rats. This model may have significant potential in facilitating future preclinical and clinical PK/PD investigations.

Predictors and Characteristics of Opioid Utilization >15 Days Following Total Knee Arthroplasty.

BACKGROUND: America is amid an opioid epidemic, best characterized by liberal prescribing practices; widespread opioid misuse, abuse, and diversion; and rising rates of prescription-related opioid overdose. While many contributors to opioid overprescribing exist, orthopedic surgery is identified as a key driver. The purpose of this study is to determine predictors of ongoing opioid use >15 days post-total knee arthroplasty (TKA) and those patients prescribed >1350 morphine milligram equivalents (MMEs) in the 15 days following surgery. METHODS: A retrospective cohort study was conducted in patients undergoing TKA (January 2016-December 2017) in an integrated healthcare system. Outcomes of interest were patient and clinical characteristics. RESULTS: A total of 621 patients were included in the study. The majority were female (57.6%), were non-Hispanic/Latino white (92.3%), and from metropolitan areas (64.3%) with fewer than 110,000 population. Mean age was 66.3. Being female (odds ratio [OR] = 1.547, P = .092), having a higher body mass index (OR = 1.043, P = .036), and receipt of more postdischarge prescriptions in the 60-day follow-up period (OR = 8.815, P < .0001) were associated with a greater likelihood of receipt of opioid prescriptions for more than 15 days. Older patients (OR = 0.954, P = .01) and those discharged to home (OR = 0.478, P = .045) were less likely to receive >1350 MME; longer length of stay (OR = 1.447, P = .013) was more likely in those prescribed >1350 MMEs. CONCLUSION: Several predictors were associated with longer duration and higher doses of opioid prescriptions post-TKA. Further research is needed to ascertain the challenges of opioid prescribing from both the metropolitan surgical team and rural healthcare provider perspective.

Rescue of Infectious Recombinant Hazara Nairovirus from cDNA Reveals the Nucleocapsid Protein DQVD Caspase Cleavage Motif Performs an Essential Role other than Cleavage.

The Nairoviridae family of the Bunyavirales order comprises tick-borne, trisegmented, negative-strand RNA viruses, with several members being associated with serious or fatal diseases in humans and animals. A notable member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is the most widely distributed tick-borne pathogen and is associated with devastating human disease, with case fatality rates averaging 30%. Hazara virus (HAZV) is closely related to CCHFV, sharing the same serogroup and many structural, biochemical, and cellular properties. To improve understanding of HAZV and nairovirus multiplication cycles, we developed, for the first time, a rescue system permitting efficient recovery of infectious HAZV from cDNA. This system now allows reverse genetic analysis of nairoviruses without the need for high-level biosafety containment, as is required for CCHFV. We used this system to test the importance of a DQVD caspase cleavage site exposed on the apex of the HAZV nucleocapsid protein arm domain that is cleaved during HAZV infection, for which the equivalent DEVD sequence was recently shown to be important for CCHFV growth in tick but not mammalian cells. Infectious HAZV bearing an uncleavable DQVE sequence was rescued and exhibited growth parameters equivalent to those of wild-type virus in both mammalian and tick cells, showing this site was dispensable for virus multiplication. In contrast, substitution of the DQVD motif with the similarly uncleavable AQVA sequence could not be rescued despite repeated efforts. Together, these results highlight the importance of this caspase cleavage site in the HAZV life cycle but reveal the DQVD sequence performs a critical role aside from caspase cleavage.IMPORTANCE HAZV is classified within the Nairoviridae family with CCHFV, which is one of the most lethal human pathogens in existence, requiring the highest biosafety level (BSL) containment (BSL4). In contrast, HAZV is not associated with human disease and thus can be studied using less-restrictive BSL2 protocols. Here, we report a system that is able to rescue HAZV from cDNAs, thus permitting reverse genetic interrogation of the HAZV replication cycle. We used this system to examine the role of a caspase cleavage site, DQVD, within the HAZV nucleocapsid protein that is also conserved in CCHFV. By engineering mutant viruses, we showed caspase cleavage at this site was not required for productive infection and this sequence performs a critical role in the virus life cycle aside from caspase cleavage. This system will accelerate nairovirus research due to its efficiency and utility under amenable BSL2 protocols.

Hazara nairovirus elicits differential induction of apoptosis and nucleocapsid protein cleavage in mammalian and tick cells.

The Nairoviridae family within the Bunyavirales order comprise tick-borne segmented negative-sense RNA viruses that cause serious disease in a broad range of mammals, yet cause a latent and lifelong infection in tick hosts. An important member of this family is Crimean-Congo haemorrhagic fever virus (CCHFV), which is responsible for serious human disease that results in case fatality rates of up to 30 %, and which exhibits the most geographically broad distribution of any tick-borne virus. Here, we explored differences in the cellular response of both mammalian and tick cells to nairovirus infection using Hazara virus (HAZV), which is a close relative of CCHFV within the CCHFV serogroup. We show that HAZV infection of human-derived SW13 cells led to induction of apoptosis, evidenced by activation of cellular caspases 3, 7 and 9. This was followed by cleavage of the classical apoptosis marker poly ADP-ribose polymerase, as well as cellular genome fragmentation. In addition, we show that the HAZV nucleocapsid (N) protein was abundantly cleaved by caspase 3 in these mammalian cells at a conserved DQVD motif exposed at the tip of its arm domain, and that cleaved HAZV-N was subsequently packaged into nascent virions. However, in stark contrast, we show for the first time that nairovirus infection of cells of the tick vector failed to induce apoptosis, as evidenced by undetectable levels of cleaved caspases and lack of cleaved HAZV-N. Our findings reveal that nairoviruses elicit diametrically opposed cellular responses in mammalian and tick cells, which may influence the infection outcome in the respective hosts.

Clinical narratives in residency education: Exploration of the learning process.

Background: Post-professional residency educational programs aim to advance the knowledge and skills of therapists in a clinical specialty area, however, little is known about the process, outcomes, or effectiveness of residency education. Purpose: The purpose of this study was to use narrative as a teaching and learning tool to gain insight into the progressive development of the residents' learning process. Design: Qualitative methods including a retrospective analysis of residents' narratives were used to explore the professional development and thought process of residents. Methods: Six physical therapy residents wrote reflective narratives across 4 time placements during their one-year residency. Qualitative content analysis was used to analyze the data for types of reflection across time frames and to construct themes based on meaning statements. Results: Four main themes evolved from the residents' clinical narratives: 1) developing clinical reasoning skills; 2) developing professional formation and identity; 3) moral agency; and 4) emerging characteristics of expertise Conclusions: In this study, clinical narratives served as a pedagogical tool to enhance aspects of clinical expertise. The utilization of clinical narrative may be used as one tool to help to create reflective practitioners with improved skills foundational to clinical practice.

Comparison of multiple thawing techniques on thaw time and stability of hemostatic proteins in canine plasma products.

OBJECTIVES: To compare thawing times of fresh frozen canine plasma between a 37 °C warm water bath, running water bath and dry plasma thawer and compare haemostatic protein stability after thawing in a warm water bath or dry plasma thawer. MATERIALS AND METHODS: To measure thawing times, a 240-mL bag of frozen plasma was thawed in warm water bath, running water bath or dry plasma thawer-10 times for each method. To evaluate stability of haemostatic proteins, fresh canine donor plasma samples were split into 120-mL bags and 3-mL control aliquots before freezing. Bags were thawed by warm water bath or dry plasma thawer and aliquots equilibrated to room temperature. Concentrations of haemostatic proteins, albumin, D-dimers, prothrombin time and partial thromboplastin time were obtained. RESULTS: The running water bath had the shortest thaw time: median thaw time of 15 minutes versus 18 minutes for both the dry plasma thawer and warm water bath. Statistically significant differences in partial thromboplastin time, factor VII, factor X, von Willebrand factor, and von Willebrand factor collagen binding assay were detected among groups but were unlikely to be clinically relevant. CLINICAL SIGNIFICANCE: A traditional running water bath provided the fastest thawing time but the dry plasma thawer resulted in the most stable haemostatic proteins.

Efficacy and Safety of Percutaneous Microwave Ablation and Cementoplasty in the Treatment of Painful Spinal Metastases and Myeloma.

BACKGROUND AND PURPOSE: Painful spinal metastases are a common cause of cancer-related morbidity. Percutaneous ablation presents an attractive minimally invasive alternative to conventional therapies. We performed a retrospective review of 69 patients with 102 painful spinal metastases undergoing microwave ablation and cementoplasty to determine the efficacy and safety of this treatment. MATERIALS AND METHODS: Procedures were performed between January 2015 and October 2016 with the patient under general anesthesia using image guidance for 102 spinal metastases in 69 patients in the following areas: cervical (n = 2), thoracic (n = 50), lumbar (n = 34), and sacral (n = 16) spine. Tumor pathologies included the following: multiple myeloma (n = 10), breast (n = 27), lung (n = 12), thyroid (n = 6), prostate (n = 5), colon (n = 4), renal cell (n = 3), oral squamous cell (n = 1), and adenocarcinoma of unknown origin (n = 1). Procedural efficacy was determined using the visual analog scale measured preprocedurally and at 2-4 weeks and 20-24 weeks postprocedure. Tumor locoregional control was assessed on follow-up cross-sectional imaging. Procedural complications were recorded to establish the safety profile. RESULTS: The median ablation time was 4 minutes 30 seconds ± 7 seconds, and energy dose, 4.1 ± 1.6 kJ. Median visual analog scale scores were the following: 7.0 ± 1.8 preprocedurally, 2 ± 1.6 at 2-4 weeks, and 2 ± 2.1 at 20-24 weeks. Eight patients died within 6 months following the procedure. Follow-up imaging in the surviving patients at 20-24 weeks demonstrated no locoregional progression in 59/61 patients. Two complications were documented (S1 nerve thermal injury and skin burn). CONCLUSIONS: Microwave ablation is an effective and safe treatment technique for painful spinal metastases. Further studies may be helpful in determining the role of microwave ablation in locoregional control of metastases.

Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the Latest Data?

Osteoporotic vertebral compression fractures frequently result in significant morbidity and health care resource use. For patients with severe and disabling pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often considered. Although vertebroplasty was introduced >30 years ago, there are conflicting opinions regarding the role of these procedures in the treatment of osteoporotic vertebral compression fractures. This review article updates clinicians on the published prospective randomized controlled data, including the most recent positive trials that followed initial negative trials in 2009. Analysis of multiple national claim datasets has also provided further insight into the utility of these procedures. Finally, we considered the recent recommendations of national organizations and medical societies that advise on the use of vertebral augmentation procedures for osteoporotic vertebral compression fractures.

Evaluation of Combination Drug Therapy for Treatment of Antibiotic-Resistant Inhalation Anthrax in a Murine Model.

Bacillus anthracis is considered a likely agent to be used as a bioweapon, and the use of a strain resistant to the first-line antimicrobial treatments is a concern. We determined treatment efficacies against a ciprofloxacin-resistant strain of B. anthracis (Cipr Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7 to 35 times the 50% lethal dose (LD50) of B. anthracis Cipr Ames spores. Commencing at 36 h postexposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacin alone (control groups), or ciprofloxacin combined with two antimicrobials, including meropenem-linezolid, meropenem-clindamycin, meropenem-rifampin, meropenem-doxycycline, penicillin-linezolid, penicillin-doxycycline, rifampin-linezolid, and rifampin-clindamycin, at appropriate dosing intervals (6 or 12 h) for the respective antibiotics. Ten mice per group were treated for 14 days and observed until day 28. The remaining animals were euthanized every 6 to 12 h, and blood, lungs, and spleens were collected for lethal factor (LF) and/or bacterial load determinations. All combination groups showed significant survival over the SWI and ciprofloxacin controls: meropenem-linezolid (P = 0.004), meropenem-clindamycin (P = 0.005), meropenem-rifampin (P = 0.012), meropenem-doxycycline (P = 0.032), penicillin-doxycycline (P = 0.012), penicillin-linezolid (P = 0.026), rifampin-linezolid (P = 0.001), and rifampin-clindamycin (P = 0.032). In controls, blood, lung, and spleen bacterial counts increased to terminal endpoints. In combination treatment groups, blood and spleen bacterial counts showed low/no colonies after 24-h treatments. The LF fell below the detection limits for all combination groups yet remained elevated in control groups. Combinations with linezolid had the greatest inhibitory effect on mean LF levels.

Biochemical evaluation of storage lesion in canine packed erythrocytes.

OBJECTIVES: To describe the biochemical changes - also known as the storage lesion - that occur in canine packed red blood cells during ex vivo storage. MATERIALS AND METHODS: Ten 125-mL units of non-leuco-reduced packed red blood cells in citrate phosphate dextrose adenine were obtained from a commercial blood bank within 24 hours of donation. Samples were aseptically collected on days 1, 4, 7, 14, 28, 35 and 42 for measurement of sodium, potassium, chloride, lactate, glucose, pH and ammonia concentrations. All units were cultured on day 42. Friedman's repeated measures test with Dunn's multiple comparison test was used for non-parametric data. A repeated-measures analysis of variance with Tukey's multiple comparison test was used for parametric data. Alpha was set to 0·05. RESULTS: All analytes changed significantly during storage. The mean ammonia on day 1 (58·14 g/dL) was significantly lower (P<0·05) than those on days 28 (1266 g/dL), 35 (1668 g/dL) and 42 (1860 g/dL). A significant increase in median lactate concentration over time was also observed, with day 1 (4·385 mmol/L) being significantly less (P<0·05) than days 14 (19·82 mmol/L), 21 (22·81 mmol/L), 35 (20·31 mmol/L) and 42 (20·81 mmol/L). Median pH was significantly decreased after day 7. All bacterial cultures were negative. CLINICAL SIGNIFICANCE: Many biochemical alterations occur in stored canine packed red blood cells, although further studies are required to determine their clinical importance.

Biochemical evaluation of the effects of storage on feline erythrocytes.

OBJECTIVE: To describe the biochemical changes that occur during storage of feline packed red blood cells. METHODS: Feline packed red blood cells were obtained from the manufacturer via overnight delivery immediately following collection. Bag spikes were placed using aseptic technique and samples were drawn on days 1, 4, 7, 14, 21, 28 and 35. Sodium, potassium, chloride, glucose, lactate, pH and ammonia were measured at each time point. Aerobic and anaerobic bacterial cultures were submitted following collection on day 35. RESULTS: There were statistically significant increases in the median concentrations of lactate and ammonia within the first 2 weeks of storage to a concentration of 12·38 mmol/L and 447·96 µmol/L, respectively. Glucose concentrations decreased significantly by day 28 to a mean of 1·86 mmol/L. Median sodium and chloride concentrations increased throughout the course of storage to a concentration of 158·20 and 131·00 mmol/L, respectively. Mean potassium concentrations decreased to a concentration of 2·40 mmol/L. CLINICAL SIGNIFICANCE: These results show that biochemical derangements within feline packed red blood cells are progressive, with some alterations, such as lactate and ammonia, occurring early within the storage periods, while others, including glucose and electrolytes, are slower to develop. Additional prospective research evaluating the clinical effects of these biochemical alterations is required.

Hendra Virus Infection Dynamics in the Grey-Headed Flying Fox (Pteropus poliocephalus) at the Southern-Most Extent of Its Range: Further Evidence This Species Does Not Readily Transmit the Virus to Horses.

Hendra virus (HeV) is an important emergent virus in Australia known to infect horses and humans in certain regions of the east coast. Whilst pteropid bats ("flying foxes") are considered the natural reservoir of HeV, which of the four mainland species is the principal reservoir has been a source of ongoing debate, particularly as shared roosting is common. To help resolve this, we sampled a colony consisting of just one of these species, the grey-headed flying fox, (Pteropus poliocephalus), at the southernmost extent of its range. Using the pooled urine sampling technique at approximately weekly intervals over a two year period, we determined the prevalence of HeV and related paramyxoviruses using a novel multiplex (Luminex) platform. Whilst all the pooled urine samples were negative for HeV nucleic acid, we successfully identified four other paramyxoviruses, including Cedar virus; a henipavirus closely related to HeV. Collection of serum from individually caught bats from the colony showed that antibodies to HeV, as estimated by a serological Luminex assay, were present in between 14.6% and 44.5% of animals. The wide range of the estimate reflects uncertainties in interpreting intermediate results. Interpreting the study in the context of HeV studies from states to the north, we add support for an arising consensus that it is the black flying fox and not the grey-headed flying fox that is the principal source of HeV in spillover events to horses.

High Confinement Mode and Edge Localized Mode Characteristics in a Near-Unity Aspect Ratio Tokamak.

Tokamak experiments at near-unity aspect ratio A≲1.2 offer new insights into the self-organized H-mode plasma confinement regime. In contrast to conventional A∼3 plasmas, the L-H power threshold P_{LH} is ∼15× higher than scaling predictions, and it is insensitive to magnetic topology, consistent with modeling. Edge localized mode (ELM) instabilities shift to lower toroidal mode numbers as A decreases. These ultralow-A operations enable heretofore inaccessible J_{edge}(R,t) measurements through an ELM that show a complex multimodal collapse and the ejection of a current-carrying filament.

Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

BACKGROUND AND PURPOSE: Ceftriaxone is a ß-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3ß were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3ß signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens.

A rare case of paediatric stridor caused by achalasia.

OBJECTIVE: This paper reports a case of achalasia in a 12-year-old girl who presented with stridor. CASE REPORT: An otherwise healthy 12-year-old girl presented to the ENT clinic with an 18-month history of dysphagia and noisy breathing on eating. Flexible fibre-optic examination showed a normal larynx with normal vocal fold movements. Fibre-optic endoscopic evaluation of swallowing was normal initially, but biphasic stridor occurred after several swallows. Microlaryngoscopy, bronchoscopy and upper oesophagoscopy showed a dilated oesophagus with normal mucosa. Bronchoscopy showed tracheomalacia of the distal trachea, which reduced the airway by approximately 75 per cent. This was caused by posterior compression from redundant oesophageal mucosa with dilatation as a result of retained fluids. Videofluoroscopy suggested achalasia, which was confirmed by oesophageal manometry. Her symptoms improved following a Heller's myotomy. CONCLUSION: This is the first paediatric case in the English literature of achalasia presenting with stridor. The condition was correctable with surgical intervention.

Fibular taping does not alter lower extremity spinal reflex excitability in individuals with chronic ankle instability.

OBJECTIVE: To determine changes in spinal reflex excitability of the soleus and fibularis longus muscles before and after fibular taping intervention. METHODS: Twenty-one individuals (age = 23.4 ± 2.7 y, height = 171.0 ± 12.8 cm, mass = 69.7 ± 11.8 kg) with chronic ankle instability (CAI) and at least 5° ankle dorsiflexion asymmetry volunteered for this randomised crossover design study. Each participant received a fibular taping with tension or fibular taping without tension during separate sessions. Spinal reflex excitability of the soleus and fibularis longus was determined by obtaining maximum values for H-reflex (Hoffmann reflex) and maximum compound muscle action potential (Mmax), which was expressed as a ratio (H/M ratio). Measures were obtained immediately before and after a fibular taping intervention. RESULTS: The application of tape to the fibula, regardless of tension, did not produce a change in spinal reflex excitability for the soleus (F1,39 = .01, P = .91) or fibularis longus (F1,39 = .001, P = .99). CONCLUSIONS: Fibular taping with and without tension did not result in an immediate change in spinal reflex excitability of the soleus or fibularis longus in individuals with CAI. Although fibular taping has been shown to reduce recurrent ankle sprains in individuals with CAI, the mechanism of effectiveness may not involve an immediate increase in spinal reflex excitability.

Impact of analgesic modality on stress response following laparoscopic colorectal surgery: a post-hoc analysis of a randomised controlled trial.

BACKGROUND: Epidural analgesia is perceived to modulate the stress response after open surgery. This study aimed to explore the feasibility and impact of measuring the stress response attenuation by post-operative analgesic modalities following laparoscopic colorectal surgery within an enhanced recovery after surgery (ERAS) protocol. METHODS: Data were collected as part of a double-blinded randomised controlled pilot trial at two UK sites. Patients undergoing elective laparoscopic colorectal resection were randomised to receive either thoracic epidural analgesia (TEA) or continuous local anaesthetic infusion to the extraction site via wound infusion catheter (WIC) post-operatively. The aim of this study was to measure the stress response to the analgesic modality by measuring peripheral venous blood samples analysed for serum concentrations of insulin, cortisol, epinephrine and interleukin-6 at induction of anaesthesia, at 3, 6, 12 and 24 h after the start of operation. Secondary endpoints included mean pain score in the first 48 h, length of hospital stay, post-operative complications and 30-day re-admission rates. RESULTS: There was a difference between the TEA and WIC groups that varies across time. In the TEA group, there was significant but transient reduced level of serum epinephrine and a higher level of insulin at 3 and 6 h. In the WIC, there was a significant reduction of interleukin-6 values, especially at 12 h. There was no significant difference observed in the other endpoints. CONCLUSIONS: There is a significant transient attenuating effect of TEA on stress response following laparoscopic colorectal surgery and within ERAS as expressed by serum epinephrine and insulin levels. Continuous wound infusion with local anaesthetic, however, attenuates cytokine response as expressed by interleukin-6.